Trends in E & G Expenditure Allocations. Indicators of Recession or Increased Productivity?

ERIC Educational Resources Information Center

Minter, John

1992-01-01

A random sample of 300 financial officers at public and independent 4-year and public 2-year institutions reveal their projected fiscal 1992 year-end expenditures and 1992-93 budget allocations. Summarized in chart form are the findings on changes in growth rates on salary and wage allocations for a variety of institutional functions. (GLR)

Exploration of Near-Field Plume Properties for Aerated-Liquid Jets Using X-Ray Radiography (Postprint)

DTIC Science & Technology

2014-02-01

nozzle exit to discharge more liquid and aerating gas , plume momentum flux increases with liquid flow rate (at the same GLR) in the region...for testing. Water and nitrogen were used as the injectant and aerating gas , respectively. It was demonstrated that the liquid -weighted plume...diameter D2 = throat diameter EPL = equivalent path length GLR = aerating gas -to- liquid mass ratio I = intensity of the transmitted light I0

Common and divergent features in transcriptional control of the homologous small RNAs GlmY and GlmZ in Enterobacteriaceae

PubMed Central

Göpel, Yvonne; Lüttmann, Denise; Heroven, Ann Kathrin; Reichenbach, Birte; Dersch, Petra; Görke, Boris

2011-01-01

Small RNAs GlmY and GlmZ compose a cascade that feedback-regulates synthesis of enzyme GlmS in Enterobacteriaceae. Here, we analyzed the transcriptional regulation of glmY/glmZ from Yersinia pseudotuberculosis, Salmonella typhimurium and Escherichia coli, as representatives for other enterobacterial species, which exhibit similar promoter architectures. The GlmY and GlmZ sRNAs of Y. pseudotuberculosis are transcribed from σ54-promoters that require activation by the response regulator GlrR through binding to three conserved sites located upstream of the promoters. This also applies to glmY/glmZ of S. typhimurium and glmY of E. coli, but as a difference additional σ70-promoters overlap the σ54-promoters and initiate transcription at the same site. In contrast, E. coli glmZ is transcribed from a single σ70-promoter. Thus, transcription of glmY and glmZ is controlled by σ54 and the two-component system GlrR/GlrK (QseF/QseE) in Y. pseudotuberculosis and presumably in many other Enterobacteria. However, in a subset of species such as E. coli this relationship is partially lost in favor of σ70-dependent transcription. In addition, we show that activity of the σ54-promoter of E. coli glmY requires binding of the integration host factor to sites upstream of the promoter. Finally, evidence is provided that phosphorylation of GlrR increases its activity and thereby sRNA expression. PMID:20965974

Comparison of Y-jet and OIL effervescent atomizers based on internal and external two-phase flow characteristics

NASA Astrophysics Data System (ADS)

Mlkvik, Marek; Zaremba, Matous; Jedelsky, Jan; Jicha, Miroslav

2016-03-01

Presented paper focuses on spraying of two viscous liquids (μ = 60 and 143 mPa·s) by two types of twinfluid atomizers with internal mixing. We compared the well-known Y-jet atomizer with the less known, "outside in liquid" (OIL), configuration of the effervescent atomizer. The required liquid viscosity was achieved by using the water-maltodextrin solutions of different concentrations. Both the liquids were sprayed at two gas inlet pressures (Δp = 0.14 and 0.28 MPa) and various gas-to-liquid ratios (GLR = 2.5%, 5%, 10% and 20%). The comparison was focused on four characteristics: liquid flow-rate (for the same working regimes, defined by Δp and GLR), internal flow regimes, Weber numbers of a liquid breakup (We) and droplet sizes. A high-speed camera and Malvern Spraytec laser diffraction system were used to obtain necessary experimental data. Comparing the results of our experiments, we can state that for both the liquids the OIL atomizer reached higher liquid flow-rates at corresponding working regimes, it was typical by annular internal flow and higher We in the near-nozzle region at all the working regimes. As a result, it produced considerably smaller droplets than the second tested atomizing device, especially for GLR < 10%.

A dual-mode generalized likelihood ratio approach to self-reorganizing digital flight control system design

NASA Technical Reports Server (NTRS)

1976-01-01

Analytic techniques have been developed for detecting and identifying abrupt changes in dynamic systems. The GLR technique monitors the output of the Kalman filter and searches for the time that the failure occured, thus allowing it to be sensitive to new data and consequently increasing the chances for fast system recovery following detection of a failure. All failure detections are based on functional redundancy. Performance tests of the F-8 aircraft flight control system and computerized modelling of the technique are presented.

Performance and sensitivity analysis of the generalized likelihood ratio method for failure detection. M.S. Thesis

NASA Technical Reports Server (NTRS)

Bueno, R. A.

1977-01-01

Results of the generalized likelihood ratio (GLR) technique for the detection of failures in aircraft application are presented, and its relationship to the properties of the Kalman-Bucy filter is examined. Under the assumption that the system is perfectly modeled, the detectability and distinguishability of four failure types are investigated by means of analysis and simulations. Detection of failures is found satisfactory, but problems in identifying correctly the mode of a failure may arise. These issues are closely examined as well as the sensitivity of GLR to modeling errors. The advantages and disadvantages of this technique are discussed, and various modifications are suggested to reduce its limitations in performance and computational complexity.

Orthogonal series generalized likelihood ratio test for failure detection and isolation. [for aircraft control

NASA Technical Reports Server (NTRS)

Hall, Steven R.; Walker, Bruce K.

1990-01-01

A new failure detection and isolation algorithm for linear dynamic systems is presented. This algorithm, the Orthogonal Series Generalized Likelihood Ratio (OSGLR) test, is based on the assumption that the failure modes of interest can be represented by truncated series expansions. This assumption leads to a failure detection algorithm with several desirable properties. Computer simulation results are presented for the detection of the failures of actuators and sensors of a C-130 aircraft. The results show that the OSGLR test generally performs as well as the GLR test in terms of time to detect a failure and is more robust to failure mode uncertainty. However, the OSGLR test is also somewhat more sensitive to modeling errors than the GLR test.

Some Thoughts on DIY Materials Design.

ERIC Educational Resources Information Center

Block, David

1991-01-01

Discusses the reasons that are often given against teacher-generated English-as-a-Foreign-Language materials and presents arguments in favor of DIY (Do It Yourself) materials design. (23 references) (GLR)

Grimm's Law: Fact or Myth?

ERIC Educational Resources Information Center

Gessman, Albert M.

1990-01-01

Discusses phonic shifting or sound shifts through an examination of Grimm's Law, or the Germanic Consonant Shift. The discussion includes comments on why the phonic shift developed and its pattern. (10 references) (GLR)

Sport Management Interns--Selection Qualifications.

ERIC Educational Resources Information Center

Cuneen, Jacquelyn; Sidwell, M. Joy

1993-01-01

Examines and rates the background qualifications and qualities, identified by sport management practitioners through an examination of paper credentials, that are desired in interviewees vying for selection into sport management internship positions. (GLR)

Monte Carlo study of a new I‐125 brachytherapy prototype seed with a ceramic radionuclide carrier and radiographic marker

PubMed Central

Paixão, Lucas; Santos, Ana Maria M.; dos Santos, Adriano Márcio; Grynberg, Suely Epsztein

2012-01-01

In prostate cancer treatment, there is an increasing interest in the permanent radioactive seeds implant technique. Currently, in Brazil, the seeds are imported with high prices, which prohibit their use in public hospitals. A ceramic matrix that can be used as a radioisotope carrier and radiographic marker was developed at our institution. The ceramic matrix is distinguished by the characteristic of maintaining the radioactive material uniformly distributed in its surface. In this work, Monte Carlo simulations were performed in order to assess the dose distributions generated by this prototype seed model, with the ceramic matrix encapsulated in titanium, in the same way as the commercial 6711 seed. The obtained data was assessed, as described in the TG‐43U1 report by the American Association of Physicists in Medicine, for two seed models: (1) the most used model 6711 source — for validation and comparison, and (2) for the prototype model with the ceramic matrix. The dosimetric parameters dose rate constant, Λ, radial dose function, gL(r), and anisotropy function, F(r,θ), were derived from simulations by the Monte Carlo method using the MCNP5 code. A Λ 0.992 (±2.33%) cGyh−1U−1 was found for the prototype model. In comparison with the 6711 model, a lower dose fall‐off on transverse axis was found, as well as a lower dose anisotropy for the radius r= 0.25 cm. In general, for all distances, the prototype seed model presents a slightly larger anisotropy between 0° ≤ Θ < 50° and anisotropy similar to the 6711 model for Θ ≥ 50°. The dosimetric characteristics of the prototype model presented in this study suggest that its use is feasible. Because of the model's characteristics, seeds of lower specific activity iodine might be necessary which, on the other hand, would help to reduce costs. However, it has to be emphasized that the proposed source is a prototype, and the required (AAPM prerequisites) experimental study and tolerance manufacturer values are pending for future studies. PACS numbers: 87.53.Jw, 87.55.K PMID:22584172

Managing Innovation and Change for Instructional Technology.

ERIC Educational Resources Information Center

Holznagel, Donald C.

1991-01-01

Introduces the term "orgware" and reviews the literature on managing technological innovation in instructional settings. Six areas of management concern are described, and advice on managing innovation and change is provided. (11 references) (GLR)

How Much Comprehensible Input Did Heinrich Schliemann Get?

ERIC Educational Resources Information Center

Krashen, Stephen D.

1991-01-01

Examines Heinrich Schliemann's method of acquiring a second language primarily by means of conscious learning. It is revealed that Schliemann probably obtained a great deal of comprehensible input in English. (nine references) (GLR)

Biomarkers to evaluate the effects of temperature and methanol on recombinant Pichia pastoris.

PubMed

Zepeda, Andrea B; Figueroa, Carolina A; Abdalla, Dulcineia S P; Maranhão, Andrea Q; Ulloa, Patricio H; Pessoa, Adalberto; Farías, Jorge G

2014-01-01

Pichia pastoris is methylotrophic yeast used as an efficient expression system for heterologous protein production. In order to evaluate the effects of temperature (10 and 30 °C) and methanol (1 and 3% (v/v)) on genetically-modified Pichia pastoris, different biomarkers were evaluated: Heat stress (HSF-1 and Hsp70), oxidative stress (OGG1 and TBARS) and antioxidant (GLR). Three yeast cultures were performed: 3X = 3% methanol-10 °C, 4X = 3% methanol-30 °C, and 5X = 1% methanol-10°C. The expression level of HIF-1α, HSF-1, HSP-70 and HSP-90 biomarkers were measured by Western blot and in situ detection was performed by immunocytochemistry. Ours results show that at 3% methanol -30 °C there is an increase of mitochondrial OGG1 (mtOGG1), Glutathione Reductase (GLR) and TBARS. In addition, there was a cytosolic expression of HSF-1 and HSP-70, which indicates a deprotection against nucleolar fragmentation (apoptosis). On the other hand, at 3% methanol -10 °C and 1% and at methanol -10 °C conditions there was nuclear expression of OGG1, lower levels of TBARS and lower expression of GLR, cytosolic expression of HSF-1 and nuclear expression HSP-70. In conclusion, our results suggest that 3% methanol-30 °C is a condition that induces a strong oxidative stress and risk factors of apoptosis in modified-genetically P. pastoris.

Biomarkers to evaluate the effects of temperature and methanol on recombinant Pichia pastoris

PubMed Central

Zepeda, Andrea B.; Figueroa, Carolina A.; Abdalla, Dulcineia S.P.; Maranhão, Andrea Q.; Ulloa, Patricio H.; Pessoa, Adalberto; Farías, Jorge G.

2014-01-01

Pichia pastoris is methylotrophic yeast used as an efficient expression system for heterologous protein production. In order to evaluate the effects of temperature (10 and 30 °C) and methanol (1 and 3% (v/v)) on genetically-modified Pichia pastoris, different biomarkers were evaluated: Heat stress (HSF-1 and Hsp70), oxidative stress (OGG1 and TBARS) and antioxidant (GLR). Three yeast cultures were performed: 3X = 3% methanol-10 °C, 4X = 3% methanol-30 °C, and 5X = 1% methanol-10°C. The expression level of HIF-1α, HSF-1, HSP-70 and HSP-90 biomarkers were measured by Western blot and in situ detection was performed by immunocytochemistry. Ours results show that at 3% methanol −30 °C there is an increase of mitochondrial OGG1 (mtOGG1), Glutathione Reductase (GLR) and TBARS. In addition, there was a cytosolic expression of HSF-1 and HSP-70, which indicates a deprotection against nucleolar fragmentation (apoptosis). On the other hand, at 3% methanol −10 °C and 1% and at methanol −10 °C conditions there was nuclear expression of OGG1, lower levels of TBARS and lower expression of GLR, cytosolic expression of HSF-1 and nuclear expression HSP-70. In conclusion, our results suggest that 3% methanol-30 °C is a condition that induces a strong oxidative stress and risk factors of apoptosis in modified-genetically P. pastoris. PMID:25242930

Money Does Matter Somewhere: A Reply to Hanushek.

ERIC Educational Resources Information Center

Hedges, Larry V.; And Others

1994-01-01

Replies to E. A. Hanushek's questioning of the validity of meta-analysis as used by the authors in analyzing resource allocation and its effects on improving student academic performance. Statistical analysis procedures are examined. (GLR)

Assessing L2 Competency in Early Immersion Classrooms.

ERIC Educational Resources Information Center

Weber, Sandra; Tardif, Claudette

1991-01-01

Reports on a study that explored the use of puppets and classroom-based interview protocols as a practical way for teachers and researchers to get feedback on young students' learning in second-language classrooms. (21 references) (GLR)

How to Talk to the Supernatural in Shakespeare.

ERIC Educational Resources Information Center

Yonglin, Yang

1991-01-01

Examines Shakespeare's use of thou forms to individual ghosts, witches, and spirits. The proposition is advanced that there is a role-governed rule in the use of this pronoun to individual supernatural beings. (31 references) (GLR)

How Do Evergreens Stay Ever-Green? Hands on Science.

ERIC Educational Resources Information Center

Kepler, Lynne

1993-01-01

Provides instructional techniques, using samples from evergreen trees, to explain to school children the concept of adaptation. The techniques help children develop skills in observation, classification, communication, inferring, and predicting. A teacher's reproducible is included. (GLR)

SU-F-T-50: Evaluation of Monte Carlo Simulations Performance for Pediatric Brachytherapy Dosimetry

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

Chatzipapas, C; Kagadis, G; Papadimitroulas, P

Purpose: Pediatric tumors are generally treated with multi-modal procedures. Brachytherapy can be used with pediatric tumors, especially given that in this patient population low toxicity on normal tissues is critical as is the suppression of the probability for late malignancies. Our goal is to validate the GATE toolkit on realistic brachytherapy applications, and evaluate brachytherapy plans on pediatrics for accurate dosimetry on sensitive and critical organs of interest. Methods: The GATE Monte Carlo (MC) toolkit was used. Two High Dose Rate (HDR) 192Ir brachytherapy sources were simulated (Nucletron mHDR-v1 and Varian VS2000), and fully validated using the AAPM and ESTROmore » protocols. A realistic brachytherapy plan was also simulated using the XCAT anthropomorphic computational model .The simulated data were compared to the clinical dose points. Finally, a 14 years old girl with vaginal rhabdomyosarcoma was modelled based on clinical procedures for the calculation of the absorbed dose per organ. Results: The MC simulations resulted in accurate dosimetry in terms of dose rate constant (Λ), radial dose gL(r) and anisotropy function F(r,θ) for both sources.The simulations were executed using ∼1010 number of primaries resulting in statistical uncertainties lower than 2%.The differences between the theoretical values and the simulated ones ranged from 0.01% up to 3.3%, with the largest discrepancy (6%) being observed in the dose rate constant calculation.The simulated DVH using an adult female XCAT model was also compared to a clinical one resulting in differences smaller than 5%. Finally, a realistic pediatric brachytherapy simulation was performed to evaluate the absorbed dose per organ and to calculate DVH with respect to heterogeneities of the human anatomy. Conclusion: GATE is a reliable tool for brachytherapy simulations both for source modeling and for dosimetry in anthropomorphic voxelized models. Our project aims to evaluate a variety of pediatric brachytherapy schemes using a population of pediatric phantoms for several pathological cases. This study is part of a project that has received funding from the European Union Horizon2020 research and innovation programme under the MarieSklodowska-Curiegrantagreement.No691203.The results published in this study reflect only the authors view and the Research Executive Agency (REA) and the European Commission is not responsible for any use that may be madeof the information it contains.« less

Cool Heads: Crisis Management for Administrators.

ERIC Educational Resources Information Center

Smiar, Nicholas P.

1992-01-01

Applies risk management models to child care administration. These models have been used by corporations to plan for crisis management. The formation of a crisis management policy and procedure is described, and features of effective communication during crises are outlined. (GLR)

The Quiet Health Care Revolution.

ERIC Educational Resources Information Center

Herzlinger, Regina

1994-01-01

Discusses how entrepreneurs have helped reduce costs in health care and examines the major changes in the health care system that are simultaneously lowering costs and increasing quality. The author then explains how current reform proposals might affect these entrepreneurial innovations. (GLR)

Literary and Electronic Hypertext: Borges, Criticism, Literary Research, and the Computer.

ERIC Educational Resources Information Center

Davison, Ned J.

1991-01-01

Examines what "hypertext" means to literary criticism on the one hand (i.e., intertextuality) and computing on the other, to determine how the two concepts may serve each other in a mutually productive way. (GLR)

The Comprehensible Output Hypothesis and Self-directed Learning: A Learner's Perspective.

ERIC Educational Resources Information Center

Liming, Yu

1990-01-01

Discusses the significance to language acquisition of pushing for comprehensible output. Three issues are examined: (1) comprehensible output and negative input, (2) comprehensible and incomprehensible output, and (3) comprehensible output and comprehensible input. (28 references) (GLR)

Computational methods in sequence and structure prediction

NASA Astrophysics Data System (ADS)

Lang, Caiyi

This dissertation is organized into two parts. In the first part, we will discuss three computational methods for cis-regulatory element recognition in three different gene regulatory networks as the following: (a) Using a comprehensive "Phylogenetic Footprinting Comparison" method, we will investigate the promoter sequence structures of three enzymes (PAL, CHS and DFR) that catalyze sequential steps in the pathway from phenylalanine to anthocyanins in plants. Our result shows there exists a putative cis-regulatory element "AC(C/G)TAC(C)" in the upstream of these enzyme genes. We propose this cis-regulatory element to be responsible for the genetic regulation of these three enzymes and this element, might also be the binding site for MYB class transcription factor PAP1. (b) We will investigate the role of the Arabidopsis gene glutamate receptor 1.1 (AtGLR1.1) in C and N metabolism by utilizing the microarray data we obtained from AtGLR1.1 deficient lines (antiAtGLR1.1). We focus our investigation on the putatively co-regulated transcript profile of 876 genes we have collected in antiAtGLR1.1 lines. By (a) scanning the occurrence of several groups of known abscisic acid (ABA) related cisregulatory elements in the upstream regions of 876 Arabidopsis genes; and (b) exhaustive scanning of all possible 6-10 bps motif occurrence in the upstream regions of the same set of genes, we are able to make a quantative estimation on the enrichment level of each of the cis-regulatory element candidates. We finally conclude that one specific cis-regulatory element group, called "ABRE" elements, are statistically highly enriched within the 876-gene group as compared to their occurrence within the genome. (c) We will introduce a new general purpose algorithm, called "fuzzy REDUCE1", which we have developed recently for automated cis-regulatory element identification. In the second part, we will discuss our newly devised protein design framework. With this framework we have developed a software package which is capable of designing novel protein structures at the atomic resolution. This software package allows us to perform protein structure design with a flexible backbone. The backbone flexibility includes loop region relaxation as well as a secondary structure collective mode relaxation scheme. (Abstract shortened by UMI.)

A Qualitative Study on the Socialization of Beginning Physical Education Teacher Educators.

ERIC Educational Resources Information Center

Williamson, Kay M.

1993-01-01

Examines the experiences of five female physical education teacher educators in their first positions as assistant professors in research-oriented universities. Data were collected using primarily qualitative methods. All participants reported experiencing role ambiguity and stress. (GLR)

Second Language Acquisition.

ERIC Educational Resources Information Center

McLaughlin, Barry; Harrington, Michael

1989-01-01

A distinction is drawn between representational and processing models of second-language acquisition. The first approach is derived primarily from linguistics, the second from psychology. Both fields, it is argued, need to collaborate more fully, overcoming disciplinary narrowness in order to achieve more fruitful research. (GLR)

Total Quality Management for Campus Facilities.

ERIC Educational Resources Information Center

Reynolds, Gary L.

1992-01-01

This article examines the total quality management (TQM) concept as it is applied to higher education campus facilities. Each of the fundamental principles of TQM are examined as follows: customer-centered orientation; leadership; improved communication; continuous improvement; accountability; and quality of life. (GLR)

Ask Dr. Sue: Center Directors Express These Health Concerns.

ERIC Educational Resources Information Center

Aronson, Susan S.

1991-01-01

A physician addresses three health concerns of child care center directors. She provides information about the increasing number of children with asthma problems, the exclusion of ill children from child care settings, and the increasing concern about lead poisoning. (GLR)

Save Money and the Planet: Make Your School Energy Efficient.

ERIC Educational Resources Information Center

Lewis, Eleanor J.; Weltman, Eric

1993-01-01

Examines ways in which schools can cut their energy costs. Suggestions are provided for making school lighting more efficient, conducting a life-cycle cost analysis to facilitate energy efficiency, and developing funding for implementing energy-efficient projects. (GLR)

Addressing Diversity: A Call for Action.

ERIC Educational Resources Information Center

Henderson, Ingeborg

1991-01-01

Suggests a series of steps that individuals in the foreign language profession can take to effectively address the issue of demographic changes in the U.S. college student populations and keeping foreign language learning a feasible discipline in the future. (26 references) (GLR)

Subjective Reactions of Rural University Students toward Different Varieties of Arabic.

ERIC Educational Resources Information Center

Hussein, Riyad F.; El-Ali, Nasser

1989-01-01

Investigates university students' attitudes toward different varieties of Arabic, including Modern Standard Arabic (MSA), Bedouin, Fallahi, and Madani. The highest rated variety was MSA, the lowest rated was Madani, and Bedouin was preferred over Madani as a colloquial variety. (GLR)

Double Exposure: The Politics of Feminist Materialist Ethnography.

ERIC Educational Resources Information Center

Roman, Leslie G.

1993-01-01

Describes a field study in which the researcher developed a feminist materialist alternative to the subject object dualism in ethnography; critiques the discourse of naturalistic ethnography and presents various political and ethical implications for forms of feminist and critical theory and praxis. (GLR)

Language Pathology.

ERIC Educational Resources Information Center

Fletcher, Paul

1989-01-01

Discusses the role of linguistics in the investigation of language disorders, focusing on the application of phonetics, descriptive grammatic frameworks, grammatical theory, and concepts from semantics and pragmatics to a variety of disorders and their remediation. Some trends and examples from the field of clinical linguistics are discussed. (GLR)

Transdermal Nicotine for Smoking Cessation.

ERIC Educational Resources Information Center

Hughes, John R.; Glaser, Mitchell

1993-01-01

Discusses the use of transdermal nicotine (TN) in smoking cessation and its value as an effective procedure. The article reveals that, compared to a placebo, TN has double the quit rate percentages, and less than 5% of smokers quit TN due to side effects. (GLR)

Grimm's Law Revisited: A Case for Natural, Typological Phonology.

ERIC Educational Resources Information Center

Caflisch, Jacob, Sr.

1990-01-01

Reviews and comments on the major points made in Albert Gessman's paper, "Grimm's Law: Fact or Myth?" Through the evaluation of the paper's 13 points, several ideas are pointed out that are believed to be crucial to Gessman's arguments. (29 references) (GLR)

Burnout in Teachers of Young Children.

ERIC Educational Resources Information Center

Townley, Kim F.; And Others

1991-01-01

Assessed the relationship of selected personal and job-related variables to burnout in teachers of young children. The Maslach Burnout Inventory and a questionnaire were administered to 363 day care teachers. Burnout and competence were identified as factors supporting the concept that burnout is multidimensional. (Author/GLR)

Psychoneuroimmunology in Health Education.

ERIC Educational Resources Information Center

Hanson, Carl

1992-01-01

Studies suggest that stress, emotions, personality, and cognition can affect the immune system's response to disease. This paper argues the need for psychoneuroimmunology to be taught in health education courses and provides a brief overview of research showing the link between the mind and the immune system. (GLR)

A dual-mode generalized likelihood ratio approach to self-reorganizing digital flight control system design

NASA Technical Reports Server (NTRS)

Bueno, R.; Chow, E.; Gershwin, S. B.; Willsky, A. S.

1975-01-01

The research is reported on the problems of failure detection and reliable system design for digital aircraft control systems. Failure modes, cross detection probability, wrong time detection, application of performance tools, and the GLR computer package are discussed.

Rhythmicity, Sequence and Syncrony of English and Japanese Face-to-Face Conversation.

ERIC Educational Resources Information Center

Hayashi, Reiko

1990-01-01

Investigates the interactional rhythmicity among a group of four people and presents a new analytic model involving two parameters, floor and time. The model is used to further investigate the emic meaning of interactional rhythm and cross-cultural differences. (47 references) (GLR)

Menopause and Physical Activity: What Is the Relationship?

ERIC Educational Resources Information Center

Lutter, Judy Mahle; And Others

1993-01-01

Examines the results of a 1991 pilot study of the characteristics of the menopausal experience for women between the ages of 45 and 55. Specific items reported are physical health data and perceptions of factors affecting health status (diet, health characteristics, stress factors, and life changes). (GLR)

Leisure Today--A Society Growing Older: Its Implications for Leisure.

ERIC Educational Resources Information Center

Foret, Claire M.; And Others

1993-01-01

Contains 10 articles addressing the aging of U.S. society and its impact on the leisure industry. Some topics are delivering of leisure services, leisure awareness and education, quality of life programs, group travel programs, ethnic group considerations, enhancing leisure participation, and fitness programming. (GLR)

Language and Aging.

ERIC Educational Resources Information Center

Kemper, Susan; Anagnopoulos, Cheryl

1989-01-01

Reviews the effects of aging on language usage focusing on three areas of exploration: (1) changes in language in relation to changes in other cognitive abilities, (2) the linguistic consequences of normal aging versus those of dementia and aphasia, and (3) age-group differences in patterns of conversational interaction. (67 references) (GLR)

Constructivism, Socioculturalism, and Popper's World 3.

ERIC Educational Resources Information Center

Bereiter, Carl

1994-01-01

Examines the concept of learning from both constructivist and sociocultural perspectives and introduces a third perspective based on K. R. Popper's philosophy of science. It is argued that constructivism cannot adequately account for the immaterial objects that Popper located in his World 3--abstract mathematical and scientific objects. (GLR)

Machiavelli and the Chief Resident.

ERIC Educational Resources Information Center

Raviglione, Mario C.

1990-01-01

Precepts from Machiavelli's "The Prince" are used in giving advice to chief residents on how to balance their responsibilities in working for the welfare of both the housestaff and the institution. Subject discussions include the difficulties of introducing change, setting good examples, and supervising former colleagues and peers. (GLR)

Behavior Management Techniques in Predoctoral and Postdoctoral Pediatric Dentistry Programs.

ERIC Educational Resources Information Center

Belanger, Gary K.; Tilliss, Terri S.

1993-01-01

A survey determined the extent to which selected pediatric dental behavior management techniques are taught both didactically and clinically in 46 predoctoral and 45 postdoctoral programs. Results and trends are reported within the four categories of sedation, restraint, parental presence, and communications behavior management. (GLR)

An Intervention Model of Constructive Conflict Resolution and Cooperative Learning.

ERIC Educational Resources Information Center

Zhang, Quanwu

1994-01-01

Tests an intervention model of constructive conflict resolution (CCR) and cooperative learning in three urban high schools. Findings show that improvements in CCR increased social support and decreased victimization for the students. These changes improved student's attitudes, self-esteem, interpersonal relations, and academic achievement. (GLR)

Conflict Resolution, Diversity, and Social Justice.

ERIC Educational Resources Information Center

Townley, Annette

1994-01-01

Briefly explores the issue of conflict resolution (CR) in education; the introduction of CR into the public schools; and whether CR processes such as mediation meet the needs of nondominant groups. It also introduces several articles that discuss specific approaches to the development and implementation of CR programs in schools. (GLR)

Fitness Load and Exercise Time in Secondary Physical Education Classes.

ERIC Educational Resources Information Center

Li, Xiao Jun; Dunham, Paul, Jr.

1993-01-01

Investigates the effect of secondary school physical education on fitness load: the product of the mean heart rate above threshold (144 bpm) and the time duration of heart rate above that threshold. Highly and moderately skilled students achieved fitness load more frequently than their lower skilled colleagues. (GLR)

Language as a Barrier to Communication between the Classes in Rosario Castellanos's "La tregua" and Jose Revueltas's "El lenguaje de nadie."

ERIC Educational Resources Information Center

Duncan, Cynthia

1991-01-01

Examines two Spanish-language short stories that use language as a codifying system for examining false institutions, antiquated prejudices, and iron-cal hierarchies that have been erected in the name of Mexican culture. (12 references) (GLR)

The ABCs of Activity-Based Costing: A Cost Containment and Reallocation Tool.

ERIC Educational Resources Information Center

Turk, Frederick J.

1992-01-01

This article describes activity-based costing (ABC) and how this tool may help management understand the costs of major activities and identify possible alternatives. Also discussed are the traditional costing systems used by higher education and ways of applying ABC to higher education. (GLR)

On Men Mentoring Women: Then and Now.

ERIC Educational Resources Information Center

Kronik, John W.

1990-01-01

Suggests that mentoring varies greatly in degree and nature of involvement, and can be perilous and abusive, particularly between male mentors and female subordinates. For the mentor system to work, the mentor/subordinate association must be based on mutual respect and allow for subtle and beneficial exercise of power. (GLR)

Southern pine veneer laminates at various moduli of elasticity

Treesearch

George E. Woodson

1972-01-01

Modulus of rigidity (GLT) of veneer laminates was shown to be unrelated to dynamic modulus of elasticity (Ed) of single veneers and also, within the range of samples tested, unrelated to specific gravity. Values determined by flexure test (GLR) were consistent with those from standard plate shear...

The Use of Molecular Modeling Programs in Medicinal Chemistry Instruction.

ERIC Educational Resources Information Center

Harrold, Marc W.

1992-01-01

This paper describes and evaluates the use of a molecular modeling computer program (Alchemy II) in a pharmaceutical education program. Provided are the hardware requirements and basic program features as well as several examples of how this program and its features have been applied in the classroom. (GLR)

ESL Student Bias in Instructional Evaluation.

ERIC Educational Resources Information Center

Wennerstrom, Ann K.; Heiser, Patty

1992-01-01

Reports on a statistical analysis of English-as-a-Second-Language (ESL) student evaluations of teachers in two large programs. Results indicated a systematic bias occurs in ESL student evaluations, raising issues of fairness in the use of student evaluations of ESL teachers for purposes of personnel decisions. (21 references) (GLR)

Assessing the Age of Goethe in the Undergraduate Curriculum: A Report.

ERIC Educational Resources Information Center

Larkin, Edward T.

1991-01-01

Presents information on how and what is taught in courses on the "Age of Goethe." Two appendices are presented that list the institutions responding to a questionnaire concerning the teaching of this course and the less familiar texts of the period that are treated by some instructors. (GLR)

The Historical Context of the Single-Sex Schooling Debate among African Americans.

ERIC Educational Resources Information Center

McCluskey, Audrey T.

1993-01-01

Argues that similarities in the socioeconomic and racial climate and the attempt to refute negative gender and race-inspired images were circumstances that were present in the emergence of single-sex schools for blacks. It examines the worth of such schools in affecting positive social change. (GLR)

Components of Understanding in Proportional Reasoning: A Fuzzy Set Representation of Developmental Progressions.

ERIC Educational Resources Information Center

Moore, Colleen F.; And Others

1991-01-01

Examined the development of proportional reasoning by means of a temperature mixture task. Results show the importance of distinguishing between intuitive knowledge and formal computational knowledge of proportional concepts. Provides a new perspective on the relation of intuitive and computational knowledge during development. (GLR)

Peer Rejection in Middle School: Subgroup Differences in Behavior, Loneliness, and Interpersonal Concerns.

ERIC Educational Resources Information Center

Parkhurst, Jennifer T.; Asher, Steven R.

1992-01-01

Studied patterns of behavior and emotional response associated with peer rejection in early adolescence. Obtained data on seventh and eighth graders' loneliness, social dissatisfaction, and concerns. The combination of aggressiveness and submissiveness with low levels of prosocial behavior was associated with peer rejection. (GLR)

Light-driven Na + pump from Gillisia limnaea: A high-affinity Na + binding site is formed transiently in the photocycle

DOE PAGES

Balashov, Sergei P.; Imasheva, Eleonora S.; Dioumaev, Andrei K.; ...

2014-11-06

A group of microbial retinal proteins most closely related to the proton pump xanthorhodopsin has a novel sequence motif and a novel function. Instead of, or in addition to, proton transport, they perform light-driven sodium ion transport, as reported for one representative of this group (KR2) from Krokinobacter. In this paper, we examine a similar protein, GLR from Gillisia limnaea, expressed in Escherichia coli, which shares some properties with KR2 but transports only Na +. The absorption spectrum of GLR is insensitive to Na + at concentrations of ≤3 M. However, very low concentrations of Na + cause profound differencesmore » in the decay and rise time of photocycle intermediates, consistent with a switch from a “Na +-independent” to a “Na +-dependent” photocycle (or photocycle branch) at ~60 μM Na +. The rates of photocycle steps in the latter, but not the former, are linearly dependent on Na + concentration. This suggests that a high-affinity Na + binding site is created transiently after photoexcitation, and entry of Na + from the bulk to this site redirects the course of events in the remainder of the cycle. A greater concentration of Na + is needed for switching the reaction path at lower pH. The data suggest therefore competition between H + and Na + to determine the two alternative pathways. The idea that a Na + binding site can be created at the Schiff base counterion is supported by the finding that upon perturbation of this region in the D251E mutant, Na + binds without photoexcitation. Furthermore, binding of Na+ to the mutant shifts the chromophore maximum to the red like that of H +, which occurs in the photocycle of the wild type.« less

Inhibiting effects of Streptococcus salivarius on competence-stimulating peptide-dependent biofilm formation by Streptococcus mutans.

PubMed

Tamura, S; Yonezawa, H; Motegi, M; Nakao, R; Yoneda, S; Watanabe, H; Yamazaki, T; Senpuku, H

2009-04-01

The effects of Streptococcus salivarius on the competence-stimulating peptide (CSP)-dependent biofilm formation by Streptococcus mutans were investigated. Biofilms were grown on 96-well microtiter plates coated with salivary components in tryptic soy broth without dextrose supplemented with 0.25% sucrose. Biofilm formations were stained using safranin and quantification of stained biofilms was performed by measuring absorbance at 492 nm. S. mutans formed substantial biofilms, whereas biofilms of S. salivarius were formed poorly in the medium conditions used. Furthermore, in combination cultures, S. salivarius strongly inhibited biofilm formation when cultured with S. mutans. This inhibition occurred in the early phase of biofilm formation and was dependent on inactivation of the CSP of S. mutans, which is associated with competence, biofilm formation, and antimicrobial activity of the bacterium, and is induced by expression of the comC gene. Comparisons between the S. mutans clinical strains FSC-3 and FSC-3DeltaglrA in separate dual-species cultures with S. salivarius indicated that the presence of the bacitracin transport ATP-binding protein gene glrA caused susceptibility to inhibition of S. mutans biofilm formation by S. salivarius, and was also associated with the regulation of CSP production by com gene-dependent quorum sensing systems. It is considered that regulation of CSP by glrA in S. mutans and CSP inactivation by S. salivarius are important functions for cell-to-cell communication between biofilm bacteria and oral streptococci such as S. salivarius. Our results provide useful information for understanding the ecosystem of oral streptococcal biofilms, as well as the competition between and coexistence of multiple species in the oral cavity.

Estrogen in cycling rats alters gene expression in the temporomandibular joint, trigeminal ganglia and trigeminal subnucleus caudalis/upper cervical cord junction

PubMed Central

Puri, Jyoti; Bellinger, Larry L.; Kramer, Phillip R.

2011-01-01

Females report temporomandibular joint (TMJ) pain more than men and studies suggest estrogen modulates this pain response. Our goal in this study was to determine genes that are modulated by physiological levels of 17β-estradiol that could have a role in TMJ pain. To complete this goal, saline or complete Freund’s adjuvant was injected in the TMJ when plasma 17β-estradiol was low or when it was at a high proestrus level. TMJ, trigeminal ganglion and trigeminal subnucleus caudalis/upper cervical cord junction (Vc/C1–2) tissues were isolated from the treated rats and expression of 184 genes was quantitated in each tissue using real time PCR. Significant changes in the amount of specific transcripts were observed in the TMJ tissues, trigeminal ganglia and Vc/C1–2 region when comparing rats with high and low estrogen. GABA A receptor subunit α6 (Gabra6) and the glycine receptor α2 (Glra2) were two genes of interest because of their direct function in neuronal activity and a greater than 29 fold increase in the trigeminal ganglia was observed in proestrus rats with TMJ inflammation. Immunohistochemical studies showed that Gabrα6 and Glrα2 neuronal and not glial expression increased when comparing rats with high and low estrogen. Estrogen receptors α and β are present in neurons of the trigeminal ganglia, whereby 17β-estradiol can alter expression of Gabrα6 and Glrα2. Also, estrogen receptor α (ERα) but not ERβ was observed in satellite glial cells of the trigeminal ganglia. These results demonstrate that genes associated with neurogenic inflammation or neuronal excitability were altered by changes in the concentration of 17β-estradiol. PMID:21321935

School Board Elections: A Study of Citizen Voting Patterns.

ERIC Educational Resources Information Center

Townley, Arthur J.; And Others

1994-01-01

Compares voter turnout in California school board elections when elections were scheduled in even-numbered years rather than odd-numbered years. Findings from selected school districts since 1985 show significant differences in voter turnout depending on the year: 43.85% voter turnout occurred in even-numbered years compared to 20.79% in odd. (GLR)

Incidence of Verbal Comparisons in Beginners' Books and in Metaphor Comprehension Research: A Search for Ecological Validity.

ERIC Educational Resources Information Center

Broderick, Victor

1992-01-01

Classifies explicit verbal comparisons in 53 popular children's books both syntactically and semantically. Comparison types found in these books were contrasted with comparisons used as comprehension stimuli in extant developmental research. Implications for the design of future stimulus sets are discussed. (17 references) (GLR)

Why Not Charter School Boards?

ERIC Educational Resources Information Center

Schlechty, Phillip C.; Cole, Robert W.

1994-01-01

Argues that for a community to maintain control over its public schools it must make the school board accountable for the performance of the school and all of its employees. The authors suggest a new approach to school-board elections, addresses key elements needed in state legislation, and explains the existing roadblocks to change. (GLR)

High-Court Ruling Transforms Battles over Desegregation at Colleges in 19 States.

ERIC Educational Resources Information Center

Jaschik, Scott

1992-01-01

This article examines the impact on institutions of higher education, particularly in 19 southern and border states, from the U.S. Supreme Court's decision on how the states must show they have removed vestiges of past segregation. Its impact on affirmative action, admissions criteria, and redistricting are examined. (GLR)

Teaching Congestive Heart Failure to Doctor of Pharmacy Students.

ERIC Educational Resources Information Center

Parker, Robert B.

1992-01-01

This paper summarizes a lecture given to pharmacy students that emphasizes the pathophysiologic mechanisms causing congestive heart failure and the effects of drugs on these mechanisms. The approach shows the importance of drug therapy in this disorder and how this knowledge can improve patient care. An appendix provides a case study. (GLR)

Discourse Features of Written Mexican Spanish: Current Research in Contrastive Rhetoric and Its Implications.

ERIC Educational Resources Information Center

Montano-Harmon, Maria Rosario

1991-01-01

Analyzes discourse features of compositions written in Spanish by secondary school students in Mexico, draws comparisons with those written in English by Anglo-American students in the United States, and discusses the implications of the results for teaching and evaluating composition skills in Spanish language programs. (29 references) (GLR)

Use of MathCAD in a Pharmacokinetics Course for PharmD Students.

ERIC Educational Resources Information Center

Sullivan, Timothy J.

1992-01-01

This paper describes the application of the Student Edition of MathCAD as a computational aid in an introductory graduate level pharmacokinetics course. The program allows the student to perform mathematical calculations and analysis on a computer screen. The advantages and disadvantages of this application are discussed. (GLR)

Blood Brothers: Albert and Allen Hughes in the Belly of the Hollywood Beast.

ERIC Educational Resources Information Center

Gates, Henry Louis, Jr.

1994-01-01

Recounts an interview with the Hughes brothers, who are twin black men who produced the film "Menace 2 Society," which is a film about urban delinquency and crime among black adolescents. Their comments include thoughts on racism, media stereotyping, being black in America, and their experiences with Hollywood. (GLR)

Promoting the Development of Mentor Teachers: Theory and Research Programs Using Guided Reflection.

ERIC Educational Resources Information Center

Reiman, Alan J.; Thies-Sprinthall, Lois

1993-01-01

Describes theory and a research program that uses guided reflection to promote the development of mentor teachers. Significant findings from a quasi-experimental study and a replication study are presented. The paper can assist teacher educators, policymakers, and school personnel who are searching for a teacher induction model. (GLR)

Self and Peer Evaluation of Writing in the Interactive ESL Classroom: An Exploratory Study.

ERIC Educational Resources Information Center

Rothschild, Dennie; Klingenberg, Felicia

1990-01-01

Investigates self- and peer evaluation of writing in the English-as-a-Second-Language classroom. The investigation is examined in two parts: (1) adapting and implementing an appropriate evaluation scale, and (2) studying the various end-of-term effects use of the scale had on students. (17 references) (GLR)

Suppression of surface-originated gate lag by a dual-channel AlN/GaN high electron mobility transistor architecture

NASA Astrophysics Data System (ADS)

Deen, David A.; Storm, David F.; Scott Katzer, D.; Bass, R.; Meyer, David J.

2016-08-01

A dual-channel AlN/GaN high electron mobility transistor (HEMT) architecture is demonstrated that leverages ultra-thin epitaxial layers to suppress surface-related gate lag. Two high-density two-dimensional electron gas (2DEG) channels are utilized in an AlN/GaN/AlN/GaN heterostructure wherein the top 2DEG serves as a quasi-equipotential that screens potential fluctuations resulting from distributed surface and interface states. The bottom channel serves as the transistor's modulated channel. Dual-channel AlN/GaN heterostructures were grown by molecular beam epitaxy on free-standing hydride vapor phase epitaxy GaN substrates. HEMTs fabricated with 300 nm long recessed gates demonstrated a gate lag ratio (GLR) of 0.88 with no degradation in drain current after bias stressed in subthreshold. These structures additionally achieved small signal metrics ft/fmax of 27/46 GHz. These performance results are contrasted with the non-recessed gate dual-channel HEMT with a GLR of 0.74 and 82 mA/mm current collapse with ft/fmax of 48/60 GHz.

Deglobalization and Its Discontents in Interconnected Regional Food, Energy, and Water Systems

NASA Astrophysics Data System (ADS)

Bielicki, J. M.; Irwin, E.; Bakshi, B.; Cai, Y.; Jackson-Smith, D.; Martin, J.; Randall, A.; Sheldon, I.; Wilson, R. S.; Fiksel, J.

2017-12-01

Increased trade has generated substantial wealth in the United States over the past 50 years, but these gains have also been accompanied by losses in manufacturing jobs, growing inequality, environmental impacts abroad, and growing support to limit U.S. integration with global markets. A policy shift towards deglobalization would alter global flows of resources and goods and impact food, energy, and water (FEW) resources and the well-being of U.S. FEW producers and consumers. This project examines the potential effects of deglobalization on the sustainability of regional FEW systems and well-being of FEW producers and consumers in the United States under various physical and policy situations. We develop a Dynamic Regional Food, Energy, and Water Systems (DR-FEWS) modeling framework that considers how uncertain changes in environmental, economic, or policy conditions at a national or global scale may influence how farmers produce food and energy, and the implications for regional land, energy, and water resources, food and energy markets, and water quality. We apply DR-FEWS to five states in the Great Lakes region (GLR) of the United States (IL, IN, MI, OH, and WI) and account for local heterogeneities using individual farmer behavioral and spatially explicit land data from the Maumee River basin. DR-FEWS is applied to a set of baseline and alternative deglobalization scenarios to evaluate the influence of various environmental, economic, and policy conditions and uncertainties on the sustainability of the GLR. We will also engage local and regional stakeholders to improve the models, develop deglobalization scenarios, and advance sustainability metrics by comparing different valued-based and physical-based sustainability criteria. In so doing, this research will generate important innovations in how scientific knowledge is created, disseminated, and applied to the management of regional FEWS in the United States with specific application to the GLR.

Effectiveness of the May 2005 rural demonstration program and the Click It or Ticket mobilization in the Great Lakes region : first year results

DOT National Transportation Integrated Search

2007-04-01

NHTSAs Great Lakes Region (GLR) implemented a Rural Demonstration Program (RDP) prior to the May 2005 Click It or Ticket (CIOT) mobilization with the goal of increasing seat belt usage in rural areas. Paid media was used to notify rural residents ...

ASL or Contact Signing: Issues of Judgment.

ERIC Educational Resources Information Center

Lucas, Ceil; Valli, Clayton

1991-01-01

Reports on one aspect of an ongoing study of language contact in the American deaf community. The ultimate goal of the study is a linguistic description of contact signing and a reexamination of claims that it is a pidgin. Patterns of language use are reviewed and the role of demographic information in judgments is examined. (29 references) (GLR)

Marketing in Higher Education: A Stage Model Concerning Where It's Been and Where It's Going.

ERIC Educational Resources Information Center

Simmons, Jeanne M.; Laczniak, Gene R.

1992-01-01

The ideas of Williford (1987) are used to propose a four-stage model describing the evolution of marketing in many colleges and universities. It elaborates on the thinking endemic to strategic marketing management and frameworks drawn from business marketing which will likely become more prominent in higher education. (Author/GLR)

Beyond Competence and Performance: Children's Class Inclusion Strategies, Superordinate Class Cues, and Verbal Justifications.

ERIC Educational Resources Information Center

Chapman, Michael; McBride, Michelle L.

1992-01-01

Children of 4 to 10 years of age were given 2 class inclusion tasks. Younger children's performance was inflated by guessing. Scores were higher in the marked task than in the unmarked task as a result of differing rates of inclusion logic. Children's verbal justifications closely approximated estimates of their true competence. (GLR)

Confronting the Moral Frames of Popular Film: Young People Respond to Historical Revisionism.

ERIC Educational Resources Information Center

Seixas, Peter

1994-01-01

Inquires about the moral dimensions of high school students' understanding of two films' representations of the past. The film "Dances with Wolves" was viewed as a transparent window on the 19th-century West, but no moral frame was examined. "The Searchers" was viewed as a deeply flawed product of the 1950s. (GLR)

The Processing Behaviours of Adult Second Language Learners and Their Relationship to Second Language Proficiency.

ERIC Educational Resources Information Center

Mangubhai, Francis

1991-01-01

Investigated the behaviors for processing language input demonstrated by five adults beginning to learn Hindi as a second language through the Total Physical Response method. The study suggests that, when adult learners are provided with comprehensive input, they engage in a variety of behaviors to extract meaning from it. (73 references) (GLR)

Using Heart Rate Monitors in Research on Fitness Levels of Children in Physical Education.

ERIC Educational Resources Information Center

Strand, Brad; Reeder, Steve

1993-01-01

Demonstrates the use of heart rate monitors (HRMs) in fitness research and examines heart rate intensity levels of middle school students while they participated in a variety of physical education activities throughout a school year. Research shows the HRM has considerable potential in assessing fitness achievements in school-age children. (GLR)

The Effects of Leisure Education on Factors Contributing to the Successful Transition of Students with Mental Retardation from School to Adult Life.

ERIC Educational Resources Information Center

Bedini, Leandra A.; And Others

1993-01-01

To determine the worth of leisure education for adolescents with mental retardation, this study tested a model program in the public schools of Wake County, North Carolina. Findings indicated positive changes in behaviors and attitudes. Limitations, implications, and recommendations are also discussed. (GLR)

Modulation of the antioxidant/pro-oxidant balance, cytotoxicity and antiviral actions of grape seed extracts.

PubMed

Ignea, Codruţa; Dorobanţu, Cristina Mihaela; Mintoff, Christopher Paul; Branza-Nichita, Norica; Ladomery, Michael R; Kefalas, Panagiotis; Chedea, Veronica Sanda

2013-12-15

Grape seed extracts (GSEs) were investigated in yeast cells harbouring defects in their antioxidant system (regarding the cellular growth and growth recovery from H2O2 insult). GSEs antioxidant activity was detected in wild-type and mutant strains Δcta1, Δgsh1 and Δoye2glr1, while pro-oxidant activity in Δsod1 cells was seen. Assessment of proliferation of prostate cancer PC3 and HBV-replicating HepG2 2.2.15 cells treated with GSEs has shown higher cytotoxicity of red grape seed extract (RW) than white grape seed extract (WW) subjective to dose and period of administration. No antiviral effect was detected by measuring the secreted virion particles in HepG2 2.2.15 cells treated with GSEs. The GSEs play a dual antioxidant/pro-oxidant role in vivo according with the cellular antioxidant system deficiencies and exhibit cytotoxic properties in PC3 and HepG2 2.2.15 cell lines, but no antiviral action against HBV. Copyright © 2013 Elsevier Ltd. All rights reserved.

Episcleral eye plaque dosimetry comparison for the Eye Physics EP917 using Plaque Simulator and Monte Carlo simulation

PubMed Central

Amoush, Ahmad; Wilkinson, Douglas A.

2015-01-01

This work is a comparative study of the dosimetry calculated by Plaque Simulator, a treatment planning system for eye plaque brachytherapy, to the dosimetry calculated using Monte Carlo simulation for an Eye Physics model EP917 eye plaque. Monte Carlo (MC) simulation using MCNPX 2.7 was used to calculate the central axis dose in water for an EP917 eye plaque fully loaded with 17 IsoAid Advantage  125I seeds. In addition, the dosimetry parameters Λ, gL(r), and F(r,θ) were calculated for the IsoAid Advantage model IAI‐125  125I seed and benchmarked against published data. Bebig Plaque Simulator (PS) v5.74 was used to calculate the central axis dose based on the AAPM Updated Task Group 43 (TG‐43U1) dose formalism. The calculated central axis dose from MC and PS was then compared. When the MC dosimetry parameters for the IsoAid Advantage  125I seed were compared with the consensus values, Λ agreed with the consensus value to within 2.3%. However, much larger differences were found between MC calculated gL(r) and F(r,θ) and the consensus values. The differences between MC‐calculated dosimetry parameters are much smaller when compared with recently published data. The differences between the calculated central axis absolute dose from MC and PS ranged from 5% to 10% for distances between 1 and 12 mm from the outer scleral surface. When the dosimetry parameters for the  125I seed from this study were used in PS, the calculated absolute central axis dose differences were reduced by 2.3% from depths of 4 to 12 mm from the outer scleral surface. We conclude that PS adequately models the central dose profile of this plaque using its defaults for the IsoAid model IAI‐125 at distances of 1 to 7 mm from the outer scleral surface. However, improved dose accuracy can be obtained by using updated dosimetry parameters for the IsoAid model IAI‐125  125I seed. PACS number: 87.55.K‐ PMID:26699577

Integrated detection, estimation, and guidance in pursuit of a maneuvering target

NASA Astrophysics Data System (ADS)

Dionne, Dany

The thesis focuses on efficient solutions of non-cooperative pursuit-evasion games with imperfect information on the state of the system. This problem is important in the context of interception of future maneuverable ballistic missiles. However, the theoretical developments are expected to find application to a broad class of hybrid control and estimation problems in industry. The validity of the results is nevertheless confirmed using a benchmark problem in the area of terminal guidance. A specific interception scenario between an incoming target with no information and a single interceptor missile with noisy measurements is analyzed in the form of a linear hybrid system subject to additive abrupt changes. The general research is aimed to achieve improved homing accuracy by integrating ideas from detection theory, state estimation theory and guidance. The results achieved can be summarized as follows. (i) Two novel maneuver detectors are developed to diagnose abrupt changes in a class of hybrid systems (detection and isolation of evasive maneuvers): a new implementation of the GLR detector and the novel adaptive- H0 GLR detector. (ii) Two novel state estimators for target tracking are derived using the novel maneuver detectors. The state estimators employ parameterized family of functions to described possible evasive maneuvers. (iii) A novel adaptive Bayesian multiple model predictor of the ballistic miss is developed which employs semi-Markov models and ideas from detection theory. (iv) A novel integrated estimation and guidance scheme that significantly improves the homing accuracy is also presented. The integrated scheme employs banks of estimators and guidance laws, a maneuver detector, and an on-line governor; the scheme is adaptive with respect to the uncertainty affecting the probability density function of the filtered state. (v) A novel discretization technique for the family of continuous-time, game theoretic, bang-bang guidance laws is introduced. The performance of the novel algorithms is assessed for the scenario of a pursuit-evasion engagement between a randomly maneuvering ballistic missile and an interceptor. Extensive Monte Carlo simulations are employed to evaluate the main statistical properties of the algorithms. (Abstract shortened by UMI.)

Construct Validity of Fluency and Implications for the Factorial Structure of Memory

ERIC Educational Resources Information Center

Jewsbury, Paul A.; Bowden, Stephen C.

2017-01-01

Fluency is an important construct in clinical assessment and in cognitive taxonomies. In the Cattell-Horn-Carroll (CHC) model, Fluency is represented by several narrow factors that form a subset of the long-term memory encoding and retrieval (Glr) broad factor. The CHC broad classification of Fluency was evaluated in five data sets, and the CHC…

Revisiting the Relations between the WJ-IV Measures of Cattell-Horn-Carroll (CHC) Cognitive Abilities and Reading Achievement during the School-Age Years

ERIC Educational Resources Information Center

Cormier, Damien C.; McGrew, Kevin S.; Bulut, Okan; Funamoto, Allyson

2017-01-01

This study examined associations between broad cognitive abilities (Fluid Reasoning [Gf], Short-Term Working Memory [Gwm], Long-Term Storage and Retrieval [Glr], Processing Speed [Gs], Comprehension-Knowledge [Gc], Visual Processing [Gv], and Auditory Processing [Ga]) and reading achievement (Basic Reading Skills, Reading Rate, Reading Fluency,…

Display Rules for Anger and Aggression in School-Age Children.

ERIC Educational Resources Information Center

Underwood, Marion K.; And Others

1992-01-01

Two studies examined the development of display rules for anger and the relationship between the use of display rules for anger and aggressiveness as rated by school peers. Findings indicate that the phenomenon of display rules for anger is complex and depends on the way display rules are defined and the age and gender of the subjects. (GLR)

Dopamine Modulation of Avoidance Behavior in Caenorhabditis elegans Requires the NMDA Receptor NMR-1

PubMed Central

Baidya, Melvin; Genovez, Marx; Torres, Marissa; Chao, Michael Y.

2014-01-01

The nematode C. elegans utilizes a relatively simple neural circuit to mediate avoidance responses to noxious stimuli such as the volatile odorant octanol. This avoidance behavior is modulated by dopamine. cat-2 mutant animals that are deficient in dopamine biosynthesis have an increased response latency to octanol compared to wild type animals, and this defect can be fully restored with the application of exogenous dopamine. Because this avoidance behavior is mediated by glutamatergic signaling between sensory neurons and premotor interneurons, we investigated the genetic interactions between dopaminergic signaling and ionotropic glutamate receptors. cat-2 mutant animals lacking either the GLR-1 or GLR-2 AMPA/kainate receptors displayed an increased response latency to octanol, which could be restored via exogenous dopamine. However, whereas cat-2 mutant animals lacking the NMR-1 NMDA receptor had increased response latency to octanol they were insensitive to exogenous dopamine. Mutants that lacked both AMPA/kainate and NMDA receptors were also insensitive to exogenous dopamine. Our results indicate that dopamine modulation of octanol avoidance requires NMR-1, consistent with NMR-1 as a potential downstream signaling target for dopamine. PMID:25089710

Suppression of surface-originated gate lag by a dual-channel AlN/GaN high electron mobility transistor architecture

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

Deen, David A., E-mail: david.deen@alumni.nd.edu; Storm, David F.; Scott Katzer, D.

A dual-channel AlN/GaN high electron mobility transistor (HEMT) architecture is demonstrated that leverages ultra-thin epitaxial layers to suppress surface-related gate lag. Two high-density two-dimensional electron gas (2DEG) channels are utilized in an AlN/GaN/AlN/GaN heterostructure wherein the top 2DEG serves as a quasi-equipotential that screens potential fluctuations resulting from distributed surface and interface states. The bottom channel serves as the transistor's modulated channel. Dual-channel AlN/GaN heterostructures were grown by molecular beam epitaxy on free-standing hydride vapor phase epitaxy GaN substrates. HEMTs fabricated with 300 nm long recessed gates demonstrated a gate lag ratio (GLR) of 0.88 with no degradation in drain currentmore » after bias stressed in subthreshold. These structures additionally achieved small signal metrics f{sub t}/f{sub max} of 27/46 GHz. These performance results are contrasted with the non-recessed gate dual-channel HEMT with a GLR of 0.74 and 82 mA/mm current collapse with f{sub t}/f{sub max} of 48/60 GHz.« less

The Effective Integration of the ICGLR Towards Sustainable Security and Economic Development in the GLR of Africa

DTIC Science & Technology

2012-06-08

political stability and absence of violence, government effectiveness, and control of corruption (World Bank Institute 2010). These aggregates are...Accountability Political stability and absence of violence Government Effectiveness Control of Corruption Period in Years 2007-2010 in % Period in...of political stability and levels of violence, voice and accountability, government effectiveness, and control of corruption. The assessment goes

On Restructurable Control System Theory

NASA Technical Reports Server (NTRS)

Athans, M.

1983-01-01

The state of stochastic system and control theory as it impacts restructurable control issues is addressed. The multivariable characteristics of the control problem are addressed. The failure detection/identification problem is discussed as a multi-hypothesis testing problem. Control strategy reconfiguration, static multivariable controls, static failure hypothesis testing, dynamic multivariable controls, fault-tolerant control theory, dynamic hypothesis testing, generalized likelihood ratio (GLR) methods, and adaptive control are discussed.

Oscillatory bursting of gel fuel droplets in a reacting environment.

PubMed

Miglani, Ankur; Nandagopalan, Purushothaman; John, Jerin; Baek, Seung Wook

2017-06-12

Understanding the combustion behavior of gel fuel droplets is pivotal for enhancing burn rates, lowering ignition delay and improving the operational performance of next-generation propulsion systems. Vapor jetting in burning gel fuel droplets is a crucial process that enables an effective transport (convectively) of unreacted fuel from the droplet domain to the flame zone and accelerates the gas-phase mixing process. Here, first we show that the combusting ethanol gel droplets (organic gellant laden) exhibit a new oscillatory jetting mode due to aperiodic bursting of the droplet shell. Second, we show how the initial gellant loading rate (GLR) leads to a distinct shell formation which self-tunes temporally to burst the droplet at different frequencies. Particularly, a weak-flexible shell is formed at low GLR that undergoes successive rupture cascades occurring in same region of the droplet. This region weakens due to repeated ruptures and causes droplet bursting at progressively higher frequencies. Contrarily, high GLRs facilitate a strong-rigid shell formation where consecutive cascades occur at scattered locations across the droplet surface. This leads to droplet bursting at random frequencies. This method of modulating jetting frequency would enable an effective control of droplet trajectory and local fuel-oxidizer ratio in any gel-spray based energy formulation.

On the spray pulsations of the effervescent atomizers

NASA Astrophysics Data System (ADS)

Mlkvik, Marek; Knizat, Branislav

2018-06-01

The presented paper focuses on the comparison of the two effervescent atomizer configurations—the outside-in-gas (OIG) and the outside-in-liquid (OIL). The comparison was based on the spray pulsation assessment by different methods. The atomizers were tested under the same operating conditions given by the constant injection pressure (0.14 MPa) and the gas to the liquid mass ratio (GLR) varying from 2.5 to 5%. The aqueous maltodextrin solution was used as the working liquid (μ = 60 and 146 mPa·s). We found that the time-averaging method does not provide sufficient spray quality description. Based on the cumulative distribution function (CDF) we found that the OIG atomizer generated the spray with non-uniform droplet size distribution at all investigated GLRs. Exceptionally large droplets were present even in the spray which appeared stable when was analyzed by the time-averaging method.

Practical Implementation of Multiple Model Adaptive Estimation Using Neyman-Pearson Based Hypothesis Testing and Spectral Estimation Tools

DTIC Science & Technology

1996-09-01

Generalized Likelihood Ratio (GLR) and voting techniques. The third class consisted of multiple hypothesis filter detectors, specifically the MMAE. The...vector version, versus a tensor if we use the matrix version of the power spectral density estimate. Using this notation, we will derive an...as MATLAB , have an intrinsic sample covariance computation available, which makes this method quite easy to implement. In practice, the mean for the

Interplay of Plasma Membrane and Vacuolar Ion Channels, Together with BAK1, Elicits Rapid Cytosolic Calcium Elevations in Arabidopsis during Aphid Feeding[OPEN

PubMed Central

Vincent, Thomas R.; Avramova, Marieta; Canham, James; Higgins, Peter; Bilkey, Natasha; Mugford, Sam T.; Pitino, Marco; Toyota, Masatsugu

2017-01-01

A transient rise in cytosolic calcium ion concentration is one of the main signals used by plants in perception of their environment. The role of calcium in the detection of abiotic stress is well documented; however, its role during biotic interactions remains unclear. Here, we use a fluorescent calcium biosensor (GCaMP3) in combination with the green peach aphid (Myzus persicae) as a tool to study Arabidopsis thaliana calcium dynamics in vivo and in real time during a live biotic interaction. We demonstrate rapid and highly localized plant calcium elevations around the feeding sites of M. persicae, and by monitoring aphid feeding behavior electrophysiologically, we demonstrate that these elevations correlate with aphid probing of epidermal and mesophyll cells. Furthermore, we dissect the molecular mechanisms involved, showing that interplay between the plant defense coreceptor BRASSINOSTEROID INSENSITIVE-ASSOCIATED KINASE1 (BAK1), the plasma membrane ion channels GLUTAMATE RECEPTOR-LIKE 3.3 and 3.6 (GLR3.3 and GLR3.6), and the vacuolar ion channel TWO-PORE CHANNEL1 (TPC1) mediate these calcium elevations. Consequently, we identify a link between plant perception of biotic threats by BAK1, cellular calcium entry mediated by GLRs, and intracellular calcium release by TPC1 during a biologically relevant interaction. PMID:28559475

Glutamate Receptor Homologs in Plants: Functions and Evolutionary Origins

PubMed Central

Price, Michelle Beth; Jelesko, John; Okumoto, Sakiko

2012-01-01

The plant glutamate-like receptor homologs (GLRs) are homologs of mammalian ionotropic glutamate receptors (iGluRs) which were discovered more than 10 years ago, and are hypothesized to be potential amino acid sensors in plants. Although initial progress on this gene family has been hampered by gene redundancy and technical issues such as gene toxicity; genetic, pharmacological, and electrophysiological approaches are starting to uncover the functions of this protein family. In parallel, there has been tremendous progress in elucidating the structure of animal glutamate receptors (iGluRs), which in turn will help understanding of the molecular mechanisms of plant GLR functions. In this review, we will summarize recent progress on the plant GLRs. Emerging evidence implicates plant GLRs in various biological processes in and beyond N sensing, and implies that there is some overlap in the signaling mechanisms of amino acids between plants and animals. Phylogenetic analysis using iGluRs from metazoans, plants, and bacteria showed that the plant GLRs are no more closely related to metazoan iGluRs as they are to bacterial iGluRs, indicating the separation of plant, other eukaryotic, and bacterial GLRs might have happened as early on as the last universal common ancestor. Structural similarities and differences with animal iGluRs, and the implication thereof, are also discussed. PMID:23115559

Orchestrating rapid long-distance signaling in plants with Ca2+ , ROS and electrical signals.

PubMed

Choi, Won-Gyu; Miller, Gad; Wallace, Ian; Harper, Jeffrey; Mittler, Ron; Gilroy, Simon

2017-05-01

Plants show a rapid systemic response to a wide range of environmental stresses, where the signals from the site of stimulus perception are transmitted to distal organs to elicit plant-wide responses. A wide range of signaling molecules are trafficked through the plant, but a trio of potentially interacting messengers, reactive oxygen species (ROS), Ca 2+ and electrical signaling ('trio signaling') appear to form a network supporting rapid signal transmission. The molecular components underlying this rapid communication are beginning to be identified, such as the ROS producing NAPDH oxidase RBOHD, the ion channel two pore channel 1 (TPC1), and glutamate receptor-like channels GLR3.3 and GLR3.6. The plant cell wall presents a plant-specific route for possible propagation of signals from cell to cell. However, the degree to which the cell wall limits information exchange between cells via transfer of small molecules through an extracellular route, or whether it provides an environment to facilitate transmission of regulators such as ROS or H + remains to be determined. Similarly, the role of plasmodesmata as both conduits and gatekeepers for the propagation of rapid cell-to-cell signaling remains a key open question. Regardless of how signals move from cell to cell, they help prepare distant parts of the plant for impending challenges from specific biotic or abiotic stresses. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Wolves in the Great Lakes region: a phylogeographic puzzle.

PubMed

Randi, Ettore

2010-10-01

Empirical studies demonstrate that natural hybridization in animals is more common than thought so far (Mallet 2005), particularly among species that originated recently through cycles of population contraction-expansion arising from climate changes over the last glacial period, the Pleistocene. In addition, the post-glacial global growth of human populations has fostered anthropogenic hybridization events, mediated by habitat changes, the persecution of large predators and the introduction of alien species (Allendorf et al. 2001). The Canis lineage shows cases of both natural and anthropogenic hybridization, exacerbating the controversy about the number of species that should be formally validated in the taxonomic lists, the evolutionary role of genetic introgression and the ways to manage hybrids with invading wild or domesticated populations. The study by Wheeldon et al. (2010), published in this issue of Molecular Ecology, adds a new piece to the intricate puzzle of evolution and taxonomy of Canis in North America. They show that sympatric wolves (C. lupus) and coyotes (C. latrans) are not (extensively) hybridizing in the western North American Great Lakes region (GLR). Widespread hybridization between coyotes and a genetically distinct, but closely related, wolf-like population (the eastern wolf) occurred in the northeastern regions of North America. In Wheeldon et al.'s (2010) opinion, these data should prove definitely that two different species of wolf (the western gray wolf C. lupus and the eastern wolf C. lycaon) and their hybrids are distributed across the GLR. © 2010 Blackwell Publishing Ltd.

Cinnamic Acid Analogs as Intervention Catalysts for Overcoming Antifungal Tolerance.

PubMed

Kim, Jong H; Chan, Kathleen L; Cheng, Luisa W

2017-10-21

Disruption of fungal cell wall should be an effective intervention strategy. However, the cell wall-disrupting echinocandin drugs, such as caspofungin (CAS), cannot exterminate filamentous fungal pathogens during treatment. For potency improvement of cell wall-disrupting agents (CAS, octyl gallate (OG)), antifungal efficacy of thirty-three cinnamic acid derivatives was investigated against Saccharomyces cerevisiae slt2 Δ, bck1 Δ, mutants of the mitogen-activated protein kinase (MAPK), and MAPK kinase kinase, respectively, in cell wall integrity system, and glr1 Δ, mutant of CAS-responsive glutathione reductase. Cell wall mutants were highly susceptible to four cinnamic acids (4-chloro-α-methyl-, 4-methoxy-, 4-methyl-, 3-methylcinnamic acids), where 4-chloro-α-methyl- and 4-methylcinnamic acids possessed the highest activity. Structure-activity relationship revealed that 4-methylcinnamic acid, the deoxygenated structure of 4-methoxycinnamic acid, overcame tolerance of glr1 Δ to 4-methoxycinnamic acid, indicating the significance of para substitution of methyl moiety for effective fungal control. The potential of compounds as chemosensitizers (intervention catalysts) to cell wall disruptants (viz., 4-chloro-α-methyl- or 4-methylcinnamic acids + CAS or OG) was assessed according to Clinical Laboratory Standards Institute M38-A. Synergistic chemosensitization greatly lowers minimum inhibitory concentrations of the co-administered drug/agents. 4-Chloro-α-methylcinnamic acid further overcame fludioxonil tolerance of Aspergillus fumigatus antioxidant MAPK mutants ( sakA Δ, mpkC Δ). Collectively, 4-chloro-α-methyl- and 4-methylcinnamic acids possess chemosensitizing capability to augment antifungal efficacy of conventional drug/agents, thus could be developed as target-based (i.e., cell wall disruption) intervention catalysts.

Comparison of TG-43 dosimetric parameters of brachytherapy sources obtained by three different versions of MCNP codes.

PubMed

Zaker, Neda; Zehtabian, Mehdi; Sina, Sedigheh; Koontz, Craig; Meigooni, Ali S

2016-03-08

Monte Carlo simulations are widely used for calculation of the dosimetric parameters of brachytherapy sources. MCNP4C2, MCNP5, MCNPX, EGS4, EGSnrc, PTRAN, and GEANT4 are among the most commonly used codes in this field. Each of these codes utilizes a cross-sectional library for the purpose of simulating different elements and materials with complex chemical compositions. The accuracies of the final outcomes of these simulations are very sensitive to the accuracies of the cross-sectional libraries. Several investigators have shown that inaccuracies of some of the cross section files have led to errors in 125I and 103Pd parameters. The purpose of this study is to compare the dosimetric parameters of sample brachytherapy sources, calculated with three different versions of the MCNP code - MCNP4C, MCNP5, and MCNPX. In these simulations for each source type, the source and phantom geometries, as well as the number of the photons, were kept identical, thus eliminating the possible uncertainties. The results of these investigations indicate that for low-energy sources such as 125I and 103Pd there are discrepancies in gL(r) values. Discrepancies up to 21.7% and 28% are observed between MCNP4C and other codes at a distance of 6 cm for 103Pd and 10 cm for 125I from the source, respectively. However, for higher energy sources, the discrepancies in gL(r) values are less than 1.1% for 192Ir and less than 1.2% for 137Cs between the three codes.

Roles of the Yap1 Transcription Factor and Antioxidants in Saccharomyces cerevisiae's Tolerance to Furfural and 5-Hydroxymethylfurfural, Which Function as Thiol-Reactive Electrophiles Generating Oxidative Stress

PubMed Central

Kim, Daehee

2013-01-01

Development of the tolerance of Saccharomyces cerevisiae strains to furfural and 5-hydroxymethylfurfural (HMF) is an important issue for cellulosic ethanol production. Although furfural and HMF are known to induce oxidative stress, the underlying mechanisms are largely unknown. In this study, we show that both furfural and HMF act as thiol-reactive electrophiles, thus directly activating the Yap1 transcription factor via the H2O2-independent pathway, depleting cellular glutathione (GSH) levels, and accumulating reactive oxygen species in Saccharomyces cerevisiae. However, furfural showed higher reactivity than did HMF toward GSH in vitro and in vivo. In line with such toxic mechanisms, overexpression of YAP1C620F, a constitutively active mutant of YAP1, and Yap1 target genes encoding catalases (CTA1 and CTT1) increased tolerance to furfural and HMF. However, increasing GSH levels by overexpression of genes for GSH biosynthesis (GSH1 and GLR1) or by the exogenous addition of GSH to the culture medium enhanced tolerance to furfural but not to HMF. PMID:23793623

Roles of the Yap1 transcription factor and antioxidants in Saccharomyces cerevisiae's tolerance to furfural and 5-hydroxymethylfurfural, which function as thiol-reactive electrophiles generating oxidative stress.

PubMed

Kim, Daehee; Hahn, Ji-Sook

2013-08-01

Development of the tolerance of Saccharomyces cerevisiae strains to furfural and 5-hydroxymethylfurfural (HMF) is an important issue for cellulosic ethanol production. Although furfural and HMF are known to induce oxidative stress, the underlying mechanisms are largely unknown. In this study, we show that both furfural and HMF act as thiol-reactive electrophiles, thus directly activating the Yap1 transcription factor via the H2O2-independent pathway, depleting cellular glutathione (GSH) levels, and accumulating reactive oxygen species in Saccharomyces cerevisiae. However, furfural showed higher reactivity than did HMF toward GSH in vitro and in vivo. In line with such toxic mechanisms, overexpression of YAP1(C620F), a constitutively active mutant of YAP1, and Yap1 target genes encoding catalases (CTA1 and CTT1) increased tolerance to furfural and HMF. However, increasing GSH levels by overexpression of genes for GSH biosynthesis (GSH1 and GLR1) or by the exogenous addition of GSH to the culture medium enhanced tolerance to furfural but not to HMF.

bZIP transcription factor CgAP1 is essential for oxidative stress tolerance and full virulence of the poplar anthracnose fungus Colletotrichum gloeosporioides.

PubMed

Sun, Yingjiao; Wang, Yonglin; Tian, Chengming

2016-10-01

Yeast AP1 transcription factor is a regulator of oxidative stress response. Here, we report the identification and characterization of CgAP1, an ortholog of YAP1 in poplar anthracnose fungus Colletotrichum gloeosporioides. The expression of CgAP1 was highly induced by reactive oxygen species. CgAP1 deletion mutants displayed enhanced sensitivity to oxidative stress compared with the wild-type strain, and their poplar leaf virulence was obviously reduced. However, the mutants exhibited no obvious defects in aerial hyphal growth, conidia production, and appressoria formation. CgAP1::eGFP fusion protein localized to the nucleus after TBH (tert-Butyl hydroperoxide) treatment, suggesting that CgAP1 functions as a redox sensor in C. gloeosporioides. In addition, CgAP1 prevented the accumulation of ROS during early stages of biotrophic growth. CgAP1 also acted as a positive regulator of several ROS-related genes (i.e., Glr1, Hyr1, and Cyt1) involved in the antioxidative response. These results highlight the key regulatory role of CgAP1 transcription factor in oxidative stress response and provide insights into the function of ROS detoxification in virulence of C. gloeosporioides. Copyright © 2016 Elsevier Inc. All rights reserved.

Modified Multiple Model Adaptive Estimation (M3AE) for Simultaneous Parameter and State Estimation

DTIC Science & Technology

1998-03-01

Contents Page Dedication : iv Acknowledgments v Table Of Contents vi List of Figures . . ; x List of Tables xv Abstract xvii Chapter 1 ...INTRODUCTION 1 1.1 Overview 1 1.2 Background 7 1.2.1 The Chi-Square Test 9 1.2.2 Generalized Likelihood Ratio (GLR) Testing 10 1.2.3 Multiple...M3AE Covariance Analysis 115 4.1.3 Simulations and Performance Analysis 121 4.1.3.1 Test Case 1 : aT = 32.0 124 4.1.3.2 Test Case 2: aT = 37.89, and

Seattle Tacoma IAP, Washington. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

DTIC Science & Technology

1982-06-21

to’loo s or S Pow Anl OUXO111 (3 ( F. . ,LCAAL CLIMATOLOGY BRANCH 2 o. AFEtAC SURFACE WINDS A’- wATHER SERVICE/MAC PERCENTAGE FREQUENCY OF WIND...wO.Ts of T@s Fa am cowun 1 --------------------------- --- j rGLr8AL CLIMATOLOGY BRANCH V R U .JSAFETAC CEILING VE S SVISIBILITY2 Ali, wATHER SERVICE...OL A) wco e , s . , .I-, o ,,oj.’il -- / [ ___ ____ ___ ____ ___, PLCBAL CLIMATOLOGY BRANCH V RU )S F E7AC CEILING VESU ISIBIITY2 A-’ wATHER SERVICE

Fluoxetine reverses behavior changes in socially isolated rats: role of the hippocampal GSH-dependent defense system and proinflammatory cytokines.

PubMed

Perić, Ivana; Stanisavljević, Andrijana; Gass, Peter; Filipović, Dragana

2017-12-01

Exposure of an organism to chronic social isolation (CSIS) has been shown to have an important role in depression. Fluoxetine (Flx) is a first-line treatment for depression; however, its downstream mechanisms of action beyond serotonergic signaling remain ill-defined. We investigated the effect of 3 weeks of Flx (15 mg/kg/day) treatment on behavioral changes and protein expression/activity of the GSH-dependent defense system, including reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GLR), and glutathione S-transferase (GST), as well as catalase (CAT), in the hippocampus of rats exposed to 6 weeks of CSIS. The subcellular distributions of nuclear factor-κB (NF-κB), as well as, cytosolic IL-1β and IL-6 protein expression, were also determined. CSIS induced depressive- and anxiety-like behaviors, evidenced by a decrease in sucrose preference and an increase in the number of buried marbles. Moreover, CSIS compromised redox homeostasis, targeting enzymes such as GPx, CAT, GST, and caused NF-κB nuclear translocation with a concomitant increase in IL-6 protein expression, without an effect on IL-1β. Flx treatment reversed CSIS-induced depressive- and anxiety-like behaviors, modulated GSH-dependent defense by increasing GLR and GST activity, and suppressed NF-κB activation and cytosolic IL-6 protein expression in socially isolated rats. The present study suggests that changes in the GSH-dependent defense system, NF-κB activation and increased IL-6 protein expression may have a role in social isolation-induced changes in a rat model of depression and anxiety, and contributes to our understanding of the mechanisms that underlie the antidepressant and anti-inflammatory activity of Flx in socially isolated rats.

Comparison of TG‐43 dosimetric parameters of brachytherapy sources obtained by three different versions of MCNP codes

PubMed Central

Zaker, Neda; Sina, Sedigheh; Koontz, Craig; Meigooni1, Ali S.

2016-01-01

Monte Carlo simulations are widely used for calculation of the dosimetric parameters of brachytherapy sources. MCNP4C2, MCNP5, MCNPX, EGS4, EGSnrc, PTRAN, and GEANT4 are among the most commonly used codes in this field. Each of these codes utilizes a cross‐sectional library for the purpose of simulating different elements and materials with complex chemical compositions. The accuracies of the final outcomes of these simulations are very sensitive to the accuracies of the cross‐sectional libraries. Several investigators have shown that inaccuracies of some of the cross section files have led to errors in  125I and  103Pd parameters. The purpose of this study is to compare the dosimetric parameters of sample brachytherapy sources, calculated with three different versions of the MCNP code — MCNP4C, MCNP5, and MCNPX. In these simulations for each source type, the source and phantom geometries, as well as the number of the photons, were kept identical, thus eliminating the possible uncertainties. The results of these investigations indicate that for low‐energy sources such as  125I and  103Pd there are discrepancies in gL(r) values. Discrepancies up to 21.7% and 28% are observed between MCNP4C and other codes at a distance of 6 cm for  103Pd and 10 cm for  125I from the source, respectively. However, for higher energy sources, the discrepancies in gL(r) values are less than 1.1% for  192Ir and less than 1.2% for  137Cs between the three codes. PACS number(s): 87.56.bg PMID:27074460

Niagara Falls IAP, New York. Revised Uniform Summary of Surface Weather Observations. Parts A-F.

DTIC Science & Technology

1987-09-30

TOTLS 1 21 . 32." 3 1. q 7 1 h .2 DO . 00 9.1 ..... .. . 30181 r, UPl’ OP O:’.rvI49A10.S: 33991? - A pPPPP,P~ppl A:. A RRRRR TY TIIII1 T0DD000D0...94.6 99.1 99.3 99.6 9’.q 99.9 530.0 10.0 130.0 100 .0 TO IAL hM "E" CF UnS[VATIONS: 9uU" .L K GLrObAL CLIPAIOLUGY BpAnFC P[.C[NfArE FkFELENCY OF

The continuum fusion theory of signal detection applied to a bi-modal fusion problem

NASA Astrophysics Data System (ADS)

Schaum, A.

2011-05-01

A new formalism has been developed that produces detection algorithms for model-based problems, in which one or more parameter values is unknown. Continuum Fusion can be used to generate different flavors of algorithm for any composite hypothesis testing problem. The methodology is defined by a fusion logic that can be translated into max/min conditions. Here it is applied to a simple sensor fusion model, but one for which the generalized likelihood ratio test is intractable. By contrast, a fusion-based response to the same problem can be devised that is solvable in closed form and represents a good approximation to the GLR test.

Mammalian TRPV4 (VR-OAC) directs behavioral responses to osmotic and mechanical stimuli in Caenorhabditis elegans

PubMed Central

Liedtke, Wolfgang; Tobin, David M.; Bargmann, Cornelia I.; Friedman, Jeffrey M.

2003-01-01

All animals detect osmotic and mechanical stimuli, but the molecular basis for these responses is incompletely understood. The vertebrate transient receptor potential channel vanilloid subfamily 4 (TRPV4) (VR-OAC) cation channel has been suggested to be an osmo/mechanosensory channel. To assess its function in vivo, we expressed TRPV4 in Caenorhabditis elegans sensory neurons and examined its ability to generate behavioral responses to sensory stimuli. C. elegans ASH neurons function as polymodal sensory neurons that generate a characteristic escape behavior in response to mechanical, osmotic, or olfactory stimuli. These behaviors require the TRPV channel OSM-9 because osm-9 mutants do not avoid nose touch, high osmolarity, or noxious odors. Expression of mammalian TRPV4 in ASH neurons of osm-9 worms restored avoidance responses to hypertonicity and nose touch, but not the response to odorant repellents. Mutations known to reduce TRPV4 channel activity also reduced its ability to direct nematode avoidance behavior. TRPV4 function in ASH required the endogenous C. elegans osmotic and nose touch avoidance genes ocr-2, odr-3, osm-10, and glr-1, indicating that TRPV4 is integrated into the normal ASH sensory apparatus. The osmotic and mechanical avoidance responses of TRPV4-expressing animals were different in their sensitivity and temperature dependence from the responses of wild-type animals, suggesting that the TRPV4 channel confers its characteristic properties on the transgenic animals' behavior. These results provide evidence that TRPV4 can function as a component of an osmotic/mechanical sensor in vivo. PMID:14581619

Feeding status and serotonin rapidly and reversibly modulate a Caenorhabditis elegans chemosensory circuit

PubMed Central

Chao, Michael Y.; Komatsu, Hidetoshi; Fukuto, Hana S.; Dionne, Heather M.; Hart, Anne C.

2004-01-01

Serotonin (5-HT) modulates synaptic efficacy in the nervous system of vertebrates and invertebrates. In the nematode Caenorhabditis elegans, many behaviors are regulated by 5-HT levels, which are in turn regulated by the presence or absence of food. Here, we show that both food and 5-HT signaling modulate chemosensory avoidance response of octanol in C. elegans, and that this modulation is both rapid and reversible. Sensitivity to octanol is decreased when animals are off food or when 5-HT levels are decreased; conversely, sensitivity is increased when animals are on food or have increased 5-HT signaling. Laser microsurgery and behavioral experiments reveal that sensory input from different subsets of octanol-sensing neurons is selectively used, depending on stimulus strength, feeding status, and 5-HT levels. 5-HT directly targets at least one pair of sensory neurons, and 5-HT signaling requires the Gα protein GPA-11. Glutamatergic signaling is required for response to octanol, and the GLR-1 glutamate receptor plays an important role in behavioral response off food but not on food. Our results demonstrate that 5-HT modulation of neuronal activity via G protein signaling underlies behavioral plasticity by rapidly altering the functional circuitry of a chemosensory circuit. PMID:15492222

Molecular characterization of a novel RhoGAP, RRC-1 of the nematode Caenorhabditis elegans

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

Delawary, Mina; Nakazawa, Takanobu; Tezuka, Tohru

2007-06-01

The GTPase-activating proteins for Rho family GTPases (RhoGAP) transduce diverse intracellular signals by negatively regulating Rho family GTPase-mediated pathways. In this study, we have cloned and characterized a novel RhoGAP for Rac1 and Cdc42, termed RRC-1, from Caenorhabditis elegans. RRC-1 was highly homologous to mammalian p250GAP and promoted GTP hydrolysis of Rac1 and Cdc42 in cells. The rrc-1 mRNA was expressed in all life stages. Using an RRC-1::GFP fusion protein, we found that RRC-1 was localized to the coelomocytes, excretory cell, GLR cells, and uterine-seam cell in adult worms. These data contribute toward understanding the roles of Rho family GTPasesmore » in C. elegans.« less

Extended target recognition in cognitive radar networks.

