Local noise reduction for emphysema scoring in low-dose CT images

NASA Astrophysics Data System (ADS)

Schilham, Arnold; Prokop, Mathias; Gietema, Hester; van Ginneken, Bram

2005-04-01

Computed Tomography (CT) has become the new reference standard for quantification of emphysema. The most popular measure for emphysema derived from CT is the Pixel Index (PI), which expresses the fraction of the lung volume with abnormally low intensity values. As PI is calculated from a single, fixed threshold on intensity, this measure is strongly influenced by noise. This effect shows up clearly when comparing the PI score for a high-dose scan to the PI score for a low-dose (i.e. noisy) scan of the same subject. This paper presents a class of noise filters that make use of a local noise estimate to specify the filtering strength: Local Noise Variance Weighted Averaging (LNVWA). The performance of the filter is assessed by comparing high-dose and low-dose PI scores for 11 subjects. LNVWA improves the reproducibility of high-dose PI scores: For an emphysema threshold of -910 HU, the root-mean-square difference in PI score drops from 10% of the lung volume to 3.3% of the lung volume if LNVWA is used.

Patient adherence to prescribed antimicrobial drug dosing regimens.

PubMed

Vrijens, Bernard; Urquhart, John

2005-05-01

The aim of this article is to review current knowledge about the clinical impact of patients' variable adherence to prescribed anti-infective drug dosing regimens, with the aim of renewing interest and exploration of this important but largely neglected area of therapeutics. Central to the estimation of a patient's adherence to a prescribed drug regimen is a reliably compiled drug dosing history. Electronic monitoring methods have emerged as the virtual 'gold standard' for compiling drug dosing histories in ambulatory patients. Reliably compiled drug dosing histories are consistently downwardly skewed, with varying degrees of under-dosing. In particular, the consideration of time intervals between protease inhibitor doses has revealed that ambulatory patients' variable execution of prescribed dosing regimens is a leading source of variance in viral response. Such analyses reveal the need for a new discipline, called pharmionics, which is the study of how ambulatory patients use prescription drugs. Properly analysed, reliable data on the time-course of patients' actual intake of prescription drugs can eliminate a major source of unallocated variance in drug responses, including the non-response that occurs and is easily misinterpreted when a patient's complete non-execution of a prescribed drug regimen is unrecognized clinically. As such, reliable compilation of ambulatory patients' drug dosing histories has the promise of being a key step in reducing unallocated variance in drug response and in improving the informational yield of clinical trials. It is also the basis for sound, measurement-guided steps taken to improve a patient's execution of a prescribed dosing regimen.

Pharmacokinetic profiles of a biosimilar filgrastim and Amgen filgrastim: results from a randomized, phase I trial

PubMed Central

Bronchud, Miguel; Mair, Stuart; Challand, Rodeina

2010-01-01

Recombinant human granulocyte colony-stimulating factor (filgrastim) has multiple hematologic and oncologic indications as Neupogen® (Amgen filgrastim). Hospira has developed a biosimilar filgrastim (Nivestim™). Here, results are reported from a phase I trial, primarily designed to compare the pharmacokinetic profiles of Hospira filgrastim and Amgen filgrastim. A phase I, single-center, open-label, randomized trial was undertaken to demonstrate equivalence of the pharmacokinetic characteristics of Hospira filgrastim and Amgen filgrastim. Forty-eight healthy volunteers were randomized to receive intravenous (i.v.) or subcutaneous (s.c.) dosing and then further randomized to order of treatment. Volunteers in each of the two dosing groups received a single 10µg/kg dose of Hospira filgrastim or Amgen filgrastim, with subsequent crossover. Bioequivalence was evaluated by analysis of variance; if the estimated 90% confidence intervals (CIs) for the ratio of ‘test’ to ‘reference’ treatment means were within the conventional equivalence limits of 0.80–1.25, then bioequivalence was concluded. Forty-six volunteers completed the study. Geometric mean area under the curve from time 0 to the last time point (primary endpoint) was similar in volunteers given Hospira filgrastim or Amgen filgrastim following i.v. (ratio of means: 0.96; 90% CI: 0.90–1.02) or s.c. (ratio of means: 1.02; 90% CI: 0.95–1.09) dosing; 90% CIs were within the predefined range necessary to demonstrate bioequivalence. Hospira filgrastim was well tolerated with no additional safety concerns over Amgen filgrastim. Hospira filgrastim is bioequivalent with Amgen filgrastim in terms of its pharmacokinetic properties and may provide a clinically effective alternative. PMID:20428872

Quantitative Comparison of Virtual Monochromatic Images of Dual Energy Computed Tomography Systems: Beam Hardening Artifact Correction and Variance in Computed Tomography Numbers: A Phantom Study.

PubMed

Wu, Rongli; Watanabe, Yoshiyuki; Satoh, Kazuhiko; Liao, Yen-Peng; Takahashi, Hiroto; Tanaka, Hisashi; Tomiyama, Noriyuki

2018-05-21

The aim of this study was to quantitatively compare the reduction in beam hardening artifact (BHA) and variance in computed tomography (CT) numbers of virtual monochromatic energy (VME) images obtained with 3 dual-energy computed tomography (DECT) systems at a given radiation dose. Five different iodine concentrations were scanned using dual-energy and single-energy (120 kVp) modes. The BHA and CT number variance were evaluated. For higher iodine concentrations, 40 and 80 mgI/mL, BHA on VME imaging was significantly decreased when the energy was higher than 50 keV (P = 0.003) and 60 keV (P < 0.001) for GE, higher than 80 keV (P < 0.001) and 70 keV (P = 0.002) for Siemens, and higher than 40 keV (P < 0.001) and 60 keV (P < 0.001) for Toshiba, compared with single-energy CT imaging. Virtual monochromatic energy imaging can decrease BHA and improve CT number accuracy in different dual-energy computed tomography systems, depending on energy levels and iodine concentrations.

Dosimetric comparison of three intensity-modulated radiation therapies for left breast cancer after breast-conserving surgery.

PubMed

Zhang, Huai-Wen; Hu, Bo; Xie, Chen; Wang, Yun-Lai

2018-05-01

This study aimed to evaluate dosimetric differences of intensity-modulated radiation therapy (IMRT) in target and normal tissues after breast-conserving surgery. IMRT five-field plan I, IMRT six-field plan II, and field-in-field-direct machine parameter optimization-IMRT plan III were designed for each of the 50 patients. One-way analysis of variance was performed to compare differences, and P < 0.05 was considered statistically significant. Homogeneity index of plan III is lower than those of plans I and II. No difference was identified in conformity index of targets. Plan I exhibited difference in mean dose (D mean ) for the heart (P < 0.05). Plan I featured smaller irradiation dose volumes in V 5 , V 20 (P < 0.05) of the left lung than II. Plan I exhibited significantly higher V 5 in the right lung than plans II and III (P < 0.05). Under plan I, irradiation dose at V 5 in the right breast is higher than that in plans II and III. Patients in plan III presented less total monitor unit and total treatment time than those in plans I and II (P < 0.05). IMRT six-field plans II, and field-in-field-direct machine parameter optimization-IMRT plans III can reduce doses and volumes to the lungs and heart better while maintaining satisfying conformity index and homogeneity index of target. Nevertheless, plan II neglects target movements caused by respiration. In the same manner, plan III can substantially reduce MU and shorten patient treatment time. Therefore, plan III, which considers target movement caused by respiration, is a more practical radiation mode. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Comparative molecular field analysis to derive pharmacophore maps for induction doses of intravenous anaesthetic agents.

PubMed

Sear, J W

2011-03-01

The present study examines the molecular basis of induction of anaesthesia by i.v. hypnotic agents using comparative molecular field analysis (CoMFA). ED(50) induction doses for 14 i.v. anaesthetics in human subjects (expressed as molar dose per kilogram body weight) were obtained from the literature. Immobilizing potency data for the same 14 agents (expressed as the EC(50) plasma free drug concentrations that abolish movement in response to a noxious stimulus in 50% patients) were taken from our previous publication. These data were used to form CoMFA models for the two aspects of anaesthetic activity. Molecular alignment was achieved by field-fit minimization techniques. The lead structure for both models was eltanolone. The final CoMFA model for the ED(50) induction dose was based on two latent variables, and explained 99.3% of the variance in observed activities. It showed good intrinsic predictability (cross-validated q(2)=0.849). The equivalent model for immobilizing activity was also based on two latent variables, with r(2)=0.988 and q(2)=0.852. Although there was a correlation between -log ED(50) and -log EC(50) (r(2)=0.779), comparison of the pharmacophore maps showed poor correlation for both electrostatic and steric regions when isocontours were constructed by linking lattice grid points, making the greatest 40% contributions; the relative contributions of electrostatic and steric interactions differing between the models (induction dose: 2.5:1; immobilizing activity 1.8:1). Comparison of two CoMFA activity models shows only small elements of commonality, suggesting that different molecular features may be responsible for these two properties of i.v. anaesthetics.

Gamma camera dual imaging with a somatostatin receptor and thymidine kinase after gene transfer with a bicistronic adenovirus in mice.

PubMed

Zinn, Kurt R; Chaudhuri, Tandra R; Krasnykh, Victor N; Buchsbaum, Donald J; Belousova, Natalya; Grizzle, William E; Curiel, David T; Rogers, Buck E

2002-05-01

To compare two systems for assessing gene transfer to cancer cells and xenograft tumors with noninvasive gamma camera imaging. A replication-incompetent adenovirus encoding the human type 2 somatostatin receptor (hSSTr2) and the herpes simplex virus thymidine kinase (TK) enzyme (Ad-hSSTr2-TK) was constructed. A-427 human lung cancer cells were infected in vitro and mixed with uninfected cells at different ratios. A-427 tumors in nude mice (n = 23) were injected with 1 x 10(6) to 5 x 10(8) plaque-forming units (pfu) of Ad-hSSTr2-TK. The expressed hSSTr2 and TK proteins were imaged owing to internally bound, or trapped, technetium 99m ((99m)Tc)-labeled hSSTr2-binding peptide (P2045) and radioiodinated 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl-5-iodouracil (FIAU), respectively. Iodine 125 ((125)I)-labeled FIAU was used in vitro and iodine 131 ((131)I)-labeled FIAU, in vivo. The (99m)Tc-labeled P2045 and (125)I- or (131)I-labeled FIAU were imaged simultaneously with different window settings with an Anger gamma camera. Treatment effects were tested with analysis of variance. Infected cells in culture trapped (125)I-labeled FIAU and (99m)Tc-labeled P2045; uptake correlated with the percentage of Ad-hSSTr2-TK-positive cells. For 100% of infected cells, 24% +/- 0.4 (mean +/- SD) of the added (99m)Tc-labeled P2045 was trapped, which is significantly lower (P <.05) than the 40% +/- 2 of (125)I-labeled FIAU that was trapped. For the highest Ad-hSSTr2-TK tumor dose (5 x 10(8) pfu), the uptake of (99m)Tc-labeled P2045 was 11.1% +/- 2.9 of injected dose per gram of tumor (thereafter, dose per gram), significantly higher (P <.05) than the uptake of (131)I-labeled FIAU at 1.6% +/- 0.4 dose per gram. (99m)Tc-labeled P2045 imaging consistently depicted hSSTr2 gene transfer in tumors at all adenovirus doses. Tumor uptake of (99m)Tc-labeled P2045 positively correlated with Ad-hSSTr2-TK dose; (131)I-labeled FIAU tumor uptake did not correlate with vector dose. The hSSTr2 and TK proteins were simultaneously imaged following dual gene transfer with an adenovirus vector. Copyright RSNA, 2002

Vitamin Concentrations in Human Milk Vary with Time within Feed, Circadian Rhythm, and Single-Dose Supplementation.

PubMed

Hampel, Daniela; Shahab-Ferdows, Setareh; Islam, M Munirul; Peerson, Janet M; Allen, Lindsay H

2017-04-01

Background: Human milk is the subject of many studies, but procedures for representative sample collection have not been established. Our improved methods for milk micronutrient analysis now enable systematic study of factors that affect its concentrations. Objective: We evaluated the effects of sample collection protocols, variations in circadian rhythms, subject variability, and acute maternal micronutrient supplementation on milk vitamin concentrations. Methods: In the BMQ (Breast-Milk-Quality) study, we recruited 18 healthy women (aged 18-26 y) in Dhaka, Bangladesh, at 2-4 mo of lactation for a 3-d supplementation study. On day 1, no supplements were given; on days 2 and 3, participants consumed ∼1 time and 2 times, respectively, the US-Canadian Recommended Dietary Allowances for vitamins at breakfast (0800-0859). Milk was collected during every feeding from the same breast over 24 h. Milk expressed in the first 2 min (aliquot I) was collected separately from the remainder (aliquot II); a third aliquot (aliquot III) was saved by combining aliquots I and II. Thiamin, riboflavin, niacin, and vitamins B-6, B-12, A, and E and fat were measured in each sample. Results: Significant but small differences (14-18%) between aliquots were found for all vitamins except for vitamins B-6 and B-12. Circadian variance was significant except for fat-adjusted vitamins A and E, with a higher contribution to total variance with supplementation. Between-subject variability accounted for most of the total variance. Afternoon and evening samples best reflected daily vitamin concentrations for all study days. Acute supplementation effects were found for thiamin, riboflavin, and vitamins B-6 and A at 2-4 h postdosing, with 0.1-6.17% passing into milk. Supplementation was reflected in fasting, 24-h postdose samples for riboflavin and vitamin B-6. Maximum amounts of dose-responding vitamins in 1 feeding ranged from 4.7% to 21.8% (day 2) and 8.2% to 35.0% (day 3) of Adequate Intake. Conclusions: In the milk of Bangladeshi mothers, differences in vitamin concentrations between aliquots within feedings and by circadian variance were significant but small. Afternoon and evening collection provided the most-representative samples. Supplementation acutely affects some breast-milk micronutrient concentrations. This trial was registered at clinicaltrials.gov as NCT02756026.

Vitamin Concentrations in Human Milk Vary with Time within Feed, Circadian Rhythm, and Single-Dose Supplementation1234

PubMed Central

Shahab-Ferdows, Setareh; Peerson, Janet M; Allen, Lindsay H

2017-01-01

Background: Human milk is the subject of many studies, but procedures for representative sample collection have not been established. Our improved methods for milk micronutrient analysis now enable systematic study of factors that affect its concentrations. Objective: We evaluated the effects of sample collection protocols, variations in circadian rhythms, subject variability, and acute maternal micronutrient supplementation on milk vitamin concentrations. Methods: In the BMQ (Breast-Milk-Quality) study, we recruited 18 healthy women (aged 18–26 y) in Dhaka, Bangladesh, at 2–4 mo of lactation for a 3-d supplementation study. On day 1, no supplements were given; on days 2 and 3, participants consumed ∼1 time and 2 times, respectively, the US-Canadian Recommended Dietary Allowances for vitamins at breakfast (0800–0859). Milk was collected during every feeding from the same breast over 24 h. Milk expressed in the first 2 min (aliquot I) was collected separately from the remainder (aliquot II); a third aliquot (aliquot III) was saved by combining aliquots I and II. Thiamin, riboflavin, niacin, and vitamins B-6, B-12, A, and E and fat were measured in each sample. Results: Significant but small differences (14–18%) between aliquots were found for all vitamins except for vitamins B-6 and B-12. Circadian variance was significant except for fat-adjusted vitamins A and E, with a higher contribution to total variance with supplementation. Between-subject variability accounted for most of the total variance. Afternoon and evening samples best reflected daily vitamin concentrations for all study days. Acute supplementation effects were found for thiamin, riboflavin, and vitamins B-6 and A at 2–4 h postdosing, with 0.1–6.17% passing into milk. Supplementation was reflected in fasting, 24-h postdose samples for riboflavin and vitamin B-6. Maximum amounts of dose-responding vitamins in 1 feeding ranged from 4.7% to 21.8% (day 2) and 8.2% to 35.0% (day 3) of Adequate Intake. Conclusions: In the milk of Bangladeshi mothers, differences in vitamin concentrations between aliquots within feedings and by circadian variance were significant but small. Afternoon and evening collection provided the most-representative samples. Supplementation acutely affects some breast-milk micronutrient concentrations. This trial was registered at clinicaltrials.gov as NCT02756026. PMID:28202638

SU-F-T-564: 3 Year Experience of Treatment Plan QualityAssurance for Vero SBRT Patients

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

Su, Z; Li, Z; Mamalui, M

2016-06-15

Purpose: To verify treatment plan monitor units from iPlan treatment planning system for Vero Stereotactic Body Radiotherapy (SBRT) treatment using both software-based and (homogeneous and heterogeneous) phantom-based approaches. Methods: Dynamic conformal arcs (DCA) were used for SBRT treatment of oligometastasis patients using Vero linear accelerator. For each plan, Monte Carlo calculated treatment plans MU (prescribed dose to water with 1% variance) is verified first by RadCalc software with 3% difference threshold. Beyond 3% differences, treatment plans were copied onto (homogeneous) Scanditronix phantom for non-lung patients and copied onto (heterogeneous) CIRS phantom for lung patients and the corresponding plan dose wasmore » measured using a cc01 ion chamber. The difference between the planed and measured dose was recorded. For the past 3 years, we have treated 180 patients with 315 targets. Out of these patients, 99 targets treatment plan RadCalc calculation exceeded 3% threshold and phantom based measurements were performed with 26 plans using Scanditronix phantom and 73 plans using CIRS phantom. Mean and standard deviation of the dose differences were obtained and presented. Results: For all patient RadCalc calculations, the mean dose difference is 0.76% with a standard deviation of 5.97%. For non-lung patient plan Scanditronix phantom measurements, the mean dose difference is 0.54% with standard deviation of 2.53%; for lung patient plan CIRS phantom measurements, the mean dose difference is −0.04% with a standard deviation of 1.09%; The maximum dose difference is 3.47% for Scanditronix phantom measurements and 3.08% for CIRS phantom measurements. Conclusion: Limitations in secondary MU check software lead to perceived large dose discrepancies for some of the lung patient SBRT treatment plans. Homogeneous and heterogeneous phantoms were used in plan quality assurance for non-lung patients and lung patients, respectively. Phantom based QA showed the relative good agreement between iPlan calculated dose and measured dose.« less

Impact of interpatient variability on organ dose estimates according to MIRD schema: Uncertainty and variance-based sensitivity analysis.

PubMed

Zvereva, Alexandra; Kamp, Florian; Schlattl, Helmut; Zankl, Maria; Parodi, Katia

2018-05-17

Variance-based sensitivity analysis (SA) is described and applied to the radiation dosimetry model proposed by the Committee on Medical Internal Radiation Dose (MIRD) for the organ-level absorbed dose calculations in nuclear medicine. The uncertainties in the dose coefficients thus calculated are also evaluated. A Monte Carlo approach was used to compute first-order and total-effect SA indices, which rank the input factors according to their influence on the uncertainty in the output organ doses. These methods were applied to the radiopharmaceutical (S)-4-(3- 18 F-fluoropropyl)-L-glutamic acid ( 18 F-FSPG) as an example. Since 18 F-FSPG has 11 notable source regions, a 22-dimensional model was considered here, where 11 input factors are the time-integrated activity coefficients (TIACs) in the source regions and 11 input factors correspond to the sets of the specific absorbed fractions (SAFs) employed in the dose calculation. The SA was restricted to the foregoing 22 input factors. The distributions of the input factors were built based on TIACs of five individuals to whom the radiopharmaceutical 18 F-FSPG was administered and six anatomical models, representing two reference, two overweight, and two slim individuals. The self-absorption SAFs were mass-scaled to correspond to the reference organ masses. The estimated relative uncertainties were in the range 10%-30%, with a minimum and a maximum for absorbed dose coefficients for urinary bladder wall and heart wall, respectively. The applied global variance-based SA enabled us to identify the input factors that have the highest influence on the uncertainty in the organ doses. With the applied mass-scaling of the self-absorption SAFs, these factors included the TIACs for absorbed dose coefficients in the source regions and the SAFs from blood as source region for absorbed dose coefficients in highly vascularized target regions. For some combinations of proximal target and source regions, the corresponding cross-fire SAFs were found to have an impact. Global variance-based SA has been for the first time applied to the MIRD schema for internal dose calculation. Our findings suggest that uncertainties in computed organ doses can be substantially reduced by performing an accurate determination of TIACs in the source regions, accompanied by the estimation of individual source region masses along with the usage of an appropriate blood distribution in a patient's body and, in a few cases, the cross-fire SAFs from proximal source regions. © 2018 American Association of Physicists in Medicine.

64-Slice multidetector row CT angiography of the abdomen: comparison of low versus high concentration iodinated contrast media in a porcine model

PubMed Central

Holalkere, N-S; Matthes, K; Kalva, S P; Brugge, W R; Sahani, D V

2011-01-01

Objective In this study we aimed to assess the image quality and degree of vascular enhancement using low-concentration contrast media (LCCM) (300 mg I ml–1) and high-concentration contrast media (HCCM) (370 mg I ml–1) on 64-slice multidetector row CT (MDCT) abdominal CT angiography (CTA). In addition, we aimed to study the feasibility of using HCCM with a reduced total iodine dose. Methods CTA of the abdomen on a 64-slice MDCT was performed on 15 anaesthetised pigs. Study pigs were divided into three groups of five each based on the iodine concentration and dose received: Group A (LCCM; 300 mg I ml–1), Group B (HCCM; 370 mg I ml–1) and Group C HCCM with 20% less iodine dose. The total iodine injected was kept constant (600 mg kg–1) in Groups A and B. Qualitative and quantitative analyses were performed to study and compare each group for image quality, visibility of the branch order of the superior mesenteric artery (SMA), artefacts, degree of enhancement in the aorta and main stem arteries and uniformity of enhancement in the aorta. Groups were compared using the analysis of variance test. Results The image quality of 64-slice MDCT angiography was excellent with a mean score of 4.63 and confident visualisation of the third to fifth order branches of the SMA in all groups. Group B demonstrated superior vascular enhancement, as compared with Groups A and C (p≤0.05). Uniform aortic enhancement was achieved with the use of LCCM and HCCM with 20% less iodine dose. Conclusion 64-slice MDCT angiography of the abdomen was of excellent quality. HCCM improves contrast enhancement and overall CTA image quality and allows the iodine dose to be reduced. PMID:21081582

Repeat Gamma-Knife Radiosurgery for Refractory or Recurrent Trigeminal Neuralgia with Consideration About the Optimal Second Dose.