PubMed

Wei, Yimin; Meng, Huadong; Liu, Yimin; Wang, Xiqin

2010-01-01

We address the problem of adaptive waveform design for extended target recognition in cognitive radar networks. A closed-loop active target recognition radar system is extended to the case of a centralized cognitive radar network, in which a generalized likelihood ratio (GLR) based sequential hypothesis testing (SHT) framework is employed. Using Doppler velocities measured by multiple radars, the target aspect angle for each radar is calculated. The joint probability of each target hypothesis is then updated using observations from different radar line of sights (LOS). Based on these probabilities, a minimum correlation algorithm is proposed to adaptively design the transmit waveform for each radar in an amplitude fluctuation situation. Simulation results demonstrate performance improvements due to the cognitive radar network and adaptive waveform design. Our minimum correlation algorithm outperforms the eigen-waveform solution and other non-cognitive waveform design approaches.

Carbon and nitrogen nutrient balance signaling in plants.

PubMed

Zheng, Zhi-Liang

2009-07-01

Cellular carbon (C) and nitrogen (N) metabolism must be tightly coordinated to sustain optimal growth and development for plants and other cellular organisms. Furthermore, C/N balance is also critical for the ecosystem response to elevated atmospheric CO(2). Despite numerous physiological and molecular studies in C/N balance or ratio response, very few genes have been shown to play important roles in C/N balance signaling. During recent five years, exciting progress was made through genetic and genomic studies. Several DNA microarray studies have shown that more than half of the transcriptome is regulated by C, N and the C-N combination. Three genetic studies involving distinct bioassays have demonstrated that a putative nitrate transporter (NTR2.1), a putative glutamate receptor (GLR1.1) and a putative methyltransferase (OSU1) have important functions in the C/N balance response. OSU1 is identical to QUA2/TSD2 which has been implicated to act in cell wall biogenesis, indicating a link between cell wall property and the C/N balance signaling. Given that many investigations are only focused on C alone or N alone, the C/N balance bioassays and gene expression patterns are discussed to assist phenotypic characterization of C/N balance signaling. Further, re-examination of those previously reported sugar or nitrogen responsive genes in C/N balance response may be necessary to dissect the C/N signaling pathways. In addition, key components involved in C-N interactions in bacterial, yeast and animal systems and whether they are functionally conserved in plants are discussed. These rapid advances have provided the first important step towards the construction of the complex yet elegant C/N balance signaling networks in plants.

COSAGE (Concepts Analysis Agency’s Combat Sample Generator) Analysis and Design Report. Volume 2

DTIC Science & Technology

1984-04-29

Law 1-0 L L- o : Ir-I- lz 9 LL 4 i-w z o Li W w-- n 17 a. I.-- I.-.- 41- In I in 4 - I.- w w 0. ---- - - - -Inn w WWw IWWL U "-J I.-n I.:-0 I.:V W...S> U) M. V) U)( -j 1-. U)CflU)iW AJLL - CA~ 0(9 9( Iij _j 4c.-...- - . . . V )V )UU0 _j .- F_ .-I -W LL WL -) 1- - .. J.J.J U U)A WO LL P.- 1.- * WWW ...I’ 4< 4 o w Q e~~ glrS . ftc- www ~w~uw ~ NW)* WNPOQO -qp t It V -I- P P.P. Dr. OD O ODif)OD 1) f) i inIS D O 40IS t ( D COD 0 O to D O Z OD GD LAI

New Statistical Approach to Apportion Dietary Sources of Iodine Intake: Findings from Kenya, Senegal and India

PubMed Central

Knowles, Jacky; Bukania, Zipporah; Camara, Boubacar; Pandav, Chandrakant S.; Mwai, John Maina; Toure, Ndeye Khady; Yadav, Kapil

2018-01-01

Progress of national Universal Salt Iodization (USI) strategies is typically assessed by household coverage of adequately iodized salt and median urinary iodine concentration (UIC) in spot urine collections. However, household coverage does not inform on the iodized salt used in preparation of processed foods outside homes, nor does the total UIC reflect the portion of population iodine intake attributable to the USI strategy. This study used data from three population-representative surveys of women of reproductive age (WRA) in Kenya, Senegal and India to develop and illustrate a new approach to apportion the population UIC levels by the principal dietary sources of iodine intake, namely native iodine, iodine in processed food salt and iodine in household salt. The technique requires measurement of urinary sodium concentrations (UNaC) in the same spot urine samples collected for iodine status assessment. Taking into account the different complex survey designs of each survey, generalized linear regression (GLR) analyses were performed in which the UIC data of WRA was set as the outcome variable that depends on their UNaC and household salt iodine (SI) data as explanatory variables. Estimates of the UIC portions that correspond to iodine intake sources were calculated with use of the intercept and regression coefficients for the UNaC and SI variables in each country’s regression equation. GLR coefficients for UNaC and SI were significant in all country-specific models. Rural location did not show a significant association in any country when controlled for other explanatory variables. The estimated UIC portion from native dietary iodine intake in each country fell below the minimum threshold for iodine sufficiency. The UIC portion arising from processed food salt in Kenya was substantially higher than in Senegal and India, while the UIC portions from household salt use varied in accordance with the mean level of household SI content in the country surveys. The UIC portions and all-salt-derived iodine intakes found in this study were illustrative of existing differences in national USI legislative frameworks and national salt supply situations between countries. The approach of apportioning the population UIC from spot urine collections may be useful for future monitoring of change in iodine nutrition from reduced salt use in processed foods and in households. PMID:29596369

TH-A-9A-04: Incorporating Liver Functionality in Radiation Therapy Treatment Planning

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

Wu, V; Epelman, M; Feng, M

2014-06-15

Purpose: Liver SBRT patients have both variable pretreatment liver function (e.g., due to degree of cirrhosis and/or prior treatments) and sensitivity to radiation, leading to high variability in potential liver toxicity with similar doses. This work aims to explicitly incorporate liver perfusion into treatment planning to redistribute dose to preserve well-functioning areas without compromising target coverage. Methods: Voxel-based liver perfusion, a measure of functionality, was computed from dynamic contrast-enhanced MRI. Two optimization models with different cost functions subject to the same dose constraints (e.g., minimum target EUD and maximum critical structure EUDs) were compared. The cost functions minimized were EUDmore » (standard model) and functionality-weighted EUD (functional model) to the liver. The resulting treatment plans delivering the same target EUD were compared with respect to their DVHs, their dose wash difference, the average dose delivered to voxels of a particular perfusion level, and change in number of high-/low-functioning voxels receiving a particular dose. Two-dimensional synthetic and three-dimensional clinical examples were studied. Results: The DVHs of all structures of plans from each model were comparable. In contrast, in plans obtained with the functional model, the average dose delivered to high-/low-functioning voxels was lower/higher than in plans obtained with its standard counterpart. The number of high-/low-functioning voxels receiving high/low dose was lower in the plans that considered perfusion in the cost function than in the plans that did not. Redistribution of dose can be observed in the dose wash differences. Conclusion: Liver perfusion can be used during treatment planning potentially to minimize the risk of toxicity during liver SBRT, resulting in better global liver function. The functional model redistributes dose in the standard model from higher to lower functioning voxels, while achieving the same target EUD and satisfying dose limits to critical structures. This project is funded by MCubed and grant R01-CA132834.« less

Dynamically accumulated dose and 4D accumulated dose for moving tumors

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

Li Heng; Li Yupeng; Zhang Xiaodong

2012-12-15

Purpose: The purpose of this work was to investigate the relationship between dynamically accumulated dose (dynamic dose) and 4D accumulated dose (4D dose) for irradiation of moving tumors, and to quantify the dose uncertainty induced by tumor motion. Methods: The authors established that regardless of treatment modality and delivery properties, the dynamic dose will converge to the 4D dose, instead of the 3D static dose, after multiple deliveries. The bounds of dynamic dose, or the maximum estimation error using 4D or static dose, were established for the 4D and static doses, respectively. Numerical simulations were performed (1) to prove themore » principle that for each phase, after multiple deliveries, the average number of deliveries for any given time converges to the total number of fractions (K) over the number of phases (N); (2) to investigate the dose difference between the 4D and dynamic doses as a function of the number of deliveries for deliveries of a 'pulsed beam'; and (3) to investigate the dose difference between 4D dose and dynamic doses as a function of delivery time for deliveries of a 'continuous beam.' A Poisson model was developed to estimate the mean dose error as a function of number of deliveries or delivered time for both pulsed beam and continuous beam. Results: The numerical simulations confirmed that the number of deliveries for each phase converges to K/N, assuming a random starting phase. Simulations for the pulsed beam and continuous beam also suggested that the dose error is a strong function of the number of deliveries and/or total deliver time and could be a function of the breathing cycle, depending on the mode of delivery. The Poisson model agrees well with the simulation. Conclusions: Dynamically accumulated dose will converge to the 4D accumulated dose after multiple deliveries, regardless of treatment modality. Bounds of the dynamic dose could be determined using quantities derived from 4D doses, and the mean dose difference between the dynamic dose and 4D dose as a function of number of deliveries and/or total deliver time was also established.« less

The Application of Elliptic Cylindrical Phantom in Brachytherapy Dosimetric Study of HDR 192Ir Source

NASA Astrophysics Data System (ADS)

Ahn, Woo Sang; Park, Sung Ho; Jung, Sang Hoon; Choi, Wonsik; Do Ahn, Seung; Shin, Seong Soo

2014-06-01

The purpose of this study is to determine the radial dose function of HDR 192Ir source based on Monte Carlo simulation using elliptic cylindrical phantom, similar to realistic shape of pelvis, in brachytherapy dosimetric study. The elliptic phantom size and shape was determined by analysis of dimensions of pelvis on CT images of 20 patients treated with brachytherapy for cervical cancer. The radial dose function obtained using the elliptic cylindrical water phantom was compared with radial dose functions for different spherical phantom sizes, including the Williamsion's data loaded into conventional planning system. The differences in the radial dose function for the different spherical water phantoms increase with radial distance, r, and the largest differences in the radial dose function appear for the smallest phantom size. The radial dose function of the elliptic cylindrical phantom significantly decreased with radial distance in the vertical direction due to different scatter condition in comparison with the Williamson's data. Considering doses to ICRU rectum and bladder points, doses to reference points can be underestimated up to 1-2% at the distance from 3 to 6 cm. The radial dose function in this study could be used as realistic data for calculating the brachytherapy dosimetry for cervical cancer.

Dose accuracy of a durable insulin pen with memory function, before and after simulated lifetime use and under stress conditions.

PubMed

Xue, Ligang; Mikkelsen, Kristian Handberg

2013-03-01

The objective of this study was to assess the dose accuracy of NovoPen® 5 in delivering low, medium and high doses of insulin before and after simulated lifetime use. A secondary objective was to evaluate the durability of the pen and its memory function under various stress conditions designed to simulate conditions that may be encountered in everyday use of an insulin pen. All testing was conducted according to International Organization for Standardization guideline 11608-1, 2000 for pen injectors. Dose accuracy was measured for the delivery of 1 unit (U) (10 mg), 30 U (300 mg) and 60 U (600 mg) test medium in standard, cool and hot conditions and before and after simulated lifetime use. Dose accuracy was also tested after preconditioning in dry heat storage; cold storage; damp cyclical heat; shock, bump and vibration; free fall and after electrostatic charge and radiated field test. Memory function was tested under all temperature and physical conditions. NovoPen 5 maintained dosing accuracy and memory function at minimum, medium and maximum doses in standard, cool and hot conditions, stress tests and simulated lifetime use. The pens remained intact and retained dosing accuracy and a working memory function at all doses after exposure to variations in temperature and after physical challenge. NovoPen 5 was accurate at all doses tested and under various functionality tests. Its durable design ensured that the dose accuracy and memory function were retained under conditions of stress likely to be encountered in everyday use.

Comparison of dose response functions for EBT3 model GafChromic™ film dosimetry system.

PubMed

Aldelaijan, Saad; Devic, Slobodan

2018-05-01

Different dose response functions of EBT3 model GafChromic™ film dosimetry system have been compared in terms of sensitivity as well as uncertainty vs. error analysis. We also made an assessment of the necessity of scanning film pieces before and after irradiation. Pieces of EBT3 film model were irradiated to different dose values in Solid Water (SW) phantom. Based on images scanned in both reflection and transmission mode before and after irradiation, twelve different response functions were calculated. For every response function, a reference radiochromic film dosimetry system was established by generating calibration curve and by performing the error vs. uncertainty analysis. Response functions using pixel values from the green channel demonstrated the highest sensitivity in both transmission and reflection mode. All functions were successfully fitted with rational functional form, and provided an overall one-sigma uncertainty of better than 2% for doses above 2 Gy. Use of pre-scanned images to calculate response functions resulted in negligible improvement in dose measurement accuracy. Although reflection scanning mode provides higher sensitivity and could lead to a more widespread use of radiochromic film dosimetry, it has fairly limited dose range and slightly increased uncertainty when compared to transmission scan based response functions. Double-scanning technique, either in transmission or reflection mode, shows negligible improvement in dose accuracy as well as a negligible increase in dose uncertainty. Normalized pixel value of the images scanned in transmission mode shows linear response in a dose range of up to 11 Gy. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Pharmacokinetic/Pharmacodynamic Modeling and Simulation of Cefiderocol, a Parenteral Siderophore Cephalosporin, for Dose Adjustment Based on Renal Function.

PubMed

Katsube, Takayuki; Wajima, Toshihiro; Ishibashi, Toru; Arjona Ferreira, Juan Camilo; Echols, Roger

2017-01-01

Cefiderocol, a novel parenteral siderophore cephalosporin, exhibits potent efficacy against most Gram-negative bacteria, including carbapenem-resistant strains. Since cefiderocol is excreted primarily via the kidneys, this study was conducted to develop a population pharmacokinetics (PK) model to determine dose adjustment based on renal function. Population PK models were developed based on data for cefiderocol concentrations in plasma, urine, and dialysate with a nonlinear mixed-effects model approach. Monte-Carlo simulations were conducted to calculate the probability of target attainment (PTA) of fraction of time during the dosing interval where the free drug concentration in plasma exceeds the MIC (T f >MIC ) for an MIC range of 0.25 to 16 μg/ml. For the simulations, dose regimens were selected to compare cefiderocol exposure among groups with different levels of renal function. The developed models well described the PK of cefiderocol for each renal function group. A dose of 2 g every 8 h with 3-h infusions provided >90% PTA for 75% T f >MIC for an MIC of ≤4 μg/ml for patients with normal renal function, while a more frequent dose (every 6 h) could be used for patients with augmented renal function. A reduced dose and/or extended dosing interval was selected for patients with impaired renal function. A supplemental dose immediately after intermittent hemodialysis was proposed for patients requiring intermittent hemodialysis. The PK of cefiderocol could be adequately modeled, and the modeling-and-simulation approach suggested dose regimens based on renal function, ensuring drug exposure with adequate bactericidal effect. Copyright © 2016 American Society for Microbiology.

Dosimetric characterizations of GZP6 60Co high dose rate brachytherapy sources: application of superimposition method

PubMed Central

Bahreyni Toossi, Mohammad Taghi; Ghorbani, Mahdi; Mowlavi, Ali Asghar; Meigooni, Ali Soleimani

2012-01-01

Background Dosimetric characteristics of a high dose rate (HDR) GZP6 Co-60 brachytherapy source have been evaluated following American Association of Physicists in MedicineTask Group 43U1 (AAPM TG-43U1) recommendations for their clinical applications. Materials and methods MCNP-4C and MCNPX Monte Carlo codes were utilized to calculate dose rate constant, two dimensional (2D) dose distribution, radial dose function and 2D anisotropy function of the source. These parameters of this source are compared with the available data for Ralstron 60Co and microSelectron192Ir sources. Besides, a superimposition method was developed to extend the obtained results for the GZP6 source No. 3 to other GZP6 sources. Results The simulated value for dose rate constant for GZP6 source was 1.104±0.03 cGyh-1U-1. The graphical and tabulated radial dose function and 2D anisotropy function of this source are presented here. The results of these investigations show that the dosimetric parameters of GZP6 source are comparable to those for the Ralstron source. While dose rate constant for the two 60Co sources are similar to that for the microSelectron192Ir source, there are differences between radial dose function and anisotropy functions. Radial dose function of the 192Ir source is less steep than both 60Co source models. In addition, the 60Co sources are showing more isotropic dose distribution than the 192Ir source. Conclusions The superimposition method is applicable to produce dose distributions for other source arrangements from the dose distribution of a single source. The calculated dosimetric quantities of this new source can be introduced as input data to the GZP6 treatment planning system (TPS) and to validate the performance of the TPS. PMID:23077455

Safety of coronary CT angiography and functional testing for stable chest pain in the PROMISE trial: A randomized comparison of test complications, incidental findings, and radiation dose.

PubMed

Lu, Michael T; Douglas, Pamela S; Udelson, James E; Adami, Elizabeth; Ghoshhajra, Brian B; Picard, Michael H; Roberts, Rhonda; Lee, Kerry L; Einstein, Andrew J; Mark, Daniel B; Velazquez, Eric J; Carter, William; Ridner, Michael; Al-Khalidi, Hussein R; Hoffmann, Udo

Coronary computed tomography angiography (CTA) and functional testing strategies for stable chest pain yield similar outcomes; one aspect that may guide test choice is safety. We compared test safety (test complications, incidental findings, and effective radiation dose) between CTA and functional testing as-tested in PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain). In the subgroup whose physicians intended nuclear stress over other functional tests if randomized to the functional arm, we compared radiation dose of CTA versus nuclear stress and identified characteristics associated with dose. Of 9470 patients, none had major and <1% had minor complications (CTA: 0.8% [37/4633] vs. functional: 0.6% [27/4837]). CTA identified more incidental findings (11.6% [539/4633] vs. 0.7% [34/4837], p < 0.001), most commonly pulmonary nodules (9.4%, 437/4633). CTA had similar 90-day cumulative radiation dose to functional testing. However, in the subgroup whose physicians intended nuclear stress (CTA 3147; nuclear 3203), CTA had lower median index test (8.8 vs. 12.6 mSv, p < 0.001) and 90-day cumulative (11.6 vs. 13.1 mSv, p < 0.001) dose, independent of patient characteristics. The lowest nuclear doses employed 1-day Tc-99m protocols (12.2 mSv). The lowest CTA doses were at sites performing ≥500 CTAs/year (6.9 mSv) and with advanced (latest available) CT scanners (5.5 mSv). Complications were negligibly rare for both CTA and functional testing. CTA detects more incidental findings. Compared to nuclear stress testing, CTA's lower radiation dose, independent of patient characteristics, makes it an attractive test choice. Radiation dose varies with imaging protocol, indicating opportunities to further reduce dose. (ClinicalTrials.gov number, NCT01174550). Copyright © 2017 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Modeling Rabbit Responses to Single and Multiple Aerosol ...

EPA Pesticide Factsheets

Journal Article Survival models are developed here to predict response and time-to-response for mortality in rabbits following exposures to single or multiple aerosol doses of Bacillus anthracis spores. Hazard function models were developed for a multiple dose dataset to predict the probability of death through specifying dose-response functions and the time between exposure and the time-to-death (TTD). Among the models developed, the best-fitting survival model (baseline model) has an exponential dose-response model with a Weibull TTD distribution. Alternative models assessed employ different underlying dose-response functions and use the assumption that, in a multiple dose scenario, earlier doses affect the hazard functions of each subsequent dose. In addition, published mechanistic models are analyzed and compared with models developed in this paper. None of the alternative models that were assessed provided a statistically significant improvement in fit over the baseline model. The general approach utilizes simple empirical data analysis to develop parsimonious models with limited reliance on mechanistic assumptions. The baseline model predicts TTDs consistent with reported results from three independent high-dose rabbit datasets. More accurate survival models depend upon future development of dose-response datasets specifically designed to assess potential multiple dose effects on response and time-to-response. The process used in this paper to dev

Renal function in atrial fibrillation patients switched from warfarin to a direct oral anticoagulant.

PubMed

Minhas, Anum S; Jiang, Qingmei; Gu, Xiaokui; Haymart, Brian; Kline-Rogers, Eva; Almany, Steve; Kozlowski, Jay; Krol, Gregory D; Kaatz, Scott; Froehlich, James B; Barnes, Geoffrey D

2016-11-01

All available direct oral anticoagulants (DOACs) are at least partially eliminated by the kidneys. These agents are increasingly being used as alternatives to warfarin for stroke prevention in patients with atrial fibrillation. The aim of this study was to identify changes in renal function and associated DOAC dosing implications in a multicenter cohort of atrial fibrillation patients switched from warfarin to DOAC treatment. We included all patients in the Michigan Anticoagulation Quality Improvement Initiative cohort who switched from warfarin to a DOAC with atrial fibrillation as their anticoagulant indication between 2009 and 2014, and who had at least two creatinine values. Compliance with FDA-recommended dosing based on renal function was assessed. Of the 189 patients switched from warfarin to a DOAC, 34 (18.0 %) had a baseline creatinine clearance <50 mL/min and 23 (12.2 %) experienced important fluctuations in renal function. Of these 23 patients, 6 (26.1 %) should have impacted the DOAC dosing, but only 1 patient actually received an appropriate dose adjustment. Additionally, 15 (7.9 %) of patients on DOACs had a dose change performed, but only one patient demonstrated a change in renal function to justify the dose adjustment. Most atrial fibrillation patients who switched from warfarin to a DOAC had stable renal function. However, the majority of patients who had a change in renal function did not receive the indicated dose change. As the use of DOACs expands, monitoring of renal function and appropriate dose adjustments are critical.

Long-term changes of renal function in relation to ace inhibitor/angiotensin receptor blocker dosing in patients with heart failure and chronic kidney disease.

PubMed

Fröhlich, Hanna; Nelges, Christoph; Täger, Tobias; Schwenger, Vedat; Cebola, Rita; Schnorbach, Johannes; Goode, Kevin M; Kazmi, Syed; Katus, Hugo A; Cleland, John G F; Clark, Andrew L; Frankenstein, Lutz

2016-08-01

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have become cornerstones of therapy for chronic heart failure (CHF). Guidelines advise high target doses for ACEIs/ARBs, but fear of worsening renal function may limit dose titration in patients with concomitant chronic kidney disease (CKD). In this retrospective observational study, we identified 722 consecutive patients with systolic CHF, stable CKD stage III/IV (estimated glomerular filtration rate [eGFR] 15-60 mL min(-1) 1.73 m(-2)) and chronic ACEI/ARB treatment from the outpatient heart failure clinics at the Universities of Hull, UK, and Heidelberg, Germany. Change of renal function, worsening CHF, and hyperkalemia at 12-month follow-up were analyzed as a function of both baseline ACEI/ARB dose and dose change from baseline. ΔeGFR was not related to baseline dose of ACEI/ARB (P = .58), or to relative (P = .18) or absolute change of ACEI/ARB dose (P = .21) during follow-up. Expressing change of renal function as a categorical variable (improved/stable/decreased) as well as subgroup analyses with respect to age, sex, New York Heart Association functional class, left ventricular ejection fraction, diabetes, concomitant aldosterone antagonists, CKD stage, hypertension, ACEI vs ARB, and congestion status yielded similar results. There was no association of dose/dose change with incidence of either worsening CHF or hyperkalemia. In patients with systolic CHF and stable CKD stage III/IV, neither continuation of high doses of ACEI/ARB nor up-titration was related to adverse changes in longer-term renal function. Conversely, down-titration was not associated with improvement in eGFR. Use of high doses of ACEI/ARB and their up-titration in patients with CHF and CKD III/IV may be appropriate provided that the patient is adequately monitored. Copyright © 2016 Elsevier Inc. All rights reserved.

The effective dose result of 18F-FDG PET-CT paediatric patients

NASA Astrophysics Data System (ADS)

Hussin, D.; Said, M. A.; Ali, N. S.; Tajuddin, A. A.; Zainon, R.

2017-05-01

Paediatric patient received high exposure from both CT and PET examination. Automatic Exposure Control (AEC) is important in CT dose reduction. This study aimed to compare the effective dose obtained from PET-CT scanner with and without the use of AEC function. In this study, 68 patients underwent PET-CT examination without the use of AEC function, while 25 patients used the AEC function during the examination. Patients involved in this study were between 2 to 15 years old with varies of malignancies and epilepsy diseases. The effective dose obtained from PET and CT examinations was calculated based on recommendation from International Commission on Radiological Protection (ICRP) Publication 106 and ICRP publication 102. The outcome of this study shows that the radiation dose was reduced up to 20% with the use of AEC function. The mean average of effective dose result obtained from PET and CT examinations without the use of AEC and AEC function were found to be as 6.67 mSv, 6.77 mSv, 6.03mSv and 4.96 mSv respectively. Where total effective dose result of PET-CT with non-AEC and AEC were found to be 13.44 mSv and 10.99 mSv respectively. Conclusion of this study is, the installation of AEC function in PET-CT machine does play important role in CT dose reduction especially for paediatric patient.

Using spatial information about recurrence risk for robust optimization of dose-painting prescription functions

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

Bender, Edward T.

Purpose: To develop a robust method for deriving dose-painting prescription functions using spatial information about the risk for disease recurrence. Methods: Spatial distributions of radiobiological model parameters are derived from distributions of recurrence risk after uniform irradiation. These model parameters are then used to derive optimal dose-painting prescription functions given a constant mean biologically effective dose. Results: An estimate for the optimal dose distribution can be derived based on spatial information about recurrence risk. Dose painting based on imaging markers that are moderately or poorly correlated with recurrence risk are predicted to potentially result in inferior disease control when comparedmore » the same mean biologically effective dose delivered uniformly. A robust optimization approach may partially mitigate this issue. Conclusions: The methods described here can be used to derive an estimate for a robust, patient-specific prescription function for use in dose painting. Two approximate scaling relationships were observed: First, the optimal choice for the maximum dose differential when using either a linear or two-compartment prescription function is proportional to R, where R is the Pearson correlation coefficient between a given imaging marker and recurrence risk after uniform irradiation. Second, the predicted maximum possible gain in tumor control probability for any robust optimization technique is nearly proportional to the square of R.« less

Assessment of target dose delivery in anal cancer using in vivo thermoluminescent dosimetry.

PubMed

Weber, D C; Nouet, P; Kurtz, J M; Allal, A S

2001-04-01

To measure anal dose during external beam radiotherapy (EBRT) using in vivo dosimetry, to study the difference of measured from prescribed dose values, and to evaluate possible associations of such differences with acute and late skin/mucosal toxicity and anorectal function. Thirty-one patients with localized anal carcinoma underwent in vivo measurements during the first EBRT session. Themoluminescent dosimeters (TLD) were placed at the center of the anal verge according to a localization protocol. No bolus was used. Patients received a median dose of 39.6 Gy (range: 36-45 Gy) by anteroposterior opposed AP/PA pelvic fields with 6 or 18 MV photons, followed by a median boost dose of 20 Gy (range: 13-24 Gy). Concomitant chemotherapy (CCT), consisting of 1-2 cycles of continuous infusion 5-fluorouracil (5-FU) and bolus mitomycin-C (MMC), was usually administered during the first weeks of the pelvic and boost EBRT courses. Acute and late skin/mucosal reactions were recorded according to the Radiation Therapy Oncology Group (RTOG) toxicity scale. Anal sphincter function was assessed using the Memorial Sloan Kettering Cancer Center (MSKCC) scale. TLD anal doses differed by a mean of 5.8% (SD: 5.8) in comparison to the central axis prescribed dose. Differences of at least 10% and at least 15% were observed in eight (26%) and three (9.7%) patients, respectively. TLD doses did not significantly correlate with acute or late grade 2-3 skin or mucosal toxicity. However, patients having good-fair MSKCC anal function had a significantly greater mean difference in anal TLD dose (10.5%, SD: 5.9) than patients having excellent function (3.8%, SD: 4.6) (P = 0.004). Prescribed dose values, length of follow-up, and age at diagnosis did not correlate with late sphincter function. These data show that AP/PA fields using megavoltage photons deliver adequate dose to the anal verge. However, in about one quarter of patients treated with this technique the anal dose varied from the prescribed dose by at least 10%. The observed correlation of TLD values and late sphincter function suggests that direct measurement of the dose delivered to the anal verge might be clinically relevant.

Optimization for high-dose-rate brachytherapy of cervical cancer with adaptive simulated annealing and gradient descent.

PubMed

Yao, Rui; Templeton, Alistair K; Liao, Yixiang; Turian, Julius V; Kiel, Krystyna D; Chu, James C H

2014-01-01

To validate an in-house optimization program that uses adaptive simulated annealing (ASA) and gradient descent (GD) algorithms and investigate features of physical dose and generalized equivalent uniform dose (gEUD)-based objective functions in high-dose-rate (HDR) brachytherapy for cervical cancer. Eight Syed/Neblett template-based cervical cancer HDR interstitial brachytherapy cases were used for this study. Brachytherapy treatment plans were first generated using inverse planning simulated annealing (IPSA). Using the same dwell positions designated in IPSA, plans were then optimized with both physical dose and gEUD-based objective functions, using both ASA and GD algorithms. Comparisons were made between plans both qualitatively and based on dose-volume parameters, evaluating each optimization method and objective function. A hybrid objective function was also designed and implemented in the in-house program. The ASA plans are higher on bladder V75% and D2cc (p=0.034) and lower on rectum V75% and D2cc (p=0.034) than the IPSA plans. The ASA and GD plans are not significantly different. The gEUD-based plans have higher homogeneity index (p=0.034), lower overdose index (p=0.005), and lower rectum gEUD and normal tissue complication probability (p=0.005) than the physical dose-based plans. The hybrid function can produce a plan with dosimetric parameters between the physical dose-based and gEUD-based plans. The optimized plans with the same objective value and dose-volume histogram could have different dose distributions. Our optimization program based on ASA and GD algorithms is flexible on objective functions, optimization parameters, and can generate optimized plans comparable with IPSA. Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

General equations for optimal selection of diagnostic image acquisition parameters in clinical X-ray imaging.

PubMed

Zheng, Xiaoming

2017-12-01

The purpose of this work was to examine the effects of relationship functions between diagnostic image quality and radiation dose on the governing equations for image acquisition parameter variations in X-ray imaging. Various equations were derived for the optimal selection of peak kilovoltage (kVp) and exposure parameter (milliAmpere second, mAs) in computed tomography (CT), computed radiography (CR), and direct digital radiography. Logistic, logarithmic, and linear functions were employed to establish the relationship between radiation dose and diagnostic image quality. The radiation dose to the patient, as a function of image acquisition parameters (kVp, mAs) and patient size (d), was used in radiation dose and image quality optimization. Both logistic and logarithmic functions resulted in the same governing equation for optimal selection of image acquisition parameters using a dose efficiency index. For image quality as a linear function of radiation dose, the same governing equation was derived from the linear relationship. The general equations should be used in guiding clinical X-ray imaging through optimal selection of image acquisition parameters. The radiation dose to the patient could be reduced from current levels in medical X-ray imaging.

Turing mechanism for homeostatic control of synaptic density during C. elegans growth

NASA Astrophysics Data System (ADS)

Brooks, Heather A.; Bressloff, Paul C.

2017-07-01

We propose a mechanism for the homeostatic control of synapses along the ventral cord of Caenorhabditis elegans during development, based on a form of Turing pattern formation on a growing domain. C. elegans is an important animal model for understanding cellular mechanisms underlying learning and memory. Our mathematical model consists of two interacting chemical species, where one is passively diffusing and the other is actively trafficked by molecular motors, which switch between forward and backward moving states (bidirectional transport). This differs significantly from the standard mechanism for Turing pattern formation based on the interaction between fast and slow diffusing species. We derive evolution equations for the chemical concentrations on a slowly growing one-dimensional domain, and use numerical simulations to demonstrate the insertion of new concentration peaks as the length increases. Taking the passive component to be the protein kinase CaMKII and the active component to be the glutamate receptor GLR-1, we interpret the concentration peaks as sites of new synapses along the length of C. elegans, and thus show how the density of synaptic sites can be maintained.

Does the KABC-II Display Ethnic Bias in the Prediction of Reading, Math, and Writing in Elementary School Through High School?

PubMed

Scheiber, Caroline

2017-09-01

This study explored whether the Kaufman Assessment Battery for Children-Second Edition (KABC-II) predicted academic achievement outcomes of the Kaufman Test of Educational Achievement-Second Edition (KTEA-II) equally well across a representative sample of African American, Hispanic, and Caucasian school-aged children ( N = 2,001) in three grade groups (1-4, 5-8, 9-12). It was of interest to study possible prediction bias in the slope and intercept of the five underlying Cattell-Horn-Carroll (CHC) cognitive factors of the KABC-II-Sequential/Gsm (Short-Term Memory), Learning/Glr (Long-Term Storage and Retrieval), Simultaneous/Gv (Visual Processing), Planning/Gf (Fluid Reasoning), and Knowledge/Gc (Crystallized Ability)-in estimating reading, writing, and math. Structural equation modeling techniques demonstrated a lack of bias in the slopes; however, four of the five CHC indexes showed a persistent overprediction of the minority groups' achievement in the intercept. The overprediction is likely attributable to institutional or societal contributions, which limit the students' ability to achieve to their fullest potential.

Optimizing global liver function in radiation therapy treatment planning

NASA Astrophysics Data System (ADS)

Wu, Victor W.; Epelman, Marina A.; Wang, Hesheng; Romeijn, H. Edwin; Feng, Mary; Cao, Yue; Ten Haken, Randall K.; Matuszak, Martha M.

2016-09-01

Liver stereotactic body radiation therapy (SBRT) patients differ in both pre-treatment liver function (e.g. due to degree of cirrhosis and/or prior treatment) and radiosensitivity, leading to high variability in potential liver toxicity with similar doses. This work investigates three treatment planning optimization models that minimize risk of toxicity: two consider both voxel-based pre-treatment liver function and local-function-based radiosensitivity with dose; one considers only dose. Each model optimizes different objective functions (varying in complexity of capturing the influence of dose on liver function) subject to the same dose constraints and are tested on 2D synthesized and 3D clinical cases. The normal-liver-based objective functions are the linearized equivalent uniform dose (\\ell \\text{EUD} ) (conventional ‘\\ell \\text{EUD} model’), the so-called perfusion-weighted \\ell \\text{EUD} (\\text{fEUD} ) (proposed ‘fEUD model’), and post-treatment global liver function (GLF) (proposed ‘GLF model’), predicted by a new liver-perfusion-based dose-response model. The resulting \\ell \\text{EUD} , fEUD, and GLF plans delivering the same target \\ell \\text{EUD} are compared with respect to their post-treatment function and various dose-based metrics. Voxel-based portal venous liver perfusion, used as a measure of local function, is computed using DCE-MRI. In cases used in our experiments, the GLF plan preserves up to 4.6 % ≤ft(7.5 % \\right) more liver function than the fEUD (\\ell \\text{EUD} ) plan does in 2D cases, and up to 4.5 % ≤ft(5.6 % \\right) in 3D cases. The GLF and fEUD plans worsen in \\ell \\text{EUD} of functional liver on average by 1.0 Gy and 0.5 Gy in 2D and 3D cases, respectively. Liver perfusion information can be used during treatment planning to minimize the risk of toxicity by improving expected GLF; the degree of benefit varies with perfusion pattern. Although fEUD model optimization is computationally inexpensive and often achieves better GLF than \\ell \\text{EUD} model optimization does, the GLF model directly optimizes a more clinically relevant metric and can further improve fEUD plan quality.

Assessment of organ-specific neutron equivalent doses in proton therapy using computational whole-body age-dependent voxel phantoms

NASA Astrophysics Data System (ADS)

Zacharatou Jarlskog, Christina; Lee, Choonik; Bolch, Wesley E.; Xu, X. George; Paganetti, Harald

2008-02-01

Proton beams used for radiotherapy will produce neutrons when interacting with matter. The purpose of this study was to quantify the equivalent dose to tissue due to secondary neutrons in pediatric and adult patients treated by proton therapy for brain lesions. Assessment of the equivalent dose to organs away from the target requires whole-body geometrical information. Furthermore, because the patient geometry depends on age at exposure, age-dependent representations are also needed. We implemented age-dependent phantoms into our proton Monte Carlo dose calculation environment. We considered eight typical radiation fields, two of which had been previously used to treat pediatric patients. The other six fields were additionally considered to allow a systematic study of equivalent doses as a function of field parameters. For all phantoms and all fields, we simulated organ-specific equivalent neutron doses and analyzed for each organ (1) the equivalent dose due to neutrons as a function of distance to the target; (2) the equivalent dose due to neutrons as a function of patient age; (3) the equivalent dose due to neutrons as a function of field parameters; and (4) the ratio of contributions to secondary dose from the treatment head versus the contribution from the patient's body tissues. This work reports organ-specific equivalent neutron doses for up to 48 organs in a patient. We demonstrate quantitatively how organ equivalent doses for adult and pediatric patients vary as a function of patient's age, organ and field parameters. Neutron doses increase with increasing range and modulation width but decrease with field size (as defined by the aperture). We analyzed the ratio of neutron dose contributions from the patient and from the treatment head, and found that neutron-equivalent doses fall off rapidly as a function of distance from the target, in agreement with experimental data. It appears that for the fields used in this study, the neutron dose lateral to the field is smaller than the reported scattered photon doses in a typical intensity-modulated photon treatment. Most importantly, our study shows that neutron doses to specific organs depend considerably on the patient's age and body stature. The younger the patient, the higher the dose deposited due to neutrons. Given the fact that the risk also increases with decreasing patient age, this factor needs to be taken into account when treating pediatric patients of very young ages and/or of small body size. The neutron dose from a course of proton therapy treatment (assuming 70 Gy in 30 fractions) could potentially (depending on patient's age, organ, treatment site and area of CT scan) be equivalent to up to ~30 CT scans.

Beneficial effect of recombinant rC1rC2 collagenases on human islet function: Efficacy of low-dose enzymes on pancreas digestion and yield.

PubMed

Loganathan, Gopalakrishnan; Subhashree, Venugopal; Breite, Andrew G; Tucker, William W; Narayanan, Siddharth; Dhanasekaran, Maheswaran; Mokshagundam, SriPrakash; Green, Michael L; Hughes, Michael G; Williams, Stuart K; Dwulet, Francis E; McCarthy, Robert C; Balamurugan, Appakalai N

2018-02-01

A high number of human islets can be isolated by using modern purified tissue dissociation enzymes; however, this requires the use of >20 Wunsch units (WU)/g of pancreas for digestion. Attempts to reduce this dose have resulted in pancreas underdigestion and poor islet recovery but improved islet function. In this study, we achieved a high number of functional islets using a low dose of recombinant collagenase enzyme mixture (RCEM-1200 WU rC2 and 10 million collagen-degrading activity [CDA] U of rC1 containing about 209 mg of collagenase to digest a 100-g pancreas). The collagenase dose used in these isolations is about 42% of the natural collagenase enzyme mixture (NCEM) dose commonly used to digest a 100-g pancreas. Low-dose RCEM was efficient in digesting entire pancreases to obtain higher yield (5535 ± 830 and 2582 ± 925 islet equivalent/g, P < .05) and less undigested tissue (16.7 ± 5% and 37.8 ± 3%, P < .05) compared with low-dose NCEM (12WU/g). Additionally, low-dose RCEM islets retained better morphology (confirmed with scanning electron microscopy) and higher in vitro basal insulin release (2391 ± 1342 and 1778 ± 978 μU/mL; P < .05) compared with standard-dose NCEM. Nude mouse bioassay demonstrated better islet function for low-dose RCEM (area under the curve [AUC] 24 968) compared with low-dose (AUC-38 225) or standard-dose NCEM (AUC-38 685), P < .05. This is the first report indicating that islet function can be improved by using low-dose rC1rC2 (RCEM). © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Radiotherapy Dose-Volume Effects on Salivary Gland Function

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

Deasy, Joseph O., E-mail: jdeasy@radonc.wustl.ed; Moiseenko, Vitali; Marks, Lawrence

2010-03-01

Publications relating parotid dose-volume characteristics to radiotherapy-induced salivary toxicity were reviewed. Late salivary dysfunction has been correlated to the mean parotid gland dose, with recovery occurring with time. Severe xerostomia (defined as long-term salivary function of <25% of baseline) is usually avoided if at least one parotid gland is spared to a mean dose of less than {approx}20 Gy or if both glands are spared to less than {approx}25 Gy (mean dose). For complex, partial-volume RT patterns (e.g., intensity-modulated radiotherapy), each parotid mean dose should be kept as low as possible, consistent with the desired clinical target volume coverage. Amore » lower parotid mean dose usually results in better function. Submandibular gland sparing also significantly decreases the risk of xerostomia. The currently available predictive models are imprecise, and additional study is required to identify more accurate models of xerostomia risk.« less

SU-F-18C-11: Diameter Dependency of the Radial Dose Distribution in a Long Polyethylene Cylinder

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

Bakalyar, D; McKenney, S; Feng, W

Purpose: The radial dose distribution in the central plane of a long cylinder following a long CT scan depends upon the diameter and composition of the cylinder. An understanding of this behavior is required for determining the spatial average of the dose in the central plane. Polyethylene, the material for construction of the TG200/ICRU phantom (30 cm in diameter) was used for this study. Size effects are germane to the principles incorporated in size specific dose estimates (SSDE); thus diameter dependency was explored as well. Method: ssuming a uniform cylinder and cylindrically symmetric conditions of irradiation, the dose distribution canmore » be described using a radial function. This function must be an even function of the radial distance due to the conditions of symmetry. Two effects are accounted for: The direct beam makes its weakest contribution at the center while the contribution due to scatter is strongest at the center and drops off abruptly at the outer radius. An analytic function incorporating these features was fit to Monte Carlo results determined for infinite polyethylene cylinders of various diameters. A further feature of this function is that it is integrable. Results: Symmetry and continuity dictate a local extremum at the center which is a minimum for the larger sizes. The competing effects described above can Resultin an absolute maximum occurring between the center and outer edge of the cylinders. For the smallest cylinders, the maximum dose may occur at the center. Conclusion: An integrable, analytic function can be used to characterize the radial dependency of dose for cylindrical CT phantoms of various sizes. One use for this is to help determine average dose distribution over the central cylinder plane when equilibrium dose has been reached.« less

On the parametrization of lateral dose profiles in proton radiation therapy.

PubMed

Bellinzona, V E; Ciocca, M; Embriaco, A; Fontana, A; Mairani, A; Mori, M; Parodi, K

2015-07-01

The accurate evaluation of the lateral dose profile is an important issue in the field of proton radiation therapy. The beam spread, due to Multiple Coulomb Scattering (MCS), is described by the Molière's theory. To take into account also the contribution of nuclear interactions, modern Treatment Planning Systems (TPSs) generally approximate the dose profiles by a sum of Gaussian functions. In this paper we have compared different parametrizations for the lateral dose profile of protons in water for therapeutical energies: the goal is to improve the performances of the actual treatment planning. We have simulated typical dose profiles at the CNAO (Centro Nazionale di Adroterapia Oncologica) beamline with the FLUKA code and validated them with data taken at CNAO considering different energies and depths. We then performed best fits of the lateral dose profiles for different functions using ROOT and MINUIT. The accuracy of the best fits was analyzed by evaluating the reduced χ(2), the number of free parameters of the functions and the calculation time. The best results were obtained with the triple Gaussian and double Gaussian Lorentz-Cauchy functions which have 6 parameters, but good results were also obtained with the so called Gauss-Rutherford function which has only 4 parameters. The comparison of the studied functions with accurate and validated Monte Carlo calculations and with experimental data from CNAO lead us to propose an original parametrization, the Gauss-Rutherford function, to describe the lateral dose profiles of proton beams. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Regional radiation dose-response modeling of functional liver in hepatocellular carcinoma patients with longitudinal sulfur colloid SPECT/CT: a proof of concept.

PubMed

Price, Ryan G; Apisarnthanarax, Smith; Schaub, Stephanie K; Nyflot, Matthew J; Chapman, Tobias R; Matesan, Manuela; Vesselle, Hubert J; Bowen, Stephen R

2018-06-19

We report on patient-specific quantitative changes in longitudinal sulfur colloid SPECT/CT as a function of regional radiation dose distributions to normal liver in a cohort of hepatocellular carcinoma patients. Dose-response thresholds and slopes varied with baseline liver function metrics, and extreme values were found in patients with fatal hepatotoxicity. Dose-response modeling of normal liver in individual HCC patients has potential to characterize in vivo radiosensitivity, identify high risk subgroups, and personalize treatment planning dose constraints. Hepatotoxicity risk in hepatocellular carcinoma (HCC) patients is modulated by radiation dose delivered to normal liver tissue, but reported dose-response data are limited. Our prior work established baseline [ 99m Tc]sulfur colloid (SC) SPECT/CT liver function imaging biomarkers that predict clinical outcomes. We conducted a proof-of-concept investigation with longitudinal SC SPECT/CT to characterize patient-specific radiation dose-response relationships as surrogates for liver radiosensitivity. SC SPECT/CT images of 15 HCC patients with variable Child-Pugh status (8 CP-A, 7 CP-B/C) were acquired in treatment position prior to and 1 month (nominal) after SBRT (n=6) or proton therapy (n=9). Localized rigid registrations between pre/post-treatment CT to planning CT scans were performed, and transformations were applied to pre/post-treatment SC SPECT images. Radiotherapy doses were converted to EQD2 α/β=3 and Gy (RBE), and binned in 5 GyEQD2 increments within tumor-subtracted livers. Mean dose and percent change (%ΔSC) between pre- and post-treatment SPECT uptake, normalized to regions receiving < 5 GyEQD2, were calculated in each binned dose region. Dose-response data were parameterized by sigmoid functions (double exponential) consisting of maximum reduction (%ΔSC max ), dose midpoint (D mid ), and dose-response slope (α mid ) parameters. Individual patient sigmoid dose-response curves had high goodness-of-fit (median R 2 = 0.96, range 0.76-0.99). Large inter-patient variability was observed, with median (range) in %ΔSC max of 44% (20-75%), D mid of 13 Gy (4-27 GyEQD2), and α mid of 0.11 GyEQD2 -1 (0.04-0.29 GyEQD2 -1 ), respectively. Eight of 15 patients had %ΔSC max = 20-45%, while 7/15 had %ΔSC max = 60-75%, with subgroups made up of variable baseline liver function status and radiation treatment modality. Fatal hepatotoxicity occurred in patients (2/15) with low TLF (< 0.12) and low D mid (< 7 GyEQD2). Longitudinal SC SPECT/CT imaging revealed patient-specific variations in dose-response, and may identify patients with poor baseline liver function and increased sensitivity to radiation therapy. Validation of this regional liver dose-response modeling concept as a surrogate for patient-specific radiosensitivity has potential to guide HCC therapy regimen selection and planning constraints. Copyright © 2018 Elsevier Inc. All rights reserved.

Sun-Induced Changes in Stratum Corneum Function Are Gender and Dose Dependent in a Chinese Population

PubMed Central

Liu, Z.; Fluhr, J.W.; Song, S.P.; Sun, Z.; Wang, H.; Shi, Y.J.; Elias, P.M.; Man, M.-Q.

2010-01-01

Previous studies have demonstrated that UVB radiation changes the epidermal permeability barrier and stratum corneum (SC) hydration. It is well known that sun exposure causes erythema, sunburn and melanoma. However, whether daily sun exposure alters SC integrity and epidermal permeability barrier function is largely unknown, especially in Chinese subjects. In the present study, we assess the SC integrity, SC hydration and epidermal permeability barrier function following various doses of sun exposure. A total of 258 subjects (124 males and 134 females) aged 18–50 years were enrolled. A multifunctional skin physiology monitor (Courage & Khazaka MPA5) was used to measure SC hydration and transepidermal water loss (TEWL) on the forearms. In males, basal TEWL was higher with higher doses of sun exposure than with lower doses and control, whereas in females, basal TEWL was higher with lower doses of sun exposure than with higher doses and control. In the group with higher doses of sun exposure, TEWL in females was significantly lower than that in males. The barrier recovery was faster in females than in males in both control and lower-dose groups. In both males and females, barrier recovery was delayed with higher doses of sun exposure. In males, sun exposure did not alter SC hydration, while in females SC hydration was lower with lower doses of sun exposure as compared with control and higher doses of sun exposure. These results demonstrated that sun-induced changes in SC function and SC hydration vary with gender and the extent of sun exposure. PMID:20571289

The energy dependence of the lateral dose response functions of detectors with various densities in photon-beam dosimetry.

PubMed

Looe, Hui Khee; Harder, Dietrich; Poppe, Björn

2017-02-07

The lateral dose response function is a general characteristic of the volume effect of a detector used for photon dosimetry in a water phantom. It serves as the convolution kernel transforming the true absorbed dose to water profile, which would be produced within the undisturbed water phantom, into the detector-measured signal profile. The shape of the lateral dose response function characterizes (i) the volume averaging attributable to the detector's size and (ii) the disturbance of the secondary electron field associated with the deviation of the electron density of the detector material from the surrounding water. In previous work, the characteristic dependence of the shape of the lateral dose response function upon the electron density of the detector material was studied for 6 MV photons by Monte Carlo simulation of a wall-less voxel-sized detector (Looe et al 2015 Phys. Med. Biol. 60 6585-07). This study is here continued for 60 Co gamma rays and 15 MV photons in comparison with 6 MV photons. It is found (1) that throughout these photon spectra the shapes of the lateral dose response functions are retaining their characteristic dependence on the detector's electron density, and (2) that their energy-dependent changes are only moderate. This appears as a practical advantage because the lateral dose response function can then be treated as practically invariant across a clinical photon beam in spite of the known changes of the photon spectrum with increasing distance from the beam axis.

Changes in Regional Ventilation During Treatment and Dosimetric Advantages of CT Ventilation Image Guided Radiation Therapy for Locally Advanced Lung Cancer.

PubMed

Yamamoto, Tokihiro; Kabus, Sven; Bal, Matthieu; Bzdusek, Karl; Keall, Paul J; Wright, Cari; Benedict, Stanley H; Daly, Megan E

2018-05-04

Lung functional image guided radiation therapy (RT) that avoids irradiating highly functional regions has potential to reduce pulmonary toxicity following RT. Tumor regression during RT is common, leading to recovery of lung function. We hypothesized that computed tomography (CT) ventilation image-guided treatment planning reduces the functional lung dose compared to standard anatomic image-guided planning in 2 different scenarios with or without plan adaptation. CT scans were acquired before RT and during RT at 2 time points (16-20 Gy and 30-34 Gy) for 14 patients with locally advanced lung cancer. Ventilation images were calculated by deformable image registration of four-dimensional CT image data sets and image analysis. We created 4 treatment plans at each time point for each patient: functional adapted, anatomic adapted, functional unadapted, and anatomic unadapted plans. Adaptation was performed at 2 time points. Deformable image registration was used for accumulating dose and calculating a composite of dose-weighted ventilation used to quantify the lung accumulated dose-function metrics. The functional plans were compared with the anatomic plans for each scenario separately to investigate the hypothesis at a significance level of 0.05. Tumor volume was significantly reduced by 20% after 16 to 20 Gy (P = .02) and by 32% after 30 to 34 Gy (P < .01) on average. In both scenarios, the lung accumulated dose-function metrics were significantly lower in the functional plans than in the anatomic plans without compromising target volume coverage and adherence to constraints to critical structures. For example, functional planning significantly reduced the functional mean lung dose by 5.0% (P < .01) compared to anatomic planning in the adapted scenario and by 3.6% (P = .03) in the unadapted scenario. This study demonstrated significant reductions in the accumulated dose to the functional lung with CT ventilation image-guided planning compared to anatomic image-guided planning for patients showing tumor regression and changes in regional ventilation during RT. Copyright © 2018 Elsevier Inc. All rights reserved.

TU-F-12A-04: Differential Radiation Avoidance of Functional Liver Regions Defined by 99mTc-Sulfur Colloid SPECT/CT with Proton Therapy

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

Bowen, S; Miyaoka, R; Kinahan, P

2014-06-15

Purpose: Radiotherapy for hepatocellular carcinoma patients is conventionally planned without consideration of spatial heterogeneity in hepatic function, which may increase risk of radiation-induced liver disease. Pencil beam scanning (PBS) proton radiotherapy (pRT) plans were generated to differentially decrease dose to functional liver volumes (FLV) defined on [{sup 99m}Tc]sulfur colloid (SC) SPECT/CT images (functional avoidance plans) and compared against conventional pRT plans. Methods: Three HCC patients underwent SC SPECT/CT scans for pRT planning acquired 15 min post injection over 24 min. Images were reconstructed with OSEM following scatter, collimator, and exhale CT attenuation correction. Functional liver volumes (FLV) were defined bymore » liver:spleen uptake ratio thresholds (43% to 90% maximum). Planning objectives to FLV were based on mean SC SPECT uptake ratio relative to GTV-subtracted liver and inversely scaled to mean liver dose of 20 Gy. PTV target coverage (V{sub 95}) was matched between conventional and functional avoidance plans. PBS pRT plans were optimized in RayStation for single field uniform dose (SFUD) and systematically perturbed to verify robustness to uncertainty in range, setup, and motion. Relative differences in FLV DVH and target dose heterogeneity (D{sub 2}-D{sub 98})/D50 were assessed. Results: For similar liver dose between functional avoidance and conventional PBS pRT plans (D{sub mean}≤5% difference, V{sub 18Gy}≤1% difference), dose to functional liver volumes were lower in avoidance plans but varied in magnitude across patients (FLV{sub 70%max} D{sub mean}≤26% difference, V{sub 18Gy}≤8% difference). Higher PTV dose heterogeneity in avoidance plans was associated with lower functional liver dose, particularly for the largest lesion [(D{sub 2}-D{sub 98})/D{sub 50}=13%, FLV{sub 90%max}=50% difference]. Conclusion: Differential avoidance of functional liver regions defined on sulfur colloid SPECT/CT is feasible with proton therapy. The magnitude of benefit appears to be patient specific and dependent on tumor location, size, and proximity to functional volumes. Further investigation in a larger cohort of patients may validate the clinical utility of functional avoidance planning of HCC radiotherapy.« less

Toxicity and motor changes in Africanized honey bees (Apis mellifera L.) exposed to fipronil and imidacloprid.

PubMed

Bovi, Thaís S; Zaluski, Rodrigo; Orsi, Ricardo O

2018-01-01

This study evaluated the in vitro toxicity and motor activity changes in African-derived adult honey bees (Apis mellifera L.) exposed to lethal or sublethal doses of the insecticides fipronil and imidacloprid. Mortality of bees was assessed to determine the ingestion and contact lethal dose for 24 h using probit analysis. Motor activities in bees exposed to lethal (LD50) and sublethal doses (1/500th of the lethal dose) of both insecticides were evaluated in a behavioral observation box at 1 and 4 h. Ingestion and contact lethal doses of fipronil were 0.2316 ? 0.0626 and 0.0080 ? 0.0021 μg/bee, respectively. Ingestion and contact lethal doses of imidacloprid were 0.1079 ? 0.0375 and 0.0308 ? 0.0218 μg/bee, respectively. Motor function of bees exposed to lethal doses of fipronil and imidacloprid was impaired; exposure to sublethal doses of fipronil but not imidacloprid impaired motor function. The insecticides evaluated in this study were highly toxic to African-derived A. mellifera and caused impaired motor function in these pollinators.

Regional Lung Function Profiles of Stage I and III Lung Cancer Patients: An Evaluation for Functional Avoidance Radiation Therapy

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

Vinogradskiy, Yevgeniy, E-mail: yevgeniy.vinogradskiy@ucdenver.edu; Schubert, Leah; Diot, Quentin

2016-07-15

Purpose: The development of clinical trials is underway to use 4-dimensional computed tomography (4DCT) ventilation imaging to preferentially spare functional lung in patients undergoing radiation therapy. The purpose of this work was to generate data to aide with clinical trial design by retrospectively characterizing dosimetric and functional profiles for patients with different stages of lung cancer. Methods and Materials: A total of 118 lung cancer patients (36% stage I and 64% stage III) from 2 institutions were used for the study. A 4DCT-ventilation map was calculated using the patient's 4DCT imaging, deformable image registration, and a density-change–based algorithm. To assessmore » each patient's spatial ventilation profile both quantitative and qualitative metrics were developed, including an observer-based defect observation and metrics based on the ventilation in each lung third. For each patient we used the clinical doses to calculate functionally weighted mean lung doses and metrics that assessed the interplay between the spatial location of the dose and high-functioning lung. Results: Both qualitative and quantitative metrics revealed a significant difference in functional profiles between the 2 stage groups (P<.01). We determined that 65% of stage III and 28% of stage I patients had ventilation defects. Average functionally weighted mean lung dose was 19.6 Gy and 5.4 Gy for stage III and I patients, respectively, with both groups containing patients with large spatial overlap between dose and high-function regions. Conclusion: Our 118-patient retrospective study found that 65% of stage III patients have regionally variant ventilation profiles that are suitable for functional avoidance. Our results suggest that regardless of disease stage, it is possible to have unique spatial interplay between dose and high-functional lung, highlighting the importance of evaluating the function of each patient and developing a personalized functional avoidance treatment approach.« less

Randomized trial of single-dose versus divided-dose rabbit anti-thymocyte globulin induction in renal transplantation: an interim report.

PubMed

Stevens, R Brian; Mercer, David F; Grant, Wendy J; Freifeld, Alison G; Lane, James T; Groggel, Gerald C; Rigley, Theodore H; Nielsen, Kathleen J; Henning, Megan E; Skorupa, Jill Y; Skorupa, Anna J; Christensen, Kecia A; Sandoz, John P; Kellogg, Anna M; Langnas, Alan N; Wrenshall, Lucile E

2008-05-27

The optimal dosing protocol for rabbit anti-thymocyte globulin (rATG) induction in renal transplantation has not been determined, but evidence exists that rATG infusion before renal allograft reperfusion improves early graft function. Infusing a large rATG dose over a short interval has not previously been evaluated for its effect on renal function and allograft nephropathy in a prospective, randomized comparison against conventional rATG induction. Between April 20, 2004 and December 26, 2007 we enrolled renal transplant patients into a prospective, randomized, nonblinded trial of two rATG dosing protocols (single dose, 6 mg/kg vs. divided doses, 1.5 mg/kg every other day x 4; target enrollment=160) followed after 6 months by calcineurin-inhibitor withdrawal. Primary endpoints are renal function by calculated glomerular filtration rate (GFR) and chronic allograft nephropathy at protocol biopsy. We now present the early GFR data of all 160 patients and safety and efficacy data of the first 142 patients with 6 months follow up and before calcineurin inhibitor withdrawal (average follow up=23.3+/-11.6 months). There were no differences between groups in rATG-related adverse events, patient and graft survival, acute rejection, or chronic allograft nephropathy rate at 6 months. Calculated DeltaGFR (POD 1-4) was significantly better in the single-dose group (P=0.02), with a trend toward improved renal function from months 2 to 6 in recipients of deceased donor kidneys (P=0.08). This study demonstrates that administering 6 mg/kg of rATG over 24 hr is safe and is associated with improved early renal function compared with administering rATG in alternate-day doses.

Low Antigen Dose in Adjuvant-Based Vaccination Selectively Induces CD4 T Cells with Enhanced Functional Avidity and Protective Efficacy

PubMed Central

Wang, Yichuan; Solaymani-Mohammadi, Shahram; Frey, Blake; Kulkarni, Shweta; Andersen, Peter; Agger, Else Marie; Sui, Yongjun

2017-01-01

T cells with high functional avidity can sense and respond to low levels of cognate Ag, a characteristic that is associated with more potent responses against tumors and many infections, including HIV. Although an important determinant of T cell efficacy, it has proven difficult to selectively induce T cells of high functional avidity through vaccination. Attempts to induce high-avidity T cells by low-dose in vivo vaccination failed because this strategy simply gave no response. Instead, selective induction of high-avidity T cells has required in vitro culturing of specific T cells with low Ag concentrations. In this study, we combined low vaccine Ag doses with a novel potent cationic liposomal adjuvant, cationic adjuvant formulation 09, consisting of dimethyldioctadecylammonium liposomes incorporating two immunomodulators (monomycolyl glycerol analog and polyinosinic-polycytidylic acid) that efficiently induces CD4 Th cells, as well as cross-primes CD8 CTL responses. We show that vaccination with low Ag dose selectively primes CD4 T cells of higher functional avidity, whereas CD8 T cell functional avidity was unrelated to vaccine dose in mice. Importantly, CD4 T cells of higher functional avidity induced by low-dose vaccinations showed higher cytokine release per cell and lower inhibitory receptor expression (PD-1, CTLA-4, and the apoptosis-inducing Fas death receptor) compared with their lower-avidity CD4 counterparts. Notably, increased functional CD4 T cell avidity improved antiviral efficacy of CD8 T cells. These data suggest that potent adjuvants, such as cationic adjuvant formulation 09, render low-dose vaccination a feasible and promising approach for generating high-avidity T cells through vaccination. PMID:28348274

The "doses" of initial, untreated hallucinations and delusions: a proof-of-concept study of enhanced predictors of first-episode symptomatology and functioning relative to duration of untreated psychosis.

PubMed

Compton, Michael T; Gordon, Tynessa L; Weiss, Paul S; Walker, Elaine F

2011-11-01

A prominent limitation of literature on duration of untreated psychosis (DUP) is that researchers have studied only unidimensional duration as an early-course predictor, neglecting potential effects of frequency/severity of initial, untreated psychosis. This study demonstrates utility of the concept of "doses" of initial, untreated hallucinations and delusions-representing more complete measures of "exposure"-as enhanced predictors of symptomatology/functioning relative to DUP alone. 109 first-episode patients with a psychotic disorder based on Structured Clinical Interview for DSM-IV Axis I Disorders criteria were assessed at 3 public-sector psychiatric units serving an urban, socially disadvantaged, predominantly African American community between July 2004 and June 2008. Dependent variables included negative symptoms, general psychopathology, insight, and global functioning at initial hospitalization. When added to a baseline model (age, gender, and premorbid academic and social functioning), DUP predicted current negative symptoms (P = .02, model R(2) = 0.20), though dose of hallucinations and dose of delusions did not. However, regarding general psychopathology symptoms, DUP was not predictive, though dose of delusions was, when controlling for the other 5 variables (P = .02, model R(2) = 0.15). DUP was not a significant predictor of insight, though dose of hallucinations was, such that a greater dose of initial, untreated hallucinations was associated with better insight at initial hospitalization (P < .01, model R(2) = 0.20). DUP was associated with global functioning (P = .05), and dose of delusions added significantly to this prediction (P = .04; model R(2) = 0.13). Doses of initial, untreated hallucinations and delusions add substantively, though differentially, to the prediction of early-course symptomatology and functioning. Findings suggest a need for focused research on frequency/severity of pretreatment psychotic symptoms beyond duration measures. © Copyright 2011 Physicians Postgraduate Press, Inc.

Laser-based irradiation apparatus and method to measure the functional dose-rate response of semiconductor devices

DOEpatents

Horn, Kevin M [Albuquerque, NM

2008-05-20

A broad-beam laser irradiation apparatus can measure the parametric or functional response of a semiconductor device to exposure to dose-rate equivalent infrared laser light. Comparisons of dose-rate response from before, during, and after accelerated aging of a device, or from periodic sampling of devices from fielded operational systems can determine if aging has affected the device's overall functionality. The dependence of these changes on equivalent dose-rate pulse intensity and/or duration can be measured with the apparatus. The synchronized introduction of external electrical transients into the device under test can be used to simulate the electrical effects of the surrounding circuitry's response to a radiation exposure while exposing the device to dose-rate equivalent infrared laser light.

Non-Malignant Thyroid Diseases Following a Wide Range of Radiation Exposures

PubMed Central

Ron, Elaine; Brenner, Alina

2013-01-01

Background The thyroid gland is one of the most radiosensitive human organs. While it is well known that radiation exposure increases the risk of thyroid cancer, less is known about its effects in relation to non-malignant thyroid diseases. Objectives The aim of this review is to evaluate the effects of high and low dose radiation on benign structural and functional diseases of the thyroid. Methods We examined the results of major studies from cancer patients treated with high-dose radiotherapy or thyrotoxicosis patients treated with high doses of iodine-131, patients treated with moderate to high dose radiotherapy for benign diseases, persons exposed to low doses from environmental radiation and survivors of the atomic bombings who were exposed to a range of doses. We evaluated radiation effects on structural (tumors, nodules), functional (hyper- and hypothyroidism), and autoimmune thyroid diseases. Results Following a wide range of doses of ionizing radiation, an increased risk of thyroid adenomas and nodules was observed in a variety of populations and settings. The dose response appeared to be linear at low to moderate doses, but in one study there was some suggestion of a reduction in risk above 5 Gy. The elevated risk for benign tumors continues for decades following exposure. Considerably less consistent findings are available regarding functional thyroid diseases including autoimmune diseases. In general, associations for these outcomes were fairly weak and significant radiation effects were most often observed following high doses, particularly for hypothyroidism. Conclusions A significant radiation dose-response relation was demonstrated for benign nodules and follicular adenomas. The effects of radiation on functional thyroid diseases are less clear, partly due to the greater difficulties studying these diseases. PMID:21128812

Calculation of Dose, Dose Equivalent, and Relative Biological Effectiveness for High Charge and Energy Ion Beams

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Reginatto, M.; Hajnal, F.; Chun, S. Y.

1995-01-01

The Green's function for the transport of ions of high charge and energy is utilized with a nuclear fragmentation database to evaluate dose, dose equivalent, and RBE for C3H1OT1/2 cell survival and neoplastic transformation as a function of depth in soft tissue. Such evaluations are useful to estimates of biological risk for high altitude aircraft, space operations, accelerator operations, and biomedical applications.

Calculation of dose, dose equivalent, and relative biological effectiveness for high charge and energy ion beams

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Chun, S. Y.; Reginatto, M.; Hajnal, F.

1995-01-01

The Green's function for the transport of ions of high charge and energy is utilized with a nuclear fragmentation database to evaluate dose, dose equivalent, and RBE for C3H10T1/2 cell survival and neo-plastic transformation as function of depth in soft tissue. Such evaluations are useful to estimates of biological risk for high altitude aircraft, space operations, accelerator operations, and biomedical application.

Systemic effects of low-dose dopamine during administration of cytarabine.

PubMed

Connelly, James; Benani, Dina J; Newman, Matthew; Burton, Bradley; Crow, Jessica; Levis, Mark

2017-09-01

Purpose Low-dose dopamine has been utilized to improve renal blood flow, urine output, and reduce drug-induced nephrotoxicity. The purpose of this study was to assess changes in renal function, cardiovascular adverse events, and neurologic toxicity in patients receiving cytarabine with or without low-dose dopamine. Methods A retrospective, single-center, cohort study of patients receiving cytarabine at 667 mg/m 2 /dose or greater, with or without dopamine at ≤5 mcg/kg/min. Cohorts were based upon initiation or absence of low-dose dopamine; cytarabine only, cytarabine + pre- and day of low-dose dopamine, and cytarabine + post-low-dose dopamine. Renal outcomes (urine output, serum creatinine, and creatinine clearance) were compared with baseline and between cohorts. Safety endpoints (arrhythmias, tachycardia, and neurotoxicity) were compared between cohorts based on low-dose dopamine exposure. Results There was no difference in urine output from baseline in all cohorts. Comparing cytarabine only and pre- and day of low-dose dopamine cohorts, there was no difference in urine output. In those receiving low-dose dopamine, there was no difference in serum creatinine and creatinine clearance from baseline. No arrhythmias were documented during the study period, and there was no difference in the incidence of tachycardia between groups (P = 0.66). Neurotoxicity was reported in three patients who were on low-dose dopamine. Conclusion Though variation existed in individual patients administered low-dose dopamine, the use of low-dose dopamine did not significantly impact renal function in this small sample at a single institution. In addition, low-dose dopamine did not negatively impact cardiovascular function.

TU-EF-204-07: Add Tube Current Modulation to a Low Dose Simulation Tool for CT Systems

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

Ding, Y.; Department of Physics, University of Arizona, Tucson, AZ; Wen, G.

2015-06-15

Purpose: We extended the capabilities of a low dose simulation tool to model Tube-Current Modulation (TCM). TCM is widely used in clinical practice to reduce radiation dose in CT scans. We expect the tool to be valuable for various clinical applications (e.g., optimize protocols, compare reconstruction techniques and evaluate TCM methods). Methods: The tube current is input as a function of z location, instead of a fixed value. Starting from the line integrals of a scan, a new Poisson noise realization at a lower dose is generated for each view. To validate the new functionality, we compared simulated scans withmore » real scans in image space. Results: First we assessed noise in the difference between the low-dose simulations and the original high-dose scan. When the simulated tube current is a step function of z location, the noise at each segment matches the noise of 3 separate constant-tube-current-simulations. Secondly, with a phantom that forces TCM, we compared a low-dose simulation with an equivalent real low-dose scan. The mean CT number of the simulated scan and the real low-dose scan were 137.7±0.6 and 137.8±0.5 respectively. Furthermore, with 240 ROIs, the noise of the simulated scan and the real low-dose scan were 24.03±0.45 and 23.99±0.43 respectively, and they were not statistically different (2-sample t-test, p-value=0.28). The facts that the noise reflected the trend of the TCM curve, and that the absolute noise measurements were not statistically different validated the TCM function. Conclusion: We successfully added tube-current modulation functionality in an existing low dose simulation tool. We demonstrated that the noise reflected an input tube-current modulation curve. In addition, we verified that the noise and mean CT number of our simulation agreed with a real low dose scan. The authors are all employees of Philips. Yijun Ding is also supported by NIBIB P41EB002035 and NIBIB R01EB000803.« less

Commissioning dose computation models for spot scanning proton beams in water for a commercially available treatment planning system

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

Zhu, X. R.; Poenisch, F.; Lii, M.

2013-04-15

Purpose: To present our method and experience in commissioning dose models in water for spot scanning proton therapy in a commercial treatment planning system (TPS). Methods: The input data required by the TPS included in-air transverse profiles and integral depth doses (IDDs). All input data were obtained from Monte Carlo (MC) simulations that had been validated by measurements. MC-generated IDDs were converted to units of Gy mm{sup 2}/MU using the measured IDDs at a depth of 2 cm employing the largest commercially available parallel-plate ionization chamber. The sensitive area of the chamber was insufficient to fully encompass the entire lateralmore » dose deposited at depth by a pencil beam (spot). To correct for the detector size, correction factors as a function of proton energy were defined and determined using MC. The fluence of individual spots was initially modeled as a single Gaussian (SG) function and later as a double Gaussian (DG) function. The DG fluence model was introduced to account for the spot fluence due to contributions of large angle scattering from the devices within the scanning nozzle, especially from the spot profile monitor. To validate the DG fluence model, we compared calculations and measurements, including doses at the center of spread out Bragg peaks (SOBPs) as a function of nominal field size, range, and SOBP width, lateral dose profiles, and depth doses for different widths of SOBP. Dose models were validated extensively with patient treatment field-specific measurements. Results: We demonstrated that the DG fluence model is necessary for predicting the field size dependence of dose distributions. With this model, the calculated doses at the center of SOBPs as a function of nominal field size, range, and SOBP width, lateral dose profiles and depth doses for rectangular target volumes agreed well with respective measured values. With the DG fluence model for our scanning proton beam line, we successfully treated more than 500 patients from March 2010 through June 2012 with acceptable agreement between TPS calculated and measured dose distributions. However, the current dose model still has limitations in predicting field size dependence of doses at some intermediate depths of proton beams with high energies. Conclusions: We have commissioned a DG fluence model for clinical use. It is demonstrated that the DG fluence model is significantly more accurate than the SG fluence model. However, some deficiencies in modeling the low-dose envelope in the current dose algorithm still exist. Further improvements to the current dose algorithm are needed. The method presented here should be useful for commissioning pencil beam dose algorithms in new versions of TPS in the future.« less

Commissioning dose computation models for spot scanning proton beams in water for a commercially available treatment planning system

PubMed Central

Zhu, X. R.; Poenisch, F.; Lii, M.; Sawakuchi, G. O.; Titt, U.; Bues, M.; Song, X.; Zhang, X.; Li, Y.; Ciangaru, G.; Li, H.; Taylor, M. B.; Suzuki, K.; Mohan, R.; Gillin, M. T.; Sahoo, N.

2013-01-01

Purpose: To present our method and experience in commissioning dose models in water for spot scanning proton therapy in a commercial treatment planning system (TPS). Methods: The input data required by the TPS included in-air transverse profiles and integral depth doses (IDDs). All input data were obtained from Monte Carlo (MC) simulations that had been validated by measurements. MC-generated IDDs were converted to units of Gy mm2/MU using the measured IDDs at a depth of 2 cm employing the largest commercially available parallel-plate ionization chamber. The sensitive area of the chamber was insufficient to fully encompass the entire lateral dose deposited at depth by a pencil beam (spot). To correct for the detector size, correction factors as a function of proton energy were defined and determined using MC. The fluence of individual spots was initially modeled as a single Gaussian (SG) function and later as a double Gaussian (DG) function. The DG fluence model was introduced to account for the spot fluence due to contributions of large angle scattering from the devices within the scanning nozzle, especially from the spot profile monitor. To validate the DG fluence model, we compared calculations and measurements, including doses at the center of spread out Bragg peaks (SOBPs) as a function of nominal field size, range, and SOBP width, lateral dose profiles, and depth doses for different widths of SOBP. Dose models were validated extensively with patient treatment field-specific measurements. Results: We demonstrated that the DG fluence model is necessary for predicting the field size dependence of dose distributions. With this model, the calculated doses at the center of SOBPs as a function of nominal field size, range, and SOBP width, lateral dose profiles and depth doses for rectangular target volumes agreed well with respective measured values. With the DG fluence model for our scanning proton beam line, we successfully treated more than 500 patients from March 2010 through June 2012 with acceptable agreement between TPS calculated and measured dose distributions. However, the current dose model still has limitations in predicting field size dependence of doses at some intermediate depths of proton beams with high energies. Conclusions: We have commissioned a DG fluence model for clinical use. It is demonstrated that the DG fluence model is significantly more accurate than the SG fluence model. However, some deficiencies in modeling the low-dose envelope in the current dose algorithm still exist. Further improvements to the current dose algorithm are needed. The method presented here should be useful for commissioning pencil beam dose algorithms in new versions of TPS in the future. PMID:23556893

Commissioning dose computation models for spot scanning proton beams in water for a commercially available treatment planning system.

PubMed

Zhu, X R; Poenisch, F; Lii, M; Sawakuchi, G O; Titt, U; Bues, M; Song, X; Zhang, X; Li, Y; Ciangaru, G; Li, H; Taylor, M B; Suzuki, K; Mohan, R; Gillin, M T; Sahoo, N

2013-04-01

To present our method and experience in commissioning dose models in water for spot scanning proton therapy in a commercial treatment planning system (TPS). The input data required by the TPS included in-air transverse profiles and integral depth doses (IDDs). All input data were obtained from Monte Carlo (MC) simulations that had been validated by measurements. MC-generated IDDs were converted to units of Gy mm(2)/MU using the measured IDDs at a depth of 2 cm employing the largest commercially available parallel-plate ionization chamber. The sensitive area of the chamber was insufficient to fully encompass the entire lateral dose deposited at depth by a pencil beam (spot). To correct for the detector size, correction factors as a function of proton energy were defined and determined using MC. The fluence of individual spots was initially modeled as a single Gaussian (SG) function and later as a double Gaussian (DG) function. The DG fluence model was introduced to account for the spot fluence due to contributions of large angle scattering from the devices within the scanning nozzle, especially from the spot profile monitor. To validate the DG fluence model, we compared calculations and measurements, including doses at the center of spread out Bragg peaks (SOBPs) as a function of nominal field size, range, and SOBP width, lateral dose profiles, and depth doses for different widths of SOBP. Dose models were validated extensively with patient treatment field-specific measurements. We demonstrated that the DG fluence model is necessary for predicting the field size dependence of dose distributions. With this model, the calculated doses at the center of SOBPs as a function of nominal field size, range, and SOBP width, lateral dose profiles and depth doses for rectangular target volumes agreed well with respective measured values. With the DG fluence model for our scanning proton beam line, we successfully treated more than 500 patients from March 2010 through June 2012 with acceptable agreement between TPS calculated and measured dose distributions. However, the current dose model still has limitations in predicting field size dependence of doses at some intermediate depths of proton beams with high energies. We have commissioned a DG fluence model for clinical use. It is demonstrated that the DG fluence model is significantly more accurate than the SG fluence model. However, some deficiencies in modeling the low-dose envelope in the current dose algorithm still exist. Further improvements to the current dose algorithm are needed. The method presented here should be useful for commissioning pencil beam dose algorithms in new versions of TPS in the future.

Hemopoietic Response to Low Dose-Rates of Ionizing Radiation Shows Stem Cell Tolerance and Adaptation

PubMed Central

Fliedner, Theodor M.; Graessle, Dieter H.; Meineke, Viktor; Feinendegen, Ludwig E.

2012-01-01

Chronic exposure of mammals to low dose-rates of ionizing radiation affects proliferating cell systems as a function of both dose-rate and the total dose accumulated. The lower the dose-rate the higher needs to be the total dose for a deterministic effect, i.e., tissue reaction to appear. Stem cells provide for proliferating, maturing and functional cells. Stem cells usually are particularly radiosensitive and damage to them may propagate to cause failure of functional cells. The paper revisits 1) medical histories with emphasis on the hemopoietic system of the victims of ten accidental chronic radiation exposures, 2) published hematological findings of long-term chronically gamma-irradiated rodents, and 3) such findings in dogs chronically exposed in large life-span studies. The data are consistent with the hypothesis that hemopoietic stem and early progenitor cells have the capacity to tolerate and adapt to being repetitively hit by energy deposition events. The data are compatible with the “injured stem cell hypothesis”, stating that radiation–injured stem cells, depending on dose-rate, may continue to deliver clones of functional cells that maintain homeostasis of hemopoiesis throughout life. Further studies perhaps on separated hemopoietic stem cells may unravel the molecular-biology mechanisms causing radiation tolerance and adaptation. PMID:23304110

Bath and Shower Effects in the Rat Parotid Gland Explain Increased Relative Risk of Parotid Gland Dysfunction After Intensity-Modulated Radiotherapy

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

Luijk, Peter van; Faber, Hette; Schippers, Jacobus M.

2009-07-15

Purpose: To assess in a rat model whether adding a subtolerance dose in a region adjacent to a high-dose irradiated subvolume of the parotid gland influences its response (bath-and-shower effect). Methods and Materials: Irradiation of the whole, cranial 50%, and/or the caudal 50% of the parotid glands of Wistar rats was performed using 150-MeV protons. To determine suitable (i.e., subtolerance) dose levels for a bath-dose, both whole parotid glands were irradiated with 5 to 25 Gy. Subsequently groups of Wistar rats received 30 Gy to the caudal 50% (shower) and 0 to 10 Gy to the cranial 50% (bath) ofmore » both parotid glands. Stimulated saliva flow rate (function) was measured before and up to 240 days after irradiation. Results: Irradiation of both glands up to a dose of 10 Gy did not result in late loss of function and is thus regarded subtolerance. Addition of a dose bath of 1 to 10 Gy to a high-dose in the caudal 50% of the glands resulted in enhanced function loss. Conclusion: Similar to the spinal cord, the parotid gland demonstrates a bath and shower effect, which may explain the less-than-expected sparing of function after IMRT.« less

Intensity Modulated Radiation Treatment of Prostate Cancer Guided by High Field MR Spectroscopic Imaging

DTIC Science & Technology

2005-05-01

constructed with incorporation of the nonuniform dose prescription. The functional unit density distribution in a sensitive structure is also considered...of the corresponding organ, and -b(i) is the target, we define the effective dose at a voxel as the physical functional unit density. The value of n...cr, tended to include the nonuniform functional unit density dis- D,(i) the calculated dose in voxel i, DO(i) the prescription tribution using Eq. (8

Methods for Probabilistic Radiological Dose Assessment at a High-Level Radioactive Waste Repository.

NASA Astrophysics Data System (ADS)

Maheras, Steven James

Methods were developed to assess and evaluate the uncertainty in offsite and onsite radiological dose at a high-level radioactive waste repository to show reasonable assurance that compliance with applicable regulatory requirements will be achieved. Uncertainty in offsite dose was assessed by employing a stochastic precode in conjunction with Monte Carlo simulation using an offsite radiological dose assessment code. Uncertainty in onsite dose was assessed by employing a discrete-event simulation model of repository operations in conjunction with an occupational radiological dose assessment model. Complementary cumulative distribution functions of offsite and onsite dose were used to illustrate reasonable assurance. Offsite dose analyses were performed for iodine -129, cesium-137, strontium-90, and plutonium-239. Complementary cumulative distribution functions of offsite dose were constructed; offsite dose was lognormally distributed with a two order of magnitude range. However, plutonium-239 results were not lognormally distributed and exhibited less than one order of magnitude range. Onsite dose analyses were performed for the preliminary inspection, receiving and handling, and the underground areas of the repository. Complementary cumulative distribution functions of onsite dose were constructed and exhibited less than one order of magnitude range. A preliminary sensitivity analysis of the receiving and handling areas was conducted using a regression metamodel. Sensitivity coefficients and partial correlation coefficients were used as measures of sensitivity. Model output was most sensitive to parameters related to cask handling operations. Model output showed little sensitivity to parameters related to cask inspections.