PubMed

Park, Seong-Cheol; Kwon, Do Hoon; Lee, Do Hee; Lee, Jung Kyo

2016-02-01

To investigate adequate radiation doses for repeat Gamma Knife radiosurgery (GKS) for trigeminal neuralgia in our series and meta-analysis. Fourteen patients treated by ipsilateral repeat GKS for trigeminal neuralgia were included. Median age of patients was 65 years (range, 28-78), the median target dose, 140-180). Patients were followed a median of 10.8 months (range, 1-151) after the second gamma-knife surgery. Brainstem dose analysis and vote-counting meta-analysis of 19 studies were performed. After the second gamma-knife radiosurgeries, pain was relieved effectively in 12 patients (86%; Barrow Neurological Institute Pain Intensity Score I-III). Post-gamma-knife radiosurgery trigeminal nerve deficits were mild in 5 patients. No serious anesthesia dolorosa was occurred. The second GKS radiation dose ≤ 60 Gy was significantly associated with worse pain control outcome (P = 0.018 in our series, permutation analysis of variance, and P = 0.009 in the meta-analysis, 2-tailed Fisher's exact test). Cumulative dose ≤ 140-150 Gy was significantly associated with poor pain control outcome (P = 0.033 in our series and P = 0.013 in the meta-analysis, 2-tailed Fisher's exact test). A cumulative brainstem edge dose >12 Gy tended to be associated with trigeminal nerve deficit (P = 0.077). Our study suggests that the second GKS dose is a potentially important factor. Copyright © 2016 Elsevier Inc. All rights reserved.

SU-E-T-192: FMEA Severity Scores - Do We Really Know?

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

Tonigan, J; Johnson, J; Kry, S

2014-06-01

Purpose: Failure modes and effects analysis (FMEA) is a subjective risk mitigation technique that has not been applied to physics-specific quality management practices. There is a need for quantitative FMEA data as called for in the literature. This work focuses specifically on quantifying FMEA severity scores for physics components of IMRT delivery and comparing to subjective scores. Methods: Eleven physical failure modes (FMs) for head and neck IMRT dose calculation and delivery are examined near commonly accepted tolerance criteria levels. Phantom treatment planning studies and dosimetry measurements (requiring decommissioning in several cases) are performed to determine the magnitude of dosemore » delivery errors for the FMs (i.e., severity of the FM). Resultant quantitative severity scores are compared to FMEA scores obtained through an international survey and focus group studies. Results: Physical measurements for six FMs have resulted in significant PTV dose errors up to 4.3% as well as close to 1 mm significant distance-to-agreement error between PTV and OAR. Of the 129 survey responses, the vast majority of the responders used Varian machines with Pinnacle and Eclipse planning systems. The average years of experience was 17, yet familiarity with FMEA less than expected. Survey reports perception of dose delivery error magnitude varies widely, in some cases 50% difference in dose delivery error expected amongst respondents. Substantial variance is also seen for all FMs in occurrence, detectability, and severity scores assigned with average variance values of 5.5, 4.6, and 2.2, respectively. Survey shows for MLC positional FM(2mm) average of 7.6% dose error expected (range 0–50%) compared to 2% error seen in measurement. Analysis of ranking in survey, treatment planning studies, and quantitative value comparison will be presented. Conclusion: Resultant quantitative severity scores will expand the utility of FMEA for radiotherapy and verify accuracy of FMEA results compared to highly variable subjective scores.« less

40 CFR 59.509 - Can I get a variance?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Can I get a variance? 59.509 Section 59... Volatile Organic Compound Emission Standards for Aerosol Coatings § 59.509 Can I get a variance? (a) Any... compliance plan proposed by the applicant can reasonably be implemented and will achieve compliance as...

Warfarin pharmacogenetics: a single VKORC1 polymorphism is predictive of dose across 3 racial groups.

PubMed

Limdi, Nita A; Wadelius, Mia; Cavallari, Larisa; Eriksson, Niclas; Crawford, Dana C; Lee, Ming-Ta M; Chen, Chien-Hsiun; Motsinger-Reif, Alison; Sagreiya, Hersh; Liu, Nianjun; Wu, Alan H B; Gage, Brian F; Jorgensen, Andrea; Pirmohamed, Munir; Shin, Jae-Gook; Suarez-Kurtz, Guilherme; Kimmel, Stephen E; Johnson, Julie A; Klein, Teri E; Wagner, Michael J

2010-05-06

Warfarin-dosing algorithms incorporating CYP2C9 and VKORC1 -1639G>A improve dose prediction compared with algorithms based solely on clinical and demographic factors. However, these algorithms better capture dose variability among whites than Asians or blacks. Herein, we evaluate whether other VKORC1 polymorphisms and haplotypes explain additional variation in warfarin dose beyond that explained by VKORC1 -1639G>A among Asians (n = 1103), blacks (n = 670), and whites (n = 3113). Participants were recruited from 11 countries as part of the International Warfarin Pharmacogenetics Consortium effort. Evaluation of the effects of individual VKORC1 single nucleotide polymorphisms (SNPs) and haplotypes on warfarin dose used both univariate and multi variable linear regression. VKORC1 -1639G>A and 1173C>T individually explained the greatest variance in dose in all 3 racial groups. Incorporation of additional VKORC1 SNPs or haplotypes did not further improve dose prediction. VKORC1 explained greater variability in dose among whites than blacks and Asians. Differences in the percentage of variance in dose explained by VKORC1 across race were largely accounted for by the frequency of the -1639A (or 1173T) allele. Thus, clinicians should recognize that, although at a population level, the contribution of VKORC1 toward dose requirements is higher in whites than in nonwhites; genotype predicts similar dose requirements across racial groups.

20180312 - Reproducibility and variance of liver effects in subchronic and chronic repeat dose toxicity studies (SOT)

EPA Science Inventory

In vivo studies provide reference data to evaluate alternative methods for predicting toxicity. However, the reproducibility and variance of effects observed across multiple in vivo studies is not well understood. The US EPA’s Toxicity Reference Database (ToxRefDB) stores d...

Parameter uncertainty and variability in evaluative fate and exposure models

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

Hertwich, E.G.; McKone, T.E.; Pease, W.S.

The human toxicity potential, a weighting scheme used to evaluate toxic emissions for life cycle assessment and toxics release inventories, is based on potential dose calculations and toxicity factors. This paper evaluates the variance in potential dose calculations that can be attributed to the uncertainty in chemical-specific input parameters as well as the variability in exposure factors and landscape parameters. A knowledge of the uncertainty allows us to assess the robustness of a decision based on the toxicity potential; a knowledge of the sources of uncertainty allows one to focus resources if the uncertainty is to be reduced. The potentialmore » does of 236 chemicals was assessed. The chemicals were grouped by dominant exposure route, and a Monte Carlo analysis was conducted for one representative chemical in each group. The variance is typically one to two orders of magnitude. For comparison, the point estimates in potential dose for 236 chemicals span ten orders of magnitude. Most of the variance in the potential dose is due to chemical-specific input parameters, especially half-lives, although exposure factors such as fish intake and the source of drinking water can be important for chemicals whose dominant exposure is through indirect routes. Landscape characteristics are generally of minor importance.« less

Iterative raw measurements restoration method with penalized weighted least squares approach for low-dose CT

NASA Astrophysics Data System (ADS)

Takahashi, Hisashi; Goto, Taiga; Hirokawa, Koichi; Miyazaki, Osamu

2014-03-01

Statistical iterative reconstruction and post-log data restoration algorithms for CT noise reduction have been widely studied and these techniques have enabled us to reduce irradiation doses while maintaining image qualities. In low dose scanning, electronic noise becomes obvious and it results in some non-positive signals in raw measurements. The nonpositive signal should be converted to positive signal so that it can be log-transformed. Since conventional conversion methods do not consider local variance on the sinogram, they have difficulty of controlling the strength of the filtering. Thus, in this work, we propose a method to convert the non-positive signal to the positive signal by mainly controlling the local variance. The method is implemented in two separate steps. First, an iterative restoration algorithm based on penalized weighted least squares is used to mitigate the effect of electronic noise. The algorithm preserves the local mean and reduces the local variance induced by the electronic noise. Second, smoothed raw measurements by the iterative algorithm are converted to the positive signal according to a function which replaces the non-positive signal with its local mean. In phantom studies, we confirm that the proposed method properly preserves the local mean and reduce the variance induced by the electronic noise. Our technique results in dramatically reduced shading artifacts and can also successfully cooperate with the post-log data filter to reduce streak artifacts.

Low Dose PET Image Reconstruction with Total Variation Using Alternating Direction Method.

PubMed

Yu, Xingjian; Wang, Chenye; Hu, Hongjie; Liu, Huafeng

2016-01-01

In this paper, a total variation (TV) minimization strategy is proposed to overcome the problem of sparse spatial resolution and large amounts of noise in low dose positron emission tomography (PET) imaging reconstruction. Two types of objective function were established based on two statistical models of measured PET data, least-square (LS) TV for the Gaussian distribution and Poisson-TV for the Poisson distribution. To efficiently obtain high quality reconstructed images, the alternating direction method (ADM) is used to solve these objective functions. As compared with the iterative shrinkage/thresholding (IST) based algorithms, the proposed ADM can make full use of the TV constraint and its convergence rate is faster. The performance of the proposed approach is validated through comparisons with the expectation-maximization (EM) method using synthetic and experimental biological data. In the comparisons, the results of both LS-TV and Poisson-TV are taken into consideration to find which models are more suitable for PET imaging, in particular low-dose PET. To evaluate the results quantitatively, we computed bias, variance, and the contrast recovery coefficient (CRC) and drew profiles of the reconstructed images produced by the different methods. The results show that both Poisson-TV and LS-TV can provide a high visual quality at a low dose level. The bias and variance of the proposed LS-TV and Poisson-TV methods are 20% to 74% less at all counting levels than those of the EM method. Poisson-TV gives the best performance in terms of high-accuracy reconstruction with the lowest bias and variance as compared to the ground truth (14.3% less bias and 21.9% less variance). In contrast, LS-TV gives the best performance in terms of the high contrast of the reconstruction with the highest CRC.

Low Dose PET Image Reconstruction with Total Variation Using Alternating Direction Method

PubMed Central

Yu, Xingjian; Wang, Chenye; Hu, Hongjie; Liu, Huafeng

2016-01-01

In this paper, a total variation (TV) minimization strategy is proposed to overcome the problem of sparse spatial resolution and large amounts of noise in low dose positron emission tomography (PET) imaging reconstruction. Two types of objective function were established based on two statistical models of measured PET data, least-square (LS) TV for the Gaussian distribution and Poisson-TV for the Poisson distribution. To efficiently obtain high quality reconstructed images, the alternating direction method (ADM) is used to solve these objective functions. As compared with the iterative shrinkage/thresholding (IST) based algorithms, the proposed ADM can make full use of the TV constraint and its convergence rate is faster. The performance of the proposed approach is validated through comparisons with the expectation-maximization (EM) method using synthetic and experimental biological data. In the comparisons, the results of both LS-TV and Poisson-TV are taken into consideration to find which models are more suitable for PET imaging, in particular low-dose PET. To evaluate the results quantitatively, we computed bias, variance, and the contrast recovery coefficient (CRC) and drew profiles of the reconstructed images produced by the different methods. The results show that both Poisson-TV and LS-TV can provide a high visual quality at a low dose level. The bias and variance of the proposed LS-TV and Poisson-TV methods are 20% to 74% less at all counting levels than those of the EM method. Poisson-TV gives the best performance in terms of high-accuracy reconstruction with the lowest bias and variance as compared to the ground truth (14.3% less bias and 21.9% less variance). In contrast, LS-TV gives the best performance in terms of the high contrast of the reconstruction with the highest CRC. PMID:28005929

Analytical probabilistic modeling of RBE-weighted dose for ion therapy.

PubMed

Wieser, H P; Hennig, P; Wahl, N; Bangert, M

2017-11-10

Particle therapy is especially prone to uncertainties. This issue is usually addressed with uncertainty quantification and minimization techniques based on scenario sampling. For proton therapy, however, it was recently shown that it is also possible to use closed-form computations based on analytical probabilistic modeling (APM) for this purpose. APM yields unique features compared to sampling-based approaches, motivating further research in this context. This paper demonstrates the application of APM for intensity-modulated carbon ion therapy to quantify the influence of setup and range uncertainties on the RBE-weighted dose. In particular, we derive analytical forms for the nonlinear computations of the expectation value and variance of the RBE-weighted dose by propagating linearly correlated Gaussian input uncertainties through a pencil beam dose calculation algorithm. Both exact and approximation formulas are presented for the expectation value and variance of the RBE-weighted dose and are subsequently studied in-depth for a one-dimensional carbon ion spread-out Bragg peak. With V and B being the number of voxels and pencil beams, respectively, the proposed approximations induce only a marginal loss of accuracy while lowering the computational complexity from order [Formula: see text] to [Formula: see text] for the expectation value and from [Formula: see text] to [Formula: see text] for the variance of the RBE-weighted dose. Moreover, we evaluated the approximated calculation of the expectation value and standard deviation of the RBE-weighted dose in combination with a probabilistic effect-based optimization on three patient cases considering carbon ions as radiation modality against sampled references. The resulting global γ-pass rates (2 mm,2%) are [Formula: see text]99.15% for the expectation value and [Formula: see text]94.95% for the standard deviation of the RBE-weighted dose, respectively. We applied the derived analytical model to carbon ion treatment planning, although the concept is in general applicable to other ion species considering a variable RBE.

Analytical probabilistic modeling of RBE-weighted dose for ion therapy

NASA Astrophysics Data System (ADS)

Wieser, H. P.; Hennig, P.; Wahl, N.; Bangert, M.

2017-12-01

Particle therapy is especially prone to uncertainties. This issue is usually addressed with uncertainty quantification and minimization techniques based on scenario sampling. For proton therapy, however, it was recently shown that it is also possible to use closed-form computations based on analytical probabilistic modeling (APM) for this purpose. APM yields unique features compared to sampling-based approaches, motivating further research in this context. This paper demonstrates the application of APM for intensity-modulated carbon ion therapy to quantify the influence of setup and range uncertainties on the RBE-weighted dose. In particular, we derive analytical forms for the nonlinear computations of the expectation value and variance of the RBE-weighted dose by propagating linearly correlated Gaussian input uncertainties through a pencil beam dose calculation algorithm. Both exact and approximation formulas are presented for the expectation value and variance of the RBE-weighted dose and are subsequently studied in-depth for a one-dimensional carbon ion spread-out Bragg peak. With V and B being the number of voxels and pencil beams, respectively, the proposed approximations induce only a marginal loss of accuracy while lowering the computational complexity from order O(V × B^2) to O(V × B) for the expectation value and from O(V × B^4) to O(V × B^2) for the variance of the RBE-weighted dose. Moreover, we evaluated the approximated calculation of the expectation value and standard deviation of the RBE-weighted dose in combination with a probabilistic effect-based optimization on three patient cases considering carbon ions as radiation modality against sampled references. The resulting global γ-pass rates (2 mm,2%) are > 99.15% for the expectation value and > 94.95% for the standard deviation of the RBE-weighted dose, respectively. We applied the derived analytical model to carbon ion treatment planning, although the concept is in general applicable to other ion species considering a variable RBE.

The underlying structure of diagnostic systems of schizophrenia: a comprehensive polydiagnostic approach.

PubMed

Peralta, Victor; Cuesta, Manuel J

2005-11-15

The objective was to ascertain the underlying factor structure of alternative definitions of schizophrenia, and to examine the distribution of schizophrenia-related variables against the resulting factor solution. Twenty-three diagnostic schemes of schizophrenia were applied to 660 patients presenting with psychotic symptoms regardless of the specific diagnosis of psychotic disorder. Factor analysis of the 23 diagnostic schemes yielded three interpretable factors explaining 58% of the variance, the first factor (general schizophrenia factor) accounting for most of the variance (36%). On the basis of the general schizophrenia factor score, the sample was divided in quintile groups representing 5 levels of schizophrenia definition (absent, doubtful, very broad, broad and narrow) and the distribution of a number of schizophrenia-related variables was examined across the groups. This grouping procedure was used for examining the comparative validity of alternative levels of categorically defined schizophrenia and an ordinal (i.e. dimensional) definition. Overall, schizophrenia-related variables displayed a dose-response relationship with level of schizophrenia definition. Logistic regression analyses revealed that the dimensional definition explained more variance in the schizophrenia-related variables than the alternative levels for defining schizophrenia categorically. These results are consistent with a unitary and dimensional construct of schizophrenia with no clear "points of rarity" at its boundaries, thus supporting the continuum hypothesis of the psychotic illness.

Dose-response relationship of autonomic nervous system responses to individualized training impulse in marathon runners.

PubMed

Manzi, Vincenzo; Castagna, Carlo; Padua, Elvira; Lombardo, Mauro; D'Ottavio, Stefano; Massaro, Michele; Volterrani, Maurizio; Iellamo, Ferdinando

2009-06-01

In athletes, exercise training induces autonomic nervous system (ANS) adaptations that could be used to monitor training status. However, the relationship between training and ANS in athletes has been investigated without regard for individual training loads. We tested the hypothesis that in long-distance athletes, changes in ANS parameters are dose-response related to individual volume/intensity training load and could predict athletic performance. A spectral analysis of heart rate (HR), systolic arterial pressure variability, and baroreflex sensitivity by the sequences technique was investigated in eight recreational athletes during a 6-mo training period culminating with a marathon. Individualized training load responses were monitored by a modified training impulse (TRIMP(i)) method, which was determined in each athlete using the individual HR and lactate profiling determined during a treadmill test. Monthly TRIMP(i) steadily increased during the training period. All the ANS parameters were significantly and very highly correlated to the dose of exercise with a second-order regression model (r(2) ranged from 0.90 to 0.99; P < 0.001). Variance, high-frequency oscillations of HR variability (HRV), and baroreflex sensitivity resembled a bell-shaped curve with a minimum at the highest TRIMP(i), whereas low-frequency oscillations of HR and systolic arterial pressure variability and the low frequency (LF)-to-high frequency ratio resembled an U-shaped curve with a maximum at the highest TRIMP(i). The LF component of HRV assessed at the last recording session was significantly and inversely correlated to the time needed to complete the nearing marathon. These results suggest that in recreational athletes, ANS adaptations to exercise training are dose related on an individual basis, showing a progressive shift toward a sympathetic predominance, and that LF oscillations in HRV at peak training load could predict athletic achievement in this athlete population.

Respondents' answers to community attitudinal surveys represent impressions of soundscapes and not merely reactions to the physical noise.

PubMed

Schomer, Paul; Mestre, Vincent; Schulte-Fortkamp, Brigitte; Boyle, James

2013-07-01

Noise dose as a sole independent variable accounts only for less than half of the variance in community response data. Non-acoustic factors, such as attitude to the noise source identified by Job [(1988). J. Acoust. Soc. Am. 83(3), 991-1001] and others, reduce the unexplained variance. This paper suggests that non-acoustic factors reflect the context in which the sonic environment is perceived; hence, these factors constitute the judgments of a soundscape. Fidell et al. [(2011). J. Acoust. Soc. Am. 130(2), 791-806] show that a "community tolerance level" (CTL) is a one-number, community-specific, independent variable that represents the aggregate influence on annoyance judgments of all non-acoustic influences. Taken together these findings suggest that: (i) CTL is a one-number quantification of a soundscape, and (ii) a soundscape can be quantified by a single, numeric variable. It follows, if one can predict or calculate the single numeric quantification of a soundscape, that number will be the CTL. These results can only be true for a soundscape judged on the basis of annoyance. Virtually no data exist for which the respondents even had the possibility to rate the sonic environment positively, i.e., pleasing, so the application of CTL to soundscapes judged positively is not clear.

Generation of uniformly distributed dose points for anatomy-based three-dimensional dose optimization methods in brachytherapy.

PubMed

Lahanas, M; Baltas, D; Giannouli, S; Milickovic, N; Zamboglou, N

2000-05-01

We have studied the accuracy of statistical parameters of dose distributions in brachytherapy using actual clinical implants. These include the mean, minimum and maximum dose values and the variance of the dose distribution inside the PTV (planning target volume), and on the surface of the PTV. These properties have been studied as a function of the number of uniformly distributed sampling points. These parameters, or the variants of these parameters, are used directly or indirectly in optimization procedures or for a description of the dose distribution. The accurate determination of these parameters depends on the sampling point distribution from which they have been obtained. Some optimization methods ignore catheters and critical structures surrounded by the PTV or alternatively consider as surface dose points only those on the contour lines of the PTV. D(min) and D(max) are extreme dose values which are either on the PTV surface or within the PTV. They must be avoided for specification and optimization purposes in brachytherapy. Using D(mean) and the variance of D which we have shown to be stable parameters, achieves a more reliable description of the dose distribution on the PTV surface and within the PTV volume than does D(min) and D(max). Generation of dose points on the real surface of the PTV is obligatory and the consideration of catheter volumes results in a realistic description of anatomical dose distributions.

Analysis of the NAEG model of transuranic radionuclide transport and dose

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

Kercher, J.R.; Anspaugh, L.R.

We analyze the model for estimating the dose from /sup 239/Pu developed for the Nevada Applied Ecology Group (NAEG) by using sensitivity analysis and uncertainty analysis. Sensitivity analysis results suggest that the air pathway is the critical pathway for the organs receiving the highest dose. Soil concentration and the factors controlling air concentration are the most important parameters. The only organ whose dose is sensitive to parameters in the ingestion pathway is the GI tract. The air pathway accounts for 100% of the dose to lung, upper respiratory tract, and thoracic lymph nodes; and 95% of its dose via ingestion.more » Leafy vegetable ingestion accounts for 70% of the dose from the ingestion pathway regardless of organ, peeled vegetables 20%; accidental soil ingestion 5%; ingestion of beef liver 4%; beef muscle 1%. Only a handful of model parameters control the dose for any one organ. The number of important parameters is usually less than 10. Uncertainty analysis indicates that choosing a uniform distribution for the input parameters produces a lognormal distribution of the dose. The ratio of the square root of the variance to the mean is three times greater for the doses than it is for the individual parameters. As found by the sensitivity analysis, the uncertainty analysis suggests that only a few parameters control the dose for each organ. All organs have similar distributions and variance to mean ratios except for the lymph modes. 16 references, 9 figures, 13 tables.« less

Dynamic Repertoire of Intrinsic Brain States Is Reduced in Propofol-Induced Unconsciousness

PubMed Central

Liu, Xiping; Pillay, Siveshigan

2015-01-01

Abstract The richness of conscious experience is thought to scale with the size of the repertoire of causal brain states, and it may be diminished in anesthesia. We estimated the state repertoire from dynamic analysis of intrinsic functional brain networks in conscious sedated and unconscious anesthetized rats. Functional resonance images were obtained from 30-min whole-brain resting-state blood oxygen level-dependent (BOLD) signals at propofol infusion rates of 20 and 40 mg/kg/h, intravenously. Dynamic brain networks were defined at the voxel level by sliding window analysis of regional homogeneity (ReHo) or coincident threshold crossings (CTC) of the BOLD signal acquired in nine sagittal slices. The state repertoire was characterized by the temporal variance of the number of voxels with significant ReHo or positive CTC. From low to high propofol dose, the temporal variances of ReHo and CTC were reduced by 78%±20% and 76%±20%, respectively. Both baseline and propofol-induced reduction of CTC temporal variance increased from lateral to medial position. Group analysis showed a 20% reduction in the number of unique states at the higher propofol dose. Analysis of temporal variance in 12 anatomically defined regions of interest predicted that the largest changes occurred in visual cortex, parietal cortex, and caudate-putamen. The results suggest that the repertoire of large-scale brain states derived from the spatiotemporal dynamics of intrinsic networks is substantially reduced at an anesthetic dose associated with loss of consciousness. PMID:24702200

Homogeneous Canine Chest Phantom Construction: A Tool for Image Quality Optimization.

PubMed

Pavan, Ana Luiza Menegatti; Rosa, Maria Eugênia Dela; Giacomini, Guilherme; Bacchim Neto, Fernando Antonio; Yamashita, Seizo; Vulcano, Luiz Carlos; Duarte, Sergio Barbosa; Miranda, José Ricardo de Arruda; de Pina, Diana Rodrigues

2016-01-01

Digital radiographic imaging is increasing in veterinary practice. The use of radiation demands responsibility to maintain high image quality. Low doses are necessary because workers are requested to restrain the animal. Optimizing digital systems is necessary to avoid unnecessary exposure, causing the phenomenon known as dose creep. Homogeneous phantoms are widely used to optimize image quality and dose. We developed an automatic computational methodology to classify and quantify tissues (i.e., lung tissue, adipose tissue, muscle tissue, and bone) in canine chest computed tomography exams. The thickness of each tissue was converted to simulator materials (i.e., Lucite, aluminum, and air). Dogs were separated into groups of 20 animals each according to weight. Mean weights were 6.5 ± 2.0 kg, 15.0 ± 5.0 kg, 32.0 ± 5.5 kg, and 50.0 ± 12.0 kg, for the small, medium, large, and giant groups, respectively. The one-way analysis of variance revealed significant differences in all simulator material thicknesses (p < 0.05) quantified between groups. As a result, four phantoms were constructed for dorsoventral and lateral views. In conclusion, the present methodology allows the development of phantoms of the canine chest and possibly other body regions and/or animals. The proposed phantom is a practical tool that may be employed in future work to optimize veterinary X-ray procedures.

Homogeneous Canine Chest Phantom Construction: A Tool for Image Quality Optimization

PubMed Central

2016-01-01

Digital radiographic imaging is increasing in veterinary practice. The use of radiation demands responsibility to maintain high image quality. Low doses are necessary because workers are requested to restrain the animal. Optimizing digital systems is necessary to avoid unnecessary exposure, causing the phenomenon known as dose creep. Homogeneous phantoms are widely used to optimize image quality and dose. We developed an automatic computational methodology to classify and quantify tissues (i.e., lung tissue, adipose tissue, muscle tissue, and bone) in canine chest computed tomography exams. The thickness of each tissue was converted to simulator materials (i.e., Lucite, aluminum, and air). Dogs were separated into groups of 20 animals each according to weight. Mean weights were 6.5 ± 2.0 kg, 15.0 ± 5.0 kg, 32.0 ± 5.5 kg, and 50.0 ± 12.0 kg, for the small, medium, large, and giant groups, respectively. The one-way analysis of variance revealed significant differences in all simulator material thicknesses (p < 0.05) quantified between groups. As a result, four phantoms were constructed for dorsoventral and lateral views. In conclusion, the present methodology allows the development of phantoms of the canine chest and possibly other body regions and/or animals. The proposed phantom is a practical tool that may be employed in future work to optimize veterinary X-ray procedures. PMID:27101001

Characteristics and associations of pain intensity in patients referred to a specialist cancer pain clinic.

PubMed

Pina, Paulo; Sabri, Elham; Lawlor, Peter G

2015-01-01

Uncontrolled cancer pain (CP) may impair quality of life. Given the multidimensional nature of CP, its poor control is often attributed to poor assessment and classification. To determine the characteristics and associations of pain intensity in a specialist CP clinic. Consecutive patients referred to the CP clinic of the Portuguese Cancer Institute (Lisbon, Portugal) had standardized initial assessments and status documentation of the following: Brief Pain Inventory ratings for 'pain now' as the outcome variable; initial pain intensity (iPI) on a 0 to 10 scale; pain mechanism (using the Douleur Neuropathique 4 tool to assess neuropathic pain); episodic pain; Eastern Cooperative Oncology Group rating; oral morphine equivalent daily dose (MEDD); Hospital Anxiety Depression Scale and Emotional Thermometer scores; and cancer diagnosis, metastases, treatment and pain duration. Univariable analyses were conducted to test the association of independent variables with iPI. Variables with P<0.1 were entered into a multivariable regression model, using backward elimination and a cut-point of P=0.2 for final model selection. Of 371 participants, 285 (77%) had moderate (4 to 6) or severe (7 to 10) iPI. The initial median MEDD was relatively low (30 mg [range 20 mg to 60 mg]). In the multivariable model, higher income, Eastern Cooperative Oncology Group rating 3 to 4, cancer diagnosis (head and neck, genitourinary and gastrointestinal), adjuvant use and initial MEDD were associated with iPI (P<0.05). The model's R2 was 18.6, which explained only 19% of iPI variance. The diversity of factors associated with pain intensity and their limited explanation of its variance underscore the biopsychosocial complexity of CP. Adequacy of CP management warrants further exploration.

SU-F-T-18: The Importance of Immobilization Devices in Brachytherapy Treatments of Vaginal Cuff

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

Shojaei, M; Dumitru, N; Pella, S

2016-06-15

Purpose: High dose rate brachytherapy is a highly localized radiation therapy that has a very high dose gradient. Thus one of the most important parts of the treatment is the immobilization. The smallest movement of the patient or applicator can result in dose variation to the surrounding tissues as well as to the tumor to be treated. We will revise the ML Cylinder treatments and their localization challenges. Methods: A retrospective study of 25 patients with 5 treatments each looking into the applicator’s placement in regard to the organs at risk. Motion possibilities for each applicator intra and inter fractionationmore » with their dosimetric implications were covered and measured in regard with their dose variance. The localization immobilization devices used were assessed for the capability to prevent motion before and during the treatment delivery. Results: We focused on the 100% isodose on central axis and a 15 degree displacement due to possible rotation analyzing the dose variations to the bladder and rectum walls. The average dose variation for bladder was 15% of the accepted tolerance, with a minimum variance of 11.1% and a maximum one of 23.14% on the central axis. For the off axis measurements we found an average variation of 16.84% of the accepted tolerance, with a minimum variance of 11.47% and a maximum one of 27.69%. For the rectum we focused on the rectum wall closest to the 120% isodose line. The average dose variation was 19.4%, minimum 11.3% and a maximum of 34.02% from the accepted tolerance values Conclusion: Improved immobilization devices are recommended. For inter-fractionation, localization devices are recommended in place with consistent planning in regards with the initial fraction. Many of the present immobilization devices produced for external radiotherapy can be used to improve the localization of HDR applicators during transportation of the patient and during treatment.« less

Optimal mapping of terrestrial gamma dose rates using geological parent material and aerogeophysical survey data.

PubMed

Rawlins, B G; Scheib, C; Tyler, A N; Beamish, D

2012-12-01

Regulatory authorities need ways to estimate natural terrestrial gamma radiation dose rates (nGy h⁻¹) across the landscape accurately, to assess its potential deleterious health effects. The primary method for estimating outdoor dose rate is to use an in situ detector supported 1 m above the ground, but such measurements are costly and cannot capture the landscape-scale variation in dose rates which are associated with changes in soil and parent material mineralogy. We investigate the potential for improving estimates of terrestrial gamma dose rates across Northern Ireland (13,542 km²) using measurements from 168 sites and two sources of ancillary data: (i) a map based on a simplified classification of soil parent material, and (ii) dose estimates from a national-scale, airborne radiometric survey. We used the linear mixed modelling framework in which the two ancillary variables were included in separate models as fixed effects, plus a correlation structure which captures the spatially correlated variance component. We used a cross-validation procedure to determine the magnitude of the prediction errors for the different models. We removed a random subset of 10 terrestrial measurements and formed the model from the remainder (n = 158), and then used the model to predict values at the other 10 sites. We repeated this procedure 50 times. The measurements of terrestrial dose vary between 1 and 103 (nGy h⁻¹). The median absolute model prediction errors (nGy h⁻¹) for the three models declined in the following order: no ancillary data (10.8) > simple geological classification (8.3) > airborne radiometric dose (5.4) as a single fixed effect. Estimates of airborne radiometric gamma dose rate can significantly improve the spatial prediction of terrestrial dose rate.

Ultralow dose dentomaxillofacial CT imaging and iterative reconstruction techniques: variability of Hounsfield units and contrast-to-noise ratio

PubMed Central

Bischel, Alexander; Stratis, Andreas; Kakar, Apoorv; Bosmans, Hilde; Jacobs, Reinhilde; Gassner, Eva-Maria; Puelacher, Wolfgang; Pauwels, Ruben

2016-01-01

Objective: The aim of this study was to evaluate whether application of ultralow dose protocols and iterative reconstruction technology (IRT) influence quantitative Hounsfield units (HUs) and contrast-to-noise ratio (CNR) in dentomaxillofacial CT imaging. Methods: A phantom with inserts of five types of materials was scanned using protocols for (a) a clinical reference for navigated surgery (CT dose index volume 36.58 mGy), (b) low-dose sinus imaging (18.28 mGy) and (c) four ultralow dose imaging (4.14, 2.63, 0.99 and 0.53 mGy). All images were reconstructed using: (i) filtered back projection (FBP); (ii) IRT: adaptive statistical iterative reconstruction-50 (ASIR-50), ASIR-100 and model-based iterative reconstruction (MBIR); and (iii) standard (std) and bone kernel. Mean HU, CNR and average HU error after recalibration were determined. Each combination of protocols was compared using Friedman analysis of variance, followed by Dunn's multiple comparison test. Results: Pearson's sample correlation coefficients were all >0.99. Ultralow dose protocols using FBP showed errors of up to 273 HU. Std kernels had less HU variability than bone kernels. MBIR reduced the error value for the lowest dose protocol to 138 HU and retained the highest relative CNR. ASIR could not demonstrate significant advantages over FBP. Conclusions: Considering a potential dose reduction as low as 1.5% of a std protocol, ultralow dose protocols and IRT should be further tested for clinical dentomaxillofacial CT imaging. Advances in knowledge: HU as a surrogate for bone density may vary significantly in CT ultralow dose imaging. However, use of std kernels and MBIR technology reduce HU error values and may retain the highest CNR. PMID:26859336

Investigation of effective decision criteria for multiobjective optimization in IMRT.

PubMed

Holdsworth, Clay; Stewart, Robert D; Kim, Minsun; Liao, Jay; Phillips, Mark H

2011-06-01

To investigate how using different sets of decision criteria impacts the quality of intensity modulated radiation therapy (IMRT) plans obtained by multiobjective optimization. A multiobjective optimization evolutionary algorithm (MOEA) was used to produce sets of IMRT plans. The MOEA consisted of two interacting algorithms: (i) a deterministic inverse planning optimization of beamlet intensities that minimizes a weighted sum of quadratic penalty objectives to generate IMRT plans and (ii) an evolutionary algorithm that selects the superior IMRT plans using decision criteria and uses those plans to determine the new weights and penalty objectives of each new plan. Plans resulting from the deterministic algorithm were evaluated by the evolutionary algorithm using a set of decision criteria for both targets and organs at risk (OARs). Decision criteria used included variation in the target dose distribution, mean dose, maximum dose, generalized equivalent uniform dose (gEUD), an equivalent uniform dose (EUD(alpha,beta) formula derived from the linear-quadratic survival model, and points on dose volume histograms (DVHs). In order to quantatively compare results from trials using different decision criteria, a neutral set of comparison metrics was used. For each set of decision criteria investigated, IMRT plans were calculated for four different cases: two simple prostate cases, one complex prostate Case, and one complex head and neck Case. When smaller numbers of decision criteria, more descriptive decision criteria, or less anti-correlated decision criteria were used to characterize plan quality during multiobjective optimization, dose to OARs and target dose variation were reduced in the final population of plans. Mean OAR dose and gEUD (a = 4) decision criteria were comparable. Using maximum dose decision criteria for OARs near targets resulted in inferior populations that focused solely on low target variance at the expense of high OAR dose. Target dose range, (D(max) - D(min)), decision criteria were found to be most effective for keeping targets uniform. Using target gEUD decision criteria resulted in much lower OAR doses but much higher target dose variation. EUD(alpha,beta) based decision criteria focused on a region of plan space that was a compromise between target and OAR objectives. None of these target decision criteria dominated plans using other criteria, but only focused on approaching a different area of the Pareto front. The choice of decision criteria implemented in the MOEA had a significant impact on the region explored and the rate of convergence toward the Pareto front. When more decision criteria, anticorrelated decision criteria, or decision criteria with insufficient information were implemented, inferior populations are resulted. When more informative decision criteria were used, such as gEUD, EUD(alpha,beta), target dose range, and mean dose, MOEA optimizations focused on approaching different regions of the Pareto front, but did not dominate each other. Using simple OAR decision criteria and target EUD(alpha,beta) decision criteria demonstrated the potential to generate IMRT plans that significantly reduce dose to OARs while achieving the same or better tumor control when clinical requirements on target dose variance can be met or relaxed.

Comparing estimates of genetic variance across different relationship models.

PubMed

Legarra, Andres

2016-02-01

Use of relationships between individuals to estimate genetic variances and heritabilities via mixed models is standard practice in human, plant and livestock genetics. Different models or information for relationships may give different estimates of genetic variances. However, comparing these estimates across different relationship models is not straightforward as the implied base populations differ between relationship models. In this work, I present a method to compare estimates of variance components across different relationship models. I suggest referring genetic variances obtained using different relationship models to the same reference population, usually a set of individuals in the population. Expected genetic variance of this population is the estimated variance component from the mixed model times a statistic, Dk, which is the average self-relationship minus the average (self- and across-) relationship. For most typical models of relationships, Dk is close to 1. However, this is not true for very deep pedigrees, for identity-by-state relationships, or for non-parametric kernels, which tend to overestimate the genetic variance and the heritability. Using mice data, I show that heritabilities from identity-by-state and kernel-based relationships are overestimated. Weighting these estimates by Dk scales them to a base comparable to genomic or pedigree relationships, avoiding wrong comparisons, for instance, "missing heritabilities". Copyright © 2015 Elsevier Inc. All rights reserved.

Denoising of polychromatic CT images based on their own noise properties

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

Kim, Ji Hye; Chang, Yongjin; Ra, Jong Beom, E-mail: jbra@kaist.ac.kr

Purpose: Because of high diagnostic accuracy and fast scan time, computed tomography (CT) has been widely used in various clinical applications. Since the CT scan introduces radiation exposure to patients, however, dose reduction has recently been recognized as an important issue in CT imaging. However, low-dose CT causes an increase of noise in the image and thereby deteriorates the accuracy of diagnosis. In this paper, the authors develop an efficient denoising algorithm for low-dose CT images obtained using a polychromatic x-ray source. The algorithm is based on two steps: (i) estimation of space variant noise statistics, which are uniquely determinedmore » according to the system geometry and scanned object, and (ii) subsequent novel conversion of the estimated noise to Gaussian noise so that an existing high performance Gaussian noise filtering algorithm can be directly applied to CT images with non-Gaussian noise. Methods: For efficient polychromatic CT image denoising, the authors first reconstruct an image with the iterative maximum-likelihood polychromatic algorithm for CT to alleviate the beam-hardening problem. We then estimate the space-variant noise variance distribution on the image domain. Since there are many high performance denoising algorithms available for the Gaussian noise, image denoising can become much more efficient if they can be used. Hence, the authors propose a novel conversion scheme to transform the estimated space-variant noise to near Gaussian noise. In the suggested scheme, the authors first convert the image so that its mean and variance can have a linear relationship, and then produce a Gaussian image via variance stabilizing transform. The authors then apply a block matching 4D algorithm that is optimized for noise reduction of the Gaussian image, and reconvert the result to obtain a final denoised image. To examine the performance of the proposed method, an XCAT phantom simulation and a physical phantom experiment were conducted. Results: Both simulation and experimental results show that, unlike the existing denoising algorithms, the proposed algorithm can effectively reduce the noise over the whole region of CT images while preventing degradation of image resolution. Conclusions: To effectively denoise polychromatic low-dose CT images, a novel denoising algorithm is proposed. Because this algorithm is based on the noise statistics of a reconstructed polychromatic CT image, the spatially varying noise on the image is effectively reduced so that the denoised image will have homogeneous quality over the image domain. Through a simulation and a real experiment, it is verified that the proposed algorithm can deliver considerably better performance compared to the existing denoising algorithms.« less

Promiscuous mating in the harem-roosting fruit bat, Cynopterus sphinx.

PubMed

Garg, Kritika M; Chattopadhyay, Balaji; Doss D, Paramanatha Swami; A K, Vinoth Kumar; Kandula, Sripathi; Ramakrishnan, Uma

2012-08-01

Observations on mating behaviours and strategies guide our understanding of mating systems and variance in reproductive success. However, the presence of cryptic strategies often results in situations where social mating system is not reflective of genetic mating system. We present such a study of the genetic mating system of a harem-forming bat Cynopterus sphinx where harems may not be true indicators of male reproductive success. This temporal study using data from six seasons on paternity reveals that social harem assemblages do not play a role in the mating system, and variance in male reproductive success is lower than expected assuming polygynous mating. Further, simulations reveal that the genetic mating system is statistically indistinguishable from promiscuity. Our results are in contrast to an earlier study that demonstrated high variance in male reproductive success. Although an outcome of behavioural mating patterns, standardized variance in male reproductive success (I(m)) affects the opportunity for sexual selection. To gain a better understanding of the evolutionary implications of promiscuity for mammals in general, we compared our estimates of I(m) and total opportunity for sexual selection (I(m) /I(f), where I(f) is standardized variance in female reproductive success) with those of other known promiscuous species. We observed a broad range of I(m) /I(f) values across known promiscuous species, indicating our poor understanding of the evolutionary implications of promiscuous mating. © 2012 Blackwell Publishing Ltd.

Dose equations for shift-variant CT acquisition modes using variable pitch, tube current, and aperture, and the meaning of their associated CTDI{sub vol}

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

Dixon, Robert L., E-mail: rdixon@wfubmc.edu; Boone, John M.; Kraft, Robert A.

2014-11-01

Purpose: With the increasing clinical use of shift-variant CT protocols involving tube current modulation (TCM), variable pitch or pitch modulation (PM), and variable aperture a(t), the interpretation of the scanner-reported CTDI{sub vol} is called into question. This was addressed for TCM in their previous paper published by Dixon and Boone [Med. Phys. 40, 111920 (14pp.) (2013)] and is extended to PM and concurrent TCM/PM as well as variable aperture in this work. Methods: Rigorous convolution equations are derived to describe the accumulated dose distributions for TCM, PM, and concurrent TCM/PM. A comparison with scanner-reported CTDI{sub vol} formulae clearly identifies themore » source of their differences with the traditional CTDI{sub vol}. Dose distribution simulations using the convolution are provided for a variety of TCM and PM scenarios including a helical shuttle used for perfusion studies (as well as constant mA)—all having the same scanner-reported CTDI{sub vol}. These new convolution simulations for TCM are validated by comparison with their previous discrete summations. Results: These equations show that PM is equivalent to TCM if the pitch variation p(z) is proportional to 1/i(z), where i(z) is the local tube current. The simulations show that the local dose at z depends only weakly on the local tube current i(z) or local pitch p(z) due to scatter from all other locations along z, and that the “local CTDI{sub vol}(z)” or “CTDI{sub vol} per slice” do not represent a local dose but rather only a relative i(z) or p(z). The CTDI-paradigm does not apply to shift-variant techniques and the scanner-reported CTDI{sub vol} for the same lacks physical significance and relevance. Conclusions: While the traditional CTDI{sub vol} at constant tube current and pitch conveys useful information (the peak dose at the center of the scan length), CTDI{sub vol} for shift-variant techniques (TCM or PM) conveys no useful information about the associated dose distribution it purportedly represents. On the other hand, the total energy absorbed E (“integral dose”) as well as its surrogate DLP remain robust (invariant) with respect to shift-variance, depending only on the total mAs = 〈i〉t{sub 0} accumulated during the total beam-on time t{sub 0} and aperture a, where 〈i〉 is the average current.« less

Jackknife for Variance Analysis of Multifactor Experiments.

DTIC Science & Technology

1982-05-01

variance-covariance matrix is generated y a subroutine named CORAN (UNIVAC, 1969). The jackknife variances are then punched on computer cards in the same...LEVEL OF: InMte CALL cORAN (oaILa.NSUR.NOAY.D,*OXflRRORR.PCOF.2K.1’)I WRITE IP97111 )1RRN.4 .1:NDAY) 0 a 3fill1UR I .’t UN 001f’..1uŔ:1 .w100710n

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.

Establishment of an Effective Radioiodide Thyroid Ablation Protocol in Mice.

PubMed

Schmohl, Kathrin A; Müller, Andrea M; Schwenk, Nathalie; Knoop, Kerstin; Rijntjes, Eddy; Köhrle, Josef; Heuer, Heike; Bartenstein, Peter; Göke, Burkhard; Nelson, Peter J; Spitzweg, Christine

2015-09-01

Due to the high variance in available protocols on iodide-131 ((131)I) ablation in rodents, we set out to establish an effective method to generate a thyroid-ablated mouse model that allows the application of the sodium iodide symporter (NIS) as a reporter gene without interference with thyroidal NIS. We tested a range of (131)I doses with and without prestimulation of thyroidal radioiodide uptake by a low-iodine diet and thyroid-stimulating hormone (TSH) application. Efficacy of induction of hypothyroidism was tested by measurement of serum T4 concentrations, pituitary TSHβ and liver deiodinase type 1 (DIO1) mRNA expression, body weight analysis, and (99m)Tc-pertechnetate scintigraphy. While 200 µCi (7.4 MBq) (131)I alone was not sufficient to abolish thyroidal T4 production, 500 µCi (18.5 MBq) (131)I combined with 1 week of a low-iodine diet decreased serum concentrations below the detection limit. However, the high (131)I dose resulted in severe side effects. A combination of 1 week of a low-iodine diet followed by injection of bovine TSH before the application of 150 µCi (5.5 MBq) (131)I decreased serum T4 concentrations below the detection limit and significantly increased pituitary TSHβ concentrations. The systemic effects of induced hypothyroidism were shown by growth arrest and a decrease in liver DIO1 expression below the detection limit. (99m)Tc-pertechnetate scintigraphy revealed absence of thyroidal (99m)Tc-pertechnetate uptake in ablated mice. In summary, we report a revised protocol for radioiodide ablation of the thyroid gland in the mouse to generate an in vivo model that allows the study of thyroid hormone action using NIS as a reporter gene.