SU-F-J-94: Development of a Plug-in Based Image Analysis Tool for Integration Into Treatment Planning

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

Owen, D; Anderson, C; Mayo, C

Purpose: To extend the functionality of a commercial treatment planning system (TPS) to support (i) direct use of quantitative image-based metrics within treatment plan optimization and (ii) evaluation of dose-functional volume relationships to assist in functional image adaptive radiotherapy. Methods: A script was written that interfaces with a commercial TPS via an Application Programming Interface (API). The script executes a program that performs dose-functional volume analyses. Written in C#, the script reads the dose grid and correlates it with image data on a voxel-by-voxel basis through API extensions that can access registration transforms. A user interface was designed through WinFormsmore » to input parameters and display results. To test the performance of this program, image- and dose-based metrics computed from perfusion SPECT images aligned to the treatment planning CT were generated, validated, and compared. Results: The integration of image analysis information was successfully implemented as a plug-in to a commercial TPS. Perfusion SPECT images were used to validate the calculation and display of image-based metrics as well as dose-intensity metrics and histograms for defined structures on the treatment planning CT. Various biological dose correction models, custom image-based metrics, dose-intensity computations, and dose-intensity histograms were applied to analyze the image-dose profile. Conclusion: It is possible to add image analysis features to commercial TPSs through custom scripting applications. A tool was developed to enable the evaluation of image-intensity-based metrics in the context of functional targeting and avoidance. In addition to providing dose-intensity metrics and histograms that can be easily extracted from a plan database and correlated with outcomes, the system can also be extended to a plug-in optimization system, which can directly use the computed metrics for optimization of post-treatment tumor or normal tissue response models. Supported by NIH - P01 - CA059827.« less

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

Devic, Slobodan; Tomic, Nada; Aldelaijan, Saad

Purpose: Despite numerous advantages of radiochromic film dosimeter (high spatial resolution, near tissue equivalence, low energy dependence) to measure a relative dose distribution with film, one needs to first measure an absolute dose (following previously established reference dosimetry protocol) and then convert measured absolute dose values into relative doses. In this work, we present result of our efforts to obtain a functional form that would linearize the inherently nonlinear dose-response curve of the radiochromic film dosimetry system. Methods: Functional form [{zeta}= (-1){center_dot}netOD{sup (2/3)}/ln(netOD)] was derived from calibration curves of various previously established radiochromic film dosimetry systems. In order to testmore » the invariance of the proposed functional form with respect to the film model used we tested it with three different GAFCHROMIC Trade-Mark-Sign film models (EBT, EBT2, and EBT3) irradiated to various doses and scanned on a same scanner. For one of the film models (EBT2), we tested the invariance of the functional form to the scanner model used by scanning irradiated film pieces with three different flatbed scanner models (Epson V700, 1680, and 10000XL). To test our hypothesis that the proposed functional argument linearizes the response of the radiochromic film dosimetry system, verification tests have been performed in clinical applications: percent depth dose measurements, IMRT quality assurance (QA), and brachytherapy QA. Results: Obtained R{sup 2} values indicate that the choice of the functional form of the new argument appropriately linearizes the dose response of the radiochromic film dosimetry system we used. The linear behavior was insensitive to both film model and flatbed scanner model used. Measured PDD values using the green channel response of the GAFCHROMIC Trade-Mark-Sign EBT3 film model are well within {+-}2% window of the local relative dose value when compared to the tabulated Cobalt-60 data. It was also found that criteria of 3%/3 mm for an IMRT QA plan and 3%/2 mm for a brachytherapy QA plan are passing 95% gamma function points. Conclusions: In this paper, we demonstrate the use of functional argument to linearize the inherently nonlinear response of a radiochromic film based reference dosimetry system. In this way, relative dosimetry can be conveniently performed using radiochromic film dosimetry system without the need of establishing calibration curve.« less

Functional Data Analysis in NTCP Modeling: A New Method to Explore the Radiation Dose-Volume Effects

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

Benadjaoud, Mohamed Amine, E-mail: mohamedamine.benadjaoud@gustaveroussy.fr; Université Paris sud, Le Kremlin-Bicêtre; Institut Gustave Roussy, Villejuif

2014-11-01

Purpose/Objective(s): To describe a novel method to explore radiation dose-volume effects. Functional data analysis is used to investigate the information contained in differential dose-volume histograms. The method is applied to the normal tissue complication probability modeling of rectal bleeding (RB) for patients irradiated in the prostatic bed by 3-dimensional conformal radiation therapy. Methods and Materials: Kernel density estimation was used to estimate the individual probability density functions from each of the 141 rectum differential dose-volume histograms. Functional principal component analysis was performed on the estimated probability density functions to explore the variation modes in the dose distribution. The functional principalmore » components were then tested for association with RB using logistic regression adapted to functional covariates (FLR). For comparison, 3 other normal tissue complication probability models were considered: the Lyman-Kutcher-Burman model, logistic model based on standard dosimetric parameters (LM), and logistic model based on multivariate principal component analysis (PCA). Results: The incidence rate of grade ≥2 RB was 14%. V{sub 65Gy} was the most predictive factor for the LM (P=.058). The best fit for the Lyman-Kutcher-Burman model was obtained with n=0.12, m = 0.17, and TD50 = 72.6 Gy. In PCA and FLR, the components that describe the interdependence between the relative volumes exposed at intermediate and high doses were the most correlated to the complication. The FLR parameter function leads to a better understanding of the volume effect by including the treatment specificity in the delivered mechanistic information. For RB grade ≥2, patients with advanced age are significantly at risk (odds ratio, 1.123; 95% confidence interval, 1.03-1.22), and the fits of the LM, PCA, and functional principal component analysis models are significantly improved by including this clinical factor. Conclusion: Functional data analysis provides an attractive method for flexibly estimating the dose-volume effect for normal tissues in external radiation therapy.« less

Scintigraphic assessment of salivary function after intensity-modulated radiotherapy for head and neck cancer: correlations with parotid dose and quality of life.

PubMed

Chen, Wen-Cheng; Lai, Chia-Hsuan; Lee, Tsair-Fwu; Hung, Chao-Hsiung; Liu, Kuo-Chi; Tsai, Ming-Fong; Wang, Wen-Hung; Chen, Hungcheng; Fang, Fu-Ming; Chen, Miao-Fen

2013-01-01

We investigated salivary function using quantitative scintigraphy and sought to identify functional correlations between parotid dose and quality of life (QoL) for head and neck cancer (HNC) patients receiving intensity-modulated radiotherapy (IMRT). Between August, 2007 and June, 2008, 31 patients treated IMRT for HNC were enrolled in this prospective study. Salivary excretion function (SEF) was previously measured by salivary scintigraphy at annual intervals for 2 years after IMRT. A dose-volume histogram of each parotid gland was calculated, and the normal tissue complication probability (NTCP) was used to determine the tolerance dose. QoL was longitudinally assessed by the EORTC QLQ-C30 and H&N35 questionnaires prior to RT, and at one, three, 12 and 24 months after RT. A significant correlation was found between the reduction of SEF and the mean parotid dose measured at 1 year (correlation coefficient, R(2)=0.651) and 2 years (R(2)=0.310) after IMRT (p<0.001). The TD(50) of the parotid gland at 1 year after IMRT is 43.6 Gy, comparable to results from western countries. We further found that contralateral parotid and submandibular gland function preservation was correlated with reduced sticky saliva and a better QoL compared to the functional preservation of both parotid glands, as determined by the EORTC QLQ-H&N35 questionnaire. A significant correlation was found between the reduction of SEF and the mean parotid dose. Preservation of contralateral parotid and submandibular gland function predicts a better QoL compared to preservation of the function of both parotid glands. Copyright © 2012 Elsevier Ltd. All rights reserved.

Postnatal glucocorticoid-induced hypomyelination, gliosis, neurologic deficits are dose-dependent, preparation-specific, and reversible

PubMed Central

Zia, Muhammad TK; Vinukonda, Govindaiah; Vose, Linnea; Bhimavarapu, Bala B.R.; Iacobas, Sanda; Pandey, Nishi K.; Beall, Ann Marie; Dohare, Preeti; LaGamma, Edmund F.; Iacobas, Dumitru A.; Ballabh, Praveen

2014-01-01

Postnatal glucocorticoids (GCs) are widely used in the prevention of chronic lung disease in premature infants. Their pharmacologic use is associated with neurodevelopmental delay and cerebral palsy. However, the effect of GC dose and preparation (dexamethasone versus betamethasone) on short and long-term neurological outcomes remains undetermined, and the mechanisms of GC-induced brain injury are unclear. We hypothesized that postnatal GC would induce hypomyelination and motor impairment in a preparation- and dose-specific manner, and that GC receptor (GR) inhibition might restore myelination and neurological function in GC-treated animals. Additionally, GC-induced hypomyelination and neurological deficit might be transient. To test our hypotheses, we treated prematurely delivered rabbit pups with high (0.5 mg/kg/day) or low (0.2 mg/kg/day) doses of dexamethasone or betamethasone. Myelin basic protein (MBP), oligodendrocyte proliferation and maturation, astrocytes, transcriptomic profile, and neurobehavioral functions were evaluated. We found that high-dose GC treatment, but not low-dose, reduced MBP expression and impaired motor function at postnatal day 14. High-dose dexamethasone induced astrogliosis, betamethasone did not. Mifepristone, a GR antagonist, reversed dexamethasone-induced myelination, but not astrogliosis. Both GCs inhibited oligodendrocyte proliferation and maturation. Moreover, high-dose dexamethasone altered genes associated with myelination, cell-cycle, GR, and Mitogen-activated protein kinase. Importantly, GC-induced hypomyelination, gliosis, and motor-deficit, observed at day 14, completely recovered by day 21. Hence, high-dose, but not low-dose, postnatal GC causes reversible reductions in myelination and motor functions. GC treatment induces hypomyelination by GR-dependent genomic mechanisms, but astrogliosis by non-genomic mechanisms. GC-induced motor impairment and neurodevelopmental delay might be transient and recover spontaneously in premature infants. PMID:25263581

Sci—Fri PM: Topics — 06: The influence of regional dose sensitivity on salivary loss and recovery in the parotid gland

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

Clark, H; BC Cancer Agency, Surrey, B.C.; BC Cancer Agency, Vancouver, B.C.

Purpose: The Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC 2010) survey of radiation dose-volume effects on salivary gland function has called for improved understanding of intragland dose sensitivity and the effectiveness of partial sparing in salivary glands. Regional dose susceptibility of sagittally- and coronally-sub-segmented parotid gland has been studied. Specifically, we examine whether individual consideration of sub-segments leads to improved prediction of xerostomia compared with whole parotid mean dose. Methods: Data from 102 patients treated for head-and-neck cancers at the BC Cancer Agency were used in this study. Whole mouth stimulated saliva was collected before (baseline), threemore » months, and one year after cessation of radiotherapy. Organ volumes were contoured using treatment planning CT images and sub-segmented into regional portions. Both non-parametric (local regression) and parametric (mean dose exponential fitting) methods were employed. A bootstrap technique was used for reliability estimation and cross-comparison. Results: Salivary loss is described well using non-parametric and mean dose models. Parametric fits suggest a significant distinction in dose response between medial-lateral and anterior-posterior aspects of the parotid (p<0.01). Least-squares and least-median squares estimates differ significantly (p<0.00001), indicating fits may be skewed by noise or outliers. Salivary recovery exhibits a weakly arched dose response: the highest recovery is seen at intermediate doses. Conclusions: Salivary function loss is strongly dose dependent. In contrast no useful dose dependence was observed for function recovery. Regional dose dependence was observed, but may have resulted from a bias in dose distributions.« less

An atlas-based organ dose estimator for tomosynthesis and radiography

NASA Astrophysics Data System (ADS)

Hoye, Jocelyn; Zhang, Yakun; Agasthya, Greeshma; Sturgeon, Greg; Kapadia, Anuj; Segars, W. Paul; Samei, Ehsan

2017-03-01

The purpose of this study was to provide patient-specific organ dose estimation based on an atlas of human models for twenty tomosynthesis and radiography protocols. The study utilized a library of 54 adult computational phantoms (age: 18-78 years, weight 52-117 kg) and a validated Monte-Carlo simulation (PENELOPE) of a tomosynthesis and radiography system to estimate organ dose. Positioning of patient anatomy was based on radiographic positioning handbooks. The field of view for each exam was calculated to include relevant organs per protocol. Through simulations, the energy deposited in each organ was binned to estimate normalized organ doses into a reference database. The database can be used as the basis to devise a dose calculator to predict patient-specific organ dose values based on kVp, mAs, exposure in air, and patient habitus for a given protocol. As an example of the utility of this tool, dose to an organ was studied as a function of average patient thickness in the field of view for a given exam and as a function of Body Mass Index (BMI). For tomosynthesis, organ doses can also be studied as a function of x-ray tube position. This work developed comprehensive information for organ dose dependencies across tomosynthesis and radiography. There was a general exponential decrease dependency with increasing patient size that is highly protocol dependent. There was a wide range of variability in organ dose across the patient population, which needs to be incorporated in the metrology of organ dose.

Skin dose mapping for non-uniform x-ray fields using a backscatter point spread function

NASA Astrophysics Data System (ADS)

Vijayan, Sarath; Xiong, Zhenyu; Shankar, Alok; Rudin, Stephen; Bednarek, Daniel R.

2017-03-01

Beam shaping devices like ROI attenuators and compensation filters modulate the intensity distribution of the xray beam incident on the patient. This results in a spatial variation of skin dose due to the variation of primary radiation and also a variation in backscattered radiation from the patient. To determine the backscatter component, backscatter point spread functions (PSF) are generated using EGS Monte-Carlo software. For this study, PSF's were determined by simulating a 1 mm beam incident on the lateral surface of an anthropomorphic head phantom and a 20 cm thick PMMA block phantom. The backscatter PSF's for the head phantom and PMMA phantom are curve fit with a Lorentzian function after being normalized to the primary dose intensity (PSFn). PSFn is convolved with the primary dose distribution to generate the scatter dose distribution, which is added to the primary to obtain the total dose distribution. The backscatter convolution technique is incorporated in the dose tracking system (DTS), which tracks skin dose during fluoroscopic procedures and provides a color map of the dose distribution on a 3D patient graphic model. A convolution technique is developed for the backscatter dose determination for the nonuniformly spaced graphic-model surface vertices. A Gafchromic film validation was performed for shaped x-ray beams generated with an ROI attenuator and with two compensation filters inserted into the field. The total dose distribution calculated by the backscatter convolution technique closely agreed with that measured with the film.

Multi-walled carbon nanotubes: A cytotoxicity study in relation to functionalization, dose and dispersion.

PubMed

Zhou, Lulu; Forman, Henry Jay; Ge, Yi; Lunec, Joseph

2017-08-01

Chemical functionalization broadens carbon nanotube (CNT) applications, conferring new functions, but at the same time potentially altering toxicity. Although considerable experimental data related to CNT toxicity, at the molecular and cellular levels, have been reported, there is very limited information available for the corresponding mechanism involved (e.g. cell apoptosis and genotoxicity). The threshold dose for safe medical application in relation to both pristine and functionalized carbon nanotubes remains ambiguous. In this study, we evaluated the in vitro cytotoxicity of pristine and functionalized (OH, COOH) multi-walled carbon nanotubes (MWCNTs) for cell viability, oxidant detection, apoptosis and DNA mutations, to determine the non-toxic dose and influence of functional group in a human lung-cancer cell line exposed to 1-1000μg/ml MWCNTs for 24, 48 and 72h. The findings suggest that pristine MWCNTs induced more cell death than functionalized MWCNTs while functionalized MWCNTs are more genotoxic compared to their pristine form. The level of both dose and dispersion in the matrix used should be taken into consideration before applying further clinical applications of MWCNTs. Copyright © 2017 Elsevier Ltd. All rights reserved.

TREFEX: Trend Estimation and Change Detection in the Response of MOX Gas Sensors

PubMed Central

Pashami, Sepideh; Lilienthal, Achim J.; Schaffernicht, Erik; Trincavelli, Marco

2013-01-01

Many applications of metal oxide gas sensors can benefit from reliable algorithms to detect significant changes in the sensor response. Significant changes indicate a change in the emission modality of a distant gas source and occur due to a sudden change of concentration or exposure to a different compound. As a consequence of turbulent gas transport and the relatively slow response and recovery times of metal oxide sensors, their response in open sampling configuration exhibits strong fluctuations that interfere with the changes of interest. In this paper we introduce TREFEX, a novel change point detection algorithm, especially designed for metal oxide gas sensors in an open sampling system. TREFEX models the response of MOX sensors as a piecewise exponential signal and considers the junctions between consecutive exponentials as change points. We formulate non-linear trend filtering and change point detection as a parameter-free convex optimization problem for single sensors and sensor arrays. We evaluate the performance of the TREFEX algorithm experimentally for different metal oxide sensors and several gas emission profiles. A comparison with the previously proposed GLR method shows a clearly superior performance of the TREFEX algorithm both in detection performance and in estimating the change time. PMID:23736853

SU-E-T-39: A Logistic Function-Based Model to Predict Organ-At-Risk (OAR) DVH in IMRT Treatment Planning

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

Chen, S; Zhang, H; Zhang, B

2015-06-15

Purpose: To investigate the feasibility of a logistic function-based model to predict organ-at-risk (OAR) DVH for IMRT planning. The predicted DVHs are compared to achieved DVHs by expert treatment planners. Methods: A logistic function is used to model the OAR dose-gradient function. This function describes the percentage of the prescription dose as a function of the normal distance to PTV surface. The slope of dose-gradient function is function of relative spatial orientation of the PTV and OARs. The OAR DVH is calculated using the OAR dose-gradient function assuming that the dose is same for voxels with same normal distance tomore » PTV. Ten previously planned prostate IMRT plans were selected to build the model, and the following plan parameters were calculated as possible features to the model: the PTV maximum/minimum dose, PTV volume, bladder/rectum volume in the radiation field, percentage of bladder/rectum overlapping with PTV, and the distance between the bladder/rectum centroid and PTV. The bladder/rectum dose-gradient function was modeled and applied on 10 additional test cases, and the predicted and achieved clinical bladder/rectum DVHs were compared: V70 (percentage of volume receiving 70Gy and above), V65, V60, V55, V50, V45, V40. Results: The following parameters were selected as model features: PTV volume, and distance of centroid of rectum/bladder to PTV. The model was tested with 10 additional patients. For bladder, the absolute difference (mean±standard deviation) between predicted and clinical DVHs is V70=−0.3±3.2, V65=−0.8±3.9, V60=1.5±4.3, V55=1.7±5.3, V50=−0.6±6.4, V45=0.6±6.5, and V40=0.9±5.7, the correlation coefficient is 0.96; for rectum, the difference is V70=1.5±3.8, V65=1.2±4.2, V60=−0.1±5.3, V55=1.0±6.6, V50=1.6±8.7, V45=1.9±9.8, and V40=1.5±10.1, and the correlation coefficient is 0.87. Conclusion: The OAR DVH can be accurately predicted using the OAR dose-gradient function in IMRT plans. This approach may be used as a quality control tool and aid less experienced planners determine benchmarks for plan quality.« less

SU-E-I-16: Scan Length Dependency of the Radial Dose Distribution in a Long Polyethylene Cylinder

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

Bakalyar, D; McKenney, S; Feng, W

Purpose: The area-averaged dose in the central plane of a long cylinder following a CT scan depends upon the radial dose distribution and the length of the scan. The ICRU/TG200 phantom, a polyethylene cylinder 30 cm in diameter and 60 cm long, was the subject of this study. The purpose was to develop an analytic function that could determine the dose for a scan length L at any point in the central plane of this phantom. Methods: Monte Carlo calculations were performed on a simulated ICRU/TG200 phantom under conditions of cylindrically symmetric conditions of irradiation. Thus, the radial dose distributionmore » function must be an even function that accounts for two competing effects: The direct beam makes its weakest contribution at the center while the scatter begins abruptly at the outer radius and grows as the center is approached. The scatter contribution also increases with scan length with the increase approaching its limiting value at the periphery faster than along the central axis. An analytic function was developed that fit the data and possessed these features. Results: Symmetry and continuity dictate a local extremum at the center which is a minimum for the ICRU/TG200 phantom. The relative depth of the minimum decreases as the scan length grows and an absolute maximum can occur between the center and outer edge of the cylinders. As the scan length grows, the relative dip in the center decreases so that for very long scan lengths, the dose profile is relatively flat. Conclusion: An analytic function characterizes the radial and scan length dependency of dose for long cylindrical phantoms. The function can be integrated with the results expressed in closed form. One use for this is to help determine average dose distribution over the central cylinder plane for any scan length.« less

SU-G-BRB-14: Uncertainty of Radiochromic Film Based Relative Dose Measurements

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

Devic, S; Tomic, N; DeBlois, F

2016-06-15

Purpose: Due to inherently non-linear dose response, measurement of relative dose distribution with radiochromic film requires measurement of absolute dose using a calibration curve following previously established reference dosimetry protocol. On the other hand, a functional form that converts the inherently non-linear dose response curve of the radiochromic film dosimetry system into linear one has been proposed recently [Devic et al, Med. Phys. 39 4850–4857 (2012)]. However, there is a question what would be the uncertainty of such measured relative dose. Methods: If the relative dose distribution is determined going through the reference dosimetry system (conversion of the response bymore » using calibration curve into absolute dose) the total uncertainty of such determined relative dose will be calculated by summing in quadrature total uncertainties of doses measured at a given and at the reference point. On the other hand, if the relative dose is determined using linearization method, the new response variable is calculated as ζ=a(netOD)n/ln(netOD). In this case, the total uncertainty in relative dose will be calculated by summing in quadrature uncertainties for a new response function (σζ) for a given and the reference point. Results: Except at very low doses, where the measurement uncertainty dominates, the total relative dose uncertainty is less than 1% for the linear response method as compared to almost 2% uncertainty level for the reference dosimetry method. The result is not surprising having in mind that the total uncertainty of the reference dose method is dominated by the fitting uncertainty, which is mitigated in the case of linearization method. Conclusion: Linearization of the radiochromic film dose response provides a convenient and a more precise method for relative dose measurements as it does not require reference dosimetry and creation of calibration curve. However, the linearity of the newly introduced function must be verified. Dave Lewis is inventor and runs a consulting company for radiochromic films.« less

Dosing of cytotoxic chemotherapy: impact of renal function estimates on dose.

PubMed

Dooley, M J; Poole, S G; Rischin, D

2013-11-01

Oncology clinicians are now routinely provided with an estimated glomerular filtration rate on pathology reports whenever serum creatinine is requested. The utility of using this for the dose determination of renally excreted drugs compared with other existing methods is needed to inform practice. Renal function was determined by [Tc(99m)]DTPA clearance in adult patients presenting for chemotherapy. Renal function was calculated using the 4-variable Modification of Diet in Renal Disease (4v-MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Cockcroft and Gault (CG), Wright and Martin formulae. Doses for renal excreted cytotoxic drugs, including carboplatin, were calculated. The concordance of the renal function estimates according to the CKD classification with measured Tc(99m)DPTA clearance in 455 adults (median age 64.0 years: range 17-87 years) for the 4v-MDRD, CKD-EPI, CG, Martin and Wright formulae was 47.7%, 56.3%, 46.2%, 56.5% and 60.2%, respectively. Concordance for chemotherapy dose for these formulae was 89.0%, 89.5%, 85.1%, 89.9% and 89.9%, respectively. Concordance for carboplatin dose specifically was 66.4%, 71.4%, 64.0%, 73.8% and 73.2%. All bedside formulae provide similar levels of concordance in dosage selection for the renal excreted chemotherapy drugs when compared with the use of a direct measure of renal function.

SU-E-J-86: Functional Conformal Planning for Stereotactic Body Radiation Therapy with CT-Pulmonary Ventilation Imaging

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

Kurosawa, T; Moriya, S; Sato, M

2015-06-15

Purpose: To evaluate the functional planning using CT-pulmonary ventilation imaging for conformal SBRT. Methods: The CT-pulmonary ventilation image was generated using the Jacobian metric in the in-house program with the NiftyReg software package. Using the ventilation image, the normal lung was split into three lung regions for functionality (high, moderate and low). The anatomical plan (AP) and functional plan (FP) were made for ten lung SBRT patients. For the AP, the beam angles were optimized with the dose-volume constraints for the normal lung sparing and the PTV coverage. For the FP, the gantry angles were also optimized with the additionalmore » constraint for high functional lung. The MLC aperture shapes were adjusted to the PTV with the additional 5 mm margin. The dosimetric parameters for PTV, the functional volumes, spinal cord and so on were compared in both plans. Results: Compared to the AP, the FP showed better dose sparing for high- and moderate-functional lungs with similar PTV coverage while not taking care of the low functional lung (High:−12.9±9.26% Moderate: −2.0±7.09%, Low: +4.1±12.2%). For the other normal organs, the FP and AP showed similar dose sparing in the eight patients. However, the FP showed that the maximum doses for spinal cord were increased with the significant increment of 16.4Gy and 21.0Gy in other two patients, respectively. Because the beam direction optimizer chose the unexpected directions passing through the spinal cord. Conclusion: Even the functional conformal SBRT can selectively reduce high- and moderatefunctional lung while keeping the PTV coverage. However, it would be careful that the optimizer would choose unexpected beam angles and the dose sparing for the other normal organs can be worse. Therefore, the planner needs to control the dose-volume constraints and also limit the beam angles in order to achieve the expected dose sparing and coverage.« less

Studies on possibility for alleviation of lifestyle diseases by low-dose irradiation or radon inhalation.

PubMed

Kataoka, Takahiro; Sakoda, Akihiro; Yoshimoto, Masaaki; Nakagawa, Shinya; Toyota, Teruaki; Nishiyama, Yuichi; Yamato, Keiko; Ishimori, Yuu; Kawabe, Atsushi; Hanamoto, Katsumi; Taguchi, Takehito; Yamaoka, Kiyonori

2011-07-01

Our previous studies showed the possibility that activation of the antioxidative function alleviates various oxidative damages, which are related to lifestyle diseases. Results showed that, low-dose X-ray irradiation activated superoxide dismutase and inhibits oedema following ischaemia-reperfusion. To alleviate ischaemia-reperfusion injury with transplantation, the changes of the antioxidative function in liver graft using low-dose X-ray irradiation immediately after exenteration were examined. Results showed that liver grafts activate the antioxidative function as a result of irradiation. In addition, radon inhalation enhances the antioxidative function in some organs, and alleviates alcohol-induced oxidative damage of mouse liver. Moreover, in order to determine the most effective condition of radon inhalation, mice inhaled radon before or after carbon tetrachloride (CCl(4)) administration. Results showed that radon inhalation alleviates CCl(4)-induced hepatopathy, especially prior inhalation. It is highly possible that adequate activation of antioxidative functions induced by low-dose irradiation can contribute to preventing or reducing oxidative damages, which are related to lifestyle diseases.

Effects of Methylphenidate on Sleep Functioning in Children with Attention-Deficit/Hyperactivity Disorder.

PubMed

Becker, Stephen P; Froehlich, Tanya E; Epstein, Jeffery N

2016-06-01

To examine the effects of stimulant medication on the sleep functioning of children with attention-deficit/hyperactivity disorder (ADHD) and identify predictors of sleep problems as a side effect of taking stimulant medication. One hundred sixty-three stimulant-naïve children (72% boys) aged 7 to 11 years diagnosed with ADHD (120 with ADHD predominantly inattentive type, 43 with ADHD combined type) participated in a 4-week, randomized, double-blind, placebo-controlled trial of once-daily (long-acting) methylphenidate (MPH). Parents completed weekly side-effect ratings including an item related to sleep problems. Ten percent of patients had parent-rated sleep problems before the initiation of medication. Rates of parent-rated sleep problems during MPH titration generally increased with increasing MPH dose (placebo: 8%; low dose: 18%; medium dose: 15%; high dose: 25%). Differences emerged between children with (n = 16) or without (n = 147) preexisting sleep problems. Although 23% of children without preexisting sleep problems went on to have sleep problems at the highest MPH dose, only 37.5% of children with preexisting sleep problems still had sleep problems at the highest MPH dose. Lower weight and lower body mass index (BMI) were associated with increased sleep problems during MPH titration. This study demonstrated a general association between increased MPH dose and increased sleep problems in children with ADHD, particularly for children of lower weight/BMI. However, a substantial proportion of children with preexisting sleep difficulties no longer had sleep problems on the highest MPH dose, which may help explain mixed findings reported to date in studies examining the impact of MPH on sleep functioning in children with ADHD and suggests that MPH dose titration should not be avoided solely on the basis of a child's premorbid sleep problems. Future research is needed to replicate and extend these findings to more specific domains of sleep functioning and to identify differences between children with persistent or improved sleep functioning as a result of MPH use.

The interaction between hippocampal GABA-B and cannabinoid receptors upon spatial change and object novelty discrimination memory function.

PubMed

Nasehi, Mohammad; Alaghmandan-Motlagh, Niyousha; Ebrahimi-Ghiri, Mohaddeseh; Nami, Mohammad; Zarrindast, Mohammad-Reza

2017-10-01

Previous studies have postulated functional links between GABA and cannabinoid systems in the hippocampus. The aim of the present study was to investigate any possible interaction between these systems in spatial change and object novelty discrimination memory consolidation in the dorsal hippocampus (CA1 region) of NMRI mice. Assessment of the spatial change and object novelty discrimination memory function was carried out in a non-associative task. The experiment comprised mice exposure to an open field containing five objects followed by the examination of their reactivity to object displacement (spatial change) and object substitution (object novelty) after three sessions of habituation. Our results showed that the post-training intraperitoneal administration of the higher dose of ACPA (0.02 mg/kg) impaired both spatial change and novelty discrimination memory functions. Meanwhile, the higher dose of GABA-B receptor agonist, baclofen, impaired the spatial change memory by itself. Moreover, the post-training intra-CA1 microinjection of a subthreshold dose of baclofen increased the ACPA effect on spatial change and novelty discrimination memory at a lower and higher dose, respectively. On the other hand, the lower and higher but not mid-level doses of GABA-B receptor antagonist, phaclofen, could reverse memory deficits induced by ACPA. However, phaclofen at its mid-level dose impaired the novelty discrimination memory and whereas the higher dose impaired the spatial change memory. Based on our findings, GABA-B receptors in the CA1 region appear to modulate the ACPA-induced cannabinoid CB1 signaling upon spatial change and novelty discrimination memory functions.

Gastrointestinal Dose-Histogram Effects in the Context of Dose-Volume–Constrained Prostate Radiation Therapy: Analysis of Data From the RADAR Prostate Radiation Therapy Trial

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

Ebert, Martin A., E-mail: Martin.Ebert@health.wa.gov.au; School of Physics, University of Western Australia, Perth, Western Australia; Foo, Kerwyn

Purpose: To use a high-quality multicenter trial dataset to determine dose-volume effects for gastrointestinal (GI) toxicity following radiation therapy for prostate carcinoma. Influential dose-volume histogram regions were to be determined as functions of dose, anatomical location, toxicity, and clinical endpoint. Methods and Materials: Planning datasets for 754 participants in the TROG 03.04 RADAR trial were available, with Late Effects of Normal Tissues (LENT) Subjective, Objective, Management, and Analytic (SOMA) toxicity assessment to a median of 72 months. A rank sum method was used to define dose-volume cut-points as near-continuous functions of dose to 3 GI anatomical regions, together with amore » comprehensive assessment of significance. Univariate and multivariate ordinal regression was used to assess the importance of cut-points at each dose. Results: Dose ranges providing significant cut-points tended to be consistent with those showing significant univariate regression odds-ratios (representing the probability of a unitary increase in toxicity grade per percent relative volume). Ranges of significant cut-points for rectal bleeding validated previously published results. Separation of the lower GI anatomy into complete anorectum, rectum, and anal canal showed the impact of mid-low doses to the anal canal on urgency and tenesmus, completeness of evacuation and stool frequency, and mid-high doses to the anorectum on bleeding and stool frequency. Derived multivariate models emphasized the importance of the high-dose region of the anorectum and rectum for rectal bleeding and mid- to low-dose regions for diarrhea and urgency and tenesmus, and low-to-mid doses to the anal canal for stool frequency, diarrhea, evacuation, and bleeding. Conclusions: Results confirm anatomical dependence of specific GI toxicities. They provide an atlas summarizing dose-histogram effects and derived constraints as functions of anatomical region, dose, toxicity, and endpoint for informing future radiation therapy planning.« less

Spatial frequency performance limitations of radiation dose optimization and beam positioning

NASA Astrophysics Data System (ADS)

Stewart, James M. P.; Stapleton, Shawn; Chaudary, Naz; Lindsay, Patricia E.; Jaffray, David A.

2018-06-01

The flexibility and sophistication of modern radiotherapy treatment planning and delivery methods have advanced techniques to improve the therapeutic ratio. Contemporary dose optimization and calculation algorithms facilitate radiotherapy plans which closely conform the three-dimensional dose distribution to the target, with beam shaping devices and image guided field targeting ensuring the fidelity and accuracy of treatment delivery. Ultimately, dose distribution conformity is limited by the maximum deliverable dose gradient; shallow dose gradients challenge techniques to deliver a tumoricidal radiation dose while minimizing dose to surrounding tissue. In this work, this ‘dose delivery resolution’ observation is rigorously formalized for a general dose delivery model based on the superposition of dose kernel primitives. It is proven that the spatial resolution of a delivered dose is bounded by the spatial frequency content of the underlying dose kernel, which in turn defines a lower bound in the minimization of a dose optimization objective function. In addition, it is shown that this optimization is penalized by a dose deposition strategy which enforces a constant relative phase (or constant spacing) between individual radiation beams. These results are further refined to provide a direct, analytic method to estimate the dose distribution arising from the minimization of such an optimization function. The efficacy of the overall framework is demonstrated on an image guided small animal microirradiator for a set of two-dimensional hypoxia guided dose prescriptions.

TROPICS 1: a phase III, randomized, double-blind, placebo-controlled study of tenecteplase for restoration of function in dysfunctional central venous catheters.

PubMed

Gabrail, Nashat; Sandler, Eric; Charu, Veena; Anas, Nick; Lim, Eduardo; Blaney, Martha; Ashby, Mark; Gillespie, Barbara S; Begelman, Susan M

2010-12-01

To evaluate the efficacy and safety of the thrombolytic tenecteplase, a fibrin-specific recombinant tissue plasminogen activator, for restoring function to dysfunctional central venous catheters (CVCs). In this double-blind, placebo-controlled study, eligible patients with dysfunctional nonhemodialysis CVCs were randomly assigned to two treatment arms. In the first arm (TNK-TNK-PBO), patients received an initial dose of intraluminal tenecteplase (TNK) (up to 2 mg), a second dose of tenecteplase if indicated, and a third placebo (PBO) dose. In the PBO-TNK-TNK arm, placebo was instilled first followed by up to two doses of tenecteplase, if needed, for restoration of catheter function. After administration of each dose, CVC function was assessed at 15, 30, and 120 minutes. There were 97 patients who received either TNK-TNK-PBO (n = 50) or PBO-TNK-TNK (n = 47). Within 120 minutes of initial study drug instillation, catheter function was restored to 30 patients (60%) in the TNK-TNK-PBO arm and 11 patients (23%) in the PBO-TNK-TNK arm, for a treatment difference of 37 percentage points (95% confidence interval 18-55; P = .0002). Cumulative restoration rates for CVC function increased to 87% after the second dose of tenecteplase in both study arms combined. Two patients developed a deep vein thrombosis (DVT) after exposure to tenecteplase; one DVT was considered to be drug related. No cases of intracranial hemorrhage, major bleeding, embolic events, catheter-related bloodstream infections, or catheter-related complications were reported. Tenecteplase was efficacious for restoration of catheter function in these study patients with dysfunctional CVCs. Copyright © 2010 SIR. Published by Elsevier Inc. All rights reserved.

Dose- and time-dependent activation of rat alveolar macrophages by glucocorticoids

PubMed Central

BROUG-HOLUB, E; KRAAL, G

1996-01-01

Effects of glucocorticoids on immune functions are generally thought to be suppressive and anti-inflammatory. However, most reports dealing with this issue describe effects of long-term treatment with high doses of glucocorticoids on immune functions. In the present study we have investigated both dose and timing effects of exposure of alveolar macrophages with dexamethasone on lipopolysaccharide (LPS)-induced IL-1β and nitric oxide secretion. For this purpose, alveolar macrophages were preincubated with various doses of dexamethasone during varying intervals, followed by stimulation of the cells with endotoxin, either in the absence or presence of dexamethasone. Subsequently, the effects of this treatment on IL-1β and nitric oxide secretion were measured. It was shown that both short-term incubation of alveolar macrophages with high doses of dexamethasone and long-term incubation with low doses of dexamethasone lead to enhanced nitric oxide and enhanced IL-1β secretion upon subsequent stimulation of the cells with LPS. In contrast, long-term incubation of alveolar macrophages with high-dose dexamethasone leads to decreased IL-1β and nitric oxide secretion upon subsequent stimulation. Thus, it is concluded that the effects of dexamethasone on rat alveolar macrophages are both time- and dose-dependent. It is therefore argued that effects of glucocorticoids on immune functions are not a priori suppressive, but that both dose and timing effects should be taken into account. PMID:8625529

Association between peak neutrophil count, clopidogrel loading dose, and left ventricular systolic function in patients with primary percutaneous coronary intervention.

PubMed

Wang, Xinyu; Yu, Haiyi; Li, Zhaoping; Li, Liuning; Zhang, Youyi; Gao, Wei

2014-01-01

Inflammation plays an important role in plaque development and left ventricular remodeling during acute myocardial infarction (AMI). Clopidogrel may exhibit some anti-inflammatory properties and high loading dose of clopidogrel results in improved clinical outcomes in patients with AMI. 357 patients who received successful primary percutaneous coronary intervention from January 2008 to March 2011 in Peking University Third Hospital were included in this study. Different loading dose of clopidogrel (300 mg, 450 mg, or 600 mg) was given at the discretion of the clinician. Neutrophils reached their peak values on the first day after AMI. Higher levels of peak neutrophil and lower left ventricular ejection fraction (LVEF) were found in patients of low clopidogrel loading dose group (300 mg or 450 mg). After adjusting for the related confounders, a logistic regression model showed that low clopidogrel loading dose remained an independent predictor of low LVEF (LVEF ≤ 50%) [OR: 1.97, 95% CI: 1.03-3.79, P = 0.04]. Low clopidogrel loading dose was associated with higher peak neutrophil count and poor left ventricular systolic function, suggesting an important role of clopidogrel loading dose in the improvement of left ventricular function and high loading dose may exhibit better anti-inflammatory properties.

WE-AB-202-02: Incorporating Regional Ventilation Function in Predicting Radiation Fibrosis After Concurrent Chemoradiotherapy for Lung Cancer

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

Lan, F; Jeudy, J; Tseng, H

Purpose: To investigate the incorporation of pre-therapy regional ventilation function in predicting radiation fibrosis (RF) in stage III non-small-cell lung cancer (NSCLC) patients treated with concurrent thoracic chemoradiotherapy. Methods: 37 stage III NSCLC patients were retrospectively studied. Patients received one cycle of cisplatin-gemcitabine, followed by two to three cycles of cisplatin-etoposide concurrently with involved-field thoracic radiotherapy between 46 and 66 Gy (2 Gy per fraction). Pre-therapy regional ventilation images of the lung were derived from 4DCT via a density-change-based image registration algorithm with mass correction. RF was evaluated at 6-months post-treatment using radiographic scoring based on airway dilation and volumemore » loss. Three types of ipsilateral lung metrics were studied: (1) conventional dose-volume metrics (V20, V30, V40, and mean-lung-dose (MLD)), (2) dose-function metrics (fV20, fV30, fV40, and functional mean-lung-dose (fMLD) generated by combining regional ventilation and dose), and (3) dose-subvolume metrics (sV20, sV30, sV40, and subvolume mean-lung-dose (sMLD) defined as the dose-volume metrics computed on the sub-volume of the lung with at least 60% of the quantified maximum ventilation status). Receiver operating characteristic (ROC) curve analysis and logistic regression analysis were used to evaluate the predictability of these metrics for RF. Results: In predicting airway dilation, the area under the ROC curve (AUC) values for (V20, MLD), (fV20, fMLD), and (sV20, and sMLD) were (0.76, 0.70), (0.80, 0.74) and (0.82, 0.80), respectively. The logistic regression p-values were (0.09, 0.18), (0.02, 0.05) and (0.004, 0.006), respectively. With regard to volume loss, the corresponding AUC values for these metrics were (0.66, 0.57), (0.67, 0.61) and (0.71, 0.69), and p-values were (0.95, 0.90), (0.43, 0.64) and (0.08, 0.12), respectively. Conclusion: The inclusion of regional ventilation function improved predictability of radiation fibrosis. Dose-subvolume metrics provided a promising method for incorporating functional information into the conventional dose-volume parameters for outcome assessment.« less

WE-AB-202-04: Statistical Evaluation of Lung Function Using 4DCT Ventilation Imaging: Proton Therapy VS IMRT

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

Huang, Q; Zhang, M; Chen, T

Purpose: Variation in function of different lung regions has been ignored so far for conventional lung cancer treatment planning, which may lead to higher risk of radiation induced lung disease. 4DCT based lung ventilation imaging provides a novel yet convenient approach for lung functional imaging as 4DCT is taken as routine for lung cancer treatment. Our work aims to evaluate the impact of accounting for spatial heterogeneity in lung function using 4DCT based lung ventilation imaging for proton and IMRT plans. Methods: Six patients with advanced stage lung cancer of various tumor locations were retrospectively evaluated for the study. Protonmore » and IMRT plans were designed following identical planning objective and constrains for each patient. Ventilation images were calculated from patients’ 4DCT using deformable image registration implemented by Velocity AI software based on Jacobian-metrics. Lung was delineated into two function level regions based on ventilation (low and high functional area). High functional region was defined as lung ventilation greater than 30%. Dose distribution and statistics in different lung function area was calculated for patients. Results: Variation in dosimetric statistics of different function lung region was observed between proton and IMRT plans. In all proton plans, high function lung regions receive lower maximum dose (100.2%–108.9%), compared with IMRT plans (106.4%–119.7%). Interestingly, three out of six proton plans gave higher mean dose by up to 2.2% than IMRT to high function lung region. Lower mean dose (lower by up to 14.1%) and maximum dose (lower by up to 9%) were observed in low function lung for proton plans. Conclusion: A systematic approach was developed to generate function lung ventilation imaging and use it to evaluate plans. This method hold great promise in function analysis of lung during planning. We are currently studying more subjects to evaluate this tool.« less

SU-F-T-113: Inherent Functional Dependence of Spinal Cord Doses of Variable Irradiated Volumes in Spine SBRT

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

Ma, L; Braunstein, S; Chiu, J

2016-06-15

Purpose: Spinal cord tolerance for SBRT has been recommended for the maximum point dose level or at irradiated volumes such as 0.35 mL or 10% of contoured volumes. In this study, we investigated an inherent functional relationship that associates these dose surrogates for irradiated spinal cord volumes of up to 3.0 mL. Methods: A hidden variable termed as Effective Dose Radius (EDR) was formulated based on a dose fall-off model to correlate dose at irradiated spinal cord volumes ranging from 0 mL (point maximum) to 3.0 mL. A cohort of 15 spine SBRT cases was randomly selected to derive anmore » EDR-parameterized formula. The mean prescription dose for the studied cases was 21.0±8.0 Gy (range, 10–40Gy) delivered in 3±1 fractions with target volumes of 39.1 ± 70.6 mL. Linear regression and variance analysis were performed for the fitting parameters of variable EDR values. Results: No direct correlation was found between the dose at maximum point and doses at variable spinal cord volumes. For example, Pearson R{sup 2} = 0.643 and R{sup 2}= 0.491 were obtained when correlating the point maximum dose with the spinal cord dose at 1 mL and 3 mL, respectively. However, near perfect correlation (R{sup 2} ≥0.99) was obtained when corresponding parameterized EDRs. Specifically, Pearson R{sup 2}= 0.996 and R{sup 2} = 0.990 were obtained when correlating EDR (maximum point dose) with EDR (dose at 1 mL) and EDR(dose at 3 mL), respectively. As a result, high confidence level look-up tables were established to correlate spinal cord doses at the maximum point to any finite irradiated volumes. Conclusion: An inherent functional relationship was demonstrated for spine SBRT. Such a relationship unifies dose surrogates at variable cord volumes and proves that a single dose surrogate (e.g. point maximum dose) is mathematically sufficient in constraining the overall spinal cord dose tolerance for SBRT.« less

Chemical and toxicological evaluation of methanol extract of Cuscuta reflexa Roxb. stem and Corchorus olitorius Linn. seed on hematological parameters and hepatorenal functions in mice.

PubMed

Mazumder, Upal Kanti; Gupta, Malaya; Pal, Dilipkumar; Bhattacharya, Shiladitya

2003-01-01

Methanol extract of Cuscuta reflexa Roxb. stem (MECR) contain flavonoids (0.2%) and Corchorus olitorius Linn. seed (MECO) was found to contain steroids and cardenolide glycosides. Effects of multiple weekly dose of MECR (25, 50, 75 mg/kg, i.p.) and MECO (15, 20, 25 mg/kg, i.p.) on liver and kidney functions and hematological parameters in mice were studied. No significant alteration of RBC count and hemoglobin content was observed in all dose level of treatment in MECR and MECO treated mice whereas significant increase of clotting time was seen in moderate and high doses in both case. MECR and MECO both caused significant increase in WBC count only in high dose level of treatment. Both the extracts in medium and high dose level increased SGOT, SGPT, NPN and plasma cholesterol significantly. Serum alkaline phosphatase and total bilirubin were also increased by both moderate and high dose level of treatments in MECR and MECO treated mice respectively. Low dose of both the extract did not exhibit any significant change of creatinine and serum protein level. But high dose level of MECR and MECO significantly increased creatinine level. Increase in plasma cholesterol may be due to decrease in cholesterol catabolism owing to liver dysfunction of due to the intake of MECO itself as it was found to be steroid in nature. Elevated level of SGOT, SGPT and serum alkaline phosphatase activity in moderate and high dose level of weekly treated mice may be due to improper liver function following the treatment. Increased urea, non protein nitrogen and creatinine content in blood have been observed with impaired renal function. The slightly higher toxicity in case of MECO treated mice may be due to the presence of cardenolide glycosides in the ME of C. olitorius seed. However, low doses of MECR and MECO (25 and 15 mg/kg, i.p. respectively) did not exhibit any remarkable change on liver and kidney functions and hematological parameters.

Functional Data Analysis Applied to Modeling of Severe Acute Mucositis and Dysphagia Resulting From Head and Neck Radiation Therapy

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

Dean, Jamie A., E-mail: jamie.dean@icr.ac.uk; Wong, Kee H.; Gay, Hiram

Purpose: Current normal tissue complication probability modeling using logistic regression suffers from bias and high uncertainty in the presence of highly correlated radiation therapy (RT) dose data. This hinders robust estimates of dose-response associations and, hence, optimal normal tissue–sparing strategies from being elucidated. Using functional data analysis (FDA) to reduce the dimensionality of the dose data could overcome this limitation. Methods and Materials: FDA was applied to modeling of severe acute mucositis and dysphagia resulting from head and neck RT. Functional partial least squares regression (FPLS) and functional principal component analysis were used for dimensionality reduction of the dose-volume histogrammore » data. The reduced dose data were input into functional logistic regression models (functional partial least squares–logistic regression [FPLS-LR] and functional principal component–logistic regression [FPC-LR]) along with clinical data. This approach was compared with penalized logistic regression (PLR) in terms of predictive performance and the significance of treatment covariate–response associations, assessed using bootstrapping. Results: The area under the receiver operating characteristic curve for the PLR, FPC-LR, and FPLS-LR models was 0.65, 0.69, and 0.67, respectively, for mucositis (internal validation) and 0.81, 0.83, and 0.83, respectively, for dysphagia (external validation). The calibration slopes/intercepts for the PLR, FPC-LR, and FPLS-LR models were 1.6/−0.67, 0.45/0.47, and 0.40/0.49, respectively, for mucositis (internal validation) and 2.5/−0.96, 0.79/−0.04, and 0.79/0.00, respectively, for dysphagia (external validation). The bootstrapped odds ratios indicated significant associations between RT dose and severe toxicity in the mucositis and dysphagia FDA models. Cisplatin was significantly associated with severe dysphagia in the FDA models. None of the covariates was significantly associated with severe toxicity in the PLR models. Dose levels greater than approximately 1.0 Gy/fraction were most strongly associated with severe acute mucositis and dysphagia in the FDA models. Conclusions: FPLS and functional principal component analysis marginally improved predictive performance compared with PLR and provided robust dose-response associations. FDA is recommended for use in normal tissue complication probability modeling.« less

Functional Data Analysis Applied to Modeling of Severe Acute Mucositis and Dysphagia Resulting From Head and Neck Radiation Therapy.

PubMed

Dean, Jamie A; Wong, Kee H; Gay, Hiram; Welsh, Liam C; Jones, Ann-Britt; Schick, Ulrike; Oh, Jung Hun; Apte, Aditya; Newbold, Kate L; Bhide, Shreerang A; Harrington, Kevin J; Deasy, Joseph O; Nutting, Christopher M; Gulliford, Sarah L

2016-11-15

Current normal tissue complication probability modeling using logistic regression suffers from bias and high uncertainty in the presence of highly correlated radiation therapy (RT) dose data. This hinders robust estimates of dose-response associations and, hence, optimal normal tissue-sparing strategies from being elucidated. Using functional data analysis (FDA) to reduce the dimensionality of the dose data could overcome this limitation. FDA was applied to modeling of severe acute mucositis and dysphagia resulting from head and neck RT. Functional partial least squares regression (FPLS) and functional principal component analysis were used for dimensionality reduction of the dose-volume histogram data. The reduced dose data were input into functional logistic regression models (functional partial least squares-logistic regression [FPLS-LR] and functional principal component-logistic regression [FPC-LR]) along with clinical data. This approach was compared with penalized logistic regression (PLR) in terms of predictive performance and the significance of treatment covariate-response associations, assessed using bootstrapping. The area under the receiver operating characteristic curve for the PLR, FPC-LR, and FPLS-LR models was 0.65, 0.69, and 0.67, respectively, for mucositis (internal validation) and 0.81, 0.83, and 0.83, respectively, for dysphagia (external validation). The calibration slopes/intercepts for the PLR, FPC-LR, and FPLS-LR models were 1.6/-0.67, 0.45/0.47, and 0.40/0.49, respectively, for mucositis (internal validation) and 2.5/-0.96, 0.79/-0.04, and 0.79/0.00, respectively, for dysphagia (external validation). The bootstrapped odds ratios indicated significant associations between RT dose and severe toxicity in the mucositis and dysphagia FDA models. Cisplatin was significantly associated with severe dysphagia in the FDA models. None of the covariates was significantly associated with severe toxicity in the PLR models. Dose levels greater than approximately 1.0 Gy/fraction were most strongly associated with severe acute mucositis and dysphagia in the FDA models. FPLS and functional principal component analysis marginally improved predictive performance compared with PLR and provided robust dose-response associations. FDA is recommended for use in normal tissue complication probability modeling. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Subtle changes in brain functions produced by single doses of mevinphos (Phosdrin).

DOT National Transportation Integrated Search

1973-02-01

Mevinphos (Phosdrin) was found to inhibit the amplitude of hippocampal evoked potentials in unanesthetized squirrel monkeys with chronically indwelling electrodes. The threshold dose was 0.050 mg/kg and the maximal dose studied was 0.200 mg/kg. Doses...

Pharmacokinetics and Safety of Bortezomib in Patients with Advanced Malignancies and Varying Degrees of Liver Dysfunction: Phase 1 NCI Organ Dysfunction Working Group Study NCI-6432

PubMed Central

LoRusso, Patricia M; Venkatakrishnan, Karthik; Ramanathan, Ramesh K; Sarantopoulos, John; Mulkerin, Daniel; Shibata, Stephen I; Hamilton, Anne; Dowlati, Afshin; Mani, Sridhar; Rudek, Michelle A; Takimoto, Chris H; Neuwirth, Rachel; Esseltine, Dixie-Lee; Ivy, Percy

2013-01-01

Purpose The proteasome inhibitor bortezomib undergoes oxidative hepatic metabolism. This study (NCI-6432; NCT00091117) was conducted to evaluate bortezomib pharmacokinetics and safety in patients with varying degrees of hepatic impairment, to inform dosing recommendations in these special populations. Methods Patients received bortezomib on days 1, 4, 8, and 11 of 21-day cycles. Patients were assigned to four hepatic function groups based on the National Cancer Institute Organ Dysfunction Working Group classification. Those with normal function received bortezomib at the 1.3 mg/m2 standard dose. Patients with severe, moderate, and mild impairment received escalating doses from 0.5, 0.7, and 1.0 mg/m2, respectively, up to a 1.3 mg/m2 maximum. Serial blood samples were collected for 24 hours post-dose on days 1 and 8, cycle 1, for bortezomib plasma concentration measurements. Results Sixty-one patients were treated, including 14 with normal hepatic function and 17, 12, and 18 with mild, moderate, and severe impairment, respectively. Mild hepatic impairment did not alter dose-normalized bortezomib exposure (AUC0-tlast) or Cmax compared with patients with normal function. Mean dose-normalized AUC0-tlast was increased by approximately 60% on day 8 in patients with moderate or severe impairment. Conclusions Patients with mild hepatic impairment do not require a starting dose adjustment of bortezomib. Patients with moderate or severe hepatic impairment should be started at a reduced dose of 0.7 mg/m2. PMID:22394984

Characteristics and verification of a car-borne survey system for dose rates in air: KURAMA-II.

PubMed

Tsuda, S; Yoshida, T; Tsutsumi, M; Saito, K

2015-01-01

The car-borne survey system KURAMA-II, developed by the Kyoto University Research Reactor Institute, has been used for air dose rate mapping after the Fukushima Dai-ichi Nuclear Power Plant accident. KURAMA-II consists of a CsI(Tl) scintillation detector, a GPS device, and a control device for data processing. The dose rates monitored by KURAMA-II are based on the G(E) function (spectrum-dose conversion operator), which can precisely calculate dose rates from measured pulse-height distribution even if the energy spectrum changes significantly. The characteristics of KURAMA-II have been investigated with particular consideration to the reliability of the calculated G(E) function, dose rate dependence, statistical fluctuation, angular dependence, and energy dependence. The results indicate that 100 units of KURAMA-II systems have acceptable quality for mass monitoring of dose rates in the environment. Copyright © 2014 Elsevier Ltd. All rights reserved.

SU-F-T-301: Planar Dose Pass Rate Inflation Due to the MapCHECK Measurement Uncertainty Function

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

Bailey, D; Spaans, J; Kumaraswamy, L

Purpose: To quantify the effect of the Measurement Uncertainty function on planar dosimetry pass rates, as analyzed with Sun Nuclear Corporation analytic software (“MapCHECK” or “SNC Patient”). This optional function is toggled on by default upon software installation, and automatically increases the user-defined dose percent difference (%Diff) tolerance for each planar dose comparison. Methods: Dose planes from 109 IMRT fields and 40 VMAT arcs were measured with the MapCHECK 2 diode array, and compared to calculated planes from a commercial treatment planning system. Pass rates were calculated within the SNC analytic software using varying calculation parameters, including Measurement Uncertainty onmore » and off. By varying the %Diff criterion for each dose comparison performed with Measurement Uncertainty turned off, an effective %Diff criterion was defined for each field/arc corresponding to the pass rate achieved with MapCHECK Uncertainty turned on. Results: For 3%/3mm analysis, the Measurement Uncertainty function increases the user-defined %Diff by 0.8–1.1% average, depending on plan type and calculation technique, for an average pass rate increase of 1.0–3.5% (maximum +8.7%). For 2%, 2 mm analysis, the Measurement Uncertainty function increases the user-defined %Diff by 0.7–1.2% average, for an average pass rate increase of 3.5–8.1% (maximum +14.2%). The largest increases in pass rate are generally seen with poorly-matched planar dose comparisons; the MapCHECK Uncertainty effect is markedly smaller as pass rates approach 100%. Conclusion: The Measurement Uncertainty function may substantially inflate planar dose comparison pass rates for typical IMRT and VMAT planes. The types of uncertainties incorporated into the function (and their associated quantitative estimates) as described in the software user’s manual may not accurately estimate realistic measurement uncertainty for the user’s measurement conditions. Pass rates listed in published reports or otherwise compared to the results of other users or vendors should clearly indicate whether the Measurement Uncertainty function is used.« less

Administration of low dose estrogen attenuates persistent inflammation, promotes angiogenesis, and improves locomotor function following chronic spinal cord injury in rats.

PubMed

Samantaray, Supriti; Das, Arabinda; Matzelle, Denise C; Yu, Shan P; Wei, Ling; Varma, Abhay; Ray, Swapan K; Banik, Naren L

2016-05-01

Spinal cord injury (SCI) causes loss of neurological function and, depending upon the severity of injury, may lead to paralysis. Currently, no FDA-approved pharmacotherapy is available for SCI. High-dose methylprednisolone is widely used, but this treatment is controversial. We have previously shown that low doses of estrogen reduces inflammation, attenuates cell death, and protects axon and myelin in SCI rats, but its effectiveness in recovery of function is not known. Therefore, the goal of this study was to investigate whether low doses of estrogen in post-SCI would reduce inflammation, protect cells and axons, and improve locomotor function during the chronic phase of injury. Injury (40 g.cm force) was induced at thoracic 10 in young adult male rats. Rats were treated with 10 or 100 μg 17β-estradiol (estrogen) for 7 days following SCI and compared with vehicle-treated injury and laminectomy (sham) controls. Histology (H&E staining), immunohistofluorescence, Doppler laser technique, and Western blotting were used to monitor tissue integrity, gliosis, blood flow, angiogenesis, the expression of angiogenic factors, axonal degeneration, and locomotor function (Basso, Beattie, and Bresnahan rating) following injury. To assess the progression of recovery, rats were sacrificed at 7, 14, or 42 days post injury. A reduction in glial reactivity, attenuation of axonal and myelin damage, protection of cells, increased expression of angiogenic factors and microvessel growth, and improved locomotor function were found following estrogen treatment compared with vehicle-treated SCI rats. These results suggest that treatment with a very low dose of estrogen has significant therapeutic implications for the improvement of locomotor function in chronic SCI. Experimental studies with low dose estrogen therapy in chronic spinal cord injury (SCI) demonstrated the potential for multi-active beneficial outcomes that could ameliorate the degenerative pathways in chronic SCI as shown in (a). Furthermore, the alterations in local spinal blood flow could be significantly alleviated with low dose estrogen therapy. This therapy led to the preservation of the structural integrity of the spinal cord (b), which in turn led to the improved functional recovery as shown (c). © 2016 International Society for Neurochemistry.

Predictive models for regional hepatic function based on 99mTc-IDA SPECT and local radiation dose for physiologic adaptive radiation therapy.

PubMed

Wang, Hesheng; Feng, Mary; Frey, Kirk A; Ten Haken, Randall K; Lawrence, Theodore S; Cao, Yue

2013-08-01

High-dose radiation therapy (RT) for intrahepatic cancer is limited by the development of liver injury. This study investigated whether regional hepatic function assessed before and during the course of RT using 99mTc-labeled iminodiacetic acid (IDA) single photon emission computed tomography (SPECT) could predict regional liver function reserve after RT. Fourteen patients treated with RT for intrahepatic cancers underwent dynamic 99mTc-IDA SPECT scans before RT, during, and 1 month after completion of RT. Indocyanine green (ICG) tests, a measure of overall liver function, were performed within 1 day of each scan. Three-dimensional volumetric hepatic extraction fraction (HEF) images of the liver were estimated by deconvolution analysis. After coregistration of the CT/SPECT and the treatment planning CT, HEF dose-response functions during and after RT were generated. The volumetric mean of the HEFs in the whole liver was correlated with ICG clearance time. Three models, dose, priori, and adaptive models, were developed using multivariate linear regression to assess whether the regional HEFs measured before and during RT helped predict regional hepatic function after RT. The mean of the volumetric liver HEFs was significantly correlated with ICG clearance half-life time (r=-0.80, P<.0001), for all time points. Linear correlations between local doses and regional HEFs 1 month after RT were significant in 12 patients. In the priori model, regional HEF after RT was predicted by the planned dose and regional HEF assessed before RT (R=0.71, P<.0001). In the adaptive model, regional HEF after RT was predicted by regional HEF reassessed during RT and the remaining planned local dose (R=0.83, P<.0001). 99mTc-IDA SPECT obtained during RT could be used to assess regional hepatic function and helped predict post-RT regional liver function reserve. This could support individualized adaptive radiation treatment strategies to maximize tumor control and minimize the risk of liver damage. Published by Elsevier Inc.

Renal function preservation with the mTOR inhibitor, Everolimus, after lung transplant.

PubMed

Schneer, Sonia; Kramer, Mordechai R; Fox, Benjamin; Rusanov, Viktoria; Fruchter, Oren; Rosengarten, Dror; Bakal, Ilana; Medalion, Benjamin; Raviv, Yael

2014-06-01

Chronic kidney disease (CKD) is a common complication of calcineurin inhibitors (CNIs) in solid organ transplantation. Previous data suggest that the use of everolimus as an immunosuppressant drug leads to improvement in renal function. The aim of our study was to establish the effect of everolimus in combination with lower doses of CNIs on renal function among lung transplant recipients. Data regarding renal function and pulmonary function were collected from 41 lung transplanted patients in whom treatment was converted to a combination of everolimus with lower doses of CNIs. Patients transferred to everolimus and low dose CNIs showed an improvement in renal function. Patients who continued treatment with everolimus showed improvement in renal function, as opposed to patients who discontinued the treatment. Subjects without proteinuria at baseline showed a better improvement compared with subjects with proteinuria. The incidence of graft rejection did not increase. We concluded that a protocol that includes everolimus and lower doses of CNIs is effective for preserving renal function in lung transplant recipients with CKD. We also believe that an early implementation of everolimus, before proteinuria occurs or creatinine clearance is reduced, could lead to better outcomes. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clinical assessment of the jaw-tracking function in IMRT for a brain tumor

NASA Astrophysics Data System (ADS)

Kim, Jin-Young; Kim, Shin-Wook; Choe, Bo-Young; Suh, Tae-Suk; Park, Sung-Kwang; Jo, Sun-Mi; Oh, Won-Yong; Shin, Jung-Wook; Cho, Gyu-Seok; Nam, Sang-Hee; Chung, Jin-Beom; Kim, Jung-Ki; Lee, Young-Kyu

2015-01-01

Intensity-modulated radiotherapy (IMRT) improves dose conformity and saves critical organs. IMRT is widely used in cases of head and neck, prostate, and brain cancer due to the close location of the targets to critical structures. However, because IMRT has a larger amount of radiation exposure than 3 dimensional-conformal radiation therapy (3D-CRT), it has disadvantages such as increases in the low dose irradiation to normal tissues and in the accumulated dose for the whole volume due to leakage and transmission of the multi-leaf collimator (MLC). The increased accumulated dose and the larger low dose may increase the occurrence of secondary malignant neoplasms. For these reasons, the jaw-tracking function of the TrueBeam (Varian Medical Systems, Palo Alto, CA) was developed to reduce the leakage and the transmission dose of the MLC with linear accelerators. However, the change in the superficial dose has not been verified with a quantitative analysis of the dose reduction in a brain tumor. Therefore, in the present study, we intended to verify the clinical possibility of utilizing the jaw-tracking function for a brain tumor by comparing treatment plans and superficial doses. To accomplish this, we made three types of original treatment plans using Eclipse11 (Varian Medical Systems, Palo Alto, CA): 1) farther than 2 cm from the organs at risk (OAR); 2) within 2 cm of the OAR; and 3) intersecting with the OAR. Jaw-tracking treatment plans were also made with copies of the original treatment plan using Smart LMC Version 11.0.31 (Varian Medical Systems, Palo Alto, CA). A comparison between the original treatment plans and jaw-tracking treatment plans was performed using the difference of the mean dose and maximum dose to the OARs in cumulative Dose Volume Histogram (DVH). In addition, the dependencies of the effects of transmission and the scattering doses according to jaw motion were assessed through the difference in the surface doses. In the DVH comparison, a maximum dose difference of 0.4% was observed between the planning methods in the case of over 2 cm distance, and the maximum dose of 0.6% was obtained for within the 2 cm distance. For the case intersecting with the OAR, the maximum dose difference of 2.3% was achieved. According to these results, the differences in the mean doses and the maximum doses to the OARs ware larger when the OARs and the planning target volume (PTV) were closer. In addition, small differences in the surface dose measurements were observed. In the case of the inside field, the differences were under 2% of the prescription dose while the difference was under 0.1% in the case of the outside field. Therefore, treatment plans with the jaw-tracking function consistently affected the dose reduction for a brain tumor, and the clinical possibility could be verified as the surface dose was not increased.

Skin dose from radionuclide contamination on clothing

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

Taylor, D.C.; Hussein, E.M.A.; Yuen, P.S.

1997-06-01

Skin dose due to radio nuclide contamination on clothing is calculated by Monte Carlo simulation of electron and photon radiation transport. Contamination due to a hot particle on some selected clothing geometries of cotton garment is simulated. The effect of backscattering in the surrounding air is taken into account. For each combination of source-clothing geometry, the dose distribution function in the skin, including the dose at tissue depths of 7 mg cm{sup -2} and 1,000 Mg cm{sup -2}, is calculated by simulating monoenergetic photon and electron sources. Skin dose due to contamination by a radionuclide is then determined by propermore » weighting of & monoenergetic dose distribution functions. The results are compared with the VARSKIN point-kernel code for some radionuclides, indicating that the latter code tends to under-estimate the dose for gamma and high energy beta sources while it overestimates skin dose for low energy beta sources. 13 refs., 4 figs., 2 tabs.« less

SU-F-T-124: Radiation Biological Equivalent Presentations OfLEM-1 and MKM Approaches in the Carbon-Ion Radiotherapy

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

Hsi, W; Jiang, G; Sheng, Y

Purpose: To study the correlations of the radiation biological equivalent doses (BED) along depth and lateral distance between LEM-1 and MKM approaches. Methods: In NIRS-MKM (Microdosimetric Kinetic Model) approach, the prescribed BED, referred as C-Eq, doses aims to present the relative biological effectiveness (RBE) for different energies of carbon-ions on a fixed 10% survival value of HCG cell with respect to convention X-ray. Instead of a fixed 10% survival, the BED doses of LEM-1 (Local Effect Model) approach, referred as X-Eq, aims to present the RBE over the whole survival curve of chordoma-like cell with alpha/beta ratio of 2.0. Themore » relationship of physical doses as a function of C-Eq and X-Eq doses were investigated along depth and lateral distance for various sizes of cubic targets in water irradiated by carbon-ions. Results: At the center of each cubic target, the trends between physical and C-Eq or X-Eq doses can be described by a linear and 2nd order polynomial functions, respectively. Using fit functions can then calculate a scaling factor between C-Eq and X-Eq doses to have similar physical doses. With equalized C-Eq and X-Eq doses at the depth of target center, over- and under-estimated X-Eq to C-Eq are seen for depths before and after the target center, respectively. Near the distal edge along depth, sharp rising of RBE value is observed for X-Eq, but sharp dropping of RBE value is observed for C-Eq. For lateral locations near and just outside 50% dose level, sharp raising of RBE value is also seen for X-Eq, while only minor increasing with fast dropping for C-Eq. Conclusion: An analytical function to model the differences between the CEq and X-Eq doses along depth and lateral distance need to further investigated to explain varied clinic outcome of specific cancers using two different approaches to calculated BED doses.« less

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

Wu, Q

Purpose: According to clinical and research requirement, we develop a function of automatic reading dose of interest from dose volume histogram(DVH), to replace the traditional method with a mouse one by one point, and it's also verified. Methods: The DVH automatic reading function will be developed in an in-house developed radiotherapy information management system(RTIMS), which is based on Apache+PHP+MySQL. A DVH ASCII file is exported from Varian Eclipse V8.6, which includes the following contents: 1. basic information of patient; 2. dose information of plan; 3. dose information of structures, including basic information and dose volume data of target volume andmore » organ at risk. And the default exported dose volume data also includes relative doses by 1% step and corresponding absolute doses and cumulative relative volumes, and the volumes are 4 decimal fraction. Clinically, we often need read the doses of some integer percent volumes, such as D50 and D30. So it couldn't be directly obtained from the above data, but we can use linear interpolation bye the near volumes and doses: Dx=D2−(V2−Vx)*(D2−D1)/(V2−V1), and program a function to search, read and calculate the corresponding data. And the doses of all preseted volume of interest of all structures can be automatically read one by one patient, and saved as a CSV file. To verify it, we select 24 IMRT plans for prostate cancer, and doses of interest are PTV D98/D95/D5/D2, bladder D30/D50, and rectum D25/D50. Two groups of data, using the automatic reading method(ARM) and pointed dose method(PDM), are analyzed with SPSS 16. The absolute difference=D-ARM-D-PDM, relative difference=absolute difference*100%/prescription dose(7600cGy). Results: The differences are as following: PTV D98/D95/D5/D2: −0.04%/− 0.04%/0.13%/0.19%, bladder D30/D50: −0.02%/0.01%, and rectum D25/D50: 0.03%/0.01%. Conclusion: Using this function, the error is very small, and can be neglected. It could greatly improve the efficiency of clinical work. Project supported by the National Natural Science Foundation of China (Grant No.81101694)« less

A real time spectrum to dose conversion system

NASA Technical Reports Server (NTRS)

Farmer, B. J.; Johnson, J. H.; Bagwell, R. G.

1972-01-01

A system has been developed which permits the determination of dose in real time or near real time directly from the pulse-height output of a radiation spectrometer. The technique involves the use of the resolution matrix of a spectrometer, the radiation energy-to-dose conversion function, and the geometrical factors, although the order of matrix operations is reversed. The new technique yields a result which is mathematically identical to the standard method while requiring no matrix manipulations or resolution matrix storage in the remote computer. It utilizes only a single function for each type dose required and each geometric factor involved.

Acetylator Status Impacts Amifampridine Phosphate (Firdapse™) Pharmacokinetics and Exposure to a Greater Extent Than Renal Function.

PubMed

Haroldsen, Peter E; Sisic, Zlatko; Datt, Joe; Musson, Donald G; Ingenito, Gary

2017-07-01

The purpose of this study is to evaluate safety, tolerability, and pharmacokinetic (PK) properties of amifampridine phosphate (Firdapse™) and its major inactive 3-N-acetyl metabolite in renally impaired and healthy individuals with slow acetylator (SA) and rapid acetylator (RA) phenotypes. This was a Phase I, multicenter, open-label study of the PK properties and safety profile of amifampridine phosphate in individuals with normal, mild, moderate, or severely impaired renal function. Amifampridine phosphate was given as a single 10 mg (base equivalent) dose, and the plasma and urine PK properties of amifampridine and its 3-N-acetyl metabolite were determined. The safety profile was evaluated by monitoring adverse events (AEs), clinical laboratory tests, and physical examinations. Amifampridine clearance was predominantly metabolic through N-acetylation, regardless of renal function in both acetylator phenotypes. In individuals with normal renal function, mean renal clearance represented approximately 3% and 18% of the total clearance of amifampridine in RA and SA, respectively. Large differences in amifampridine exposure were observed between acetylation phenotypes across renal function levels. Mean amifampridine exposure values of AUC 0-∞ and C max were up to 8.8-fold higher in the SA group compared with the RA group across renal function levels. By comparison, mean AUC 0-∞ was less affected by renal function within an acetylator group, only 2- to 3-fold higher in individuals with severe renal impairment (RI) compared with those with normal renal function. Exposure to amifampridine in the SA group with normal renal function was higher (AUC 0-∞, approximately 1.8-fold; C max, approximately 4.1-fold) than the RA group with severe RI. Exposure to the inactive 3-N-acetyl metabolite was higher than amifampridine in both acetylator groups, independent of renal function level. The metabolite is cleared by renal excretion, and exposure was clearly dependent on renal function with 4.0- to 6.8-fold increases in AUC 0-∞ from normal to severe RI. No new tolerability findings were observed. A single dose of 10 mg of amifampridine phosphate was well tolerated, independent of renal function and acetylator status. The results indicate that the PK profile of amifampridine is affected by metabolic acetylator phenotype to a greater extent than by renal function level, supporting Firdapse™ administration in individuals with RI in line with current labeling recommendations. Amifampridine should be dosed to effect per the individual patient need, altering administration frequency and dose in normal through severe RI. The therapeutic dose of amifampridine phosphate should be tailored to the individual patient needs by gradual dose titration up to the present maximum recommended dose (60-80 mg/day) or until dose-limiting AEs intervene to avoid overdosing and underdosing. EudraCT identifier: 2013-005349-35. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Using quality of life measures in a Phase I clinical trial of noni in patients with advanced cancer to select a Phase II dose.

PubMed

Issell, Brian F; Gotay, Carolyn C; Pagano, Ian; Franke, Adrian A

2009-01-01

ABSTRACT. The purpose of this study was to determine a maximum tolerated dose of noni in cancer patients and whether an optimal quality of life-sustaining dose could be identified as an alternative way to select a dose for subsequent Phase II efficacy trials. Dose levels started at two capsules twice daily (2 g), the suggested dose for the marketed product, and were escalated by 2 g daily in cohorts of at least five patients until a maximum tolerated dose was found. Patients completed subscales of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 quality of life (physical functioning, pain, and fatigue) the brief fatigue inventory (BFI), questionnaires at baseline and at approximately 4-week intervals. Blood and urine were collected at baseline and at approximately 4-week intervals for measurement of scopoletin. Fifty-one patients were enrolled at seven dose levels. The maximum tolerated dose was six capsules four times daily (12 g). Although no dose-limiting toxicity was found, seven of eight patients at the next level (14 g), withdrew due to the challenges of ingesting so many capsules. There were dose-related differences in self-reported physical functioning and pain and fatigue control. Overall, patients taking three or four capsules four times daily experienced better outcomes than patients taking lower or higher doses. Blood and urinary scopoletin concentrations related to noni dose. We concluded that it is feasible to use quality of life measures to select a Phase II dose. Three or four capsules four times daily (6-8 g) is recommended when controlling fatigue, pain, and maintaining physical function are the efficacies of interest. Scopoletin, a bioactive component of noni fruit extract, is measurable in blood and urine following noni ingestion and can be used to study the pharmacokinetics of noni in cancer patients.

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

Purwaningsih, Anik

Dosimetric data for a brachytherapy source should be known before it used for clinical treatment. Iridium-192 source type H01 was manufactured by PRR-BATAN aimed to brachytherapy is not yet known its dosimetric data. Radial dose function and anisotropic dose distribution are some primary keys in brachytherapy source. Dose distribution for Iridium-192 source type H01 was obtained from the dose calculation formalism recommended in the AAPM TG-43U1 report using MCNPX 2.6.0 Monte Carlo simulation code. To know the effect of cavity on Iridium-192 type H01 caused by manufacturing process, also calculated on Iridium-192 type H01 if without cavity. The result ofmore » calculation of radial dose function and anisotropic dose distribution for Iridium-192 source type H01 were compared with another model of Iridium-192 source.« less

Nandrolone decanoate as anabolic therapy in chronic kidney disease: a randomized phase II dose-finding study.

PubMed

Macdonald, Jamie H; Marcora, Samuele M; Jibani, Mahdi M; Kumwenda, Mick J; Ahmed, Wasim; Lemmey, Andrew B

2007-01-01

In patients with chronic kidney disease (CKD) receiving adequate erythropoietin therapy, the ideal dose of nandrolone decanoate (ND) to enhance muscle mass is not known. In this phase II dose-finding study, 54 patients with CKD stage 5 were randomized to either low, medium or high doses of ND (50, 100 or 200 mg/week for 24 weeks, respectively, in males; doses halved in females), while 7 patients acted as non-randomized controls. The primary outcome measure was appendicular lean mass (ALM) by dual-energy X-ray absorptiometry. Fluid overload (hydration of the fat-free mass) and indicators of physical functioning were secondary measures. Harms were also recorded. Data were analysed using Quade's (1967) non-parametric analysis of covariance. ND increased ALM in a dose-responsive manner (change scores = 0.3 +/- 0.3 vs. 0.8 +/- 0.3 vs. 1.5 +/- 0.5 vs. 2.1 +/- 0.4 kg, control vs. low vs. medium vs. high dose groups, respectively, p < 0.001) with no increases in fluid overload but no consistent effect on physical functioning. The highest dose of ND (100 mg/week) was intolerable in females because of virilizing effects. If goals of future studies are to improve body composition, dosing of ND up to 200 mg/week in males and 50 mg/week in females should be investigated. However, to realize improvements in physical functioning, future phase III trials of ND may require additional interventions such as exercise training. Copyright 2007 S. Karger AG, Basel.

Effects of supplementation with higher levels of manganese and magnesium on immune function.

PubMed

Son, Eun-Wha; Lee, Sung-Ryul; Choi, Hye-Sook; Koo, Hyun-Jung; Huh, Jung-Eun; Kim, Mi-Hyun; Pyo, Suhkneung

2007-06-01

The magnesium (Mg) and manganese (Mn) were evaluated for its effectiveness as an immunomodulator in rats. The treatments were as follows: Group 1, AIN-93M diet (0.05% Mg, 0.001% Mn); Group 2, high-dose Mg (0.1% Mg, 0.001% Mn); and Group 3, high dose Mn (0.05% Mg, 0.01% Mn) (n-12/group). After 12 weeks of supplementation, rats were sacrificed to assess the effect on a range of innate responses (tumoricidal activity, oxidative burst and nitric oxide) and the mitogen-stimulated lymphoproliferative response. Immune function was significantly affected in both the high dose Mg and the Mn group. Lymphocyte proliferative responses and NK cell activity were measured in pooled spleen from each group. The mitogen response of lymphocytes to LPS in the spleen was significantly reduced in high dose Mg-treated groups, whereas the response to ConA was not affected in both high dose minerals-treated groups. The reactive oxygen species level of macrophages was decreased in both groups. These effects were more pronounced in high dose Mg-treated group. Nitric oxide production was also decreased in high dose minerals-treated group. In addition, tumoricidal activities of splenic NK cell and peritoneal macrophage in mineral exposed rats were significantly increased. Moreover, percent death of macrophage was reduced in two groups receiving high dose mineral supplements. Taken together, the present data suggest that high dose trace min erals exert a differential effect on the function of immune cells.

Current dosing of low-molecular-weight heparins does not reflect licensed product labels: an international survey

PubMed Central

Barras, Michael A; Kirkpatrick, Carl M J; Green, Bruce

2010-01-01

AIMS Low-molecular-weight heparins (LMWHs) are used globally to treat thromboembolic diseases; however, there is much debate on how to prescribe effectively for patients who have renal impairment and/or obesity. We aimed to investigate the strategies used to dose-individualize LMWH therapy. METHODS We conducted an online survey of selected hospitals in Australia, New Zealand (NZ), United Kingdom (UK) and the United States (US). Outcome measures included: the percentage of hospitals which recommended that LMWHs were prescribed according to the product label (PL), the percentage of hospitals that dose-individualized LMWHs outside the PL based on renal function, body weight and anti-Xa activity and a summary of methods used to dose-individualize therapy. RESULTS A total of 257 surveys were suitable for analysis: 84 (33%) from Australia, 79 (31%) from the UK, 73 (28%) from the US and 21 (8%) from NZ. Formal dosing protocols were used in 207 (81%) hospitals, of which 198 (96%) did not adhere to the PL. Of these 198 hospitals, 175 (87%) preferred to dose-individualize based on renal function, 128 (62%) on body weight and 48 (23%) by monitoring anti-Xa activity. All three of these variables were used in 29 (14%) hospitals, 98 (47%) used two variables and 71 (34%) used only one variable. CONCLUSIONS Dose-individualization strategies for LMWHs, which contravene the PL, were present in 96% of surveyed hospitals. Common individualization methods included dose-capping, use of lean body size descriptors to calculate renal function and the starting dose, followed by post dose anti-Xa monitoring. PMID:20573088

Current dosing of low-molecular-weight heparins does not reflect licensed product labels: an international survey.

PubMed

Barras, Michael A; Kirkpatrick, Carl M J; Green, Bruce

2010-05-01

Low-molecular-weight heparins (LMWHs) are used globally to treat thromboembolic diseases; however, there is much debate on how to prescribe effectively for patients who have renal impairment and/or obesity. We aimed to investigate the strategies used to dose-individualize LMWH therapy. We conducted an online survey of selected hospitals in Australia, New Zealand (NZ), United Kingdom (UK) and the United States (US). Outcome measures included: the percentage of hospitals which recommended that LMWHs were prescribed according to the product label (PL), the percentage of hospitals that dose-individualized LMWHs outside the PL based on renal function, body weight and anti-Xa activity and a summary of methods used to dose-individualize therapy. A total of 257 surveys were suitable for analysis: 84 (33%) from Australia, 79 (31%) from the UK, 73 (28%) from the US and 21 (8%) from NZ. Formal dosing protocols were used in 207 (81%) hospitals, of which 198 (96%) did not adhere to the PL. Of these 198 hospitals, 175 (87%) preferred to dose-individualize based on renal function, 128 (62%) on body weight and 48 (23%) by monitoring anti-Xa activity. All three of these variables were used in 29 (14%) hospitals, 98 (47%) used two variables and 71 (34%) used only one variable. Dose-individualization strategies for LMWHs, which contravene the PL, were present in 96% of surveyed hospitals. Common individualization methods included dose-capping, use of lean body size descriptors to calculate renal function and the starting dose, followed by post dose anti-Xa monitoring.

EFFECTS OF REACTOR RADIATION ON THE ELECTRICAL PROPERTIES OF ELECTRONIC COMPONENTS. PART II. VACUUM TUBES, TRANSISTORS AND TRANSFORMERS

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

Miglicco, P.S.; Spears, A.B.; Howell, D.B.

1957-11-22

Several types of vacuum tubes, transistors and transformers were irradiated with the Convair-Fort Worth Ground Test Reactor. The components were subjected to five different fluxes ranging from 10/sup 6/ to 10/sup 10/n/sub F// cm/sup 2/-sec and 10/sup 8/ to 10/sup 12/ gamma /cm/sup 2/-sec. The total integrated flux received was 10/sup 14/n/sub F//cm/sup 2/ and 10/sup 16/ gamma / cm/sup 2/. An attempt was made to separate radiation damage as a function of dose rate from radiation damage as a function of dose. The components were irradiated first at several low dose rates so that dose rate effects could bemore » studied while the accumulated dose was small, and then at a high dose rate to obtain the desired dose. However, because of the long time required to complete a data gathering cycle, the accumulated dose hindered the separation of dose rate and dose effects. Thus, in the report, the damage to the components is reported as a function of integrated flux. For reference, the integrated flux accumulated at each power level is given. The transformers exhibited the greatest resistance to irradiation. Every important parameter of the transistors deteriorated in the radiation field. Postirradiation tests at room temperature showed no significant recovery in the transistor's characteristics. The plate current of 65% of the tubes tested increased during irradiation. This effect, based on postirradiation tests, is considered permanent. (auth)« less

[Effect of polysaccharides in processed Sibiraea on immunologic function of immunosuppression mice].

PubMed

Duan, Bowen; Li, Yun; Liu, Xin; Yang, Yongjian

2010-06-01

To study the effect of polysaccharides in processed Sibiraea on the immunologic function of immunosuppression mice. The immunosuppressed mice were induced by cyclophosphamide. After the treatment, the organ weight index and the delayed type hypersensitivity of the mice were investigated. The humoral immune function was determined by serum hemolysin assay. Non-specific immune function was determined by carbon clearance method. Cellular immune function was determined by spleen lymphocyte proliferation test. Two hundred kunming mice were randomly divided into five groups: normal controls, model group, low-dose group (110 mg x kg(-1)), middle-dose group (220 mg x kg(-1)), high-dose group (440 mg x kg(-1)). Drugs were given to the mice by oral gavage every day. The immunosuppressed mice treated with Sibiraea polysibcharide at intragastrica dose of 110-440 mg x kg(-1) have increased weight of the immune organs, increased content of DTH and content in serum hemolysin lgG and lgM. Mean while the rate of carbon clearance was enhanced and the proliferation of spleen lymphocyte was increased. Polysaccharides in processed Sibiraea can increase the weight of the immune organs. At the same time, non-specific immune, DTH, humoral immune and cellular immune function were enhanced significantly.

Alcohol Dose Effects on Brain Circuits During Simulated Driving: An fMRI Study

PubMed Central

Meda, Shashwath A.; Calhoun, Vince D.; Astur, Robert S.; Turner, Beth M.; Ruopp, Kathryn; Pearlson, Godfrey D.

2009-01-01

Driving while intoxicated remains a major public health hazard. Driving is a complex task involving simultaneous recruitment of multiple cognitive functions. The investigators studied the neural substrates of driving and their response to different blood alcohol concentrations (BACs), using functional magnetic resonance imaging (fMRI) and a virtual reality driving simulator. We used independent component analysis (ICA) to isolate spatially independent and temporally correlated driving-related brain circuits in 40 healthy, adult moderate social drinkers. Each subject received three individualized, separate single-blind doses of beverage alcohol to produce BACs of 0.05% (moderate), 0.10% (high), or 0% (placebo). 3 T fMRI scanning and continuous behavioral measurement occurred during simulated driving. Brain function was assessed and compared using both ICA and a conventional general linear model (GLM) analysis. ICA results replicated and significantly extended our previous 1.5T study (Calhoun et al. [2004a]: Neuropsychopharmacology 29:2097–2017). GLM analysis revealed significant dose-related functional differences, complementing ICA data. Driving behaviors including opposite white line crossings and mean speed independently demonstrated significant dose-dependent changes. Behavior-based factors also predicted a frontal-basal-temporal circuit to be functionally impaired with alcohol dosage across baseline scaled, good versus poorly performing drivers. We report neural correlates of driving behavior and found dose-related spatio-temporal disruptions in critical driving-associated regions including the superior, middle and orbito frontal gyri, anterior cingulate, primary/supplementary motor areas, basal ganglia, and cerebellum. Overall, results suggest that alcohol (especially at high doses) causes significant impairment of both driving behavior and brain functionality related to motor planning and control, goal directedness, error monitoring, and memory. PMID:18571794

Dose-Dependent Effects of Theta Burst rTMS on Cortical Excitability and Resting-State Connectivity of the Human Motor System

PubMed Central

Nettekoven, Charlotte; Volz, Lukas J.; Kutscha, Martha; Pool, Eva-Maria; Rehme, Anne K.; Eickhoff, Simon B.; Fink, Gereon R.