Establishment of an Effective Radioiodide Thyroid Ablation Protocol in Mice

PubMed Central

Schmohl, Kathrin A.; Müller, Andrea M.; Schwenk, Nathalie; Knoop, Kerstin; Rijntjes, Eddy; Köhrle, Josef; Heuer, Heike; Bartenstein, Peter; Göke, Burkhard; Nelson, Peter J.; Spitzweg, Christine

2015-01-01

Due to the high variance in available protocols on iodide-131 (131I) ablation in rodents, we set out to establish an effective method to generate a thyroid-ablated mouse model that allows the application of the sodium iodide symporter (NIS) as a reporter gene without interference with thyroidal NIS. We tested a range of 131I doses with and without prestimulation of thyroidal radioiodide uptake by a low-iodine diet and thyroid-stimulating hormone (TSH) application. Efficacy of induction of hypothyroidism was tested by measurement of serum T4 concentrations, pituitary TSHβ and liver deiodinase type 1 (DIO1) mRNA expression, body weight analysis, and 99mTc-pertechnetate scintigraphy. While 200 µCi (7.4 MBq) 131I alone was not sufficient to abolish thyroidal T4 production, 500 µCi (18.5 MBq) 131I combined with 1 week of a low-iodine diet decreased serum concentrations below the detection limit. However, the high 131I dose resulted in severe side effects. A combination of 1 week of a low-iodine diet followed by injection of bovine TSH before the application of 150 µCi (5.5 MBq) 131I decreased serum T4 concentrations below the detection limit and significantly increased pituitary TSHβ concentrations. The systemic effects of induced hypothyroidism were shown by growth arrest and a decrease in liver DIO1 expression below the detection limit. 99mTc-pertechnetate scintigraphy revealed absence of thyroidal 99mTc-pertechnetate uptake in ablated mice. In summary, we report a revised protocol for radioiodide ablation of the thyroid gland in the mouse to generate an in vivo model that allows the study of thyroid hormone action using NIS as a reporter gene. PMID:26601076

Coffee intake and the incident risk of cognitive disorders: A dose-response meta-analysis of nine prospective cohort studies.

PubMed

Wu, Lei; Sun, Dali; He, Yao

2017-06-01

Previous epidemiological studies have provided inconsistent conclusions on the impact of coffee consumption in the developing of cognitive disorders. However, no previous meta-analysis has pooled the evidence from the prospective cohort studies to assess the influence of coffee drinking and its potential dose-response patterns on the risk of developing cognitive disorders specifically. Two databases (PubMed and Embase) were searched for evidence of cohort studies from inception to February 2016. We used a generic inverse-variance method with a random-effects model to pool the fully adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs). In the dose-response analyses, a generalized least-squares trend estimation model was applied to computing the study-specific slopes. Nine prospective cohort studies involving 34,282 participants were included in our study. The duration of follow-up years ranged from 1.3 to 28. Compared with <1 cup, daily drinking of 1-2 cups of coffee was inversely linked with the occurrence of cognitive disorders (i.e., Alzheimer's disease, dementia, cognitive decline, and cognitive impairment), and the pooled RR (95% CI) was 0.82 (0.71, 0.94) with evidence of non-significant heterogeneity (I 2  = 25%). Non-significant differences were presented for the association between coffee consumption (>3 vs. <1 cup/d) and incident cognitive disorders. The dose-response analysis showed a "J-shaped" curve relationship of the risk of developing cognitive disorders with coffee consumption. A "J-shaped" association was presented between coffee intake and incident cognitive disorders, with the lowest risk of incident cognitive disorders at a daily consumption level of 1-2 cups of coffee. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Assessing the uncertainty in a normal tissue complication probability difference (∆NTCP): radiation-induced liver disease (RILD) in liver tumour patients treated with proton vs X-ray therapy.

PubMed

Kobashi, Keiji; Prayongrat, Anussara; Kimoto, Takuya; Toramatsu, Chie; Dekura, Yasuhiro; Katoh, Norio; Shimizu, Shinichi; Ito, Yoichi M; Shirato, Hiroki

2018-03-01

Modern radiotherapy technologies such as proton beam therapy (PBT) permit dose escalation to the tumour and minimize unnecessary doses to normal tissues. To achieve appropriate patient selection for PBT, a normal tissue complication probability (NTCP) model can be applied to estimate the risk of treatment-related toxicity relative to X-ray therapy (XRT). A methodology for estimating the difference in NTCP (∆NTCP), including its uncertainty as a function of dose to normal tissue, is described in this study using the Delta method, a statistical method for evaluating the variance of functions, considering the variance-covariance matrix. We used a virtual individual patient dataset of radiation-induced liver disease (RILD) in liver tumour patients who were treated with XRT as a study model. As an alternative option for individual patient data, dose-bin data, which consists of the number of patients who developed toxicity in each dose level/bin and the total number of patients in that dose level/bin, are useful for multi-institutional data sharing. It provides comparable accuracy with individual patient data when using the Delta method. With reliable NTCP models, the ∆NTCP with uncertainty might potentially guide the use of PBT; however, clinical validation and a cost-effectiveness study are needed to determine the appropriate ∆NTCP threshold.

Variance analysis of x-ray CT sinograms in the presence of electronic noise background.

PubMed

Ma, Jianhua; Liang, Zhengrong; Fan, Yi; Liu, Yan; Huang, Jing; Chen, Wufan; Lu, Hongbing

2012-07-01

Low-dose x-ray computed tomography (CT) is clinically desired. Accurate noise modeling is a fundamental issue for low-dose CT image reconstruction via statistics-based sinogram restoration or statistical iterative image reconstruction. In this paper, the authors analyzed the statistical moments of low-dose CT data in the presence of electronic noise background. The authors first studied the statistical moment properties of detected signals in CT transmission domain, where the noise of detected signals is considered as quanta fluctuation upon electronic noise background. Then the authors derived, via the Taylor expansion, a new formula for the mean-variance relationship of the detected signals in CT sinogram domain, wherein the image formation becomes a linear operation between the sinogram data and the unknown image, rather than a nonlinear operation in the CT transmission domain. To get insight into the derived new formula by experiments, an anthropomorphic torso phantom was scanned repeatedly by a commercial CT scanner at five different mAs levels from 100 down to 17. The results demonstrated that the electronic noise background is significant when low-mAs (or low-dose) scan is performed. The influence of the electronic noise background should be considered in low-dose CT imaging.

Variance analysis of x-ray CT sinograms in the presence of electronic noise background

PubMed Central

Ma, Jianhua; Liang, Zhengrong; Fan, Yi; Liu, Yan; Huang, Jing; Chen, Wufan; Lu, Hongbing

2012-01-01

Purpose: Low-dose x-ray computed tomography (CT) is clinically desired. Accurate noise modeling is a fundamental issue for low-dose CT image reconstruction via statistics-based sinogram restoration or statistical iterative image reconstruction. In this paper, the authors analyzed the statistical moments of low-dose CT data in the presence of electronic noise background. Methods: The authors first studied the statistical moment properties of detected signals in CT transmission domain, where the noise of detected signals is considered as quanta fluctuation upon electronic noise background. Then the authors derived, via the Taylor expansion, a new formula for the mean–variance relationship of the detected signals in CT sinogram domain, wherein the image formation becomes a linear operation between the sinogram data and the unknown image, rather than a nonlinear operation in the CT transmission domain. To get insight into the derived new formula by experiments, an anthropomorphic torso phantom was scanned repeatedly by a commercial CT scanner at five different mAs levels from 100 down to 17. Results: The results demonstrated that the electronic noise background is significant when low-mAs (or low-dose) scan is performed. Conclusions: The influence of the electronic noise background should be considered in low-dose CT imaging. PMID:22830738

Integrating mean and variance heterogeneities to identify differentially expressed genes.

PubMed

Ouyang, Weiwei; An, Qiang; Zhao, Jinying; Qin, Huaizhen

2016-12-06

In functional genomics studies, tests on mean heterogeneity have been widely employed to identify differentially expressed genes with distinct mean expression levels under different experimental conditions. Variance heterogeneity (aka, the difference between condition-specific variances) of gene expression levels is simply neglected or calibrated for as an impediment. The mean heterogeneity in the expression level of a gene reflects one aspect of its distribution alteration; and variance heterogeneity induced by condition change may reflect another aspect. Change in condition may alter both mean and some higher-order characteristics of the distributions of expression levels of susceptible genes. In this report, we put forth a conception of mean-variance differentially expressed (MVDE) genes, whose expression means and variances are sensitive to the change in experimental condition. We mathematically proved the null independence of existent mean heterogeneity tests and variance heterogeneity tests. Based on the independence, we proposed an integrative mean-variance test (IMVT) to combine gene-wise mean heterogeneity and variance heterogeneity induced by condition change. The IMVT outperformed its competitors under comprehensive simulations of normality and Laplace settings. For moderate samples, the IMVT well controlled type I error rates, and so did existent mean heterogeneity test (i.e., the Welch t test (WT), the moderated Welch t test (MWT)) and the procedure of separate tests on mean and variance heterogeneities (SMVT), but the likelihood ratio test (LRT) severely inflated type I error rates. In presence of variance heterogeneity, the IMVT appeared noticeably more powerful than all the valid mean heterogeneity tests. Application to the gene profiles of peripheral circulating B raised solid evidence of informative variance heterogeneity. After adjusting for background data structure, the IMVT replicated previous discoveries and identified novel experiment-wide significant MVDE genes. Our results indicate tremendous potential gain of integrating informative variance heterogeneity after adjusting for global confounders and background data structure. The proposed informative integration test better summarizes the impacts of condition change on expression distributions of susceptible genes than do the existent competitors. Therefore, particular attention should be paid to explicitly exploit the variance heterogeneity induced by condition change in functional genomics analysis.

Method for simulating dose reduction in digital mammography using the Anscombe transformation.

PubMed

Borges, Lucas R; Oliveira, Helder C R de; Nunes, Polyana F; Bakic, Predrag R; Maidment, Andrew D A; Vieira, Marcelo A C

2016-06-01

This work proposes an accurate method for simulating dose reduction in digital mammography starting from a clinical image acquired with a standard dose. The method developed in this work consists of scaling a mammogram acquired at the standard radiation dose and adding signal-dependent noise. The algorithm accounts for specific issues relevant in digital mammography images, such as anisotropic noise, spatial variations in pixel gain, and the effect of dose reduction on the detective quantum efficiency. The scaling process takes into account the linearity of the system and the offset of the detector elements. The inserted noise is obtained by acquiring images of a flat-field phantom at the standard radiation dose and at the simulated dose. Using the Anscombe transformation, a relationship is created between the calculated noise mask and the scaled image, resulting in a clinical mammogram with the same noise and gray level characteristics as an image acquired at the lower-radiation dose. The performance of the proposed algorithm was validated using real images acquired with an anthropomorphic breast phantom at four different doses, with five exposures for each dose and 256 nonoverlapping ROIs extracted from each image and with uniform images. The authors simulated lower-dose images and compared these with the real images. The authors evaluated the similarity between the normalized noise power spectrum (NNPS) and power spectrum (PS) of simulated images and real images acquired with the same dose. The maximum relative error was less than 2.5% for every ROI. The added noise was also evaluated by measuring the local variance in the real and simulated images. The relative average error for the local variance was smaller than 1%. A new method is proposed for simulating dose reduction in clinical mammograms. In this method, the dependency between image noise and image signal is addressed using a novel application of the Anscombe transformation. NNPS, PS, and local noise metrics confirm that this method is capable of precisely simulating various dose reductions.

The Role of Rainfall Patterns in Seasonal Malaria Transmission

NASA Astrophysics Data System (ADS)

Bomblies, A.

2010-12-01

Seasonal total precipitation is well known to affect malaria transmission because Anopheles mosquitoes depend on standing water for breeding habitat. However, the within-season temporal pattern of the rainfall influences persistence of standing water and thus rainfall patterns also affect mosquito population dynamics. In this talk, I show that intraseasonal rainfall pattern describes 40% of the variance in simulated mosquito abundance in a Niger Sahel village where malaria is endemic but highly seasonal, demonstrating the necessity for detailed distributed hydrology modeling to explain the variance from this important effect. I apply a field validated, high spatial- and temporal-resolution hydrology model coupled with an entomology model. Using synthetic rainfall time series generated using a stationary first-order Markov Chain model, I hold all variables except hourly rainfall constant, thus isolating the contribution of rainfall pattern to variance in mosquito abundance. I further show the utility of hydrology modeling to assess precipitation effects by analyzing collected water. Time-integrated surface area of pools explains 70% of the variance in mosquito abundance, and time-integrated surface area of pools persisting longer than seven days explains 82% of the variance, showing an improved predictive ability when pool persistence is explicitly modeled at high spatio-temporal resolution. I extend this analysis to investigate the impacts of this effect on malaria vector mosquito populations under climate shift scenarios, holding all climate variables except precipitation constant. In these scenarios, rainfall mean and variance change with climatic change, and the modeling approach evaluates the impact of non-stationarity in rainfall and the associated rainfall patterns on expected mosquito activity.

Effect of contrast leakage on the detection of abnormal brain tumor vasculature in high-grade glioma.

PubMed

LaViolette, Peter S; Daun, Mitchell K; Paulson, Eric S; Schmainda, Kathleen M

2014-02-01

Abnormal brain tumor vasculature has recently been highlighted by a dynamic susceptibility contrast (DSC) MRI processing technique. The technique uses independent component analysis (ICA) to separate arterial and venous perfusion. The overlap of the two, i.e. arterio-venous overlap or AVOL, preferentially occurs in brain tumors and predicts response to anti-angiogenic therapy. The effects of contrast agent leakage on the AVOL biomarker have yet to be established. DSC was acquired during two separate contrast boluses in ten patients undergoing clinical imaging for brain tumor diagnosis. Three components were modeled with ICA, which included the arterial and venous components. The percentage of each component as well as a third component were determined within contrast enhancing tumor and compared. AVOL within enhancing tumor was also compared between doses. The percentage of enhancing tumor classified as not arterial or venous and instead into a third component with contrast agent leakage apparent in the time-series was significantly greater for the first contrast dose compared to the second. The amount of AVOL detected within enhancing tumor was also significantly greater with the second dose compared to the first. Contrast leakage results in large signal variance classified as a separate component by the ICA algorithm. The use of a second dose mitigates the effect and allows measurement of AVOL within enhancement.

Dose-Dependent Effects of Statins for Patients with Aneurysmal Subarachnoid Hemorrhage: Meta-Regression Analysis.

PubMed

To, Minh-Son; Prakash, Shivesh; Poonnoose, Santosh I; Bihari, Shailesh

2018-05-01

The study uses meta-regression analysis to quantify the dose-dependent effects of statin pharmacotherapy on vasospasm, delayed ischemic neurologic deficits (DIND), and mortality in aneurysmal subarachnoid hemorrhage. Prospective, retrospective observational studies, and randomized controlled trials (RCTs) were retrieved by a systematic database search. Summary estimates were expressed as absolute risk (AR) for a given statin dose or control (placebo). Meta-regression using inverse variance weighting and robust variance estimation was performed to assess the effect of statin dose on transformed AR in a random effects model. Dose-dependence of predicted AR with 95% confidence interval (CI) was recovered by using Miller's Freeman-Tukey inverse. The database search and study selection criteria yielded 18 studies (2594 patients) for analysis. These included 12 RCTs, 4 retrospective observational studies, and 2 prospective observational studies. Twelve studies investigated simvastatin, whereas the remaining studies investigated atorvastatin, pravastatin, or pitavastatin, with simvastatin-equivalent doses ranging from 20 to 80 mg. Meta-regression revealed dose-dependent reductions in Freeman-Tukey-transformed AR of vasospasm (slope coefficient -0.00404, 95% CI -0.00720 to -0.00087; P = 0.0321), DIND (slope coefficient -0.00316, 95% CI -0.00586 to -0.00047; P = 0.0392), and mortality (slope coefficient -0.00345, 95% CI -0.00623 to -0.00067; P = 0.0352). The present meta-regression provides weak evidence for dose-dependent reductions in vasospasm, DIND and mortality associated with acute statin use after aneurysmal subarachnoid hemorrhage. However, the analysis was limited by substantial heterogeneity among individual studies. Greater dosing strategies are a potential consideration for future RCTs. Copyright © 2018 Elsevier Inc. All rights reserved.

Evaluation of hyperglycaemic response to intra-operative dexamethasone administration in patients undergoing elective intracranial surgery: A randomised, prospective study.

PubMed

Sethi, Rakesh; Naqash, Imtiaz A; Bajwa, Sukhminder Jit Singh; Dutta, Vikas; Ramzan, Altaf Umar; Zahoor, Syed Amir

2016-01-01

The glucocorticoid dexamethasone in a bolus dose of 8-10 mg followed by quarterly dose of 4 mg is commonly used during intracranial surgery so as to reduce oedema and vascular permeability. However, the detrimental hyperglycaemic effects of dexamethasone may override its potentially beneficial effects. The present prospective, randomised study aimed at comparing the degree and magnitude of hyperglycaemia induced by prophylactic administration of dexamethasone in patients undergoing elective craniotomy. Sixty American Society of Anaesthesiologist (ASA) grade-I and II patients were randomly assigned to three groups of 20 patients each. Group-I received dexamethasone during surgery for the first time. Group-II received dexamethasone in addition to receiving it pre-operatively, whereas Group-III (control group) patients were administered normal saline as placebo. Baseline blood glucose (BG) was measured in all the three groups before induction of anaesthesia and thereafter after every hour for 4 h and then two-hourly. Besides intra- and intergroup comparison of BG, peak BG concentration was also recorded for each patient. Statistical analysis was carried out with analysis of variance (ANOVA) and Student's t-test and value of P < 0.05 was considered statistically significant. Baseline BG reading were higher and statistically significant in Group-II as compared with Group-I and Group-III (P < 0.05). However, peak BG levels were significantly higher in Group-I than in Group-II and III (P < 0.05). Similarly, the magnitude of change in peak BG was significantly higher in Group-I as compared to Group-II and III (P < 0.05). Peri-operative administration of dexamethasone during neurosurgical procedures can cause significant increase in BG concentration especially in patients who receive dexamethasone intra-operatively only.

Evaluation of hyperglycaemic response to intra-operative dexamethasone administration in patients undergoing elective intracranial surgery: A randomised, prospective study

PubMed Central

Sethi, Rakesh; Naqash, Imtiaz A.; Bajwa, Sukhminder Jit Singh; Dutta, Vikas; Ramzan, Altaf Umar; Zahoor, Syed Amir

2016-01-01

Background and Aim: The glucocorticoid dexamethasone in a bolus dose of 8-10 mg followed by quarterly dose of 4 mg is commonly used during intracranial surgery so as to reduce oedema and vascular permeability. However, the detrimental hyperglycaemic effects of dexamethasone may override its potentially beneficial effects. The present prospective, randomised study aimed at comparing the degree and magnitude of hyperglycaemia induced by prophylactic administration of dexamethasone in patients undergoing elective craniotomy. Materials and Methods: Sixty American Society of Anaesthesiologist (ASA) grade-I and II patients were randomly assigned to three groups of 20 patients each. Group-I received dexamethasone during surgery for the first time. Group-II received dexamethasone in addition to receiving it pre-operatively, whereas Group-III (control group) patients were administered normal saline as placebo. Baseline blood glucose (BG) was measured in all the three groups before induction of anaesthesia and thereafter after every hour for 4 h and then two-hourly. Besides intra- and intergroup comparison of BG, peak BG concentration was also recorded for each patient. Statistical analysis was carried out with analysis of variance (ANOVA) and Student's t-test and value of P < 0.05 was considered statistically significant. Results: Baseline BG reading were higher and statistically significant in Group-II as compared with Group-I and Group-III (P < 0.05). However, peak BG levels were significantly higher in Group-I than in Group-II and III (P < 0.05). Similarly, the magnitude of change in peak BG was significantly higher in Group-I as compared to Group-II and III (P < 0.05). Conclusion: Peri-operative administration of dexamethasone during neurosurgical procedures can cause significant increase in BG concentration especially in patients who receive dexamethasone intra-operatively only. PMID:27057213

Integrating Variances into an Analytical Database

NASA Technical Reports Server (NTRS)

Sanchez, Carlos

2010-01-01

For this project, I enrolled in numerous SATERN courses that taught the basics of database programming. These include: Basic Access 2007 Forms, Introduction to Database Systems, Overview of Database Design, and others. My main job was to create an analytical database that can handle many stored forms and make it easy to interpret and organize. Additionally, I helped improve an existing database and populate it with information. These databases were designed to be used with data from Safety Variances and DCR forms. The research consisted of analyzing the database and comparing the data to find out which entries were repeated the most. If an entry happened to be repeated several times in the database, that would mean that the rule or requirement targeted by that variance has been bypassed many times already and so the requirement may not really be needed, but rather should be changed to allow the variance's conditions permanently. This project did not only restrict itself to the design and development of the database system, but also worked on exporting the data from the database to a different format (e.g. Excel or Word) so it could be analyzed in a simpler fashion. Thanks to the change in format, the data was organized in a spreadsheet that made it possible to sort the data by categories or types and helped speed up searches. Once my work with the database was done, the records of variances could be arranged so that they were displayed in numerical order, or one could search for a specific document targeted by the variances and restrict the search to only include variances that modified a specific requirement. A great part that contributed to my learning was SATERN, NASA's resource for education. Thanks to the SATERN online courses I took over the summer, I was able to learn many new things about computers and databases and also go more in depth into topics I already knew about.

On the impact of relatedness on SNP association analysis.

PubMed

Gross, Arnd; Tönjes, Anke; Scholz, Markus

2017-12-06

When testing for SNP (single nucleotide polymorphism) associations in related individuals, observations are not independent. Simple linear regression assuming independent normally distributed residuals results in an increased type I error and the power of the test is also affected in a more complicate manner. Inflation of type I error is often successfully corrected by genomic control. However, this reduces the power of the test when relatedness is of concern. In the present paper, we derive explicit formulae to investigate how heritability and strength of relatedness contribute to variance inflation of the effect estimate of the linear model. Further, we study the consequences of variance inflation on hypothesis testing and compare the results with those of genomic control correction. We apply the developed theory to the publicly available HapMap trio data (N=129), the Sorbs (a self-contained population with N=977 characterised by a cryptic relatedness structure) and synthetic family studies with different sample sizes (ranging from N=129 to N=999) and different degrees of relatedness. We derive explicit and easily to apply approximation formulae to estimate the impact of relatedness on the variance of the effect estimate of the linear regression model. Variance inflation increases with increasing heritability. Relatedness structure also impacts the degree of variance inflation as shown for example family structures. Variance inflation is smallest for HapMap trios, followed by a synthetic family study corresponding to the trio data but with larger sample size than HapMap. Next strongest inflation is observed for the Sorbs, and finally, for a synthetic family study with a more extreme relatedness structure but with similar sample size as the Sorbs. Type I error increases rapidly with increasing inflation. However, for smaller significance levels, power increases with increasing inflation while the opposite holds for larger significance levels. When genomic control is applied, type I error is preserved while power decreases rapidly with increasing variance inflation. Stronger relatedness as well as higher heritability result in increased variance of the effect estimate of simple linear regression analysis. While type I error rates are generally inflated, the behaviour of power is more complex since power can be increased or reduced in dependence on relatedness and the heritability of the phenotype. Genomic control cannot be recommended to deal with inflation due to relatedness. Although it preserves type I error, the loss in power can be considerable. We provide a simple formula for estimating variance inflation given the relatedness structure and the heritability of a trait of interest. As a rule of thumb, variance inflation below 1.05 does not require correction and simple linear regression analysis is still appropriate.