2014-01-01

Theta burst stimulation (TBS), a specific protocol of repetitive transcranial magnetic stimulation (rTMS), induces changes in cortical excitability that last beyond stimulation. TBS-induced aftereffects, however, vary between subjects, and the mechanisms underlying these aftereffects to date remain poorly understood. Therefore, the purpose of this study was to investigate whether increasing the number of pulses of intermittent TBS (iTBS) (1) increases cortical excitability as measured by motor-evoked potentials (MEPs) and (2) alters functional connectivity measured using resting-state fMRI, in a dose-dependent manner. Sixteen healthy, human subjects received three serially applied iTBS blocks of 600 pulses over the primary motor cortex (M1 stimulation) and the parieto-occipital vertex (sham stimulation) to test for dose-dependent iTBS effects on cortical excitability and functional connectivity (four sessions in total). iTBS over M1 increased MEP amplitudes compared with sham stimulation after each stimulation block. Although the increase in MEP amplitudes did not differ between the first and second block of M1 stimulation, we observed a significant increase after three blocks (1800 pulses). Furthermore, iTBS enhanced resting-state functional connectivity between the stimulated M1 and premotor regions in both hemispheres. Functional connectivity between M1 and ipsilateral dorsal premotor cortex further increased dose-dependently after 1800 pulses of iTBS over M1. However, no correlation between changes in MEP amplitudes and functional connectivity was detected. In summary, our data show that increasing the number of iTBS stimulation blocks results in dose-dependent effects at the local level (cortical excitability) as well as at a systems level (functional connectivity) with a dose-dependent enhancement of dorsal premotor cortex-M1 connectivity. PMID:24828639

Sodium Iodate Selectively Injuries the Posterior Pole of the Retina in a Dose-Dependent Manner: Morphological and Electrophysiological Study

PubMed Central

Machalińska, Anna; Lubiński, Wojciech; Kłos, Patrycja; Kawa, Miłosz; Baumert, Bartłomiej; Penkala, Krzysztof; Grzegrzółka, Ryszard; Karczewicz, Danuta; Wiszniewska, Barbara

2010-01-01

Sequential morphological and functional features of retinal damage in mice exposed to different doses (40 vs. 20 mg/kg) of sodium iodate (NaIO3) were analyzed. Retinal morphology, apoptosis (TUNEL assay), and function (electroretinography; ERG) were examined at several time points after NaIO3 administration. The higher dose of NaIO3 caused progressive degeneration of the whole retinal area and total suppression of scotopic and photopic ERG. In contrast, the lower dose induced much less severe degeneration in peripheral part of retina along with a moderate decline of b- and a-wave amplitudes in ERG, corroborating the presence of regions within retina that retain their function. The peak of photoreceptor apoptosis was found on the 3rd day, but the lower dose induced more intense reaction within the central retina than in its peripheral region. In conclusion, these results indicate that peripheral area of the retina reveals better resistance to NaIO3 injury than its central part. PMID:20725778

Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction Versus Treatment Switch

PubMed Central

Krämer, Johannes; Duning, Thomas; Lenders, Malte; Canaan-Kühl, Sima; Krebs, Alice; González, Hans Guerrero; Sommer, Claudia; Üçeyler, Nurcan; Niemann, Markus; Störk, Stefan; Schelleckes, Michael; Reiermann, Stefanie; Stypmann, Jörg; Brand, Stefan-Martin; Wanner, Christoph; Brand, Eva

2014-01-01

Because of the shortage of agalsidase-beta in 2009, many patients with Fabry disease were treated with lower doses or were switched to agalsidase-alfa. This observational study assessed end-organ damage and clinical symptoms during dose reduction or switch to agalsidase-alfa. A total of 105 adult patients with Fabry disease who had received agalsidase-beta (1.0 mg/kg body weight) for ≥1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=38), receive a reduced dose of 0.3–0.5 mg/kg (dose-reduction group, n=29), or switch to 0.2 mg/kg agalsidase-alfa (switch group) and were followed prospectively for 1 year. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD); changes in cardiac, renal, and neurologic function; and Fabry-related symptoms (neuropathic pain, hypohidrosis, diarrhea, and disease severity scores). Organ function and Fabry-related symptoms remained stable in the regular-dose group. In contrast, estimated GFR decreased by about 3 ml/min per 1.73 m2 (P=0.01) in the dose-reduction group, and the median albumin-to-creatinine ratio increased from 114 (0–606) mg/g to 216 (0–2062) mg/g (P=0.03) in the switch group. Furthermore, mean Mainz Severity Score Index scores and frequencies of pain attacks, chronic pain, gastrointestinal pain, and diarrhea increased significantly in the dose-reduction and switch groups. In conclusion, patients receiving regular agalsidase-beta dose had a stable disease course, but dose reduction led to worsening of renal function and symptoms. Switching to agalsidase-alfa is safe, but microalbuminuria may progress and Fabry-related symptoms may deteriorate. PMID:24556354

Patients with Fabry disease after enzyme replacement therapy dose reduction versus treatment switch.

PubMed

Weidemann, Frank; Krämer, Johannes; Duning, Thomas; Lenders, Malte; Canaan-Kühl, Sima; Krebs, Alice; Guerrero González, Hans; Sommer, Claudia; Üçeyler, Nurcan; Niemann, Markus; Störk, Stefan; Schelleckes, Michael; Reiermann, Stefanie; Stypmann, Jörg; Brand, Stefan-Martin; Wanner, Christoph; Brand, Eva

2014-04-01

Because of the shortage of agalsidase-beta in 2009, many patients with Fabry disease were treated with lower doses or were switched to agalsidase-alfa. This observational study assessed end-organ damage and clinical symptoms during dose reduction or switch to agalsidase-alfa. A total of 105 adult patients with Fabry disease who had received agalsidase-beta (1.0 mg/kg body weight) for ≥1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=38), receive a reduced dose of 0.3-0.5 mg/kg (dose-reduction group, n=29), or switch to 0.2 mg/kg agalsidase-alfa (switch group) and were followed prospectively for 1 year. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD); changes in cardiac, renal, and neurologic function; and Fabry-related symptoms (neuropathic pain, hypohidrosis, diarrhea, and disease severity scores). Organ function and Fabry-related symptoms remained stable in the regular-dose group. In contrast, estimated GFR decreased by about 3 ml/min per 1.73 m(2) (P=0.01) in the dose-reduction group, and the median albumin-to-creatinine ratio increased from 114 (0-606) mg/g to 216 (0-2062) mg/g (P=0.03) in the switch group. Furthermore, mean Mainz Severity Score Index scores and frequencies of pain attacks, chronic pain, gastrointestinal pain, and diarrhea increased significantly in the dose-reduction and switch groups. In conclusion, patients receiving regular agalsidase-beta dose had a stable disease course, but dose reduction led to worsening of renal function and symptoms. Switching to agalsidase-alfa is safe, but microalbuminuria may progress and Fabry-related symptoms may deteriorate.

Effect of aspirin on acute changes in peripheral arterial stiffness and endothelial function following exertional heat stress in firefighters: The factorial group results of the Enhanced Firefighter Rehab Trial.

PubMed

Olafiranye, Oladipupo; Hostler, David; Winger, Daniel G; Wang, Li; Reis, Steven E

2015-06-01

Peripheral arterial stiffness and endothelial function, which are independent predictors of cardiac events, are abnormal in firefighters. We examined the effects of aspirin on peripheral arterial stiffness and endothelial function in firefighters. Fifty-two firefighters were randomized to receive daily 81 mg aspirin or placebo for 14 days before treadmill exercise in thermal protection clothing, and a single dose of 325 mg aspirin or placebo immediately following exertion. Peripheral arterial augmentation index adjusted for a heart rate of 75 (AI75) and reactive hyperemia index (RHI) were determined immediately before, and 30, 60, and 90 minutes after exertion. Low-dose aspirin was associated with lower AI75 (-15.25±9.25 vs -8.08±10.70, p=0.014) but not RHI. On repeated measures analysis, treatment with low-dose aspirin before, but not single-dose aspirin after exertion, was associated with lower AI75 following exertional heat stress (p=0.018). Low-dose aspirin improved peripheral arterial stiffness and wave reflection but not endothelial function in firefighters. © The Author(s) 2015.

Acute effects of a wild green-oat (Avena sativa) extract on cognitive function in middle-aged adults: A double-blind, placebo-controlled, within-subjects trial.

PubMed

Kennedy, David O; Jackson, Philippa A; Forster, Joanne; Khan, Julie; Grothe, Torsten; Perrinjaquet-Moccetti, Tania; Haskell-Ramsay, Crystal F

2017-02-01

A wild green-oats extract (Neuravena ® ) containing a range of potentially bioactive components, including flavonoids and triterpene saponins, has previously been shown to enhance animal stress responses and memory, and improve cognitive performance in humans at a dose of 1600 mg. Methods This double-blind, placebo-controlled, counterbalanced cross-over study assessed the effects of single doses of the green-oat extract (GOE) across a broad range of cognitive domains in healthy adults aged 40-65 years who self-reported that they felt that their memory had declined with age. Participants attended on six occasions, receiving a single dose of either placebo, 800, or 1600 mg GOE on each occasion, with the counterbalanced order of treatments repeated twice for each participant. Cognitive function was assessed with a range of computerized tasks measuring attention, spatial/working/episodic memory, and executive function pre-dose and at 1, 2.5, 4, and 6 hours post-dose. Results The results showed that 800mg GOE increased the speed of performance across post-dose assessments on a global measure including data from all of the timed tasks. It also improved performance of a delayed word recall task in terms of errors and an executive function task (Peg and Ball) in terms of decreased thinking time and overall completion time. Working memory span (Corsi blocks) was also increased, but only on the second occasion that this dose was taken. Discussion These results confirm the acute cognitive effects of GOE seen in previous research, and suggest that the optimal dose lies at or below 800 mg.

SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function

PubMed Central

Price, Nathan L.; Gomes, Ana P.; Ling, Alvin J.Y.; Duarte, Filipe V.; Martin-Montalvo, Alejandro; North, Brian J.; Agarwal, Beamon; Ye, Lan; Ramadori, Giorgio; Teodoro, Joao S.; Hubbard, Basil P.; Varela, Ana T.; Davis, James G.; Varamini, Behzad; Hafner, Angela; Moaddel, Ruin; Rolo, Anabela P.; Coppari, Roberto; Palmeira, Carlos M.; de Cabo, Rafael; Baur, Joseph A.; Sinclair, David A.

2012-01-01

SUMMARY Resveratrol induces mitochondrial biogenesis and protects against metabolic decline but whether SIRT1 mediates these benefits is the subject of debate. To circumvent the developmental defects of germ-line SIRT1 knockouts, we have developed the first inducible system that permits whole-body deletion of SIRT1 in adult mice. Mice treated with a moderate dose of resveratrol showed increased mitochondrial biogenesis and function, AMPK activation and increased NAD+ levels in skeletal muscle, whereas SIRT1 knockouts displayed none of these benefits. A mouse overexpressing SIRT1 mimicked these effects. A high dose of resveratrol activated AMPK in a SIRT1-independent manner, demonstrating that resveratrol dosage is a critical factor. Importantly, at both doses of resveratrol no improvements in mitochondrial function were observed in animals lacking SIRT1. Together these data indicate that SIRT1 plays an essential role in the ability of moderate doses of resveratrol to stimulate AMPK and improve mitochondrial function both in vitro and in vivo. PMID:22560220

A phase I dose-finding study of silybin phosphatidylcholine (milk thistle) in patients with advanced hepatocellular carcinoma.

PubMed

Siegel, Abby B; Narayan, Rupa; Rodriguez, Rosa; Goyal, Abhishek; Jacobson, Judith S; Kelly, Kara; Ladas, Elena; Lunghofer, Paul J; Hansen, Ryan J; Gustafson, Daniel L; Flaig, Thomas W; Tsai, Wei Yann; Wu, David P H; Lee, Valerie; Greenlee, Heather

2014-01-01

To determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction. Patients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks. Three participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug. Short-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests.

Repeatability of dose painting by numbers treatment planning in prostate cancer radiotherapy based on multiparametric magnetic resonance imaging

NASA Astrophysics Data System (ADS)

van Schie, Marcel A.; Steenbergen, Peter; Viet Dinh, Cuong; Ghobadi, Ghazaleh; van Houdt, Petra J.; Pos, Floris J.; Heijmink, Stijn W. T. J. P.; van der Poel, Henk G.; Renisch, Steffen; Vik, Torbjørn; van der Heide, Uulke A.

2017-07-01

Dose painting by numbers (DPBN) refers to a voxel-wise prescription of radiation dose modelled from functional image characteristics, in contrast to dose painting by contours which requires delineations to define the target for dose escalation. The direct relation between functional imaging characteristics and DPBN implies that random variations in images may propagate into the dose distribution. The stability of MR-only prostate cancer treatment planning based on DPBN with respect to these variations is as yet unknown. We conducted a test-retest study to investigate the stability of DPBN for prostate cancer in a semi-automated MR-only treatment planning workflow. Twelve patients received a multiparametric MRI on two separate days prior to prostatectomy. The tumor probability (TP) within the prostate was derived from image features with a logistic regression model. Dose mapping functions were applied to acquire a DPBN prescription map that served to generate an intensity modulated radiation therapy (IMRT) treatment plan. Dose calculations were done on a pseudo-CT derived from the MRI. The TP and DPBN map and the IMRT dose distribution were compared between both MRI sessions, using the intraclass correlation coefficient (ICC) to quantify repeatability of the planning pipeline. The quality of each treatment plan was measured with a quality factor (QF). Median ICC values for the TP and DPBN map and the IMRT dose distribution were 0.82, 0.82 and 0.88, respectively, for linear dose mapping and 0.82, 0.84 and 0.94 for square root dose mapping. A median QF of 3.4% was found among all treatment plans. We demonstrated the stability of DPBN radiotherapy treatment planning in prostate cancer, with excellent overall repeatability and acceptable treatment plan quality. Using validated tumor probability modelling and simple dose mapping techniques it was shown that despite day-to-day variations in imaging data still consistent treatment plans were obtained.

A randomized dose-response trial of aerobic exercise and health-related quality of life in colon cancer survivors.

PubMed

Brown, Justin C; Damjanov, Nevena; Courneya, Kerry S; Troxel, Andrea B; Zemel, Babette S; Rickels, Michael R; Ky, Bonnie; Rhim, Andrew D; Rustgi, Anil K; Schmitz, Kathryn H

2018-04-01

To examine the dose-response effects of aerobic exercise on health-related quality of life (HRQoL) among colon cancer survivors. Thirty-nine stage I to III colon cancer survivors were randomized to 1 of 3 groups: usual-care control, 150 min·wk -1 of aerobic exercise (low-dose) and 300 min·wk -1 of aerobic exercise (high-dose) for 6 months. HRQoL outcomes included the Short Form (SF)-36 physical and mental component summary, Functional Assessment of Cancer Therapy-Colorectal, Pittsburgh Sleep Quality Index, Fear of Cancer Recurrence Inventory, Fatigue Symptom Inventory, and North Central Cancer Treatment Group bowel function questionnaire, assessed at baseline and post intervention. The primary hypothesis was that exercise would improve HRQoL outcomes in a dose-response fashion, such that high-dose aerobic exercise would yield the largest improvements in HRQoL outcomes. Over 6 months, the low-dose group completed 141 ± 10 min·wk -1 of aerobic exercise, and the high-dose group completed 247 ± 11 min·wk -1 of aerobic exercise. Over 6 months, exercise improved the physical component summary score of the SF-36 (P trend  = 0.002), the Functional Assessment of Cancer Therapy-Colorectal (P trend  = 0.025), the Pittsburgh Sleep Quality Index (P trend  = 0.049), and the Fatigue Symptom Inventory (P trend  = 0.045) in a dose-response fashion. Between-group standardized mean difference effects sizes for the above-described findings were small to moderate in magnitude (0.35-0.75). No dose-response effects were observed for the mental component summary score of the SF-36, the Fear of Cancer Recurrence Inventory, or bowel function. Higher doses of aerobic exercise, up to 300 min·wk -1 , improve multiple HRQoL outcomes among stage I to III colon cancer survivors. These findings provide evidence that aerobic exercise may provide multiple health benefits for colon cancer survivors. Copyright © 2018 John Wiley & Sons, Ltd.

SU-F-T-12: Monte Carlo Dosimetry of the 60Co Bebig High Dose Rate Source for Brachytherapy

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

Campos, L T; Almeida, C E V de

Purpose: The purpose of this work is to obtain the dosimetry parameters in accordance with the AAPM TG-43U1 formalism with Monte Carlo calculations regarding the BEBIG 60Co high-dose-rate brachytherapy. The geometric design and material details of the source was provided by the manufacturer and was used to define the Monte Carlo geometry. Methods: The dosimetry studies included the calculation of the air kerma strength Sk, collision kerma in water along the transverse axis with an unbounded phantom, dose rate constant and radial dose function. The Monte Carlo code system that was used was EGSnrc with a new cavity code, whichmore » is a part of EGS++ that allows calculating the radial dose function around the source. The XCOM photon cross-section library was used. Variance reduction techniques were used to speed up the calculation and to considerably reduce the computer time. To obtain the dose rate distributions of the source in an unbounded liquid water phantom, the source was immersed at the center of a cube phantom of 100 cm3. Results: The obtained dose rate constant for the BEBIG 60Co source was 1.108±0.001 cGyh-1U-1, which is consistent with the values in the literature. The radial dose functions were compared with the values of the consensus data set in the literature, and they are consistent with the published data for this energy range. Conclusion: The dose rate constant is consistent with the results of Granero et al. and Selvam and Bhola within 1%. Dose rate data are compared to GEANT4 and DORZnrc Monte Carlo code. However, the radial dose function is different by up to 10% for the points that are notably near the source on the transversal axis because of the high-energy photons from 60Co, which causes an electronic disequilibrium at the interface between the source capsule and the liquid water for distances up to 1 cm.« less

Assessment of hepatic function decline after stereotactic body radiation therapy for primary liver cancer.

PubMed

Toesca, Diego A S; Osmundson, Evan C; von Eyben, Rie; Shaffer, Jenny L; Koong, Albert C; Chang, Daniel T

This study aims to determine how the albumin-bilirubin (ALBI) score compares with the Child-Pugh (CP) score for assessing liver function following stereotactic body radiation therapy (SBRT). In total, 60 patients, 40 with hepatocellular carcinoma (HCC) and 20 with cholangiocarcinoma (CCA), were treated with SBRT. Liver function panels were obtained before and at 1, 3, 6, and 12 months after SBRT. Laboratory values were censored after locoregional recurrence, further liver-directed therapies, or liver transplant. A significant decline in hepatic function occurred after SBRT for HCC patients only (P = .001 by ALBI score; P < .0001 by CP score). By converting radiation doses to biologically equivalent doses by using a standard linear quadratic model using α/β of 10, the strongest dosimetric predictor of liver function decline for HCC was the volume of normal liver irradiated by a dose of 40 Gy when assessing liver function by the ALBI score (P = .07), and the volume of normal liver irradiated by a dose of 20 Gy by using the CP score (P= .0009). For CCA patients, the volume of normal liver irradiated by a dose of 40 Gy remained the strongest dosimetric predictor when using the ALBI score (P = .002), but no dosimetric predictor was significant using the CP score. Hepatic function decline correlated with worse overall survival for HCC (by ALBI, P = .0005; by CP, P < .0001) and for CCA (by ALBI, P = NS; by CP, P = .008). ALBI score was similarly able to predict hepatic function decline compared with CP score, and both systems correlated with survival. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Improved radial dose function estimation using current version MCNP Monte-Carlo simulation: Model 6711 and ISC3500 125I brachytherapy sources.

PubMed

Duggan, Dennis M

2004-12-01

Improved cross-sections in a new version of the Monte-Carlo N-particle (MCNP) code may eliminate discrepancies between radial dose functions (as defined by American Association of Physicists in Medicine Task Group 43) derived from Monte-Carlo simulations of low-energy photon-emitting brachytherapy sources and those from measurements on the same sources with thermoluminescent dosimeters. This is demonstrated for two 125I brachytherapy seed models, the Implant Sciences Model ISC3500 (I-Plant) and the Amersham Health Model 6711, by simulating their radial dose functions with two versions of MCNP, 4c2 and 5.

Dose-response relationships for environmentally mediated infectious disease transmission models

PubMed Central

Eisenberg, Joseph N. S.

2017-01-01

Environmentally mediated infectious disease transmission models provide a mechanistic approach to examining environmental interventions for outbreaks, such as water treatment or surface decontamination. The shift from the classical SIR framework to one incorporating the environment requires codifying the relationship between exposure to environmental pathogens and infection, i.e. the dose–response relationship. Much of the work characterizing the functional forms of dose–response relationships has used statistical fit to experimental data. However, there has been little research examining the consequences of the choice of functional form in the context of transmission dynamics. To this end, we identify four properties of dose–response functions that should be considered when selecting a functional form: low-dose linearity, scalability, concavity, and whether it is a single-hit model. We find that i) middle- and high-dose data do not constrain the low-dose response, and different dose–response forms that are equally plausible given the data can lead to significant differences in simulated outbreak dynamics; ii) the choice of how to aggregate continuous exposure into discrete doses can impact the modeled force of infection; iii) low-dose linear, concave functions allow the basic reproduction number to control global dynamics; and iv) identifiability analysis offers a way to manage multiple sources of uncertainty and leverage environmental monitoring to make inference about infectivity. By applying an environmentally mediated infectious disease model to the 1993 Milwaukee Cryptosporidium outbreak, we demonstrate that environmental monitoring allows for inference regarding the infectivity of the pathogen and thus improves our ability to identify outbreak characteristics such as pathogen strain. PMID:28388665

On the new metrics for IMRT QA verification.

PubMed

Garcia-Romero, Alejandro; Hernandez-Vitoria, Araceli; Millan-Cebrian, Esther; Alba-Escorihuela, Veronica; Serrano-Zabaleta, Sonia; Ortega-Pardina, Pablo

2016-11-01

The aim of this work is to search for new metrics that could give more reliable acceptance/rejection criteria on the IMRT verification process and to offer solutions to the discrepancies found among different conventional metrics. Therefore, besides conventional metrics, new ones are proposed and evaluated with new tools to find correlations among them. These new metrics are based on the processing of the dose-volume histogram information, evaluating the absorbed dose differences, the dose constraint fulfillment, or modified biomathematical treatment outcome models such as tumor control probability (TCP) and normal tissue complication probability (NTCP). An additional purpose is to establish whether the new metrics yield the same acceptance/rejection plan distribution as the conventional ones. Fifty eight treatment plans concerning several patient locations are analyzed. All of them were verified prior to the treatment, using conventional metrics, and retrospectively after the treatment with the new metrics. These new metrics include the definition of three continuous functions, based on dose-volume histograms resulting from measurements evaluated with a reconstructed dose system and also with a Monte Carlo redundant calculation. The 3D gamma function for every volume of interest is also calculated. The information is also processed to obtain ΔTCP or ΔNTCP for the considered volumes of interest. These biomathematical treatment outcome models have been modified to increase their sensitivity to dose changes. A robustness index from a radiobiological point of view is defined to classify plans in robustness against dose changes. Dose difference metrics can be condensed in a single parameter: the dose difference global function, with an optimal cutoff that can be determined from a receiver operating characteristics (ROC) analysis of the metric. It is not always possible to correlate differences in biomathematical treatment outcome models with dose difference metrics. This is due to the fact that the dose constraint is often far from the dose that has an actual impact on the radiobiological model, and therefore, biomathematical treatment outcome models are insensitive to big dose differences between the verification system and the treatment planning system. As an alternative, the use of modified radiobiological models which provides a better correlation is proposed. In any case, it is better to choose robust plans from a radiobiological point of view. The robustness index defined in this work is a good predictor of the plan rejection probability according to metrics derived from modified radiobiological models. The global 3D gamma-based metric calculated for each plan volume shows a good correlation with the dose difference metrics and presents a good performance in the acceptance/rejection process. Some discrepancies have been found in dose reconstruction depending on the algorithm employed. Significant and unavoidable discrepancies were found between the conventional metrics and the new ones. The dose difference global function and the 3D gamma for each plan volume are good classifiers regarding dose difference metrics. ROC analysis is useful to evaluate the predictive power of the new metrics. The correlation between biomathematical treatment outcome models and the dose difference-based metrics is enhanced by using modified TCP and NTCP functions that take into account the dose constraints for each plan. The robustness index is useful to evaluate if a plan is likely to be rejected. Conventional verification should be replaced by the new metrics, which are clinically more relevant.

The use of spatial dose gradients and probability density function to evaluate the effect of internal organ motion for prostate IMRT treatment planning

NASA Astrophysics Data System (ADS)

Jiang, Runqing; Barnett, Rob B.; Chow, James C. L.; Chen, Jeff Z. Y.

2007-03-01

The aim of this study is to investigate the effects of internal organ motion on IMRT treatment planning of prostate patients using a spatial dose gradient and probability density function. Spatial dose distributions were generated from a Pinnacle3 planning system using a co-planar, five-field intensity modulated radiation therapy (IMRT) technique. Five plans were created for each patient using equally spaced beams but shifting the angular displacement of the beam by 15° increments. Dose profiles taken through the isocentre in anterior-posterior (A-P), right-left (R-L) and superior-inferior (S-I) directions for IMRT plans were analysed by exporting RTOG file data from Pinnacle. The convolution of the 'static' dose distribution D0(x, y, z) and probability density function (PDF), denoted as P(x, y, z), was used to analyse the combined effect of repositioning error and internal organ motion. Organ motion leads to an enlarged beam penumbra. The amount of percentage mean dose deviation (PMDD) depends on the dose gradient and organ motion probability density function. Organ motion dose sensitivity was defined by the rate of change in PMDD with standard deviation of motion PDF and was found to increase with the maximum dose gradient in anterior, posterior, left and right directions. Due to common inferior and superior field borders of the field segments, the sharpest dose gradient will occur in the inferior or both superior and inferior penumbrae. Thus, prostate motion in the S-I direction produces the highest dose difference. The PMDD is within 2.5% when standard deviation is less than 5 mm, but the PMDD is over 2.5% in the inferior direction when standard deviation is higher than 5 mm in the inferior direction. Verification of prostate organ motion in the inferior directions is essential. The margin of the planning target volume (PTV) significantly impacts on the confidence of tumour control probability (TCP) and level of normal tissue complication probability (NTCP). Smaller margins help to reduce the dose to normal tissues, but may compromise the dose coverage of the PTV. Lower rectal NTCP can be achieved by either a smaller margin or a steeper dose gradient between PTV and rectum. With the same DVH control points, the rectum has lower complication in the seven-beam technique used in this study because of the steeper dose gradient between the target volume and rectum. The relationship between dose gradient and rectal complication can be used to evaluate IMRT treatment planning. The dose gradient analysis is a powerful tool to improve IMRT treatment plans and can be used for QA checking of treatment plans for prostate patients.

The use of spatial dose gradients and probability density function to evaluate the effect of internal organ motion for prostate IMRT treatment planning.

PubMed

Jiang, Runqing; Barnett, Rob B; Chow, James C L; Chen, Jeff Z Y

2007-03-07

The aim of this study is to investigate the effects of internal organ motion on IMRT treatment planning of prostate patients using a spatial dose gradient and probability density function. Spatial dose distributions were generated from a Pinnacle3 planning system using a co-planar, five-field intensity modulated radiation therapy (IMRT) technique. Five plans were created for each patient using equally spaced beams but shifting the angular displacement of the beam by 15 degree increments. Dose profiles taken through the isocentre in anterior-posterior (A-P), right-left (R-L) and superior-inferior (S-I) directions for IMRT plans were analysed by exporting RTOG file data from Pinnacle. The convolution of the 'static' dose distribution D0(x, y, z) and probability density function (PDF), denoted as P(x, y, z), was used to analyse the combined effect of repositioning error and internal organ motion. Organ motion leads to an enlarged beam penumbra. The amount of percentage mean dose deviation (PMDD) depends on the dose gradient and organ motion probability density function. Organ motion dose sensitivity was defined by the rate of change in PMDD with standard deviation of motion PDF and was found to increase with the maximum dose gradient in anterior, posterior, left and right directions. Due to common inferior and superior field borders of the field segments, the sharpest dose gradient will occur in the inferior or both superior and inferior penumbrae. Thus, prostate motion in the S-I direction produces the highest dose difference. The PMDD is within 2.5% when standard deviation is less than 5 mm, but the PMDD is over 2.5% in the inferior direction when standard deviation is higher than 5 mm in the inferior direction. Verification of prostate organ motion in the inferior directions is essential. The margin of the planning target volume (PTV) significantly impacts on the confidence of tumour control probability (TCP) and level of normal tissue complication probability (NTCP). Smaller margins help to reduce the dose to normal tissues, but may compromise the dose coverage of the PTV. Lower rectal NTCP can be achieved by either a smaller margin or a steeper dose gradient between PTV and rectum. With the same DVH control points, the rectum has lower complication in the seven-beam technique used in this study because of the steeper dose gradient between the target volume and rectum. The relationship between dose gradient and rectal complication can be used to evaluate IMRT treatment planning. The dose gradient analysis is a powerful tool to improve IMRT treatment plans and can be used for QA checking of treatment plans for prostate patients.

Polynomial expressions of electron depth dose as a function of energy in various materials: application to thermoluminescence (TL) dosimetry

NASA Astrophysics Data System (ADS)

Deogracias, E. C.; Wood, J. L.; Wagner, E. C.; Kearfott, K. J.

1999-02-01

The CEPXS/ONEDANT code package was used to produce a library of depth-dose profiles for monoenergetic electrons in various materials for energies ranging from 500 keV to 5 MeV in 10 keV increments. The various materials for which depth-dose functions were derived include: lithium fluoride (LiF), aluminum oxide (Al 2O 3), beryllium oxide (BeO), calcium sulfate (CaSO 4), calcium fluoride (CaF 2), lithium boron oxide (LiBO), soft tissue, lens of the eye, adiopose, muscle, skin, glass and water. All materials data sets were fit to five polynomials, each covering a different range of electron energies, using a least squares method. The resultant three dimensional, fifth-order polynomials give the dose as a function of depth and energy for the monoenergetic electrons in each material. The polynomials can be used to describe an energy spectrum by summing the doses at a given depth for each energy, weighted by the spectral intensity for that energy. An application of the polynomial is demonstrated by explaining the energy dependence of thermoluminescent detectors (TLDs) and illustrating the relationship between TLD signal and actual shallow dose due to beta particles.

TH-CD-202-08: Feasibility Study of Planning Phase Optimization Using Patient Geometry-Driven Information for Better Dose Sparing of Organ at Risks

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

Kang, S; Kim, D; Kim, T

2016-06-15

Purpose: To propose a simple and effective cost value function to search optimal planning phase (gating window) and demonstrated its feasibility for respiratory correlated radiation therapy. Methods: We acquired 4DCT of 10 phases for 10 lung patients who have tumor located near OARs such as esophagus, heart, and spinal cord (i.e., central lung cancer patients). A simplified mathematical optimization function was established by using overlap volume histogram (OVH) between the target and organ at risk (OAR) at each phase and the tolerance dose of selected OARs to achieve surrounding OARs dose-sparing. For all patients and all phases, delineation of themore » target volume and selected OARs (esophagus, heart, and spinal cord) was performed (by one observer to avoid inter-observer variation), then cost values were calculated for all phases. After the breathing phases were ranked according to cost value function, the relationship between score and dose distribution at highest and lowest cost value phases were evaluated by comparing the mean/max dose. Results: A simplified mathematical cost value function showed noticeable difference from phase to phase, implying it is possible to find optimal phases for gating window. The lowest cost value which may result in lower mean/max dose to OARs was distributed at various phases for all patients. The mean doses of the OARs significantly decreased about 10% with statistical significance for all 3 OARs at the phase with the lowest cost value. Also, the max doses of the OARs were decreased about 2∼5% at the phase with the lowest cost value compared to the phase with the highest cost value. Conclusion: It is demonstrated that optimal phases (in dose distribution perspective) for gating window could exist differently through each patient and the proposed cost value function can be a useful tool for determining such phases without performing dose optimization calculations. This research was supported by the Mid-career Researcher Program through NRF funded by the Ministry of Science, ICT & Future Planning of Korea (NRF-2014R1A2A1A10050270) and by the Radiation Technology R&D program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (No. 2013M2A2A7038291)« less

Testing the dose-response specification in epidemiology: public health and policy consequences for lead.

PubMed

Rothenberg, Stephen J; Rothenberg, Jesse C

2005-09-01

Statistical evaluation of the dose-response function in lead epidemiology is rarely attempted. Economic evaluation of health benefits of lead reduction usually assumes a linear dose-response function, regardless of the outcome measure used. We reanalyzed a previously published study, an international pooled data set combining data from seven prospective lead studies examining contemporaneous blood lead effect on IQ (intelligence quotient) of 7-year-old children (n = 1,333). We constructed alternative linear multiple regression models with linear blood lead terms (linear-linear dose response) and natural-log-transformed blood lead terms (log-linear dose response). We tested the two lead specifications for nonlinearity in the models, compared the two lead specifications for significantly better fit to the data, and examined the effects of possible residual confounding on the functional form of the dose-response relationship. We found that a log-linear lead-IQ relationship was a significantly better fit than was a linear-linear relationship for IQ (p = 0.009), with little evidence of residual confounding of included model variables. We substituted the log-linear lead-IQ effect in a previously published health benefits model and found that the economic savings due to U.S. population lead decrease between 1976 and 1999 (from 17.1 microg/dL to 2.0 microg/dL) was 2.2 times (319 billion dollars) that calculated using a linear-linear dose-response function (149 billion dollars). The Centers for Disease Control and Prevention action limit of 10 microg/dL for children fails to protect against most damage and economic cost attributable to lead exposure.

Frequency of Acute Kidney Injury Caused by Tazobactam/Piperacillin in Patients with Pneumonia and Chronic Kidney Disease: A Retrospective Observational Study.

PubMed

Morimoto, Takeyori; Nagashima, Hiroki; Morimoto, Yasuko; Tokuyama, Shogo

2017-01-01

 Tazobactam/piperacillin (TAZ/PIPC) is a combination antibiotic frequently used to treat pneumonia. It has recently been reported that TAZ/PIPC worsens renal function in patients with existing renal impairment. Creatinine clearance is generally between 10 and 40 mL/min in Japanese patients, so TAZ/PIPC is given at a dose of 2.25 g three times daily or 4.5 g twice daily. If pneumonia is severe or intractable, the dose frequency may be increased to 2.25 g four times daily and 4.5 g three times daily. We examined the effect of these different dosing regimens on renal function. We studied a cohort of 57 patients with impaired renal function hospitalized with pneumonia and treated with TAZ/PIPC between January 2015 and November 2016. Patients were classified into four groups according to TAZ/PIPC dose: 2.25 g three times daily (Group A); 2.25 g four times daily (B); 4.5 g twice daily (C) and 4.5 g three times daily (D). We examined the frequency of acute kidney injury (AKI) and treatment effectiveness. In Groups A, B, C and D, AKI occurred in 5.6%, 0.0%, 25.0% and 38.5% of patient. In groups C and D, hydration and dose reduction were required to address early signs of impending AKI. Our findings suggest that the higher TAZ/PIPC dose of 4.5 g was responsible for the decline in renal function, even if the dose frequency was reduced.

Time- and dose-dependent effects of total-body ionizing radiation on muscle stem cells

PubMed Central

Masuda, Shinya; Hisamatsu, Tsubasa; Seko, Daiki; Urata, Yoshishige; Goto, Shinji; Li, Tao-Sheng; Ono, Yusuke

2015-01-01

Exposure to high levels of genotoxic stress, such as high-dose ionizing radiation, increases both cancer and noncancer risks. However, it remains debatable whether low-dose ionizing radiation reduces cellular function, or rather induces hormetic health benefits. Here, we investigated the effects of total-body γ-ray radiation on muscle stem cells, called satellite cells. Adult C57BL/6 mice were exposed to γ-radiation at low- to high-dose rates (low, 2 or 10 mGy/day; moderate, 50 mGy/day; high, 250 mGy/day) for 30 days. No hormetic responses in proliferation, differentiation, or self-renewal of satellite cells were observed in low-dose radiation-exposed mice at the acute phase. However, at the chronic phase, population expansion of satellite cell-derived progeny was slightly decreased in mice exposed to low-dose radiation. Taken together, low-dose ionizing irradiation may suppress satellite cell function, rather than induce hormetic health benefits, in skeletal muscle in adult mice. PMID:25869487

Dosimetric feasibility of 4DCT-ventilation imaging guided proton therapy for locally advanced non-small-cell lung cancer.

PubMed

Huang, Qijie; Jabbour, Salma K; Xiao, Zhiyan; Yue, Ning; Wang, Xiao; Cao, Hongbin; Kuang, Yu; Zhang, Yin; Nie, Ke

2018-04-25

The principle aim of this study is to incorporate 4DCT ventilation imaging into functional treatment planning that preserves high-functioning lung with both double scattering and scanning beam techniques in proton therapy. Eight patients with locally advanced non-small-cell lung cancer were included in this study. Deformable image registration was performed for each patient on their planning 4DCTs and the resultant displacement vector field with Jacobian analysis was used to identify the high-, medium- and low-functional lung regions. Five plans were designed for each patient: a regular photon IMRT vs. anatomic proton plans without consideration of functional ventilation information using double scattering proton therapy (DSPT) and intensity modulated proton therapy (IMPT) vs. functional proton plans with avoidance of high-functional lung using both DSPT and IMPT. Dosimetric parameters were compared in terms of tumor coverage, plan heterogeneity, and avoidance of normal tissues. Our results showed that both DSPT and IMPT plans gave superior dose advantage to photon IMRTs in sparing low dose regions of the total lung in terms of V5 (volume receiving 5Gy). The functional DSPT only showed marginal benefit in sparing high-functioning lung in terms of V5 or V20 (volume receiving 20Gy) compared to anatomical plans. Yet, the functional planning in IMPT delivery, can further reduce the low dose in high-functioning lung without degrading the PTV dosimetric coverages, compared to anatomical proton planning. Although the doses to some critical organs might increase during functional planning, the necessary constraints were all met. Incorporating 4DCT ventilation imaging into functional proton therapy is feasible. The functional proton plans, in intensity modulated proton delivery, are effective to further preserve high-functioning lung regions without degrading the PTV coverage.

A new treatment planning formalism for catheter-based beta sources used in intravascular brachytherapy.

PubMed

Patel, N S; Chiu-Tsao, S T; Tsao, H S; Harrison, L B

2001-01-01

Intravascular brachytherapy (IVBT) is an emerging modality for the treatment of atherosclerotic lesions in the artery. As part of the refinement in this rapidly evolving modality of treatment, the current simplistic dosimetry approach based on a fixed-point prescription must be challenged by future rigorous dosimetry method employing image-based three-dimensional (3D) treatment planning. The goals of 3D IVBT treatment planning calculations include (1) achieving high accuracy in a slim cylindrical region of interest, (2) accounting for the edge effect around the source ends, and (3) supporting multiple dwell positions. The formalism recommended by Task Group 60 (TG-60) of the American Association of Physicists in Medicine (AAPM) is applicable for gamma sources, as well as short beta sources with lengths less than twice the beta particle range. However, for the elongated beta sources and/or seed trains with lengths greater than twice the beta range, a new formalism is required to handle their distinctly different dose characteristics. Specifically, these characteristics consist of (a) flat isodose curves in the central region, (b) steep dose gradient at the source ends, and (c) exponential dose fall-off in the radial direction. In this paper, we present a novel formalism that evolved from TG-60 in maintaining the dose rate as a product of four key quantities. We propose to employ cylindrical coordinates (R, Z, phi), which are more natural and suitable to the slim cylindrical shape of the volume of interest, as opposed to the spherical coordinate system (r, theta, phi) used in the TG-60 formalism. The four quantities used in this formalism include (1) the distribution factor, H(R, Z), (2) the modulation function, M(R, Z), (3) the transverse dose function, h(R), and (4) the reference dose rate at 2 mm along the perpendicular bisector, D(R0=2 mm, Z0=0). The first three are counterparts of the geometry factor, the anisotropy function and the radial dose function in the TG-60 formalism, respectively. The reference dose rate is identical to that recommended by TG-60. The distribution factor is intended to resemble the dose profile due to the spatial distribution of activity in the elongated beta source, and it is a modified Fermi-Dirac function in mathematical form. The utility of this formalism also includes the slow-varying nature of the modulation function, allowing for more accurate treatment planning calculations based on interpolation. The transverse dose function describes the exponential fall-off of the dose in the radial direction, and an exponential or a polynomial can fit it. Simultaneously, the decoupling nature of these dose-related quantities facilitates image-based 3D treatment planning calculations for long beta sources used in IVBT. The new formalism also supports the dosimetry involving multiple dwell positions required for lesions longer than the source length. An example of the utilization of this formalism is illustrated for a 90Y coil source in a carbon dioxide-filled balloon. The pertinent dosimetric parameters were generated and tabulated for future use.

Dose Estimating Application Software Modification: Additional Function of a Size-Specific Effective Dose Calculator and Auto Exposure Control.

PubMed

Kobayashi, Masanao; Asada, Yasuki; Matsubara, Kosuke; Suzuki, Shouichi; Matsunaga, Yuta; Haba, Tomonobu; Kawaguchi, Ai; Daioku, Tomihiko; Toyama, Hiroshi; Kato, Ryoichi

2017-05-01

Adequate dose management during computed tomography is important. In the present study, the dosimetric application software ImPACT was added to a functional calculator of the size-specific dose estimate and was part of the scan settings for the auto exposure control (AEC) technique. This study aimed to assess the practicality and accuracy of the modified ImPACT software for dose estimation. We compared the conversion factors identified by the software with the values reported by the American Association of Physicists in Medicine Task Group 204, and we noted similar results. Moreover, doses were calculated with the AEC technique and a fixed-tube current of 200 mA for the chest-pelvis region. The modified ImPACT software could estimate each organ dose, which was based on the modulated tube current. The ability to perform beneficial modifications indicates the flexibility of the ImPACT software. The ImPACT software can be further modified for estimation of other doses. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Functional image-guided stereotactic body radiation therapy planning for patients with hepatocellular carcinoma

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

Tsegmed, Uranchimeg; Kimura, Tomoki, E-mail: tkkimura@hiroshima-u.ac.jp; Nakashima, Takeo

The aim of the current planning study is to evaluate the ability of gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI)–guided stereotactic body radiation therapy (SBRT) planning by using intensity-modulated radiation therapy (IMRT) techniques in sparing the functional liver tissues during SBRT for hepatocellular carcinoma. In this study, 20 patients with hepatocellular carcinoma were enrolled. Functional liver tissues were defined according to quantitative liver-spleen contrast ratios ≥ 1.5 on a hepatobiliary phase scan. Functional images were fused with the planning computed tomography (CT) images; the following 2 SBRT plans were designed using a “step-and-shoot” static IMRT technique for each patient: (1) an anatomicalmore » SBRT plan optimization based on the total liver; and (2) a functional SBRT plan based on the functional liver. The total prescribed dose was 48 gray (Gy) in 4 fractions. Dosimetric parameters, including dose to 95% of the planning target volume (PTV D{sub 95%}), percentages of total and functional liver volumes, which received doses from 5 to 30 Gy (V5 to V30 and fV5 to fV30), and mean doses to total and functional liver (MLD and fMLD, respectively) of the 2 plans were compared. Compared with anatomical plans, functional image-guided SBRT plans reduced MLD (mean: plan A, 5.5 Gy; and plan F, 5.1 Gy; p < 0.0001) and fMLD (mean: plan A, 5.4 Gy; and plan F, 4.9 Gy; p < 0.0001), as well as V5 to V30 and fV5 to fV30. No differences were noted in PTV coverage and nonhepatic organs at risk (OARs) doses. In conclusion, EOB-MRI–guided SBRT planning using the IMRT technique may preserve functional liver tissues in patients with hepatocellular carcinoma (HCC).« less

Effects of Phonation Time and Magnitude Dose on Vocal Fold Epithelial Genes, Barrier Integrity, and Function

PubMed Central

Kojima, Tsuyoshi; Valenzuela, Carla V.; Novaleski, Carolyn K.; Van Deusen, Mark; Mitchell, Joshua R.; Garrett, C. Gaelyn; Sivasankar, M. Preeti; Rousseau, Bernard

2014-01-01

Objective To investigate the effects of increasing time and magnitude doses of vibration exposure on transcription of the vocal fold's junctional proteins, structural alterations, and functional tissue outcomes. Study Design Animal study. Methods 100 New Zealand White breeder rabbits were studied. Dependent variables were measured in response to increasing time doses (30, 60, or 120 minutes) and magnitude doses (control, modal intensity, and raised intensity) of vibration exposure. Messenger RNA expression of occludin, zonula occluden-1 (ZO-1), E-cadherin, β-catenin, interleukin 1β (IL-1β), cyclooxygenase-2 (COX-2), transforming growth factor β-1 (TGFβ1), and fibronectin were measured. Tissue structural alterations were assessed using transmission electron microscopy (TEM). Transepithelial resistance was used to measure functional tissue outcomes. Results Occludin gene expression was downregulated in vocal folds exposed to 120 minute time doses of raised intensity phonation, relative to control, and modal intensity phonation. ZO-1 gene expression was upregulated following a 120 minute time dose of modal intensity phonation, compared to control, and downregulated after a 120 minute time dose of raised intensity phonation, compared to modal intensity phonation. E-cadherin gene expression was downregulated after a120 minute time dose of raised intensity phonation, compared to control and modal intensity phonation. TEM revealed extensive desquamation of the stratified squamous epithelial cells with increasing time and magnitude doses of vibration exposure. A general observation of lower transepithelial resistance measures was made in tissues exposed to raised intensity phonation, compared to all other groups. Conclusions This study provides evidence of vocal fold tissue responses to varying time and magnitude doses of vibration exposure. Level of Evidence N/A PMID:25073715

Concept of proton radiography using energy resolved dose measurement.

PubMed

Bentefour, El H; Schnuerer, Roland; Lu, Hsiao-Ming

2016-08-21

Energy resolved dosimetry offers a potential path to single detector based proton imaging using scanned proton beams. This is because energy resolved dose functions encrypt the radiological depth at which the measurements are made. When a set of predetermined proton beams 'proton imaging field' are used to deliver a well determined dose distribution in a specific volume, then, at any given depth x of this volume, the behavior of the dose against the energies of the proton imaging field is unique and characterizes the depth x. This concept applies directly to proton therapy scanning delivery methods (pencil beam scanning and uniform scanning) and it can be extended to the proton therapy passive delivery methods (single and double scattering) if the delivery of the irradiation is time-controlled with a known time-energy relationship. To derive the water equivalent path length (WEPL) from the energy resolved dose measurement, one may proceed in two different ways. A first method is by matching the measured energy resolved dose function to a pre-established calibration database of the behavior of the energy resolved dose in water, measured over the entire range of radiological depths with at least 1 mm spatial resolution. This calibration database can also be made specific to the patient if computed using the patient x-CT data. A second method to determine the WEPL is by using the empirical relationships between the WEPL and the integral dose or the depth at 80% of the proximal fall off of the energy resolved dose functions in water. In this note, we establish the evidence of the fundamental relationship between the energy resolved dose and the WEPL at the depth of the measurement. Then, we illustrate this relationship with experimental data and discuss its imaging dynamic range for 230 MeV protons.

A Proposed In Vitro Method to Assess Effects of Inhaled Particles on Lung Surfactant Function.

PubMed

Sørli, Jorid B; Da Silva, Emilie; Bäckman, Per; Levin, Marcus; Thomsen, Birthe L; Koponen, Ismo K; Larsen, Søren T

2016-03-01

The lung surfactant (LS) lining is a thin liquid film covering the air-liquid interface of the respiratory tract. LS reduces surface tension, enabling lung surface expansion and contraction with minimal work during respiration. Disruption of surface tension is believed to play a key role in severe lung conditions. Inhalation of aerosols that interfere with the LS may induce a toxic response and, as a part of the safety assessment of chemicals and inhaled medicines, it may be relevant to study their impact on LS function. Here, we present a novel in vitro method, based on the constrained drop surfactometer, to study LS functionality after aerosol exposure. The applicability of the method was investigated using three inhaled asthma medicines, micronized lactose, a pharmaceutical excipient used in inhaled medication, and micronized albumin, a known inhibitor of surfactant function. The surfactometer was modified to allow particles mixed in air to flow through the chamber holding the surfactant drop. The deposited dose was measured with a custom-built quartz crystal microbalance. The alterations allowed the study of continuously increasing quantified doses of particles, allowing determination of the dose of particles that affects the LS function. The tested pharmaceuticals did not inhibit the function of a model LS even at extreme doses--neither did lactose. Micronized albumin, however, impaired surfactant function. The method can discriminate between safe inhaled aerosols--as exemplified by the approved inhaled medicines and the pharmaceutical excipient lactose--and albumin known to impair lung functionality by inhibiting LS function.

Monthly high dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial

USDA-ARS?s Scientific Manuscript database

Importance: Vitamin D deficiency has been associated with poor physical performance. Objective: To determine the effectiveness of high dose vitamin D in lowering the risk of functional decline. Design, Setting, and Participants: One-year double-blind, randomized clinical trial conducted in Zurich,...

Optimization of equivalent uniform dose using the L-curve criterion.

PubMed

Chvetsov, Alexei V; Dempsey, James F; Palta, Jatinder R

2007-10-07

Optimization of equivalent uniform dose (EUD) in inverse planning for intensity-modulated radiation therapy (IMRT) prevents variation in radiobiological effect between different radiotherapy treatment plans, which is due to variation in the pattern of dose nonuniformity. For instance, the survival fraction of clonogens would be consistent with the prescription when the optimized EUD is equal to the prescribed EUD. One of the problems in the practical implementation of this approach is that the spatial dose distribution in EUD-based inverse planning would be underdetermined because an unlimited number of nonuniform dose distributions can be computed for a prescribed value of EUD. Together with ill-posedness of the underlying integral equation, this may significantly increase the dose nonuniformity. To optimize EUD and keep dose nonuniformity within reasonable limits, we implemented into an EUD-based objective function an additional criterion which ensures the smoothness of beam intensity functions. This approach is similar to the variational regularization technique which was previously studied for the dose-based least-squares optimization. We show that the variational regularization together with the L-curve criterion for the regularization parameter can significantly reduce dose nonuniformity in EUD-based inverse planning.

Physics must join with biology in better assessing risk from low-dose irradiation.

PubMed

Feinendegen, L E; Neumann, R D

2005-01-01

This review summarises the complex response of mammalian cells and tissues to low doses of ionising radiation. This thesis encompasses induction of DNA damage, and adaptive protection against both renewed damage and against propagation of damage from the basic level of biological organisation to the clinical expression of detriment. The induction of DNA damage at low radiation doses apparently is proportional to absorbed dose at the physical/chemical level. However, any propagation of such damage to higher levels of biological organisation inherently follows a sigmoid function. Moreover, low-dose-induced inhibition of damage propagation is not linear, but instead follows a dose-effect function typical for adaptive protection, after an initial rapid rise it disappears at doses higher than approximately 0.1-0.2 Gy to cells. The particular biological response duality at low radiation doses precludes the validity of the linear-no-threshold hypothesis in the attempt to relate absorbed dose to cancer. In fact, theory and observation support not only a lower cancer incidence than expected from the linear-no-threshold hypothesis, but also a reduction of spontaneously occurring cancer, a hormetic response, in the healthy individual.

A mathematical deconvolution formulation for superficial dose distribution measurement by Cerenkov light dosimetry.

PubMed

Brost, Eric Edward; Watanabe, Yoichi

2018-06-01

Cerenkov photons are created by high-energy radiation beams used for radiation therapy. In this study, we developed a Cerenkov light dosimetry technique to obtain a two-dimensional dose distribution in a superficial region of medium from the images of Cerenkov photons by using a deconvolution method. An integral equation was derived to represent the Cerenkov photon image acquired by a camera for a given incident high-energy photon beam by using convolution kernels. Subsequently, an equation relating the planar dose at a depth to a Cerenkov photon image using the well-known relationship between the incident beam fluence and the dose distribution in a medium was obtained. The final equation contained a convolution kernel called the Cerenkov dose scatter function (CDSF). The CDSF function was obtained by deconvolving the Cerenkov scatter function (CSF) with the dose scatter function (DSF). The GAMOS (Geant4-based Architecture for Medicine-Oriented Simulations) Monte Carlo particle simulation software was used to obtain the CSF and DSF. The dose distribution was calculated from the Cerenkov photon intensity data using an iterative deconvolution method with the CDSF. The theoretical formulation was experimentally evaluated by using an optical phantom irradiated by high-energy photon beams. The intensity of the deconvolved Cerenkov photon image showed linear dependence on the dose rate and the photon beam energy. The relative intensity showed a field size dependence similar to the beam output factor. Deconvolved Cerenkov images showed improvement in dose profiles compared with the raw image data. In particular, the deconvolution significantly improved the agreement in the high dose gradient region, such as in the penumbra. Deconvolution with a single iteration was found to provide the most accurate solution of the dose. Two-dimensional dose distributions of the deconvolved Cerenkov images agreed well with the reference distributions for both square fields and a multileaf collimator (MLC) defined, irregularly shaped field. The proposed technique improved the accuracy of the Cerenkov photon dosimetry in the penumbra region. The results of this study showed initial validation of the deconvolution method for beam profile measurements in a homogeneous media. The new formulation accounted for the physical processes of Cerenkov photon transport in the medium more accurately than previously published methods. © 2018 American Association of Physicists in Medicine.

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

Gagne, Nolan L.; Leonard, Kara L.; Rivard, Mark J.

Purpose: Clinical optimization of Collaborative Ocular Melanoma Study (COMS) eye plaque brachytherapy is currently limited to tumor coverage, consensus prescription dosage, and dose calculations to ocular structures. The biologically effective dose (BED) of temporary brachytherapy treatments is a function of both chosen radionuclide R and implant duration T. This study endeavored to evaluate BED delivered to the tumor volume and surrounding ocular structures as a function of plaque position P, prescription dose, R, and T. Methods: Plaque-heterogeneity-corrected dose distributions were generated with MCNP5 for the range of currently available COMS plaques loaded with sources using three available low-energy radionuclides. Thesemore » physical dose distributions were imported into the PINNACLE{sup 3} treatment planning system using the TG-43 hybrid technique and used to generate dose volume histograms for a T = 7 day implant within a reference eye geometry including the ciliary body, cornea, eyelid, foveola, lacrimal gland, lens, optic disc, optic nerve, retina, and tumor at eight standard treatment positions. The equation of Dale and Jones was employed to create biologically effective dose volume histograms (BEDVHs), allowing for BED volumetric analysis of all ROIs. Isobiologically effective prescription doses were calculated for T = 5 days down to 0.01 days, with BEDVHs subsequently generated for all ROIs using correspondingly reduced prescription doses. Objective functions were created to evaluate the BEDVHs as a function of R and T. These objective functions are mathematically accessible and sufficiently general to be applied to temporary or permanent brachytherapy implants for a variety of disease sites. Results: Reducing T from 7 to 0.01 days for a 10 mm plaque produced an average BED benefit of 26%, 20%, and 17% for {sup 103}Pd, {sup 125}I, and {sup 131}Cs, respectively, for all P; 16 and 22 mm plaque results were more position-dependent. {sup 103}Pd produced a 16%-35% BED benefit over {sup 125}I, whereas {sup 131}Cs produced a 3%-7% BED detriment, independent of P, T, and plaque size. Additionally, corresponding organ at risk physical doses were lowest using {sup 103}Pd in all circumstances. Conclusions: The results suggest that shorter implant durations may correlate with more favorable outcomes compared to 7 day implants when treating small or medium intraocular lesions. The data also indicate that implant duration may be safely reduced if the prescription physical dose is likewise diminished and that {sup 103}Pd offers a substantial radiobiological benefit over {sup 125}I and {sup 131}Cs irrespective of plaque position, implant duration, and tumor size.« less

Theoretical study of the influence of a heterogeneous activity distribution on intratumoral absorbed dose distribution.

PubMed

Bao, Ande; Zhao, Xia; Phillips, William T; Woolley, F Ross; Otto, Randal A; Goins, Beth; Hevezi, James M

2005-01-01

Radioimmunotherapy of hematopoeitic cancers and micrometastases has been shown to have significant therapeutic benefit. The treatment of solid tumors with radionuclide therapy has been less successful. Previous investigations of intratumoral activity distribution and studies on intratumoral drug delivery suggest that a probable reason for the disappointing results in solid tumor treatment is nonuniform intratumoral distribution coupled with restricted intratumoral drug penetrance, thus inhibiting antineoplastic agents from reaching the tumor's center. This paper describes a nonuniform intratumoral activity distribution identified by limited radiolabeled tracer diffusion from tumor surface to tumor center. This activity was simulated using techniques that allowed the absorbed dose distributions to be estimated using different intratumoral diffusion capabilities and calculated for tumors of varying diameters. The influences of these absorbed dose distributions on solid tumor radionuclide therapy are also discussed. The absorbed dose distribution was calculated using the dose point kernel method that provided for the application of a three-dimensional (3D) convolution between a dose rate kernel function and an activity distribution function. These functions were incorporated into 3D matrices with voxels measuring 0.10 x 0.10 x 0.10 mm3. At this point fast Fourier transform (FFT) and multiplication in frequency domain followed by inverse FFT (iFFT) were used to effect this phase of the dose calculation process. The absorbed dose distribution for tumors of 1, 3, 5, 10, and 15 mm in diameter were studied. Using the therapeutic radionuclides of 131I, 186Re, 188Re, and 90Y, the total average dose, center dose, and surface dose for each of the different tumor diameters were reported. The absorbed dose in the nearby normal tissue was also evaluated. When the tumor diameters exceed 15 mm, a much lower tumor center dose is delivered compared with tumors between 3 and 5 mm in diameter. Based on these findings, the use of higher beta-energy radionuclides, such as 188Re and 90Y is more effective in delivering a higher absorbed dose to the tumor center at tumor diameters around 10 mm.

Use of PET and Other Functional Imaging to Guide Target Delineation in Radiation Oncology.

PubMed

Verma, Vivek; Choi, J Isabelle; Sawant, Amit; Gullapalli, Rao P; Chen, Wengen; Alavi, Abass; Simone, Charles B

2018-06-01

Molecular and functional imaging is increasingly being used to guide radiotherapy (RT) management and target delineation. This review summarizes existing data in several disease sites of various functional imaging modalities, chiefly positron emission tomography/computed tomography (PET/CT), with respect to RT target definition and management. For gliomas, differentiation between postoperative changes and viable tumor is discussed, as well as focal dose escalation and reirradiation. Head and neck neoplasms may also benefit from precise PET/CT-based target delineation, especially for cancers of unknown primary; focal dose escalation is also described. In lung cancer, PET/CT can influence coverage of tumor volumes, dose escalation, and adaptive management. For cervical cancer, PET/CT as an adjunct to magnetic resonance imaging planning is discussed, as are dose escalation and delineation of avoidance targets such as the bone marrow. The emerging role of choline-based PET for prostate cancer and its impact on dose escalation is also described. Lastly, given the essential role of PET/CT for target definition in lymphoma, phase III trials of PET-directed management are reviewed, along with novel imaging modalities. Taken together, molecular and functional imaging approaches offer a major step to individualize radiotherapeutic care going forward. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of Admission Oral Diuretic Dose on Response to Continuous versus Bolus Intravenous Diuretics in Acute Heart Failure: An Analysis from DOSE-AHF

PubMed Central

Shah, Ravi V.; McNulty, Steven; O'Connor, Christopher M.; Felker, G. Michael; Braunwald, Eugene; Givertz, Michael M.

2014-01-01

Background Results from the Diuretic Optimization Strategies in Acute Heart Failure (DOSE-AHF) study suggest that an initial continuous infusion of loop diuretics is not superior to bolus dosing with regard to clinical endpoints in AHF. We hypothesized that outpatient furosemide dose was associated with congestion and poorer renal function, and explored the hypothesis that a continuous infusion may be more effective in patients on higher outpatient diuretic doses. Methods DOSE-AHF randomized 308 patients within 24 hours of admission to high vs. low initial intravenous diuretic dose given as either a continuous infusion or bolus. We compared baseline characteristics and assessed associations between mode of administration (bolus vs. continuous) and outcomes in patients receiving high-dose (≥120 mg furosemide equivalent, n=177) versus low-dose (<120 mg furosemide equivalent, n=131) outpatient diuretics. Results Patients on higher doses of furosemide were less frequently on renin-angiotensin system inhibitors (P=.01), and had worse renal function and more advanced symptoms. There was a significant interaction between outpatient dose and mode of therapy (P=0.01) with respect to net fluid loss at 72 hours after adjusting for creatinine and intensification strategy. Admission diuretic dose was associated with an increased risk of death or rehospitalization at 60 days (adjusted HR=1.08 per 20-mg increment in dose, 95% CI 1.01–1.16, P=.03). Conclusions In acute HF, patients on higher diuretic doses have greater disease severity, and may benefit from an initial bolus strategy. PMID:23194486

Predictive Models for Regional Hepatic Function Based on 99mTc-IDA SPECT and Local Radiation Dose for Physiologic Adaptive Radiation Therapy

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

Wang, Hesheng, E-mail: hesheng@umich.edu; Feng, Mary; Frey, Kirk A.

2013-08-01

Purpose: High-dose radiation therapy (RT) for intrahepatic cancer is limited by the development of liver injury. This study investigated whether regional hepatic function assessed before and during the course of RT using 99mTc-labeled iminodiacetic acid (IDA) single photon emission computed tomography (SPECT) could predict regional liver function reserve after RT. Methods and Materials: Fourteen patients treated with RT for intrahepatic cancers underwent dynamic 99mTc-IDA SPECT scans before RT, during, and 1 month after completion of RT. Indocyanine green (ICG) tests, a measure of overall liver function, were performed within 1 day of each scan. Three-dimensional volumetric hepatic extraction fraction (HEF)more » images of the liver were estimated by deconvolution analysis. After coregistration of the CT/SPECT and the treatment planning CT, HEF dose–response functions during and after RT were generated. The volumetric mean of the HEFs in the whole liver was correlated with ICG clearance time. Three models, dose, priori, and adaptive models, were developed using multivariate linear regression to assess whether the regional HEFs measured before and during RT helped predict regional hepatic function after RT. Results: The mean of the volumetric liver HEFs was significantly correlated with ICG clearance half-life time (r=−0.80, P<.0001), for all time points. Linear correlations between local doses and regional HEFs 1 month after RT were significant in 12 patients. In the priori model, regional HEF after RT was predicted by the planned dose and regional HEF assessed before RT (R=0.71, P<.0001). In the adaptive model, regional HEF after RT was predicted by regional HEF reassessed during RT and the remaining planned local dose (R=0.83, P<.0001). Conclusions: 99mTc-IDA SPECT obtained during RT could be used to assess regional hepatic function and helped predict post-RT regional liver function reserve. This could support individualized adaptive radiation treatment strategies to maximize tumor control and minimize the risk of liver damage.« less

A Phase I Dose-Finding Study of Silybin Phosphatidylcholine (Milk Thistle) in Patients With Advanced Hepatocellular Carcinoma

PubMed Central

Siegel, Abby B.; Narayan, Rupa; Rodriguez, Rosa; Goyal, Abhishek; Jacobson, Judith S.; Kelly, Kara; Ladas, Elena; Lunghofer, Paul J.; Hansen, Ryan J.; Gustafson, Daniel L.; Flaig, Thomas W.; Tsai, Wei Yann; Wu, David P. H.; Lee, Valerie; Greenlee, Heather

2013-01-01

Purpose To determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction. Experimental Design Patients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks. Results Three participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug. Conclusion Short-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests. PMID:23757319

Succinic acid production from glycerol by Actinobacillus succinogenes using dimethylsulfoxide as electron acceptor.

PubMed

Carvalho, Margarida; Matos, Mariana; Roca, Christophe; Reis, Maria A M

2014-01-25

Glycerol, a highly abundant byproduct of the biodiesel industry, constitutes today a cheap feedstock for biobased succinic acid (SA) production. Actinobacillus succinogenes is one of the best SA producers. However, glycerol consumption by this biocatalyst is limited because of a redox imbalance during cell growth. The use of an external electron acceptor may improve the metabolism of SA synthesis by A. succinogenes in glycerol. In this study, the effect of dimethylsulfoxide (DMSO), an electron acceptor, on glycerol consumption and SA production by A. succinogenes under controlled fermentation conditions was investigated. Concentrations of DMSO between 1 and 4% (v/v) greatly promoted glycerol consumption and SA production by A. succinogenes. During fed-batch cultivation, SA concentration reached 49.62 g/L, with a product yield of 0.87 gSA/gGLR and a maximum production rate of 2.31 gSA/Lh, the highest values so far reported in the literature for A. succinogenes using glycerol as carbon source. These results show that using DMSO as external electron acceptor significantly promotes glycerol consumption and succinic acid production by A. succinogenes and may be used as a co-substrate, opening new perspectives for the use of glycerol by this biocatalyst. Copyright © 2013 Elsevier B.V. All rights reserved.

The effect of aspirin dosing on platelet function in diabetic and nondiabetic patients: an analysis from the aspirin-induced platelet effect (ASPECT) study.

PubMed

DiChiara, Joseph; Bliden, Kevin P; Tantry, Udaya S; Hamed, Miruais S; Antonino, Mark J; Suarez, Thomas A; Bailon, Oscar; Singla, Anand; Gurbel, Paul A

2007-12-01

Diabetic patients may have a higher prevalence of platelet aspirin resistance than nondiabetic patients. Our goal was to analyze platelet aspirin responsiveness to various aspirin doses in diabetic and nondiabetic patients. We examined the effect of aspirin (81, 162, and 325 mg/day for 4 weeks each) on platelet aspirin responsiveness in 120 stable outpatients (30 diabetic patients and 90 nondiabetic patients) with coronary artery disease (CAD) using light transmittance aggregometry (LTA), VerifyNow, platelet function analyzer (PFA)-100, and levels of urinary 11-dehydro-thromboxane B(2) (11-dh-TxB(2)). In the total group, a low prevalence (0-2%) of aspirin resistance was observed with all aspirin doses as determined by arachidonic acid-induced LTA. Aspirin resistance was higher at the 81-mg dose in diabetic versus nondiabetic patients using collagen-induced LTA (27 vs. 4%, P = 0.001), VerifyNow (13 vs. 3%, P = 0.05), and urinary 11-dh-TxB(2) (37 vs. 17%, P = 0.03). Diabetic patients treated with 81 mg exhibited higher platelet function measured by VerifyNow, collagen- and ADP-induced LTA, and 11-dh-TxB(2) levels (P

The dose response relation for rat spinal cord paralysis analyzed in terms of the effective size of the functional subunit

NASA Astrophysics Data System (ADS)

Adamus-Górka, Magdalena; Mavroidis, Panayiotis; Brahme, Anders; Lind, Bengt K.

2008-11-01

Radiobiological models for estimating normal tissue complication probability (NTCP) are increasingly used in order to quantify or optimize the clinical outcome of radiation therapy. A good NTCP model should fulfill at least the following two requirements: (a) it should predict the sigmoid shape of the corresponding dose-response curve and (b) it should accurately describe the probability of a specified response for arbitrary non-uniform dose delivery for a given endpoint as accurately as possible, i.e. predict the volume dependence. In recent studies of the volume effect of a rat spinal cord after irradiation with narrow and broad proton beams the authors claim that none of the existing NTCP models is able to describe their results. Published experimental data have been used here to try to quantify the change in the effective dose (D50) causing 50% response for different field sizes. The present study was initiated to describe the induction of white matter necrosis in a rat spinal cord after irradiation with narrow proton beams in terms of the mean dose to the effective volume of the functional subunit (FSU). The physically delivered dose distribution was convolved with a function describing the effective size or, more accurately, the sensitivity distribution of the FSU to obtain the effective mean dose deposited in it. This procedure allows the determination of the mean D50 value of the FSUs of a certain size which is of interest for example if the cell nucleus of the oligodendrocyte is the sensitive target. Using the least-squares method to compare the effective doses for different sizes of the functional subunits with the experimental data the best fit was obtained with a length of about 9 mm. For the non-uniform dose distributions an effective FSU length of 8 mm gave the optimal fit with the probit dose-response model. The method could also be used to interpret the so-called bath and shower experiments where the heterogeneous dose delivery was used in the convolution process. The assumption of an effective FSU size is consistent with most of the effects seen when different portions of the rat spinal cord are irradiated to different doses. The effective FSU length from these experiments is about 8.5 ± 0.5 mm. This length could be interpreted as an effective size of the functional subunits in a rat spinal cord, where multiple myelin sheaths are connected by a single oligodendrocyte and repair is limited by the range of oligodendrocyte progenitor cell diffusion. It was even possible to suggest a more likely than uniform effective FSU sensitivity distribution from the experimental data.

Response functions for computing absorbed dose to skeletal tissues from photon irradiation—an update

NASA Astrophysics Data System (ADS)

Johnson, Perry B.; Bahadori, Amir A.; Eckerman, Keith F.; Lee, Choonsik; Bolch, Wesley E.

2011-04-01

A comprehensive set of photon fluence-to-dose response functions (DRFs) is presented for two radiosensitive skeletal tissues—active and total shallow marrow—within 15 and 32 bone sites, respectively, of the ICRP reference adult male. The functions were developed using fractional skeletal masses and associated electron-absorbed fractions as reported for the UF hybrid adult male phantom, which in turn is based upon micro-CT images of trabecular spongiosa taken from a 40 year male cadaver. The new DRFs expand upon both the original set of seven functions produced in 1985, and a 2007 update calculated under the assumption of secondary electron escape from spongiosa. In this study, it is assumed that photon irradiation of the skeleton will yield charged particle equilibrium across all spongiosa regions at energies exceeding 200 keV. Kerma coefficients for active marrow, inactive marrow, trabecular bone and spongiosa at higher energies are calculated using the DRF algorithm setting the electron-absorbed fraction for self-irradiation to unity. By comparing kerma coefficients and DRF functions, dose enhancement factors and mass energy-absorption coefficient (MEAC) ratios for active marrow to spongiosa were derived. These MEAC ratios compared well with those provided by the NIST Physical Reference Data Library (mean difference of 0.8%), and the dose enhancement factors for active marrow compared favorably with values calculated in the well-known study published by King and Spiers (1985 Br. J. Radiol. 58 345-56) (mean absolute difference of 1.9 percentage points). Additionally, dose enhancement factors for active marrow were shown to correlate well with the shallow marrow volume fraction (R2 = 0.91). Dose enhancement factors for the total shallow marrow were also calculated for 32 bone sites representing the first such derivation for this target tissue.

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

Pantelis, Evaggelos, E-mail: vpantelis@phys.uoa.g; Medical Physics Laboratory, Medical School, University of Athens, Athens; Papadakis, Nikolaos

Purpose: To study the efficacy of the integration of functional magnetic resonance imaging (fMRI) and diffusion tensor imaging tractography data into stereotactic radiosurgery clinical practice. Methods and Materials: fMRI and tractography data sets were acquired and fused with corresponding anatomical MR and computed tomography images of patients with arteriovenous malformation (AVM), astrocytoma, brain metastasis, or hemangioma and referred for stereotactic radiosurgery. The acquired data sets were imported into a CyberKnife stereotactic radiosurgery system and used to delineate the target, organs at risk, and nearby functional structures and fiber tracts. Treatment plans with and without the incorporation of the functional structuresmore » and the fiber tracts into the optimization process were developed and compared. Results: The nearby functional structures and fiber tracts could receive doses of >50% of the maximum dose if they were excluded from the planning process. In the AVM case, the doses received by the Broadmann-17 structure and the optic tract were reduced to 700 cGy from 1,400 cGy and to 1,200 cGy from 2,000 cGy, respectively, upon inclusion into the optimization process. In the metastasis case, the motor cortex received 850 cGy instead of 1,400 cGy; and in the hemangioma case, the pyramidal tracts received 780 cGy instead of 990 cGy. In the astrocytoma case, the dose to the motor cortex bordering the lesion was reduced to 1,900 cGy from 2,100 cGy, and therefore, the biologically equivalent dose in three fractions was delivered instead. Conclusions: Functional structures and fiber tracts could receive high doses if they were not considered during treatment planning. With the aid of fMRI and tractography images, they can be delineated and spared.« less

In vitro and in vivo assessment of platelet function in healthy dogs during administration of a low-dose aspirin regimen.

PubMed

Haines, Jillian M; Thomason, John M; Seage, Eileen C; Wills, Robert W; Bulla, Camilo; Lunsford, Kari V; Mackin, Andrew J

2016-02-01

To assess the in vitro and in vivo platelet function of healthy dogs during administration of a low-dose aspirin regimen. 16 dogs. Dogs received aspirin (1 mg/kg, PO, q 24 h) for 7 days. Blood and urine samples were collected before (day 1; baseline) and on days 3 and 7 of the low-dose aspirin regimen. Platelet function was evaluated by use of turbidimetric and conventional impedance aggregometry, multiple-electrode impedance aggregometry, a platelet function analyzer (PFA), and determination of urine 11-dehydro-thromboxane B2 concentration. Turbidimetric aggregometry results were compared with the results obtained by the other 4 methods. Fourteen days after cessation of aspirin, platelet-rich plasma was incubated with acetylsalicylic acid and platelet function was assessed by turbidimetric aggregometry to determine whether this technique could accurately identify dogs that responded to the low-dose aspirin regimen. Of the 16 dogs, 13 had turbidimetric and conventional impedance aggregometry results that were decreased by > 25% from baseline on days 3 and 7, and 4 and 7 dogs had PFA closure times > 300 seconds on days 3 and 7, respectively. The median urine 11-dehydro-thromboxane B2 concentration-to-creatinine concentration ratio decreased by 49% between days 1 and 7. Turbidimetric aggregometry results were correlated with conventional impedance aggregometry results. There was poor agreement between the turbidimetric aggregometry and PFA results. The multiple-electrode impedance aggregometry protocol failed to reliably detect aspirin-induced platelet dysfunction. In vitro incubation of platelet-rich plasma with acetylsalicylic acid followed by turbidimetric aggregometry did not predict whether dogs responded to the low-dose aspirin regimen. Results indicated that the response to a low-dose aspirin regimen varied among healthy dogs.

Response functions for computing absorbed dose to skeletal tissues from photon irradiation--an update.

PubMed

Johnson, Perry B; Bahadori, Amir A; Eckerman, Keith F; Lee, Choonsik; Bolch, Wesley E

2011-04-21

A comprehensive set of photon fluence-to-dose response functions (DRFs) is presented for two radiosensitive skeletal tissues-active and total shallow marrow-within 15 and 32 bone sites, respectively, of the ICRP reference adult male. The functions were developed using fractional skeletal masses and associated electron-absorbed fractions as reported for the UF hybrid adult male phantom, which in turn is based upon micro-CT images of trabecular spongiosa taken from a 40 year male cadaver. The new DRFs expand upon both the original set of seven functions produced in 1985, and a 2007 update calculated under the assumption of secondary electron escape from spongiosa. In this study, it is assumed that photon irradiation of the skeleton will yield charged particle equilibrium across all spongiosa regions at energies exceeding 200 keV. Kerma coefficients for active marrow, inactive marrow, trabecular bone and spongiosa at higher energies are calculated using the DRF algorithm setting the electron-absorbed fraction for self-irradiation to unity. By comparing kerma coefficients and DRF functions, dose enhancement factors and mass energy-absorption coefficient (MEAC) ratios for active marrow to spongiosa were derived. These MEAC ratios compared well with those provided by the NIST Physical Reference Data Library (mean difference of 0.8%), and the dose enhancement factors for active marrow compared favorably with values calculated in the well-known study published by King and Spiers (1985 Br. J. Radiol. 58 345-56) (mean absolute difference of 1.9 percentage points). Additionally, dose enhancement factors for active marrow were shown to correlate well with the shallow marrow volume fraction (R(2) = 0.91). Dose enhancement factors for the total shallow marrow were also calculated for 32 bone sites representing the first such derivation for this target tissue.

RESPONSE FUNCTIONS FOR COMPUTING ABSORBED DOSE TO SKELETAL TISSUES FROM PHOTON IRRADIATION – AN UPDATE

PubMed Central

Johnson, Perry; Bahadori, Amir; Eckerman, Keith; Lee, Choonsik; Bolch, Wesley E.

2014-01-01

A comprehensive set of photon fluence-to-dose response functions (DRFs) are presented for two radiosensitive skeletal tissues – active and total shallow marrow – within 15 and 32 bones sites, respectively, of the ICRP reference adult male. The functions were developed using fractional skeletal masses and associated electron absorbed fractions as reported for the UF hybrid adult male phantom, which in turn is based upon microCT images of trabecular spongiosa taken from a 40-year male cadaver. The new DRFs expand upon both the original set of seven functions produced in 1985, as well as a 2007 update calculated under the assumption of secondary electron escape from spongiosa. In the present study, it is assumed that photon irradiation of the skeleton will yield charged particle equilibrium across all spongiosa regions at energies exceeding 200 keV. Kerma factors for active marrow, inactive marrow, trabecular bone, and spongiosa at higher energies are calculated using the DRF algorithm setting the electron absorbed fraction for self-irradiation to unity. By comparing kerma factors and DRF functions, dose enhancement factors and mass energy-absorption coefficient (MEAC) ratios for active marrow to spongiosa were derived. These MEAC ratios compared well with those provided by the NIST Physical Reference Data Library (mean difference of 0.8%), and the dose enhancement factors for active marrow compared favorably with values calculated in the well-known study published by King and Spiers (1985) (mean absolute difference of 1.9 percentage points). Additionally, dose enhancement factors for active marrow were shown to correlate well with the shallow marrow volume fraction (R2 = 0.91). Dose enhancement factors for the total shallow marrow were also calculated for 32 bone sites PMID:21427484

Is more better than less? An analysis of children's mental health services.

PubMed Central

Foster, E M

2000-01-01

OBJECTIVE: To assess the dose-response relationship for outpatient therapy received by children and adolescents-that is, to determine the impact of added outpatient visits on key mental health outcomes (functioning and symptomatology). DATA SOURCES/STUDY SETTING: The results presented involve analyses of data from the Fort Bragg Demonstration and are based on a sample of 301 individuals using outpatient services. STUDY DESIGN: This article provides estimates of the impact of outpatient therapy based on comparisons of individuals receiving differing treatment doses. Those comparisons involve standard multiple regression analyses as well as instrumental variables estimation. The latter provides a means of adjusting comparisons for unobserved or unmeasured differences among individuals receiving differing doses, differences that would otherwise be confounded with the impact of treatment dose. DATA COLLECTION/EXTRACTION METHODS: Using structured diagnostic interviews and behavior checklists completed by the child and his or her caretaker, detailed data on psychopathology, symptomatology, and psychosocial functioning were collected on individuals included in these analyses. Information on the use of mental health services was taken from insurance claims and a management information system. Services data were used to describe the use of outpatient therapy within the year following entry into the study. PRINCIPAL FINDINGS/CONCLUSIONS: Instrumental variables estimation indicates that added outpatient therapy improves functioning among children and adolescents. The effect is statistically significant and of moderate practical magnitude. These results imply that conventional analyses of the dose-response relationship may understate the impact of additional treatment on functioning. This finding is robust to choice of functional form, length of time over which outcomes are measured, and model specification. Dose does not appear to influence symptomatology. PMID:11130814

HIGH DOSES OF ASPARTAME HAVE NO EFFECTS ON SENSORIMOTOR FUNCTION OR LEARNING AND MEMORY IN RATS

EPA Science Inventory

Acute or repeated (14 days) intragastric administration of L-d-aspartyl-L-phenylalanine methyl ester suspended in saline and Tween-80 in doses of up to 1,000 mg/kg had no significant effect in male Fischer-344 rats on routine measures of sensorimotor function, including spontaneo...

Comparative assessment of onion and garlic extracts on endogenous hepatic and renal antioxidant status in rat.

PubMed

Suru, Stephen M; Ugwu, Chidiebere E

2015-07-01

Despite growing claims of functional health benefits in folkloric medicine, the safety of chronic/elevated intakes of onion and garlic cannot be assumed. Therefore, this study assesses oral administration of varied doses of onion and garlic on some biomarkers of hepatic and renal functions in rats. Animals were divided into five groups: control group received vehicle and extract-treated groups received varied doses of onion or garlic extract (0.5 mL and 1.0 mL/100 g bwt/day) for 6 weeks. Both doses of onion caused marked (p<0.05) increase in hepatic and renal levels of glutathione (GSH), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and marked (p<0.05) decrease in malondialdehyde (MDA). Treatment with low dose of garlic elicited similar trend except in hepatic CAT, renal SOD and GST levels. A high dose of garlic only caused marked (p<0.05) increase in hepatic GST, renal GST, and SOD. Both doses of onion and low dose of garlic significantly (p<0.05) enhanced renal Na+/K+-ATPase activity. Only a high dose of onion caused significant (p<0.05) increase in hepatic aspartate transaminase (AST), alkaline phosphatase (ALP), and decrease in plasma AST activities. These findings suggest antioxidant enhancing capability for both doses of onion and low dose of garlic, while high dose of garlic elicited pro-oxidant conditions.

Linear response theory for annealing of radiation damage in semiconductor devices

NASA Technical Reports Server (NTRS)

Litovchenko, Vitaly

1988-01-01

A theoretical study of the radiation/annealing response of MOS ICs is described. Although many experiments have been performed in this field, no comprehensive theory dealing with radiation/annealing response has been proposed. Many attempts have been made to apply linear response theory, but no theoretical foundation has been presented. The linear response theory outlined here is capable of describing a broad area of radiation/annealing response phenomena in MOS ICs, in particular, both simultaneous irradiation and annealing, as well as short- and long-term annealing, including the case when annealing is nearing completion. For the first time, a simple procedure is devised to determine the response function from experimental radiation/annealing data. In addition, this procedure enables us to study the effect of variable temperature and dose rate, effects which are of interest in spaceflight. In the past, the shift in threshold potential due to radiation/annealing has usually been assumed to depend on one variable: the time lapse between an impulse dose and the time of observation. While such a suggestion of uniformity in time is certainly true for a broad range of radiation annealing phenomena, it may not hold for some ranges of the variables of interest (temperature, dose rate, etc.). A response function is projected which is dependent on two variables: the time of observation and the time of the impulse dose. This dependence on two variables allows us to extend the theory to the treatment of a variable dose rate. Finally, the linear theory is generalized to the case in which the response is nonlinear with impulse dose, but is proportional to some impulse function of dose. A method to determine both the impulse and response functions is presented.

A comparison of mean parotid gland dose with measures of parotid gland function after radiotherapy for head-and-neck cancer: Implications for future trials

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

Roesink, Judith M.; Schipper, Maria; Busschers, Wim

2005-11-15

Purpose: To determine the most adequate parameter to measure the consequences of reducing the parotid gland dose. Methods and Materials: One hundred eight patients treated with radiotherapy for various malignancies of the head and neck were prospectively evaluated using three methods. Parotid gland function was objectively determined by measuring stimulated parotid flow using Lashley cups and scintigraphy. To assess xerostomia-related quality of life, the head-and-neck cancer module European Organization for Research and Treatment of Cancer QLQ (Quality of Life Questionnaire) H and N35 was used. Measurements took place before radiotherapy and 6 weeks and 12 months after the completion ofmore » radiotherapy. Complication was defined for each method using cutoff values. The correlation between these complications and the mean parotid gland dose was investigated to find the best measure for parotid gland function. Results: For both flow and scintigraphy data, the best definition for objective parotid gland toxicity seemed to be reduction of stimulated parotid flow to {<=}25% of the preradiotherapy flow. Of all the subjective variables, only the single item dry mouth 6 weeks after radiotherapy was found to be significant. The best correlation with the mean parotid gland dose was found for the stimulated flow measurements. The predictive ability was the highest for the time point 1 year after radiotherapy. Subjective findings did not correlate with the mean parotid dose. Conclusions: Stimulated flow measurements using Lashley cups, with a complication defined as flow {<=}25% of the preradiotherapy output, correlated best with the mean parotid gland dose. When reduction of the mean dose to the parotid gland is intended, the stimulated flow measurement is the best method for evaluating parotid gland function.« less

Extracting the normal lung dose-response curve from clinical DVH data: a possible role for low dose hyper-radiosensitivity, increased radioresistance

NASA Astrophysics Data System (ADS)

Gordon, J. J.; Snyder, K.; Zhong, H.; Barton, K.; Sun, Z.; Chetty, I. J.; Matuszak, M.; Ten Haken, R. K.

2015-09-01

In conventionally fractionated radiation therapy for lung cancer, radiation pneumonitis’ (RP) dependence on the normal lung dose-volume histogram (DVH) is not well understood. Complication models alternatively make RP a function of a summary statistic, such as mean lung dose (MLD). This work searches over damage profiles, which quantify sub-volume damage as a function of dose. Profiles that achieve best RP predictive accuracy on a clinical dataset are hypothesized to approximate DVH dependence. Step function damage rate profiles R(D) are generated, having discrete steps at several dose points. A range of profiles is sampled by varying the step heights and dose point locations. Normal lung damage is the integral of R(D) with the cumulative DVH. Each profile is used in conjunction with a damage cutoff to predict grade 2 plus (G2+) RP for DVHs from a University of Michigan clinical trial dataset consisting of 89 CFRT patients, of which 17 were diagnosed with G2+ RP. Optimal profiles achieve a modest increase in predictive accuracy—erroneous RP predictions are reduced from 11 (using MLD) to 8. A novel result is that optimal profiles have a similar distinctive shape: enhanced damage contribution from low doses (<20 Gy), a flat contribution from doses in the range ~20-40 Gy, then a further enhanced contribution from doses above 40 Gy. These features resemble the hyper-radiosensitivity / increased radioresistance (HRS/IRR) observed in some cell survival curves, which can be modeled using Joiner’s induced repair model. A novel search strategy is employed, which has the potential to estimate RP dependence on the normal lung DVH. When applied to a clinical dataset, identified profiles share a characteristic shape, which resembles HRS/IRR. This suggests that normal lung may have enhanced sensitivity to low doses, and that this sensitivity can affect RP risk.

Fieldable computer system for determining gamma-ray pulse-height distributions, flux spectra, and dose rates from Little Boy

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

Moss, C.E.; Lucas, M.C.; Tisinger, E.W.

1984-01-01

Our system consists of a LeCroy 3500 data acquisition system with a built-in CAMAC crate and eight bismuth-germanate detectors 7.62 cm in diameter and 7.62 cm long. Gamma-ray pulse-height distributions are acquired simultaneously for up to eight positions. The system was very carefully calibrated and characterized from 0.1 to 8.3 MeV using gamma-ray spectra from a variety of radioactive sources. By fitting the pulse-height distributions from the sources with a function containing 17 parameters, we determined theoretical repsonse functions. We use these response functions to unfold the distributions to obtain flux spectra. A flux-to-dose-rate conversion curve based on the workmore » of Dimbylow and Francis is then used to obtain dose rates. Direct use of measured spectra and flux-to-dose-rate curves to obtain dose rates avoids the errors that can arise from spectrum dependence in simple gamma-ray dosimeter instruments. We present some gamma-ray doses for the Little Boy assembly operated at low power. These results can be used to determine the exposures of the Hiroshima survivors and thus aid in the establishment of radation exposure limits for the nuclear industry.« less

Dose-dependent effects of theta burst rTMS on cortical excitability and resting-state connectivity of the human motor system.

PubMed

Nettekoven, Charlotte; Volz, Lukas J; Kutscha, Martha; Pool, Eva-Maria; Rehme, Anne K; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

2014-05-14

Theta burst stimulation (TBS), a specific protocol of repetitive transcranial magnetic stimulation (rTMS), induces changes in cortical excitability that last beyond stimulation. TBS-induced aftereffects, however, vary between subjects, and the mechanisms underlying these aftereffects to date remain poorly understood. Therefore, the purpose of this study was to investigate whether increasing the number of pulses of intermittent TBS (iTBS) (1) increases cortical excitability as measured by motor-evoked potentials (MEPs) and (2) alters functional connectivity measured using resting-state fMRI, in a dose-dependent manner. Sixteen healthy, human subjects received three serially applied iTBS blocks of 600 pulses over the primary motor cortex (M1 stimulation) and the parieto-occipital vertex (sham stimulation) to test for dose-dependent iTBS effects on cortical excitability and functional connectivity (four sessions in total). iTBS over M1 increased MEP amplitudes compared with sham stimulation after each stimulation block. Although the increase in MEP amplitudes did not differ between the first and second block of M1 stimulation, we observed a significant increase after three blocks (1800 pulses). Furthermore, iTBS enhanced resting-state functional connectivity between the stimulated M1 and premotor regions in both hemispheres. Functional connectivity between M1 and ipsilateral dorsal premotor cortex further increased dose-dependently after 1800 pulses of iTBS over M1. However, no correlation between changes in MEP amplitudes and functional connectivity was detected. In summary, our data show that increasing the number of iTBS stimulation blocks results in dose-dependent effects at the local level (cortical excitability) as well as at a systems level (functional connectivity) with a dose-dependent enhancement of dorsal premotor cortex-M1 connectivity. Copyright © 2014 the authors 0270-6474/14/346849-11$15.00/0.

Comparison of the hypothetical 57Co brachytherapy source with the 192Ir source

PubMed Central

Toossi, Mohammad Taghi Bahreyni; Rostami, Atefeh; Khosroabadi, Mohsen; Khademi, Sara; Knaup, Courtney

2016-01-01

Aim of the study The 57Co radioisotope has recently been proposed as a hypothetical brachytherapy source due to its high specific activity, appropriate half-life (272 days) and medium energy photons (114.17 keV on average). In this study, Task Group No. 43 dosimetric parameters were calculated and reported for a hypothetical 57Co source. Material and methods A hypothetical 57Co source was simulated in MCNPX, consisting of an active cylinder with 3.5 mm length and 0.6 mm radius encapsulated in a stainless steel capsule. Three photon energies were utilized (136 keV [10.68%], 122 keV [85.60%], 14 keV [9.16%]) for the 57Co source. Air kerma strength, dose rate constant, radial dose function, anisotropy function, and isodose curves for the source were calculated and compared to the corresponding data for a 192Ir source. Results The results are presented as tables and figures. Air kerma strength per 1 mCi activity for the 57Co source was 0.46 cGyh–1 cm 2 mCi–1. The dose rate constant for the 57Co source was determined to be 1.215 cGyh–1U–1. The radial dose function for the 57Co source has an increasing trend due to multiple scattering of low energy photons. The anisotropy function for the 57Co source at various distances from the source is more isotropic than the 192Ir source. Conclusions The 57Co source has advantages over 192Ir due to its lower energy photons, longer half-life, higher dose rate constant and more isotropic anisotropic function. However, the 192Ir source has a higher initial air kerma strength and more uniform radial dose function. These properties make 57Co a suitable source for use in brachytherapy applications. PMID:27688731

Praseodymium-142 glass seeds for the brachytherapy of prostate cancer

NASA Astrophysics Data System (ADS)

Jung, Jae Won

A beta-emitting glass seed was proposed for the brachytherapy treatment of prostate cancer. Criteria for seed design were derived and several beta-emitting nuclides were examined for suitability. 142Pr was selected as the isotope of choice. Seeds 0.08 cm in diameter and 0.9 cm long were manufactured for testing. The seeds were activated in the Texas A&M University research reactor. The activity produced was as expected when considering the meta-stable state and epi-thermal neutron flux. The MCNP5 Monte Carlo code was used to calculate the quantitative dosimetric parameters suggested in the American Association of Physicists in Medicine (AAPM) TG-43/60. The Monte Carlo calculation results were compared with those from a dose point kernel code. The dose profiles agree well with each other. The gamma dose of 142Pr was evaluated. The gamma dose is 0.3 Gy at 1.0 cm with initial activity of 5.95 mCi and is insignificant to other organs. Measurements were performed to assess the 2-dimensional axial dose distributions using Gafchromic radiochromic film. The radiochromic film was calibrated using an X-ray machine calibrated against a National Institute of Standards and Technology (NIST) traceable ion chamber. A calibration curve was derived using a least squares fit of a second order polynomial. The measured dose distribution agrees well with results from the Monte Carlo simulation. The dose was 130.8 Gy at 6 mm from the seed center with initial activity of 5.95 mCi. AAPM TG-43/60 parameters were determined. The reference dose rate for 2 mm and 6 mm were 0.67 and 0.02 cGy/s/mCi, respectively. The geometry function, radial dose function and anisotropy function were generated.

SU-F-19A-05: Experimental and Monte Carlo Characterization of the 1 Cm CivaString 103Pd Brachytherapy Source

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

Reed, J; Micka, J; Culberson, W

Purpose: To determine the in-air azimuthal anisotropy and in-water dose distribution for the 1 cm length of the CivaString {sup 103}Pd brachytherapy source through measurements and Monte Carlo (MC) simulations. American Association of Physicists in Medicine Task Group No. 43 (TG-43) dosimetry parameters were also determined for this source. Methods: The in-air azimuthal anisotropy of the source was measured with a NaI scintillation detector and simulated with the MCNP5 radiation transport code. Measured and simulated results were normalized to their respective mean values and compared. The TG-43 dose-rate constant, line-source radial dose function, and 2D anisotropy function for this sourcemore » were determined from LiF:Mg,Ti thermoluminescent dosimeter (TLD) measurements and MC simulations. The impact of {sup 103}Pd well-loading variability on the in-water dose distribution was investigated using MC simulations by comparing the dose distribution for a source model with four wells of equal strength to that for a source model with strengths increased by 1% for two of the four wells. Results: NaI scintillation detector measurements and MC simulations of the in-air azimuthal anisotropy showed that ≥95% of the normalized data were within 1.2% of the mean value. TLD measurements and MC simulations of the TG-43 dose-rate constant, line-source radial dose function, and 2D anisotropy function agreed to within the experimental TLD uncertainties (k=2). MC simulations showed that a 1% variability in {sup 103}Pd well-loading resulted in changes of <0.1%, <0.1%, and <0.3% in the TG-43 dose-rate constant, radial dose distribution, and polar dose distribution, respectively. Conclusion: The CivaString source has a high degree of azimuthal symmetry as indicated by the NaI scintillation detector measurements and MC simulations of the in-air azimuthal anisotropy. TG-43 dosimetry parameters for this source were determined from TLD measurements and MC simulations. {sup 103}Pd well-loading variability results in minimal variations in the in-water dose distribution according to MC simulations. This work was partially supported by CivaTech Oncology, Inc. through an educational grant for Joshua Reed, John Micka, Wesley Culberson, and Larry DeWerd and through research support for Mark Rivard.« less

Early irradiation syndrome. A study of the functional changes in the rabbit following whole-body $gamma$ exposure at sublethal doses (in French)

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

Dufour, R.; Collignon, Y.; Vincent, F.

1975-05-01

A method of simultaneous observation of several physiological functions was developed in the unanaesthetized rabbit. Arterial blood pressure, local brain circulation, internal body temperature and arterial blodd acido-basic balance were thus followed before, during and after $gamma$-irradiation. There appeared two periods in the development of this early syndrome: they were related to two processes, a central one, mainly of sympathetic origin was hardly sensitive to the dose, the other is dose-dependent. (FR)

Intravenous Nicotine Self-Administration in Smokers: Dose-Response Function and Sex Differences.

PubMed

Jensen, Kevin P; DeVito, Elise E; Valentine, Gerald; Gueorguieva, Ralitza; Sofuoglu, Mehmet

2016-07-01

Sex differences in the sensitivity to nicotine may influence vulnerability to tobacco dependence. The goal of this study was to investigate the dose-response function for the reinforcing and subjective effects of intravenous nicotine in male and female smokers. Tobacco-dependent subjects (12 male and 14 female) participated in four experimental sessions in which they received sample infusions of saline and nicotine (0.1, 0.2, 0.3, or 0.4 mg doses) in a randomized double-blind crossover design. During each session, subjects first received the sample infusions, and heart rate (HR), blood pressure, and subjective stimulatory, pleasurable and aversive responses were monitored. Immediately following the sample infusions, subjects self-administered either nicotine or saline in six double-blind forced-choice trials. A sex by dose interaction was observed in the nicotine choice paradigm. Nicotine self-administration rate was negatively correlated with nicotine dose in males (males displayed choice preference for low doses of nicotine over high doses of nicotine), but no significant relationship between dose and choice preference was evident in females. Relative to placebo, sample doses of nicotine increased heart rate and blood pressure, and induced stimulatory, pleasurable, and aversive subjective effects. Diastolic blood pressure increased dose dependently in males, but not in females. These findings, which demonstrate sex differences in nicotine self-administration for doses that are near to the reinforcement threshold, suggest that male and female smokers may respond differently to the changes in nicotine doses available for self-administration.

Enhanced Medial Collateral Ligament Healing using Mesenchymal Stem Cells: Dosage Effects on Cellular Response and Cytokine Profile

PubMed Central

Saether, Erin E.; Chamberlain, Connie S.; Leiferman, Ellen M.; Kondratko-Mittnacht, Jaclyn R.; Li, Wan Ju; Brickson, Stacey L.; Vanderby, Ray

2013-01-01

Mesenchymal stem cells (MSCs) have potential therapeutic applications for musculoskeletal injuries due to their ability to differentiate into several tissue cell types and modulate immune and inflammatory responses. These immune-modulatory properties were examined in vivo during early stage rat medial collateral ligament healing. Two different cell doses (low dose 1×106 or high dose 4×106 MSCs) were administered at the time of injury and compared with normal ligament healing at days 5 and 14 post-injury. At both times, the high dose MSC group demonstrated a significant decrease in M2 macrophages compared to controls. At day 14, fewer M1 macrophages were detected in the low dose group compared to the high dose group. These results, along with significant changes in procollagen I, proliferating cells, and endothelialization suggest that MSCs can alter the cellular response during healing in a dose-dependent manner. The higher dose ligaments also had increased expression of several pro-inflammatory cytokines at day 5 (IL-1β, IFNγ, IL-2) and increased expression of IL-12 at day 14. Mechanical testing at day 14 revealed increased failure strength and stiffness in low dose ligaments compared to controls. Based on these improved mechanical properties, MSCs enhanced functional healing when applied at a lower dose. Different doses of MSCs uniquely affected the cellular response and cytokine expression in healing ligaments. Interestingly, the lower dose of cells proved to be most effective in improving functional properties. PMID:24174129

Acute ethanol ingestion produces dose-dependent effects on motor behavior in the honey bee (Apis mellifera).

PubMed

Maze, Ian S; Wright, Geraldine A; Mustard, Julie A

2006-01-01

Ethanol consumption produces characteristic behavioral states in animals that include sedation, disorientation, and disruption of motor function. Using individual honey bees, we assessed the effects of ethanol ingestion on motor function via continuous observations of their behavior. Consumption of 1 M sucrose solutions containing a range of ethanol doses led to hemolymph ethanol levels of approximately 40-100 mM. Using ethanol doses in this range, we observed time and dose-dependent effects of ethanol on the percent of time our subjects spent walking, stopped, or upside down, and on the duration and frequency of bouts of behavior. The effects on grooming and flying behavior were more complex. Behavioral recovery from ethanol treatment was both time and ethanol dose dependent, occurring between 12 and 24 h post-ingestion for low doses and at 24-48 h for higher doses. Furthermore, the amount of ethanol measured in honey bee hemolymph appeared to correlate with recovery. We predict that the honey bee will prove to be an excellent model system for studying the influence of ethanol on the neural mechanisms underlying behavior.

Recirculating cardiac delivery of AAV2/1SERCA2a improves myocardial function in an experimental model of heart failure in large animals.

PubMed

Byrne, M J; Power, J M; Preovolos, A; Mariani, J A; Hajjar, R J; Kaye, D M

2008-12-01

Abnormal excitation-contraction coupling is a key pathophysiologic component of heart failure (HF), and at a molecular level reduced expression of the sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA2a) is a major contributor. Previous studies in small animals have suggested that restoration of SERCA function is beneficial in HF. Despite this promise, the means by which this information might be translated into potential clinical application remains uncertain. Using a recently established cardiac-directed recirculating method of gene delivery, we administered adeno-associated virus 2 (AAV2)/1SERCA2a to sheep with pacing-induced HF. We explored the effects of differing doses of AAV2/1SERCA2a (low 1 x 10(10) d.r.p.; medium 1 x 10(12) d.r.p. and high 1 x 10(13) d.r.p.) in conjunction with an intra-coronary delivery group (2.5 x 10(13) d.r.p.). At the end of the study, haemodynamic, echocardiographic, histopathologic and molecular biologic assessments were performed. Cardiac recirculation delivery of AAV2/1SERCA2a elicited a dose-dependent improvement in cardiac performance determined by left ventricular pressure analysis, (+d P/d t(max); low dose -220+/-70, P>0.05; medium dose 125+/-53, P<0.05; high dose 287+/-104, P<0.05) and echocardiographically (fractional shortening: low dose -3+/-2, P>0.05; medium dose 1+/-2, P>0.05; high dose 6.5+/-3.9, P<0.05). In addition to favourable haemodynamic effects, brain natriuretic peptide expression was reduced consistent with reversal of the HF molecular phenotype. In contrast, direct intra-coronary infusion did not elicit any effect on ventricular function. As such, AAV2/1SERCA2a elicits favourable functional and molecular actions when delivered in a mechanically targeted manner in an experimental model of HF. These observations lay a platform for potential clinical translation.

Systemic SMAD7 Gene Therapy Increases Striated Muscle Mass and Enhances Exercise Capacity in a Dose-Dependent Manner.

PubMed

Maricelli, Joseph W; Bishaw, Yemeserach M; Wang, Bo; Du, Min; Rodgers, Buel D

2018-03-01

Striated muscle wasting occurs with a variety of disease indications, contributing to mortality and compromising life quality. Recent studies indicate that the recombinant adeno-associated virus (serotype 6) Smad7 gene therapeutic, AVGN7, enhances skeletal and cardiac muscle mass and prevents cancer-induced wasting of both tissues. This is accomplished by attenuating ActRIIb intracellular signaling and, as a result, the physiological actions of myostatin and other ActRIIb ligands. AVGN7 also enhances isolated skeletal muscle twitch force, but is unknown to improve systemic muscle function similarly, especially exercise capacity. A 2-month-long dose-escalation study was therefore conducted using 5 × 10 11 , 1 × 10 12 , and 5 × 10 12 vg/mouse and different tests of systemic muscle function. Body mass, skeletal muscle mass, heart mass, and forelimb grip strength were all increased in a dose-dependent manner, as was the fiber cross-sectional area of tibialis anterior muscles. Maximal oxygen consumption (VO 2 max), a measure of metabolic rate, was similarly enhanced during forced treadmill running, and although the total distance traveled was only elevated by the highest dose, all doses reduced the energy expenditure rate compared to control mice injected with an empty vector. Such improvements in VO 2 max are consistent with physiological cardiac hypertrophy, which is highly beneficial and a normal adaptive response to exercise. This was particularly evident at the lowest dose tested, which had minimal significant effects on skeletal muscle mass and/or function, but increased heart weight and exercise capacity. These results together suggest that AVGN7 enhances striated muscle mass and systemic muscle function. They also define minimally effective and optimal doses for future preclinical trials and toxicology studies and in turn will aid in establishing dose ranges for clinical trials.

Analysis of a Statistical Relationship Between Dose and Error Tallies in Semiconductor Digital Integrated Circuits for Application to Radiation Monitoring Over a Wireless Sensor Network

NASA Astrophysics Data System (ADS)

Colins, Karen; Li, Liqian; Liu, Yu

2017-05-01

Mass production of widely used semiconductor digital integrated circuits (ICs) has lowered unit costs to the level of ordinary daily consumables of a few dollars. It is therefore reasonable to contemplate the idea of an engineered system that consumes unshielded low-cost ICs for the purpose of measuring gamma radiation dose. Underlying the idea is the premise of a measurable correlation between an observable property of ICs and radiation dose. Accumulation of radiation-damage-induced state changes or error events is such a property. If correct, the premise could make possible low-cost wide-area radiation dose measurement systems, instantiated as wireless sensor networks (WSNs) with unshielded consumable ICs as nodes, communicating error events to a remote base station. The premise has been investigated quantitatively for the first time in laboratory experiments and related analyses performed at the Canadian Nuclear Laboratories. State changes or error events were recorded in real time during irradiation of samples of ICs of different types in a 60Co gamma cell. From the error-event sequences, empirical distribution functions of dose were generated. The distribution functions were inverted and probabilities scaled by total error events, to yield plots of the relationship between dose and error tallies. Positive correlation was observed, and discrete functional dependence of dose quantiles on error tallies was measured, demonstrating the correctness of the premise. The idea of an engineered system that consumes unshielded low-cost ICs in a WSN, for the purpose of measuring gamma radiation dose over wide areas, is therefore tenable.

Monte Carlo calculated TG-60 dosimetry parameters for the {beta}{sup -} emitter {sup 153}Sm brachytherapy source

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

Sadeghi, Mahdi; Taghdiri, Fatemeh; Hamed Hosseini, S.

Purpose: The formalism recommended by Task Group 60 (TG-60) of the American Association of Physicists in Medicine (AAPM) is applicable for {beta} sources. Radioactive biocompatible and biodegradable {sup 153}Sm glass seed without encapsulation is a {beta}{sup -} emitter radionuclide with a short half-life and delivers a high dose rate to the tumor in the millimeter range. This study presents the results of Monte Carlo calculations of the dosimetric parameters for the {sup 153}Sm brachytherapy source. Methods: Version 5 of the (MCNP) Monte Carlo radiation transport code was used to calculate two-dimensional dose distributions around the source. The dosimetric parameters ofmore » AAPM TG-60 recommendations including the reference dose rate, the radial dose function, the anisotropy function, and the one-dimensional anisotropy function were obtained. Results: The dose rate value at the reference point was estimated to be 9.21{+-}0.6 cGy h{sup -1} {mu}Ci{sup -1}. Due to the low energy beta emitted from {sup 153}Sm sources, the dose fall-off profile is sharper than the other beta emitter sources. The calculated dosimetric parameters in this study are compared to several beta and photon emitting seeds. Conclusions: The results show the advantage of the {sup 153}Sm source in comparison with the other sources because of the rapid dose fall-off of beta ray and high dose rate at the short distances of the seed. The results would be helpful in the development of the radioactive implants using {sup 153}Sm seeds for the brachytherapy treatment.« less

Dosimetric characterization of the (60)Co BEBIG Co0.A86 high dose rate brachytherapy source using PENELOPE.

PubMed

Guerrero, Rafael; Almansa, Julio F; Torres, Javier; Lallena, Antonio M

2014-12-01

(60)Co sources are being used as an alternative to (192)Ir sources in high dose rate brachytherapy treatments. In a recent document from AAPM and ESTRO, a consensus dataset for the (60)Co BEBIG (model Co0.A86) high dose rate source was prepared by using results taken from different publications due to discrepancies observed among them. The aim of the present work is to provide a new calculation of the dosimetric characteristics of that (60)Co source according to the recommendations of the AAPM and ESTRO report. Radial dose function, anisotropy function, air-kerma strength, dose rate constant and absorbed dose rate in water have been calculated and compared to the results of previous works. Simulations using the two different geometries considered by other authors have been carried out and the effect of the cable density and length has been studied. Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Relationship between Eustachian tube dysfunction and otitis media with effusion in radiotherapy patients.

PubMed

Akazawa, K; Doi, H; Ohta, S; Terada, T; Fujiwara, M; Uwa, N; Tanooka, M; Sakagami, M

2018-02-01

This study evaluated the relationship between radiation and Eustachian tube dysfunction, and examined the radiation dose required to induce otitis media with effusion. The function of 36 Eustachian tubes in 18 patients with head and neck cancer were examined sonotubometrically before, during, and 1, 2 and 3 months after, intensity-modulated radiotherapy. Patients with an increase of 5 dB or less in sound pressure level (dB) during swallowing were categorised as being in the dysfunction group. Additionally, radiation dose distributions were assessed in all Eustachian tubes using three dose-volume histogram parameters. Twenty-two of 25 normally functioning Eustachian tubes before radiotherapy (88.0 per cent) shifted to the dysfunction group after therapy. All ears that developed otitis media with effusion belonged to the dysfunction group. The radiation dose threshold evaluation revealed that ears with otitis media with effusion received significantly higher doses to the Eustachian tubes. The results indicate a relationship between radiation dose and Eustachian tube dysfunction and otitis media with effusion.

Influence of sensitization on the discriminative stimulus effects of methylphenidate in mice.

PubMed

McGovern, Robin; Luderman, Lauryn; Knecht, Kelly; Griffin, William C

2014-12-01

Methylphenidate (MPH) remains an important therapy for attention-deficit hyperactivity disorder, but aspects of its pharmacology remain unclear. In the present study, we used a regimen of MPH (8 mg/kg daily×14 days) in C57BL/6J mice to determine whether establishing locomotor sensitization to MPH influenced the acquisition and the dose-response function of MPH in a classic drug discrimination procedure. MPH-sensitized mice (SENS group) showed enhanced locomotor activity to the 8 mg/kg exposure dose as well as a 2 mg/kg dose before discrimination training. However, the SENS mice did not acquire discrimination of either a low dose (2 mg/kg) or a higher dose (4 mg/kg) of MPH any more rapidly than the CTRL mice. Further, during generalization testing, the dose-response functions for the SENS and CTRL mice were identical. Therefore, we did not find that previous exposure to MPH, which produced a sensitized locomotor response, facilitated MPH discrimination.

The effects of two different doses of hydrocortisone on cognition in patients with secondary adrenal insufficiency--results from a randomized controlled trial.

PubMed

Werumeus Buning, Jorien; Brummelman, Pauline; Koerts, Janneke; Dullaart, Robin P F; van den Berg, Gerrit; van der Klauw, Melanie M; Tucha, Oliver; Wolffenbuttel, Bruce H R; van Beek, André P

2015-05-01

A wide variety in hydrocortisone (HC) substitution dose-regimens are considered physiological for patients with secondary adrenal insufficiency (SAI). However, it is likely that cognition is negatively influenced by higher cortisol exposure to the brain. To examine the effects of a high physiological HC dose in comparison to a low physiological HC dose on cognition. This study was a randomized double blind cross-over study at the University Medical Center Groningen. This study is registered with ClinicalTrials.gov, number NCT01546922. Forty-seven patients (29 males, 18 females; mean [SD] age, 51 [14] years, range 19-73) with SAI participated. Patients randomly received first a low dose of HC (0.2-0.3 mg/kg body weight/day) during 10 weeks followed by a high dose (0.4-0.6 mg/kg body weight/day) for another 10 weeks, or vice versa. HC substitution was given in three divided doses with the highest dose in the morning. Cognitive performance (memory, attention, executive functioning and social cognition) of patients was measured at baseline and after each treatment period using a battery of 12 standardized cognitive tests. The higher dose of HC resulted in significantly higher systemic cortisol exposure for example measured at 1h after first dose ingestion (mean [SD], low dose: 653 [281] nmol/L; high dose: 930 [148] nmol/L; P<0.001). No differences in cognitive performance were found between the two dose regimens. No negative influence on memory, attention, executive functioning and social cognition was observed after 10 weeks of treatment with a higher physiological dose of HC in patients with SAI when compared to a lower dose. Copyright © 2015 Elsevier Ltd. All rights reserved.

SU-G-206-06: Analytic Dose Function for CT Scans in Infinite Cylinders as a Function of Scan Length and Cylinder Radius

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

Bakalyar, D; Feng, W; McKenney, S

Purpose: The radiation dose absorbed at a particular radius ρ within the central plane of a long cylinder following a CT scan is a function of the length of the scan L and the cylinder radius R along with kVp and cylinder composition. An analytic function was created that that not only expresses these dependencies but is integrable in closed form over the area of the central plane. This feature facilitates explicit calculation of the planar average dose. The “approach to equilibrium” h(L) discussed in the TG111 report is seamlessly included in this function. Methods: For a cylindrically symmetric radiationmore » field, Monte Carlo calculations were performed to compute the dose distribution to long polyethylene cylinders for scans of varying L for cylinders ranging in radius from 5 to 20 cm. The function was developed from the resultant Monte Carlo data. In addition, the function was successfully fit to data taken from measurements on the 30 cm diameter ICRU/TG200 phantom using a real-time dosimeter. Results: Symmetry and continuity dictate a local extremum at the center which is a minimum for the larger sizes. There are competing effects as the beam penetrates the cylinder from the outside: attenuation, resulting in a decrease; scatter, abruptly increasing at the circumference. This competition may result in an absolute maximum between the center and outer edge leading to a “gull wing” shape for the radial dependence. For the smallest cylinders, scatter may dominate to the extent that there is an absolute maximum at the center. Conclusion: An integrable, analytic function has been developed that provides the radial dependency of dose for the central plane of a scan of length L for cylinders of varying diameter. Equivalently, we have developed h(L,R,ρ).« less

Interactive Dose Shaping - efficient strategies for CPU-based real-time treatment planning

NASA Astrophysics Data System (ADS)

Ziegenhein, P.; Kamerling, C. P.; Oelfke, U.

2014-03-01

Conventional intensity modulated radiation therapy (IMRT) treatment planning is based on the traditional concept of iterative optimization using an objective function specified by dose volume histogram constraints for pre-segmented VOIs. This indirect approach suffers from unavoidable shortcomings: i) The control of local dose features is limited to segmented VOIs. ii) Any objective function is a mathematical measure of the plan quality, i.e., is not able to define the clinically optimal treatment plan. iii) Adapting an existing plan to changed patient anatomy as detected by IGRT procedures is difficult. To overcome these shortcomings, we introduce the method of Interactive Dose Shaping (IDS) as a new paradigm for IMRT treatment planning. IDS allows for a direct and interactive manipulation of local dose features in real-time. The key element driving the IDS process is a two-step Dose Modification and Recovery (DMR) strategy: A local dose modification is initiated by the user which translates into modified fluence patterns. This also affects existing desired dose features elsewhere which is compensated by a heuristic recovery process. The IDS paradigm was implemented together with a CPU-based ultra-fast dose calculation and a 3D GUI for dose manipulation and visualization. A local dose feature can be implemented via the DMR strategy within 1-2 seconds. By imposing a series of local dose features, equal plan qualities could be achieved compared to conventional planning for prostate and head and neck cases within 1-2 minutes. The idea of Interactive Dose Shaping for treatment planning has been introduced and first applications of this concept have been realized.

Hardness, function, emotional well-being, satisfaction and the overall sexual experience in men using 100-mg fixed-dose or flexible-dose sildenafil citrate

PubMed Central

Ströberg, P; Kaminetsky, J C; Park, N C; Goldfischer, E R; Creanga, D L; Stecher, V J

2010-01-01

The prescribing information for sildenafil citrate (VIAGRA, Pfizer, New York, NY, USA) recommends flexible dosing (50 mg initially, adjusted to 100 or 25 mg based on effectiveness and tolerability) in most men with erectile dysfunction (ED). In many men, however, 100 mg may be the most appropriate initial dose because it would reduce the need for titration and could prevent discouragement and treatment abandonment should 50 mg be insufficient. Results of two previously published double-blind, placebo-controlled sildenafil trials of similar design except for a fixed-dose vs flexible-dose regimen were analyzed. Relative to the flexible-dose, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg. In addition, tolerability was similar, and improvements from baseline in outcomes on validated, ED-specific, patient-reported questionnaires were either similar (erectile function and the percentage of completely hard and fully rigid erections) or greater (emotional well-being and the overall sexual experience). The similarity in outcomes is not surprising given that almost 90% of the men in the flexible-dose trial titrated to 100 mg after 2 weeks. These data suggest prescription of an initial dose of 100 mg for men with ED, except in those for whom it is inappropriate. PMID:20596083

A novel method of estimating cost of therapy by using patient population characteristics: analysis of fluoroquinolones in various populations with different distributions of renal function.

PubMed

Enzweiler, Kevin A; Bosso, John A; White, Roger L

2003-07-01

Formulary decisions regarding a given drug class are often made in the absence of patient outcome and/or sophisticated pharmacoeconomic data. Analyses that consider factors beyond simple acquisition costs may be useful in such situations. For example, the cost implications of using manufacturers' recommendations for dosing in patients with renal dysfunction may be important, depending on the distribution of various levels of renal function within a patient population. Using four 1000-patient populations representing different renal function distributions and a fifth population of our medical center's distribution, we determined the costs of therapy for intravenous and oral levofloxacin, gatifloxacin, and moxifloxacin for a 10-day course of therapy for community-acquired pneumonia. Costs considered were average wholesale prices (AWPs), 50% of AWP, or same daily price, plus intravenous dose preparation and administration costs when applicable. Costs for each renal function distribution were examined for significant differences with an analysis-of-variance test. Also, costs of failing to adjust dosing regimens for decreased renal function were determined. Differences in fluoroquinolone costs (AWP, 50% AWP, or when matched as the same daily price) among the populations were found. When considering same daily prices, differences among populations ranged from about 35,000 dollars with intravenous gatifloxacin to more than 51,000 dollars for intravenous levofloxacin (all fluoroquinolones, p>0.05). Within a population, differences in costs among the intravenous fluoroquinolones ranged from 47,000-99,000 dollars. Rank orders of the drugs and population costs of therapy were affected by the pricing structure used and varied by the specific population and drug. Differences among the fluoroquinolones or populations were much smaller (<2100 dollars) when considering oral regimens. Costs potentially incurred by failing to adjust dosing for renal function were substantial. Formulary decisions can be facilitated by considering factors such as patient characteristics and related dosing in addition to simple acquisition costs. In our example, consideration of the distribution of renal function within a given patient population and related dosing for these fluoroquinolones revealed potentially important differences within the class.

Impact of mycophenolate mofetil dose posttransplantation on 12-month renal function: analysis of the MOST database.

PubMed

Salvadori, M; Bock, A; Chapman, J; Dussol, B; Fritsche, L; Kliem, V; Lebranchu, Y; Oppenheimer, F; Pohanka, E; Tufveson, G; Rosati, A; Puig, X; Corbetta, G

2005-01-01

Mycophenolate mofetil (MMF) has greatly reduced the risk of acute rejection episodes (ARE) after renal transplantation, but dose reductions/withdrawals could jeopardize long-term results. The MOST database of "de novo" patients treated with MMF at month 1 and functioning grafts at month 12 were divided into 2 groups: groups 1, 2 g MMF at month 1 and month 12; and group 2, 2 g MMF at month 1 but MMF <2 g at month 12 to evaluate renal function glonerular filtration rate (GFR). In this study, 1136 patients were receiving 2 g MMF at month 1. On month 12, 645 were on 2 g (56.8%, group 1) and 431 were on <2 g (43.2%, group 2). Group 1 included younger recipients of younger donors with fewer patients with delayed graft function (DGF). Group 1 showed more ARE during month 1 and more patients who received induction. Mean Neoral daily doses at month 1/month 12 were 5.3/3.0 and 5.3/3.1 mg/kg in group 1 and group 2, respectively (P = .05 at month 12). GFR in group 1 and group 2 were 59.06 (CI 57.10-60.60) and 53.81 (CI 52-55.7) at month 1 (P < .001); 63.7 (CI 62.1-65.30) and 55.9 (CI 54.1-57.7) mL/min*1.73 m(2) at month 12 (P < .001). The mean increases in GFR between month 1 and month 12 were 4.64 and 1.94 mL/min*1.73 m(2), respectively (P < .05). A multivariate analysis also included 795 patients from the "maintenance" patient database with retrospective detailed information. The following parameters were highly predictive for good renal function at month 12: donor age younger than 60 years, recipient age younger than 60 years, immediate graft function, 12-month MMF dose = 2 g, absence of CMV infection, and 12-month Neoral dose <3 mg/kg/d. Maintenance of MMF dose at 2 g/d during the first year appears to facilitate the attainment of optimal renal function at 12-months after kidney transplantation.

Recovery from welding-fume-exposure-induced lung fibrosis and pulmonary function changes in sprague dawley rats.

PubMed

Sung, Jae Hyuck; Choi, Byung-Gil; Maeng, Seung-Hee; Kim, Soo-Jin; Chung, Yong Hyun; Han, Jeong Hee; Song, Kyung Seuk; Lee, Yong Hwan; Cho, Yong Bong; Cho, Myung-Haing; Kim, Kwang Jong; Hyun, Jin Suk; Yu, Il Je

2004-12-01

Welder's pneumoconiosis has generally been determined as benign based on the absence of pulmonary function abnormalities in welders with marked radiographic abnormalities. Yet, there have also been several reports on welders with respiratory symptoms, indicating lung function impairment, X-ray abnormalities, and extensive fibrosis. Accordingly, this study attempted to investigate the inflammatory responses and pulmonary function changes in rats during a 60-day welding-fume-inhalation exposure period to elucidate the process of fibrosis. The rats were exposed to manual metal-arc stainless-steel welding fumes (MMA-SS) with total suspended particulate concentrations of 64.8 +/- 0.9 (low dose) and 107.8 +/- 2.6 mg/m3 (high dose) for 2 h per day in an inhalation chamber for 60 days. Animals were sacrificed after the initial 2-h exposure and after 15, 30, and 60 days, and the pulmonary function was also measured every week after the daily exposure. Elevated cellular differential counts were also measured in the acellular bronchoalveolar lavage fluid of the rats exposed to the MMA-SS fumes for 60 days. Among the pulmonary function test parameters, only the tidal volume showed a statistically significant and dose-dependent decrease after 35 to 60 days of MMA-SS welding-fume exposure. When the rats exposed to the welding fumes were left for 60 days to recover their lung function and cellular differentiation, recovery was observed in both the high and low-dose rats exposed up to 30 days, resulting in the disappearance of inflammatory cells and restoration of the tidal volume. The rats exposed for 60 days at the low dose also recovered from the inflammation and tidal volume loss, yet the rats exposed for 60 days at the high dose did not fully recover even after a 60-day recovery period. Therefore, when taken together, the results of the current study suggest that a decrease in the tidal volume could be used as an early indicator of pulmonary fibrosis induced by welding-fume exposure in Sprague Dawley rats, and fibrosis would seem to be preventable if the exposure is short-term and moderate.

Parotid Gland Sparing With Helical Tomotherapy in Head-and-Neck Cancer

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

Voordeckers, Mia, E-mail: mia.voordeckers@uzbrussel.be; Farrag, Ashraf; Assiut University

Purpose: This study evaluated the ability of helical tomotherapy to spare the function of the parotid glands in patients with head-and-neck cancer by analyzing dose-volume histograms, salivary gland scintigraphy, and quality of life assessment. Methods and Materials: Data from 76 consecutive patients treated with helical tomotherapy (Hi-Art Tomotherapy) at University Hospital Brussel were analyzed. During planning, priority was given to planning target volume (PTV) coverage: {>=}95% of the dose must be delivered to {>=}95% of the PTV. Elective nodal regions received 54 Gy (1.8 Gy/fraction). A dose of 70.5 Gy (2.35 Gy/fraction) was prescribed to the primary tumor and pathologicmore » lymph nodes (simultaneous integrated boost scheme). Objective scoring of salivary excretion was performed by salivary gland scintigraphy. Subjective scoring of salivary gland function was evaluated by the European Organization for Research and Treatment of Cancer quality of life questionnaires Quality of Life Questionnaire-C30 (QLQ-C30) and Quality of Life Questionnaire-Head and Neck 35 (H and N35). Results: Analysis of dose-volume histograms (DVHs) showed excellent coverage of the PTV. The volume of PTV receiving 95% of the prescribed dose (V95%) was 99.4 (range, 96.3-99.9). DVH analysis of parotid gland showed a median value of the mean parotid dose of 32.1 Gy (range, 17.5-70.3 Gy). The median parotid volume receiving a dose <26 Gy was 51.2%. Quality of life evaluation demonstrated an initial deterioration of almost all scales and items in QLQ-C30 and QLQ-H and N35. Most items improved in time, and some reached baseline values 18 months after treatment. Conclusion: DVH analysis, scintigraphic evaluation of parotid function, and quality of life assessment of our patient group showed that helical tomotherapy makes it possible to preserve parotid gland function without compromising disease control. We recommend mean parotid doses of <34 Gy and doses <26 Gy to a maximum 47% of the parotid volume as planning goals. Intensity-modulated radiotherapy should be considered as standard treatment in patients with head-and-neck cancer.« less

Safety, Pharmacokinetic, and Functional Effects of the Nogo-A Monoclonal Antibody in Amyotrophic Lateral Sclerosis: A Randomized, First-In-Human Clinical Trial

PubMed Central

Meininger, Vincent; Pradat, Pierre-François; Corse, Andrea; Al-Sarraj, Safa; Rix Brooks, Benjamin; Caress, James B.; Cudkowicz, Merit; Kolb, Stephen J.; Lange, Dale; Leigh, P. Nigel; Meyer, Thomas; Milleri, Stefano; Morrison, Karen E.; Orrell, Richard W.; Peters, Gary; Rothstein, Jeffrey D.; Shefner, Jeremy; Lavrov, Arseniy; Williams, Nicola; Overend, Phil; Price, Jeffrey; Bates, Stewart; Bullman, Jonathan; Krull, David; Berges, Alienor; Abila, Bams; Meno-Tetang, Guy; Wurthner, Jens

2014-01-01

The neurite outgrowth inhibitor, Nogo-A, has been shown to be overexpressed in skeletal muscle in amyotrophic lateral sclerosis (ALS); it is both a potential biomarker and therapeutic target. We performed a double-blind, two-part, dose-escalation study, in subjects with ALS, assessing safety, pharmacokinetics (PK) and functional effects of ozanezumab, a humanized monoclonal antibody against Nogo-A. In Part 1, 40 subjects were randomized (3∶1) to receive single dose intravenous ozanezumab (0.01, 0.1, 1, 5, or 15 mg/kg) or placebo. In Part 2, 36 subjects were randomized (3∶1) to receive two repeat doses of intravenous ozanezumab (0.5, 2.5, or 15 mg/kg) or placebo, approximately 4 weeks apart. The primary endpoints were safety and tolerability (adverse events [AEs], vital signs, electrocardiogram (ECG), and clinical laboratory tests). Secondary endpoints included PK, immunogenicity, functional endpoints (clinical and electrophysiological), and biomarker parameters. Overall, ozanezumab treatment (0.01–15 mg/kg) was well tolerated. The overall incidence of AEs in the repeat dose 2.5 mg/kg and 15 mg/kg ozanezumab groups was higher than in the repeat dose placebo group and repeat dose 0.5 mg/kg ozanezumab group. The majority were considered not related to study drug by the investigators. Six serious AEs were reported in three subjects receiving ozanezumab; none were considered related to study drug. No study drug-related patterns were identified for ECG, laboratory, or vital signs parameters. One subject (repeat dose 15 mg/kg ozanezumab) showed a weak, positive anti-ozanezumab-antibody result. PK results were generally consistent with monoclonal antibody treatments. No apparent treatment effects were observed for functional endpoints or muscle biomarkers. Immunohistochemical staining showed dose-dependent co-localization of ozanezumab with Nogo-A in skeletal muscle. In conclusion, single and repeat dose ozanezumab treatment was well tolerated and demonstrated co-localization at the site of action. These findings support future studies with ozanezumab in ALS. Trial Registration ClinicalTrials.gov NCT00875446 GSK-ClinicalStudyRegister.com GSK ID 111330 PMID:24841795

Comparison of capnovolumetry-derived dead space parameters with pulmonary function test in normal adults using histamine provocation.

PubMed

Sun, Xiaoli; Zhang, Yan; Yang, Wenlan; Liu, Jinming

2015-04-01

This study in healthy adults was conducted to explore the clinical application of capnovolumetric indices as compared to lung function parameters using histamine provocation. Forty healthy subjects received aerosol histamine or salbutamol in an automatic stimulation system with escalating doses of histamine. Dead space volumes of capnovolumetry and lung function parameters were examined with increased concentrations of histamine at a fixed time interval. The doses of histamine were selected from 0.0562 mg-2.2 mg and 0.1 mg salbutamol was inhaled when a maximal dose of histamine was reached. Baseline values in each group were calculated prior to histamine inhalation. Fowler dead space (VDF), Wolff dead space (VDW), threshold dead space (VDT), Bohr dead space (VDB), forced expiratory volume in 1 s (FEV1 ) and peak expiratory flow (PEF) showed a dose-dependent reduction following histamine provocation, but there were no statistical differences in the measurements at baseline and post S6 provocation. The value of dC3/DV at the maximal dose was significantly increased over its baseline value (P < 0.05). VDF, VDT and VDW were significantly increased after bronchodilator use (P < 0.05 or <0.01). The changes in capnovolumetry did not correspond with the results of lung function test. The dC3/DV and airway dead spaces of capnovolumetry in healthy adults are significantly increased compared to lung function parameters before or after bronchodilator use, suggesting that capnovolumetry is feasible in diagnostic evaluation of airway reactivity, especially for persons who are unable to undertake lung function test. © 2014 John Wiley & Sons Ltd.

Insecticide imidacloprid influences cognitive functions and alters learning performance and related gene expression in a rat model.

PubMed

Kara, Murat; Yumrutas, Onder; Demir, Caner F; Ozdemir, Hasan Huseyin; Bozgeyik, Ibrahim; Coskun, Salih; Eraslan, Ersen; Bal, Ramazan

2015-10-01

The potential toxic effects of several pesticides, including imidacloprid on non-target organisms have not been clearly established. Also, the chronic effects of non-toxic doses on cognitive function in mammals are unknown. In this study, the effects of different doses of imidacloprid on learning and memory of infant and adult rats were evaluated, and the expressions of genes synthesizing proteins known to be associated with learning in brain tissues were also documented. 0.5, 2 and 8 mg/kg doses of imidacloprid were administered to newborn infant and adult Wistar albino rats by gavage. Their learning activities were evaluated, and the expression levels of the inotropic glutamate receptor GRIN1, synoptophysin, growth-associated protein 43 and the muscarinic receptor M1 in hippocampus were determined by real-time PCR method. Learning activities were diminished significantly at 2 and 8 mg/kg doses in the infant model groups and at 8 mg/kg dose in adult rats. Also, expression levels of GRIN1, SYP and GAP-43 were found to be insignificantly altered. Only the expression of M1 were significantly changed in high doses of adult group. Thus imidacloprid in high doses causes deterioration in cognitive functions particularly in infant rats, and this deterioration may be associated with changes in the expressions of related genes. © 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.

Rasagiline for dysexecutive symptoms during wearing-off in Parkinson's disease: a pilot study.

PubMed

Rinaldi, Domiziana; Assogna, Francesca; Sforza, Michela; Tagliente, Stefania; Pontieri, Francesco E

2018-01-01

Wearing-off refers to the predictable worsening of motor and sometimes non-motor symptoms of Parkinson's disease occurring at the end of levodopa dose that improves with the next drug dose. Here, we investigated the efficacy of rasagiline on executive functions at the end of levodopa dose in patients displaying symptoms of wearing-off. Rasagiline was well-tolerated and produced a significant improvement at the Frontal Assessment Battery, together with improvement of motor symptoms at the end of levodopa dose. These results suggest that treatment of motor symptoms of wearing-off with rasagiline may be accompanied by improvement of executive functions, and further support the need for optimizing dopamine replacement therapy in fluctuating Parkinson's disease patients.

Biology Based Lung Cancer Model for Chronic Low Radon Exposures

NASA Astrophysics Data System (ADS)

TruÅ£ǎ-Popa, Lucia-Adina; Hofmann, Werner; Fakir, Hatim; Cosma, Constantin

2008-08-01

Low dose effects of alpha particles at the tissue level are characterized by the interaction of single alpha particles, affecting only a small fraction of the cells within that tissue. Alpha particle intersections of bronchial target cells during a given exposure period were simulated by an initiation-promotion model, formulated in terms of cellular hits within the cycle time of the cell (dose-rate) and then integrated over the whole exposure period (dose). For a given average number of cellular hits during the lifetime of bronchial cells, the actual number of single and multiple hits was selected from a Poisson distribution. While oncogenic transformation is interpreted as the primary initiation step, stimulated mitosis by killing adjacent cells is assumed to be the primary radiological promotion event. Analytical initiation and promotion functions were derived from experimental in vitro data on oncogenic transformation and cellular survival. To investigate the shape of the lung cancer risk function at chronic, low level exposures in more detail, additional biological factors describing the tissue response and operating specifically at low doses were incorporated into the initiation-promotion model. These mechanisms modifying the initial response at the cellular level were: adaptive response, genomic instability, induction of apoptosis by surrounding cells, and detrimental as well as protective bystander mechanisms. To quantify the effects of these mechanisms as functions of dose, analytical functions were derived from the experimental evidence presently available. Predictions of lung cancer risk, including these mechanisms, exhibit a distinct sublinear dose-response relationship at low exposures, particularly for very low exposure rates.

Effect of kefir and low-dose aspirin on arterial blood pressure measurements and renal apoptosis in unhypertensive rats with 4 weeks salt diet.

PubMed

Kanbak, Güngör; Uzuner, Kubilay; Kuşat Ol, Kevser; Oğlakçı, Ayşegül; Kartkaya, Kazım; Şentürk, Hakan

2014-01-01

Abstract We aim to study the effect of low-dose aspirin and kefir on arterial blood pressure measurements and renal apoptosis in unhypertensive rats with 4 weeks salt diet. Forty adult male Sprague-Dawley rats were divided into five groups: control, high-salt (HS) (8.0% NaCl), HS+aspirin (10 mg/kg), HS+kefir (10.0%w/v), HS+aspirin +kefir. We measured sistolic blood pressure (SBP), mean arterial pressure (MAP), diastolic pressure, pulse pressure in the rats. Cathepsin B, L, DNA fragmentation and caspase-3 activities were determined from rat kidney tissues and rats clearance of creatinine calculated. Although HS diet increased significantly SBP, MAP, diastolic pressure, pulse pressure parameters compared the control values. They were not as high as accepted hypertension levels. When compared to HS groups, kefir groups significantly decrease Cathepsin B and DNA fragmentation levels. Caspase levels were elevated slightly in other groups according to control group. While, we also found that creatinine clearance was higher in HS+kefir and HS+low-dose aspirin than HS group. Thus, using low-dose aspirin had been approximately decreased of renal function damage. Kefir decreased renal function damage playing as Angiotensin-converting enzyme inhibitor. But, low-dose aspirin together with kefir worsened rat renal function damage. Cathepsin B might play role both apoptosis and prorenin-processing enzyme. But not caspase pathway may be involved in the present HS diet induced apoptosis. In conclusion, kefir and low-dose aspirin used independently protect renal function and renal damage induced by HS diet in rats.

Developmental Exposure to Perchlorate Alters Synaptic Transmission in Hippocampus of the Adult Rat

PubMed Central

Gilbert, Mary E.; Sui, Li

2008-01-01

Background Perchlorate is an environmental contaminant that blocks iodine uptake into the thyroid gland and reduces thyroid hormones. This action of perchlorate raises significant concern over its effects on brain development. Objectives The purpose of this study was to evaluate neurologic function in rats after developmental exposure to perchlorate. Methods Pregnant rats were exposed to 0, 30, 300, or 1,000 ppm perchlorate in drinking water from gestational day 6 until weaning. Adult male offspring were evaluated on a series of behavioral tasks and neurophysiologic measures of synaptic function in the hippocampus. Results At the highest perchlorate dose, triiodothyronine (T3) and thyroxine (T4) were reduced in pups on postnatal day 21. T4 in dams was reduced relative to controls by 16%, 28%, and 60% in the 30-, 300-, and 1,000-ppm dose groups, respectively. Reductions in T4 were associated with increases in thyroid-stimulating hormone in the high-dose group. No changes were seen in serum T3. Perchlorate did not impair motor activity, spatial learning, or fear conditioning. However, significant reductions in baseline synaptic transmission were observed in hippocampal field potentials at all dose levels. Reductions in inhibitory function were evident at 300 and 1,000 ppm, and augmentations in long-term potentiation were observed in the population spike measure at the highest dose. Conclusions Dose-dependent deficits in hippocampal synaptic function were detectable with relatively minor perturbations of the thyroid axis, indicative of an irreversible impairment in synaptic transmission in response to developmental exposure to perchlorate. PMID:18560531

Dual role of betel leaf extract on thyroid function in male mice.

PubMed

Panda, S; Kar, A

1998-12-01

The effects of betel leaf extract (0.10, 0.40, 0.80 and 2.0 g kg-1 day-1 for 15 days) on the alterations in thyroid hormone concentrations. lipid peroxidation (LPO) and on the activities of superoxide dismutase (SOD) and catalase (CAT) were investigated in male Swiss mice. Administration of betel leaf extract exhibited a dual role, depending on the different doses. While the lowest dose decreased thyroxine (T4) and increased serum triiodothyronine (T3) concentrations, reverse effects were observed at two higher doses. Higher doses also increased LPO with a concomitant decrease in SOD and CAT activities. However, with the lowest dose most of these effects were reversed. These findings suggest that betel leaf can be both stimulatory and inhibitory to thyroid function, particularly for T3 generation and lipid peroxidation in male mice, depending on the amount consumed.

[Effect of Codonopsis Radix maintained with sulfur fumigation on immune function in mice].

PubMed

Liu, Cheng-song; Wang, Yu-ping; Shi, Yan-bin; Ma, Xing-ming; Li, Hui-li; Zhang, Xiao-yun; Li, Shou-tang

2014-11-01

To investigate the immune function of mice being given the extract of Codonopsis Radix maintained with sulfur fumigation. Mice were divided into five groups. Except the normal control group, the mice were fed with the extract of Codonopsis Radix maintained with sulfur fumigation at the high,medium and low doses, as well as medium dose of Codonopsis Radix maintained with low-temperature vacuum method, respectively. Mice were treated once a day for 10 continuous days. Weight change,organ indexes, blood cell indices, macrophage phagocytic function, and IL-2 and IFN-γ levels were measured. Compared with normal control group, Codonopsis Radix maintained with sulfur fumigation at medium and high doses inhibited body weight increase of mice; white blood cell count of high dose group was significantly increased; significant increase of macrophage phagocytosis were observed for all groups except the normal control group; and spleen index and IFN-γ level of Codonopsis Radix maintained with sulfur fumigation medium dose group were increased significantly. Codonopsis Radix maintained with sulfur fumigation can promote mouse immune function to a certain degree. There was no difference in immune effect between Codonopsis Radix maintained with sulfur fumigation and low-temperature vacuum method during experimental period. However,taking the extract of Codonopsis Radix maintained with sulfur fumigation can exert negative effect on appetite and body weight in mice.

Gamma Low-Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate–Dependent Manner

PubMed Central

Vieira Dias, Juliana; Gloaguen, Celine; Kereselidze, Dimitri; Manens, Line; Tack, Karine; Ebrahimian, Teni G

2018-01-01

A central question in radiation protection research is whether low-dose and low-dose-rate (LDR) exposures to ionizing radiation play a role in progression of cardiovascular disease. The response of endothelial cells to different LDR exposures may help estimate risk of cardiovascular disease by providing the biological mechanism involved. We investigated the effect of chronic LDR radiation on functional and molecular responses of human aorta endothelial cells (HAoECs). Human aorta endothelial cells were continuously irradiated at LDR (6 mGy/h) for 15 days and analyzed at time points when the cumulative dose reached 0.05, 0.5, 1.0, and 2.0 Gy. The same doses were administered acutely at high-dose rate (HDR; 1 Gy/min). The threshold for the loss of angiogenic capacity for both LDR and HDR radiations was between 0.5 and 1.0 Gy. At 2.0 Gy, angiogenic capacity returned to normal only for HAoEC exposed to LDR radiation, associated with increased expression of antioxidant and anti-inflammatory genes. Pre-LDR, but not pre-HDR, radiation, followed by a single acute 2.0 Gy challenge dose sustained the expression of antioxidant and anti-inflammatory genes and stimulated angiogenesis. Our results suggest that dose rate is important in cellular response and that a radioadaptive response is involved for a 2.0 Gy dose at LDR. PMID:29531508

Gamma Low-Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate-Dependent Manner.

PubMed

Vieira Dias, Juliana; Gloaguen, Celine; Kereselidze, Dimitri; Manens, Line; Tack, Karine; Ebrahimian, Teni G

2018-01-01

A central question in radiation protection research is whether low-dose and low-dose-rate (LDR) exposures to ionizing radiation play a role in progression of cardiovascular disease. The response of endothelial cells to different LDR exposures may help estimate risk of cardiovascular disease by providing the biological mechanism involved. We investigated the effect of chronic LDR radiation on functional and molecular responses of human aorta endothelial cells (HAoECs). Human aorta endothelial cells were continuously irradiated at LDR (6 mGy/h) for 15 days and analyzed at time points when the cumulative dose reached 0.05, 0.5, 1.0, and 2.0 Gy. The same doses were administered acutely at high-dose rate (HDR; 1 Gy/min). The threshold for the loss of angiogenic capacity for both LDR and HDR radiations was between 0.5 and 1.0 Gy. At 2.0 Gy, angiogenic capacity returned to normal only for HAoEC exposed to LDR radiation, associated with increased expression of antioxidant and anti-inflammatory genes. Pre-LDR, but not pre-HDR, radiation, followed by a single acute 2.0 Gy challenge dose sustained the expression of antioxidant and anti-inflammatory genes and stimulated angiogenesis. Our results suggest that dose rate is important in cellular response and that a radioadaptive response is involved for a 2.0 Gy dose at LDR.

Repair-dependent cell radiation survival and transformation: an integrated theory.

PubMed

Sutherland, John C

2014-09-07

The repair-dependent model of cell radiation survival is extended to include radiation-induced transformations. The probability of transformation is presumed to scale with the number of potentially lethal damages that are repaired in a surviving cell or the interactions of such damages. The theory predicts that at doses corresponding to high survival, the transformation frequency is the sum of simple polynomial functions of dose; linear, quadratic, etc, essentially as described in widely used linear-quadratic expressions. At high doses, corresponding to low survival, the ratio of transformed to surviving cells asymptotically approaches an upper limit. The low dose fundamental- and high dose plateau domains are separated by a downwardly concave transition region. Published transformation data for mammalian cells show the high-dose plateaus predicted by the repair-dependent model for both ultraviolet and ionizing radiation. For the neoplastic transformation experiments that were analyzed, the data can be fit with only the repair-dependent quadratic function. At low doses, the transformation frequency is strictly quadratic, but becomes sigmodial over a wider range of doses. Inclusion of data from the transition region in a traditional linear-quadratic analysis of neoplastic transformation frequency data can exaggerate the magnitude of, or create the appearance of, a linear component. Quantitative analysis of survival and transformation data shows good agreement for ultraviolet radiation; the shapes of the transformation components can be predicted from survival data. For ionizing radiations, both neutrons and x-rays, survival data overestimate the transforming ability for low to moderate doses. The presumed cause of this difference is that, unlike UV photons, a single x-ray or neutron may generate more than one lethal damage in a cell, so the distribution of such damages in the population is not accurately described by Poisson statistics. However, the complete sigmodial dose-response data for neoplastic transformations can be fit using the repair-dependent functions with all parameters determined only from transformation frequency data.

Accounting for the economic risk caused by variation in disease severity in fungicide dose decisions, exemplified for Mycosphaerella graminicola on winter wheat.

PubMed

Te Beest, D E; Paveley, N D; Shaw, M W; van den Bosch, F

2013-07-01

A method is presented to calculate economic optimum fungicide doses accounting for the risk aversion of growers responding to variability in disease severity between crops. Simple dose-response and disease-yield loss functions are used to estimate net disease-related costs (fungicide cost plus disease-induced yield loss) as a function of dose and untreated severity. With fairly general assumptions about the shapes of the probability distribution of disease severity and the other functions involved, we show that a choice of fungicide dose which minimizes net costs, on average, across seasons results in occasional large net costs caused by inadequate control in high disease seasons. This may be unacceptable to a grower with limited capital. A risk-averse grower can choose to reduce the size and frequency of such losses by applying a higher dose as insurance. For example, a grower may decide to accept "high-loss" years 1 year in 10 or 1 year in 20 (i.e., specifying a proportion of years in which disease severity and net costs will be above a specified level). Our analysis shows that taking into account disease severity variation and risk aversion will usually increase the dose applied by an economically rational grower. The analysis is illustrated with data on Septoria tritici leaf blotch of wheat caused by Mycosphaerella graminicola. Observations from untreated field plots at sites across England over 3 years were used to estimate the probability distribution of disease severities at mid-grain filling. In the absence of a fully reliable disease forecasting scheme, reducing the frequency of high-loss years requires substantially higher doses to be applied to all crops. Disease-resistant cultivars reduce both the optimal dose at all levels of risk and the disease-related costs at all doses.

Derivation of the expressions for γ50 and D50 for different individual TCP and NTCP models

NASA Astrophysics Data System (ADS)

Stavreva, N.; Stavrev, P.; Warkentin, B.; Fallone, B. G.

2002-10-01

This paper presents a complete set of formulae for the position (D50) and the normalized slope (γ50) of the dose-response relationship based on the most commonly used radiobiological models for tumours as well as for normal tissues. The functional subunit response models (critical element and critical volume) are used in the derivation of the formulae for the normal tissue. Binomial statistics are used to describe the tumour control probability, the functional subunit response as well as the normal tissue complication probability. The formulae are derived for the single hit and linear quadratic models of cell kill in terms of the number of fractions and dose per fraction. It is shown that the functional subunit models predict very steep, almost step-like, normal tissue individual dose-response relationships. Furthermore, the formulae for the normalized gradient depend on the cellular parameters α and β when written in terms of number of fractions, but not when written in terms of dose per fraction.

Mixed-effects Gaussian process functional regression models with application to dose-response curve prediction.

PubMed

Shi, J Q; Wang, B; Will, E J; West, R M

2012-11-20

We propose a new semiparametric model for functional regression analysis, combining a parametric mixed-effects model with a nonparametric Gaussian process regression model, namely a mixed-effects Gaussian process functional regression model. The parametric component can provide explanatory information between the response and the covariates, whereas the nonparametric component can add nonlinearity. We can model the mean and covariance structures simultaneously, combining the information borrowed from other subjects with the information collected from each individual subject. We apply the model to dose-response curves that describe changes in the responses of subjects for differing levels of the dose of a drug or agent and have a wide application in many areas. We illustrate the method for the management of renal anaemia. An individual dose-response curve is improved when more information is included by this mechanism from the subject/patient over time, enabling a patient-specific treatment regime. Copyright © 2012 John Wiley & Sons, Ltd.

Enhancement of Cognitive and Electrophysiological Measures of Hippocampal Functioning in Rats by a Low, But Not High, Dose of Dehydroepiandrosterone Sulfate (DHEAS)

PubMed Central

Diamond, David M.

2004-01-01

Dehydroepiandrosterone sulfate (DHEAS) is a steroid hornone that is synthesized, de novo, in the brain. Endogenous DHEAS levels correlate with the quality of mental and physical health, where the highest levels of DHEAS occur in healthy young adults and reduced levels of DHEAS are found with advanced age, disease, or extreme stress. DHEAS supplementation, therefore, may serve as a therapeutic agent against a broad range of maladies. This paper summarizes laboratory findings on dose-response relationships between DHEAS and cognitive and electrophysiological measures of hippocampal functioning. It was found that a low, but not a high, dose of DHEAS enhanced hippocampal primed burst potentiation (a physiological model of memory) as well as spatial (hippocampal-dependent) memory in rats. This complex dose-response function of DHEAS effects on the brain and memory may contribute toward the inconsistent findings that have been obtained by other investigators in studies on DHEAS administration in people. PMID:19330152

Biological-based and physical-based optimization for biological evaluation of prostate patient's plans

NASA Astrophysics Data System (ADS)

Sukhikh, E.; Sheino, I.; Vertinsky, A.

2017-09-01

Modern modalities of radiation treatment therapy allow irradiation of the tumor to high dose values and irradiation of organs at risk (OARs) to low dose values at the same time. In this paper we study optimal radiation treatment plans made in Monaco system. The first aim of this study was to evaluate dosimetric features of Monaco treatment planning system using biological versus dose-based cost functions for the OARs and irradiation targets (namely tumors) when the full potential of built-in biological cost functions is utilized. The second aim was to develop criteria for the evaluation of radiation dosimetry plans for patients based on the macroscopic radiobiological criteria - TCP/NTCP. In the framework of the study four dosimetric plans were created utilizing the full extent of biological and physical cost functions using dose calculation-based treatment planning for IMRT Step-and-Shoot delivery of stereotactic body radiation therapy (SBRT) in prostate case (5 fractions per 7 Gy).

Initial apixaban dosing in patients with atrial fibrillation.

PubMed

Buchholz, Alexander; Ueberham, Laura; Gorczynska, Kaja; Dinov, Borislav; Hilbert, Sebastian; Dagres, Nikolaos; Husser, Daniela; Hindricks, Gerhard; Bollmann, Andreas

2018-05-01

Apixaban is a non-vitamin K oral anticoagulant approved for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF). Current labeling recommends dose reduction based on patient age, weight, and renal function. The aim of this study was to analyze adherence to current labeling instructions concerning initial apixaban dosing in clinical practice and identify factors associated with inappropriate dose reduction. Patients with AF initiated on apixaban in 2016 were identified in the Heart Center Leipzig database. Records were screened to identify patient characteristics, prescribed apixaban dose, renal function, and further dosing-relevant secondary diagnoses and co-medication. We identified 569 consecutive patients with AF initiated on apixaban. In 301 (52.9%) patients, apixaban was prescribed in standard dose (5 mg b.i.d.) and in 268 (47.1%) in a reduced dose (2.5 mg b.i.d.). Of 268 patients receiving a reduced dose, 163 (60.8%) did not meet labeling criteria for dose reduction. In univariate and multivariate regression analysis, age (OR: 0.736, 95% CI: 0.664-0.816, P < 0.0001), patient weight (OR: 1.120, 95% CI: 1.076-1.166, P < 0.0001), and serum creatinine level (OR: 0.910, 95% CI: 0.881-0.940, P < 0.0001) were independent predictors for apixaban underdosage. In clinical practice, apixaban dosing is frequently inconsistent with labeling. Factors associated with inappropriate dose reduction are age, patient weight, and serum creatinine level, the same factors used as criteria for dose adjustment. However, in underdosed patients, the 3 factors did not meet the criteria for dose reduction. © 2018 Wiley Periodicals, Inc.

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

Mao, R; Tian, L; Ge, H

Purpose: To evaluate the dosimetry of microscopic disease (MD) region of lung cancer in stereotactic body radiation therapy (SBRT). Methods: For simplicity, we assume organ moves along one dimension. The probability distribution function of tumor position was calculated according to the breathing cycle. The dose to the MD region was obtained through accumulating the treatment planning system calculated doses at different positions in a breathing cycle. A phantom experiment was then conducted to validate the calculated results using a motion phantom (The CIRS ‘Dynamic’ Thorax Phantom). The simulated breathing pattern used a cos4(x) curve with an amplitude of 10mm. Amore » 3-D conformal 7-field plan with 6X energy was created and the dose was calculated in the average intensity projection (AIP) simulation CT images. Both films (EBT2) and optically stimulated luminescence (OSL) detectors were inserted in the target of the phantom to measure the dose during radiation delivery (Varian Truebeam) and results were compared to planning dose parameters. Results: The Gamma analysis (3%/3mm) between measured dose using EBT2 film and calculated dose using AIP was 80.5%, indicating substantial dosimetric differences. While the Gamma analysis (3%/3mm) between measured dose using EBT2 and accumulated dose using 4D-CT was 98.9%, indicating the necessity of dose accumulation using 4D-CT. The measured doses using OSL and theoretically calculated doses using probability distribution function at the corresponding position were comparable. Conclusion: Use of static dose calculation in the treatment planning system could substantially underestimate the actually delivered dose in the MD region for a moving target. Funding Supported by NSFC, No.81372436.« less

The usefulness of sLORETA in evaluating the effect of high-dose ARA-C on brain connectivity in patients with acute myeloid leukemia: an exploratory study

PubMed Central

Zarabla, Alessia; Ungania, Sara; Cacciatore, Alessandra; Maialetti, Andrea; Petreri, Gianluca; Mengarelli, Andrea; Spadea, Antonio; Marchesi, Francesco; Renzi, Daniela; Gumenyuk, Svitlana; Strigari, Lidia; Maschio, Marta

2017-01-01

Summary Cytosine arabinoside (Ara-C) is one of the key drugs for treating acute myeloid leukemia (AML). High intravenous doses may produce a number of central nervous system (CNS) toxicities and contribute to modifications in brain functional connectivity. sLORETA is a software used for localizing brain electrical activity and functional connectivity. The aim of this study was to apply sLORETA in the evaluation of possible effects of Ara-C on brain connectivity in patients with AML without CNS involvement. We studied eight patients with AML; four were administered standard doses of Ara-C while the other four received high doses. sLORETA was computed from computerized EEG data before treatment and after six months of treatment. Three regions of interest, corresponding to specific combinations of Brodmann areas, were defined. In the patients receiving high-dose Ara-C, a statistically significant reduction in functional connectivity was observed in the frontoparietal network, which literature data suggest is involved in attentional processes. Our data highlight the possibility of using novel techniques to study potential CNS toxicity of cancer therapy.

LTC1877 High Efficiency Regulator Total Ionizing Dose Test Report

NASA Technical Reports Server (NTRS)

Oldham, Timothy; Pellish, Jonathan; Boutte, Alvin

2012-01-01

This report presents total ionizing dose evaluation data for the Linear Technology Corporation LTC1877 high efficiency monolithic synchronous step-down regulator. Data sheet parameters were tracked as a function of ionizing dose up to a total of 20 krad(SiO2). Control devices were also used.

ORGAN-SPECIFIC EXTERNAL DOSE COEFFICIENTS AND PROTECTIVE APRON TRANSMISSION FACTORS FOR HISTORICAL DOSE RECONSTRUCTION FOR MEDICAL PERSONNEL

PubMed Central

Simon, Steven L.

2014-01-01

While radiation absorbed dose (Gy) to the skin or other organs is sometimes estimated for patients from diagnostic radiologic examinations or therapeutic procedures, rarely is occupationally-received radiation absorbed dose to individual organs/tissues estimated for medical personnel, e.g., radiologic technologists or radiologists. Generally, for medical personnel, equivalent or effective radiation doses are estimated for compliance purposes. In the very few cases when organ doses to medical personnel are reconstructed, the data is usually for the purpose of epidemiologic studies, e.g., a study of historical doses and risks to a cohort of about 110,000 radiologic technologists presently underway at the U.S. National Cancer Institute. While ICRP and ICRU have published organ-specific external dose conversion coefficients (DCCs), i.e., absorbed dose to organs and tissues per unit air kerma and dose equivalent per unit air kerma, those factors have been primarily published for mono-energetic photons at selected energies. This presents two related problems for historical dose reconstruction, both of which are addressed here. It is necessary to derive conversion factors values for (i) continuous distributions of energy typical of diagnostic medical x rays (bremsstrahlung radiation), and (ii) for energies of particular radioisotopes used in medical procedures, neither of which are presented in published tables. For derivation of DCCs for bremsstrahlung radiation, combinations of x-ray tube potentials and filtrations were derived for different time periods based on a review of relevant literature. Three peak tube potentials (70 kV, 80 kV, and 90 kV) with four different amounts of beam filtration were determined to be applicable for historic dose reconstruction. The probability of these machine settings were assigned to each of the four time periods (earlier than 1949, 1949-1954, 1955-1968, and after 1968). Continuous functions were fit to each set of discrete values of the ICRP/ICRU mono-energetic DCCs and the functions integrated over the air-kerma weighted photon fluence of the 12 defined x-ray spectra. The air kerma-weighted DCCs in this work were developed specifically for an irradiation geometry of anterior to posterior (AP) and for the following tissues: thyroid, breast, ovary, lens of eye, lung, colon, testes, heart, skin (anterior side only), red bone marrow (RBM), heart, and brain. In addition, a series of functional relationships to predict DT per Ka values for RBM dependent on body mass index [BMI (kg m−2) ≡ weight per height2] and average photon energy were derived from a published analysis. Factors to account for attenuation of radiation by protective lead aprons were also developed. Because lead protective aprons often worn by radiology personnel not only reduce the intensity of x-ray exposure but also appreciably harden the transmitted fluence of bremsstrahlung x rays, DCCs were separately calculated for organs possibly protected by lead aprons by considering three cases: no apron, 0.25 mm Pb apron, and 0.5 mm Pb apron. For estimation of organ doses from conducting procedures with radioisotopes, continuous functions of the reported mono-energetic values were developed and DCCs were derived by estimation of the function at relevant energies. By considering the temporal changes in primary exposure-related parameters, e.g., energy distribution, the derived DCCs and transmission factors presented here allow for more realistic historical dose reconstructions for medical personnel when monitoring badge readings are the primary data on which estimation of an individual's organ doses are based. PMID:21617389

Organ-specific external dose coefficients and protective apron transmission factors for historical dose reconstruction for medical personnel.

PubMed

Simon, Steven L

2011-07-01

While radiation absorbed dose (Gy) to the skin or other organs is sometimes estimated for patients from diagnostic radiologic examinations or therapeutic procedures, rarely is occupationally-received radiation absorbed dose to individual organs/tissues estimated for medical personnel; e.g., radiologic technologists or radiologists. Generally, for medical personnel, equivalent or effective radiation doses are estimated for compliance purposes. In the very few cases when organ doses to medical personnel are reconstructed, the data is usually for the purpose of epidemiologic studies; e.g., a study of historical doses and risks to a cohort of about 110,000 radiologic technologists presently underway at the U.S. National Cancer Institute. While ICRP and ICRU have published organ-specific external dose conversion coefficients (DCCs) (i.e., absorbed dose to organs and tissues per unit air kerma and dose equivalent per unit air kerma), those factors have been published primarily for mono-energetic photons at selected energies. This presents two related problems for historical dose reconstruction, both of which are addressed here. It is necessary to derive conversion factor values for (1) continuous distributions of energy typical of diagnostic medical x-rays (bremsstrahlung radiation), and (2) energies of particular radioisotopes used in medical procedures, neither of which are presented in published tables. For derivation of DCCs for bremsstrahlung radiation, combinations of x-ray tube potentials and filtrations were derived for different time periods based on a review of relevant literature. Three peak tube potentials (70 kV, 80 kV, and 90 kV) with four different amounts of beam filtration were determined to be applicable for historic dose reconstruction. The probabilities of these machine settings were assigned to each of the four time periods (earlier than 1949, 1949-1954, 1955-1968, and after 1968). Continuous functions were fit to each set of discrete values of the ICRP/ICRU mono-energetic DCCs and the functions integrated over the air-kerma weighted photon fluence of the 12 defined x-ray spectra. The air kerma-weighted DCCs in this work were developed specifically for an irradiation geometry of anterior to posterior (AP) and for the following tissues: thyroid, breast, ovary, lens of eye, lung, colon, testes, heart, skin (anterior side only), red bone marrow (RBM), and brain. In addition, a series of functional relationships to predict DT Ka-1 values for RBM dependent on body mass index [BMI (kg m-2) ≡ weight per height] and average photon energy were derived from a published analysis. Factors to account for attenuation of radiation by protective lead aprons were also developed. Because lead protective aprons often worn by radiology personnel not only reduce the intensity of x-ray exposure but also appreciably harden the transmitted fluence of bremsstrahlung x-rays, DCCs were separately calculated for organs possibly protected by lead aprons by considering three cases: no apron, 0.25 mm Pb apron, and 0.5 mm Pb apron. For estimation of organ doses from conducting procedures with radioisotopes, continuous functions of the reported mono-energetic values were developed, and DCCs were derived by estimation of the function at relevant energies. By considering the temporal changes in primary exposure-related parameters (e.g., energy distribution), the derived DCCs and transmission factors presented here allow for more realistic historical dose reconstructions for medical personnel when monitoring badge readings are the primary data on which estimation of an individual's organ doses are based.

Effects of Bisphosphonates and Calcium plus Vitamin-D Supplements on Cognitive Function in Postmenopausal Osteoporosis§.

PubMed

Safer, Umut; Safer, Vildan Binay; Demir, Sibel Ozbudak; Yanikoglu, Inci

2016-01-01

Postmenopausal osteoporosis has been linked to accelerated cognitive decline; however, little is known about the effects of medical treatment on cognitive functions. In this prospective study, we evaluated the effects of bisphosphonate treatment and calcium plus vitamin D supplementation on cognitive functions in 45 women with postmenopausal osteoporosis who were started on medical treatment. The medications included alendronate, zoledronic acid, risedronate, or ibandronic acid along with a low or high dose of calcium plus vitamin D supplements. The cognitive function was assessed by the mini-mental state examination (MMSE) test. All subjects underwent bone mineral density (BMD) measurement via dual-energy X-ray absorptiometry at baseline and at study completion. The mean T-score improved significantly at 1 year, except for neck of the femur area. The mean MMSE score did not change significantly at 12 months (26.40 ± 2.07 vs. 26.48 ± 2.07; p = 0.513), with no difference among bisphosphonates combined with calcium plus vitamin D. Higher dose (1200 mg/800 U/day) of calcium plus vitamin D supplementation tended to have a greater improvement as compared with lower dose (600 mg/400 U/day) (Δ MMSE: 0.11 ± 0.72 vs. -0.14 ± 0.69). Cognitive functions in the women remained unaltered, whereas bone BMD T-scores were significantly improved at the 12(th) month after the administration of bisphosphonates and calcium plus vitamin D supplements. Higher doses of calcium plus vitamin D supplements were likely to have better cognitive effects as compared with lower doses.

Ir-192 HDR transit dose and radial dose function determination using alanine/EPR dosimetry

NASA Astrophysics Data System (ADS)

Guzmán Calcina, Carmen S.; de Almeida, Adelaide; Oliveira Rocha, José R.; Abrego, Felipe Chen; Baffa, Oswaldo

2005-03-01

Source positioning close to the tumour in high dose rate (HDR) brachytherapy is not instantaneous. An increment of dose will be delivered during the movement of the source in the trajectory to its static position. This increment is the transit dose, often not taken into account in brachytherapeutic treatment planning. The transit dose depends on the prescribed dose, number of treatment fractions, velocity and activity of the source. Combining all these factors, the transit dose can be 5% higher than the prescribed absorbed dose value (Sang-Hyun and Muller-Runkel, 1994 Phys. Med. Biol. 39 1181 8, Nath et al 1995 Med. Phys. 22 209 34). However, it cannot exceed this percentage (Nath et al 1995). In this work, we use the alanine-EPR (electron paramagnetic resonance) dosimetric system using analysis of the first derivative of the signal. The transit dose was evaluated for an HDR system and is consistent with that already presented for TLD dosimeters (Bastin et al 1993 Int. J. Radiat. Oncol. Biol. Phys. 26 695 702). Also using the same dosimetric system, the radial dose function, used to evaluate the geometric dose degradation around the source, was determined and its behaviour agrees better with those obtained by Monte Carlo simulations (Nath et al 1995, Williamson and Nath 1991 Med. Phys. 18 434 48, Ballester et al 1997 Med. Phys. 24 1221 8, Ballester et al 2001 Phys. Med. Biol. 46 N79 90) than with TLD measurements (Nath et al 1990 Med. Phys. 17 1032 40).

Ir-192 HDR transit dose and radial dose function determination using alanine/EPR dosimetry.

PubMed

Calcina, Carmen S Guzmán; de Almeida, Adelaide; Rocha, José R Oliveira; Abrego, Felipe Chen; Baffa, Oswaldo

2005-03-21

Source positioning close to the tumour in high dose rate (HDR) brachytherapy is not instantaneous. An increment of dose will be delivered during the movement of the source in the trajectory to its static position. This increment is the transit dose, often not taken into account in brachytherapeutic treatment planning. The transit dose depends on the prescribed dose, number of treatment fractions, velocity and activity of the source. Combining all these factors, the transit dose can be 5% higher than the prescribed absorbed dose value (Sang-Hyun and Muller-Runkel, 1994 Phys. Med. Biol. 39 1181-8, Nath et al 1995 Med. Phys. 22 209-34). However, it cannot exceed this percentage (Nath et al 1995). In this work, we use the alanine-EPR (electron paramagnetic resonance) dosimetric system using analysis of the first derivative of the signal. The transit dose was evaluated for an HDR system and is consistent with that already presented for TLD dosimeters (Bastin et al 1993 Int. J. Radiat. Oncol. Biol. Phys. 26 695-702). Also using the same dosimetric system, the radial dose function, used to evaluate the geometric dose degradation around the source, was determined and its behaviour agrees better with those obtained by Monte Carlo simulations (Nath et al 1995, Williamson and Nath 1991 Med. Phys. 18 434-48, Ballester et al 1997 Med. Phys. 24 1221-8, Ballester et al 2001 Phys. Med. Biol. 46 N79-90) than with TLD measurements (Nath et al 1990 Med. Phys. 17 1032-40).

A system to track skin dose for neuro-interventional cone-beam computed tomography (CBCT)

NASA Astrophysics Data System (ADS)

Vijayan, Sarath; Xiong, Zhenyu; Rudin, Stephen; Bednarek, Daniel R.

2016-03-01

The skin-dose tracking system (DTS) provides a color-coded illustration of the cumulative skin-dose distribution on a closely-matching 3D graphic of the patient during fluoroscopic interventions in real-time for immediate feedback to the interventionist. The skin-dose tracking utility of DTS has been extended to include cone-beam computed tomography (CBCT) of neurointerventions. While the DTS was developed to track the entrance skin dose including backscatter, a significant part of the dose in CBCT is contributed by exit primary radiation and scatter due to the many overlapping projections during the rotational scan. The variation of backscatter inside and outside the collimated beam was measured with radiochromic film and a curve was fit to obtain a scatter spread function that could be applied in the DTS. Likewise, the exit dose distribution was measured with radiochromic film for a single projection and a correction factor was determined as a function of path length through the head. Both of these sources of skin dose are added for every projection in the CBCT scan to obtain a total dose mapping over the patient graphic. Results show the backscatter to follow a sigmoidal falloff near the edge of the beam, extending outside the beam as far as 8 cm. The exit dose measured for a cylindrical CTDI phantom was nearly 10 % of the entrance peak skin dose for the central ray. The dose mapping performed by the DTS for a CBCT scan was compared to that measured with radiochromic film and a CTDI-head phantom with good agreement.

Carcinogenesis From Inhaled (PuO2)-Pu-239 in Beagles: Evidence for Radiation Homeostasis at Low Doses?

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

Fisher, Darrell R.; Weller, Richard E.

From the early 1970s to the late 1980s, Pacific Northwest National Laboratory conducted life-span studies in beagle dogs on the biological effects of inhaled plutonium (239PuO2, 238PuO2, and 239Pu[NO3]4) to help predict risks associated with accidental intakes in workers. Years later, the purpose of the present follow-up study is to reassess the dose-response relationship for lung cancer induction in the 239PuO2 dogs compared to controls, with particular focus on the dose-response at low lung doses. A 239PuO2 aerosol (2.3 μm AMAD, 1.9 μm GSD) was administered to six groups of 20 young (18-month old) beagle dogs (10 males and 10more » females) by inhalation at six different activity levels, as previously described in Laboratory reports. Control dogs were sham-exposed. In dose level 1, initial pulmonary lung depositions were 130 ± 48 Bq (3.5 ± 1.3 nCi), corresponding to 1 Bq g-1 lung tissue (0.029 ± 0.001 nCi g-1. Groups 2 through 6 received initial lung depositions (mean values) of 760, 2724, 10345, 37900, and 200000 Bq (22, 79, 300, 1100, and 5800 nCi) 239PuO2, respectively. For each dog, the absorbed dose to lungs was calculated from the initial lung burden and the final lung burden at time of death and lung mass, assuming a single, long-term retention function. Insoluble plutonium oxide exhibited long retention times in the lungs. Increased dose-dependent mortality due to lung cancer (bronchiolar-alveolar carcinoma, adenocarcinoma, epidermoid carcinoma) and radiation pneumonitis (highest exposures group) was observed in dogs exposed to 239PuO2. Calculated lung doses ranged from a few cGy in early-sacrificed dogs to 7764 cGy in dogs that experienced early deaths from radiation pneumonitis. Data were regrouped by lifetime lung dose and plotted as a function of lung tumor incidence. Lung tumor incidence in controls and zero-dose exposed dogs was 18% (5/28). However, no lung tumors were observed in 16 dogs with the lowest lung doses (8 to 22 cGy, mean 14.4 ± 7.6 cGy), and only one lung tumor was observed in 10 dogs with lung doses ranging from 27 to 48 cGy (mean 37.5 ± 10.9 cGy). By least-squares analysis, a quadratic function represented the overall dose-response (n = 137, r = 0.96) with no dose threshold. Reducing this function to three linear dose-response components, risk coefficients were calculated for each. The incidence of lung tumors at zero dose was significantly greater than the incidence at low dose (at the p ≤ 0.053 confidence level), suggesting a protective effect (radiation homeostasis) of alpha-particle radiation from 239PuO2. If a threshold for lung cancer incidence exists, it will be observed in the range 15 to 40 cGy.« less

Dose response effect of NutriTek on leukocyte functionality during a dexamethasone challenge in Holstein steer calves.