Mammographic film-processor temperature, development time, and chemistry: effect on dose, contrast, and noise.

PubMed

Kimme-Smith, C; Rothschild, P A; Bassett, L W; Gold, R H; Moler, C

1989-01-01

Six different combinations of film-processor temperature (33.3 degrees C, 35 degrees C), development time (22 sec, 44 sec), and chemistry (Du Pont medium contrast developer [MCD] and Kodak rapid process [RP] developer) were each evaluated by separate analyses with Hurter and Driffield curves, test images of plastic step wedges, noise variance analysis, and phantom images; each combination also was evaluated clinically. Du Pont MCD chemistry produced greater contrast than did Kodak RP chemistry. A change in temperature from 33.3 degrees C (92 degrees F) to 35 degrees C (95 degrees F) had the least effect on dose and image contrast. Temperatures of 36.7 degrees C (98 degrees F) and 38.3 degrees C (101 degrees F) also were tested with extended processing. The speed increased for 36.7 degrees C but decreased at 38.3 degrees C. Base plus fog increased, but contrast decreased for these higher temperatures. Increasing development time had the greatest effect on decreasing the dose required for equivalent film darkening when imaging BR12 breast equivalent test objects; ion chamber measurements showed a 32% reduction in dose when the development time was increased from 22 to 44 sec. Although noise variance doubled in images processed with the extended development time, diagnostic capability was not compromised. Extending the processing time for mammographic films was an effective method of dose reduction, whereas varying the processing temperature and chemicals had less effect on contrast and dose.

Genetic variance in micro-environmental sensitivity for milk and milk quality in Walloon Holstein cattle.

PubMed

Vandenplas, J; Bastin, C; Gengler, N; Mulder, H A

2013-09-01

Animals that are robust to environmental changes are desirable in the current dairy industry. Genetic differences in micro-environmental sensitivity can be studied through heterogeneity of residual variance between animals. However, residual variance between animals is usually assumed to be homogeneous in traditional genetic evaluations. The aim of this study was to investigate genetic heterogeneity of residual variance by estimating variance components in residual variance for milk yield, somatic cell score, contents in milk (g/dL) of 2 groups of milk fatty acids (i.e., saturated and unsaturated fatty acids), and the content in milk of one individual fatty acid (i.e., oleic acid, C18:1 cis-9), for first-parity Holstein cows in the Walloon Region of Belgium. A total of 146,027 test-day records from 26,887 cows in 747 herds were available. All cows had at least 3 records and a known sire. These sires had at least 10 cows with records and each herd × test-day had at least 5 cows. The 5 traits were analyzed separately based on fixed lactation curve and random regression test-day models for the mean. Estimation of variance components was performed by running iteratively expectation maximization-REML algorithm by the implementation of double hierarchical generalized linear models. Based on fixed lactation curve test-day mean models, heritability for residual variances ranged between 1.01×10(-3) and 4.17×10(-3) for all traits. The genetic standard deviation in residual variance (i.e., approximately the genetic coefficient of variation of residual variance) ranged between 0.12 and 0.17. Therefore, some genetic variance in micro-environmental sensitivity existed in the Walloon Holstein dairy cattle for the 5 studied traits. The standard deviations due to herd × test-day and permanent environment in residual variance ranged between 0.36 and 0.45 for herd × test-day effect and between 0.55 and 0.97 for permanent environmental effect. Therefore, nongenetic effects also contributed substantially to micro-environmental sensitivity. Addition of random regressions to the mean model did not reduce heterogeneity in residual variance and that genetic heterogeneity of residual variance was not simply an effect of an incomplete mean model. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

SU-E-T-454: Dosimetric Comparison between Pencil Beam and Monte Carlo Algorithms for SBRT Lung Treatment Using IPlan V4.1 TPS and CIRS Thorax Phantom.

PubMed

Fernandez, M Castrillon; Venencia, C; Garrigó, E; Caussa, L

2012-06-01

To compare measured and calculated doses using Pencil Beam (PB) and Monte Carlo (MC) algorithm on a CIRS thorax phantom for SBRT lung treatments. A 6MV photon beam generated by a Primus linac with an Optifocus MLC (Siemens) was used. Dose calculation was done using iPlan v4.1.2 TPS (BrainLAB) by PB and MC (dose to water and dose to medium) algorithms. The commissioning of both algorithms was done reproducing experimental measurements in water. A CIRS thorax phantom was used to compare doses using a Farmer type ion chamber (PTW) and EDR2 radiographic films (KODAK). The ionization chamber, into a tissue equivalent insert, was placed in two position of lung tissue and was irradiated using three treatments plans. Axial dose distributions were measured for four treatments plans using conformal and IMRT technique. Dose distribution comparisons were done by dose profiles and gamma index (3%/3mm). For the studied beam configurations, ion chamber measurements shows that PB overestimate the dose up to 8.5%, whereas MC has a maximum variation of 1.6%. Dosimetric analysis using dose profiles shows that PB overestimates the dose in the region corresponding to the lung up to 16%. For axial dose distribution comparison the percentage of pixels with gamma index bigger than one for MC and PB was, plan 1: 95.6% versus 87.4%, plan 2: 91.2% versus 77.6%, plan 3: 99.7% versus 93.1% and for plan 4: 98.8% versus 91.7%. It was confirmed that the lower dosimetric errors calculated applying MC algorithm appears when the spatial resolution and variance decrease at the expense of increased computation time. The agreement between measured and calculated doses, in a phantom with lung heterogeneities, is better with MC algorithm. PB algorithm overestimates the doses in lung tissue, which could have a clinical impact in SBRT lung treatments. © 2012 American Association of Physicists in Medicine.

SU-E-T-135: Investigation of Commercial-Grade Flatbed Scanners and a Medical- Grade Scanner for Radiochromic EBT Film Dosimetry.

PubMed

Syh, J; Patel, B; Syh, J; Wu, H; Rosen, L; Durci, M; Katz, S; Sibata, C

2012-06-01

To evaluate the characteristics of commercial-grade flatbed scanners and medical-grade scanners for radiochromic EBT film dosimetry. Performance aspects of a Vidar Dosimetry Pro Advantage (Red), Epson 750 Pro, Microtek ArtixScan 1800f, and Microtek ScanMaker 8700 scanner for EBT2 Gafchromic film were evaluated in the categories of repeatability, maximum distinguishable optical density (OD) differentiation, OD variance, and dose curve characteristics. OD step film by Stouffer Industries containing 31 steps ranging from 0.05 to 3.62 OD was used. EBT films were irradiated with dose ranging from 20 to 600 cGy in 6×6 cm 2 field sizes and analyzed 24 hours later using RIT113 and Tomotherapy Film Analyzer software. Scans were performed in transmissive mode, landscape orientation, 16-bit image. The mean and standard deviation Analog to Digital (A/D) scanner value was measured by selecting a 3×3 mm 2 uniform area in the central region of each OD step from a total of 20 scans performed over several weeks. Repeatability was determined from the variance of OD step 0.38. Maximum distinguishable OD was defined as the last OD step whose range of A/D values does not overlap with its neighboring step. Repeatability uncertainty ranged from 0.1% for Vidar to 4% for Epson. Average standard deviation of OD steps ranged from 0.21% for Vidar to 6.4% for ArtixScan 1800f. Maximum distinguishable optical density ranged from 3.38 for Vidar to 1.32 for ScanMaker 8700. A/D range of each OD step corresponds to a dose range. Dose ranges of OD steps varied from 1% for Vidar to 20% for ScanMaker 8700. The Vidar exhibited a dose curve that utilized a broader range of OD values than the other scanners. Vidar exhibited higher maximum distinguishable OD, smaller variance in repeatability, smaller A/D value deviation per OD step, and a shallower dose curve with respect to OD. © 2012 American Association of Physicists in Medicine.

Feasibility Study for Design of a Biocybernetic Communication System

DTIC Science & Technology

1975-08-01

electrode for the Within Words variance and Between Words variance for each of the 255 data samples in the 6-sec epoch. If a given sample point was not...contributing to the computer classification of the word, the ratio of the two variances (i.e., the F-statistic) should be small. On the other hand...if the Between Word variance was signifi- cantly higher than the Within Word variance for a given sample point, we can assume with some confidence

Variability in CT lung-nodule quantification: Effects of dose reduction and reconstruction methods on density and texture based features.

PubMed

Lo, P; Young, S; Kim, H J; Brown, M S; McNitt-Gray, M F

2016-08-01

To investigate the effects of dose level and reconstruction method on density and texture based features computed from CT lung nodules. This study had two major components. In the first component, a uniform water phantom was scanned at three dose levels and images were reconstructed using four conventional filtered backprojection (FBP) and four iterative reconstruction (IR) methods for a total of 24 different combinations of acquisition and reconstruction conditions. In the second component, raw projection (sinogram) data were obtained for 33 lung nodules from patients scanned as a part of their clinical practice, where low dose acquisitions were simulated by adding noise to sinograms acquired at clinical dose levels (a total of four dose levels) and reconstructed using one FBP kernel and two IR kernels for a total of 12 conditions. For the water phantom, spherical regions of interest (ROIs) were created at multiple locations within the water phantom on one reference image obtained at a reference condition. For the lung nodule cases, the ROI of each nodule was contoured semiautomatically (with manual editing) from images obtained at a reference condition. All ROIs were applied to their corresponding images reconstructed at different conditions. For 17 of the nodule cases, repeat contours were performed to assess repeatability. Histogram (eight features) and gray level co-occurrence matrix (GLCM) based texture features (34 features) were computed for all ROIs. For the lung nodule cases, the reference condition was selected to be 100% of clinical dose with FBP reconstruction using the B45f kernel; feature values calculated from other conditions were compared to this reference condition. A measure was introduced, which the authors refer to as Q, to assess the stability of features across different conditions, which is defined as the ratio of reproducibility (across conditions) to repeatability (across repeat contours) of each feature. The water phantom results demonstrated substantial variability among feature values calculated across conditions, with the exception of histogram mean. Features calculated from lung nodules demonstrated similar results with histogram mean as the most robust feature (Q ≤ 1), having a mean and standard deviation Q of 0.37 and 0.22, respectively. Surprisingly, histogram standard deviation and variance features were also quite robust. Some GLCM features were also quite robust across conditions, namely, diff. variance, sum variance, sum average, variance, and mean. Except for histogram mean, all features have a Q of larger than one in at least one of the 3% dose level conditions. As expected, the histogram mean is the most robust feature in their study. The effects of acquisition and reconstruction conditions on GLCM features vary widely, though trending toward features involving summation of product between intensities and probabilities being more robust, barring a few exceptions. Overall, care should be taken into account for variation in density and texture features if a variety of dose and reconstruction conditions are used for the quantification of lung nodules in CT, otherwise changes in quantification results may be more reflective of changes due to acquisition and reconstruction conditions than in the nodule itself.

ORANGE: a Monte Carlo dose engine for radiotherapy.

PubMed

van der Zee, W; Hogenbirk, A; van der Marck, S C

2005-02-21

This study presents data for the verification of ORANGE, a fast MCNP-based dose engine for radiotherapy treatment planning. In order to verify the new algorithm, it has been benchmarked against DOSXYZ and against measurements. For the benchmarking, first calculations have been done using the ICCR-XIII benchmark. Next, calculations have been done with DOSXYZ and ORANGE in five different phantoms (one homogeneous, two with bone equivalent inserts and two with lung equivalent inserts). The calculations have been done with two mono-energetic photon beams (2 MeV and 6 MeV) and two mono-energetic electron beams (10 MeV and 20 MeV). Comparison of the calculated data (from DOSXYZ and ORANGE) against measurements was possible for a realistic 10 MV photon beam and a realistic 15 MeV electron beam in a homogeneous phantom only. For the comparison of the calculated dose distributions and dose distributions against measurements, the concept of the confidence limit (CL) has been used. This concept reduces the difference between two data sets to a single number, which gives the deviation for 90% of the dose distributions. Using this concept, it was found that ORANGE was always within the statistical bandwidth with DOSXYZ and the measurements. The ICCR-XIII benchmark showed that ORANGE is seven times faster than DOSXYZ, a result comparable with other accelerated Monte Carlo dose systems when no variance reduction is used. As shown for XVMC, using variance reduction techniques has the potential for further acceleration. Using modern computer hardware, this brings the total calculation time for a dose distribution with 1.5% (statistical) accuracy within the clinical range (less then 10 min). This means that ORANGE can be a candidate for a dose engine in radiotherapy treatment planning.

Fast patient-specific Monte Carlo brachytherapy dose calculations via the correlated sampling variance reduction technique

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

Sampson, Andrew; Le Yi; Williamson, Jeffrey F.

2012-02-15

Purpose: To demonstrate potential of correlated sampling Monte Carlo (CMC) simulation to improve the calculation efficiency for permanent seed brachytherapy (PSB) implants without loss of accuracy. Methods: CMC was implemented within an in-house MC code family (PTRAN) and used to compute 3D dose distributions for two patient cases: a clinical PSB postimplant prostate CT imaging study and a simulated post lumpectomy breast PSB implant planned on a screening dedicated breast cone-beam CT patient exam. CMC tallies the dose difference, {Delta}D, between highly correlated histories in homogeneous and heterogeneous geometries. The heterogeneous geometry histories were derived from photon collisions sampled inmore » a geometrically identical but purely homogeneous medium geometry, by altering their particle weights to correct for bias. The prostate case consisted of 78 Model-6711 {sup 125}I seeds. The breast case consisted of 87 Model-200 {sup 103}Pd seeds embedded around a simulated lumpectomy cavity. Systematic and random errors in CMC were unfolded using low-uncertainty uncorrelated MC (UMC) as the benchmark. CMC efficiency gains, relative to UMC, were computed for all voxels, and the mean was classified in regions that received minimum doses greater than 20%, 50%, and 90% of D{sub 90}, as well as for various anatomical regions. Results: Systematic errors in CMC relative to UMC were less than 0.6% for 99% of the voxels and 0.04% for 100% of the voxels for the prostate and breast cases, respectively. For a 1 x 1 x 1 mm{sup 3} dose grid, efficiency gains were realized in all structures with 38.1- and 59.8-fold average gains within the prostate and breast clinical target volumes (CTVs), respectively. Greater than 99% of the voxels within the prostate and breast CTVs experienced an efficiency gain. Additionally, it was shown that efficiency losses were confined to low dose regions while the largest gains were located where little difference exists between the homogeneous and heterogeneous doses. On an AMD 1090T processor, computing times of 38 and 21 sec were required to achieve an average statistical uncertainty of 2% within the prostate (1 x 1 x 1 mm{sup 3}) and breast (0.67 x 0.67 x 0.8 mm{sup 3}) CTVs, respectively. Conclusions: CMC supports an additional average 38-60 fold improvement in average efficiency relative to conventional uncorrelated MC techniques, although some voxels experience no gain or even efficiency losses. However, for the two investigated case studies, the maximum variance within clinically significant structures was always reduced (on average by a factor of 6) in the therapeutic dose range generally. CMC takes only seconds to produce an accurate, high-resolution, low-uncertainly dose distribution for the low-energy PSB implants investigated in this study.« less

Dose range finding study for the efficacy of meloxicam administered prior to sodium urate-induced synovitis in cats.

PubMed

Carroll, Gwendolyn L; Narbe, Ruediger; Kerwin, Sharon C; Taylor, Lathrop; Peterson, Kurt; Hartsfield, Sandee M

2011-07-01

To determine the lowest efficacious dose of oral meloxicam for relieving pain in cats with a sodium urate (SU)-induced acute inflammatory synovitis. Randomized, blinded, controlled, and four-way crossover study. Eight surgically neutered cats (four males, four females) paired according to sex. Each pair of cats was treated with 0 (placebo), 0.025, 0.05, or 0.075 mg kg(-1) oral meloxicam once daily for 4 days prior to injection, into alternating stifles, of 1 mL of 20 mg mL(-1) SU crystals, beginning with the right stifle. Each cat received each of the four treatments, separated by at least 21 days. Analgesic efficacy was evaluated based on objective (e.g., pressure mat data total force, contact pressure, and contact area) and subjective (e.g., scores for Analgesia Scale [AS], Lameness Scale [LS], and Visual Analog Scale [VAS]) outcome measures for pain assessment. All outcome measures were recorded before and during 30 hours after SU injection. The pre-defined primary outcome measure was the area under the response-time curve (AUC(0-30) hours) of the total force of the injected limb. Data were analyzed by analysis of variance. A sequential test procedure was applied and the test sequence stopped in case of a nonsignificant result. Meloxicam at doses of 0.05 and 0.075 mg kg(-1) day(-1) PO was significantly different from placebo for the pre-defined primary outcome measure (i.e., AUC(0-30) hours of total force). All tested meloxicam doses were lower than placebo for the subjective outcome measures (i.e., AUC(0-30) hours of AS, LS, and VAS). The lowest efficacious dose of meloxicam for relieving pain in cats with an SU-induced synovitis was 0.05 mg kg(-1) day(-1) PO according to the pre-defined primary outcome measure. However, lower doses may also be effective as seen in the subjective outcome measures. © 2011 The Authors. Veterinary Anaesthesia and Analgesia. © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Optimal dose of combined rocuronium and cisatracurium during minor surgery

PubMed Central

Park, Woo Young; Choi, Jae Chan; Yun, Hey Jeong; Jeon, Yeong Gwan; Park, Gisoon; Choi, Jong Bum

2018-01-01

Abstract Background: Combined rocuronium and cisatracurium have synergistic effects. We investigated whether reduced doses are effective during coadministration, by monitoring neuromuscular relaxation during surgery. Methods: This randomized, controlled clinical trial was registered at http://clinicaltrials.gov (registration number NCT02495038). The participants were 81 patients scheduled for elective mastoidectomy and tympanoplasty. Participants were assigned to groups, including the intubating dose group (Group I, n = 27; combined ED95 rocuronium and ED95 cisatracurium), the small reduction group (Group S, n = 27; dose reduced by 10% of each ED95), or the large reduction group (Group L, n = 27; dose reduced by 20% of each ED95). Drugs were administered to patients and a timer was started using TOF-Watch monitoring. TOF (train-of-four) was monitored at the ulnar nerve, at a setting of 2 Hz/12 s. We recorded the time to TOF ratio = 0 (onset), time to first TOF ratio > 25% (duration 25%), and TOF 25–75% (recovery index) under total intravenous anesthesia. One-way analysis of variance was used for statistical analyses (α = 0.05, β = 0.2). Results: There were no significant demographic differences between groups. Group L had a longer duration to onset (mean ± standard deviation, 399.3 ± 147.8 seconds) and shorter duration 25% (39.4 ± 6.8 minutes) compared to Group I (212.8 ± 56.0 s and 51.3 ± 8.47 minutes, respectively) and Group S (230.7 ± 60.6 s and 47.9 ± 10.7 minutes, respectively). There were no other significant differences between groups. Conclusion: Our findings contribute to determining clinically effective combinations of rocuronium and cisatracurium, as well as to predicting the pharmacokinetic characteristics of the synergistic effects. We suggest that reducing doses of both drugs by approximately 10% of their respective ED95 values is sufficient to maintain neuromuscular relaxation during minor surgery. PMID:29517695

Multiple indicators, multiple causes measurement error models

DOE PAGES

Tekwe, Carmen D.; Carter, Randy L.; Cullings, Harry M.; ...

2014-06-25

Multiple indicators, multiple causes (MIMIC) models are often employed by researchers studying the effects of an unobservable latent variable on a set of outcomes, when causes of the latent variable are observed. There are times, however, when the causes of the latent variable are not observed because measurements of the causal variable are contaminated by measurement error. The objectives of this study are as follows: (i) to develop a novel model by extending the classical linear MIMIC model to allow both Berkson and classical measurement errors, defining the MIMIC measurement error (MIMIC ME) model; (ii) to develop likelihood-based estimation methodsmore » for the MIMIC ME model; and (iii) to apply the newly defined MIMIC ME model to atomic bomb survivor data to study the impact of dyslipidemia and radiation dose on the physical manifestations of dyslipidemia. Finally, as a by-product of our work, we also obtain a data-driven estimate of the variance of the classical measurement error associated with an estimate of the amount of radiation dose received by atomic bomb survivors at the time of their exposure.« less

Multiple indicators, multiple causes measurement error models

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

Tekwe, Carmen D.; Carter, Randy L.; Cullings, Harry M.

Multiple indicators, multiple causes (MIMIC) models are often employed by researchers studying the effects of an unobservable latent variable on a set of outcomes, when causes of the latent variable are observed. There are times, however, when the causes of the latent variable are not observed because measurements of the causal variable are contaminated by measurement error. The objectives of this study are as follows: (i) to develop a novel model by extending the classical linear MIMIC model to allow both Berkson and classical measurement errors, defining the MIMIC measurement error (MIMIC ME) model; (ii) to develop likelihood-based estimation methodsmore » for the MIMIC ME model; and (iii) to apply the newly defined MIMIC ME model to atomic bomb survivor data to study the impact of dyslipidemia and radiation dose on the physical manifestations of dyslipidemia. Finally, as a by-product of our work, we also obtain a data-driven estimate of the variance of the classical measurement error associated with an estimate of the amount of radiation dose received by atomic bomb survivors at the time of their exposure.« less

Prediction of the Pharmacokinetic Parameters of Triptolide in Rats Based on Endogenous Molecules in Pre-Dose Baseline Serum

PubMed Central

Aa, Jiye; Zheng, Tian; Shi, Jian; Li, Mengjie; Wang, Xinwen; Zhao, Chunyan; Xiao, Wenjing; Yu, Xiaoyi; Sun, Runbin; Gu, Rongrong; Zhou, Jun; Wu, Liang; Hao, Gang; Zhu, Xuanxuan; Wang, Guangji

2012-01-01

Background Individual variances usually affect drug metabolism and disposition, and hence result in either ineffectiveness or toxicity of a drug. In addition to genetic polymorphism, the multiple confounding factors of lifestyles, such as dietary preferences, contribute partially to individual variances. However, the difficulty of quantifying individual diversity greatly challenges the realization of individualized drug therapy. This study aims at quantitative evaluating the association between individual variances and the pharmacokinetics. Methodology/Principal Findings Molecules in pre-dose baseline serum were profiled using gas chromatography mass spectrometry to represent the individual variances of the model rats provided with high fat diets (HFD), routine chows and calorie restricted (CR) chows. Triptolide and its metabolites were determined using high performance liquid chromatography mass spectrometry. Metabonomic and pharmacokinetic data revealed that rats treated with the varied diets had distinctly different metabolic patterns and showed differential Cmax values, AUC and drug metabolism after oral administration of triptolide. Rats with fatty chows had the lowest Cmax and AUC values and the highest percentage of triptolide metabolic transformation, while rats with CR chows had the highest Cmax and AUC values and the least percentage of triptolide transformation. Multivariate linear regression revealed that in baseline serum, the concentrations of creatinine and glutamic acid, which is the precursor of GSH, were linearly negatively correlated to Cmax and AUC values. The glutamic acid and creatinine in baseline serum were suggested as the potential markers to represent individual diversity and as predictors of the disposal and pharmacokinetics of triptolide. Conclusions/Significance These results highlight the robust potential of metabonomics in characterizing individual variances and identifying relevant markers that have the potential to facilitate individualized drug therapy. PMID:22912866

Shifting patterns of variance in adolescent alcohol use: Testing consumption as a developing trait-state.