USDA-ARS?s Scientific Manuscript database

The objective of this study was to determine the dose response effects of supplementing NutriTek® on leukocyte functionality and ex vivo cytokine production during a dexamethasone (DEX) challenge. Holstein steers (125.1±8.16kg; N=32) were assigned to treatments including 0, 20, 40, or 60g/head/d of ...

Effects of Aerobic Exercise on Overweight Children's Cognitive Functioning: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Davis, Catherine L.; Tomporowski, Phillip D.; Boyle, Colleen A.; Waller, Jennifer L.; Miller, Patricia H.; Naglieri, Jack A.; Gregoski, Mathew

2007-01-01

The study tested the effect of aerobic exercise training on executive function in overweight children. Ninety-four sedentary, overweight but otherwise healthy children (mean age = 9.2 years, body mass index [greater than or equal to] 85th percentile) were randomized to a low-dose (20 min/day exercise), high-dose (40 min/day exercise), or control…

The acute effects of different spironolactone doses on cardiac function in streptozotocin-induced diabetic rats.

PubMed

Vranic, Aleksandra; Simovic, Stefan; Ristic, Petar; Nikolic, Tamara; Stojic, Isidora; Srejovic, Ivan; Zivkovic, Vladimir; Jakovljevic, Vladimir; Djuric, Dusan

2017-11-01

Currently, cardiovascular diseases are the leading cause of global mortality, while diabetes mellitus remains an important cause of cardiovascular morbidity. A recent study showed that patients with diabetes mellitus treated with mineralocorticoid receptor antagonists have improved coronary microvascular function, leading to improved diastolic dysfunction. In this study, we evaluated the influence of acute administration of spironolactone on myocardial function in rats with streptozotocin-induced diabetes mellitus, with special emphasis on cardiodynamic parameters in diabetic rat hearts. The present study was carried out on 40 adult male Wistar albino rats (8 weeks old). Rats were randomly divided into 4 groups (10 animals per group): healthy rats treated with 0.1 μmol/L of spironolactone, diabetic rats treated with 0.1 μmol/L of spironolactone, healthy rats treated with 3 μmol/L of spironolactone, and diabetic rats treated with 3 μmol/L of spironolactone. Different, dose-dependent, acute responses of spironolactone treatment on isolated, working diabetic and healthy rat heart were observed in our study. In healthy rats, better systolic function was achieved with higher spironolactone dose, while in diabetic rats, similar effects of low and high spironolactone dose were observed.

Thyroid hormones and thyroid disease in relation to perchlorate dose and residence near a superfund site.

PubMed

Gold, Ellen B; Blount, Benjamin C; O'Neill Rasor, Marianne; Lee, Jennifer S; Alwis, Udeni; Srivastav, Anup; Kim, Kyoungmi

2013-07-01

Perchlorate is a widely occurring contaminant, which can competitively inhibit iodide uptake and thus thyroid hormone production. The health effects of chronic low dose perchlorate exposure are largely unknown. In a community-based study, we compared thyroid function and disease in women with differing likelihoods of prior and current perchlorate exposure. Residential blocks were randomly selected from areas: (1) with potential perchlorate exposure via drinking water; (2) with potential exposure to environmental contaminants; and (3) neighboring but without such exposures. Eligibility included having lived in the area for ≥6 months and aged 20-50 years during 1988-1996 (during documented drinking water well contamination). We interviewed 814 women and collected blood samples (assayed for thyroid stimulating hormone and free thyroxine) from 431 interviewed women. Daily urine samples were assayed for perchlorate and iodide for 178 premenopausal women with blood samples. We performed multivariable regression analyses comparing thyroid function and disease by residential area and by urinary perchlorate dose adjusted for urinary iodide levels. Residential location and current perchlorate dose were not associated with thyroid function or disease. No persistent effect of perchlorate on thyroid function or disease was found several years after contaminated wells were capped.

Potential implications of dose and diet for the effects of cocoa flavanols on cardiometabolic function.

PubMed

Davison, Kade; Howe, Peter R C

2015-11-18

The metabolic syndrome is a pathological state whereby cardiovascular and metabolic dysfunction coexist and typically progress in a mutual feed-forward manner to further dysfunction and ultimately disease. The health and function of the vascular endothelium is integral in this phenomenon and thus represents a logical target for intervention. Consumption of foods high in cocoa flavanols has demonstrated a capacity to markedly improve endothelial function and key markers of the metabolic syndrome including blood pressure and insulin sensitivity. The typically high energy content of foods containing sufficient doses of cocoa flavanols has caused some reservations around its therapeutic use, but this is dependent upon the particulars of the food matrix used. Further to this, the food matrix appears to influence the dose response curve of cocoa flavanols, particularly on blood pressure, with dark chocolate appearing to be 8 times more effective in systolic blood pressure reduction than a cocoa powder drink for the equivalent dose of flavanol. Cocoa flavanol consumption conclusively demonstrates a positive impact on cardiometabolic function; however, more research is needed to understand how best to consume it to maximize the benefit while avoiding excessive fat and sugar consumption.

Evaluation of the Effect of Different Doses of Low Energy Shock Wave Therapy on the Erectile Function of Streptozotocin (STZ)-Induced Diabetic Rats

PubMed Central

Liu, Jing; Zhou, Feng; Li, Guang-Yong; Wang, Lin; Li, Hui-Xi; Bai, Guang-Yi; Guan, Rui-Li; Xu, Yong-De; Gao, Ze-Zhu; Tian, Wen-Jie; Xin, Zhong-Cheng

2013-01-01

To investigate the therapeutic effect of different doses of low energy shock wave therapy (LESWT) on the erectile dysfunction (ED) in streptozotocin (STZ) induced diabetic rats. SD rats (n = 75) were randomly divided into 5 groups (normal control, diabetic control, 3 different dose LESWT treated diabetic groups). Diabetic rats were induced by intra-peritoneal injection of STZ (60 mg/kg) and rats with fasting blood glucose ≥ 300 mg/dL were selected as diabetic models. Twelve weeks later, different doses of LESWT (100, 200 and 300 shocks each time) treatment on penises were used to treat ED (7.33 MPa, 2 shocks/s) three times a week for two weeks. The erectile function was evaluated by intracavernous pressure (ICP) after 1 week washout period. Then the penises were harvested for histological study. The results showed LESWT could significantly improve the erectile function of diabetic rats, increase smooth muscle and endothelial contents, up-regulate the expression of α-SMA, vWF, nNOS and VEGF, and down- regulate the expression of RAGE in corpus cavernosum. The therapeutic effect might relate to treatment dose positively, and the maximal therapeutic effect was noted in the LESWT300 group. Consequently, 300 shocks each time might be the ideal LESWT dose for diabetic ED treatment. PMID:23698784

Evaluation of the effect of different doses of low energy shock wave therapy on the erectile function of streptozotocin (STZ)-induced diabetic rats.

PubMed

Liu, Jing; Zhou, Feng; Li, Guang-Yong; Wang, Lin; Li, Hui-Xi; Bai, Guang-Yi; Guan, Rui-Li; Xu, Yong-De; Gao, Ze-Zhu; Tian, Wen-Jie; Xin, Zhong-Cheng

2013-05-21

To investigate the therapeutic effect of different doses of low energy shock wave therapy (LESWT) on the erectile dysfunction (ED) in streptozotocin (STZ) induced diabetic rats. SD rats (n = 75) were randomly divided into 5 groups (normal control, diabetic control, 3 different dose LESWT treated diabetic groups). Diabetic rats were induced by intra-peritoneal injection of STZ (60 mg/kg) and rats with fasting blood glucose ≥ 300 mg/dL were selected as diabetic models. Twelve weeks later, different doses of LESWT (100, 200 and 300 shocks each time) treatment on penises were used to treat ED (7.33 MPa, 2 shocks/s) three times a week for two weeks. The erectile function was evaluated by intracavernous pressure (ICP) after 1 week washout period. Then the penises were harvested for histological study. The results showed LESWT could significantly improve the erectile function of diabetic rats, increase smooth muscle and endothelial contents, up-regulate the expression of α-SMA, vWF, nNOS and VEGF, and down- regulate the expression of RAGE in corpus cavernosum. The therapeutic effect might relate to treatment dose positively, and the maximal therapeutic effect was noted in the LESWT300 group. Consequently, 300 shocks each time might be the ideal LESWT dose for diabetic ED treatment.

Dose-response study of caffeine effects on cerebral functional activity with a specific focus on dependence.

PubMed

Nehlig, A; Boyet, S

2000-03-06

Caffeine is a behavioral stimulant consumed on a worldwide basis. The question of whether caffeine is addictive has been debated for over a decade. Caffeine acts as a mild positive reinforcer but is not consistently self-administered in humans or animals. With [14C]2-deoxyglucose autoradiography, we studied the effects of increasing doses of caffeine on cerebral glucose utilization in rats. At 1 mg/kg, caffeine activated the caudate nucleus mediating locomotion, and the raphe nuclei and locus coeruleus involved with mood and sleep. After 2.5 and 5 mg/kg caffeine, metabolic activation spread to other components of the nigrostriatal dopaminergic system, the thalamus, ventral tegmental area and amygdala. The functional activation of the shell of the nucleus accumbens, an area involved in addiction and reward, was only induced by the highest dose of caffeine, 10 mg/kg. At this dose, the activation of the shell of the nucleus accumbens occurred together with that of the core of the nucleus accumbens and of most other brain regions. These data correlate well with the known sensitivity of locomotion, mood and sleep to low doses of caffeine. They also show that low doses of caffeine which reflect the usual human level of consumption fail to activate reward circuits in the brain and thus provide functional evidence of the very low addictive potential of caffeine.

A new method for calculation of the chlorine demand of natural and treated waters.

PubMed

Warton, Ben; Heitz, Anna; Joll, Cynthia; Kagi, Robert

2006-08-01

Conventional methods of calculating chlorine demand are dose dependent, making intercomparison of samples difficult, especially in cases where the samples contain substantially different concentrations of dissolved organic carbon (DOC), or other chlorine-consuming species. Using the method presented here, the values obtained for chlorine demand are normalised, allowing valid comparison of chlorine demand between samples, independent of the chlorine dose. Since the method is not dose dependent, samples with substantially differing water quality characteristics can be reliably compared. In our method, we dosed separate aliquots of a water sample with different chlorine concentrations, and periodically measured the residual chlorine concentrations in these subsamples. The chlorine decay data obtained in this way were then fitted to first-order exponential decay functions, corresponding to short-term demand (0-4h) and long-term demand (4-168 h). From the derived decay functions, the residual concentrations at a given time within the experimental time window were calculated and plotted against the corresponding initial chlorine concentrations, giving a linear relationship. From this linear function, it was then possible to determine the residual chlorine concentration for any initial concentration (i.e. dose). Thus, using this method, the initial chlorine dose required to give any residual chlorine concentration can be calculated for any time within the experimental time window, from a single set of experimental data.

Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch-2-Year Follow-Up.

PubMed

Lenders, Malte; Canaan-Kühl, Sima; Krämer, Johannes; Duning, Thomas; Reiermann, Stefanie; Sommer, Claudia; Stypmann, Jörg; Blaschke, Daniela; Üçeyler, Nurcan; Hense, Hans-Werner; Brand, Stefan-Martin; Wanner, Christoph; Weidemann, Frank; Brand, Eva

2016-03-01

Because of the shortage of agalsidase-β supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-α. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-α. A total of 89 adult patients with Fabry disease who had received agalsidase-β (1.0 mg/kg body wt) for >1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=24), to receive a reduced dose of 0.3-0.5 mg/kg and a subsequent switch to 0.2 mg/kg agalsidase-α (dose-reduction-switch group, n=28), or to directly switch to 0.2 mg/kg agalsidase-α (switch group, n=37) and were followed-up for 2 years. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD), changes in cardiac and renal function, Fabry-related symptoms (pain, hypohidrosis, diarrhea), and disease severity scores. Determination of renal function by creatinine and cystatin C-based eGFR revealed decreasing eGFRs in the dose-reduction-switch group and the switch group. The Mainz Severity Score Index increased significantly in these two groups (P=0.02 and P<0.001, respectively), and higher frequencies of gastrointestinal pain occurred during follow-up. In conclusion, after 2 years of observation, all groups showed a stable clinical disease course with respect to serious clinical events. However, patients under agalsidase-β dose-reduction and switch or a direct switch to agalsidase-α showed a decline of renal function independent of the eGFR formula used. Copyright © 2016 by the American Society of Nephrology.

Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch–2-Year Follow-Up

PubMed Central

Lenders, Malte; Canaan-Kühl, Sima; Krämer, Johannes; Duning, Thomas; Reiermann, Stefanie; Sommer, Claudia; Stypmann, Jörg; Blaschke, Daniela; Üçeyler, Nurcan; Hense, Hans-Werner; Brand, Stefan-Martin; Wanner, Christoph; Weidemann, Frank

2016-01-01

Because of the shortage of agalsidase-β supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-α. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-α. A total of 89 adult patients with Fabry disease who had received agalsidase-β (1.0 mg/kg body wt) for >1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=24), to receive a reduced dose of 0.3–0.5 mg/kg and a subsequent switch to 0.2 mg/kg agalsidase-α (dose-reduction-switch group, n=28), or to directly switch to 0.2 mg/kg agalsidase-α (switch group, n=37) and were followed-up for 2 years. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD), changes in cardiac and renal function, Fabry-related symptoms (pain, hypohidrosis, diarrhea), and disease severity scores. Determination of renal function by creatinine and cystatin C–based eGFR revealed decreasing eGFRs in the dose-reduction-switch group and the switch group. The Mainz Severity Score Index increased significantly in these two groups (P=0.02 and P<0.001, respectively), and higher frequencies of gastrointestinal pain occurred during follow-up. In conclusion, after 2 years of observation, all groups showed a stable clinical disease course with respect to serious clinical events. However, patients under agalsidase-β dose-reduction and switch or a direct switch to agalsidase-α showed a decline of renal function independent of the eGFR formula used. PMID:26185201

Modelling of the optimal bupivacaine dose for spinal anaesthesia in ambulatory surgery based on data from systematic review.

PubMed

Lemoine, Adrien; Mazoit, Jean X; Bonnet, Francis

2016-11-01

Spinal bupivacaine is used for day-case surgery but the appropriate dose that guarantees hospital discharge is unknown. We sought to determine the spinal bupivacaine dose that prevents delayed hospital discharge in ambulatory surgery. Systematic review of clinical trials. Comprehensive search in electronic databases of studies published between 1996 and 2014 reporting the use of spinal bupivacaine in ambulatory patients. Additional articles were retrieved through hyperlinks and by manually searching reference lists in original articles, review articles and correspondence published in English and French. Data were used to calculate, motor block duration and discharge time, an estimated maximal effect (Emax: maximum theoretical time of motor block) and the effective dose to obtain half of Emax (D50) with 95% confidence intervals (CIs). A simulation was performed to determine the dose corresponding to a time to recovery of 300 min for motor function, and 360 min for discharge, in 95% of the patients. In total, 23 studies (1062 patients) were included for analysis of the time to recovery of motor function, and 12 studies (618 patients) for the time to hospital discharge. The Emax for recovery of motor function was 268 min [95% CI (189 to 433 min)] and the D50 was 3.9 mg [95% CI (2.3 to 6.2 mg)]. A 7.5-mg dose of bupivacaine enables resolution of motor block and ambulation within 300 min in 95% of the patients. A 5-mg dose or less was associated with an unacceptable failure rate. Ambulatory surgery is possible under spinal anaesthesia with bupivacaine although the dose range that ensures reliable anaesthesia with duration short enough to guarantee ambulatory management is narrow.

Association of High-Dose Ibuprofen Use, Lung Function Decline, and Long-Term Survival in Children with Cystic Fibrosis.

PubMed

Konstan, Michael W; VanDevanter, Donald R; Sawicki, Gregory S; Pasta, David J; Foreman, Aimee J; Neiman, Evgueni A; Morgan, Wayne J

2018-04-01

Cystic fibrosis deaths result primarily from lung function loss, so chronic respiratory therapies, intended to preserve lung function, are cornerstones of cystic fibrosis care. Although treatment-associated reduction in rate of lung function loss should ultimately improve cystic fibrosis survival, no such relationship has been described for any chronic cystic fibrosis therapy. In part, this is because the ages of most rapid lung function decline-early adolescence-precede the median age of cystic fibrosis deaths by more than a decade. To study associations of high-dose ibuprofen treatment with the rate of forced expiratory volume in 1 second decline and mortality among children followed in the Epidemiologic Study of Cystic Fibrosis and subsequently in the U.S. Cystic Fibrosis Foundation Patient Registry. We performed a matched cohort study using data from Epidemiologic Study of Cystic Fibrosis. Exposure was defined as high-dose ibuprofen use reported at ≥80% of encounters over 2 years. Unexposed children were matched to exposed children 5:1 using propensity scores on the basis of demographic, clinical, and treatment covariates. The rate of decline of percent predicted forced expiratory volume in 1 second during the 2-year follow-up period was estimated by mixed-effects modeling with random slopes and intercepts. Survival over 16 follow-up years in the U.S. Cystic Fibrosis Foundation Patient Registry was compared between treatment groups by using proportional hazards modeling controlling for matching and covariates. We included 775 high-dose ibuprofen users and 3,665 nonusers who were well matched on demographic, clinical, and treatment variables. High-dose ibuprofen users declined on average 1.10 percent predicted forced expiratory volume in 1 second/yr (95% confidence interval; 0.51, 1.69) during the 2-year treatment period, whereas nonusers declined at a rate of 1.76% percent predicted forced expiratory volume in 1 second/yr (95% confidence interval; 1.48, 2.04) during the corresponding 2-year period, a 37.5% slower decline among users compared with nonusers (95% confidence interval; 0.4%, 71.3%; P = 0.046). The users had better subsequent survival (P < 0.001): the unadjusted and adjusted hazard ratios for mortality (high-dose ibuprofen/non-high-dose ibuprofen) (95% confidence interval) were 0.75 (0.64, 0.87) and 0.82 (0.69, 0.96). In a propensity-score matched cohort study of children with cystic fibrosis, we observed an association between high-dose ibuprofen use and both slower lung function decline and improved long-term survival. These results are consistent with the hypothesis that treatment-associated reduction of lung function decline in children with cystic fibrosis leads to improved survival.

Extension of applicable neutron energy of DARWIN up to 1 GeV.

PubMed

Satoh, D; Sato, T; Endo, A; Matsufuji, N; Takada, M

2007-01-01

The radiation-dose monitor, DARWIN, needs a set of response functions of the liquid organic scintillator to assess a neutron dose. SCINFUL-QMD is a Monte Carlo based computer code to evaluate the response functions. In order to improve the accuracy of the code, a new light-output function based on the experimental data was developed for the production and transport of protons deuterons, tritons, (3)He nuclei and alpha particles, and incorporated into the code. The applicable energy of DARWIN was extended to 1 GeV using the response functions calculated by the modified SCINFUL-QMD code.

A Path Model for Evaluating Dosing Parameters for Children With Cerebral Palsy

PubMed Central

Christy, Jennifer B.; Heathcock, Jill C.; Kolobe, Thubi H.A.

2014-01-01

Dosing of pediatric rehabilitation services for children with cerebral palsy (CP) has been identified as a national priority. Establishing dosing parameters for pediatric physical therapy interventions is critical for informing clinical decision making, health policy, and guidelines for reimbursement. The purpose of this perspective article is to describe a path model for evaluating dosing parameters of interventions for children with CP. The model is intended for dose-related and effectiveness studies of pediatric physical therapy interventions. The premise of the model is: Intervention type (focus on body structures, activity, or the environment) acts on a child first through the family, then through the dose (frequency, intensity, time), to yield structural and behavioral changes. As a result, these changes are linked to improvements in functional independence. Community factors affect dose as well as functional independence (performance and capacity), influencing the relationships between type of intervention and intervention responses. The constructs of family characteristics; child characteristics (eg, age, level of severity, comorbidities, readiness to change, preferences); plastic changes in bone, muscle, and brain; motor skill acquisition; and community access warrant consideration from researchers who are designing intervention studies. Multiple knowledge gaps are identified, and a framework is provided for conceptualizing dosing parameters for children with CP. PMID:24231231

Effect of processor temperature on film dosimetry

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

Srivastava, Shiv P.; Das, Indra J., E-mail: idas@iupui.edu

2012-07-01

Optical density (OD) of a radiographic film plays an important role in radiation dosimetry, which depends on various parameters, including beam energy, depth, field size, film batch, dose, dose rate, air film interface, postexposure processing time, and temperature of the processor. Most of these parameters have been studied for Kodak XV and extended dose range (EDR) films used in radiation oncology. There is very limited information on processor temperature, which is investigated in this study. Multiple XV and EDR films were exposed in the reference condition (d{sub max.}, 10 Multiplication-Sign 10 cm{sup 2}, 100 cm) to a given dose. Anmore » automatic film processor (X-Omat 5000) was used for processing films. The temperature of the processor was adjusted manually with increasing temperature. At each temperature, a set of films was processed to evaluate OD at a given dose. For both films, OD is a linear function of processor temperature in the range of 29.4-40.6 Degree-Sign C (85-105 Degree-Sign F) for various dose ranges. The changes in processor temperature are directly related to the dose by a quadratic function. A simple linear equation is provided for the changes in OD vs. processor temperature, which could be used for correcting dose in radiation dosimetry when film is used.« less

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

Wyrobek, A. J.; Manohar, C. F.; Nelson, D. O.

We investigated the low dose dependency of the transcriptional response of human cells to characterize the shape and biological functions associated with the dose response curve and to identify common and conserved functions of low dose expressed genes across cells and tissues. Human lymphoblastoid (HL) cells from two unrelated individuals were exposed to graded doses of radiation spanning the range of 1-10 cGy were analyzed by transcriptome profiling, qPCR and bioinformatics, in comparison to sham irradiated samples. A set of {approx}80 genes showed consistent responses in both cell lines; these genes were associated with homeostasis mechanisms (e.g., membrane signaling, moleculemore » transport), subcellular locations (e.g., Golgi, and endoplasmic reticulum), and involved diverse signal transduction pathways. The majority of radiation-modulated genes had plateau-like responses across 1-10 cGy, some with suggestive evidence that transcription was modulated at doses below 1 cGy. MYC, FOS and TP53 were the major network nodes of the low-dose response in HL cells. Comparison our low dose expression findings in HL cells with those of prior studies in mouse brain after whole body exposure, in human keratinocyte cultures, and in endothelial cells cultures, indicates that certain components of the low dose radiation response are broadly conserved across cell types and tissues, independent of proliferation status.« less

Effect of Jiangzhi tablet on gastrointestinal propulsive function in mice

NASA Astrophysics Data System (ADS)

Wang, Xiangrong; Geng, Xiuli; Zhao, Jingsheng; Fan, Lili; Zhang, Zhengchen

2018-04-01

This paper aims to study the effect of lipid-lowering tablets on gastric emptying and small intestinal propulsion in mice. Mice were randomly divided into control group, Digestant Pill group, Jiangzhi tablet group, middle dose and small dose, the mice gastric emptying phenolsulfonphthalein, gastric residual rate of phenol red indicator to evaluate the gastric emptying rate, residual rate of detection in mouse stomach; small intestine propulsion and selection of carbon ink as the experimental index. Effects were observed to promote the function of normal mice gastric emptying and intestine. The gastric emptying and small intestinal motor function of normal mice were all promoted by each administration group, and the effect was most obvious in small dose group. The effect of reducing blood lipid on gastrointestinal motility of mice ware obviously enhanced.

Using Quality of Life Measures in a Phase I Clinical Trial of Noni in Patients with Advanced Cancer to Select a Phase II Dose

PubMed Central

Issell, Brian F.; Gotay, Carolyn C.; Pagano, Ian; Franke, A. Adrian

2015-01-01

Purpose We conducted a Phase I study of noni in patients with advanced cancer. Quality of life measures were examined as an alternate way to select a Phase II dose of this popular dietary supplement. Patients and Methods Starting at two capsules twice daily (2 grams), the dose suggested for marketed products, dose levels were escalated by 2 grams daily in cohorts of at least five patients until a maximum tolerated dose was found. Patients completed QLQ-C30 Quality of Life, and the Brief Fatigue Inventory (BFI), questionnaires at baseline and at four week intervals. Scopoletin was measured in blood and urine collected at baseline and at approximately four week intervals. Results Fifty-one patients were enrolled at seven dose levels. Seven capsules four times daily (14 grams) was the maximum tolerated dose. No dose limiting toxicity was found but four of eight patients at this level withdrew from the study due to the challenges of ingesting so many capsules. There was a dose response for self reported physical functioning and the control of pain and fatigue. Patients taking four capsules four times daily experienced less fatigue than patients taking lower or higher doses. A relationship between noni dose and blood and urinary scopoletin concentrations was found. Conclusion Measuring quality of life to determine a dose for subsequent Phase II testing is feasible. A noni dose of four capsules four times daily (8 grams) is recommended for Phase II testing where controlling fatigue and maintaining physical function is the efficacy of interest. Scopoletin is a measurable noni ingredient for pharmacokinetic studies in patients with cancer. PMID:22435516

Acute ethanol ingestion produces dose-dependent effects on motor behavior in the honey bee (Apis mellifera)

PubMed Central

Maze, Ian S.; Wright, Geraldine A.; Mustard, Julie A.

2006-01-01

Ethanol consumption produces characteristic behavioral states in animals that include sedation, disorientation, and disruption of motor function. Using individual honey bees, we assessed the effects of ethanol ingestion on motor function via continuous observations of their behavior. Consumption of 1 M sucrose solutions containing a range of ethanol doses lead to hemolymph ethanol levels of approximately 40 to 100 mM. Using ethanol doses in this range, we observed time and dose-dependent effects of ethanol on the percent of time our subjects spent walking, stopped, or upside down, and on the duration and frequency of bouts of behavior. The effects on grooming and flying behavior were more complex. Behavioral recovery from ethanol treatment was both time and ethanol dose dependent, occurring between 12 and 24 hr post-ingestion for low doses and at 24 to 48 hours for higher doses. Furthermore, the amount of ethanol measured in honey bee hemolymph appeared to correlate with recovery. We predict that the honey bee will prove to be an excellent model system for studying the influence of ethanol on the neural mechanisms underlying behavior. PMID:17070538

Space dosimetry with the application of a 3D silicon detector telescope: response function and inverse algorithm.

PubMed

Pázmándi, Tamás; Deme, Sándor; Láng, Edit

2006-01-01

One of the many risks of long-duration space flights is the excessive exposure to cosmic radiation, which has great importance particularly during solar flares and higher sun activity. Monitoring of the cosmic radiation on board space vehicles is carried out on the basis of wide international co-operation. Since space radiation consists mainly of charged heavy particles (protons, alpha and heavier particles), the equivalent dose differs significantly from the absorbed dose. A radiation weighting factor (w(R)) is used to convert absorbed dose (Gy) to equivalent dose (Sv). w(R) is a function of the linear energy transfer of the radiation. Recently used equipment is suitable for measuring certain radiation field parameters changing in space and over time, so a combination of different measurements and calculations is required to characterise the radiation field in terms of dose equivalent. The objectives of this project are to develop and manufacture a three-axis silicon detector telescope, called Tritel, and to develop software for data evaluation of the measured energy deposition spectra. The device will be able to determine absorbed dose and dose equivalent of the space radiation.

Different Sequences of Fractionated Low-Dose Proton and Single Iron-Radiation-Induced Divergent Biological Responses in the Heart.

PubMed

Sasi, Sharath P; Yan, Xinhua; Zuriaga-Herrero, Marian; Gee, Hannah; Lee, Juyong; Mehrzad, Raman; Song, Jin; Onufrak, Jillian; Morgan, James; Enderling, Heiko; Walsh, Kenneth; Kishore, Raj; Goukassian, David A

2017-08-01

Deep-space travel presents risks of exposure to ionizing radiation composed of a spectrum of low-fluence protons ( 1 H) and high-charge and energy (HZE) iron nuclei (e.g., 56 Fe). When exposed to galactic cosmic rays, each cell in the body may be traversed by 1 H every 3-4 days and HZE nuclei every 3-4 months. The effects of low-dose sequential fractionated 1 H or HZE on the heart are unknown. In this animal model of simulated ionizing radiation, middle-aged (8-9 months old) male C57BL/6NT mice were exposed to radiation as follows: group 1, nonirradiated controls; group 2, three fractionated doses of 17 cGy 1 H every other day ( 1 H × 3); group 3, three fractionated doses of 17 cGy 1 H every other day followed by a single low dose of 15 cGy 56 Fe two days after the final 1 H dose ( 1 H × 3 + 56 Fe); and group 4, a single low dose of 15 cGy 56 Fe followed (after 2 days) by three fractionated doses of 17 cGy 1 H every other day ( 56 Fe + 1 H × 3). A subgroup of mice from each group underwent myocardial infarction (MI) surgery at 28 days postirradiation. Cardiac structure and function were assessed in all animals at days 7, 14 and 28 after MI surgery was performed. Compared to the control animals, the treatments that groups 2 and 3 received did not induce negative effects on cardiac function or structure. However, compared to all other groups, the animals in group 4, showed depressed left ventricular (LV) functions at 1 month with concomitant enhancement in cardiac fibrosis and induction of cardiac hypertrophy signaling at 3 months. In the irradiated and MI surgery groups compared to the control group, the treatments received by groups 2 and 4 did not induce negative effects at 1 month postirradiation and MI surgery. However, in group 3 after MI surgery, there was a 24% increase in mortality, significant decreases in LV function and a 35% increase in post-infarction size. These changes were associated with significant decreases in the angiogenic and cell survival signaling pathways. These data suggest that fractionated doses of radiation induces cellular and molecular changes that result in depressed heart functions both under basal conditions and particularly after myocardial infarction.

Long-term accumulation of uranium in bones of Wistar rats as a function of intake dosages.

PubMed

Arruda-Neto, J D T; Guevara, M V Manso; Nogueira, G P; Saiki, M; Cestari, A C; Shtejer, K; Deppman, A; Pereira Filho, J W; Garcia, F; Geraldo, L P; Gouveia, A N; Guzmán, F; Mesa, J; Rodriguez, O; Semmler, R; Vanin, V R

2004-01-01

Groups of Wistar rats were fed with ration doped with uranyl nitrate at concentration A ranging from 0.5 to 100 ppm, starting after the weaning period and lasting until the postpuberty period when the animals were sacrificed. Uranium in the ashes of bones was determined by neutron activation analysis. It was found that the uranium concentration in the bones, as a function of A, exhibits a change in its slope at approximately 20 ppm-a probable consequence of the malfunctioning of kidneys. The uranium transfer coefficient was obtained and an analytical expression was fitted into the data, thus allowing extrapolation down to low doses. Internal and localized doses were calculated. Absorbed doses exceeded the critical dose, even for the lowest uranium dosage.

SU-D-202-01: Functional Lung Avoidance and Response-Adaptive Escalation (FLARE) RT: Feasibility of a Precision Radiation Oncology Strategy

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

Bowen, S; Lee, E; Miyaoka, R

Purpose: NSCLC patient RT is planned without consideration of spatial heterogeneity in lung function or tumor response, which may have contributed to failed uniform dose escalation in a randomized trial. The feasibility of functional lung avoidance and response-adaptive escalation (FLARE) RT to reduce dose to [{sup 99m}Tc]MAA-SPECT/CT perfused lung while redistributing 74Gy within [{sup 18}F]FDG-PET/CT biological target volumes was assessed. Methods: Eight Stage IIB–IIIB NSCLC patients underwent FDG-PET/CT and MAA-SPECT/CT treatment planning scans. Perfused lung objectives were derived from scatter/collimator/attenuation-corrected MAA-SPECT uptake relative to ITV-subtracted lung to maintain <20Gy mean lung dose (MLD). Prescriptions included 60Gy to PTV and concomitantmore » boost of 74Gy mean to biological target volumes (BTV=GTV+PET margin) scaled to each BTV voxel by relative FDG-PET SUV. Dose-painting-by-numbers prescriptions were integrated into commercial TPS via previously reported ROI discretization. Dose constraints for lung, heart, cord, and esophagus were defined. FLARE RT plans were optimized with VMAT, proton pencil beam scanning (PBS) with 3%-3mm robust optimization, and combination PBS (avoidance) plus VMAT (escalation). Dosimetric differences were evaluated by Friedman non-parametric paired test with multiple sampling correction. Results: PTV and normal tissue objectives were not violated in 24 FLARE RT plans. Population median of mean BTV dose was 73.7Gy (68.5–75.5Gy), mean FDG-PET peak dose was 89.7Gy (73.5–103Gy), MLD was 12.3Gy (7.5–19.6Gy), and perfused MLD was 4.8Gy (0.9–12.1Gy). VMAT achieved higher dose to the FDG-PET peak subvolume (p=0.01), while PBS delivered lower dose to lung (p<0.001). Voxelwise linear correlation between BTV dose and FDG-PET uptake was higher for VMAT (R=0.93) and PBS+VMAT (R=0.94) compared to PBS alone (R=0.89). Conclusion: FLARE RT is feasible with VMAT and PBS. A combination of PBS for functional lung avoidance and VMAT for FDG-PET dose escalation balances target/normal tissue objective tradeoffs. These results support future testing of FLARE RT safety and efficacy within a precision radiation oncology trial. This work was supported by a Research Scholar grant from the Radiological Society of North American Research & Education Foundation.« less

TU-H-207A-08: Estimating Radiation Dose From Low-Dose Lung Cancer Screening CT Exams Using Tube Current Modulation

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

Hardy, A; Bostani, M; McMillan, K

Purpose: The purpose of this work is to estimate effective and lung doses from a low-dose lung cancer screening CT protocol using Tube Current Modulation (TCM) across patient models of different sizes. Methods: Monte Carlo simulation methods were used to estimate effective and lung doses from a low-dose lung cancer screening protocol for a 64-slice CT (Sensation 64, Siemens Healthcare) that used TCM. Scanning parameters were from the AAPM protocols. Ten GSF voxelized patient models were used and had all radiosensitive organs identified to facilitate estimating both organ and effective doses. Predicted TCM schemes for each patient model were generatedmore » using a validated method wherein tissue attenuation characteristics and scanner limitations were used to determine the TCM output as a function of table position and source angle. The water equivalent diameter (WED) was determined by estimating the attenuation at the center of the scan volume for each patient model. Monte Carlo simulations were performed using the unique TCM scheme for each patient model. Lung doses were tallied and effective doses were estimated using ICRP 103 tissue weighting factors. Effective and lung dose values were normalized by scanspecific 32 cm CTDIvol values based upon the average tube current across the entire simulated scan. Absolute and normalized doses were reported as a function of WED for each patient. Results: For all ten patients modeled, the effective dose using TCM protocols was below 1.5 mSv. Smaller sized patient models experienced lower absolute doses compared to larger sized patients. Normalized effective and lung doses showed some dependence on patient size (R2 = 0.77 and 0.78, respectively). Conclusion: Effective doses for a low-dose lung screening protocol using TCM were below 1.5 mSv for all patient models used in this study. Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical Systems; Consultant, Samsung Electronics.« less

Early brain response to low-dose radiation exposure involves molecular networks and pathways associated with cognitive functions, advanced aging and Alzheimer's disease.

PubMed

Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J

2009-01-01

Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy and environmental nuclear contamination as well as for Earth-orbit and space missions. Analyses of transcriptome profiles of mouse brain tissue after whole-body irradiation showed that low-dose exposures (10 cGy) induced genes not affected by high-dose radiation (2 Gy) and that low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues and pathways that were specific for brain tissue. Low-dose genes clustered into a saturated network (P < 10(-53)) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified nine neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose irradiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down-regulated in normal human aging and Alzheimer's disease.

Dependency of EBT2 film calibration curve on postirradiation time

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

Chang, Liyun, E-mail: liyunc@isu.edu.tw; Ding, Hueisch-Jy; Ho, Sheng-Yow

2014-02-15

Purpose: The Ashland Inc. product EBT2 film model is a widely used quality assurance tool, especially for verification of 2-dimensional dose distributions. In general, the calibration film and the dose measurement film are irradiated, scanned, and calibrated at the same postirradiation time (PIT), 1-2 days after the films are irradiated. However, for a busy clinic or in some special situations, the PIT for the dose measurement film may be different from that of the calibration film. In this case, the measured dose will be incorrect. This paper proposed a film calibration method that includes the effect of PIT. Methods: Themore » dose versus film optical density was fitted to a power function with three parameters. One of these parameters was PIT dependent, while the other two were found to be almost constant with a standard deviation of the mean less than 4%. The PIT-dependent parameter was fitted to another power function of PIT. The EBT2 film model was calibrated using the PDD method with 14 different PITs ranging from 1 h to 2 months. Ten of the fourteen PITs were used for finding the fitting parameters, and the other four were used for testing the model. Results: The verification test shows that the differences between the delivered doses and the film doses calculated with this modeling were mainly within 2% for delivered doses above 60 cGy, and the total uncertainties were generally under 5%. The errors and total uncertainties of film dose calculation were independent of the PIT using the proposed calibration procedure. However, the fitting uncertainty increased with decreasing dose or PIT, but stayed below 1.3% for this study. Conclusions: The EBT2 film dose can be modeled as a function of PIT. For the ease of routine calibration, five PITs were suggested to be used. It is recommended that two PITs be located in the fast developing period (1∼6 h), one in 1 ∼ 2 days, one around a week, and one around a month.« less

Low-dose controlled release of mTOR inhibitors maintains T cell plasticity and promotes central memory T cells.

PubMed

Gammon, Joshua M; Gosselin, Emily A; Tostanoski, Lisa H; Chiu, Yu-Chieh; Zeng, Xiangbin; Zeng, Qin; Jewell, Christopher M

2017-10-10

An important goal for improving vaccine and immunotherapy technologies is the ability to provide further control over the specific phenotypes of T cells arising from these agents. Along these lines, frequent administration of rapamycin (Rapa), a small molecule inhibitor of the mammalian target of rapamycin (mTOR), exhibits a striking ability to polarize T cells toward central memory phenotypes (T CM ), or to suppress immune function, depending on the concentrations and other signals present during administration. T CM exhibit greater plasticity and proliferative capacity than effector memory T cells (T EFF ) and, therefore, polarizing vaccine-induced T cells toward T CM is an intriguing strategy to enhance T cell expansion and function against pathogens or tumors. Here we combined biodegradable microparticles encapsulating Rapa (Rapa MPs) with vaccines composed of soluble peptide antigens and molecular adjuvants to test if this approach allows polarization of differentiating T cells toward T CM . We show Rapa MPs modulate DC function, enhancing secretion of inflammatory cytokines at very low doses, and suppressing function at high doses. While Rapa MP treatment reduced - but did not stop - T cell proliferation in both CD4 + and CD8 + transgenic T cell co-cultures, the expanding CD8 + T cells differentiated to higher frequencies of T CM at low doses of MP Rapa MPs. Lastly, we show in mice that local delivery of Rapa MPs to lymph nodes during vaccination either suppresses or enhances T cell function in response to melanoma antigens, depending on the dose of drug in the depots. In particular, at low Rapa MP doses, vaccines increased antigen-specific T CM , resulting in enhanced T cell expansion measured during subsequent booster injections over at least 100days. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Magnetic field influences on the lateral dose response functions of photon-beam detectors: MC study of wall-less water-filled detectors with various densities.

PubMed

Looe, Hui Khee; Delfs, Björn; Poppinga, Daniela; Harder, Dietrich; Poppe, Björn

2017-06-21

The distortion of detector reading profiles across photon beams in the presence of magnetic fields is a developing subject of clinical photon-beam dosimetry. The underlying modification by the Lorentz force of a detector's lateral dose response function-the convolution kernel transforming the true cross-beam dose profile in water into the detector reading profile-is here studied for the first time. The three basic convolution kernels, the photon fluence response function, the dose deposition kernel, and the lateral dose response function, of wall-less cylindrical detectors filled with water of low, normal and enhanced density are shown by Monte Carlo simulation to be distorted in the prevailing direction of the Lorentz force. The asymmetric shape changes of these convolution kernels in a water medium and in magnetic fields of up to 1.5 T are confined to the lower millimetre range, and they depend on the photon beam quality, the magnetic flux density and the detector's density. The impact of this distortion on detector reading profiles is demonstrated using a narrow photon beam profile. For clinical applications it appears as favourable that the magnetic flux density dependent distortion of the lateral dose response function, as far as secondary electron transport is concerned, vanishes in the case of water-equivalent detectors of normal water density. By means of secondary electron history backtracing, the spatial distribution of the photon interactions giving rise either directly to secondary electrons or to scattered photons further downstream producing secondary electrons which contribute to the detector's signal, and their lateral shift due to the Lorentz force is elucidated. Electron history backtracing also serves to illustrate the correct treatment of the influences of the Lorentz force in the EGSnrc Monte Carlo code applied in this study.

Dose of physical activity, physical functioning and disability risk in mobility-limited older adults: Results from the LIFE study randomized trial

PubMed Central

Guralnik, Jack M.; King, Abby C.; Pahor, Marco; McDermott, Mary M.; Tudor-Locke, Catrine; Manini, Todd M.; Glynn, Nancy W.; Marsh, Anthony P.; Axtell, Robert S.; Hsu, Fang-Chi; Rejeski, W. Jack

2017-01-01

Understanding the minimal dose of physical activity required to achieve improvement in physical functioning and reductions in disability risk is necessary to inform public health recommendations. To examine the effect of physical activity dose on changes in physical functioning and the onset of major mobility disability in The Lifestyle Interventions and Independence for Elders (LIFE) Study. We conducted a multicenter single masked randomized controlled trial that enrolled participants in 2010 and 2011 and followed them for an average of 2.6 years. 1,635 sedentary men and women aged 70–89 years who had functional limitations were randomized to a structured moderate intensity walking, resistance, and flexibility physical activity program or a health education program. Physical activity dose was assessed by 7-day accelerometry and self-report at baseline and 24 months. Outcomes included the 400 m walk gait speed, the Short Physical Performance Battery (SPPB), assessed at baseline, 6, 12, and 24 months, and onset of major mobility disability (objectively defined by loss of ability to walk 400 m in 15 min). When the physical activity arm or the entire sample were stratified by change in physical activity from baseline to 24 months, there was a dose-dependent increase in the change in gait speed and SPPB from baseline at 6, 12, and 24 months. In addition, the magnitude of change in physical activity over 24 months was related to the reduction in the onset of major mobility disability (overall P < 0.001) (highest versus the lowest quartile of physical activity change HR 0.23 ((95% CI:0.10–0.52) P = 0.001) in the physical activity arm. We observed a dose-dependent effect of objectively monitored physical activity on physical functioning and onset of major mobility disability. Relatively small increases (> 48 minutes per week) in regular physical activity participation had significant and clinically meaningful effects on these outcomes. Trial registration: ClinicalsTrials.gov NCT00116194 PMID:28820909

Dose of physical activity, physical functioning and disability risk in mobility-limited older adults: Results from the LIFE study randomized trial.

PubMed

Fielding, Roger A; Guralnik, Jack M; King, Abby C; Pahor, Marco; McDermott, Mary M; Tudor-Locke, Catrine; Manini, Todd M; Glynn, Nancy W; Marsh, Anthony P; Axtell, Robert S; Hsu, Fang-Chi; Rejeski, W Jack

2017-01-01

Understanding the minimal dose of physical activity required to achieve improvement in physical functioning and reductions in disability risk is necessary to inform public health recommendations. To examine the effect of physical activity dose on changes in physical functioning and the onset of major mobility disability in The Lifestyle Interventions and Independence for Elders (LIFE) Study. We conducted a multicenter single masked randomized controlled trial that enrolled participants in 2010 and 2011 and followed them for an average of 2.6 years. 1,635 sedentary men and women aged 70-89 years who had functional limitations were randomized to a structured moderate intensity walking, resistance, and flexibility physical activity program or a health education program. Physical activity dose was assessed by 7-day accelerometry and self-report at baseline and 24 months. Outcomes included the 400 m walk gait speed, the Short Physical Performance Battery (SPPB), assessed at baseline, 6, 12, and 24 months, and onset of major mobility disability (objectively defined by loss of ability to walk 400 m in 15 min). When the physical activity arm or the entire sample were stratified by change in physical activity from baseline to 24 months, there was a dose-dependent increase in the change in gait speed and SPPB from baseline at 6, 12, and 24 months. In addition, the magnitude of change in physical activity over 24 months was related to the reduction in the onset of major mobility disability (overall P < 0.001) (highest versus the lowest quartile of physical activity change HR 0.23 ((95% CI:0.10-0.52) P = 0.001) in the physical activity arm. We observed a dose-dependent effect of objectively monitored physical activity on physical functioning and onset of major mobility disability. Relatively small increases (> 48 minutes per week) in regular physical activity participation had significant and clinically meaningful effects on these outcomes. ClinicalsTrials.gov NCT00116194.

Stochastic dosimetry model for radon progeny in the rat lung.

PubMed

Winkler-HeiI, R; Hofmann, W; Hussain, M

2014-07-01

The stochastic dosimetry model presented here considers the distinctly asymmetric, stochastic branching pattern reported in morphometric measurements. This monopodial structure suggests that an airway diameter is a more appropriate morphometric parameter to classify bronchial dose distributions for inhaled radon progeny than the commonly assigned airway generation numbers. Bronchial doses were calculated for the typical exposure conditions reported for the Pacific Northwest National Laboratory rat inhalation studies, yielding an average bronchial dose of 7.75 mGy WLM(-1). If plotted as functions of airway generations, the resulting dose distributions are highest in the central bronchial airways, while significantly decreasing towards peripheral generations. However, if plotted as functions of airway diameters, doses are much more uniformly distributed among bronchial airways. The comparison between rat and human lungs indicates that dose conversion coefficients for the rat lung are higher than the corresponding values for the human lung by a factor of 1.34 for the experimental PNNL exposure conditions, and of 1.25 for typical human indoor conditions. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Comparison of Cognitive Performance Tests for Promethazine Pharmacodynamics in Human Subjects

NASA Technical Reports Server (NTRS)

Vaksman, Z.; Boyd, J. L.; Wang, Z.; Putcha, L.

2005-01-01

The objective of this study is to compare cognitive function tests, Automated Neurological Assessment Metrics (ANAM) based Readiness Evaluation System (ARES(Registered TradeMark)) on a Palm Pilot and Windows based Spaceflight Cognitive Assessment Tool (WinSCAT(Registered TradeMark)) on a personal computer (PC) to assess performance effects of promethazine (PMZ) after administration to human subjects. In a randomized placebo-controlled cross-over design, subjects received 12.5, 25, and 50 mg intramuscular (IM) PMZ or a placebo and completed 14 sessions with WinSCAT(Registered TradeMark) (v. 1.26) and ARES(Registered TradeMark) (v. 1.27) consecutively for 72 h post dose. Maximum plasma concentrations (4.25, 6.25 and 13.33 ng/ml) were linear with dose and were achieved by 0.75, 8, and 24 h after dosing for the three doses, respectively. No significant differences in cognitive function after PMZ dosing were detected using WinSCAT(Registered TradeMark), however, tests from ARES(Registered TradeMark) demonstrated concentration dependent decrements in reaction time associated with PMZ dose.

PATHOPHYSIOLOGICAL CONSEQUENCES OF TAT-HKII PEPTIDE ADMINISTRATION ARE INDEPENDENT OF IMPAIRED VASCULAR FUNCTION AND ENSUING ISCHEMIA

PubMed Central

Nederlof, Rianne; Xie, Chaoqin; Eerbeek, Otto; Koeman, Anneke; Milstein, Dan MJ; Hollmann, Markus W; Mik, Egbert G; Warley, Alice; Southworth, Richard; Akar, Fadi G.; Zuurbier, Coert J

2013-01-01

Rationale We have shown that partial dissociation of HKII from mitochondria in the intact heart using low dose (200 nM) TAT-HKII prevents the cardioprotective effects of ischemic preconditioning (IPC) whereas high-dose (10 μM) TAT-HKII administration results in rapid myocardial dysfunction, mitochondrial depolarization and disintegration. In this issue of Circulation Research, Pasdois et al argue that the deleterious effects of TAT-HKII administration on cardiac function are likely due to vasoconstriction and ensuing ischemia. Objective To investigate whether altered vascular function and ensuing ischemia recapitulate the deleterious effects of TAT-HKII in intact myocardium. Methods and Results Using a variety of complementary techniques, including mitochondrial membrane potential (ΔΨm) imaging, high-resolution optical action potential (AP) mapping, analysis of lactate production, NADH epifluorescence, lactate dehydrogenase (LDH) release, and electron microscopy, we provide direct evidence that refutes the notion that acute myocardial dysfunction by high-dose TAT-HKII peptide administration is a consequence of impaired vascular function. Moreover, we demonstrate that low-dose TAT-HKII treatment, which abrogates the protective effects of IPC, is not associated with ischemia or ischemic-injury. Conclusions Our findings challenge the notion that the effects of TAT-HKII are attributable to impaired vascular function and ensuing ischemia; thereby, lending further credence to the role of mitochondria bound HKII as a critical regulator of cardiac function, ischemia-reperfusion (IR) injury, and cardioprotection by IPC. PMID:23329797

A phase III, open-label, single-arm study of tenecteplase for restoration of function in dysfunctional central venous catheters.

PubMed

Tebbi, Cameron; Costanzi, John; Shulman, Robert; Dreisbach, Luke; Jacobs, Brian R; Blaney, Martha; Ashby, Mark; Gillespie, Barbara S; Begelman, Susan M

2011-08-01

To evaluate, in a phase III, single-arm study, the safety and efficacy of the thrombolytic agent tenecteplase in restoring function to dysfunctional central venous catheters (CVCs). Pediatric and adult patients with dysfunctional CVCs were eligible to receive as much as 2 mL (2 mg) of intraluminal tenecteplase, which was left to dwell in the CVC lumen for a maximum of 120 minutes. If CVC function was not restored at 120 minutes, a second dose was instilled for an additional 120 minutes. Tenecteplase was administered to 246 patients. Mean patient age was 44 years (range, 0-92 y); 72 patients (29%) were younger than 17 years of age. Chemotherapy was the most common reason for catheter insertion. Restoration of CVC function was achieved in 177 patients (72%) within 120 minutes after the first dose. After instillation of a maximum of two doses of tenecteplase, CVC function was restored in 200 patients (81%), with similar frequencies in pediatric (83%) and adult (80%) patients. Adverse events (AEs) were reported in 31 patients (13%); fever (2%), neutropenia (1%), and nausea (0.8%) were most common. One serious AE, an allergic hypersensitivity reaction, was judged to be related to tenecteplase and/or a chemotherapeutic agent that the patient was receiving concurrently. Consecutive administration of one or two doses of tenecteplase into CVCs showed efficacy in the restoration of catheter function in patients with dysfunctional CVCs. Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.

Effects of tennis play on executive function in 6-11-year-old children: a 12-month longitudinal study.

PubMed

Ishihara, Toru; Mizuno, Masao

2018-06-01

The present study aimed to assess the effects of 12 months of frequent tennis play on executive functions and the relationships of daily moderate-to-vigorous physical activity (MVPA), physical competence, and enjoyment of playing tennis to executive functions in children. Thirty-two children (6-11 years old) who had regularly played tennis (once a week; mean = 3 years, range = 0-6 years) before the study were enrolled in a 12-month intervention. Participants were allocated into two groups: low-dose (maintain current frequency of tennis play, N = 19) or high-dose (increased frequency of tennis play to four times per week, N = 13). Participants' MVPA, physical competence, enjoyment of playing tennis, and executive functions (i.e. inhibitory control, working memory, and cognitive flexibility) were evaluated before and after this intervention. The high-dose group demonstrated a greater improvement in working memory than the low-dose group, while there was no group difference in MVPA, physical competence, and enjoyment of playing tennis. Changes in MVPA were associated with improvements in cognitive flexibility. Changes in physical competence were associated with improvements in working memory and cognitive flexibility. Changes in the enjoyment of playing tennis were associated with improvements in inhibitory control. The current findings suggest that replacement of MVPA with sports activity, such as tennis enhances executive functions development, and suggest that sports programmes that seek to build competence and enjoyment might help support the development of executive functions in children.

Effect of sulfonylurea agents on reverse cholesterol transport in vitro and vivo.

PubMed

Terao, Yoshio; Ayaori, Makoto; Ogura, Masatsune; Yakushiji, Emi; Uto-Kondo, Harumi; Hisada, Tetsuya; Ozasa, Hideki; Takiguchi, Shunichi; Nakaya, Kazuhiro; Sasaki, Makoto; Komatsu, Tomohiro; Iizuka, Maki; Horii, Shunpei; Mochizuki, Seibu; Yoshimura, Michihiro; Ikewaki, Katsunori

2011-01-01

Reverse cholesterol transport (RCT) is a critical mechanism for the anti-atherogenic property of HDL. The inhibitory effect of the sulfonylurea agent (SUA) glibenclamide on ATP binding-cassette transporter (ABC) A1 may decrease HDL function but it remains unclear whether it attenuates RCT in vivo. We therefore investigated how the SUAs glibenclamide and glimepiride affected the functionality of ABCA1/ABCG1 and scavenger receptor class B type I (SR-BI) expression in macrophages in vitro and overall RCT in vivo. RAW264.7, HEK293 and BHK-21 cells were used for in vitro studies. To investigate RCT in vivo, 3H-cholesterol-labeled and acetyl LDL-loaded RAW264.7 cells were injected into mice. High dose (500µM) of glibenclamide inhibited ABCA1 function and apolipoprotein A-I (apoA-I)-mediated cholesterol efflux, and attenuated ABCA1 expression. Although glimepiride maintained apoA-I-mediated cholesterol efflux from RAW264.7 cells, like glibenclamide, it inhibited ABCA1-mediated cholesterol efflux from transfected HEK293 cells. Similarly, the SUAs inhibited SR-BI-mediated cholesterol efflux from transfected BHK-21 cells. High doses of SUAs increased ABCG1 expression in RAW264.7 cells, promoting HDL-mediated cholesterol efflux in an ABCG1-independent manner. Low doses (0.1-100 µM) of SUAs did not affect cholesterol efflux from macrophages despite dose-dependent increases in ABCA1/G1 expression. Furthermore, they did not change RCT or plasma lipid levels in mice. High doses of SUAs inhibited the functionality of ABCA1/SR-BI, but not ABCG1. At lower doses, they had no unfavorable effects on cholesterol efflux or overall RCT in vivo. These results indicate that SUAs do not have adverse effects on atherosclerosis contrary to previous findings for glibenclamide.

Changes in balance, functional performance and fall risk following whole body vibration training and vitamin D supplementation in institutionalized elderly women. A 6 month randomized controlled trial.

PubMed

Bogaerts, An; Delecluse, Christophe; Boonen, Steven; Claessens, Albrecht L; Milisen, Koen; Verschueren, Sabine M P

2011-03-01

Falls in the elderly constitute a growing public health problem. This randomized controlled trial investigated the potential benefit of 6 months of whole body vibration (WBV) training and/or vitamin D supplementation on balance, functionality and estimated fall risk in institutionalized elderly women. A total of 113 women (mean age: 79.6) were randomly assigned to either a WBV or a no-training group, receiving either a conventional dose (880 IU/d) or a high dose (1600 IU/d) of vitamin D3. The WBV group performed exercises on a vibration platform 3×/week. Balance was evaluated by computerized posturography. Functionality was assessed by 10 m walk test, Timed up and Go (TUG) performance and endurance capacity (Shuttle Walk). Fall risk was determined with the Physiological Profile Assessment. Performance on the 10 m walk test and on TUG improved over time in all groups. For none of the parameters, high-dose vitamin D resulted in a better performance than conventional dosing. The improvements in the WBV group in endurance capacity, walking at preferred speed, and TUG were significantly larger than the changes with supplementation alone. No additional benefit of WBV training could be detected on fall risk and postural control, although sway velocity and maximal isometric knee extension strength improved only in the WBV group. This trial showed that a high-dose vitamin D supplementation is not more efficient than conventional dosing in improving functionality in institutionalized elderly. WBV training on top of vitamin D supplementation provided an added benefit with regard to walking, TUG performance, and endurance capacity. Copyright © 2010 Elsevier B.V. All rights reserved.

Graded-threshold parametric response maps: towards a strategy for adaptive dose painting

NASA Astrophysics Data System (ADS)

Lausch, A.; Jensen, N.; Chen, J.; Lee, T. Y.; Lock, M.; Wong, E.

2014-03-01

Purpose: To modify the single-threshold parametric response map (ST-PRM) method for predicting treatment outcomes in order to facilitate its use for guidance of adaptive dose painting in intensity-modulated radiotherapy. Methods: Multiple graded thresholds were used to extend the ST-PRM method (Nat. Med. 2009;15(5):572-576) such that the full functional change distribution within tumours could be represented with respect to multiple confidence interval estimates for functional changes in similar healthy tissue. The ST-PRM and graded-threshold PRM (GT-PRM) methods were applied to functional imaging scans of 5 patients treated for hepatocellular carcinoma. Pre and post-radiotherapy arterial blood flow maps (ABF) were generated from CT-perfusion scans of each patient. ABF maps were rigidly registered based on aligning tumour centres of mass. ST-PRM and GT-PRM analyses were then performed on overlapping tumour regions within the registered ABF maps. Main findings: The ST-PRMs contained many disconnected clusters of voxels classified as having a significant change in function. While this may be useful to predict treatment response, it may pose challenges for identifying boost volumes or for informing dose-painting by numbers strategies. The GT-PRMs included all of the same information as ST-PRMs but also visualized the full tumour functional change distribution. Heterogeneous clusters in the ST-PRMs often became more connected in the GT-PRMs by voxels with similar functional changes. Conclusions: GT-PRMs provided additional information which helped to visualize relationships between significant functional changes identified by ST-PRMs. This may enhance ST-PRM utility for guiding adaptive dose painting.

Novel oxytocin receptor variants in laboring women requiring high doses of oxytocin.

PubMed

Reinl, Erin L; Goodwin, Zane A; Raghuraman, Nandini; Lee, Grace Y; Jo, Erin Y; Gezahegn, Beakal M; Pillai, Meghan K; Cahill, Alison G; de Guzman Strong, Cristina; England, Sarah K

2017-08-01

Although oxytocin commonly is used to augment or induce labor, it is difficult to predict its effectiveness because oxytocin dose requirements vary significantly among women. One possibility is that women requiring high or low doses of oxytocin have variations in the oxytocin receptor gene. To identify oxytocin receptor gene variants in laboring women with low and high oxytocin dosage requirements. Term, nulliparous women requiring oxytocin doses of ≤4 mU/min (low-dose-requiring, n = 83) or ≥20 mU/min (high-dose-requiring, n = 104) for labor augmentation or induction provided consent to a postpartum blood draw as a source of genomic DNA. Targeted-amplicon sequencing (coverage >30×) with MiSeq (Illumina) was performed to discover variants in the coding exons of the oxytocin receptor gene. Baseline relevant clinical history, outcomes, demographics, and oxytocin receptor gene sequence variants and their allele frequencies were compared between low-dose-requiring and high-dose-requiring women. The Scale-Invariant Feature Transform algorithm was used to predict the effect of variants on oxytocin receptor function. The Fisher exact or χ 2 tests were used for categorical variables, and Student t tests or Wilcoxon rank sum tests were used for continuous variables. A P value < .05 was considered statistically significant. The high-dose-requiring women had greater rates of obesity and diabetes and were more likely to have undergone labor induction and required prostaglandins. High-dose-requiring women were more likely to undergo cesarean delivery for first-stage arrest and less likely to undergo cesarean delivery for nonreassuring fetal status. Targeted sequencing of the oxytocin receptor gene in the total cohort (n = 187) revealed 30 distinct coding variants: 17 nonsynonymous, 11 synonymous, and 2 small structural variants. One novel variant (A243T) was found in both the low- and high-dose-requiring groups. Three novel variants (Y106H, A240_A249del, and P197delfs*206) resulting in an amino acid substitution, loss of 9 amino acids, and a frameshift stop mutation, respectively, were identified only in low-dose-requiring women. Nine nonsynonymous variants were unique to the high-dose-requiring group. These included 3 known variants (R151C, G221S, and W228C) and 6 novel variants (M133V, R150L, H173R, A248V, G253R, and I266V). Of these, R150L, R151C, and H173R were predicted by Scale-Invariant Feature Transform algorithm to damage oxytocin receptor function. There was no statistically significant association between the numbers of synonymous and nonsynonymous substitutions in the patient groups. Obesity, diabetes, and labor induction were associated with the requirement for high doses of oxytocin. We did not identify significant differences in the prevalence of oxytocin receptor variants between low-dose-requiring and high-dose-requiring women, but novel oxytocin receptor variants were enriched in the high-dose-requiring women. We also found 3 oxytocin receptor variants (2 novel, 1 known) that were predicted to damage oxytocin receptor function and would likely increase an individual's risk for requiring a high oxytocin dose. Further investigation of oxytocin receptor variants and their effects on protein function will inform precision medicine in pregnant women. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Cerebral Cortex Regions Selectively Vulnerable to Radiation Dose-Dependent Atrophy

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

Seibert, Tyler M.; Karunamuni, Roshan; Kaifi, Samar

Purpose and Objectives: Neurologic deficits after brain radiation therapy (RT) typically involve decline in higher-order cognitive functions such as attention and memory rather than sensory defects or paralysis. We sought to determine whether areas of the cortex critical to cognition are selectively vulnerable to radiation dose-dependent atrophy. Methods and Materials: We measured change in cortical thickness in 54 primary brain tumor patients who underwent fractionated, partial brain RT. The study patients underwent high-resolution, volumetric magnetic resonance imaging (T1-weighted; T2 fluid-attenuated inversion recovery, FLAIR) before RT and 1 year afterward. Semiautomated software was used to segment anatomic regions of the cerebral cortex formore » each patient. Cortical thickness was measured for each region before RT and 1 year afterward. Two higher-order cortical regions of interest (ROIs) were tested for association between radiation dose and cortical thinning: entorhinal (memory) and inferior parietal (attention/memory). For comparison, 2 primary cortex ROIs were also tested: pericalcarine (vision) and paracentral lobule (somatosensory/motor). Linear mixed-effects analyses were used to test all other cortical regions for significant radiation dose-dependent thickness change. Statistical significance was set at α = 0.05 using 2-tailed tests. Results: Cortical atrophy was significantly associated with radiation dose in the entorhinal (P=.01) and inferior parietal ROIs (P=.02). By contrast, no significant radiation dose-dependent effect was found in the primary cortex ROIs (pericalcarine and paracentral lobule). In the whole-cortex analysis, 9 regions showed significant radiation dose-dependent atrophy, including areas responsible for memory, attention, and executive function (P≤.002). Conclusions: Areas of cerebral cortex important for higher-order cognition may be most vulnerable to radiation-related atrophy. This is consistent with clinical observations that brain radiation patients experience deficits in domains of memory, executive function, and attention. Correlations of regional cortical atrophy with domain-specific cognitive functioning in prospective trials are warranted.« less

Tolerance to the Diuretic Effects of Cannabinoids and Cross-Tolerance to a κ-Opioid Agonist in THC-Treated Mice.

PubMed

Chopda, Girish R; Parge, Viraj; Thakur, Ganesh A; Gatley, S John; Makriyannis, Alexandros; Paronis, Carol A

2016-08-01

Daily treatment with cannabinoids results in tolerance to many, but not all, of their behavioral and physiologic effects. The present studies investigated the effects of 7-day exposure to 10 mg/kg daily of Δ(9)-tetrahydrocannabinol (THC) on the diuretic and antinociceptive effects of THC and the synthetic cannabinoid AM4054. Comparison studies determined diuretic responses to the κ-opioid agonist U50,488 and furosemide. After determination of control dose-response functions, mice received 10 mg/kg daily of THC for 7 days, and dose-response functions were re-determined 24 hours, 7 days, or 14 days later. THC and AM4054 had biphasic diuretic effects under control conditions with maximum effects of 30 and 35 ml/kg of urine, respectively. In contrast, antinociceptive effects of both drugs increased monotonically with dose to >90% of maximal possible effect. Treatment with THC produced 9- and 7-fold rightward shifts of the diuresis and antinociception dose-response curves for THC and, respectively, 7- and 3-fold rightward shifts in the AM4054 dose-response functions. U50,488 and furosemide increased urine output to >35 ml/kg under control conditions. The effects of U50,488 were attenuated after 7-day treatment with THC, whereas the effects of furosemide were unaltered. Diuretic effects of THC and AM4054 recovered to near-baseline levels within 14 days after stopping daily THC injections, whereas tolerance to the antinociceptive effects persisted longer than 14 days. The tolerance induced by 7-day treatment with THC was accompanied by a 55% decrease in the Bmax value for cannabinoid receptors (CB1). These data indicate that repeated exposure to THC produces similar rightward shifts in the ascending and descending limbs of cannabinoid diuresis dose-effect curves and to antinociceptive effects while resulting in a flattening of the U50,488 diuresis dose-effect function. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Acute effects of quercetin-3-O-glucoside on endothelial function and blood pressure: a randomized dose-response study.

PubMed

Bondonno, Nicola P; Bondonno, Catherine P; Rich, Lisa; Mas, Emilie; Shinde, Sujata; Ward, Natalie C; Hodgson, Jonathan M; Croft, Kevin D

2016-07-01

Epidemiologic studies have suggested that a flavonoid-rich diet can reduce the risk of developing cardiovascular disease. Certain flavonoids, in particular quercetin, have been shown to ameliorate endothelial dysfunction and reduce blood pressure (BP), possibly by increasing the bioavailability of the potent vasodilator nitric oxide (NO). Several studies have indicated that improvements in measures of cardiovascular health do not occur linearly, but rather, plateau or decrease with an increasing dose of flavonoids. We determined whether the acute administration of increasing doses of a common quercetin glycoside (quercetin-3-O-glucoside) improves endothelial function and reduces BP in a dose-dependent manner. We also explored whether any effects were correlated with changes in plasma NO production. A randomized, controlled, crossover study was performed in 15 healthy volunteers who each completed 5 visits with a minimum washout period of 1 wk between testing days. Participants received each of the following 5 interventions in a random order: 1) 0, 2) 50, 3) 100, 4) 200, or 5) 400 mg quercetin-3-O-glucoside. Endothelial function and BP were assessed before and 60 min after intervention. A blood sample was taken before and 90 min after intervention for the analysis of plasma nitrate and nitrite as markers of NO production as well as of plasma quercetin metabolites. Although we observed a significant correlation between the dose of quercetin-3-O-glucoside and plasma concentrations of total quercetin (R(2) = 0.52, P < 0.001) and isorhamnetin (R(2) = 0.12, P = 0.005), we showed no improvements in endothelial function or BP and no changes in NO production after any dose. From these results, we conclude that there are no acute changes in BP or the NO-mediated endothelium-dependent relaxation of the brachial artery with doses of quercetin ranging from 50 to 400 mg in healthy men and women. This trial was registered at www.anzctr.org.au as ACTRN12615001338550. © 2016 American Society for Nutrition.

Focal exposure of limited lung volumes to high-dose irradiation down-regulated organ development-related functions and up-regulated the immune response in mouse pulmonary tissues.

PubMed

Kim, Bu-Yeo; Jin, Hee; Lee, Yoon-Jin; Kang, Ga-Young; Cho, Jaeho; Lee, Yun-Sil

2016-01-27

Despite the emergence of stereotactic body radiotherapy (SBRT) for treatment of medically inoperable early-stage non-small-cell lung cancer patients, the molecular effects of focal exposure of limited lung volumes to high-dose radiation have not been fully characterized. This study was designed to identify molecular changes induced by focal high-dose irradiation using a mouse model of SBRT. Central areas of the mouse left lung were focally-irradiated (3 mm in diameter) with a single high-dose of radiation (90 Gy). Temporal changes in gene expression in the irradiated and non-irradiated neighboring lung regions were analyzed by microarray. For comparison, the long-term effect (12 months) of 20 Gy radiation on a diffuse region of lung was also measured. The majority of genes were down-regulated in the focally-irradiated lung areas at 2 to 3 weeks after irradiation. This pattern of gene expression was clearly different than gene expression in the diffuse region of lungs exposed to low-dose radiation. Ontological and pathway analyses indicated these down-regulated genes were mainly associated with organ development. Although the number was small, genes that were up-regulated after focal irradiation were associated with immune-related functions. The temporal patterns of gene expression and the associated biological functions were also similar in non-irradiated neighboring lung regions, although statistical significance was greatly reduced when compared with those from focally-irradiated areas of the lung. From network analysis of temporally regulated genes, we identified inter-related modules associated with diverse functions, including organ development and the immune response, in both the focally-irradiated regions and non-irradiated neighboring lung regions. Focal exposure of lung tissue to high-dose radiation induced expression of genes associated with organ development and the immune response. This pattern of gene expression was also observed in non-irradiated neighboring areas of lung tissue, indicating a global lung response to focal high-dose irradiation.

Photobiomodulation therapy protects skeletal muscle and improves muscular function of mdx mice in a dose-dependent manner through modulation of dystrophin.

PubMed

Albuquerque-Pontes, Gianna Móes; Casalechi, Heliodora Leão; Tomazoni, Shaiane Silva; Serra, Andrey Jorge; Ferreira, Cheila de Sousa Bacelar; Brito, Rodrigo Barbosa de Oliveira; de Melo, Brunno Lemes; Vanin, Adriane Aver; Monteiro, Kadma Karênina Damasceno Soares; Dellê, Humberto; Frigo, Lucio; Marcos, Rodrigo Labat; de Carvalho, Paulo de Tarso Camillo; Leal-Junior, Ernesto Cesar Pinto

2018-05-01

This study aimed to analyze the protective effects of photobiomodulation therapy (PBMT) with combination of low-level laser therapy (LLLT) and light emitting diode therapy (LEDT) on skeletal muscle tissue to delay dystrophy progression in mdx mice (DMD mdx ). To this aim, mice were randomly divided into five different experimental groups: wild type (WT), placebo-control (DMD mdx ), PBMT with doses of 1 J (DMD mdx ), 3 J (DMD mdx ), and 10 J (DMD mdx ). PBMT was performed employing a cluster probe with 9 diodes (1 x 905nm super-pulsed laser diode; 4 x 875nm infrared LEDs; and 4 x 640nm red LEDs, manufactured by Multi Radiance Medical®, Solon - OH, USA), 3 times a week for 14 weeks. PBMT was applied on a single point (tibialis anterior muscle-bilaterally). We analyzed functional performance, muscle morphology, and gene and protein expression of dystrophin. PBMT with a 10 J dose significantly improved (p < 0.001) functional performance compared to all other experimental groups. Muscle morphology was improved by all PBMT doses, with better outcomes with the 3 and 10 J doses. Gene expression of dystrophin was significantly increased with 3 J (p < 0.01) and 10 J (p < 0.01) doses when compared to placebo-control group. Regarding protein expression of dystrophin, 3 J (p < 0.001) and 10 J (p < 0.05) doses also significantly showed increase compared to placebo-control group. We conclude that PBMT can mainly preserve muscle morphology and improve muscular function of mdx mice through modulation of gene and protein expression of dystrophin. Furthermore, since PBMT is a non-pharmacological treatment which does not present side effects and is easy to handle, it can be seen as a promising tool for treating Duchenne's muscular dystrophy.

Mechanistic simulation of normal-tissue damage in radiotherapy—implications for dose-volume analyses

NASA Astrophysics Data System (ADS)

Rutkowska, Eva; Baker, Colin; Nahum, Alan

2010-04-01

A radiobiologically based 3D model of normal tissue has been developed in which complications are generated when 'irradiated'. The aim is to provide insight into the connection between dose-distribution characteristics, different organ architectures and complication rates beyond that obtainable with simple DVH-based analytical NTCP models. In this model the organ consists of a large number of functional subunits (FSUs), populated by stem cells which are killed according to the LQ model. A complication is triggered if the density of FSUs in any 'critical functioning volume' (CFV) falls below some threshold. The (fractional) CFV determines the organ architecture and can be varied continuously from small (series-like behaviour) to large (parallel-like). A key feature of the model is its ability to account for the spatial dependence of dose distributions. Simulations were carried out to investigate correlations between dose-volume parameters and the incidence of 'complications' using different pseudo-clinical dose distributions. Correlations between dose-volume parameters and outcome depended on characteristics of the dose distributions and on organ architecture. As anticipated, the mean dose and V20 correlated most strongly with outcome for a parallel organ, and the maximum dose for a serial organ. Interestingly better correlation was obtained between the 3D computer model and the LKB model with dose distributions typical for serial organs than with those typical for parallel organs. This work links the results of dose-volume analyses to dataset characteristics typical for serial and parallel organs and it may help investigators interpret the results from clinical studies.

Autonomous functioning thyroid nodules and 131I in diagnosis and therapy after 50 years of experience: what is still open to debate?

PubMed

Ronga, Giuseppe; Filesi, Mauro; D'Apollo, Rosaria; Toteda, Maria; Di Nicola, Angelo Domenico; Colandrea, Marzia; Travascio, Laura; Vestri, Anna Rita; Montesano, Teresa

2013-05-01

Autonomous functioning thyroid nodules (AFTN), defined as "hot nodules" at thyroid scan, are often cured by radioiodine treatment. The aim of our study was to investigate the long-term outcome in patients treated with an 131I calculated dose, to identify a possible "size-tailored" dose, and to simplify follow-up procedures. Retrospective analysis was carried out on 1402 cases, covering a period of 50 years, of AFTN treated with an 131I calculated dose. Our study focused on nodular size and mean administered dose. Concordance between thyroid scan and serum TSH levels at 3-6 months from treatment was considered. A single 131I dose was effective for the vast majority of patients (93%). The outcome was influenced by nodular size. On the basis of the Italian dose limit for outpatient treatment, our population was divided into subgroups according to administered doses (more or less than 16 mCi) and nodular dimensions: no differences in outcome were observed for each class of nodule size. A dose ≤10 mCi was effective on the smaller nodules (50.1% of our population). The agreement between TSH and scan after treatment was 90.3% at 3 months and 94.5% at 6 months. 131I therapy with a calculated dose is an effective treatment of AFTN. If a fixed dose is chosen, 16 mCi is often resolutive and for nodules <3 cm a dose of 10 mCi can suffice. Nodules >5 cm are eligible for surgery. TSH is the only parameter required to evaluate the outcome.

Speed and convergence properties of gradient algorithms for optimization of IMRT.

PubMed

Zhang, Xiaodong; Liu, Helen; Wang, Xiaochun; Dong, Lei; Wu, Qiuwen; Mohan, Radhe

2004-05-01

Gradient algorithms are the most commonly employed search methods in the routine optimization of IMRT plans. It is well known that local minima can exist for dose-volume-based and biology-based objective functions. The purpose of this paper is to compare the relative speed of different gradient algorithms, to investigate the strategies for accelerating the optimization process, to assess the validity of these strategies, and to study the convergence properties of these algorithms for dose-volume and biological objective functions. With these aims in mind, we implemented Newton's, conjugate gradient (CG), and the steepest decent (SD) algorithms for dose-volume- and EUD-based objective functions. Our implementation of Newton's algorithm approximates the second derivative matrix (Hessian) by its diagonal. The standard SD algorithm and the CG algorithm with "line minimization" were also implemented. In addition, we investigated the use of a variation of the CG algorithm, called the "scaled conjugate gradient" (SCG) algorithm. To accelerate the optimization process, we investigated the validity of the use of a "hybrid optimization" strategy, in which approximations to calculated dose distributions are used during most of the iterations. Published studies have indicated that getting trapped in local minima is not a significant problem. To investigate this issue further, we first obtained, by trial and error, and starting with uniform intensity distributions, the parameters of the dose-volume- or EUD-based objective functions which produced IMRT plans that satisfied the clinical requirements. Using the resulting optimized intensity distributions as the initial guess, we investigated the possibility of getting trapped in a local minimum. For most of the results presented, we used a lung cancer case. To illustrate the generality of our methods, the results for a prostate case are also presented. For both dose-volume and EUD based objective functions, Newton's method far outperforms other algorithms in terms of speed. The SCG algorithm, which avoids expensive "line minimization," can speed up the standard CG algorithm by at least a factor of 2. For the same initial conditions, all algorithms converge essentially to the same plan. However, we demonstrate that for any of the algorithms studied, starting with previously optimized intensity distributions as the initial guess but for different objective function parameters, the solution frequently gets trapped in local minima. We found that the initial intensity distribution obtained from IMRT optimization utilizing objective function parameters, which favor a specific anatomic structure, would lead to a local minimum corresponding to that structure. Our results indicate that from among the gradient algorithms tested, Newton's method appears to be the fastest by far. Different gradient algorithms have the same convergence properties for dose-volume- and EUD-based objective functions. The hybrid dose calculation strategy is valid and can significantly accelerate the optimization process. The degree of acceleration achieved depends on the type of optimization problem being addressed (e.g., IMRT optimization, intensity modulated beam configuration optimization, or objective function parameter optimization). Under special conditions, gradient algorithms will get trapped in local minima, and reoptimization, starting with the results of previous optimization, will lead to solutions that are generally not significantly different from the local minimum.

Dose response effect of NutriTek on leukocyte functionality and ex vivo cytokine production during a dexamethasone challenge in Holstein steer calves

USDA-ARS?s Scientific Manuscript database

The objective of this study was to determine the dose response effects of supplementing NutriTek on leukocyte functionality and ex vivo cytokine production during a dexamethasone (DEX) challenge. Holstein steers (125.1 ± 8.16 kg; N = 32) were assigned to treatments including 0, 20, 40, or 60 g/head/...

SU-E-J-85: Leave-One-Out Perturbation (LOOP) Fitting Algorithm for Absolute Dose Film Calibration

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

Chu, A; Ahmad, M; Chen, Z

2014-06-01

Purpose: To introduce an outliers-recognition fitting routine for film dosimetry. It cannot only be flexible with any linear and non-linear regression but also can provide information for the minimal number of sampling points, critical sampling distributions and evaluating analytical functions for absolute film-dose calibration. Methods: The technique, leave-one-out (LOO) cross validation, is often used for statistical analyses on model performance. We used LOO analyses with perturbed bootstrap fitting called leave-one-out perturbation (LOOP) for film-dose calibration . Given a threshold, the LOO process detects unfit points (“outliers”) compared to other cohorts, and a bootstrap fitting process follows to seek any possibilitiesmore » of using perturbations for further improvement. After that outliers were reconfirmed by a traditional t-test statistics and eliminated, then another LOOP feedback resulted in the final. An over-sampled film-dose- calibration dataset was collected as a reference (dose range: 0-800cGy), and various simulated conditions for outliers and sampling distributions were derived from the reference. Comparisons over the various conditions were made, and the performance of fitting functions, polynomial and rational functions, were evaluated. Results: (1) LOOP can prove its sensitive outlier-recognition by its statistical correlation to an exceptional better goodness-of-fit as outliers being left-out. (2) With sufficient statistical information, the LOOP can correct outliers under some low-sampling conditions that other “robust fits”, e.g. Least Absolute Residuals, cannot. (3) Complete cross-validated analyses of LOOP indicate that the function of rational type demonstrates a much superior performance compared to the polynomial. Even with 5 data points including one outlier, using LOOP with rational function can restore more than a 95% value back to its reference values, while the polynomial fitting completely failed under the same conditions. Conclusion: LOOP can cooperate with any fitting routine functioning as a “robust fit”. In addition, it can be set as a benchmark for film-dose calibration fitting performance.« less

Cognitive Function Before and After Intensity-Modulated Radiation Therapy in Patients With Nasopharyngeal Carcinoma: A Prospective Study

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

Hsiao, Kuan-Yin; Department of Medical Imaging and Radiological Science, I-Shou University, Kaohsiung, Taiwan; Yeh, Shyh-An, E-mail: yehsa@hotmail.co

Purpose: To evaluate the effects of radiation therapy (RT) on neurocognitive function in patients with nasopharyngeal carcinoma (NPC). Methods and Materials: Thirty patients with NPC treated with intensity-modulated RT were included. Dose-volume histograms of the temporal lobes were obtained in every patient. Neurocognitive tests were administered individually to each patient 1 day before initiation of RT and at least 12 months after completion of RT. Cognitive functioning status was evaluated as change in scores over time. Results: Among the total of 30 patients, 23 patients (76.7%) had significantly lower post-RT cognitive functioning scores compared with their pre-RT scores (p =more » 0.033). The cognitive functioning scores had significantly declined in the domains of short-term memory, language abilities, and list-generating fluency (p = 0.020, 0.023, and 0.001, respectively). Compared with patients with a mean dose to the temporal lobes of 36 Gy or less, patients with a mean dose of greater than 36 Gy had a significantly greater reduction in cognitive functioning scores (p = 0.017). Patients in whom V60 of the temporal lobes (i.e., the percentage of the temporal lobe volume that had received >60 Gy) was greater than 10% also had a greater reduction in cognitive functioning scores than those in whom V60 was 10% or less (p = 0.039). Conclusions: The results of our study indicated that RT could have deleterious effects on cognitive function in patients with NPC. Efforts should be made to reduce the radiation dose and irradiated volume of temporal lobes without compromising the coverage of target volume.« less

Cardiac I-1c overexpression with reengineered AAV improves cardiac function in swine ischemic heart failure.

PubMed

Ishikawa, Kiyotake; Fish, Kenneth M; Tilemann, Lisa; Rapti, Kleopatra; Aguero, Jaume; Santos-Gallego, Carlos G; Lee, Ahyoung; Karakikes, Ioannis; Xie, Chaoqin; Akar, Fadi G; Shimada, Yuichi J; Gwathmey, Judith K; Asokan, Aravind; McPhee, Scott; Samulski, Jade; Samulski, Richard Jude; Sigg, Daniel C; Weber, Thomas; Kranias, Evangelia G; Hajjar, Roger J

2014-12-01

Cardiac gene therapy has emerged as a promising option to treat advanced heart failure (HF). Advances in molecular biology and gene targeting approaches are offering further novel options for genetic manipulation of the cardiovascular system. The aim of this study was to improve cardiac function in chronic HF by overexpressing constitutively active inhibitor-1 (I-1c) using a novel cardiotropic vector generated by capsid reengineering of adeno-associated virus (BNP116). One month after a large anterior myocardial infarction, 20 Yorkshire pigs randomly received intracoronary injection of either high-dose BNP116.I-1c (1.0 × 10(13) vector genomes (vg), n = 7), low-dose BNP116.I-1c (3.0 × 10(12) vg, n = 7), or saline (n = 6). Compared to baseline, mean left ventricular ejection fraction increased by 5.7% in the high-dose group, and by 5.2% in the low-dose group, whereas it decreased by 7% in the saline group. Additionally, preload-recruitable stroke work obtained from pressure-volume analysis demonstrated significantly higher cardiac performance in the high-dose group. Likewise, other hemodynamic parameters, including stroke volume and contractility index indicated improved cardiac function after the I-1c gene transfer. Furthermore, BNP116 showed a favorable gene expression pattern for targeting the heart. In summary, I-1c overexpression using BNP116 improves cardiac function in a clinically relevant model of ischemic HF.

Cardiac I-1c Overexpression With Reengineered AAV Improves Cardiac Function in Swine Ischemic Heart Failure

PubMed Central

Ishikawa, Kiyotake; Fish, Kenneth M; Tilemann, Lisa; Rapti, Kleopatra; Aguero, Jaume; Santos-Gallego, Carlos G; Lee, Ahyoung; Karakikes, Ioannis; Xie, Chaoqin; Akar, Fadi G; Shimada, Yuichi J; Gwathmey, Judith K; Asokan, Aravind; McPhee, Scott; Samulski, Jade; Samulski, Richard Jude; Sigg, Daniel C; Weber, Thomas; Kranias, Evangelia G; Hajjar, Roger J

2014-01-01

Cardiac gene therapy has emerged as a promising option to treat advanced heart failure (HF). Advances in molecular biology and gene targeting approaches are offering further novel options for genetic manipulation of the cardiovascular system. The aim of this study was to improve cardiac function in chronic HF by overexpressing constitutively active inhibitor-1 (I-1c) using a novel cardiotropic vector generated by capsid reengineering of adeno-associated virus (BNP116). One month after a large anterior myocardial infarction, 20 Yorkshire pigs randomly received intracoronary injection of either high-dose BNP116.I-1c (1.0 × 1013 vector genomes (vg), n = 7), low-dose BNP116.I-1c (3.0 × 1012 vg, n = 7), or saline (n = 6). Compared to baseline, mean left ventricular ejection fraction increased by 5.7% in the high-dose group, and by 5.2% in the low-dose group, whereas it decreased by 7% in the saline group. Additionally, preload-recruitable stroke work obtained from pressure–volume analysis demonstrated significantly higher cardiac performance in the high-dose group. Likewise, other hemodynamic parameters, including stroke volume and contractility index indicated improved cardiac function after the I-1c gene transfer. Furthermore, BNP116 showed a favorable gene expression pattern for targeting the heart. In summary, I-1c overexpression using BNP116 improves cardiac function in a clinically relevant model of ischemic HF. PMID:25023328

The use of new GAFCHROMIC EBT film for 125I seed dosimetry in Solid Water phantom.

PubMed

Chiu-Tsao, Sou-Tung; Medich, David; Munro, John

2008-08-01

Radiochromic film dosimetry has been extensively used for intravascular brachytherapy applications for near field within 1 cm from the sources. With the recent introduction of new model of radiochromic films, GAFCHROMIC EBT, with higher sensitivity than earlier models, it is promising to extend the distances out to 5 cm for low dose rate (LDR) source dosimetry. In this study, the use of new model GAFCHROMIC EBT film for 125I seed dosimetry in Solid Water was evaluated for radial distances from 0.06 cm out to 5 cm. A multiple film technique was employed for four 125I seeds (Implant Sciences model 3500) with NIST traceable air kerma strengths. Each experimental film was positioned in contact with a 125I seed in a Solid Water phantom. The products of the air kerma strength and exposure time ranged from 8 to 3158 U-h, with the initial air kerma strength of 6 U in a series of 25 experiments. A set of 25 calibration films each was sequentially exposed to one 125I seed at about 0.58 cm distance for doses from 0.1 to 33 Gy. A CCD camera based microdensitometer, with interchangeable green (520 nm) and red (665 nm) light boxes, was used to scan all the films with 0.2 mm pixel resolution. The dose to each 125I calibration film center was calculated using the air kerma strength of the seed (incorporating decay), exposure time, distance from seed center to film center, and TG43U1S1 recommended dosimetric parameters. Based on the established calibration curve, dose conversion from net optical density was achieved for each light source. The dose rate constant was determined as 0.991 cGy U(-1)h(-1) (+/-6.9%) and 1.014 cGy U(-1)h(-1) (+/-6.8%) from films scanned using green and red light sources, respectively. The difference between these two values was within the uncertainty of the measurement. Radial dose function and 2D anisotropy function were also determined. The results obtained using the two light sources corroborated each other. We found good agreement with the TG43U1S1 recommended values of radial dose function and 2D anisotropy function, to within the uncertainty of the measurement. We also verified the dosimetric parameters in the near field calculated by Rivard using Monte Carlo method. The radial dose function values in Solid Water were lower than those in water recommended by TG43U1S1, by about 2%, 3%, 7%, and 14% at 2, 3, 4, and 5 cm, respectively, partially due to the difference in the phantom material composition. Radiochromic film dosimetry using GAFCHROMIC EBT model is feasible in determining 2D dose distributions around low dose rate 125I seed. It is a viable alternative to TLD dosimetry for 125I seed dose characterization.

Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial.

PubMed

Chen, Horng H; Anstrom, Kevin J; Givertz, Michael M; Stevenson, Lynne W; Semigran, Marc J; Goldsmith, Steven R; Bart, Bradley A; Bull, David A; Stehlik, Josef; LeWinter, Martin M; Konstam, Marvin A; Huggins, Gordon S; Rouleau, Jean L; O'Meara, Eileen; Tang, W H Wilson; Starling, Randall C; Butler, Javed; Deswal, Anita; Felker, G Michael; O'Connor, Christopher M; Bonita, Raphael E; Margulies, Kenneth B; Cappola, Thomas P; Ofili, Elizabeth O; Mann, Douglas L; Dávila-Román, Víctor G; McNulty, Steven E; Borlaug, Barry A; Velazquez, Eric J; Lee, Kerry L; Shah, Monica R; Hernandez, Adrian F; Braunwald, Eugene; Redfield, Margaret M

2013-12-18

Small studies suggest that low-dose dopamine or low-dose nesiritide may enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction; however, neither strategy has been rigorously tested. To test the 2 independent hypotheses that, compared with placebo, addition of low-dose dopamine (2 μg/kg/min) or low-dose nesiritide (0.005 μg/kg/min without bolus) to diuretic therapy will enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction. Multicenter, double-blind, placebo-controlled clinical trial (Renal Optimization Strategies Evaluation [ROSE]) of 360 hospitalized patients with acute heart failure and renal dysfunction (estimated glomerular filtration rate of 15-60 mL/min/1.73 m2), randomized within 24 hours of admission. Enrollment occurred from September 2010 to March 2013 across 26 sites in North America. Participants were randomized in an open, 1:1 allocation ratio to the dopamine or nesiritide strategy. Within each strategy, participants were randomized in a double-blind, 2:1 ratio to active treatment or placebo. The dopamine (n = 122) and nesiritide (n = 119) groups were independently compared with the pooled placebo group (n = 119). Coprimary end points included 72-hour cumulative urine volume (decongestion end point) and the change in serum cystatin C from enrollment to 72 hours (renal function end point). Compared with placebo, low-dose dopamine had no significant effect on 72-hour cumulative urine volume (dopamine, 8524 mL; 95% CI, 7917-9131 vs placebo, 8296 mL; 95% CI, 7762-8830 ; difference, 229 mL; 95% CI, -714 to 1171 mL; P = .59) or on the change in cystatin C level (dopamine, 0.12 mg/L; 95% CI, 0.06-0.18 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, 0.01; 95% CI, -0.08 to 0.10; P = .72). Similarly, low-dose nesiritide had no significant effect on 72-hour cumulative urine volume (nesiritide, 8574 mL; 95% CI, 8014-9134 vs placebo, 8296 mL; 95% CI, 7762-8830; difference, 279 mL; 95% CI, -618 to 1176 mL; P = .49) or on the change in cystatin C level (nesiritide, 0.07 mg/L; 95% CI, 0.01-0.13 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, -0.04; 95% CI, -0.13 to 0.05; P = .36). Compared with placebo, there was no effect of low-dose dopamine or nesiritide on secondary end points reflective of decongestion, renal function, or clinical outcomes. In participants with acute heart failure and renal dysfunction, neither low-dose dopamine nor low-dose nesiritide enhanced decongestion or improved renal function when added to diuretic therapy. clinicaltrials.gov Identifier: NCT01132846.

Dose to mass for evaluation and optimization of lung cancer radiation therapy.

PubMed

Tyler Watkins, William; Moore, Joseph A; Hugo, Geoffrey D; Siebers, Jeffrey V

2017-11-01

To evaluate potential organ at risk dose-sparing by using dose-mass-histogram (DMH) objective functions compared with dose-volume-histogram (DVH) objective functions. Treatment plans were retrospectively optimized for 10 locally advanced non-small cell lung cancer patients based on DVH and DMH objectives. DMH-objectives were the same as DVH objectives, but with mass replacing volume. Plans were normalized to dose to 95% of the PTV volume (PTV-D95v) or mass (PTV-D95m). For a given optimized dose, DVH and DMH were intercompared to ascertain dose-to-volume vs. dose-to-mass differences. Additionally, the optimized doses were intercompared using DVH and DMH metrics to ascertain differences in optimized plans. Mean dose to volume, D v ‾, mean dose to mass, D M ‾, and fluence maps were intercompared. For a given dose distribution, DVH and DMH differ by >5% in heterogeneous structures. In homogeneous structures including heart and spinal cord, DVH and DMH are nearly equivalent. At fixed PTV-D95v, DMH-optimization did not significantly reduce dose to OARs but reduced PTV-D v ‾ by 0.20±0.2Gy (p=0.02) and PTV-D M ‾ by 0.23±0.3Gy (p=0.02). Plans normalized to PTV-D95m also result in minor PTV dose reductions and esophageal dose sparing (D v ‾ reduced 0.45±0.5Gy, p=0.02 and D M ‾ reduced 0.44±0.5Gy, p=0.02) compared to DVH-optimized plans. Optimized fluence map comparisons indicate that DMH optimization reduces dose in the periphery of lung PTVs. DVH- and DMH-dose indices differ by >5% in lung and lung target volumes for fixed dose distributions, but optimizing DMH did not reduce dose to OARs. The primary difference observed in DVH- and DMH-optimized plans were variations in fluence to the periphery of lung target PTVs, where low density lung surrounds tumor. Copyright © 2017 Elsevier B.V. All rights reserved.

IMRT: Improvement in treatment planning efficiency using NTCP calculation independent of the dose-volume-histogram

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

Grigorov, Grigor N.; Chow, James C.L.; Grigorov, Lenko

2006-05-15

The normal tissue complication probability (NTCP) is a predictor of radiobiological effect for organs at risk (OAR). The calculation of the NTCP is based on the dose-volume-histogram (DVH) which is generated by the treatment planning system after calculation of the 3D dose distribution. Including the NTCP in the objective function for intensity modulated radiation therapy (IMRT) plan optimization would make the planning more effective in reducing the postradiation effects. However, doing so would lengthen the total planning time. The purpose of this work is to establish a method for NTCP determination, independent of a DVH calculation, as a quality assurancemore » check and also as a mean of improving the treatment planning efficiency. In the study, the CTs of ten randomly selected prostate patients were used. IMRT optimization was performed with a PINNACLE3 V 6.2b planning system, using planning target volume (PTV) with margins in the range of 2 to 10 mm. The DVH control points of the PTV and OAR were adapted from the prescriptions of Radiation Therapy Oncology Group protocol P-0126 for an escalated prescribed dose of 82 Gy. This paper presents a new model for the determination of the rectal NTCP ({sub R}NTCP). The method uses a special function, named GVN (from Gy, Volume, NTCP), which describes the {sub R}NTCP if 1 cm{sup 3} of the volume of intersection of the PTV and rectum (R{sub int}) is irradiated uniformly by a dose of 1 Gy. The function was 'geometrically' normalized using a prostate-prostate ratio (PPR) of the patients' prostates. A correction of the {sub R}NTCP for different prescribed doses, ranging from 70 to 82 Gy, was employed in our model. The argument of the normalized function is the R{sub int}, and parameters are the prescribed dose, prostate volume, PTV margin, and PPR. The {sub R}NTCPs of another group of patients were calculated by the new method and the resulting difference was <{+-}5% in comparison to the NTCP calculated by the PINNACLE3 software where Kutcher's dose-response model for NTCP calculation is adopted.« less

Environmental standards for ionizing radiation: theoretical basis for dose-response curves.

PubMed Central

Upton, A C

1983-01-01

The types of injury attributable to ionizing radiation are subdivided, for purposes of risk assessment and radiological protection, into two broad categories: stochastic effects and nonstochastic effects. Stochastic effects are viewed as probablistic phenomena, varying in frequency but not severity as a function of the dose, without any threshold; nonstochastic effects are viewed as deterministic phenomena, varying in both frequency and severity as a function of the dose, with clinical thresholds. Included among stochastic effects are heritable effects (mutations and chromosome aberrations) and carcinogenic effects. Both types of effects are envisioned as unicellular phenomena which can result from nonlethal injury of individual cells, without the necessity of damage to other cells. For the induction of mutations and chromosome aberrations in the low-to-intermediate dose range, the dose-response curve with high-linear energy transfer (LET) radiation generally conforms to a linear nonthreshold relationship and varies relatively little with the dose rate. In contrast, the curve with low-LET radiation generally conforms to a linear-quadratic relationship, rising less steeply than the curve with high-LET radiation and increasing in slope with increasing dose and dose rate. The dose-response curve for carcinogenic effects varies widely from one type of neoplasm to another in the intermediate-to-high dose range, in part because of differences in the way large doses of radiation can affect the promotion and progression of different neoplasms. Information about dose-response relations for low-level irradiation is fragmentary but consistent, in general, with the hypothesis that the neoplastic transformation may result from mutation, chromosome aberration or genetic recombination in a single susceptible cell. PMID:6653536

External dose-rate conversion factors of radionuclides for air submersion, ground surface contamination and water immersion based on the new ICRP dosimetric setting.

PubMed

Yoo, Song Jae; Jang, Han-Ki; Lee, Jai-Ki; Noh, Siwan; Cho, Gyuseong

2013-01-01

For the assessment of external doses due to contaminated environment, the dose-rate conversion factors (DCFs) prescribed in Federal Guidance Report 12 (FGR 12) and FGR 13 have been widely used. Recently, there were significant changes in dosimetric models and parameters, which include the use of the Reference Male and Female Phantoms and the revised tissue weighting factors, as well as the updated decay data of radionuclides. In this study, the DCFs for effective and equivalent doses were calculated for three exposure settings: skyshine, groundshine and water immersion. Doses to the Reference Phantoms were calculated by Monte Carlo simulations with the MCNPX 2.7.0 radiation transport code for 26 mono-energy photons between 0.01 and 10 MeV. The transport calculations were performed for the source volume within the cut-off distances practically contributing to the dose rates, which were determined by a simplified calculation model. For small tissues for which the reduction of variances are difficult, the equivalent dose ratios to a larger tissue (with lower statistical errors) nearby were employed to make the calculation efficient. Empirical response functions relating photon energies, and the organ equivalent doses or the effective doses were then derived by the use of cubic-spline fitting of the resulting doses for 26 energy points. The DCFs for all radionuclides considered important were evaluated by combining the photon emission data of the radionuclide and the empirical response functions. Finally, contributions of accompanied beta particles to the skin equivalent doses and the effective doses were calculated separately and added to the DCFs. For radionuclides considered in this study, the new DCFs for the three exposure settings were within ±10 % when compared with DCFs in FGR 13.

Pharmacokinetic Profile and Tolerability of Liposomal Bupivacaine Following a Repeated Dose via Local Subcutaneous Infiltration in Healthy Volunteers.

PubMed

Rice, David; Heil, Justin W; Biernat, Lukasz

2017-03-01

Liposomal bupivacaine is indicated for administration into the surgical site to produce post-surgical analgesia. The objectives of this study were to characterize the pharmacokinetic and safety profiles of liposomal bupivacaine following a repeated dose in healthy volunteers. Healthy adults were assigned to receive liposomal bupivacaine via subcutaneous infiltration in a single 266 mg dose (cohort 1) or in two 266 mg doses, with the second dose given immediately, 24, 48, or 72 h after the first dose (cohorts 2-5). Pharmacokinetic parameters were estimated from blood samples collected up to day 14. Subjects were monitored for adverse events and assessed for neurologic function, cardiac function, and infiltration area abnormalities. Twelve subjects were assigned to each cohort. The mean ± standard deviation maximum observed plasma concentration (C max ) of bupivacaine after a single dose was 129 ± 47 ng/mL. The mean C max after the second dose was higher, but always less than double the C max for cohort 1. The highest individual C max (589 ng/mL) was observed in a subject who received the second dose 24 h after the first dose (cohort 4), but was well below the reported thresholds for neurotoxicity and cardiac toxicity (2000 and 4000 ng/mL, respectively). A single and repeated dose were well-tolerated, and there were no clinically meaningful findings regarding neurologic examinations and electrocardiography. The mean C max following a repeated dose of liposomal bupivacaine remained well below accepted values for central nervous system and cardiac toxicity. Liposomal bupivacaine was well-tolerated and revealed no clinically important safety signals. CLINICALTRIALS. NCT02210247.

External dose-rate conversion factors of radionuclides for air submersion, ground surface contamination and water immersion based on the new ICRP dosimetric setting

PubMed Central

Yoo, Song Jae; Jang, Han-Ki; Lee, Jai-Ki; Noh, Siwan; Cho, Gyuseong

2013-01-01

For the assessment of external doses due to contaminated environment, the dose-rate conversion factors (DCFs) prescribed in Federal Guidance Report 12 (FGR 12) and FGR 13 have been widely used. Recently, there were significant changes in dosimetric models and parameters, which include the use of the Reference Male and Female Phantoms and the revised tissue weighting factors, as well as the updated decay data of radionuclides. In this study, the DCFs for effective and equivalent doses were calculated for three exposure settings: skyshine, groundshine and water immersion. Doses to the Reference Phantoms were calculated by Monte Carlo simulations with the MCNPX 2.7.0 radiation transport code for 26 mono-energy photons between 0.01 and 10 MeV. The transport calculations were performed for the source volume within the cut-off distances practically contributing to the dose rates, which were determined by a simplified calculation model. For small tissues for which the reduction of variances are difficult, the equivalent dose ratios to a larger tissue (with lower statistical errors) nearby were employed to make the calculation efficient. Empirical response functions relating photon energies, and the organ equivalent doses or the effective doses were then derived by the use of cubic-spline fitting of the resulting doses for 26 energy points. The DCFs for all radionuclides considered important were evaluated by combining the photon emission data of the radionuclide and the empirical response functions. Finally, contributions of accompanied beta particles to the skin equivalent doses and the effective doses were calculated separately and added to the DCFs. For radionuclides considered in this study, the new DCFs for the three exposure settings were within ±10 % when compared with DCFs in FGR 13. PMID:23542764

Investigation of practical approaches to evaluating cumulative dose for cone beam computed tomography (CBCT) from standard CT dosimetry measurements: a Monte Carlo study.

PubMed

Abuhaimed, Abdullah; Martin, Colin J; Sankaralingam, Marimuthu; Gentle, David J

2015-07-21

A function called Gx(L) was introduced by the International Commission on Radiation Units and Measurements (ICRU) Report-87 to facilitate measurement of cumulative dose for CT scans within long phantoms as recommended by the American Association of Physicists in Medicine (AAPM) TG-111. The Gx(L) function is equal to the ratio of the cumulative dose at the middle of a CT scan to the volume weighted CTDI (CTDIvol), and was investigated for conventional multi-slice CT scanners operating with a moving table. As the stationary table mode, which is the basis for cone beam CT (CBCT) scans, differs from that used for conventional CT scans, the aim of this study was to investigate the extension of the Gx(L) function to CBCT scans. An On-Board Imager (OBI) system integrated with a TrueBeam linac was simulated with Monte Carlo EGSnrc/BEAMnrc, and the absorbed dose was calculated within PMMA, polyethylene (PE), and water head and body phantoms using EGSnrc/DOSXYZnrc, where the body PE body phantom emulated the ICRU/AAPM phantom. Beams of width 40-500 mm and beam qualities at tube potentials of 80-140 kV were studied. Application of a modified function of beam width (W) termed Gx(W), for which the cumulative dose for CBCT scans f (0) is normalized to the weighted CTDI (CTDIw) for a reference beam of width 40 mm, was investigated as a possible option. However, differences were found in Gx(W) with tube potential, especially for body phantoms, and these were considered to be due to differences in geometry between wide beams used for CBCT scans and those for conventional CT. Therefore, a modified function Gx(W)100 has been proposed, taking the form of values of f (0) at each position in a long phantom, normalized with respect to dose indices f 100(150)x measured with a 100 mm pencil ionization chamber within standard 150 mm PMMA phantoms, using the same scanning parameters, beam widths and positions within the phantom. f 100(150)x averages the dose resulting from a CBCT scan over the 100 mm length. Like the Gx(L) function, the Gx(W)100 function showed only a weak dependency on tube potential at most positions for the phantoms studied. The results were fitted to polynomial equations from which f (0) within the longer PMMA, PE, or water phantoms can be evaluated from measurements of f 100(150)x. Comparisons with other studies, suggest that these functions may be suitable for application to any CT or CBCT scan acquired with stationary table mode.

Fractionated radiation facilitates repair and functional motor recovery after spinal cord transection in rat.

PubMed

Kalderon, N; Xu, S; Koutcher, J A; Fuks, Z

2001-06-22

Previous studies suggest that motor recovery does not occur after spinal cord injury because reactive glia abort the natural repair processes. A permanent wound gap is left in the cord and the brain-cord circuitry consequently remains broken. Single-dose x-irradiation destroys reactive glia at the damage site in transected adult rat spinal cord. The wound then heals naturally, and a partially functional brain-cord circuitry is reconstructed. Timing is crucial; cell ablation is beneficial only within the third week after injury. Data presented here point to the possibility of translating these observations into a clinical therapy for preventing the paralysis following spinal cord injury in the human. The lesion site (at low thoracic level) in severed adult rat spinal cord was treated daily, over the third week postinjury, with protocols of fractionated radiation similar to those for treating human spinal cord tumors. This resulted, as with the single-dose protocol, in wound healing and restoration of some hindquarter motor function; in addition, the beneficial outcome was augmented. Of the restored hindlimb motor functions, weight-support and posture in stance was the only obvious one. Recovery of this motor function was partial to substantial and its incidence was 100% instead of about 50% obtained with the single-dose treatment. None of the hindlimbs, however, regained frequent stepping or any weight-bearing locomotion. These data indicate that the therapeutic outcome may be further augmented by tuning the radiation parameters within the critical time-window after injury. These data also indicate that dose-fractionation is an effective strategy and better than the single-dose treatment for targeting of reactive cells that abort the natural repair, suggesting that radiation therapy could be developed into a therapeutic procedure for repairing injured spinal cord.

Treatment with a nitric oxide-donating NSAID alleviates functional muscle ischemia in the mouse model of Duchenne muscular dystrophy.

PubMed

Thomas, Gail D; Ye, Jianfeng; De Nardi, Claudio; Monopoli, Angela; Ongini, Ennio; Victor, Ronald G

2012-01-01

In patients with Duchenne muscular dystrophy (DMD) and the standard mdx mouse model of DMD, dystrophin deficiency causes loss of neuronal nitric oxide synthase (nNOSμ) from the sarcolemma, producing functional ischemia when the muscles are exercised. We asked if functional muscle ischemia would be eliminated and normal blood flow regulation restored by treatment with an exogenous nitric oxide (NO)-donating drug. Beginning at 8 weeks of age, mdx mice were fed a standard diet supplemented with 1% soybean oil alone or in combination with a low (15 mg/kg) or high (45 mg/kg) dose of HCT 1026, a NO-donating nonsteroidal anti-inflammatory agent which has previously been shown to slow disease progression in the mdx model. After 1 month of treatment, vasoconstrictor responses to intra-arterial norepinephrine (NE) were compared in resting and contracting hindlimbs. In untreated mdx mice, the usual effect of muscle contraction to attenuate NE-mediated vasoconstriction was impaired, resulting in functional ischemia: NE evoked similar decreases in femoral blood flow velocity and femoral vascular conductance (FVC) in the contracting compared to resting hindlimbs (ΔFVC contraction/ΔFVC rest=0.88 ± 0.03). NE-induced functional ischemia was unaffected by low dose HCT 1026 (ΔFVC ratio=0.92 ± 0.04; P>0.05 vs untreated), but was alleviated by the high dose of the drug (ΔFVC ratio=0.22 ± 0.03; P<0.05 vs untreated or low dose). The beneficial effect of high dose HCT 1026 was maintained with treatment up to 3 months. The effect of the NO-donating drug HCT 1026 to normalize blood flow regulation in contracting mdx mouse hindlimb muscles suggests a putative novel treatment for DMD. Further translational research is warranted.

Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model

PubMed Central

Botelho, Danielle; Leo, Bey F.; Massa, Christopher; Sarkar, Srijata; Tetley, Terry; Chung, Kian F.; Chen, Shu; Ryan, Mary P.; Porter, Alexandra; Atochina-Vasserman, Elena N.; Zhang, Junfeng; Schwander, Stephan; Gow, Andrew J.

2018-01-01

Here we examine the organ level toxicology of both carbon black (CB) and silver nanoparticles (AgNP). We aim to determine metal-specific effects to respiratory function, inflammation and potential interactions with lung lining fluid (LLF). C57Bl6/J male mice were intratracheally instilled with saline (control), low (0.05 μg/g) or high (0.5 μg/g) doses of either AgNP or CB 15 nm nanospheres. Lung histology, cytology, surfactant composition and function, inflammatory gene expression, and pulmonary function were measured at 1, 3, and 7 days post-exposure. Acutely, high dose CB resulted in an inflammatory response, increased neutrophilia and cytokine production, without alteration in surfactant composition or respiratory mechanics. Low dose CB had no effect. Neither low nor high dose AgNPs resulted in an acute inflammatory response, but there was an increase in work of breathing. Three days post-exposure with CB, a persistent neutrophilia was noted. High dose AgNP resulted in an elevated number of macrophages and invasion of lymphocytes. Additionally, AgNP treated mice displayed increased expression of IL1B, IL6, CCL2, and IL10. However, there were no significant changes in respiratory mechanics. At day 7, inflammation had resolved in AgNP-treated mice, but tissue stiffness and resistance were significantly decreased, which was accompanied by an increase in surfactant protein D (SP-D) content. These data demonstrate that the presence of metal alters the response of the lung to nanoparticle exposure. AgNP-surfactant interactions may alter respiratory function and result in a delayed immune response, potentially due to modified airway epithelial cell function. PMID:29632485

Radiation dose reduction in computed tomography perfusion using spatial-temporal Bayesian methods

NASA Astrophysics Data System (ADS)

Fang, Ruogu; Raj, Ashish; Chen, Tsuhan; Sanelli, Pina C.

2012-03-01

In current computed tomography (CT) examinations, the associated X-ray radiation dose is of significant concern to patients and operators, especially CT perfusion (CTP) imaging that has higher radiation dose due to its cine scanning technique. A simple and cost-effective means to perform the examinations is to lower the milliampere-seconds (mAs) parameter as low as reasonably achievable in data acquisition. However, lowering the mAs parameter will unavoidably increase data noise and degrade CT perfusion maps greatly if no adequate noise control is applied during image reconstruction. To capture the essential dynamics of CT perfusion, a simple spatial-temporal Bayesian method that uses a piecewise parametric model of the residual function is used, and then the model parameters are estimated from a Bayesian formulation of prior smoothness constraints on perfusion parameters. From the fitted residual function, reliable CTP parameter maps are obtained from low dose CT data. The merit of this scheme exists in the combination of analytical piecewise residual function with Bayesian framework using a simpler prior spatial constrain for CT perfusion application. On a dataset of 22 patients, this dynamic spatial-temporal Bayesian model yielded an increase in signal-tonoise-ratio (SNR) of 78% and a decrease in mean-square-error (MSE) of 40% at low dose radiation of 43mA.

Memantine elicits spinal blockades of motor function, proprioception, and nociception in rats.

PubMed

Chen, Yu-Wen; Chiu, Chong-Chi; Liu, Kuo-Sheng; Hung, Ching-Hsia; Wang, Jhi-Joung

2015-12-01

Although memantine blocks sodium currents and produces local skin anesthesia, spinal anesthesia with memantine is unknown. The purpose of the study was to evaluate the local anesthetic effect of memantine in spinal anesthesia and its comparison with a widely used local anesthetic lidocaine. After intrathecally injecting the rats with five doses of each drug, the dose-response curves of memantine and lidocaine were constructed. The potencies of the drugs and durations of spinal anesthetic effects on motor function, proprioception, and nociception were compared with those of lidocaine. We showed that memantine produced dose-dependent spinal blockades in motor function, proprioception, and nociception. On a 50% effective dose (ED50 ) basis, the rank of potency was lidocaine greater than memantine (P < 0.05 for the differences). At the equipotent doses (ED25 , ED50 , ED75 ), the block duration produced by memantine was longer than that produced by lidocaine (P < 0.05 for the differences). Memantine, but not lidocaine, displayed more sensory/nociceptive block than motor block. The preclinical data demonstrated that memantine is less potent than lidocaine, whereas memantine produces longer duration of spinal anesthesia than lidocaine. Memantine shows a more sensory-selective action over motor blockade. © 2015 Société Française de Pharmacologie et de Thérapeutique.

Tetrahydrocannabinol-induced suppression of macrophage spreading and phagocytic activity in vitro.

PubMed

Lopez-Cepero, M; Friedman, M; Klein, T; Friedman, H

1986-06-01

The effects of tetrahydrocannabinol (THC) on several parameters of macrophage function in vitro were assessed. Delta 9 THC added to cultures of normal mouse peritoneal cells in vitro affected the ability of the cells to spread on glass surfaces and also had some effect on their ability to phagocytize yeast. These effects were dose related. A concentration of 20 micrograms of THC almost completely inhibited macrophage spreading, but it also decreased viability and the total number of these cells. Doses of 10 or 5 micrograms of THC also inhibited spreading but had little effect on cell viability or number. A dose of 1.0 microgram of THC had some inhibitory effect on spreading and the lowest dose affecting spreading appeared to be about 0.05 micrograms per culture. Higher doses of THC were necessary to inhibit phagocytosis of yeast particles as determined by direct microscopic examination or use of radiolabeled yeast as the test particles. These results indicate that several readily measured functions of macrophages may be suppressed by THC.

Functional heartburn: the stimulus, the pain, and the brain

PubMed Central

Fass, R; Tougas, G

2002-01-01

Functional heartburn is a common disorder and appears to be composed of several distinct subgroups. Identifying the different subgroups based on clinical history only is not achievable at present. The mechanisms responsible for pain, clinical characteristics, and the optimal therapeutic approach remain poorly understood. Response to potent antireflux treatment is relatively limited. Current and future treatment strategies for functional heartburn patients who have failed standard dose proton pump inhibitors (PPIs) include increased PPI dose in some, as well as addition of pain modulators in others. PMID:12427796

Structural, thermal, functional, antioxidant & antimicrobial properties of β-d-glucan extracted from baker's yeast (Saccharomyces cereviseae)-Effect of γ-irradiation.

PubMed

Khan, Asma Ashraf; Gani, Adil; Masoodi, F A; Amin, Furheen; Wani, Idrees Ahmed; Khanday, Firdous Ahmad; Gani, Asir

2016-04-20

This study was carried out to evaluate the effect of γ-irradiation (0, 5, 10, 20, 30 & 50kGy) on the structural, functional, antioxidant and antimicrobial properties of yeast β-d-glucan. The samples were characterized by ATR-FTIR, gel permeation chromatography (GPC) and the thermal properties were studied using DSC. There was a decrease in the average molecular weight of β-d-glucan as the irradiation dose increased. The functional properties of irradiated yeast β-d-glucan were largely influenced by the action of gamma radiation like swelling power and viscosity decreases with increase in the irradiation dose while as fat binding capacity, emulsifying properties, foaming properties and bile acid binding capacity shows an increasing trend. All the antioxidant properties carried out using six different assays increased significantly (p≤0.05) in a dose dependent manner. The antibacterial activity of yeast β-d-glucan also showed an increasing trend with increase in the irradiation dose from 5 to 50kDa. Copyright © 2016 Elsevier Ltd. All rights reserved.

Absolute dose calibration of an X-ray system and dead time investigations of photon-counting techniques

NASA Astrophysics Data System (ADS)

Carpentieri, C.; Schwarz, C.; Ludwig, J.; Ashfaq, A.; Fiederle, M.

2002-07-01

High precision concerning the dose calibration of X-ray sources is required when counting and integrating methods are compared. The dose calibration for a dental X-ray tube was executed with special dose calibration equipment (dosimeter) as function of exposure time and rate. Results were compared with a benchmark spectrum and agree within ±1.5%. Dead time investigations with the Medipix1 photon-counting chip (PCC) have been performed by rate variations. Two different types of dead time, paralysable and non-paralysable will be discussed. The dead time depends on settings of the front-end electronics and is a function of signal height, which might lead to systematic defects of systems. Dead time losses in excess of 30% have been found for the PCC at 200 kHz absorbed photons per pixel.

[Evaluation of immunotoxicity tests using cyclosporin A-treated rats: the International Collaborative Immunotoxicity Study II (cyclosporin A)].

PubMed

Ochiai, T; Naito, K; Murakami, O; Ohno, K; Sekita, K; Furuya, T; Kurokawa, Y; Matsumoto, K; Saito, Y; Hachisuka, A

1993-01-01

Immunotoxicological effects of cyclosporin A (CsA) were studied by enhanced histopathological and functional tests in rats. Male F344 rats were orally administered with CsA in doses of 0, 2.5, 10, and 40 mg/kg/day for 28 successive days. Hematological examination revealed that the CsA treatment brought about a marked dose-dependent decrease in the number of WBCs, which was attributed to a decrease in the number of lymphocytes. In the femoral bone marrow, a significant reduction in the number of nucleated cells was observed, which was attributed to a decrease in the number of lymphocytes and erythroblasts. Histopathologically, diminution of thymic medullas, appearance of tangible body macrophages in thymic cortices, and calcification and basophilic changes in kidneys were observed in the middle and high dose groups. Immunohistological examination with anti-rat T lymphocyte antibody showed a decrease in the number of T cells at the periarterial lymphatic sheaths in the spleens. As for the functional tests, CsA treatment remarkably reduced the PFC number even in the low dose group. The Con A response of spleen cells was decreased in the middle and high dose groups. The STM response was reduced only in the high dose group. The NK activity was little affected. Thus, in the CsA-treated F344 rats, the enhanced histopathological and some functional tests which were proposed by ICICIS, were found to be useful to detect damages to the immune system.

Influence of gamma-radiation on the nutritional and functional qualities of lotus seed flour.

PubMed

Bhat, Rajeev; Sridhar, Kandikere Ramaiah; Karim, Alias A; Young, Chiu C; Arun, Ananthapadmanabha B

2009-10-28

In the present study, we investigated the physicochemical and functional properties of lotus seed flour exposed to low and high doses of gamma-radiation (0-30 kGy; the dose recommended for quarantine and hygienic purposes). The results indicated raw seed flour to be rich in nutrients with minimal quantities of antinutritional factors. Irradiation resulted in a dose-dependent increase in some of the proximal constituents. The raw and gamma-irradiated seeds meet the Food and Agricultural Organization-World Health Organization recommended pattern of essential amino acids. Some of the antinutritional factors (phytic acid, total phenolics, and tannins) were lowered with gamma-irradiation, while the seed flours were devoid of lectins, L-3,4-dihydroxyphenylalanine, and polonium-210. The functional properties of the seed flour were significantly improved with gamma-radiation. gamma-radiation selectively preserved or improved the desired nutritional and functional traits of lotus seeds, thus ensuring a safe production of appropriate nutraceutically valued products.

Effects of Home-Based Constraint-Induced Therapy versus Dose-Matched Control Intervention on Functional Outcomes and Caregiver Well-Being in Children with Cerebral Palsy

ERIC Educational Resources Information Center

Lin, Keh-chung; Wang, Tien-ni; Wu, Ching-yi; Chen, Chia-ling; Chang, Kai-chieh; Lin, Yu-chan; Chen, Yi-ju

2011-01-01

This study compared home-based constraint-induced therapy (CIT) with a dose-matched home-based control intervention for children with cerebral palsy (CP). The differences in unilateral and bilateral motor performance, daily functions, and quality of parental well-being (i.e., the stress level of their parents) were evaluated. The study included 21…

Antimalarial Activity of Cocos nucifera Husk Fibre: Further Studies

PubMed Central

Adebayo, J. O.; Balogun, E. A.; Malomo, S. O.; Soladoye, A. O.; Olatunji, L. A.; Kolawole, O. M.; Oguntoye, O. S.; Babatunde, A. S.; Akinola, O. B.; Aguiar, A. C. C.; Andrade, I. M.; Souza, N. B.; Krettli, A. U.

2013-01-01

In this study, the antimalarial and toxicity potentials of husk fibre extracts of five Nigerian varieties of Cocos nucifera were evaluated in vitro. The only active extract fraction, West African Tall (WAT) ethyl acetate extract fraction, was then evaluated for its phytochemical constituents, antimalarial and toxicity potentials at varying doses (31.25–500 mg/kg body weight) using various organ function indices. The results revealed that WAT ethyl acetate extract fraction (WATEAEF) contained alkaloids, tannins, and flavonoids and was active against Plasmodium falciparum W2 strain maintained in continuous culture, with a selectivity index of 30.3. The same extract fraction was active in vivo against Plasmodium berghei NK65, causing more than 50% reduction in parasitaemia on days 4 and 6 after inoculation at various doses administered. WATEAEF did not significantly alter (P > 0.05) function indices of the liver and cardiovascular system at all doses administered but significantly increased (P < 0.05) plasma creatinine concentration at 250 and 500 mg/Kg body weight compared to controls. The results of this study suggest that WATEAEF possesses antimalarial activity and may not adversely affect normal liver function nor predispose subjects to cardiovascular diseases but may impair normal kidney function at higher doses. Further studies are underway to isolate the active principles. PMID:23983800

Antimalarial Activity of Cocos nucifera Husk Fibre: Further Studies.

PubMed

Adebayo, J O; Balogun, E A; Malomo, S O; Soladoye, A O; Olatunji, L A; Kolawole, O M; Oguntoye, O S; Babatunde, A S; Akinola, O B; Aguiar, A C C; Andrade, I M; Souza, N B; Krettli, A U

2013-01-01

In this study, the antimalarial and toxicity potentials of husk fibre extracts of five Nigerian varieties of Cocos nucifera were evaluated in vitro. The only active extract fraction, West African Tall (WAT) ethyl acetate extract fraction, was then evaluated for its phytochemical constituents, antimalarial and toxicity potentials at varying doses (31.25-500 mg/kg body weight) using various organ function indices. The results revealed that WAT ethyl acetate extract fraction (WATEAEF) contained alkaloids, tannins, and flavonoids and was active against Plasmodium falciparum W2 strain maintained in continuous culture, with a selectivity index of 30.3. The same extract fraction was active in vivo against Plasmodium berghei NK65, causing more than 50% reduction in parasitaemia on days 4 and 6 after inoculation at various doses administered. WATEAEF did not significantly alter (P > 0.05) function indices of the liver and cardiovascular system at all doses administered but significantly increased (P < 0.05) plasma creatinine concentration at 250 and 500 mg/Kg body weight compared to controls. The results of this study suggest that WATEAEF possesses antimalarial activity and may not adversely affect normal liver function nor predispose subjects to cardiovascular diseases but may impair normal kidney function at higher doses. Further studies are underway to isolate the active principles.

Thyroid Hormones and Thyroid Disease in Relation to Perchlorate Dose and Residence Near a Superfund Site

PubMed Central

Gold, Ellen B.; Blount, Benjamin C.; Rasor, Marianne O’Neill; Lee, Jennifer S.; Alwis, Udeni; Srivastav, Anup; Kim, Kyoungmi

2013-01-01

Background Perchlorate is a widely occurring contaminant, which can competitively inhibit iodide uptake and thus thyroid hormone production. The health effects of chronic low dose perchlorate exposure are largely unknown. Objectives In a community-based study, we compared thyroid function and disease in women with differing likelihoods of prior and current perchlorate exposure. Methods Residential blocks were randomly selected from areas: 1) with potential perchlorate exposure via drinking water; 2) with potential exposure to environmental contaminants; and 3) neighboring but without such exposures. Eligibility included having lived in the area for ≥6 months and aged 20–50 years during 1988–1996 (during documented drinking water well contamination). We interviewed 814 women and collected blood samples (assayed for thyroid stimulating hormone [TSH] and free thyroxine [fT4]) from 431 interviewed women. Daily urine samples were assayed for perchlorate and iodide for 178 premenopausal women with blood samples. We performed multivariable regression analyses comparing thyroid function and disease by residential area and by urinary perchlorate dose adjusted for urinary iodide levels. Results Residential location and current perchlorate dose were not associated with thyroid function or disease. Conclusions No persistent effect of perchlorate on thyroid function or disease was found several years after contaminated wells were capped. PMID:22968349

Depletion of florfenicol amine in tilapia (Oreochromis sp.) maintained in a recirculating aquaculture system following Aquaflor®-medicated feed therapy

USGS Publications Warehouse

Gaikowski, Mark P.; Whitsel, Melissa K.; Charles, Shawn; Schleis, Susan M.; Crouch, Louis S.; Endris, Richard G.

2015-01-01

Aquaflor® [50% w w−1 florfenicol (FFC)], is approved for use in freshwater-reared warmwater finfish which include tilapia Oreochromis spp. in the United States to control mortality from Streptococcus iniae. The depletion of florfenicol amine (FFA), the marker residue of FFC, was evaluated after feeding FFC-medicated feed to deliver a nominal 20 mg FFC kg−1 BW d−1 dose (1.33× the label use of 15 mg FFC kg−1 BW d−1) to Nile tilapia O. niloticus and hybrid tilapia O. niloticus × O. aureus held in a recirculating aquaculture system (RAS) at production-scale holding densities. Florfenicol amine concentrations were determined in fillets taken from 10 fish before dosing and from 20 fish at nine time points after dosing (from 1 to 240 h post-dosing). Water samples were assayed for FFC before, during and after the dosing period. Parameters monitored included daily feed consumption and biofilter function (levels of ammonia, nitrite and nitrate). Mean fillet FFA concentration decreased from 13.77 μg g−1 at 1-h post dosing to 0.39 μg g−1 at 240-h post dosing. Water FFC concentration decreased from a maximum of 1400 ng mL−1 at 1 day post-dosing to 847 ng mL−1 at 240 h post-dosing. There were no adverse effects noted on fish, feed consumption or biofilter function associated with FFC-medicated feed administration to tilapia.

Chronic dietary exposure to a low-dose mixture of genistein and vinclozolin modifies the reproductive axis, testis transcriptome, and fertility.

PubMed

Eustache, Florence; Mondon, Françoise; Canivenc-Lavier, Marie Chantal; Lesaffre, Corinne; Fulla, Yvonne; Berges, Raymond; Cravedi, Jean Pierre; Vaiman, Daniel; Auger, Jacques

2009-08-01

The reproductive consequences and mechanisms of action of chronic exposure to low-dose endocrine disruptors are poorly understood. We assessed the effects of a continuous, low-dose exposure to a phytoestrogen (genistein) and/or an antiandrogenic food contaminant (vinclozolin) on the male reproductive tract and fertility. Male rats were exposed by gavage to genistein and vinclozolin from conception to adulthood, alone or in combination, at low doses (1 mg/kg/day) or higher doses (10 and 30 mg/kg/day). We studied a number of standard reproductive toxicology end points and also assessed testicular mRNA expression profiles using long-oligonucleotide microarrays. The low-dose mixture and high-dose vinclozolin produced the most significant alterations in adults: decreased sperm counts, reduced sperm motion parameters, decreased litter sizes, and increased post implantation loss. Testicular mRNA expression profiles for these exposure conditions were strongly correlated. Functional clustering indicated that many of the genes induced belong to the "neuroactive ligand-receptor interactions" family encompassing several hormonally related actors (e.g., follicle-stimulating hormone and its receptor). All exposure conditions decreased the levels of mRNAs involved in ribosome function, indicating probable decreased protein production. Our study shows that chronic exposure to a mixture of a dose of a phytoestrogen equivalent to that in the human diet and a low dose-albeit not environmental-of a common anti-androgenic food contaminant may seriously affect the male reproductive tract and fertility.

Irradiation doses on thyroid gland during the postoperative irradiation for breast cancer.

PubMed

Akın, Mustafa; Ergen, Arzu; Unal, Aysegul; Bese, Nuran

2014-01-01

Thyroid gland is one of the radiosensitive endocrine organs in the body. It has been shown that direct irradiation of thyroid with total doses of 26 to 30 Gy can lead to functional abnormalities. In this study, irradiation doses on thyroid gland of the patients who received postoperative chest-wall/breast and regional nodal irradiation were assessed. Retrospective analyses of treatment plans from 122 breast cancer patients who were treated with 3D conformal radiotherapy (3D CRT) planning was performed. All patients received irradiation to supraclavicular/level III lymph nodes in addition to chest-wall/breast. A total dose of 46 Gy was delivered in 25 days to supraclavicular/level III lymph node region while a total dose of 50 Gy was delivered to whole breast/chest-wall. Thyroid gland was contoured on 2-5 mm thickness of computed tomography scans. Absolute thyroid volume, mean thyroid doses were calculated. The mean thyroid volume of all patients was 16.7 cc (min: 1.9 cc, max: 41.6 cc). The mean irradiation dose on was 22.5 Gy (0.32 Gy-46.5 Gy). The level of dose was higher than 26 Gy in 44% of the patients. In majority of the node-positive breast cancer patients treated with 3D CRT, the thyroid gland was exposed to considerable doses. On the other hand, for 44% of the patients are at risk for developing thyroid function abnormalities which should be considered during the routine follow-up.

Failure-probability driven dose painting

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

Vogelius, Ivan R.; Håkansson, Katrin; Due, Anne K.

Purpose: To demonstrate a data-driven dose-painting strategy based on the spatial distribution of recurrences in previously treated patients. The result is a quantitative way to define a dose prescription function, optimizing the predicted local control at constant treatment intensity. A dose planning study using the optimized dose prescription in 20 patients is performed.Methods: Patients treated at our center have five tumor subvolumes from the center of the tumor (PET positive volume) and out delineated. The spatial distribution of 48 failures in patients with complete clinical response after (chemo)radiation is used to derive a model for tumor control probability (TCP). Themore » total TCP is fixed to the clinically observed 70% actuarial TCP at five years. Additionally, the authors match the distribution of failures between the five subvolumes to the observed distribution. The steepness of the dose–response is extracted from the literature and the authors assume 30% and 20% risk of subclinical involvement in the elective volumes. The result is a five-compartment dose response model matching the observed distribution of failures. The model is used to optimize the distribution of dose in individual patients, while keeping the treatment intensity constant and the maximum prescribed dose below 85 Gy.Results: The vast majority of failures occur centrally despite the small volumes of the central regions. Thus, optimizing the dose prescription yields higher doses to the central target volumes and lower doses to the elective volumes. The dose planning study shows that the modified prescription is clinically feasible. The optimized TCP is 89% (range: 82%–91%) as compared to the observed TCP of 70%.Conclusions: The observed distribution of locoregional failures was used to derive an objective, data-driven dose prescription function. The optimized dose is predicted to result in a substantial increase in local control without increasing the predicted risk of toxicity.« less

SU-F-BRD-05: Robustness of Dose Painting by Numbers in Proton Therapy

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

Montero, A Barragan; Sterpin, E; Lee, J

Purpose: Proton range uncertainties may cause important dose perturbations within the target volume, especially when steep dose gradients are present as in dose painting. The aim of this study is to assess the robustness against setup and range errors for high heterogeneous dose prescriptions (i.e., dose painting by numbers), delivered by proton pencil beam scanning. Methods: An automatic workflow, based on MATLAB functions, was implemented through scripting in RayStation (RaySearch Laboratories). It performs a gradient-based segmentation of the dose painting volume from 18FDG-PET images (GTVPET), and calculates the dose prescription as a linear function of the FDG-uptake value on eachmore » voxel. The workflow was applied to two patients with head and neck cancer. Robustness against setup and range errors of the conventional PTV margin strategy (prescription dilated by 2.5 mm) versus CTV-based (minimax) robust optimization (2.5 mm setup, 3% range error) was assessed by comparing the prescription with the planned dose for a set of error scenarios. Results: In order to ensure dose coverage above 95% of the prescribed dose in more than 95% of the GTVPET voxels while compensating for the uncertainties, the plans with a PTV generated a high overdose. For the nominal case, up to 35% of the GTVPET received doses 5% beyond prescription. For the worst of the evaluated error scenarios, the volume with 5% overdose increased to 50%. In contrast, for CTV-based plans this 5% overdose was present only in a small fraction of the GTVPET, which ranged from 7% in the nominal case to 15% in the worst of the evaluated scenarios. Conclusion: The use of a PTV leads to non-robust dose distributions with excessive overdose in the painted volume. In contrast, robust optimization yields robust dose distributions with limited overdose. RaySearch Laboratories is sincerely acknowledged for providing us with RayStation treatment planning system and for the support provided.« less

Efficacy of Continuous Dosing of Tadalafil Once Daily vs Tadalafil On Demand in Clinical Subgroups of Men With Erectile Dysfunction: A Descriptive Comparison Using the Integrated Tadalafil Databases.

PubMed

Brock, Gerald; Ni, Xiao; Oelke, Matthias; Mulhall, John; Rosenberg, Matt; Seftel, Allen; D'Souza, Deborah; Barry, Jane

2016-05-01

Various factors play a role in the development of erectile dysfunction (ED). To provide a descriptive comparison of erectile function response for tadalafil on-demand (PRN) and once-daily (OAD) dosing regimens in patients with common comorbid conditions, treatments, or risk factors that can be considered when treating ED. In total, 17 PRN and 4 OAD placebo-controlled studies were included in the integrated database in these pooled analyses. Data were analyzed from patients treated with placebo, tadalafil 10 mg (low dose), and 20 mg (high dose) for the PRN studies and placebo, tadalafil 2.5 mg (low dose), and 5 mg (high dose) for the OAD studies. The effects of tadalafil were measured using the International Index of Erectile Function administered from baseline to week 12. A descriptive comparison of the efficacy of tadalafil PRN vs OAD was examined in the clinical populations. Baseline characteristics of 4,354 men were comparable between the PRN and OAD groups, with differences seen only in the variables of race, body mass index (BMI) of at least 30 kg/m(2), and alcohol use. Tadalafil was efficacious at improving erectile function for all clinical populations, except for the low-dose OAD group, which demonstrated a weaker effect vs placebo than the high-dose OAD group, and the low- and high-dose PRN groups vs placebo for patients with BMI of at least 30 kg/m(2) for patients without a cardiovascular disorder, smokers, patients with ED duration shorter than 1 year, and patients without previous phosphodiesterase type 5 inhibitor use. Tadalafil was efficacious for patients with or without diabetes mellitus, arterial hypertension, hyperlipidemia, and alcohol use at baseline. Tadalafil OAD and PRN regimens showed efficacy in patients with ED. No clinical populations of patients with ED seemed to benefit overwhelmingly from one dose regimen over the other. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Penalization of aperture complexity in inversely planned volumetric modulated arc therapy

PubMed Central

Younge, Kelly C.; Matuszak, Martha M.; Moran, Jean M.; McShan, Daniel L.; Fraass, Benedick A.; Roberts, Donald A.

2012-01-01

Purpose: Apertures obtained during volumetric modulated arc therapy (VMAT) planning can be small and irregular, resulting in dosimetric inaccuracies during delivery. Our purpose is to develop and integrate an aperture-regularization objective function into the optimization process for VMAT, and to quantify the impact of using this objective function on dose delivery accuracy and optimized dose distributions. Methods: An aperture-based metric (“edge penalty”) was developed that penalizes complex aperture shapes based on the ratio of MLC side edge length and aperture area. To assess the utility of the metric, VMAT plans were created for example paraspinal, brain, and liver SBRT cases with and without incorporating the edge penalty in the cost function. To investigate the dose calculation accuracy, Gafchromic EBT2 film was used to measure the 15 highest weighted apertures individually and as a composite from each of two paraspinal plans: one with and one without the edge penalty applied. Films were analyzed using a triple-channel nonuniformity correction and measurements were compared directly to calculations. Results: Apertures generated with the edge penalty were larger, more regularly shaped and required up to 30% fewer monitor units than those created without the edge penalty. Dose volume histogram analysis showed that the changes in doses to targets, organs at risk, and normal tissues were negligible. Edge penalty apertures that were measured with film for the paraspinal plan showed a notable decrease in the number of pixels disagreeing with calculation by more than 10%. For a 5% dose passing criterion, the number of pixels passing in the composite dose distributions for the non-edge penalty and edge penalty plans were 52% and 96%, respectively. Employing gamma with 3% dose/1 mm distance criteria resulted in a 79.5% (without penalty)/95.4% (with penalty) pass rate for the two plans. Gradient compensation of 3%/1 mm resulted in 83.3%/96.2% pass rates. Conclusions: The use of the edge penalty during optimization has the potential to markedly improve dose delivery accuracy for VMAT plans while still maintaining high quality optimized dose distributions. The penalty regularizes aperture shape and improves delivery efficiency. PMID:23127107

High resolution MR based polymer dosimetry versus film densitometry: a systematic study based on the modulation transfer function approach.

PubMed

Berg, A; Pernkopf, M; Waldhäusl, C; Schmidt, W; Moser, E

2004-09-07

Precise methods of modem radiation therapy such as intensity modulated radiotherapy (IMRT), brachytherapy (BT) and high LET irradiation allow for high dose localization in volumes of a few mm3. However, most dosimetry methods-ionization chambers, TLD arrangements or silicon detectors, for example-are not capable of detecting sub-mm dose variations or do not allow for simple dose imaging. Magnetic resonance based polymer dosimetry (MRPD) appears to be well suited to three-dimensional high resolution relative dosimetry but the spatial resolution based on a systematic modulation transfer function (MTF) approach has not yet been investigated. We offer a theoretical construct for addressing the spatial resolution in different dose imaging systems, i.e. the dose modulation transfer function (DMTF) approach, an experimental realization of this concept with a phantom and quantitative comparisons between two dosimetric systems: polymer gel and film dosimetry. Polymer gel samples were irradiated by Co-60 photons through an absorber grid which is characterized by periodic structures of different spatial period (a), the smallest one at width of a/2 = 280 microm. The modulation in dose under the grid is visualized via calibrated, high resolution, parameter-selective (T2) and dose images based on multi-echo MR imaging. The DMTF is obtained from the modulation depth of the spin-spin relaxation time (T2) after calibration. Voxel sizes below 0.04 mm3 could be achieved, which are significantly smaller than those reported in MR based dose imaging on polymer gels elsewhere, using a powerful gradient system and a highly sensitive small birdcage resonator on a whole-body 3T MR scanner. Dose modulations at 22% of maximum dose amplitude could be observed at about 2 line pairs per mm. The polymer DMTF results are compared to those of a typical clinical film-scanner system. This study demonstrates that MR based gel dosimetry at 200 microm pixel resolution might even be superior, with reference to relative spatial resolution, to the results of a standard film-scanner system offering a nominal scan resolution of 200 microm.

SU-F-18C-01: Minimum Detectability Analysis for Comprehensive Sized Based Optimization of Image Quality and Radiation Dose Across CT Protocols

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

Smitherman, C; Chen, B; Samei, E

2014-06-15

Purpose: This work involved a comprehensive modeling of task-based performance of CT across a wide range of protocols. The approach was used for optimization and consistency of dose and image quality within a large multi-vendor clinical facility. Methods: 150 adult protocols from the Duke University Medical Center were grouped into sub-protocols with similar acquisition characteristics. A size based image quality phantom (Duke Mercury Phantom) was imaged using these sub-protocols for a range of clinically relevant doses on two CT manufacturer platforms (Siemens, GE). The images were analyzed to extract task-based image quality metrics such as the Task Transfer Function (TTF),more » Noise Power Spectrum, and Az based on designer nodule task functions. The data were analyzed in terms of the detectability of a lesion size/contrast as a function of dose, patient size, and protocol. A graphical user interface (GUI) was developed to predict image quality and dose to achieve a minimum level of detectability. Results: Image quality trends with variations in dose, patient size, and lesion contrast/size were evaluated and calculated data behaved as predicted. The GUI proved effective to predict the Az values representing radiologist confidence for a targeted lesion, patient size, and dose. As an example, an abdomen pelvis exam for the GE scanner, with a task size/contrast of 5-mm/50-HU, and an Az of 0.9 requires a dose of 4.0, 8.9, and 16.9 mGy for patient diameters of 25, 30, and 35 cm, respectively. For a constant patient diameter of 30 cm, the minimum detected lesion size at those dose levels would be 8.4, 5, and 3.9 mm, respectively. Conclusion: The designed CT protocol optimization platform can be used to evaluate minimum detectability across dose levels and patient diameters. The method can be used to improve individual protocols as well as to improve protocol consistency across CT scanners.« less

The effect of a paraffin screen on the neutron dose at the maze door of a 15 MV linear accelerator

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

Krmar, M.; Kuzmanović, A.; Nikolić, D.

2013-08-15

Purpose: The purpose of this study was to explore the effects of a paraffin screen located at various positions in the maze on the neutron dose equivalent at the maze door.Methods: The neutron dose equivalent was measured at the maze door of a room containing a 15 MV linear accelerator for x-ray therapy. Measurements were performed for several positions of the paraffin screen covering only 27.5% of the cross-sectional area of the maze. The neutron dose equivalent was also measured at all screen positions. Two simple models of the neutron source were considered in which the first assumed that themore » source was the cross-sectional area at the inner entrance of the maze, radiating neutrons in an isotropic manner. In the second model the reduction in the neutron dose equivalent at the maze door due to the paraffin screen was considered to be a function of the mean values of the neutron fluence and energy at the screen.Results: The results of this study indicate that the equivalent dose at the maze door was reduced by a factor of 3 through the use of a paraffin screen that was placed inside the maze. It was also determined that the contributions to the dosage from areas that were not covered by the paraffin screen as viewed from the dosimeter, were 2.5 times higher than the contributions from the covered areas. This study also concluded that the contributions of the maze walls, ceiling, and floor to the total neutron dose equivalent were an order of magnitude lower than those from the surface at the far end of the maze.Conclusions: This study demonstrated that a paraffin screen could be used to reduce the neutron dose equivalent at the maze door by a factor of 3. This paper also found that the reduction of the neutron dose equivalent was a linear function of the area covered by the maze screen and that the decrease in the dose at the maze door could be modeled as an exponential function of the product φ·E at the screen.« less

Aspirin administered to women at 100 mg every other day produces less platelet inhibition than aspirin administered at 81 mg per day: implications for interpreting the women's health study.

PubMed

Swaim, Lisa; Hillman, Robert S

2009-07-01

We aimed to determine the relative level of platelet inhibition achieved with low-dose aspirin (81 mg daily) compared with a very low-dose (100 mg every other day). The Womens Health Study (WHS) found that a dose of 100 mg every other day of aspirin provided protection against stroke as primary prophylaxis, but not myocardial infarction. In the United States, the most commonly prescribed dose of aspirin for primary prophylaxis is 81 mg per day. As a result, it is important to know whether these doses are equivalent before extrapolating the results of the WHS to women in the U.S. To achieve this goal, we have studied the effects of these two dosing regimens on platelet function in healthy women meeting the WHS inclusion criteria using a randomized design. We enrolled 49 healthy female volunteers and used a sequential, crossover design to compare the two regimens. The participants received a 17-day course of each aspirin-dosing regimen separated by a 7-day washout period. The degree of platelet inhibition was measured on days 14-17 of each dosing regimen using a point-of-care platelet function assay utilizing arachidonic acid to activate platelets (VerifyNow-Aspirin). Participants platelet response, expressed as Aspirin Response Unit (ARU) attained a significantly greater level of platelet inhibition on days 14-17 while taking aspirin 81 mg daily compared to aspirin 100 mg every other day (31.3% vs. 12.7%, P < 0.0001) with mean +/- SD ARU values of 445 +/- 50 and 570 +/- 68, P < 0.0001. Significantly more daily readings in participants were >or=550 ARU, a value correlated with clinical outcomes in several studies, with the 100 mg every other day regimen (72.0% vs. 6.4% with 81 mg daily, P < 0.0001), and this alternate-day regimen also resulted in more day-to-day variability in platelet function (P = 0.0002). We found significantly less inhibition of platelet function with the dose used in the WHS than the usual U.S. dose. We observed that the degree of platelet inhibition was significantly less with aspirin 100 mg every other day compared with aspirin 81 mg daily, suggesting that results of the Women's Health Study may have underestimated both the efficacy and toxicity of aspirin as it is commonly administered. These data need to be considered when developing recommendations about the use of aspirin in the primary prevention of cardiovascular disease in women.

Dose-response relationship between hand-transmitted vibration and hand-arm vibration syndrome in a tropical environment.

PubMed

Su, Anselm Ting; Maeda, Setsuo; Fukumoto, Jin; Darus, Azlan; Hoe, Victor C W; Miyai, Nobuyuki; Isahak, Marzuki; Takemura, Shigeki; Bulgiba, Awang; Yoshimasu, Kouichi; Miyashita, Kazuhisa

2013-07-01

The dose-response relationship for hand-transmitted vibration has been investigated extensively in temperate environments. Since the clinical features of hand-arm vibration syndrome (HAVS) differ between the temperate and tropical environment, we conducted this study to investigate the dose-response relationship of HAVS in a tropical environment. A total of 173 male construction, forestry and automobile manufacturing plant workers in Malaysia were recruited into this study between August 2011 and 2012. The participants were interviewed for history of vibration exposure and HAVS symptoms, followed by hand functions evaluation and vibration measurement. Three types of vibration doses-lifetime vibration dose (LVD), total operating time (TOT) and cumulative exposure index (CEI)-were calculated and its log values were regressed against the symptoms of HAVS. The correlation between each vibration exposure dose and the hand function evaluation results was obtained. The adjusted prevalence ratio for finger tingling and numbness was 3.34 (95% CI 1.27 to 8.98) for subjects with lnLVD≥20 ln m(2) s(-4) against those <16 ln m(2) s(-4). Similar dose-response pattern was found for CEI but not for TOT. No subject reported white finger. The prevalence of finger coldness did not increase with any of the vibration doses. Vibrotactile perception thresholds correlated moderately with lnLVD and lnCEI. The dose-response relationship of HAVS in a tropical environment is valid for finger tingling and numbness. The LVD and CEI are more useful than TOT when evaluating the dose-response pattern of a heterogeneous group of vibratory tools workers.

Methylphenidate Exerts Dose-Dependent Effects on Glutamate Receptors and Behaviors

PubMed Central

Cheng, Jia; Xiong, Zhe; Duffney, Lara J.; Wei, Jing; Liu, Aiyi; Liu, Sihang; Chen, Guo-Jun; Yan, Zhen

2014-01-01

Background Methylphenidate (MPH), a psychostimulant drug for the treatment of attention-deficit hyperactivity disorder (ADHD), produces the effects of increasing alertness and improving attention, while its misuse has been associated with an increased risk of aggression and psychosis. In this study, we sought to determine the molecular mechanism underlying the complex actions of MPH. Methods Adolescent (4-week-old) rats were given one injection of MPH at different doses. The impact of MPH on glutamatergic signaling in pyramidal neurons of prefrontal cortex (PFC) was measured. MPH-induced behavioral changes were also examined in parallel. Results We found that administration of low-dose (0.5 mg/kg) MPH selectively potentiated NMDAR-mediated excitatory synaptic currents (EPSCs) via adrenergic receptor activation, while the high-dose (10 mg/kg) MPH suppressed both NMDAR- and AMPAR-EPSCs. The dual effects of MPH on EPSCs were associated with bi-directional changes in the surface level of glutamate receptor subunits. Behavioral tests also indicated that low-dose MPH facilitated the PFC-mediated temporal order recognition memory (TORM) and attention, while animals injected with high-dose MPH exhibited significantly elevated locomotive activity. Inhibiting the function of SNAP-25, a key SNARE proteins involved in NMDAR exocytosis, blocked the increase of NMDAR-EPSC by low-dose MPH. In animals exposed to repeated stress, administration of low-dose MPH effectively restored NMDAR function and TORM via a mechanism dependent on SNAP-25. Conclusions Our results have provided a potential mechanism underlying the cognitive enhancing effects of low-dose MPH, as well as the psychosis-inducing effects of high-dose MPH. PMID:24832867

A dosing algorithm for metformin based on the relationships between exposure and renal clearance of metformin in patients with varying degrees of kidney function.

PubMed

Duong, Janna K; Kroonen, M Y A M; Kumar, S S; Heerspink, H L; Kirkpatrick, C M; Graham, G G; Williams, K M; Day, R O

2017-08-01

The aims of this study were to investigate the relationship between metformin exposure, renal clearance (CL R ), and apparent non-renal clearance of metformin (CL NR /F) in patients with varying degrees of kidney function and to develop dosing recommendations. Plasma and urine samples were collected from three studies consisting of patients with varying degrees of kidney function (creatinine clearance, CL CR ; range, 14-112 mL/min). A population pharmacokinetic model was built (NONMEM) in which the oral availability (F) was fixed to 0.55 with an estimated inter-individual variability (IIV). Simulations were performed to estimate AUC 0-τ , CL R , and CL NR /F. The data (66 patients, 327 observations) were best described by a two-compartment model, and CL CR was a covariate for CL R . Mean CL R was 17 L/h (CV 22%) and mean CL NR /F was 1.6 L/h (69%).The median recovery of metformin in urine was 49% (range 19-75%) over a dosage interval. When CL R increased due to improved renal function, AUC 0-τ decreased proportionally, while CL NR /F did not change with kidney function. Target doses (mg/day) of metformin can be reached using CL CR /3 × 100 to obtain median AUC 0-12 of 18-26 mg/L/h for metformin IR and AUC 0-24 of 38-51 mg/L/h for metformin XR, with C max  < 5 mg/L. The proposed dosing algorithm can be used to dose metformin in patients with various degrees of kidney function to maintain consistent drug exposure. However, there is still marked IIV and therapeutic drug monitoring of metformin plasma concentrations is recommended.

Effect of a single intraoperative high-dose ATG-Fresenius on delayed graft function in donation after cardiac-death donor renal allograft recipients: a randomized study.

PubMed

van den Hoogen, Martijn W F; Kho, Marcia M L; Abrahams, Alferso C; van Zuilen, Arjan D; Sanders, Jan-Stephan; van Dijk, Marja; Hilbrands, Luuk B; Weimar, Willem; Hoitsma, Andries J

2013-04-01

Reducing the incidence of delayed graft function after transplant with donation after cardiac death donor renal allografts would facilitate managing recipients during their first weeks after a transplant. To reduce this incidence, in most studies, induction therapy with depleting anti-T-lymphocyte antibodies is coupled with a reduction of the dosage of the calcineurin inhibitor. The separate effect of anti-T-cell therapy on the incidence and duration of delayed graft function is therefore difficult to assess. We performed a randomized study to evaluate the effect of a single intraoperative high-dose of anti-T-lymphocyte immunoglobulin (ATG)-Fresenius (9 mg/kg body weight) on the incidence of delayed graft function. Eligible adult recipients of a first donation after cardiac death donor renal allograft were randomly assigned to ATG-Fresenius or no induction therapy. Maintenance immunosuppression consisted of tacrolimus, in an unadjusted dose, mycophenolate mofetil, and steroids. The study was prematurely terminated because of a lower-than-anticipated inclusion rate. Baseline characteristics were comparable in the ATG-Fresenius group (n=28) and the control group (n=24). Twenty-two patients in the ATG-Fresenius group (79%) had delayed graft function, compared with 13 in the control group (54%; P = .06). Allograft and patient survival were comparable in both groups. Serious adverse events occurred more frequently in the ATG-Fresenius group than they did in the control group (57% vs 29%; P < .05). Intraoperative administration of a single high-dose of ATG-Fresenius in donation after cardiac death donor renal allograft recipients, followed by triple immunosuppression with an unadjusted tacrolimus dose, seems ineffective to reduce the incidence of delayed graft function. Moreover, this was associated with a higher rate of serious adverse events (EudraCT-number, 2007-000210-36.).

A dose related response of 6-OHDA on chicken spectral sensitivity and oscillatory potentials of recording electroretinograms.

PubMed

Li, X; Schaeffel, F; Konrad, K; Eberhart, Z

1996-10-01

To further study the contribution of dopamine system to the local growth controlling mechanisms, a dose related response of 6-hydroxydopamine (6-OHDA) was studied by recording electroretinograms (ERGs). The spectral sensitivity of the b-waves and spectral efficiency function of oscillatory potentials (OPs) including OP1, OP2 and OP3 in 4 different doses group were measured. The effect of ascorbate that must be contained in solution of 6-OHDA was first tested with the spectral sensitivity of the b-waves and a correlation between response of the OPs and age, as well as a difference in both own eyes was analyzed for determining an intra-subject and inter-subject variance. An enhanced response was found in OP1, OP2 with doses of 175 micrograms and OP3 with dose of 150 micrograms, and the effect of OPs was mainly in wavelength from 620 nm to 480 nm. No significant increase was found in the spectral sensitivity of the b-waves. The dose 200 micrograms seemed to be toxic to the retina estimated by both spectral sensitivity of the b-waves and spectral efficiency function of the OPs. The dose 175 micrograms and 150 micrograms of 6-OHDA yielded an effect on the chicken retina.

Effective chemotherapy of heterogeneous and drug-resistant early colon cancers by intermittent dose schedules: a computer simulation study.

PubMed

Axelrod, David E; Vedula, Sudeepti; Obaniyi, James

2017-05-01

The effectiveness of cancer chemotherapy is limited by intra-tumor heterogeneity, the emergence of spontaneous and induced drug-resistant mutant subclones, and the maximum dose to which normal tissues can be exposed without adverse side effects. The goal of this project was to determine if intermittent schedules of the maximum dose that allows colon crypt maintenance could overcome these limitations, specifically by eliminating mixtures of drug-resistant mutants from heterogeneous early colon adenomas while maintaining colon crypt function. A computer model of cell dynamics in human colon crypts was calibrated with measurements of human biopsy specimens. The model allowed simulation of continuous and intermittent dose schedules of a cytotoxic chemotherapeutic drug, as well as the drug's effect on the elimination of mutant cells and the maintenance of crypt function. Colon crypts can tolerate a tenfold greater intermittent dose than constant dose. This allows elimination of a mixture of relatively drug-sensitive and drug-resistant mutant subclones from heterogeneous colon crypts. Mutants can be eliminated whether they arise spontaneously or are induced by the cytotoxic drug. An intermittent dose, at the maximum that allows colon crypt maintenance, can be effective in eliminating a heterogeneous mixture of mutant subclones before they fill the crypt and form an adenoma.

Characterization and optical studies of 90/10 (wt/wt%) PVA/β-chitin blend irradiated with γ-rays.

PubMed

Abd El-Kader, F H; Gaafer, S A; Abd El-Kader, M F H

2014-10-15

X-ray diffraction, IR spectroscopy and UV/visible spectra were studied as a function of gamma irradiation doses (5-100kGy) for 90/10 (wt/wt%) PVA/β-chitin. A new intense reflection peak at 2θ=21.5° appeared in the X-ray spectrum of the sample irradiated at 50kGy γ-dose. Besides, the band centered at 2931cm(-1) in IR spectrum splits into two clearly separated bands around 2919 and 2941cm(-1) for the sample irradiated at 10kGy γ-dose. The disappearance of the absorption band at 280nm of PVA in the blend sample indicates that the ligand PVA becomes opaque in the UV region and provides evidence for the miscibility between homopolymers. The value of absorbance, in UV/visible range, at 10kGy γ-dose was the highest one compared to the other γ-doses. The location of the γ-doses on the chromaticity diagram was different, indicating the change in the spectral colors of the investigated blend. In addition, the absorption edge, band tail and color parameters values were determined as a function of γ-doses. Copyright © 2014 Elsevier B.V. All rights reserved.

Sci—Fri PM: Dosimetry—04: Radiation out-of-field dose in the treatment of pediatric central nervous system malignancies

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

Taddei, P J; Tannous, J; Nabha, R

Children diagnosed with central nervous system (CNS) malignancies often receive radiotherapy, which can cause radiogenic late effects. In order to identify and reduce the risk of these late effects, we must understand the radiation doses that these children receive. Modern treatment planning systems accurately estimate the absorbed dose within the treatment fields but poorly estimate the dose outside them. The purpose of our study was to measure the out-of-field dose for children receiving localized radiotherapy for CNS cancer and apply an analytical model for estimating dose as a function of distance from the field edge. Radiation fields designed for amore » 12-year-old boy treated in our clinic were applied to an anthropomorphic phantom containing more than 200 thermoluminescent dosimeters. A double-Gaussian function of absorbed dose versus distance from the field edge (i.e., 50% isodose line) was applied, and parameters were allowed to vary and were fit to the model by minimizing the root mean square deviation, RMSD. The fitted model accurately predicted the dose from distances of 4 cm to 50 cm (RMSD = 0.54 cGy/Gy), but the model was not useful in estimating dose for distances less than 4 cm because of wide variation in measured dose, and the double-Gaussian model failed by systematically underestimating the dose beyond 50 cm. In conclusion, the double-Gaussian model may be applicable for points at distances from the field edge between 4 cm and 50 cm, where most children's radiosensitive tissues are located, but for points beyond 50 cm, an improvement should be investigated.« less

Novel high dose rate lip brachytherapy technique to improve dose homogeneity and reduce toxicity by customized mold.

PubMed

Feldman, Jon; Appelbaum, Limor; Sela, Mordechay; Voskoboinik, Ninel; Kadouri, Sarit; Weinberger, Jeffrey; Orion, Itzhak; Meirovitz, Amichay

2014-12-23

The purpose of this study is to describe a novel brachytherapy technique for lip Squamous Cell Carcinoma, utilizing a customized mold with embedded brachytherapy sleeves, which separates the lip from the mandible, and improves dose homogeneity. Seven patients with T2 lip cancer treated with a "sandwich" technique of High Dose Rate (HDR) brachytherapy to the lip, consisting of interstitial catheters and a customized mold with embedded catheters, were reviewed for dosimetry and outcome using 3D planning. Dosimetric comparison was made between the "sandwich" technique to "classic" - interstitial catheters only plan. We compared dose volume histograms for Clinical Tumor Volume (CTV), normal tissue "hot spots" and mandible dose. We are reporting according to the ICRU 58 and calculated the Conformal Index (COIN) to show the advantage of our technique. The seven patients (ages 36-81 years, male) had median follow-up of 47 months. Four patients received Brachytherapy and External Beam Radiation Therapy, 3 patients received brachytherapy alone. All achieved local control, with excellent esthetic and functional results. All patients are disease free. The Customized Mold Sandwich technique (CMS) reduced the high dose region receiving 150% (V150) by an average of 20% (range 1-47%), The low dose region (les then 90% of the prescribed dose) improved by 73% in average by using the CMS technique. The COIN value for the CMS was in average 0.92 as opposed to 0.88 for the interstitial catheter only. All differences (excluding the low dose region) were statistically significant. The CMS technique significantly reduces the high dose volume and increases treatment homogeneity. This may reduce the potential toxicity to the lip and adjacent mandible, and results in excellent tumor control, cosmetic and functionality.

SU-E-T-430: Modeling MLC Leaf End in 2D for Sliding Window IMRT and Arc Therapy

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

Liang, X; Zhu, T

2014-06-01

Purpose: To develop a 2D geometric model for MLC accounting for leaf end dose leakage for dynamic IMRT and Rapidarc therapy. Methods: Leaf-end dose leakage is one of the problems for MLC dose calculation and modeling. Dosimetric leaf gap used to model the MLC and to count for leakage in dose calculation, but may not be accurate for smaller leaf gaps. We propose another geometric modeling method to compensate for the MLC round-shape leaf ends dose leakage, and improve the accuracy of dose calculation and dose verification. A triangular function is used to geometrically model the MLC leaf end leakagemore » in the leaf motion direction, and a step function is used in the perpendicular direction. Dose measurements with different leaf gap, different window width, and different window height were conducted, and the results were used to fit the analytical model to get the model parameters. Results: Analytical models have been obtained for stop-and-shoot and dynamic modes for MLC motion. Parameters a=0.4, lw'=5.0 mm for 6X and a=0.54, lw'=4.1 mm for 15x were obtained from the fitting process. The proposed MLC leaf end model improves the dose profile at the two ends of the sliding window opening. This improvement is especially significant for smaller sliding window openings, which are commonly used for highly modulated IMRT plans and arc therapy plans. Conclusion: This work models the MLC round leaf end shape and movement pattern for IMRT dose calculation. The theory, as well as the results in this work provides a useful tool for photon beam IMRT dose calculation and verification.« less

SU-E-T-549: Modeling Relative Biological Effectiveness of Protons for Radiation Induced Brain Necrosis

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

Mirkovic, D; Peeler, C; Grosshans, D

Purpose: To develop a model of the relative biological effectiveness (RBE) of protons as a function of dose and linear energy transfer (LET) for induction of brain necrosis using clinical data. Methods: In this study, treatment planning information was exported from a clinical treatment planning system (TPS) and used to construct a detailed Monte Carlo model of the patient and the beam delivery system. The physical proton dose and LET were computed in each voxel of the patient volume using Monte Carlo particle transport. A follow-up magnetic resonance imaging (MRI) study registered to the treatment planning CT was used tomore » determine the region of the necrosis in the brain volume. Both, the whole brain and the necrosis volumes were segmented from the computed tomography (CT) dataset using the contours drawn by a physician and the corresponding voxels were binned with respect to dose and LET. The brain necrosis probability was computed as a function of dose and LET by dividing the total volume of all necrosis voxels with a given dose and LET with the corresponding total brain volume resulting in a set of NTCP-like curves (probability as a function of dose parameterized by LET). Results: The resulting model shows dependence on both dose and LET indicating the weakness of the constant RBE model for describing the brain toxicity. To the best of our knowledge the constant RBE model is currently used in all clinical applications which may Result in increased rate of brain toxicities in patients treated with protons. Conclusion: Further studies are needed to develop more accurate brain toxicity models for patients treated with protons and other heavy ions.« less

Irradiation of shell egg on the physicochemical and functional properties of liquid egg white.

PubMed

Min, B; Nam, K C; Jo, C; Ahn, D U

2012-10-01

This study was aimed at determining the effect of irradiation of shell eggs on the physiochemical and functional properties of liquid egg white during storage. Color and textural parameters of irradiated liquid egg white after cooking were also determined. Shell eggs were irradiated at 0, 2.5, 5, or 10 kGy using a linear accelerator. Egg white was separated from yolk and stored in at 4°C up to 14 d. Viscosity, pH, turbidity, foaming properties, color, and volatile profile of liquid egg white, and color and texture properties of cooked egg white were determined at 0, 7, and 14 d of storage. Irradiation increased the turbidity but decreased viscosity of liquid egg white. Foaming capacity and foam stability were not affected by irradiation at lower dose (2.5 kGy), but were deteriorated at higher doses (≥5.0 kGy) of irradiation. Sulfur-containing volatiles were generated by irradiation and their amounts increased as the irradiation dose increased. However, the sulfur volatiles disappeared during storage under aerobic conditions. Lightness (L* value) and yellowness (b* value) decreased, but greenness (-a* value) increased in cooked egg white in irradiation dose-dependent manners. All textural parameters (hardness, adhesiveness, cohesiveness, chewiness, and resilience) of cooked egg white increased as the irradiation dose increased, but those changes were marginal. Our results indicated that irradiation of shell egg at lower doses (up to 2.5 kGy) had little negative impact on the physiochemical and functional properties of liquid egg white, but can improve the efficiency of egg processing due to its viscosity-lowering effect. Therefore, irradiation of shell eggs at the lower doses has high potential to be used by the egg processing industry to improve the safety of liquid egg without compromising its quality.

Gamma knife radiosurgery for vestibular schwannomas: tumor control and functional preservation in 70 patients.

PubMed

Arthurs, Benjamin J; Lamoreaux, Wayne T; Mackay, Alexander R; Demakas, John J; Giddings, Neil A; Fairbanks, Robert K; Cooke, Barton S; Elaimy, Ameer L; Peressini, Ben; Lee, Christopher M

2011-06-01

We present the previously unreported outcomes of 70 patients treated with Gamma knife radiosurgery for vestibular schwannoma (VS), including comprehensive analysis of clinical outcomes and the effects of lower marginal doses. We performed a retrospective study of patients treated for VS at Gamma knife of Spokane between 2003 and 2008. Endpoints measured include tumor control, hearing preservation, and facial nerve preservation, including the effect of tumor size and marginal dose. Statistical analysis was performed with Wilcoxon signed-rank test, paired Student t test, Mann-Whitney U test, Kendall's rank correlation, Fisher exact test, and Liddell's exact χ(2) test for matched pairs. With a mean follow-up of 26 months, 93.8% of tumors either shrank or remained static after receiving a mean marginal dose of 12.7 Gy. Tumor control was independent of marginal dose or tumor size. Hearing preservation was achieved in 64% of patients with serviceable function before the treatment. Hearing changes were independent of dose or tumor size. Preservation of good facial nerve function was achieved in 95% of patients. Post-treatment hydrocephalus occurred in 4.4% of patients, but no other significant morbidities were elucidated. In the treatment of VS, contemporary radiosurgical techniques and the use of marginal doses below 13 Gy offer excellent tumor control, at high rates relative to surgical intervention. These findings are independent of marginal dose and tumor size. Patients should be informed about the benefits and risks of radiosurgery and microsurgery before choosing an intervention. Further analysis of post-treatment outcomes should be encouraged as follow-up times increase and the treatment protocols continue to evolve.

Interrogating two schedules of the AKT inhibitor MK-2206 in patients with advanced solid tumors incorporating novel pharmacodynamic and functional imaging biomarkers

PubMed Central

Yap, Timothy A.; Yan, Li; Patnaik, Amita; Tunariu, Nina; Biondo, Andrea; Fearen, Ivy; Papadopoulos, Kyriakos P.; Olmos, David; Baird, Richard; Delgado, Liliana; Tetteh, Ernestina; Beckman, Robert A.; Lupinacci, Lisa; Riisnaes, Ruth; Decordova, Shaun; Heaton, Simon P.; Swales, Karen; deSouza, Nandita M; Leach, Martin O.; Garrett, Michelle D.; Sullivan, Daniel M.; de Bono, Johann S.; Tolcher, Anthony W.

2014-01-01

Purpose Multiple cancers harbor genetic aberrations that impact AKT signaling. MK-2206 is a potent pan-AKT inhibitor with a maximum tolerated dose (MTD) previously established at 60mg on alternate days (QOD). Due to a long half-life (60-80h), a weekly (QW) MK-2206 schedule was pursued to compare intermittent QW and continuous QOD dosing. Experimental Design Patients with advanced cancers were enrolled onto a QW dose-escalation phase I study to investigate the safety and pharmacokinetic-pharmacodynamic profiles of tumor and platelet-rich plasma (PRP). The QOD MTD of MK-2206 was also assessed in patients with ovarian and castration-resistant prostate cancers, and patients with advanced cancers undergoing multiparametric functional magnetic resonance imaging (MRI) studies, including dynamic contrast-enhanced MRI, diffusion-weighted imaging, magnetic resonance spectroscopy and intrinsic susceptibility-weighted MRI. Results Seventy-one patients were enrolled; 38 patients had 60mg MK-2206 QOD, while 33 received MK-2206 at 90mg, 135mg, 150mg, 200mg, 250mg, and 300mg QW. The QW MK-2206 MTD was established at 200mg following dose-limiting rash at 250mg and 300mg. QW dosing appeared to be similarly tolerated to QOD, with toxicities including rash, gastrointestinal symptoms, fatigue, and hyperglycemia. Significant AKT pathway blockade was observed with both continuous QOD and intermittent QW dosing of MK-2206 in serially-obtained tumor and PRP specimens. The functional imaging studies demonstrated that complex multiparametric MRI protocols may be effectively implemented in a phase I trial. Conclusions MK-2206 safely results in significant AKT pathway blockade in QOD and QW schedules. The intermittent dose of 200mg QW is currently used in phase II MK-2206 monotherapy and combination studies. PMID:25239610

Interrogating two schedules of the AKT inhibitor MK-2206 in patients with advanced solid tumors incorporating novel pharmacodynamic and functional imaging biomarkers.

PubMed

Yap, Timothy A; Yan, Li; Patnaik, Amita; Tunariu, Nina; Biondo, Andrea; Fearen, Ivy; Papadopoulos, Kyriakos P; Olmos, David; Baird, Richard; Delgado, Liliana; Tetteh, Ernestina; Beckman, Robert A; Lupinacci, Lisa; Riisnaes, Ruth; Decordova, Shaun; Heaton, Simon P; Swales, Karen; deSouza, Nandita M; Leach, Martin O; Garrett, Michelle D; Sullivan, Daniel M; de Bono, Johann S; Tolcher, Anthony W

2014-11-15

Multiple cancers harbor genetic aberrations that impact AKT signaling. MK-2206 is a potent pan-AKT inhibitor with a maximum tolerated dose (MTD) previously established at 60 mg on alternate days (QOD). Due to a long half-life (60-80 hours), a weekly (QW) MK-2206 schedule was pursued to compare intermittent QW and continuous QOD dosing. Patients with advanced cancers were enrolled in a QW dose-escalation phase I study to investigate the safety and pharmacokinetic-pharmacodynamic profiles of tumor and platelet-rich plasma (PRP). The QOD MTD of MK-2206 was also assessed in patients with ovarian and castration-resistant prostate cancers and patients with advanced cancers undergoing multiparametric functional magnetic resonance imaging (MRI) studies, including dynamic contrast-enhanced MRI, diffusion-weighted imaging, magnetic resonance spectroscopy, and intrinsic susceptibility-weighted MRI. A total of 71 patients were enrolled; 38 patients had 60 mg MK-2206 QOD, whereas 33 received MK-2206 at 90, 135, 150, 200, 250, and 300 mg QW. The QW MK-2206 MTD was established at 200 mg following dose-limiting rash at 250 and 300 mg. QW dosing appeared to be similarly tolerated to QOD, with toxicities including rash, gastrointestinal symptoms, fatigue, and hyperglycemia. Significant AKT pathway blockade was observed with both continuous QOD and intermittent QW dosing of MK-2206 in serially obtained tumor and PRP specimens. The functional imaging studies demonstrated that complex multiparametric MRI protocols may be effectively implemented in a phase I trial. Treatment with MK-2206 safely results in significant AKT pathway blockade in QOD and QW schedules. The intermittent dose of 200 mg QW is currently used in phase II MK-2206 monotherapy and combination studies (NCT00670488). ©2014 American Association for Cancer Research.