PubMed

Nealis, Logan J; Thompson, Kara D; Krank, Marvin D; Stewart, Sherry H

2016-04-01

While average rates of change in adolescent alcohol consumption are frequently studied, variability arising from situational and dispositional influences on alcohol use has been comparatively neglected. We used variance decomposition to test differences in variability resulting from year-to-year fluctuations in use (i.e., state-like) and from stable individual differences (i.e., trait-like) using data from the Project on Adolescent Trajectories and Health (PATH), a cohort-sequential study spanning grades 7 to 11 using three cohorts starting in grades seven, eight, and nine, respectively. We tested variance components for alcohol volume, frequency, and quantity in the overall sample, and changes in components over time within each cohort. Sex differences were tested. Most variability in alcohol use reflected state-like variation (47-76%), with a relatively smaller proportion of trait-like variation (19-36%). These proportions shifted across cohorts as youth got older, with increases in trait-like variance from early adolescence (14-30%) to later adolescence (30-50%). Trends were similar for males and females, although females showed higher trait-like variance in alcohol frequency than males throughout development (26-43% vs. 11-25%). For alcohol volume and frequency, males showed the greatest increase in trait-like variance earlier in development (i.e., grades 8-10) compared to females (i.e., grades 9-11). The relative strength of situational and dispositional influences on adolescent alcohol use has important implications for preventative interventions. Interventions should ideally target problematic alcohol use before it becomes more ingrained and trait-like. Copyright © 2015 Elsevier Ltd. All rights reserved.

Doses to Carotid Arteries After Modern Radiation Therapy for Hodgkin Lymphoma: Is Stroke Still a Late Effect of Treatment?

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

Maraldo, Maja V., E-mail: dra.maraldo@gmail.com; Brodin, Patrick; Aznar, Marianne C.

2013-10-01

Purpose: Hodgkin lymphoma (HL) survivors are at an increased risk of stroke because of carotid artery irradiation. However, for early-stage HL involved node radiation therapy (INRT) reduces the volume of normal tissue exposed to high doses. Here, we evaluate 3-dimensional conformal radiation therapy (3D-CRT), volumetric-modulated arc therapy (VMAT), and proton therapy (PT) delivered as INRT along with the extensive mantle field (MF) by comparing doses to the carotid arteries and corresponding risk estimates. Methods and Materials: We included a cohort of 46 supradiaphragmatic stage I-II classical HL patients. All patients were initially treated with chemotherapy and INRT delivered as 3D-CRTmore » (30 Gy). For each patient, we simulated MF (36 Gy) and INRT plans using VMAT and PT (30 Gy). Linear dose-response curves for the 20-, 25-, and 30-year risk of stroke were derived from published HL data. Risks of stroke with each technique were calculated for all patients. Statistical analyses were performed with repeated measures analysis of variance. Results: The mean doses to the right and left common carotid artery were significantly lower with modern treatment compared with MF, with substantial patient variability. The estimated excess risk of stroke after 20, 25, and 30 years was 0.6%, 0.86%, and 1.3% for 3D-CRT; 0.67%, 0.96%, and 1.47% for VMAT; 0.61%, 0.96%, and 1.33% for PT; and 1.3%, 1.72%, and 2.61% for MF. Conclusions: INRT reduces the dose delivered to the carotid arteries and corresponding estimated risk of stroke for HL survivors. Even for the subset of patients with lymphoma close to the carotid arteries, the estimated risk is low.« less

Method for simulating dose reduction in digital mammography using the Anscombe transformation

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

Borges, Lucas R., E-mail: lucas.rodrigues.borges@usp.br; Oliveira, Helder C. R. de; Nunes, Polyana F.

2016-06-15

Purpose: This work proposes an accurate method for simulating dose reduction in digital mammography starting from a clinical image acquired with a standard dose. Methods: The method developed in this work consists of scaling a mammogram acquired at the standard radiation dose and adding signal-dependent noise. The algorithm accounts for specific issues relevant in digital mammography images, such as anisotropic noise, spatial variations in pixel gain, and the effect of dose reduction on the detective quantum efficiency. The scaling process takes into account the linearity of the system and the offset of the detector elements. The inserted noise is obtainedmore » by acquiring images of a flat-field phantom at the standard radiation dose and at the simulated dose. Using the Anscombe transformation, a relationship is created between the calculated noise mask and the scaled image, resulting in a clinical mammogram with the same noise and gray level characteristics as an image acquired at the lower-radiation dose. Results: The performance of the proposed algorithm was validated using real images acquired with an anthropomorphic breast phantom at four different doses, with five exposures for each dose and 256 nonoverlapping ROIs extracted from each image and with uniform images. The authors simulated lower-dose images and compared these with the real images. The authors evaluated the similarity between the normalized noise power spectrum (NNPS) and power spectrum (PS) of simulated images and real images acquired with the same dose. The maximum relative error was less than 2.5% for every ROI. The added noise was also evaluated by measuring the local variance in the real and simulated images. The relative average error for the local variance was smaller than 1%. Conclusions: A new method is proposed for simulating dose reduction in clinical mammograms. In this method, the dependency between image noise and image signal is addressed using a novel application of the Anscombe transformation. NNPS, PS, and local noise metrics confirm that this method is capable of precisely simulating various dose reductions.« less

Method for simulating dose reduction in digital mammography using the Anscombe transformation

PubMed Central

Borges, Lucas R.; de Oliveira, Helder C. R.; Nunes, Polyana F.; Bakic, Predrag R.; Maidment, Andrew D. A.; Vieira, Marcelo A. C.

2016-01-01

Purpose: This work proposes an accurate method for simulating dose reduction in digital mammography starting from a clinical image acquired with a standard dose. Methods: The method developed in this work consists of scaling a mammogram acquired at the standard radiation dose and adding signal-dependent noise. The algorithm accounts for specific issues relevant in digital mammography images, such as anisotropic noise, spatial variations in pixel gain, and the effect of dose reduction on the detective quantum efficiency. The scaling process takes into account the linearity of the system and the offset of the detector elements. The inserted noise is obtained by acquiring images of a flat-field phantom at the standard radiation dose and at the simulated dose. Using the Anscombe transformation, a relationship is created between the calculated noise mask and the scaled image, resulting in a clinical mammogram with the same noise and gray level characteristics as an image acquired at the lower-radiation dose. Results: The performance of the proposed algorithm was validated using real images acquired with an anthropomorphic breast phantom at four different doses, with five exposures for each dose and 256 nonoverlapping ROIs extracted from each image and with uniform images. The authors simulated lower-dose images and compared these with the real images. The authors evaluated the similarity between the normalized noise power spectrum (NNPS) and power spectrum (PS) of simulated images and real images acquired with the same dose. The maximum relative error was less than 2.5% for every ROI. The added noise was also evaluated by measuring the local variance in the real and simulated images. The relative average error for the local variance was smaller than 1%. Conclusions: A new method is proposed for simulating dose reduction in clinical mammograms. In this method, the dependency between image noise and image signal is addressed using a novel application of the Anscombe transformation. NNPS, PS, and local noise metrics confirm that this method is capable of precisely simulating various dose reductions. PMID:27277017

SU-E-T-287: Patterns of Patient Specific Dosimetry in Total Body Irradiation.

PubMed

Akino, Y; McMullen, K; Das, I

2012-06-01

Total body irradiation (TBI) is commonly used for conditioning prior to transplant in hematologic and immunologic diseases. Due to variability in body thickness, achieving dose uniformity across body within ±10% of the prescribed dose is challenging. The dose uniformity is further complicated by, techniques and beam energy used, lung shielding and selection of detector. The translational table technique for TBI could compensate for estimated delivered dose to whole body by adjusting couch speed during treatment. However, it is difficult to accurately estimate the dose by calculation and hence in vivo dosimetry (IVD) is routinely performed for TBI. The patterns of patient specific dosimetry, IVD are presented in this study. Under IRB exempt status, 161 patients who received TBI treatment between 2006 and 2011 were retrospectively analyzed using the treatment records from Cobalt-60 teletherapy unit and translational treatment couch. During treatment, IVD detectors (TLD, diode, or MOSFET) were placed on patient surface; both entrance and exit dose were recorded at the patient's head, neck, mediastinum, umbilicus, and knee. When large differences between prescribed and measured dose were observed, the dose delivery was corrected for subsequent fractions by adjustment in couch speed and/or bolus placement. Across the entire cohort, the mean (range) percent variance between calculated and measured dose were -2.3% (-66.2 - 35.3), 1.1% (-62.2 - 40.3), -1.9% (-66.4 - 46.6), -1.1% (-35.2 - 42.9), and 3.4% (-47.9 - 108.5) for head, neck, mediastinum, umbilicus, and knee, respectively. When the dose differences for multiple fractions were averaged, the compliance (±10%) between prescription and measured dose was improved as at umbilicus from 83.9% to 98.5%. Actual dose measurement analysis of TBI patients reveals a potentially wide variance from calculated dose. Dose uniformity can be significantly improved with immediate feedback after the first fraction prior to subsequent treatments. This work was supported by the JSPS Core-to-Core Program No. 23003. © 2012 American Association of Physicists in Medicine.

Choice in experiential learning: True preferences or experimental artifacts?

PubMed

Ashby, Nathaniel J S; Konstantinidis, Emmanouil; Yechiam, Eldad

2017-03-01

The rate of selecting different options in the decisions-from-feedback paradigm is commonly used to measure preferences resulting from experiential learning. While convergence to a single option increases with experience, some variance in choice remains even when options are static and offer fixed rewards. Employing a decisions-from-feedback paradigm followed by a policy-setting task, we examined whether the observed variance in choice is driven by factors related to the paradigm itself: Continued exploration (e.g., believing options are non-stationary) or exploitation of perceived outcome patterns (i.e., a belief that sequential choices are not independent). Across two studies, participants showed variance in their choices, which was related (i.e., proportional) to the policies they set. In addition, in Study 2, participants' reported under-confidence was associated with the amount of choice variance in later choices and policies. These results suggest that variance in choice is better explained by participants lacking confidence in knowing which option is better, rather than methodological artifacts (i.e., exploration or failures to recognize outcome independence). As such, the current studies provide evidence for the decisions-from-feedback paradigm's validity as a behavioral research method for assessing learned preferences. Copyright © 2017 Elsevier B.V. All rights reserved.

The Impact of Acquisition Dose on Quantitative Breast Density Estimation with Digital Mammography: Results from ACRIN PA 4006.

PubMed

Chen, Lin; Ray, Shonket; Keller, Brad M; Pertuz, Said; McDonald, Elizabeth S; Conant, Emily F; Kontos, Despina

2016-09-01

Purpose To investigate the impact of radiation dose on breast density estimation in digital mammography. Materials and Methods With institutional review board approval and Health Insurance Portability and Accountability Act compliance under waiver of consent, a cohort of women from the American College of Radiology Imaging Network Pennsylvania 4006 trial was retrospectively analyzed. All patients underwent breast screening with a combination of dose protocols, including standard full-field digital mammography, low-dose digital mammography, and digital breast tomosynthesis. A total of 5832 images from 486 women were analyzed with previously validated, fully automated software for quantitative estimation of density. Clinical Breast Imaging Reporting and Data System (BI-RADS) density assessment results were also available from the trial reports. The influence of image acquisition radiation dose on quantitative breast density estimation was investigated with analysis of variance and linear regression. Pairwise comparisons of density estimations at different dose levels were performed with Student t test. Agreement of estimation was evaluated with quartile-weighted Cohen kappa values and Bland-Altman limits of agreement. Results Radiation dose of image acquisition did not significantly affect quantitative density measurements (analysis of variance, P = .37 to P = .75), with percent density demonstrating a high overall correlation between protocols (r = 0.88-0.95; weighted κ = 0.83-0.90). However, differences in breast percent density (1.04% and 3.84%, P < .05) were observed within high BI-RADS density categories, although they were significantly correlated across the different acquisition dose levels (r = 0.76-0.92, P < .05). Conclusion Precision and reproducibility of automated breast density measurements with digital mammography are not substantially affected by variations in radiation dose; thus, the use of low-dose techniques for the purpose of density estimation may be feasible. (©) RSNA, 2016 Online supplemental material is available for this article.

The Impact of Acquisition Dose on Quantitative Breast Density Estimation with Digital Mammography: Results from ACRIN PA 4006

PubMed Central

Chen, Lin; Ray, Shonket; Keller, Brad M.; Pertuz, Said; McDonald, Elizabeth S.; Conant, Emily F.

2016-01-01

Purpose To investigate the impact of radiation dose on breast density estimation in digital mammography. Materials and Methods With institutional review board approval and Health Insurance Portability and Accountability Act compliance under waiver of consent, a cohort of women from the American College of Radiology Imaging Network Pennsylvania 4006 trial was retrospectively analyzed. All patients underwent breast screening with a combination of dose protocols, including standard full-field digital mammography, low-dose digital mammography, and digital breast tomosynthesis. A total of 5832 images from 486 women were analyzed with previously validated, fully automated software for quantitative estimation of density. Clinical Breast Imaging Reporting and Data System (BI-RADS) density assessment results were also available from the trial reports. The influence of image acquisition radiation dose on quantitative breast density estimation was investigated with analysis of variance and linear regression. Pairwise comparisons of density estimations at different dose levels were performed with Student t test. Agreement of estimation was evaluated with quartile-weighted Cohen kappa values and Bland-Altman limits of agreement. Results Radiation dose of image acquisition did not significantly affect quantitative density measurements (analysis of variance, P = .37 to P = .75), with percent density demonstrating a high overall correlation between protocols (r = 0.88–0.95; weighted κ = 0.83–0.90). However, differences in breast percent density (1.04% and 3.84%, P < .05) were observed within high BI-RADS density categories, although they were significantly correlated across the different acquisition dose levels (r = 0.76–0.92, P < .05). Conclusion Precision and reproducibility of automated breast density measurements with digital mammography are not substantially affected by variations in radiation dose; thus, the use of low-dose techniques for the purpose of density estimation may be feasible. © RSNA, 2016 Online supplemental material is available for this article. PMID:27002418

Gender Performance Differences in Biochemistry

ERIC Educational Resources Information Center

Rauschenberger, Matthew M.; Sweeder, Ryan D.

2010-01-01

This study examined the historical performance of students at Michigan State University in a two-part biochemistry series Biochem I (n = 5,900) and Biochem II (n = 5,214) for students enrolled from 1997 to 2009. Multiple linear regressions predicted 54.9-87.5% of the variance in student from Biochem I grade and 53.8-76.1% of the variance in…

The Genealogical Consequences of Fecundity Variance Polymorphism

PubMed Central

Taylor, Jesse E.

2009-01-01

The genealogical consequences of within-generation fecundity variance polymorphism are studied using coalescent processes structured by genetic backgrounds. I show that these processes have three distinctive features. The first is that the coalescent rates within backgrounds are not jointly proportional to the infinitesimal variance, but instead depend only on the frequencies and traits of genotypes containing each allele. Second, the coalescent processes at unlinked loci are correlated with the genealogy at the selected locus; i.e., fecundity variance polymorphism has a genomewide impact on genealogies. Third, in diploid models, there are infinitely many combinations of fecundity distributions that have the same diffusion approximation but distinct coalescent processes; i.e., in this class of models, ancestral processes and allele frequency dynamics are not in one-to-one correspondence. Similar properties are expected to hold in models that allow for heritable variation in other traits that affect the coalescent effective population size, such as sex ratio or fecundity and survival schedules. PMID:19433628

’Exact’ Two-Sided Confidence Intervals on Nonnegative Linear Combinations of Variances.

DTIC Science & Technology

1980-07-01

Colorado State University ( 042_402) II. CONTrOLLING OFFICE NAME AND ADDRESS It. REPORT OAT Office of Naval Rsearch -// 1 Jul MjW80 Statistics and...MONNEGATIVE LINEAR COMBINATIONS OF VARIANCES by Franklin A. Graybill Colorado State University and Chih-Ming Wang SPSS Inc. 1. Introduction In a paper to soon...1 + a2’ called the Nodf Led Lace Sample (HLS) confidence interval, is in 2. Aoce-3Ion For DDC TAO u*.- *- -. n c edI Ju.-’I if iction_, i !~BV . . I

Influence of monte carlo variance with fluence smoothing in VMAT treatment planning with Monaco TPS.

PubMed

Sarkar, B; Manikandan, A; Nandy, M; Munshi, A; Sayan, P; Sujatha, N

2016-01-01

The study aimed to investigate the interplay between Monte Carlo Variance (MCV) and fluence smoothing factor (FSF) in volumetric modulated arc therapy treatment planning by using a sample set of complex treatment planning cases and a X-ray Voxel Monte Carlo-based treatment planning system equipped with tools to tune fluence smoothness as well as MCV. The dosimetric (dose to tumor volume, and organ at risk) and physical characteristic (treatment time, number of segments, and so on) of a set 45 treatment plans for all combinations of 1%, 3%, 5% MCV and 1, 3, 5 FSF were evaluated for five carcinoma esophagus cases under the study. Increase in FSF reduce the treatment time. Variation of MCV and FSF gives a highest planning target volume (PTV), heart and lung dose variation of 3.6%, 12.8% and 4.3%, respectively. The heart dose variation was highest among all organs at risk. Highest variation of spinal cord dose was 0.6 Gy. Variation of MCV and FSF influences the organ at risk (OAR) doses significantly but not PTV coverage and dose homogeneity. Variation in FSF causes difference in dosimetric and physical parameters for the treatment plans but variation of MCV does not. MCV 3% or less do not improve the plan quality significantly (physical and clinical) compared with MCV greater than 3%. The use of MCV between 3% and 5% gives similar results as 1% with lesser calculation time. Minimally detected differences in plan quality suggest that the optimum FSF can be set between 3 and 5.

Effect of non-normality on test statistics for one-way independent groups designs.

PubMed

Cribbie, Robert A; Fiksenbaum, Lisa; Keselman, H J; Wilcox, Rand R

2012-02-01

The data obtained from one-way independent groups designs is typically non-normal in form and rarely equally variable across treatment populations (i.e., population variances are heterogeneous). Consequently, the classical test statistic that is used to assess statistical significance (i.e., the analysis of variance F test) typically provides invalid results (e.g., too many Type I errors, reduced power). For this reason, there has been considerable interest in finding a test statistic that is appropriate under conditions of non-normality and variance heterogeneity. Previously recommended procedures for analysing such data include the James test, the Welch test applied either to the usual least squares estimators of central tendency and variability, or the Welch test with robust estimators (i.e., trimmed means and Winsorized variances). A new statistic proposed by Krishnamoorthy, Lu, and Mathew, intended to deal with heterogeneous variances, though not non-normality, uses a parametric bootstrap procedure. In their investigation of the parametric bootstrap test, the authors examined its operating characteristics under limited conditions and did not compare it to the Welch test based on robust estimators. Thus, we investigated how the parametric bootstrap procedure and a modified parametric bootstrap procedure based on trimmed means perform relative to previously recommended procedures when data are non-normal and heterogeneous. The results indicated that the tests based on trimmed means offer the best Type I error control and power when variances are unequal and at least some of the distribution shapes are non-normal. © 2011 The British Psychological Society.

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

Venencia, C; Pino, M; Caussa, L

Purpose: The purpose of this work was to quantify the dosimetric impact of Monte Carlo (MC) dose calculation algorithm compared to Pencil Beam (PB) on Spine SBRT with HybridARC (HA) and sliding windows IMRT (dMLC) treatment modality. Methods: A 6MV beam (1000MU/min) produced by a Novalis TX (BrainLAB-Varian) equipped with HDMLC was used. HA uses 1 arc plus 8 IMRT beams (arc weight between 60–40%) and dIMRT 15 beams. Plans were calculated using iPlan v.4.5.3 (BrainLAB) and the treatment dose prescription was 27Gy in 3 fractions. Dose calculation was done by PB (4mm spatial resolution) with heterogeneity correction and MCmore » dose to water (4mm spatial resolution and 4% mean variance). PTV and spinal cord dose comparison were done. Study was done on 12 patients. IROC Spine Phantom was used to validate HA and quantify dose variation using PB and MC algorithm. Results: The difference between PB and MC for PTV D98%, D95%, Dmean, D2% were 2.6% [−5.1, 6.8], 0.1% [−4.2, 5.4], 0.9% [−1.5, 3.8] and 2.4% [−0.5, 8.3]. The difference between PB and MC for spinal cord Dmax, D1.2cc and D0.35cc were 5.3% [−6.4, 18.4], 9% [−7.0, 17.0] and 7.6% [−0.6, 14.8] respectively. IROC spine phantom shows PTV TLD dose variation of 0.98% for PB and 1.01% for MC. Axial and sagittal film plane gamma index (5%-3mm) was 95% and 97% for PB and 95% and 99% for MC. Conclusion: PB slightly underestimates the dose for the PTV. For the spinal cord PB underestimates the dose and dose differences could be as high as 18% which could have unexpected clinical impact. CI shows no variation between PB and MC for both treatment modalities Treatment modalities have no impact with the dose calculation algorithms used. Following the IROC pass-fail criteria, treatment acceptance requirement was fulfilled for PB and MC.« less

77 FR 9637 - Process for Requesting a Variance From Vegetation Standards for Levees and Floodwalls; Additional...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-17

...-2502, Retaining and Flood Walls, 29 September 1989. h. Engineer Technical Letter (ETL) 1110-2-575... vegetation variance request. h. All final documentation for the vegetation variance request shall be uploaded..., especially for I-walls of concern as identified per Paragraph 3.h. For floodwalls, the landside and waterside...