Sci-Sat AM(2): Brachy-05: Dosimetry effects of the TG-43 approximations for two iodine seeds in LDR brachytherapy.

PubMed

Furstoss, C; Bertrand, M J; Poon, E; Reniers, B; Pignol, J P; Carrier, J F; Beaulieu, L; Verhaegen, F

2008-07-01

This work consists of studying the interseed and tissue composition effects for two model iodine seeds: the IBt Interseed-125 and the 6711 model seed. Three seeds were modeled with the MCNP MC code in a water sphere to evaluate the interseed effect. The dose calculated at different distances from the centre was compared to the dose summed when the seeds were simulated separately. The tissue composition effect was studied calculating the radial dose function for different tissues. Before carrying out post-implant studies, the absolute dose calculated by MC was compared to experiment results: with LiF TLDs in an acrylic breast phantom and with an EBT Gafchromic film placed in a water tank. Afterwards, the TG-43 approximation effects were studied for a prostate and breast post-implant. The interseed effect study shows that this effect is more important for model 6711 (15%) than for IBt (10%) due to the silver rod in 6711. For both seed models the variations of the radial dose function as a function of the tissue composition are quasi similar. The absolute dose comparisons between MC calculations and experiments give good agreement (inferior to 3% in general). For the prostate and breast post-implant studies, a 10% difference between MC calculations and the TG-43 is found for both models of seeds. This study shows that the differences in dose distributions between TG43 and MC are quite similar for the two models of seeds and are about 10% for the studied post-implant treatments. © 2008 American Association of Physicists in Medicine.

Optimal timing and frequency of bone marrow soup therapy for functional restoration of salivary glands injured by single-dose or fractionated irradiation.

PubMed

Fang, Dongdong; Shang, Sixia; Liu, Younan; Bakkar, Mohammed; Sumita, Yoshinori; Seuntjens, Jan; Tran, Simon D

2018-02-01

Injections of bone marrow (BM) cell extract, known as 'BM soup', were previously reported to mitigate ionizing radiation (IR) injury to salivary glands (SGs). However, the optimal starting time and frequency to maintain BM soup therapeutic efficacy remains unknown. This study tested the optimal starting time and frequency of BM soup injections in mice radiated with either a single dose or a fractionated dose. First, BM soup treatment was started at 1, 3 or 7 weeks post-IR; positive (non-IR) and negative (IR) control mice received injections of saline (vehicle control). Second, BM soup-treated mice received injections at different frequencies (1, 2, 3 and 5 weekly injections). Third, a 'fractionated-dose radiation' model to injure mouse SGs was developed (5 Gy × 5 days) and compared with the single high dose radiation model. All mice (n = 65) were followed for 16 weeks post-IR. The results showed that starting injections of BM soup between 1 and 3 weeks mitigated the effect of IR-induced injury to SGs and improved the restoration of salivary function. Although the therapeutic effect of BM soup lessens after 8 weeks, it can be sustained by increasing the frequency of weekly injections. Moreover, both single-dose and fractionated-dose radiation models are efficient and comparable in inducing SG injury and BM soup treatments are effective in restoring salivary function in both radiation models. In conclusion, starting injections of BM soup within 3 weeks post-radiation, with 5 weekly injections, maintains 90-100% of saliva flow in radiated mice. Copyright © 2017 John Wiley & Sons, Ltd.

Measurement and simulation of lineal energy distribution at the CERN high energy facility with a tissue equivalent proportional counter.

PubMed

Rollet, S; Autischer, M; Beck, P; Latocha, M

2007-01-01

The response of a tissue equivalent proportional counter (TEPC) in a mixed radiation field with a neutron energy distribution similar to the radiation field at commercial flight altitudes has been studied. The measurements have been done at the CERN-EU High-Energy Reference Field (CERF) facility where a well-characterised radiation field is available for intercomparison. The TEPC instrument used by the ARC Seibersdorf Research is filled with pure propane gas at low pressure and can be used to determine the lineal energy distribution of the energy deposition in a mass of gas equivalent to a 2 microm diameter volume of unit density tissue, of similar size to the nuclei of biological cells. The linearity of the detector response was checked both in term of dose and dose rate. The effect of dead-time has been corrected. The influence of the detector exposure location and orientation in the radiation field on the dose distribution was also studied as a function of the total dose. The microdosimetric distribution of the absorbed dose as a function of the lineal energy has been obtained and compared with the same distribution simulated with the FLUKA Monte Carlo transport code. The dose equivalent was calculated by folding this distribution with the quality factor as a function of linear energy transfer. The comparison between the measured and simulated distributions show that they are in good agreement. As a result of this study the detector is well characterised, thanks also to the numerical simulations the instrument response is well understood, and it's currently being used onboard the aircrafts to evaluate the dose to aircraft crew caused by cosmic radiation.

Experimental determination of the lateral dose response functions of detectors to be applied in the measurement of narrow photon-beam dose profiles.

PubMed

Poppinga, D; Meyners, J; Delfs, B; Muru, A; Harder, D; Poppe, B; Looe, H K

2015-12-21

This study aims at the experimental determination of the detector-specific 1D lateral dose response function K(x) and of its associated rotational symmetric counterpart K(r) for a set of high-resolution detectors presently used in narrow-beam photon dosimetry. A combination of slit-beam, radiochromic film, and deconvolution techniques served to accomplish this task for four detectors with diameters of their sensitive volumes ranging from 1 to 2.2 mm. The particular aim of the experiment was to examine the existence of significant negative portions of some of these response functions predicted by a recent Monte-Carlo-simulation (Looe et al 2015 Phys. Med. Biol. 60 6585-607). In a 6 MV photon slit beam formed by the Siemens Artiste collimation system and a 0.5 mm wide slit between 10 cm thick lead blocks serving as the tertiary collimator, the true cross-beam dose profile D(x) at 3 cm depth in a large water phantom was measured with radiochromic film EBT3, and the detector-affected cross-beam signal profiles M(x) were recorded with a silicon diode, a synthetic diamond detector, a miniaturized scintillation detector, and a small ionization chamber. For each detector, the deconvolution of the convolution integral M(x)  =  K(x)  ∗  D(x) served to obtain its specific 1D lateral dose response function K(x), and K(r) was calculated from it. Fourier transformations and back transformations were performed using function approximations by weighted sums of Gaussian functions and their analytical transformation. The 1D lateral dose response functions K(x) of the four types of detectors and their associated rotational symmetric counterparts K(r) were obtained. Significant negative curve portions of K(x) and K(r) were observed in the case of the silicon diode and the diamond detector, confirming the Monte-Carlo-based prediction (Looe et al 2015 Phys. Med. Biol. 60 6585-607). They are typical for the perturbation of the secondary electron field by a detector with enhanced electron density compared with the surrounding water. In the cases of the scintillation detector and the small ionization chamber, the negative curve portions of K(x) practically vanish. It is planned to use the measured functions K(x) and K(r) to deconvolve clinical narrow-beam signal profiles and to correct the output factor values obtained with various high-resolution detectors.

The relationship between ovarian function and ovarian limited dose in radiotherapy postoperation of ovarian transposition in young patients with cervical cancer.

PubMed

Du, Zhenhua; Qu, Hui

2017-03-01

In this study, the relationship between ovarian function and ovarian limited dose in radiotherapy was evaluated in young patients with cervical cancer who underwent ovarian transposition (Fig1B). Moreover, the novel ovarian dose limit for a better preservation of ovarian function in intensity-modulated radiation therapy (IMRT) was determined. We retrospectively analyzed data from 86 patients with cervical cancer who received radical hysterectomy and ovarian transposition from January 2013 to June 2015. In agreement with the National Comprehensive Cancer Network Guidelines (NCCN) for Cervical Cancer Version 2.2015, 65 patients with pathological high-risk factors were administered adjuvant radiotherapy-20 of them received three-dimensional conformal radiotherapy (Observation Group A), 24 patients received IMRT with no limitation on radiation dose to ovaries (Observation Group B), and 21 patients underwent IMRT with limited radiation dose(V 10 <20%) to ovaries (Observation Group C). Twenty-one patients without any predetermined high-risk factors did not received radiation therapy (Control Group D). Patients from all four groups were followed up, and sex hormone levels (E 2 , P, follicle-stimulating hormone [FSH], LH) before radiation, postradiation, 3 month, and 6 month after the radiation therapy were measured by electrochemiluminescence immunoassay. Subsequently, changes in sex hormone levels in all four groups of patients at various time points were analyzed. The levels of sexual hormones (E 2 , P, FSH, LH) before radiation, postradiation, 3 month, and 6 month after the radiation therapy in patients from all three observation groups were significantly lower than those in patients of the control group (P < 0.05). There was no statistically significant difference in the levels of sex hormones in patients of the control group at different time points (P > 0.05). Within each observation group, there was a statistically significant difference in the sex hormone levels in patients before the radiation and after the radiation (P < 0.05); however, when data from all three observation groups were compared, only the difference in the levels of FSH and LH between the patients from Group A and Group C was statistically significant (P < 0.05). The results of receiver-operating characteristic (ROC) curve analysis suggested that limiting ovarian radiation dose to V 7.5  < 26% in IMRT prevents the disruption of ovarian function (area under ROC curve was 0.740, confidence interval [CI] = 0.606-0.874). In young patients with cervical cancer who underwent radical hysterectomy and ovarian transposition without receiving adjuvant radiotherapy, ovarian endocrine function was well preserved. In patients who received any type of postoperative radiotherapy, ovarian function was affected, suggesting that the standard ovarian limited dose used in IMRT disrupted ovarian function. The results of the ROC curve analysis suggested that the new optimal dose limit of V 7.5  < 26% should be used in IMRT to preserve ovarian function (P = 0.003). © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Study of the dose rate effect of 180 nm nMOSFETs

NASA Astrophysics Data System (ADS)

He, Bao-Ping; Yao, Zhi-Bin; Sheng, Jiang-Kun; Wang, Zu-Jun; Huang, Shao-Yan; Liu, Min-Bo; Xiao, Zhi-Gang

2015-01-01

Radiation induced offstate leakage in the shallow trench isolation regions of SIMC 0.18 μm nMOSFETs is studied as a function of dose rate. A “true” dose rate effect (TDRE) is observed. Increased damage is observed at low dose rate (LDR) than at high dose rate (HDR) when annealing is taken into account. A new method of simulating radiation induced degradation in shallow trench isolation (STI) is presented. A comparison of radiation induced offstate leakage current in test nMOSFETs between total dose irradiation experiments and simulation results exhibits excellent agreement. The investigation results imply that the enhancement of the leakage current may be worse for the dose rate encountered in the environment of space.

Functional Evaluation of the DOZA DKG-05D Electronic Dosimeter System

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

Piper, Roman K.; Scherpelz, Robert I.

2009-11-04

The DOZA DKG-05D electronic personal dosimeter (EPD) was the subject of a limited type-test evaluation in support of Plutonium Production Reactor Agreement (PPRA) Implementation. The primary goal of this evaluation was to provide confidence in the functionality of the dosimeter and identify potential weaknesses in PPRA applications. The tests were based on IEC-61526, recommendations of the International Electrotechnical Commission pertaining to EPDs. All tests were performed in Pacific Northwest National Laboratory’s (PNNL) Radiological Calibrations and Standards Facility in the 318 building. The first testing category was functional considerations. The tests found that the mechanical characteristics of the DKG-05D support usability.more » However, user controls are not intuitive and straightforward, and the user instructions were unclear and difficult to follow. The unit functioned in a variety of humidity conditions. In high temperature conditions it performed well. However, in cold conditions the display began to fade, which limits its usefulness below about 5 °C. The vendor claims that the unit functions to -20 °C, and it may be correctly recording doses at that low temperature, but the doses cannot be read in real time. Testing found that battery life is generally good, operating for 200 hours on a full charge. This is far more than needed for the intended application. Charging the battery, however, had some pitfalls resulting from two charging modes. The high-current mode would be automatically selected if the battery charge fell below a threshold value when inserted in the charger. Otherwise, a low-current mode would be selected. In some cases a battery needing recharging would not get sufficient current to fully charge in a reasonable time period. There were also problems found in the low-battery indication and there was a possibility for data loss in the low-battery condition. The EPD generally performed well in measuring dose and dose rate. There were some small problems with non-linearity over a range of doses, but these non-linearities were at extremely low and very high doses and would not adversely affect the performance in our intended application. The testing resulted in the general conclusion that the DOZA DKG-05D is suitable for use in PPRA applications for real-time indication of dose received by a user and for estimation of stay times in radiation zones. It can be used as a supplement to a passive dosimeter, but it should not be used for measuring the user’s dose of record.« less

Mechanisms of Radiation Induced Effects in Carbon Nanotubes

DTIC Science & Technology

2016-10-01

the defect types created for both ionizing and non-ionizing particles under exposure to high total ionization and displacement damage doses. Carbon...and displacement damage doses. Additionally, the radiation effects on CNT carrier transport parameters (mobility, lifetime, conductivity) have been...thermal oxidation. 2. Radiation Testing of SWCNTs 2.1 Displacement Damage Dose Effects as a Function of SWCNT Electronic-Type Displacement damage does

Radiation dose in temporomandibular joint zonography

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

Coucke, M.E.; Bourgoignie, R.R.; Dermaut, L.R.

1991-06-01

Temporomandibular joint morphology and function can be evaluated by panoramic zonography. Thermoluminescent dosimetry was applied to evaluate the radiation dose to predetermined sites on a phantom eye, thyroid, pituitary, and parotid, and the dose distribution on the skin of the head and neck when the TMJ program of the Zonarc panoramic x-ray unit was used. Findings are discussed with reference to similar radiographic techniques.

Sanitation of chicken eggs by ionizing radiation: functional and nutritional assessment

NASA Astrophysics Data System (ADS)

Pinto, P.; Ribeiro, R.; Sousa, L.; Verde, S. Cabo; Lima, M. G.; Dinis, M.; Santana, A.; Botelho, M. L.

2004-09-01

Alternative technologies must be developed and implemented considering sanitation and preservation of eggs mainly for risk population. Food irradiation is an alternative to free Salmonella spp. and Campylobacter spp. eggs, as a low dose point to a safety assurance. This study presents the correlation between irradiation doses (0.5 kGy up to 5 kGy at dose rate of 1.0 kGy/h) and some of functional and nutritional egg properties. Viscosimetry of non-irradiated and irradiated eggs was evaluated by means of VT550 Haake with an NV sensor and co-axes cylinders. After irradiation at 5 kGy, the yolk colour die (pale yellow) and the white egg was modified to a turbid yellow. The Cross equation was utilized to viscosimetry curves. Based on the assymptotics viscosimetry data indicated that increase of doses corresponds to an increase of the yolk and a decrease of white egg viscosimetry as such a Newton behaviour. Irradiation effects on nutritional properties were evaluated by means of egg protein patterns that were assessed by polyacrylamide gel electrophoresis. Lipids were identified by TLC. Based on results the sanitation dose is lower than the limit dose for the decrease of the main eggs properties.

The effect of glucose dose and fasting interval on cognitive function: a double-blind, placebo-controlled, six-way crossover study.

PubMed

Owen, Lauren; Scholey, Andrew B; Finnegan, Yvonne; Hu, Henglong; Sünram-Lea, Sandra I

2012-04-01

Previous research has identified a number of factors that appear to moderate the behavioural response to glucose administration. These include physiological state, dose, types of cognitive tasks used and level of cognitive demand. Another potential moderating factor is the length of the fasting interval prior to a glucose load. Therefore, we aimed to examine the effect of glucose dose and fasting interval on mood and cognitive function. The current study utilised a double-blind, placebo-controlled, balanced, six period crossover design to examine potential interactions between length of fasting interval (2 versus 12 hours) and optimal dose for cognition enhancement. Results demonstrated that the higher dose (60 g) increased working memory performance following an overnight fast, whereas the lower dose (25 g) enhanced working memory performance following a 2-h fast. The data suggest that optimal glucose dosage may differ under different conditions of depleted blood glucose resources. In addition, glucoregulation was observed to be a moderating factor. However, further research is needed to develop a model of the moderating and mediating factors under which glucose facilitation is best achieved.

Impact of Efavirenz on Intestinal Metabolism and Transport: Insights From an Interaction Study With Ezetimibe in Healthy Volunteers

PubMed Central

Oswald, S; zu Schwabedissen, HE Meyer; Nassif, A; Modess, C; Desta, Z; Ogburn, ET; Mostertz, J; Keiser, M; Jia, J; Hubeny, A; Ulrich, A; Runge, D; Marinova, M; Lütjohann, D; Kroemer, HK; Siegmund, W

2013-01-01

Hypercholesterolemia frequently occurs in patients treated with efavirenz who cannot be treated adequately with statins because of drug interactions. These patients may benefit from cholesterol-lowering therapy with ezetimibe. This study determined the influence of single-dose and multiple-dose efavirenz (400 mg/day for 9 days) on the pharmacokinetics and sterol-lowering of ezetimibe (10 mg) in 12 healthy subjects. In addition, the influence of efavirenz on genome-wide intestinal expression and in vitro function of ABCB1, ABCC2, UGT1A1, and OATP1B1 was studied. Efavirenz (multiple dose) had no influence on the pharmacokinetics and lipid-lowering functions of ezetimibe. Intestinal expression of enzymes and transporters (e.g., ABCB1, ABCC2, and UGT1A1) was not affected by chronic efavirenz. Efavirenz (single dose) slightly increased ezetimibe absorption and markedly decreased exposure to ezetimibe-glucuronide (single dose and multiple dose), which may be explained by inhibition of UGT1A1 and ABCB1 (in vitro data). Ezetimibe had no effect on the disposition of efavirenz. Consequently, ezetimibe may be a safe and efficient therapeutic option in patients with HIV infection. PMID:22297387

Portable neutron spectrometer and dosimeter

DOEpatents

Waechter, D.A.; Erkkila, B.H.; Vasilik, D.G.

The disclosure relates to a battery operated neutron spectrometer/dosimeter utilizing a microprocessor, a built-in tissue equivalent LET neutron detector, and a 128-channel pulse height analyzer with integral liquid crystal display. The apparatus calculates doses and dose rates from neutrons incident on the detector and displays a spectrum of rad or rem as a function of keV per micron of equivalent tissue and also calculates and displays accumulated dose in millirads and millirem as well as neutron dose rates in millirads per hour and millirem per hour.

Portable neutron spectrometer and dosimeter

DOEpatents

Waechter, David A.; Erkkila, Bruce H.; Vasilik, Dennis G.

1985-01-01

The disclosure relates to a battery operated neutron spectrometer/dosimeter utilizing a microprocessor, a built-in tissue equivalent LET neutron detector, and a 128-channel pulse height analyzer with integral liquid crystal display. The apparatus calculates doses and dose rates from neutrons incident on the detector and displays a spectrum of rad or rem as a function of keV per micron of equivalent tissue and also calculates and displays accumulated dose in millirads and millirem as well as neutron dose rates in millirads per hour and millirem per hour.

MCNP simulations of material exposure experiments (u)

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

Temple, Brian A

2010-12-08

Simulations of proposed material exposure experiments were performed using MCNP6. The experiments will expose ampules containing different materials of interest with radiation to observe the chemical breakdown of the materials. Simulations were performed to map out dose in materials as a function of distance from the source, dose variation between materials, dose variation due to ampule orientation, and dose variation due to different source energy. This write up is an overview of the simulations and will provide guidance on how to use the data in the spreadsheet.

Dose-Related Effects of Alcohol on Cognitive Functioning

PubMed Central

Dry, Matthew J.; Burns, Nicholas R.; Nettelbeck, Ted; Farquharson, Aaron L.; White, Jason M.

2012-01-01

We assessed the suitability of six applied tests of cognitive functioning to provide a single marker for dose-related alcohol intoxication. Numerous studies have demonstrated that alcohol has a deleterious effect on specific areas of cognitive processing but few have compared the effects of alcohol across a wide range of different cognitive processes. Adult participants (N = 56, 32 males, 24 females aged 18–45 years) were randomized to control or alcohol treatments within a mixed design experiment involving multiple-dosages at approximately one hour intervals (attained mean blood alcohol concentrations (BACs) of 0.00, 0.048, 0.082 and 0.10%), employing a battery of six psychometric tests; the Useful Field of View test (UFOV; processing speed together with directed attention); the Self-Ordered Pointing Task (SOPT; working memory); Inspection Time (IT; speed of processing independent from motor responding); the Traveling Salesperson Problem (TSP; strategic optimization); the Sustained Attention to Response Task (SART; vigilance, response inhibition and psychomotor function); and the Trail-Making Test (TMT; cognitive flexibility and psychomotor function). Results demonstrated that impairment is not uniform across different domains of cognitive processing and that both the size of the alcohol effect and the magnitude of effect change across different dose levels are quantitatively different for different cognitive processes. Only IT met the criteria for a marker for wide-spread application: reliable dose-related decline in a basic process as a function of rising BAC level and easy to use non-invasive task properties. PMID:23209840

Characterisation of mega-voltage electron pencil beam dose distributions: viability of a measurement-based approach.

PubMed

Barnes, M P; Ebert, M A

2008-03-01

The concept of electron pencil-beam dose distributions is central to pencil-beam algorithms used in electron beam radiotherapy treatment planning. The Hogstrom algorithm, which is a common algorithm for electron treatment planning, models large electron field dose distributions by the superposition of a series of pencil beam dose distributions. This means that the accurate characterisation of an electron pencil beam is essential for the accuracy of the dose algorithm. The aim of this study was to evaluate a measurement based approach for obtaining electron pencil-beam dose distributions. The primary incentive for the study was the accurate calculation of dose distributions for narrow fields as traditional electron algorithms are generally inaccurate for such geometries. Kodak X-Omat radiographic film was used in a solid water phantom to measure the dose distribution of circular 12 MeV beams from a Varian 21EX linear accelerator. Measurements were made for beams of diameter, 1.5, 2, 4, 8, 16 and 32 mm. A blocked-field technique was used to subtract photon contamination in the beam. The "error function" derived from Fermi-Eyges Multiple Coulomb Scattering (MCS) theory for corresponding square fields was used to fit resulting dose distributions so that extrapolation down to a pencil beam distribution could be made. The Monte Carlo codes, BEAM and EGSnrc were used to simulate the experimental arrangement. The 8 mm beam dose distribution was also measured with TLD-100 microcubes. Agreement between film, TLD and Monte Carlo simulation results were found to be consistent with the spatial resolution used. The study has shown that it is possible to extrapolate narrow electron beam dose distributions down to a pencil beam dose distribution using the error function. However, due to experimental uncertainties and measurement difficulties, Monte Carlo is recommended as the method of choice for characterising electron pencil-beam dose distributions.

TH-E-BRF-02: 4D-CT Ventilation Image-Based IMRT Plans Are Dosimetrically Comparable to SPECT Ventilation Image-Based Plans

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

Kida, S; University of Tokyo Hospital, Bunkyo, Tokyo; Bal, M

Purpose: An emerging lung ventilation imaging method based on 4D-CT can be used in radiotherapy to selectively avoid irradiating highly-functional lung regions, which may reduce pulmonary toxicity. Efforts to validate 4DCT ventilation imaging have been focused on comparison with other imaging modalities including SPECT and xenon CT. The purpose of this study was to compare 4D-CT ventilation image-based functional IMRT plans with SPECT ventilation image-based plans as reference. Methods: 4D-CT and SPECT ventilation scans were acquired for five thoracic cancer patients in an IRB-approved prospective clinical trial. The ventilation images were created by quantitative analysis of regional volume changes (amore » surrogate for ventilation) using deformable image registration of the 4D-CT images. A pair of 4D-CT ventilation and SPECT ventilation image-based IMRT plans was created for each patient. Regional ventilation information was incorporated into lung dose-volume objectives for IMRT optimization by assigning different weights on a voxel-by-voxel basis. The objectives and constraints of the other structures in the plan were kept identical. The differences in the dose-volume metrics have been evaluated and tested by a paired t-test. SPECT ventilation was used to calculate the lung functional dose-volume metrics (i.e., mean dose, V20 and effective dose) for both 4D-CT ventilation image-based and SPECT ventilation image-based plans. Results: Overall there were no statistically significant differences in any dose-volume metrics between the 4D-CT and SPECT ventilation imagebased plans. For example, the average functional mean lung dose of the 4D-CT plans was 26.1±9.15 (Gy), which was comparable to 25.2±8.60 (Gy) of the SPECT plans (p = 0.89). For other critical organs and PTV, nonsignificant differences were found as well. Conclusion: This study has demonstrated that 4D-CT ventilation image-based functional IMRT plans are dosimetrically comparable to SPECT ventilation image-based plans, providing evidence to use 4D-CT ventilation imaging for clinical applications. Supported in part by Free to Breathe Young Investigator Research Grant and NIH/NCI R01 CA 093626. The authors thank Philips Radiation Oncology Systems for the Pinnacle3 treatment planning systems.« less

Functional liver image guided hepatic therapy (FLIGHT) with hepatobiliary iminodiacetic acid (HIDA) scans.

PubMed

Long, David E; Tann, Mark; Huang, Ke Colin; Bartlett, Gregory; Galle, James O; Furukawa, Yukie; Maluccio, Mary; Cox, John A; Kong, Feng-Ming Spring; Ellsworth, Susannah G

2018-05-01

Hepatobiliary iminodiacetic acid (HIDA) scans provide global and regional assessments of liver function that can serve as a road map for functional avoidance in stereotactic body radiation therapy (SBRT) planning. Functional liver image guided hepatic therapy (FLIGHT), an innovative planning technique, is described and compared with standard planning using functional dose-volume histograms. Thresholds predicting for decompensation during follow up are evaluated. We studied 17 patients who underwent HIDA scans before SBRT. All SBRT cases were replanned using FLIGHT. The following dosimetric endpoints were compared for FLIGHT versus standard SBRT planning: functional residual capacity <15 Gy (FRC 15 HIDA), mean liver dose (MLD), equivalent uniform dose (EUD), and functional EUD (FEUD). Receiver operating characteristics curves were used to evaluate whether baseline HIDA values, standard cirrhosis scoring, and/or dosimetric data predicted clinical decompensation. Compared with standard planning, FLIGHT significantly improved FRC 15 HIDA (mean improvement: 5.3%) as well as MLD, EUD, and FEUD (P < .05). Considerable interindividual variations in the extent of benefit were noted. Decompensation during follow-up was associated with baseline global HIDA <2.915%/min/m 2 , FRC 15 HIDA <2.11%/min/m 2 , and MELD ≥11 (P < .05). FLIGHT with HIDA-based parameters may complement blood chemistry-based assessments of liver function and facilitate individualized, adaptive liver SBRT planning. Copyright © 2018. Published by Elsevier Inc.

Targeting L-Selectin to Improve Neurologic and Urologic Function After Spinal Cord Injury

DTIC Science & Technology

2015-10-01

demonstrated locomotor recovery in mice receiving 40mg/kg DFA up to 3 hours following spinal cord injury -We demonstrated improved locomotor recovery...health, as evaluated by body weight -We identified no added locomotor recovery due to multiple, successive doses of DFA. Moreover, additional doses...bladder function Significance: We have identified robust locomotor recovery in both mild and severe spinal cord injured mice that received DFA up

Dose reduction of risperidone and olanzapine can improve cognitive function and negative symptoms in stable schizophrenic patients: A single-blinded, 52-week, randomized controlled study.

PubMed

Zhou, Yanling; Li, Guannan; Li, Dan; Cui, Hongmei; Ning, Yuping

2018-05-01

The long-term effects of dose reduction of atypical antipsychotics on cognitive function and symptomatology in stable patients with schizophrenia remain unclear. We sought to determine the change in cognitive function and symptomatology after reducing risperidone or olanzapine dosage in stable schizophrenic patients. Seventy-five stabilized schizophrenic patients prescribed risperidone (≥4 mg/day) or olanzapine (≥10 mg/day) were randomly divided into a dose-reduction group ( n=37) and a maintenance group ( n=38). For the dose-reduction group, the dose of antipsychotics was reduced by 50%; for the maintenance group, the dose remained unchanged throughout the whole study. The Positive and Negative Syndrome Scale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery were measured at baseline, 12, 28, and 52 weeks. Linear mixed models were performed to compare the Positive and Negative Syndrome Scale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects and MATRICS Consensus Cognitive Battery scores between groups. The linear mixed model showed significant time by group interactions on the Positive and Negative Syndrome Scale negative symptoms, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, speed of processing, attention/vigilance, working memory and total score of MATRICS Consensus Cognitive Battery (all p<0.05). Post hoc analyses showed significant improvement in Positive and Negative Syndrome Scale negative subscale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, speed of processing, working memory and total score of MATRICS Consensus Cognitive Battery for the dose reduction group compared with those for the maintenance group (all p<0.05). This study indicated that a risperidone or olanzapine dose reduction of 50% may not lead to more severe symptomatology but can improve speed of processing, working memory and negative symptoms in patients with stabilized schizophrenia.

SU-E-T-385: 4D Radiobiology

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

Fourkal, E; Hossain, M; Veltchev, I

2014-06-01

Purpose: The linear-quadratic model is the most prevalent model for planning dose fractionation in radiation therapy in the low dose per fraction regimens. However for high-dose fractions, used in SRS/SBRT/HDR treatments the LQ model does not yield accurate predictions, due to neglecting the reduction in the number of sublethal lesions as a result of their conversion to lethal lesions with subsequent irradiation. Proper accounting for this reduction in the number of sublethally damaged lesions leads to the dependence of the survival fraction on the temporal structure of the dose. The main objective of this work is to show that themore » functional dependence of the dose rate on time in each voxel is an important additional factor that can significantly influence the TCP. Methods: Two SBRT lung plans have been used to calculate the TCPs for the same patient. One plan is a 3D conformal plan and the other is an IMRT plan. Both plans are normalized so that 99.5% of PTV volume receives the same prescription dose of 50 Gy in 5 fractions. The dose rate in each individual voxel is calculated as a function of treatment time and subsequently used in the calculation of TCP. Results: The calculated TCPs show that shorter delivery times lead to greater TCP, despite all delivery times being short compared to the repair half-time for sublethal lesions. Furthermore, calculated TCP(IMRT) =0.308 for the IMRT plan is smaller than TCP(3D) =0.425 for 3D conformal, even though it shows greater tumor hot spots and equal PTV coverage. The calculated TCPs are considerably lower compared to those based on the LQ model for which TCP=1 for both plans. Conclusion: The functional dependence of the voxel-by-voxel dose rate on time may be an important factor in predicting the treatment outcome and cannot be neglected in radiobiological modeling.« less

Low doses of arsenic, via perturbing p53, promotes tumorigenesis

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

Ganapathy, Suthakar, E-mail: s.ganapathy@neu.edu

In drinking water and in workplace or living environments, low doses of arsenic can exist and operate as a potent carcinogen. Due to insufficient understanding and information on the pervasiveness of environmental exposures to arsenic, there is an urgent need to elucidate the underlying molecular mechanisms of arsenic regarding its carcinogenic effect on human health. In this study, we demonstrate that low doses of arsenic exposure mitigate or mask p53 function and further perturb intracellular redox state, which triggers persistent endoplasmic reticulum (ER) stress and activates UPR (unfolded protein response), leading to transformation or tumorigenesis. Thus, the results suggest thatmore » low doses of arsenic exposure, through attenuating p53-regulated tumor suppressive function, change the state of intracellular redox and create a microenvironment for tumorigenesis. Our study also provides the information for designing more effective strategies to prevent or treat human cancers initiated by arsenic exposure.« less

Physicochemical and functional properties of gamma irradiated buckwheat and potato starch

NASA Astrophysics Data System (ADS)

Verma, Ruchi; Jan, Shumaila; Rani, Savita; Jan, Kulsum; Swer, Tanya L.; Prakash, Kumar S.; Dar, M. Z.; Bashir, Khalid

2018-03-01

Starches isolated from buckwheat and potato were subject to different doses of irradiation at 0, 5, 10, 15 and 20 kGy. Native and irradiated starch samples were evaluated for their physicochemical and functional properties to assess the effect of gamma irradiation. Apparent amylose content decreased significantly from 26.84% to 22.12% and 27.01 to 16.11% for buckwheat and potato starch respectively as the dose increased. A significant decrease was observed in pH, swelling power and syneresis as the dose increased for both buckwheat and potato starch. pH decreased from 5.20 to 3.81 and 5.81 to 3.95 for buckwheat and potato starch, respectively. Carboxyl content, freeze thaw stability, water and oil absorption capacity and transmittance showed increasing trend with increasing irradiation dose. Carboxyl content increased from 0% to 0.23% and 0-0.22% for buckwheat and potato starch, respectively.

Short-term therapy with relatively low-dose cerivastatin improves endothelial function independently of its lipid-lowering effect: Evaluation of brachial artery vasodilatation using B-mode ultrasound imaging.

PubMed

Sakabe, Koichi; Fukuda, Nobuo; Nada, Teru; Onose, Yukiko; Soeki, Takeshi; Shinohara, Hisanori; Tamura, Yoshiyuki

2002-12-01

Administration of 0.4 to 0.8 mg of cerivastatin per day for 2 weeks has been reported to have pleiotropic effects and improve endothelial function. Whether low-dose cerivastatin would produce these rapid pleiotropic effects in the clinical setting remains uncertain, however. We investigated the effect of short-term therapy with relatively low-dose cerivastatin (0.15 mg/day) on endothelial function, thrombostatic parameters, and C-reactive protein (CRP) levels in hypercholesterolemic patients. Thirteen patients with LDL-cholesterol>160 mg/dl were treated with daily doses of 0.15 mg of cerivastatin for 2 weeks. Endothelial function, thrombostatic parameters (tissue-type plasminogen activator [t-PA], plasminogen activator inhibitor type 1 [PAI-1], and CRP were estimated at baseline and again after 2 weeks of treatment. Endothelial function was measured as flow-mediated vasodilation. Flow-mediated vasodilatation was assessed by measuring the percent change in the diameter of the brachial artery in response to reactive hyperemia using high-resolution ultrasound. Endothelium-independent vasodilatation was also measured using sublingual nitroglycerin. No major complications developed after the treatment. Total cholesterol decreased significantly, from 258±32 to 211±21 mg/dl, and LDL-cholesterol also decreased from 171±15 to 133±16 mg/dl after the treatment. Flow-mediated vasodilatation increased significantly, from 4.6±1.3 percent to 8.7±3.5 percent after 2 weeks of therapy, although endothelium-independent vasodilatation was not affected (9.5±2.4% vs 8.8±3.1%). No relation was found between percent change in flow-mediated vasodilatation and improvement in levels of LDL-cholesterol after therapy (r=0.07). PAI-1, t-PA, and CRP were not significantly changed by 2 weeks of therapy. (1) Evaluating vasodilation of the brachial artery with B-mode ultrasound imaging was useful in investigating the effect of statin on endothelial function. (2) Although no effect was detected in PAI-1, t-PA, or CRP, relatively low-dose cerivastatin therapy for 2 weeks improved endothelial function and lipid level independently and safely in hypercholesterolemic patients.

TLD measurements of in vivo mammographic exposures and the calculated mean glandular dose across the United States.

PubMed

Gentry, J R; DeWerd, L A

1996-06-01

An analysis is presented of the exposures received by TLDs placed on the breasts of 4400 women obtaining mammograms at 170 institutions across the United States. Mean glandular dose and exposure were examined as a function of compressed breast thickness. The exposure and mean glandular dose were found to increase linearly with breast thickness. The mean glandular dose typically delivered by the institutions was well below the limit of 3.0 mGy for the 4.5-cm breast. However, some institutions tend to uniformly give higher doses. In such institutions approximately 25% of 4.5-cm-thick breasts received a mean glandular dose exceeding 3.0 mGy.

Gamma irradiator dose mapping simulation using the MCNP code and benchmarking with dosimetry.

PubMed

Sohrabpour, M; Hassanzadeh, M; Shahriari, M; Sharifzadeh, M

2002-10-01

The Monte Carlo transport code, MCNP, has been applied in simulating dose rate distribution in the IR-136 gamma irradiator system. Isodose curves, cumulative dose values, and system design data such as throughputs, over-dose-ratios, and efficiencies have been simulated as functions of product density. Simulated isodose curves, and cumulative dose values were compared with dosimetry values obtained using polymethyle-methacrylate, Fricke, ethanol-chlorobenzene, and potassium dichromate dosimeters. The produced system design data were also found to agree quite favorably with those of the system manufacturer's data. MCNP has thus been found to be an effective transport code for handling of various dose mapping excercises for gamma irradiators.

[Pharmacological correction of central nervous system function in exposure to Coriolis acceleration].

PubMed

Karkishchenko, N N; Dimitriadi, N A; Molchanovskiĭ, V V

1986-01-01

Healthy volunteers with a low vestibular tolerance were exposed to Coriolis acceleration. Potassium orotate, pyracetame and riboxine were used as prophylactic measures against disorders in the function of the vestibular apparatus and higher compartments of the higher nervous system. The central nervous function was assessed with respect to the spectral power of electroencephalograms, short-term memory and mental performance. Potassium orotate given at a dose of 40 mg/kg body weight/day during 12-14 days as well as pyracetame given at a dose of 30 mg/kg body weight/day during 3 or 7 days increased significantly statokinetic tolerance and produced a protective effect on the central nervous function against Coriolis acceleration.

[Effect of substance P on cardiac autonomic nervous function in rats].

PubMed

Deng, Lijun; Li, Jing; Yan, Fuping; Lu, Jie

2009-12-01

Forty SD rats were divided into 5 groups: control group, SP groups (5 microg/kg,10 microg/kg, 20 microg/kg) and spantide II plus SP group. An analysis of heart rate variability (HRV) was used to detect the changes of HRV parameters before and after intravenous injection of SP in order to investigate the effect of substance P on cardiac autonomic nervous function and the corresponding mechanism. (1) There were significant differences in most HRV parameters for the three different doses of SP. Mean heart period (MHP), absolute power of ultra-low frequency and high frequency band (APU, APH), total power (TPV) and ratio of power in ultra-low to high frequency band (RUH) increased, while mean heart rate (MHR) and chaos intensity (HCC) decreased during the 30 minutes. Each peak amplitude of HRV parameters went higher and showed up ahead of the upward doses of SP. (2) Significant change was seen in each of the parameters between spantide II plus SP group and high-dose SP group. These data idicate that, after intravenous injection of different doses of SP, both cardiac sympathetic nervous system activity and parasympathetic nervous system activity increase, and the function of cardiac autonomic nervous becomes instable and unbalanced. The effect of SP may be dose dependent, and it is possibly mediated by neurokinin-1(NK-1) receptor.

Effects of a Single Dose of Parecoxib on Inflammatory Response and Ischemic Tubular Injury Caused by Hemorrhagic Shock in Rats.

PubMed

Takaku, Mariana; da Silva, Andre Carnevali; Iritsu, Nathalie Izumi; Vianna, Pedro Thadeu Galvao; Castiglia, Yara Marcondes Machado

2018-01-01

Parecoxib, a selective COX-2 inhibitor, is used to improve analgesia in postoperative procedures. Here we evaluated whether pretreatment with a single dose of parecoxib affects the function, cell injury, and inflammatory response of the kidney of rats subjected to acute hemorrhage. Inflammatory response was determined according to serum and renal tissue cytokine levels (IL-1 α , IL-1 β , IL-6, IL-10, and TNF- α ). Forty-four adult Wistar rats anesthetized with sevoflurane were randomized into four groups: placebo/no hemorrhage (Plc/NH); parecoxib/no hemorrhage (Pcx/NH); placebo/hemorrhage (Plc/H); and parecoxib/hemorrhage (Pcx/H). Pcx groups received a single dose of intravenous parecoxib while Plc groups received a single dose of placebo (isotonic saline). Animals in hemorrhage groups underwent bleeding of 30% of blood volume. Renal function and renal histology were then evaluated. Plc/H showed the highest serum levels of cytokines, suggesting that pretreatment with parecoxib reduced the inflammatory response in rats subjected to hemorrhage. No difference in tissue cytokine levels between groups was observed. Plc/H showed higher percentage of tubular dilation and degeneration, indicating that parecoxib inhibited tubular injury resulting from renal hypoperfusion. Our findings indicate that pretreatment with a single dose of parecoxib reduced the inflammatory response and tubular renal injury without altering renal function in rats undergoing acute hemorrhage.

A flexible Monte Carlo tool for patient or phantom specific calculations: comparison with preliminary validation measurements

NASA Astrophysics Data System (ADS)

Davidson, S.; Cui, J.; Followill, D.; Ibbott, G.; Deasy, J.

2008-02-01

The Dose Planning Method (DPM) is one of several 'fast' Monte Carlo (MC) computer codes designed to produce an accurate dose calculation for advanced clinical applications. We have developed a flexible machine modeling process and validation tests for open-field and IMRT calculations. To complement the DPM code, a practical and versatile source model has been developed, whose parameters are derived from a standard set of planning system commissioning measurements. The primary photon spectrum and the spectrum resulting from the flattening filter are modeled by a Fatigue function, cut-off by a multiplying Fermi function, which effectively regularizes the difficult energy spectrum determination process. Commonly-used functions are applied to represent the off-axis softening, increasing primary fluence with increasing angle ('the horn effect'), and electron contamination. The patient dependent aspect of the MC dose calculation utilizes the multi-leaf collimator (MLC) leaf sequence file exported from the treatment planning system DICOM output, coupled with the source model, to derive the particle transport. This model has been commissioned for Varian 2100C 6 MV and 18 MV photon beams using percent depth dose, dose profiles, and output factors. A 3-D conformal plan and an IMRT plan delivered to an anthropomorphic thorax phantom were used to benchmark the model. The calculated results were compared to Pinnacle v7.6c results and measurements made using radiochromic film and thermoluminescent detectors (TLD).

Sperm quality and DNA damage in men from Jilin Province, China, who are occupationally exposed to ionizing radiation.

PubMed

Zhou, D D; Hao, J L; Guo, K M; Lu, C W; Liu, X D

2016-03-22

Long-term radiation exposure affects human health. Ionizing radiation has long been known to raise the risk of cancer. In addition to high doses of radiation, low-dose ionizing radiation might increase the risk of cardiovascular disease, lens opacity, and some other non-cancerous diseases. Low- and high-dose exposures to ionizing radiation elicit different signaling events at the molecular level, and may involve different response mechanisms. The health risks arising from exposure to low doses of ionizing radiation should be re-evaluated. Health workers exposed to ionizing radiation experience low-dose radiation and have an increased risk of hematological malignancies. Reproductive function is sensitive to changes in the physical environment, including ionizing radiation. However, data is scarce regarding the association between occupational radiation exposure and risk to human fertility. Sperm DNA integrity is a functional parameter of male fertility evaluation. Hence, we aimed to report sperm quality and DNA damage in men from Jilin Province, China, who were occupationally exposed to ionizing radiation. Sperm motility and normal morphology were significantly lower in the exposed compared with the non-exposed men. There was no statistically significant difference in sperm concentration between exposed and non-exposed men. The sperm DNA fragmentation index was significantly higher in the exposed than the non-exposed men. Chronic long-term exposure to low doses of ionizing radiation could affect sperm motility, normal morphology, and the sperm DNA fragmentation index in the Chinese population. Sperm quality and DNA integrity are functional parameters that could be used to evaluate occupational exposure to ionizing radiation.

Modelling the occurrence and severity of enoxaparin-induced bleeding and bruising events

PubMed Central

Barras, Michael A; Duffull, Stephen B; Atherton, John J; Green, Bruce

2009-01-01

AIMS To develop a population pharmacokinetic–pharmacodynamic model to describe the occurrence and severity of bleeding or bruising as a function of enoxaparin exposure. METHODS Data were obtained from a randomized controlled trial (n = 118) that compared conventional dosing of enoxaparin (product label) with an individualized dosing regimen. Anti-Xa concentrations were sampled using a sparse design and the size, location and type of bruising and bleeding event, during enoxaparin therapy, were collected daily. A population pharmacokinetic–pharmacodynamic analysis was performed using nonlinear mixed effects techniques. The final model was used to explore how the probability of events in patients with obesity and/or renal impairment varied under differing dosing strategies. RESULTS Three hundred and forty-nine anti-Xa concentrations were available for analysis. A two-compartment first-order absorption and elimination model best fit the data, with lean body weight describing between-subject variability in clearance and central volume of distribution. A three-category proportional-odds model described the occurrence and severity of events as a function of both cumulative enoxaparin AUC (cAUC) and subject age. Simulations showed that individualized dosing decreased the probability of a bleeding or major bruising event when compared with conventional dosing, which was most noticeable in subjects with obesity and renal impairment. CONCLUSIONS The occurrence and severity of a bleeding or major bruising event to enoxaparin, administered for the treatment of a thromboembolic disease, can be described as a function of both cAUC and subject age. Individualized dosing of enoxaparin will reduce the probability of an event. PMID:19916994

Local and Systemic Inflammation May Mediate Diesel Engine Exhaust-Induced Lung Function Impairment in a Chinese Occupational Cohort.

PubMed

Wang, Haitao; Duan, Huawei; Meng, Tao; Yang, Mo; Cui, Lianhua; Bin, Ping; Dai, Yufei; Niu, Yong; Shen, Meili; Zhang, Liping; Zheng, Yuxin; Leng, Shuguang

2018-04-01

Diesel exhaust (DE) as the major source of vehicle-emitted particle matter in ambient air impairs lung function. The objectives were to assess the contribution of local (eg, the fraction of exhaled nitric oxide [FeNO] and serum Club cell secretory protein [CC16]) and systemic (eg, serum C-reaction protein [CRP] and interleukin-6 [IL-6]) inflammation to DE-induced lung function impairment using a unique cohort of diesel engine testers (DETs, n = 137) and non-DETs (n = 127), made up of current and noncurrent smokers. Urinary metabolites, FeNO, serum markers, and spirometry were assessed. A 19% reduction in CC16 and a 94% increase in CRP were identified in DETs compared with non-DETs (all p values <10-4), which were further corroborated by showing a dose-response relationship with internal dose for DE exposure (all p values <.04) and a time-course relationship with DE exposure history (all p values <.005). Mediation analysis showed that 43% of the difference in FEV1 between DETs and non-DETs can be explained by circulating CC16 and CRP (permuted p < .001). An inverse dose-dependent relationship between FeNO and internal dose for cigarette smoke was identified (p = .0003). A range of 95% lower bounds of benchmark dose of 1.0261-1.4513 μg phenanthrols/g creatinine in urine as an internal dose was recommended for regulatory risk assessment. Local and systemic inflammation may be key processes that contribute to the subsequent development of obstructive lung disease in DE-exposed populations.

Evaluation of a Proposed Biodegradable 188Re Source for Brachytherapy Application

PubMed Central

Khorshidi, Abdollah; Ahmadinejad, Marjan; Hamed Hosseini, S.

2015-01-01

Abstract This study aimed to evaluate dosimetric characteristics based on Monte Carlo (MC) simulations for a proposed beta emitter bioglass 188Re seed for internal radiotherapy applications. The bioactive glass seed has been developed using the sol-gel technique. The simulations were performed for the seed using MC radiation transport code to investigate the dosimetric factors recommended by the AAPM Task Group 60 (TG-60). Dose distributions due to the beta and photon radiation were predicted at different radial distances surrounding the source. The dose rate in water at the reference point was calculated to be 7.43 ± 0.5 cGy/h/μCi. The dosimetric factors consisting of the reference point dose rate, D(r0,θ0), the radial dose function, g(r), the 2-dimensional anisotropy function, F(r,θ), the 1-dimensional anisotropy function, φan(r), and the R90 quantity were estimated and compared with several available beta-emitting sources. The element 188Re incorporated in bioactive glasses produced by the sol-gel technique provides a suitable solution for producing new materials for seed implants applied to brachytherapy applications in prostate and liver cancers treatment. Dose distribution of 188Re seed was greater isotropic than other commercially attainable encapsulated seeds, since it has no end weld to attenuate radiation. The beta radiation-emitting 188Re source provides high doses of local radiation to the tumor tissue and the short range of the beta particles limit damage to the adjacent normal tissue. PMID:26181543

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

Blanck, Oliver, E-mail: oliver.blanck@uksh.de; CyberKnife Center Northern Germany, Guestrow; Bode, Frank

Purpose: To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation. Methods and Materials: Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm{sup 3}). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination. Results: Transmural scarringmore » of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy. Conclusions: Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.« less

A radiobiological model of metastatic burden reduction for molecular radiotherapy: application to patients with bone metastases

NASA Astrophysics Data System (ADS)

Denis-Bacelar, Ana M.; Chittenden, Sarah J.; Murray, Iain; Divoli, Antigoni; McCready, V. Ralph; Dearnaley, David P.; O'Sullivan, Joe M.; Johnson, Bernadette; Flux, Glenn D.

2017-04-01

Skeletal tumour burden is a biomarker of prognosis and survival in cancer patients. This study proposes a novel method based on the linear quadratic model to predict the reduction in metastatic tumour burden as a function of the absorbed doses delivered from molecular radiotherapy treatments. The range of absorbed doses necessary to eradicate all the bone lesions and to reduce the metastatic burden was investigated in a cohort of 22 patients with bone metastases from castration-resistant prostate cancer. A metastatic burden reduction curve was generated for each patient, which predicts the reduction in metastatic burden as a function of the patient mean absorbed dose, defined as the mean of all the lesion absorbed doses in any given patient. In the patient cohort studied, the median of the patient mean absorbed dose predicted to reduce the metastatic burden by 50% was 89 Gy (interquartile range: 83-105 Gy), whilst a median of 183 Gy (interquartile range: 107-247 Gy) was found necessary to eradicate all metastases in a given patient. The absorbed dose required to eradicate all the lesions was strongly correlated with the variability of the absorbed doses delivered to multiple lesions in a given patient (r  =  0.98, P  <  0.0001). The metastatic burden reduction curves showed a potential large reduction in metastatic burden for a small increase in absorbed dose in 91% of patients. The results indicate the range of absorbed doses required to potentially obtain a significant survival benefit. The metastatic burden reduction method provides a simple tool that could be used in routine clinical practice for patient selection and to indicate the required administered activity to achieve a predicted patient mean absorbed dose and reduction in metastatic tumour burden.

Thermoluminescence dosimetry for in-vivo verification of high dose rate brachytherapy for prostate cancer.

PubMed

Das, R; Toye, W; Kron, T; Williams, S; Duchesne, G

2007-09-01

It was the aim of the study to verify dose delivered in urethra and rectum during High Dose Rate brachytherapy boost (HDRBB) of prostate cancer patients. During the first fraction of HDRBB measurement catheters were placed in the urethra and rectum of prostate cancer patients. These contained LiF:Mg,Ti Thermoluminescence Dosimetry (TLD) rods of 1 mm diameter, with up to 11 detectors positioned every 16 mm separated by radio-opaque markers. A Lorentzian peak function was used to fit the data. Measurements from 50 patients were evaluated and measured doses were compared with predictions from the treatment planning system (Plato Vs 13.5 to 14.1). Prospective urinary and rectal toxicity scores were collected following treatment. In more than 90% of cases, the Lorentzian peak function provided a good fit to both experimental and planning urethral data (r2 > 0.9). In general there was good agreement between measured and predicted doses with the average difference between measured and planned maximum dose being 0.1 Gy. No significant association between dose and any clinical endpoints was observed in 43 patients available for clinical evaluation. An average inferior shift of 2 mm between the plan and the measurement performed approximately 1 hour after the planning CT scan was found for the dose distribution in the cohort of patients for the urethra measurements. Rectal measurements proved to be more difficult to interpret as there is more variability of TLD position between planning and treatment. TLD in-vivo measurements are easily performed in urethra and rectum during HDR brachytherapy of prostate patients. They verify the delivery and provide information about the dose delivered to critical structures. The latter may be of particular interest if higher doses are to be given per fraction such as in HDR monotherapy.

Individual variations in dose response for spatial memory learning among outbred wistar rats exposed from 5 to 20 cGy of (56) Fe particles.

PubMed

Wyrobek, Andrew J; Britten, Richard A

2016-06-01

Exposures of brain tissue to ionizing radiation can lead to persistent deficits in cognitive functions and behaviors. However, little is known about the quantitative relationships between exposure dose and neurological risks, especially for lower doses and among genetically diverse individuals. We investigated the dose relationship for spatial memory learning among genetically outbred male Wistar rats exposed to graded doses of (56) Fe particles (sham, 5, 10, 15, and 20 cGy; 1 GeV/n). Spatial memory learning was assessed on a Barnes maze using REL3 ratios measured at three months after exposure. Irradiated animals showed dose-dependent declines in spatial memory learning that were fit by a linear regression (P for slope <0.0002). The irradiated animals showed significantly impaired learning at 10 cGy exposures, no detectable learning between 10 and 15 cGy, and worsened performances between 15 and 20 cGy. The proportions of poor learners and the magnitude of their impairment were fit by linear regressions with doubling doses of ∼10 cGy. In contrast, there were no detectable deficits in learning among the good learners in this dose range. Our findings suggest that genetically diverse individuals can vary substantially in their spatial memory learning, and that exposures at low doses appear to preferentially impact poor learners. This hypothesis invites future investigations of the genetic and physiological mechanisms of inter-individual variations in brain function related to spatial memory learning after low-dose HZE radiation exposures and to determine whether it also applies to physical trauma to brain tissue and exposures to chemical neurotoxicants. Environ. Mol. Mutagen. 57:331-340, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Monte Carlo investigation of backscatter point spread function for x-ray imaging examinations

NASA Astrophysics Data System (ADS)

Xiong, Zhenyu; Vijayan, Sarath; Rudin, Stephen; Bednarek, Daniel R.

2017-03-01

X-ray imaging examinations, especially complex interventions, may result in relatively high doses to the patient's skin inducing skin injuries. A method was developed to determine the skin-dose distribution for non-uniform x-ray beams by convolving the backscatter point-spread-function (PSF) with the primary-dose distribution to generate the backscatter distribution that, when added to the primary dose, gives the total-dose distribution. This technique was incorporated in the dose-tracking system (DTS), which provides a real-time color-coded 3D-mapping of skin dose during fluoroscopic procedures. The aim of this work is to investigate the variation of the backscatter PSF with different parameters. A backscatter PSF of a 1-mm x-ray beam was generated by EGSnrc Monte-Carlo code for different x-ray beam energies, different soft-tissue thickness above bone, different bone thickness and different entrance-beam angles, as well as for different locations on the SK-150 anthropomorphic head phantom. The results show a reduction of the peak scatter to primary dose ratio of 48% when X-ray beam voltage is increased from 40 keV to 120 keV. The backscatter dose was reduced when bone was beneath the soft tissue layer and this reduction increased with thinner soft tissue and thicker bone layers. The backscatter factor increased about 21% as the angle of incidence of the beam with the entrance surface decreased from 90° (perpendicular) to 30°. The backscatter PSF differed for different locations on the SK-150 phantom by up to 15%. The results of this study can be used to improve the accuracy of dose calculation when using PSF convolution in the DTS.

Tolerance to 3,4-Methylenedioxymethamphetamine (MDMA) in Rats Exposed to Single High-Dose Binges

PubMed Central

Baumann, Michael H.; Clark, Robert D.; Franken, Frederick H.; Rutter, John J.; Rothman, Richard B.

2008-01-01

3,4-Methylenedioxymethamphetamine (MDMA or Ecstasy) stimulates the transporter-mediated release of monoamines, including serotonin (5-HT). High-dose exposure to MDMA causes persistent 5-HT deficits (e.g., depletion of brain 5-HT) in animals, yet the functional and clinical relevance of such deficits are poorly defined. Here we examine functional consequences of MDMA-induced 5-HT depletions in rats. Male rats received binges of 3 ip injections of MDMA or saline, one injection every 2 h; MDMA was given at a threshold pharmacological dose (1.5 mg/kg × 3, low dose) or at a 5-fold higher amount (7.5 mg/kg × 3, high dose). One week later, jugular catheters and intracerebral guide cannulae were implanted. Two weeks after binges, rats received acute iv challenge injections of 1 and 3 mg/kg MDMA. Neuroendocrine effects evoked by iv MDMA (prolactin and corticosterone secretion) were assessed via serial blood sampling, while neurochemical effects (5-HT and dopamine release) were assessed via microdialysis in brain. MDMA binges elevated core temperatures only in the high-dose group, with these same rats exhibiting ~50% loss of forebrain 5-HT two weeks later. Prior exposure to MDMA did not alter baseline plasma hormones or dialysate monoamines, and effects of iv MDMA were similar in saline and low-dose groups. By contrast, rats pretreated with high-dose MDMA displayed significant reductions in evoked hormone secretion and 5-HT release when challenged with iv MDMA. As tolerance developed only in rats exposed to high-dose binges, hyperthermia and 5-HT depletion are implicated in this phenomenon. Our results suggest that MDMA tolerance in humans may reflect 5-HT deficits which could contribute to further dose escalation. PMID:18313226

Assessment of the effects of ISIS 2302, an anti-sense inhibitor of human ICAM-1, on cellular and humoral immunity in mice.

PubMed

Henry, Scott P; Levin, Arthur A; White, Kimber; Mennear, John H

2006-12-01

ISIS 2302 is a phosphorothioate oligonucleotide designed to inhibit human ICAM-1 and is intended for treatment of inflammatory diseases. Molecules of this class are known to elicit pro-inflammatory effects, and immunotoxicity studies were performed in mice to elucidate the nature of effects of ISIS 2302 on mammalian immune function. ISIS 2302 (1, 5, 20, or 50 mg/kg/dose) was administered intravenously every other day for 27 days. The pro-inflammatory properties of the drug were observed at doses > or = 20 mg/kg. A dose-dependent increase in spleen weight was associated with increased absolute splenocyte and B-lymphocyte counts after the 50 mg/kg/dose regimen. The mitogenic response of B-lymphocytes to bacterial lipopolysaccharide was increased after the 20 and 50 mg/kg/doses but antibody-forming cell activities remained unchanged. Total serum IgG concentration was decreased after the 20 and 50 mg/kg/dose regimens but IgM titers were unchanged. Increases in IL-6, IL-12, and MCP-1 as well as NK cell activity were observed after administration of 20 and 50 mg/kg/dose. Cytotoxic T-lymphocyte activity was decreased by the 50 mg/kg/dose regimen. Other changes in immune function were not observed in ISIS 2302-dosed mice. ISIS 3082, a murine active ICAM-1 inhibitor, was used to demonstrate the anti-inflammatory activity of ICAM-1 inhibition in the 2,4-dinitrofluorobenzene-induced contact sensitization model. Intravenous administration of 1 mg/kg of ISIS 3082 every other day for 27 days was unequivocally anti-inflammatory in the contact sensitization test. The results of these experiments support the conclusion that the prophlogistic effects of ISIS 2302 in mice are observed only at suprapharmacologic doses.

The evaluation the magnitude radiation exposure dose rate in digital radiography room design

NASA Astrophysics Data System (ADS)

Dwiyanto, Agung; Setia Budi, Wahyu; Hardiman, Gagoek

2017-12-01

This study discusses the dose rate in digital radiography room, buit according to meet the provisions of KEMENKES No.1014 / Menkes / SK / XI / 2008 and Regulation of BAPETEN No. 8 / 2011. The provisions primary concern of radiation safety, not comfort, by considering the space design. There are five aspects to consider in designing the space: functionality, comfort, security, movement activities and aesthetics. However provisions only met three aspects of the design, which are a function, security and movement activity. Therefore, it is necessary to evaluate digital radiography room in terms of its ability to control external radiation exposure to be safe and comfortable The dose rate is measured by the range of primary and secondary radiation in the observation points by using Surveymeter. All data are obtained by the preliminary survey prior to the study. Furthermore, the review of digital radiography room is done based on architectural design theory. The dose rate for recommended improvement room is recalculated using the same method as the actual room with the help of computer modeling. The result of dose rate calculation at the inner and outer part of digital radiography observation room shows that in-room dose for a week at each measuring point exceeds the allowable dose limit both for staff and public. During a week of observation, the outdoor dose at some measuring points exceeds the dose limit set by the KEMENKES No.1014 / Menkes / SK / XI / 2008 and Regulation BEPETEN No 8/2011. Meanwhile, the result of dose rate calculation in the inner and outer part of the improved digital radiography room can meet the applicable regulations better.

Study of Dose Perturbation at Bone-Tissue Interfaces in Megavoltage Photon Beam Therapy.

NASA Astrophysics Data System (ADS)

Das, Indra Jeet

Dose perturbations during photon beam irradiation occur at interfaces between two dissimilar media due to the loss of electronic equilibrium. The human body contains many different types of interfaces between soft tissue and other media such as, air cavities, lungs, bones, and high atomic number (Z) materials. The dose to critical organs in the vicinity of high Z interfaces, is what leads to this project. This work describes the dose perturbation at high Z (from bone to lead) interfaces with soft tissue for clinically used megavoltage photon beams in the range of CO-60 gamma rays to 24 MV X-rays. It is divided into three main sections: (1) the dose outside the inhomogeneity in the direction of backscatter, (2) the dose inside the inhomogeneity, and (3) the dose on the photon transmission side of the inhomogeneity. Using different types of parallel plate ion chambers, TLD (powder and chip), and film as dosimeters, the dose perturbation is studied as a function of photon energy, thickness, width, and depth of inhomogeneity, distance from the interface and radiation field size. The concept of Bragg-Gray cavity theory is applied and verified for dose determination inside the inhomogeneity. A significant dose enhancement has been observed on the backscatter side for all photon energies. It is strongly dependent on the atomic number of the inhomogeneity and less dependent on the photon energy, thickness, depth, width, and field size. In the forward direction, a dose reduction occurs at the interface at beam energies lower than 10 MV, whereas a dose enhancement occurs for higher photon energies. The interface effect persists up to a few millimeters on the backscatter side but a distance equivalent to the secondary electron range for the particular photon beams in the forward direction. The dose perturbation is explained on the basis of production and transport of secondary electrons. Empirical functions are derived from the experimental data to predict the dose distribution in the vicinity of an inhomogeneity. These equations could form the basis of a treatment planning system that would accurately represent the dose both at the interface and surrounding tissue.

Low-Dose Tissue Plasminogen Activator in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

PubMed

Cheng, Ji-Wei; Zhang, Xiao-Jing; Cheng, Li-Shan; Li, Guo-Yi; Zhang, Li-Jun; Ji, Kang-Xiang; Zhao, Qing; Bai, Yu

2018-02-01

Intravenous thrombolysis using tissue plasminogen activator (tPA) improves significantly the neurologic function in patients with acute ischemic stroke (AIS). However, it brings financial burden to patients and is associated with symptomatic intracranial hemorrhage (SICH). Whether low-dose tPA can effectively reduce SICH and has the same efficacy as standard-dose tPA is still controversial. We searched for English clinical trials published before March, 2017on the comparison of the efficacy and safety between low and standard dose of tPA in the treatment of AIS using MEDLINE, Embase, and Cochrane Library. The modified Rankin scale (mRS) score was used as the primary efficacy outcome. The mRS1 corresponded to 0-1, whereas mRS2 corresponded to 0-2. The SICH and mortality were adopted as primary safety outcomes. Twelve high-quality studies were selected, including 7686 patients (low-dose: 2888, standard-dose: 4798). With no statistical heterogeneity, the fixed effects model was adopted in the analysis. Similarly to standard doses, low-dose tPA improved the mRS scores (mRS1: odds ratio [OR] = .92, 95% confidence interval [CI] .84-1.02; P = .12; mRS2: OR = .97, 95% CI .88-1.08; P = .57). Compared with standard-dose tPA, low-dose tPA reduced the incidence of SICH (by National Institute of Neurological Disorders and Stroke [NINDS] definition: OR = .71, 95% CI .57-0.89; P = .003; by Safe Implementation of Thrombolysis in Stroke Monitoring Study [SITS-MOST] definition: OR = .64, 95% CI .42-0.99; P = .04), while both reduced mortality (OR = .87, 95% CI .74-1.02; P = .08). Low-dose tPA is comparable to standard-dose tPA in improving the neurologic function and reducing mortality in AIS patients. Moreover, low-dose tPA can reduce the incidence of SICH compared with standard-dose tPA. Therefore, low-dose tPA is highly recommended in AIS patients. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Statistical methods for biodosimetry in the presence of both Berkson and classical measurement error

NASA Astrophysics Data System (ADS)

Miller, Austin

In radiation epidemiology, the true dose received by those exposed cannot be assessed directly. Physical dosimetry uses a deterministic function of the source term, distance and shielding to estimate dose. For the atomic bomb survivors, the physical dosimetry system is well established. The classical measurement errors plaguing the location and shielding inputs to the physical dosimetry system are well known. Adjusting for the associated biases requires an estimate for the classical measurement error variance, for which no data-driven estimate exists. In this case, an instrumental variable solution is the most viable option to overcome the classical measurement error indeterminacy. Biological indicators of dose may serve as instrumental variables. Specification of the biodosimeter dose-response model requires identification of the radiosensitivity variables, for which we develop statistical definitions and variables. More recently, researchers have recognized Berkson error in the dose estimates, introduced by averaging assumptions for many components in the physical dosimetry system. We show that Berkson error induces a bias in the instrumental variable estimate of the dose-response coefficient, and then address the estimation problem. This model is specified by developing an instrumental variable mixed measurement error likelihood function, which is then maximized using a Monte Carlo EM Algorithm. These methods produce dose estimates that incorporate information from both physical and biological indicators of dose, as well as the first instrumental variable based data-driven estimate for the classical measurement error variance.

Methodological improvements in quantifying cognitive change in clinical trials: an example with single-dose administration of donepezil.

PubMed

Pietrzak, R H; Maruff, P; Snyder, P J

2009-03-01

Change in cognitive function in response to a pharmacologic challenge can be observed with greater sensitivity by employing cognitive tests with optimal psychometric properties and a statistical approach that more accurately accounts for individual variability in performance. To demonstrate this approach we examined the cognitive effects of a single acute dose administration of an acetylcholinesterase inhibitor, donepezil, in healthy older adults and in older adults with mild Alzheimer's disease (AD). Placebo-controlled crossover study with three separate testing days: baseline, placebo, and donepezil, with assessments at baseline, and 1-, 2-, 3-, 6-, and 8-hrs post-dosing on each day. Early phase I clinical trial. 15 healthy older adults; 14 older adults with mild Alzheimer's disease. Single acute dose of 5mg donepezil. Performance on the Groton Maze Learning Test (GMLT), a computerized neuropsychological measure of spatial working memory and error monitoring. A single acute dose of donepezil improved GMLT performance in healthy older adults (effect size: 0.83 at 6 hrs post-dosing) and older adults with mild AD (effect size: 0.58 at 3 hrs post-dosing). The GMLT detected cognitive improvement following a single, acute dose administration of donepezil in healthy older adults and older adults with mild AD. The choice of cognitive tests designed for repeated administration, as well as an analytic approach that emphasizes individual-level change in cognitive function, provides a sensitive approach to detecting central nervous system drug penetration and activity of cognitive-enhancing agents.

Multiple nicotine training doses in mice as a basis for differentiating the effects of smoking cessation aids.

PubMed

Cunningham, Colin S; McMahon, Lance R

2013-07-01

Receptor mechanisms underlying the behavioral effects of clinically used nicotinic acetylcholine receptor agonists have not been fully established. Drug discrimination was used to compare receptor mechanisms underlying the effects of smoking cessation aids. Separate groups of male C57BL/6J mice discriminated 0.56, 1, or 1.78 mg/kg of nicotine base. Nicotine, varenicline, and cytisine were administered alone, in combination with each other, and in combination with mecamylamine and dihydro-β-erythroidine (DHβE). Midazolam and morphine were tested to examine sensitivity to non-nicotinics. The ED50 value of nicotine to produce discriminative stimulus effects systematically increased as training dose increased. Varenicline and cytisine did not fully substitute for nicotine and, as compared with nicotine, their ED50 values varied less systematically as a function of nicotine training dose. Morphine did not substitute for nicotine, whereas midazolam substituted for the low and not the higher training doses of nicotine. As training dose increased, the dose of mecamylamine needed to produce a significant rightward shift in the nicotine dose-effect function also increased. DHβE antagonized nicotine in animals discriminating the smallest dose of nicotine. Varenicline did not antagonize the effects of nicotine, whereas cytisine produced a modest though significant antagonism of nicotine. These results suggest that differences in pharmacologic mechanism between nicotine, varenicline, and cytisine include not only differences in efficacy at a common subtype of nicotinic acetylcholine receptor, but also differential affinity and/or efficacy at multiple receptor subtypes.

SU-F-T-336: A Quick Auto-Planning (QAP) Method for Patient Intensity Modulated Radiotherapy (IMRT)

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

Peng, J; Zhang, Z; Wang, J

2016-06-15

Purpose: The aim of this study is to develop a quick auto-planning system that permits fast patient IMRT planning with conformal dose to the target without manual field alignment and time-consuming dose distribution optimization. Methods: The planning target volume (PTV) of the source and the target patient were projected to the iso-center plane in certain beameye- view directions to derive the 2D projected shapes. Assuming the target interior was isotropic for each beam direction boundary analysis under polar coordinate was performed to map the source shape boundary to the target shape boundary to derive the source-to-target shape mapping function. Themore » derived shape mapping function was used to morph the source beam aperture to the target beam aperture over all segments in each beam direction. The target beam weights were re-calculated to deliver the same dose to the reference point (iso-center) as the source beam did in the source plan. The approach was tested on two rectum patients (one source patient and one target patient). Results: The IMRT planning time by QAP was 5 seconds on a laptop computer. The dose volume histograms and the dose distribution showed the target patient had the similar PTV dose coverage and OAR dose sparing with the source patient. Conclusion: The QAP system can instantly and automatically finish the IMRT planning without dose optimization.« less

Radiation dose response of N channel MOSFET submitted to filtered X-ray photon beam

NASA Astrophysics Data System (ADS)

Gonçalves Filho, Luiz C.; Monte, David S.; Barros, Fabio R.; Santos, Luiz A. P.

2018-01-01

MOSFET can operate as a radiation detector mainly in high-energy photon beams, which are normally used in cancer treatments. In general, such an electronic device can work as a dosimeter from threshold voltage shift measurements. The purpose of this article is to show a new way for measuring the dose-response of MOSFETs when they are under X-ray beams generated from 100kV potential range, which is normally used in diagnostic radiology. Basically, the method consists of measuring the MOSFET drain current as a function of the radiation dose. For this the type of device, it has to be biased with a high value resistor aiming to see a substantial change in the drain current after it has been irradiated with an amount of radiation dose. Two types of N channel device were used in the experiment: a signal transistor and a power transistor. The delivered dose to the device was varied and the electrical curves were plotted. Also, a sensitivity analysis of the power MOSFET response was made, by varying the tube potential of about 20%. The results show that both types of devices have responses very similar, the shift in the electrical curve is proportional to the radiation dose. Unlike the power MOSFET, the signal transistor does not provide a linear function between the dose rate and its drain current. We also have observed that the variation in the tube potential of the X-ray equipment produces a very similar dose-response.

Characterization and recovery of Deep Sub Micron (DSM) technologies behavior under radiation

NASA Technical Reports Server (NTRS)

Stoica, Adrian; Wang, Xiao

2005-01-01

This paper serves a twofold purpose: characterize the behavior of a reconfigurable chip exposed to radiation; and demonstrate a method for functionality recovery due to Total Ionizing Dose (TID) effects. The experiments are performed using a PL developed reconfigurable device, a Field Programmable Transistor Array (FPTA). The paper initially describes experiments on the characterization of the NMOS transistor behavior for TID values up to 300krad. The behavior of analog and digital circuits downloaded onto the FPTA chip is also assessed for TID effects. This paper also presents a novel approach for circuit functionality recovery due to radiation effects based on Evolvable Hardware. The key idea is to reconfigure a programmable device, in-situ, to compensate, or bypass its degraded or damaged components. Experiments with total radiation dose up to 300kRad show that while the functionality of a variety of circuits, including digital gates, a rectifier and a Digital to Analog Converter implemented on a FPTA-2 chip is degraded/lost at levels before 200kRad, the correct functionality can be recovered through the proposed evolutionary approach and the chips are able to survive higher radiation, for several functions in excess of total radiation dose of 250kRad.

Cognitive enhancement and antipsychotic-like activity following repeated dosing with the selective M4 PAM VU0467154.

PubMed

Gould, Robert W; Grannan, Michael D; Gunter, Barak W; Ball, Jacob; Bubser, Michael; Bridges, Thomas M; Wess, Jurgen; Wood, Michael W; Brandon, Nicholas J; Duggan, Mark E; Niswender, Colleen M; Lindsley, Craig W; Conn, P Jeffrey; Jones, Carrie K

2018-01-01

Although selective activation of the M 1 muscarinic acetylcholine receptor (mAChR) subtype has been shown to improve cognitive function in animal models of neuropsychiatric disorders, recent evidence suggests that enhancing M 4 mAChR function can also improve memory performance. Positive allosteric modulators (PAMs) targeting the M 4 mAChR subtype have shown therapeutic potential for the treatment of multiple symptoms observed in schizophrenia, including positive and cognitive symptoms when assessed in acute preclinical dosing paradigms. Since the cholinergic system has been implicated in multiple stages of learning and memory, we evaluated the effects of repeated dosing with the highly selective M 4 PAM VU0467154 on either acquisition and/or consolidation of learning and memory when dosed alone or after pharmacologic challenge with the N-methyl-d-aspartate subtype of glutamate receptors (NMDAR) antagonist MK-801. MK-801 challenge represents a well-documented preclinical model of NMDAR hypofunction that is thought to underlie some of the positive and cognitive symptoms observed in schizophrenia. In wildtype mice, 10-day, once-daily dosing of VU0467154 either prior to, or immediately after daily testing enhanced the rate of learning in a touchscreen visual pairwise discrimination task; these effects were absent in M 4 mAChR knockout mice. Following a similar 10-day, once-daily dosing regimen of VU0467154, we also observed 1) improved acquisition of memory in a cue-mediated conditioned freezing paradigm, 2) attenuation of MK-801-induced disruptions in the acquisition of memory in a context-mediated conditioned freezing paradigm and 3) reversal of MK-801-induced hyperlocomotion. Comparable efficacy and plasma and brain concentrations of VU0467154 were observed after repeated dosing as those previously reported with an acute, single dose administration of this M 4 PAM. Together, these studies are the first to demonstrate that cognitive enhancing and antipsychotic-like activity are not subject to the development of tolerance following repeated dosing with a selective M 4 PAM in mice and further suggest that activation of M 4 mAChRs may modulate both acquisition and consolidation of memory functions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dose-dependent effects of 6-hydroxy dopamine on deprivation myopia, electroretinograms, and dopaminergic amacrine cells in chickens.

PubMed

Li, X X; Schaeffel, F; Kohler, K; Zrenner, E

1992-11-01

We found that a single intravitreal injection of 6-hydroxy dopamine (6-OHDA) is highly efficient in blocking the development of deprivation-induced myopia in young chickens. To investigate the effects of 6-OHDA on retinal function, we studied electroretinograms (ERGs) in chickens aged 15-25 days, 4 days subsequent to the injection. Both spectral sensitivity and oscillatory potentials were tested. In addition, a histological examination was performed of dopaminergic amacrine cells labeled by a monoclonal antibody against tyrosine hydroxylase. We found that, at doses of 6-OHDA sufficient to suppress deprivation myopia entirely, no effect could be detected on either the ERGs or on the density and appearance of dopaminergic amacrine cells. For higher doses, spectral sensitivity and the number of dopaminergic amacrine cells declined gradually. In contrast, as doses increased, oscillatory potentials 1 and 2 grew in amplitude only to decline at the highest doses. The results indicate that (1) development of deprivation myopia requires normal retinal function and that (2) slight changes in the gains of dopaminergic pathways are sufficient to block the development of deprivation myopia.

Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function.

PubMed

Lundgaard, Iben; Wang, Wei; Eberhardt, Allison; Vinitsky, Hanna Sophia; Reeves, Benjamin Cameron; Peng, Sisi; Lou, Nanhong; Hussain, Rashad; Nedergaard, Maiken

2018-02-02

Prolonged intake of excessive amounts of ethanol is known to have adverse effects on the central nervous system (CNS). Here we investigated the effects of acute and chronic ethanol exposure and withdrawal from chronic ethanol exposure on glymphatic function, which is a brain-wide metabolite clearance system connected to the peripheral lymphatic system. Acute and chronic exposure to 1.5 g/kg (binge level) ethanol dramatically suppressed glymphatic function in awake mice. Chronic exposure to 1.5 g/kg ethanol increased GFAP expression and induced mislocation of the astrocyte-specific water channel aquaporin 4 (AQP4), but decreased the levels of several cytokines. Surprisingly, glymphatic function increased in mice treated with 0.5 g/kg (low dose) ethanol following acute exposure, as well as after one month of chronic exposure. Low doses of chronic ethanol intake were associated with a significant decrease in GFAP expression, with little change in the cytokine profile compared with the saline group. These observations suggest that ethanol has a J-shaped effect on the glymphatic system whereby low doses of ethanol increase glymphatic function. Conversely, chronic 1.5 g/kg ethanol intake induced reactive gliosis and perturbed glymphatic function, which possibly may contribute to the higher risk of dementia observed in heavy drinkers.

Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation

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

Daila S. Gridley, PhD

2012-03-30

FINAL TECHNICAL REPORT Supported by the Low Dose Radiation Research Program, Office of Science U.S. Department of Energy Grant No. DE-FG02-07ER64345 Project ID: 0012965 Award Register#: ER64345 Project Manager: Noelle F. Metting, Sc.D. Phone: 301-903-8309 Division SC-23.2 noelle.metting@science.doe.gov Submitted March 2012 To: https://www.osti.gov/elink/241.3.jsp Title: Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation PI: Daila S. Gridley, Ph.D. Human low dose radiation data have been derived primarily from studies of space and airline flight personnel, nuclear plant workers and others exposed occupationally, as well as victims in the vicinity of atomic bomb explosions. The findingsmore » remain inconclusive due to population inconsistencies and complex interactions among total dose, dose rate, radiation quality and age at exposure. Thus, safe limits for low dose occupational irradiation are currently based on data obtained with doses far exceeding the levels expected for the general population and health risks have been largely extrapolated using the linear-nonthreshold dose-response model. The overall working hypothesis of the present study is that priming with low dose, low-linear energy transfer (LET) radiation can ameliorate the response to acute high-dose radiation exposure. We also propose that the efficacy of low-dose induced protection will be dependent upon the form and regimen of the high-dose exposure: photons versus protons versus simulated solar particle event protons (sSPE). The emphasis has been on gene expression and function of CD4+ T helper (Th) lymphocytes harvested from spleens of whole-body irradiated C57BL/6 mice, a strain that provides the genetic background for many genetically engineered strains. Evaluations of the responses of other selected cells, tissues such as skin, and organs such as lung, liver and brain were also initiated (partially funded by other sources). The long-term goal is to provide information that will be useful in estimating human health risks due to radiation that may occur during exposures in the work environment, nuclear/radiological catastrophes, as well as radiotherapy. Several papers have been published, accepted for publication or are in preparation. A number of poster and oral presentations have been made at scientific conferences and workshops. Archived tissues of various types will continue to be evaluated via funding from other sources (the DoE Low Dose Radiation Research Program, Office of Science and this specific grant will be appropriately included in the Acknowledgements of all subsequent publications/presentations). A post-doc and several students have participated in this study. More detailed description of the accomplishments is described in attached file.« less

Pharmacogenetic testing for clopidogrel using the rapid INFINITI analyzer: a dose-escalation study.

PubMed

Gladding, Patrick; White, Harvey; Voss, Jamie; Ormiston, John; Stewart, Jim; Ruygrok, Peter; Bvaldivia, Badi; Baak, Ruth; White, Catherine; Webster, Mark

2009-11-01

Our aim was to assess whether a higher clopidogrel maintenance dose has a greater antiplatelet effect in CYP2C19*2 allele carriers compared with noncarriers. Clopidogrel is a prodrug that is biotransformed by the cytochrome P450 enzymes CYP2C19, 2C9, and 3A4, 2B6, 1A2. The CYPC219*2 loss of function variant has been associated with a reduced antiplatelet response to clopidogrel and a 3-fold risk of stent thrombosis. Forty patients on standard maintenance dosage clopidogrel (75 mg), for 9.4 +/- 9.2 weeks, were enrolled into a dose escalation study. Platelet function was assessed at baseline and after 1 week of 150 mg once daily using the VerifyNow platelet function analyzer (Accumetrics Ltd., San Diego, California). Genomic DNA was hybridized to a BioFilmChip microarray on the INFINITI analyzer (AutoGenomics Inc., Carlsbad, California) and analyzed for the CYP19*2, *4, *17, and CYP2C9*2, *3 polymorphisms. Platelet inhibition increased over 1 week, mean +8.6 +/- 13.5% (p = 0.0003). Carriers of the CYP2C19*2 allele had significantly reduced platelet inhibition at baseline (median 18%, range 0% to 72%) compared with wildtype (wt) (median 59%, range 11% to 95%, p = 0.01) and at 1 week (p = 0.03). CYP2C19*2 allele carriers had an increase in platelet inhibition of (mean +9 +/- 11%, p = 0.03) and reduction in platelet reactivity (mean -26 +/- 38 platelet response unit, p = 0.04) with a higher dose. Together CYP2C19*2 and CYP2C9*3 loss of function carriers had a greater change in platelet inhibition with 150 mg daily than wt/wt (+10.9% vs. +0.7%, p = 0.04). Increasing the dose of clopidogrel in patients with nonresponder polymorphisms can increase antiplatelet response. Personalizing clopidogrel dosing using pharmacogenomics may be an effective method of optimizing treatment.

Inflammatory Pain Promotes Increased Opioid Self-Administration: Role of Dysregulated Ventral Tegmental Area μ Opioid Receptors

PubMed Central

Hipólito, Lucia; Wilson-Poe, Adrianne; Campos-Jurado, Yolanda; Zhong, Elaine; Gonzalez-Romero, Jose; Virag, Laszlo; Whittington, Robert; Comer, Sandra D.; Carlton, Susan M.; Walker, Brendan M.; Bruchas, Michael R.

2015-01-01

Pain management in opioid abusers engenders ethical and practical difficulties for clinicians, often resulting in pain mismanagement. Although chronic opioid administration may alter pain states, the presence of pain itself may alter the propensity to self-administer opioids, and previous history of drug abuse comorbid with chronic pain promotes higher rates of opioid misuse. Here, we tested the hypothesis that inflammatory pain leads to increased heroin self-administration resulting from altered mu opioid receptor (MOR) regulation of mesolimbic dopamine (DA) transmission. To this end, the complete Freund's adjuvant (CFA) model of inflammation was used to assess the neurochemical and functional changes induced by inflammatory pain on MOR-mediated mesolimbic DA transmission and on rat intravenous heroin self-administration under fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. In the presence of inflammatory pain, heroin intake under an FR schedule was increased for high, but attenuated for low, heroin doses with concomitant alterations in mesolimbic MOR function suggested by DA microdialysis. Consistent with the reduction in low dose FR heroin self-administration, inflammatory pain reduced motivation for a low dose of heroin, as measured by responding under a PR schedule of reinforcement, an effect dissociable from high heroin dose PR responding. Together, these results identify a connection between inflammatory pain and loss of MOR function in the mesolimbic dopaminergic pathway that increases intake of high doses of heroin. These findings suggest that pain-induced loss of MOR function in the mesolimbic pathway may promote opioid dose escalation and contribute to opioid abuse-associated phenotypes. SIGNIFICANCE STATEMENT This study provides critical new insights that show that inflammatory pain alters heroin intake through a desensitization of MORs located within the VTA. These findings expand our knowledge of the interactions between inflammatory pain and opioid abuse liability, and should help to facilitate the development of novel and safer opioid-based strategies for treating chronic pain. PMID:26338332