Calibration and error analysis of metal-oxide-semiconductor field-effect transistor dosimeters for computed tomography radiation dosimetry.

PubMed

Trattner, Sigal; Prinsen, Peter; Wiegert, Jens; Gerland, Elazar-Lars; Shefer, Efrat; Morton, Tom; Thompson, Carla M; Yagil, Yoad; Cheng, Bin; Jambawalikar, Sachin; Al-Senan, Rani; Amurao, Maxwell; Halliburton, Sandra S; Einstein, Andrew J

2017-12-01

Metal-oxide-semiconductor field-effect transistors (MOSFETs) serve as a helpful tool for organ radiation dosimetry and their use has grown in computed tomography (CT). While different approaches have been used for MOSFET calibration, those using the commonly available 100 mm pencil ionization chamber have not incorporated measurements performed throughout its length, and moreover, no previous work has rigorously evaluated the multiple sources of error involved in MOSFET calibration. In this paper, we propose a new MOSFET calibration approach to translate MOSFET voltage measurements into absorbed dose from CT, based on serial measurements performed throughout the length of a 100-mm ionization chamber, and perform an analysis of the errors of MOSFET voltage measurements and four sources of error in calibration. MOSFET calibration was performed at two sites, to determine single calibration factors for tube potentials of 80, 100, and 120 kVp, using a 100-mm-long pencil ion chamber and a cylindrical computed tomography dose index (CTDI) phantom of 32 cm diameter. The dose profile along the 100-mm ion chamber axis was sampled in 5 mm intervals by nine MOSFETs in the nine holes of the CTDI phantom. Variance of the absorbed dose was modeled as a sum of the MOSFET voltage measurement variance and the calibration factor variance, the latter being comprised of three main subcomponents: ionization chamber reading variance, MOSFET-to-MOSFET variation and a contribution related to the fact that the average calibration factor of a few MOSFETs was used as an estimate for the average value of all MOSFETs. MOSFET voltage measurement error was estimated based on sets of repeated measurements. The calibration factor overall voltage measurement error was calculated from the above analysis. Calibration factors determined were close to those reported in the literature and by the manufacturer (~3 mV/mGy), ranging from 2.87 to 3.13 mV/mGy. The error σ V of a MOSFET voltage measurement was shown to be proportional to the square root of the voltage V: σV=cV where c = 0.11 mV. A main contributor to the error in the calibration factor was the ionization chamber reading error with 5% error. The usage of a single calibration factor for all MOSFETs introduced an additional error of about 5-7%, depending on the number of MOSFETs that were used to determine the single calibration factor. The expected overall error in a high-dose region (~30 mGy) was estimated to be about 8%, compared to 6% when an individual MOSFET calibration was performed. For a low-dose region (~3 mGy), these values were 13% and 12%. A MOSFET calibration method was developed using a 100-mm pencil ion chamber and a CTDI phantom, accompanied by an absorbed dose error analysis reflecting multiple sources of measurement error. When using a single calibration factor, per tube potential, for different MOSFETs, only a small error was introduced into absorbed dose determinations, thus supporting the use of a single calibration factor for experiments involving many MOSFETs, such as those required to accurately estimate radiation effective dose. © 2017 American Association of Physicists in Medicine.

SU-F-T-323: A Post-Mastectomy Radiation Therapy Dose Distribution Study Using Nanodots and Films

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

Qian, X; Vaidya, K; Puckett, L

Purpose: In post-mastectomy radiation therapy (RT), skin dose must be accurately estimated to assess skin reactions such as erythema, desquamation and necrosis. Planning systems cannot always provide accurate dosimetry for target volumes distal to skin. Therefore, in-vivo dosimetry is necessary. A female anthropomorphic phantom was used with optically stimulated luminescence dosimeters (nanoDots) to measure dose to chest wall skin. In addition, EBT2 films was employed to measure dose to left lung and heart in post-mastectomy RT. Methods: Films and nanoDots were calibrated under full buildup conditions at 100cm SAD for 6MV photons. Five pieces of films were placed between slabsmore » of Rando phantom to assess dose to left lung and heart. Two layers of 0.5cm thick bolus were used to cover the whole left chest. Six pairs of nanoDots were placed at medical and lateral aspects on the bolus surface, between the 0.5cm bolus layers, and under the bolus. Three control nanoDots were placed on chest wall to quantify imaging dose. The phantom was CT scanned with all dosimeters in place, and treatment planning was performed with tangential fields (200cGy). All dosimeters were contoured on CT and dose was extracted. NanoDots were read using nanoDot reader and films were scanned using film scanner. The measured and calculated doses were tabulated. Results: Dose to 12 nanoDots were evaluated. Dose variance for surface nanoDots were +3.8%, +2.7%, −5% and −9.8%. Those at lateral positions, with greater beam obliquity had larger variance than the medial positions. A similar trend was observed for other nanoDots (Table1). Point doses from films for heart and the left lung were 112.7cGy and 108.7cGy, with +10.2% and +9.04% deviation from calculated values, respectively. Conclusion: Dosimetry provided by the advanced planning system was verified using NanoDots and films. Both nanoDots and films provided good estimation of dose distribution in post-mastectomy RT.« less

Psychological functioning and adherence to the recommended dose of physical activity in later life: results from a national health survey.

PubMed

Netz, Yael; Dunsky, Ayelet; Zach, Sima; Goldsmith, Rebecca; Shimony, Tal; Goldbourt, Uri; Zeev, Aviva

2012-12-01

Official health organizations have established the dose of physical activity needed for preserving both physical and psychological health in old age. The objective of this study was to explore whether adherence to the recommended criterion of physical activity accounted for better psychological functioning in older adults in Israel. A random sample of 1,663 (799 men) Israelis reported their physical activity routine, and based on official guidelines were divided into sufficiently active, insufficiently active, and inactive groups. The General Health Questionnaire (GHQ) was used for assessing mental health and the Mini-Mental State Examination (MMSE) for assessing cognitive functioning. Factor analysis performed on the GHQ yielded two factors - positive and negative. Logistic regressions for the GHQ factors and for the MMSE were conducted for explaining their variance, with demographic variables entered first, followed by health and then physical activity. The explained variance in the three steps was Cox and Snell R2 = 0.022, 0.023, 0.039 for the positive factor, 0.066, 0.093, 0.101 for the negative factor, and 0.204, 0.206, 0.209 for the MMSE. Adherence to the recommended dose of physical activity accounted for better psychological functioning beyond demographic and health variables; however, the additional explained variance was small. More specific guidelines of physical activity may elucidate a stronger relationship, but only randomized controlled trials can reveal cause-effect relationship between physical activity and psychological functioning. More studies are needed focusing on the positive factor of psychological functioning.

Investigation of sarizotan's impact on the pharmacokinetics of probe drugs for major cytochrome P450 isoenzymes: a combined cocktail trial.

PubMed

Krösser, Sonja; Neugebauer, Roland; Dolgos, Hugues; Fluck, Markus; Rost, Karl-Ludwig; Kovar, Andreas

2006-04-01

The 5HT(1A) receptor agonist sarizotan is in clinical development for the treatment of dyskinesia, a potentially disabling complication in Parkinson's disease. We investigated the effect of sarizotan on the clinical pharmacokinetics of probe drugs for cytochrome P450 (CYP) to evaluate the risk of CYP-related drug-drug interactions. This was a double-blind, randomised, two-period cross-over interaction study with repeated administration of 5 mg sarizotan HCl or placebo b.i.d. for 8 days in 18 healthy volunteers. On day 4, a single dose of 100 mg metoprolol (CYP2D6 probe) was administered. On day 8, single doses of 100 mg caffeine (CYP1A2 probe), 50 mg diclofenac (CYP2C9 probe), 100 mg mephenytoin (CYP2C19 probe) and 7.5 mg midazolam (CYP3A4 probe) were simultaneously applied. Pharmacokinetic parameters for probe drugs and their metabolites in plasma and urinary recovery were determined. Concentration-time profiles and pharmacokinetic parameters of all probes and their metabolites remained unchanged after co-administration of sarizotan, compared with placebo. Analysis of variance of the area under the plasma concentration-time curve for probe drugs/metabolites, metabolic ratios and urinary excretion resulted in 90% confidence intervals within the acceptance range (0.8-1.25), indicating the absence of drug-drug interactions. At a dose higher than that intended for clinical use (1 mg b.i.d.), sarizotan had no effect on the metabolism and pharmacokinetics of specific probe drugs for CYP isoenzymes 1A2, 2C19, 2C9, 2D6 and 3A4. Pharmacokinetic interactions with co-administered drugs metabolised by these CYP isoforms are not expected, and dose adjustment of co-administered CYP substrates is not necessary.

40 CFR 264.97 - General ground-water monitoring requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... paragraph (i) of this section. (1) A parametric analysis of variance (ANOVA) followed by multiple... mean levels for each constituent. (2) An analysis of variance (ANOVA) based on ranks followed by...

75 FR 38130 - Keystone Steel and Wire Company; Notice of Application for a Permanent Variance, Grant of an...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-01

...] Keystone Steel and Wire Company; Notice of Application for a Permanent Variance, Grant of an Interim Order...: Keystone Steel and Wire Company (KSW) is applying for a permanent variance from the provisions of the OSHA... OSHA's Web page at http://www.osha.gov . I. Notice of Application Keystone Steel and Wire Company...

Consequences of Assumption Violations Revisited: A Quantitative Review of Alternatives to the One-Way Analysis of Variance "F" Test.

ERIC Educational Resources Information Center

Lix, Lisa M.; And Others

1996-01-01

Meta-analytic techniques were used to summarize the statistical robustness literature on Type I error properties of alternatives to the one-way analysis of variance "F" test. The James (1951) and Welch (1951) tests performed best under violations of the variance homogeneity assumption, although their use is not always appropriate. (SLD)

SU-C-202-05: Pilot Study of Online Treatment Evaluation and Adaptive Re-Planning for Laryngeal SBRT

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

Mao, W; Henry Ford Health System, Detroit, MI; Liu, C

Purpose: We have instigated a phase I trial of 5-fraction stereotactic body radiotherapy (SBRT) for advanced-stage laryngeal cancer. We conducted this pilot dosimetric study to confirm the potential utility of online adaptive re-planning to preserve treatment quality. Methods: Ten cases of larynx cancer were evaluated. Baseline and daily SBRT treatment plans were generated per trial protocol. Daily volumetric images were acquired prior to every fraction of treatment. Reference simulation CT images were deformably registered to daily volumetric images using Eclipse. Planning contours were then deformably propagated to daily images. Reference SBRT plans were directly copied to calculate delivered dose distributionsmore » on deformed reference CT images. In-house software platform has been developed to calculate cumulative dose over a course of treatment in four steps: 1) deforming delivered dose grid to reference CT images using deformation information exported from Eclipse; 2) generating tetrahedrons using deformed dose grid as vertices; 3) resampling dose to a high resolution within every tetrahedron; 4) calculating dose-volume histograms. Our inhouse software was benchmarked with a commercial software, Mirada. Results: In all ten cases including 49 fractions of treatments, delivered daily doses were completely evaluated and treatment could be re-planned within 10 minutes. Prescription dose coverage of PTV was less than intended in 53% of fractions of treatment (mean: 94%, range: 84%–98%) while minimum coverage of CTV and GTV was 94% and 97%, respectively. Maximum bystander point dose limits to arytenoids, parotids, and spinal cord remained respected in all cases, although variances in carotid artery doses were observed in a minority of cases. Conclusion: Although GTV and CTV coverage is preserved by in-room 3D image guidance of larynx SBRT, PTV coverage can vary significantly from intended plans. Online adaptive treatment evaluation and re-planning is potentially necessary and our procedure is clinically applicable to fully preserve treatment quality. This project is supported by CPRIT Individual Investigator Research Award RP150386.« less

A Shearlet-based algorithm for quantum noise removal in low-dose CT images

NASA Astrophysics Data System (ADS)

Zhang, Aguan; Jiang, Huiqin; Ma, Ling; Liu, Yumin; Yang, Xiaopeng

2016-03-01

Low-dose CT (LDCT) scanning is a potential way to reduce the radiation exposure of X-ray in the population. It is necessary to improve the quality of low-dose CT images. In this paper, we propose an effective algorithm for quantum noise removal in LDCT images using shearlet transform. Because the quantum noise can be simulated by Poisson process, we first transform the quantum noise by using anscombe variance stabilizing transform (VST), producing an approximately Gaussian noise with unitary variance. Second, the non-noise shearlet coefficients are obtained by adaptive hard-threshold processing in shearlet domain. Third, we reconstruct the de-noised image using the inverse shearlet transform. Finally, an anscombe inverse transform is applied to the de-noised image, which can produce the improved image. The main contribution is to combine the anscombe VST with the shearlet transform. By this way, edge coefficients and noise coefficients can be separated from high frequency sub-bands effectively. A number of experiments are performed over some LDCT images by using the proposed method. Both quantitative and visual results show that the proposed method can effectively reduce the quantum noise while enhancing the subtle details. It has certain value in clinical application.

ANALYSES OF NEUROBEHAVIORAL SCREENING DATA: BENCHMARK DOSE ESTIMATION.

EPA Science Inventory

Analysis of neurotoxicological screening data such as those of the functional observational battery (FOB) traditionally relies on analysis of variance (ANOVA) with repeated measurements, followed by determination of a no-adverse-effect level (NOAEL). The US EPA has proposed the ...

Sinogram noise reduction for low-dose CT by statistics-based nonlinear filters

NASA Astrophysics Data System (ADS)

Wang, Jing; Lu, Hongbing; Li, Tianfang; Liang, Zhengrong

2005-04-01

Low-dose CT (computed tomography) sinogram data have been shown to be signal-dependent with an analytical relationship between the sample mean and sample variance. Spatially-invariant low-pass linear filters, such as the Butterworth and Hanning filters, could not adequately handle the data noise and statistics-based nonlinear filters may be an alternative choice, in addition to other choices of minimizing cost functions on the noisy data. Anisotropic diffusion filter and nonlinear Gaussian filters chain (NLGC) are two well-known classes of nonlinear filters based on local statistics for the purpose of edge-preserving noise reduction. These two filters can utilize the noise properties of the low-dose CT sinogram for adaptive noise reduction, but can not incorporate signal correlative information for an optimal regularized solution. Our previously-developed Karhunen-Loeve (KL) domain PWLS (penalized weighted least square) minimization considers the signal correlation via the KL strategy and seeks the PWLS cost function minimization for an optimal regularized solution for each KL component, i.e., adaptive to the KL components. This work compared the nonlinear filters with the KL-PWLS framework for low-dose CT application. Furthermore, we investigated the nonlinear filters for post KL-PWLS noise treatment in the sinogram space, where the filters were applied after ramp operation on the KL-PWLS treated sinogram data prior to backprojection operation (for image reconstruction). By both computer simulation and experimental low-dose CT data, the nonlinear filters could not outperform the KL-PWLS framework. The gain of post KL-PWLS edge-preserving noise filtering in the sinogram space is not significant, even the noise has been modulated by the ramp operation.

SU-E-J-83: CBCT Based Rectum and Bladder Dose Tracking in the Prostate Radiotherapy

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

Chen, Z; Wang, J; Yang, Z

2015-06-15

Purpose: The aim of this study is to monitor the volume changes of bladder and rectum and evaluate the dosimetric changes of bladder and rectum using daily cone-beam CT for prostate radiotherapy. Methods: The data of this study were obtained from 12 patients, totally 222 CBCTs. All the volume of the bladder and the rectum on the CBCT were normalized to the bladder and the rectum on their own original CT to monitory the volume changes. To evaluate dose delivered to the OARs, volumes that receive 70Gy (V70Gy), 60Gy, 50Gy, 40Gy and 30Gy are calculated for the bladder and themore » rectum, V20Gy and V10Gy for rectum additionally. And the deviation of the mean dose to the bladder and the rectum are also chosen as the evaluation parameter. Linear regression analysis was performed to identify the mean dose change of the volume change using SPSS 19. Results: The results show that the variances of the normalize volume of the bladder and the rectum are 0.15–0.58 and 0.13–0.50. The variances of V70Gy, V60Gy, V50Gy, V40Gy and V30Gy of bladder are bigger than rectum for 11 patients. The linear regression analysis indicated a negative correlation between the volume and the mean dose of the bladder (p < 0.05). A 10% increase in bladder volume will cause 5.1% (±4.3%) reduction in mean dose. Conclusion: The bladder volume change is more significant than that for rectum for the prostate cancer patient. The volume changes of rectum are not significant except air gap in the rectum. Bladder volume varies will cause significant dose change. The bladder volume monitoring before fractional treatment delivery would be crucial for accuracy dose delivery.« less

The link between diffusion MRI and tumor heterogeneity: Mapping cell eccentricity and density by diffusional variance decomposition (DIVIDE).

PubMed

Szczepankiewicz, Filip; van Westen, Danielle; Englund, Elisabet; Westin, Carl-Fredrik; Ståhlberg, Freddy; Lätt, Jimmy; Sundgren, Pia C; Nilsson, Markus

2016-11-15

The structural heterogeneity of tumor tissue can be probed by diffusion MRI (dMRI) in terms of the variance of apparent diffusivities within a voxel. However, the link between the diffusional variance and the tissue heterogeneity is not well-established. To investigate this link we test the hypothesis that diffusional variance, caused by microscopic anisotropy and isotropic heterogeneity, is associated with variable cell eccentricity and cell density in brain tumors. We performed dMRI using a novel encoding scheme for diffusional variance decomposition (DIVIDE) in 7 meningiomas and 8 gliomas prior to surgery. The diffusional variance was quantified from dMRI in terms of the total mean kurtosis (MK T ), and DIVIDE was used to decompose MK T into components caused by microscopic anisotropy (MK A ) and isotropic heterogeneity (MK I ). Diffusion anisotropy was evaluated in terms of the fractional anisotropy (FA) and microscopic fractional anisotropy (μFA). Quantitative microscopy was performed on the excised tumor tissue, where structural anisotropy and cell density were quantified by structure tensor analysis and cell nuclei segmentation, respectively. In order to validate the DIVIDE parameters they were correlated to the corresponding parameters derived from microscopy. We found an excellent agreement between the DIVIDE parameters and corresponding microscopy parameters; MK A correlated with cell eccentricity (r=0.95, p<10 -7 ) and MK I with the cell density variance (r=0.83, p<10 -3 ). The diffusion anisotropy correlated with structure tensor anisotropy on the voxel-scale (FA, r=0.80, p<10 -3 ) and microscopic scale (μFA, r=0.93, p<10 -6 ). A multiple regression analysis showed that the conventional MK T parameter reflects both variable cell eccentricity and cell density, and therefore lacks specificity in terms of microstructure characteristics. However, specificity was obtained by decomposing the two contributions; MK A was associated only to cell eccentricity, and MK I only to cell density variance. The variance in meningiomas was caused primarily by microscopic anisotropy (mean±s.d.) MK A =1.11±0.33 vs MK I =0.44±0.20 (p<10 -3 ), whereas in the gliomas, it was mostly caused by isotropic heterogeneity MK I =0.57±0.30 vs MK A =0.26±0.11 (p<0.05). In conclusion, DIVIDE allows non-invasive mapping of parameters that reflect variable cell eccentricity and density. These results constitute convincing evidence that a link exists between specific aspects of tissue heterogeneity and parameters from dMRI. Decomposing effects of microscopic anisotropy and isotropic heterogeneity facilitates an improved interpretation of tumor heterogeneity as well as diffusion anisotropy on both the microscopic and macroscopic scale. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Technical Note: Statistical dependences between channels in radiochromic film readings. Implications in multichannel dosimetry.

PubMed

González-López, Antonio; Vera-Sánchez, Juan Antonio; Ruiz-Morales, Carmen

2016-05-01

This note studies the statistical relationships between color channels in radiochromic film readings with flatbed scanners. The same relationships are studied for noise. Finally, their implications for multichannel film dosimetry are discussed. Radiochromic films exposed to wedged fields of 6 MV energy were read in a flatbed scanner. The joint histograms of pairs of color channels were used to obtain the joint and conditional probability density functions between channels. Then, the conditional expectations and variances of one channel given another channel were obtained. Noise was extracted from film readings by means of a multiresolution analysis. Two different dose ranges were analyzed, the first one ranging from 112 to 473 cGy and the second one from 52 to 1290 cGy. For the smallest dose range, the conditional expectations of one channel given another channel can be approximated by linear functions, while the conditional variances are fairly constant. The slopes of the linear relationships between channels can be used to simplify the expression that estimates the dose by means of the multichannel method. The slopes of the linear relationships between each channel and the red one can also be interpreted as weights in the final contribution to dose estimation. However, for the largest dose range, the conditional expectations of one channel given another channel are no longer linear functions. Finally, noises in different channels were found to correlate weakly. Signals present in different channels of radiochromic film readings show a strong statistical dependence. By contrast, noise correlates weakly between channels. For the smallest dose range analyzed, the linear behavior between the conditional expectation of one channel given another channel can be used to simplify calculations in multichannel film dosimetry.

Performance of DS/SSMA (Direct-Sequence Spread-Spectrum Multiple-Access) Communications in Impulsive Channels.

DTIC Science & Technology

1986-11-01

mother and my brother. Their support and encouragement made this research exciting and enjoyable. I am grateful to my advisor, Professor H. Vincent Poor...the model. The m! M A variance of a random variable with density given by (A. 1) is a2 KmC 2 2A(I+l’)• (A.2) With the variance of the random variable

Comparing the Performance of Approaches for Testing the Homogeneity of Variance Assumption in One-Factor ANOVA Models

ERIC Educational Resources Information Center

Wang, Yan; Rodríguez de Gil, Patricia; Chen, Yi-Hsin; Kromrey, Jeffrey D.; Kim, Eun Sook; Pham, Thanh; Nguyen, Diep; Romano, Jeanine L.

2017-01-01

Various tests to check the homogeneity of variance assumption have been proposed in the literature, yet there is no consensus as to their robustness when the assumption of normality does not hold. This simulation study evaluated the performance of 14 tests for the homogeneity of variance assumption in one-way ANOVA models in terms of Type I error…

MO-E-17A-06: Organ Dose in Abdomen-Pelvis CT: Does TG 111 Equilibrium Dose Concept Better Accounts for KVp Dependence Than Conventional CTDI?

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

Li, X; Morgan, A; Davros, W

Purpose: In CT imaging, a desirable quality assurance (QA) dose quantity should account for the dose variability across scan parameters and scanner models. Recently, AAPM TG 111 proposed to use equilibrium dose-pitch product, in place of CT dose index (CTDI100), for scan modes involving table translation. The purpose of this work is to investigate whether this new concept better accounts for the kVp dependence of organ dose than the conventional CTDI concept. Methods: The adult reference female extended cardiac-torso (XCAT) phantom was used for this study. A Monte Carlo program developed and validated for a 128-slice CT system (Definition Flash,more » Siemens Healthcare) was used to simulate organ dose for abdomenpelvis scans at five tube voltages (70, 80, 100, 120, 140 kVp) with a pitch of 0.8 and a detector configuration of 2x64x0.6 mm. The same Monte Carlo program was used to simulate CTDI100 and equilibrium dose-pitch product. For both metrics, the central and peripheral values were used together with helical pitch to calculate a volume-weighted average, i.e., CTDIvol and (Deq)vol, respectively. Results: While other scan parameters were kept constant, organ dose depended strongly on kVp; the coefficient of variation (COV) across the five kVp values ranged between 70–75% for liver, spleen, stomach, pancreas, kidneys, colon, small intestine, bladder, and ovaries, all of which were inside the primary radiation beam. One-way analysis of variance (ANOVA) for the effect of kVp was highly significant (p=3e−30). When organ dose was normalized by CTDIvol, the COV across the five kVp values reduced to 7–16%. The effect of kVp was still highly significant (p=4e−4). When organ dose was normalized by (Deq)vol, the COV further reduced to 4−12%. The effect of kVp was borderline significant (p=0.04). Conclusion: In abdomen-pelvis CT, TG 111 equilibrium dose concept better accounts for kVp dependence than the conventional CTDI. This work is supported by a faculty startup fund from the Cleveland State University.« less

Good genes, genetic compatibility and the evolution of polyandry: use of the diallel cross to address competing hypotheses.

PubMed

Ivy, T M

2007-03-01

Genetic benefits can enhance the fitness of polyandrous females through the high intrinsic genetic quality of females' mates or through the interaction between female and male genes. I used a full diallel cross, a quantitative genetics design that involves all possible crosses among a set of genetically homogeneous lines, to determine the mechanism through which polyandrous female decorated crickets (Gryllodes sigillatus) obtain genetic benefits. I measured several traits related to fitness and partitioned the phenotypic variance into components representing the contribution of additive genetic variance ('good genes'), nonadditive genetic variance (genetic compatibility), as well as maternal and paternal effects. The results reveal a significant variance attributable to both nonadditive and additive sources in the measured traits, and their influence depended on which trait was considered. The lack of congruence in sources of phenotypic variance among these fitness-related traits suggests that the evolution and maintenance of polyandry are unlikely to have resulted from one selective influence, but rather are the result of the collective effects of a number of factors.

High variance in reproductive success generates a false signature of a genetic bottleneck in populations of constant size: a simulation study

PubMed Central

2013-01-01

Background Demographic bottlenecks can severely reduce the genetic variation of a population or a species. Establishing whether low genetic variation is caused by a bottleneck or a constantly low effective number of individuals is important to understand a species’ ecology and evolution, and it has implications for conservation management. Recent studies have evaluated the power of several statistical methods developed to identify bottlenecks. However, the false positive rate, i.e. the rate with which a bottleneck signal is misidentified in demographically stable populations, has received little attention. We analyse this type of error (type I) in forward computer simulations of stable populations having greater than Poisson variance in reproductive success (i.e., variance in family sizes). The assumption of Poisson variance underlies bottleneck tests, yet it is commonly violated in species with high fecundity. Results With large variance in reproductive success (Vk ≥ 40, corresponding to a ratio between effective and census size smaller than 0.1), tests based on allele frequencies, allelic sizes, and DNA sequence polymorphisms (heterozygosity excess, M-ratio, and Tajima’s D test) tend to show erroneous signals of a bottleneck. Similarly, strong evidence of population decline is erroneously detected when ancestral and current population sizes are estimated with the model based method MSVAR. Conclusions Our results suggest caution when interpreting the results of bottleneck tests in species showing high variance in reproductive success. Particularly in species with high fecundity, computer simulations are recommended to confirm the occurrence of a population bottleneck. PMID:24131797

Evaluating Effect of Albendazole on Trichuris trichiura Infection: A Systematic Review Article.

PubMed

Ahmadi Jouybari, Toraj; Najaf Ghobadi, Khadije; Lotfi, Bahare; Alavi Majd, Hamid; Ahmadi, Nayeb Ali; Rostami-Nejad, Mohammad; Aghaei, Abbas

2016-01-01

The aim of the study was assessment of defaults and conducted meta-analysis of the efficacy of single-dose oral albendazole against T. trichiura infection. We searched PubMed, ISI Web of Science, Science Direct, the Cochrane Central Register of Controlled Trials, and WHO library databases between 1983 and 2014. Data from 13 clinical trial articles were used. Each article was included the effect of single oral dose (400 mg) albendazole and placebo in treating two groups of patients with T. trichiura infection. For both groups in each article, sample size, the number of those with T. trichiura infection, and the number of those recovered following the intake of albendazole were identified and recorded. The relative risk and variance were computed. Funnel plot, Beggs and Eggers tests were used for assessment of publication bias. The random effect variance shift outlier model and likelihood ratio test were applied for detecting outliers. In order to detect influence, DFFITS values, Cook's distances and COVRATIO were used. Data were analyzed using STATA and R software. The article number 13 and 9 were outlier and influence, respectively. Outlier is diagnosed by variance shift of target study in inferential method and by RR value in graphical method. Funnel plot and Beggs test did not show the publication bias ( P =0.272). However, the Eggers test confirmed it ( P =0.034). Meta-analysis after removal of article 13 showed that relative risk was 1.99 (CI 95% 1.71 - 2.31). The estimated RR and our meta-analyses show that treatment of T. trichiura with single oral doses of albendazole is unsatisfactory. New anthelminthics are urgently needed.

Quantitative evaluation of variance in secondary dentition eruption among ethnic groups in Hawai'i.

PubMed

Greer, Mark H K; Loo, Kevin J

2003-03-01

Though little scientific evidence existed to support the belief among dentists who treat Pacific Islander populations that many children of the region erupt secondary teeth earlier and at an eruption rate which exceeds Caucasian children. Based upon a data set created in Hawai'i during the 1998-1999 school year, of 26,097 public school children, the opportunity presented itself to examine for variance in eruption timing and sequence. Hawai'i is an ethnic diverse community, with a majority population comprised of Asians and Pacific Islanders. Children, 5 through 9 years of age, were examined for gender and ethnic variance. In the aggregate, at all ages, girls erupted teeth earlier than boys, however, while generally true among individual tooth types, that variance was not always statistically significant. By ethnic group, African Americans exhibited earlier eruption by contrast with Caucasians, however, Caucasian children caught up by nine years of age. Native Hawaiian, Samoan and Tongan children exhibited earlier and high rates of secondary dentition eruption than Caucasian or African American children. Children of various Asian cohorts did not exhibit significant variance by contrast with Caucasians. Based upon these findings, the authors recommend that dietary fluoride supplementation of Native Hawaiian, Samoan and Tongan children begin at birth rather than 6 months of age and that these children be targeted for pit & fissure sealants as early as five years of age.

Short-term intravenous citalopram augmentation in partial/nonresponders with major depression: a randomized placebo-controlled study.

PubMed

Altamura, Alfredo Carlo; Dell'Osso, Bernardo; Buoli, Massimiliano; Bosi, Monica; Mundo, Emanuela

2008-07-01

Approximately 30-45% of patients with major depressive episode (MDE) do not fully respond to standard recommended treatments and further strategies of intervention, including pharmacological augmentation, have been proposed for these patients. This study was aimed to evaluate the efficacy of short-term, low-dose (10 mg/day) intravenous (i.v.) citalopram augmentation versus placebo in a sample of patients with MDE and partial or no response to selective serotonin reuptake inhibitors (SSRIs). Thirty-six patients with a Diagnostic and Statistical Manual for Mental Disorders, 4th edition, text revision criteria MDE and partial or no response to oral SSRIs were selected and randomly assigned to citalopram (n=18) or to placebo (n=18) i.v. augmentation. The augmentation regimen lasted 5 consecutive days during which the patients were maintained on their current treatment with oral SSRIs. Analyses of variance with repeated measures on Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale total scores, administered daily with blind-raters conditions, were done. With regard to the Hamilton Depression Rating Scale total scores, a significant time effect (F=42.02, P<0.0001) and timextreatment effect (F=21.17, P<0.0001) were found in favor of citalopram. Similar results were obtained from the analysis on Montgomery-Asberg Depression Rating Scale total scores: time effect (F=50.07, P<0.0001), timextreatment effect (F=19.91, P<0.0001), and treatment effect (F=4.07, P=0.05). Even though referred to a small sample, the present findings seem to suggest that short-term, low-dose, i.v. citalopram augmentation may be effective in depressed patients with partial or no response to oral SSRIs. Further controlled studies performed with double-blind conditions are warranted to confirm the present results.

SU-E-I-09: The Impact of X-Ray Scattering On Image Noise for Dedicated Breast CT

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

Yang, K; Gazi, P; Boone, J

2015-06-15

Purpose: To quantify the impact of detected x-ray scatter on image noise in flat panel based dedicated breast CT systems and to determine the optimal scanning geometry given practical trade-offs between radiation dose and scatter reduction. Methods: Four different uniform polyethylene cylinders (104, 131, 156, and 184 mm in diameter) were scanned as the phantoms on a dedicated breast CT scanner developed in our laboratory. Both stationary projection imaging and rotational cone-beam CT imaging was performed. For each acquisition type, three different x-ray beam collimations were used (12, 24, and 109 mm measured at isocenter). The aim was to quantifymore » image noise properties (pixel variance, SNR, and image NPS) under different levels of x-ray scatter, in order to optimize the scanning geometry. For both projection images and reconstructed CT images, individual pixel variance and NPS were determined and compared. Noise measurement from the CT images were also performed with different detector binning modes and reconstruction matrix sizes. Noise propagation was also tracked throughout the intermediate steps of cone-beam CT reconstruction, including the inverse-logarithmic process, Fourier-filtering before backprojection. Results: Image noise was lower in the presence of higher scatter levels. For the 184 mm polyethylene phantom, the image noise (measured in pixel variance) was ∼30% lower with full cone-beam acquisition compared to a narrow (12 mm) fan-beam acquisition. This trend is consistent across all phantom sizes and throughout all steps of CT image reconstruction. Conclusion: From purely a noise perspective, the cone-beam geometry (i.e. the full cone-angle acquisition) produces lower image noise compared to the lower-scatter fan-beam acquisition for breast CT. While these results are relevant in homogeneous phantoms, the full impact of scatter on noise in bCT should involve contrast-to-noise-ratio measurements in heterogeneous phantoms if the goal is to optimize the scanning geometry for dedicated breast CT. This work was supported by a grant from the National Institute for Biomedical Imaging and Bioengineering (R01 EB002138)« less

iTemplate: A template-based eye movement data analysis approach.

PubMed

Xiao, Naiqi G; Lee, Kang

2018-02-08

Current eye movement data analysis methods rely on defining areas of interest (AOIs). Due to the fact that AOIs are created and modified manually, variances in their size, shape, and location are unavoidable. These variances affect not only the consistency of the AOI definitions, but also the validity of the eye movement analyses based on the AOIs. To reduce the variances in AOI creation and modification and achieve a procedure to process eye movement data with high precision and efficiency, we propose a template-based eye movement data analysis method. Using a linear transformation algorithm, this method registers the eye movement data from each individual stimulus to a template. Thus, users only need to create one set of AOIs for the template in order to analyze eye movement data, rather than creating a unique set of AOIs for all individual stimuli. This change greatly reduces the error caused by the variance from manually created AOIs and boosts the efficiency of the data analysis. Furthermore, this method can help researchers prepare eye movement data for some advanced analysis approaches, such as iMap. We have developed software (iTemplate) with a graphic user interface to make this analysis method available to researchers.

‘Catalytic’ doses of fructose may benefit glycaemic control without harming cardiometabolic risk factors: a small meta-analysis of randomised controlled feeding trials

PubMed Central

Sievenpiper, John L.; Chiavaroli, Laura; de Souza, Russell J.; Mirrahimi, Arash; Cozma, Adrian I.; Ha, Vanessa; Wang, D. David; Yu, Matthew E.; Carleton, Amanda J.; Beyene, Joseph; Di Buono, Marco; Jenkins, Alexandra L.; Leiter, Lawrence A.; Wolever, Thomas M. S.; Kendall, Cyril W. C.; Jenkins, David J. A.

2012-01-01

Contrary to concerns that fructose may have adverse metabolic effects, there is evidence that small, ‘catalytic’ doses ( ≤ 10 g/meal) of fructose decrease the glycaemic response to high-glycaemic index meals in human subjects. To assess the longer-term effects of ‘catalytic’ doses of fructose, we undertook a meta-analysis of controlled feeding trials. We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library. Analyses included all controlled feeding trials ≥ 7 d featuring ‘catalytic’ fructose doses ( ≤ 36 g/d) in isoenergetic exchange for other carbohydrates. Data were pooled by the generic inverse variance method using random-effects models and expressed as mean differences (MD) with 95 % CI. Heterogeneity was assessed by the Q statistic and quantified by I2. The Heyland Methodological Quality Score assessed study quality. A total of six feeding trials (n 118) met the eligibility criteria. ‘Catalytic’ doses of fructose significantly reduced HbA1c (MD − 0·40, 95 % CI − 0·72, − 0·08) and fasting glucose (MD − 0·25, 95 % CI − 0·44, − 0·07). This benefit was seen in the absence of adverse effects on fasting insulin, body weight, TAG or uric acid. Subgroup and sensitivity analyses showed evidence of effect modification under certain conditions. The small number of trials and their relatively short duration limit the strength of the conclusions. In conclusion, this small meta-analysis shows that ‘catalytic’ fructose doses ( ≤ 36 g/d) may improve glycaemic control without adverse effects on body weight, TAG, insulin and uric acid. There is a need for larger, longer ( ≥ 6 months) trials using ‘catalytic’ fructose to confirm these results. PMID:22354959

Some New Results on Grubbs’ Estimators.

DTIC Science & Technology

1983-06-01

8217 ESTIMATORS DENNIS A. BRINDLEY AND RALPH A. BRADLEY* Consider a two-way classification with n rows and r columns and the usual model of analysis of variance...except that the error components of the model may have heterogeneous variances, by columns. -Grubbs provided unbiased estimators Q. of a . that depend...of observations yij, i = 1, ... , n, j 1, ... , r, and the model , Yij = Ili + ij + Ej, (1) when Vi represents the mean response of row i, . represents

40 CFR 63.562 - Standards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... barrels per day; and (C) For 1997, 1,445,000 barrels per day. (ii) Maximum extent practicable means that... (thermocouples, pressure transducers, continuous emissions monitors (CEMS), etc.) variances. (i) The plan shall... monitoring equipment functions properly and variances of the control equipment and monitoring equipment are...

21 CFR 1010.4 - Variances.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (formerly the Radiation Control for Health and Safety Act of 1968), and: (i) The scope of the requested... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) RADIOLOGICAL HEALTH... and Radiological Health, Food and Drug Administration, may grant a variance from one or more...

Variance components of short-term biomarkers of manganese exposure in an inception cohort of welding trainees.

PubMed

Baker, Marissa G; Simpson, Christopher D; Sheppard, Lianne; Stover, Bert; Morton, Jackie; Cocker, John; Seixas, Noah

2015-01-01

Various biomarkers of exposure have been explored as a way to quantitatively estimate an internal dose of manganese (Mn) exposure, but given the tight regulation of Mn in the body, inter-individual variability in baseline Mn levels, and variability in timing between exposure and uptake into various biological tissues, identification of a valuable and useful biomarker for Mn exposure has been elusive. Thus, a mixed model estimating variance components using restricted maximum likelihood was used to assess the within- and between-subject variance components in whole blood, plasma, and urine (MnB, MnP, and MnU, respectively) in a group of nine newly-exposed apprentice welders, on whom baseline and subsequent longitudinal samples were taken over a three month period. In MnB, the majority of variance was found to be between subjects (94%), while in MnP and MnU the majority of variance was found to be within subjects (79% and 99%, respectively), even when controlling for timing of sample. While blood seemed to exhibit a homeostatic control of Mn, plasma and urine, with the majority of the variance within subjects, did not. Results presented here demonstrate the importance of repeat measure or longitudinal study designs when assessing biomarkers of Mn, and the spurious associations that could result from cross-sectional analyses. Copyright © 2014 Elsevier GmbH. All rights reserved.

Genetic gain and economic values of selection strategies including semen traits in three- and four-way crossbreeding systems for swine production.

PubMed

González-Peña, D; Knox, R V; MacNeil, M D; Rodriguez-Zas, S L

2015-03-01

Four semen traits: volume (VOL), concentration (CON), progressive motility of spermatozoa (MOT), and abnormal spermatozoa (ABN) provide complementary information on boar fertility. Assessment of the impact of selection for semen traits is hindered by limited information on economic parameters. Objectives of this study were to estimate economic values for semen traits and to evaluate the genetic gain when these traits are incorporated into traditional selection strategies in a 3-tier system of swine production. Three-way (maternal nucleus lines A and B and paternal nucleus line C) and 4-way (additional paternal nucleus line D) crossbreeding schemes were compared. A novel population structure that accommodated selection for semen traits was developed. Three selection strategies were simulated. Selection Strategy I (baseline) encompassed selection for maternal traits: number of pigs born alive (NBA), litter birth weight (LBW), adjusted 21-d litter weight (A21), and number of pigs at 21 d (N21); and paternal traits: number of days to 113.5 kg (D113), backfat (BF), ADG, feed efficiency (FE), and carcass lean % (LEAN). Selection Strategy II included Strategy I and the number of usable semen doses per collection (DOSES), a function of the 4 semen traits. Selection Strategy III included Strategy I and the 4 semen traits individually. The estimated economic values of VOL, CON, MOT, ABN, and DOSES for 7 to 1 collections/wk ranged from $0.21 to $1.44/mL, $0.12 to $0.83/10 spermatozoa/mm, $0.61 to $12.66/%, -$0.53 to -$10.88/%, and $2.01 to $41.43/%, respectively. The decrease in the relative economic values of semen traits and DOSES with higher number of collections per wk was sharper between 1 and 2.33 collections/wk than between 2.33 and 7 collections/wk. The higher economic value of MOT and ABN relative to VOL and CON could be linked to the genetic variances and covariances of these traits. Average genetic gains for the maternal traits were comparable across strategies. Genetic gains for paternal traits, excluding semen traits, were greater in selection Strategy I than Strategies III and II. Genetic gains for paternal and maternal traits were greater in the 4- and 3-way schemes, respectively. The selection strategy including the 4 semen traits is recommended because this approach enables genetic gains for these traits without compromising the genetic gains for maternal traits and with minimal losses in genetic gains for paternal traits.

Characteristics of Water Vapor Turbulence Profiles in Convective Boundary Layers During the Dry and Wet Seasons Over Darwin

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

Osman, Mohammed K.; Turner, D. D.; Heus, T.

Here, this study explores water vapor turbulence in the convective boundary layer (CBL) using the Raman lidar observations from the Atmospheric Radiation Measurement site located at Darwin, Australia. An autocovariance technique was used to separate out the random instrument error from the atmospheric variability during time periods when the CBL is cloud–free, quasi–stationary, and well mixed. We identified 45 cases, comprising of 8 wet and 37 dry seasons events, over the 5–year data record period. The dry season in Darwin is known by warm and dry sunny days, while the wet season is characterized by high humidity and monsoonal rains.more » The inherent variability of the latter resulted in a more limited number of cases during the wet season. Profiles of the integral scale, variance, coefficient of the structure function, and skewness were analyzed and compared with similar observations from the Raman lidar at the Atmospheric Radiation Measurement Southern Great Plains (SGP) site. The wet season shows larger median variance profiles than the dry season, while the median profile of the variance from the dry season and the SGP site are found to be more comparable particularly between 0.4 and 0.75 z i. The variance and coefficient of the structure function show qualitatively the same vertical pattern. Furthermore, deeper CBL, larger gradient of water vapor mixing ratio at z i, and the strong correlation with the water vapor variance at z i are seen during the dry season. The median value in the skewness is mostly positive below 0.6 z i unlike the SGP site.« less

Characteristics of Water Vapor Turbulence Profiles in Convective Boundary Layers During the Dry and Wet Seasons Over Darwin

DOE PAGES

Osman, Mohammed K.; Turner, D. D.; Heus, T.; ...

2018-04-23

Here, this study explores water vapor turbulence in the convective boundary layer (CBL) using the Raman lidar observations from the Atmospheric Radiation Measurement site located at Darwin, Australia. An autocovariance technique was used to separate out the random instrument error from the atmospheric variability during time periods when the CBL is cloud–free, quasi–stationary, and well mixed. We identified 45 cases, comprising of 8 wet and 37 dry seasons events, over the 5–year data record period. The dry season in Darwin is known by warm and dry sunny days, while the wet season is characterized by high humidity and monsoonal rains.more » The inherent variability of the latter resulted in a more limited number of cases during the wet season. Profiles of the integral scale, variance, coefficient of the structure function, and skewness were analyzed and compared with similar observations from the Raman lidar at the Atmospheric Radiation Measurement Southern Great Plains (SGP) site. The wet season shows larger median variance profiles than the dry season, while the median profile of the variance from the dry season and the SGP site are found to be more comparable particularly between 0.4 and 0.75 z i. The variance and coefficient of the structure function show qualitatively the same vertical pattern. Furthermore, deeper CBL, larger gradient of water vapor mixing ratio at z i, and the strong correlation with the water vapor variance at z i are seen during the dry season. The median value in the skewness is mostly positive below 0.6 z i unlike the SGP site.« less

Accelerator shield design of KIPT neutron source facility

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

Zhong, Z.; Gohar, Y.

Argonne National Laboratory (ANL) of the United States and Kharkov Institute of Physics and Technology (KIPT) of Ukraine have been collaborating on the design development of a neutron source facility at KIPT utilizing an electron-accelerator-driven subcritical assembly. Electron beam power is 100 kW, using 100 MeV electrons. The facility is designed to perform basic and applied nuclear research, produce medical isotopes, and train young nuclear specialists. The biological shield of the accelerator building is designed to reduce the biological dose to less than 0.5-mrem/hr during operation. The main source of the biological dose is the photons and the neutrons generatedmore » by interactions of leaked electrons from the electron gun and accelerator sections with the surrounding concrete and accelerator materials. The Monte Carlo code MCNPX serves as the calculation tool for the shield design, due to its capability to transport electrons, photons, and neutrons coupled problems. The direct photon dose can be tallied by MCNPX calculation, starting with the leaked electrons. However, it is difficult to accurately tally the neutron dose directly from the leaked electrons. The neutron yield per electron from the interactions with the surrounding components is less than 0.01 neutron per electron. This causes difficulties for Monte Carlo analyses and consumes tremendous computation time for tallying with acceptable statistics the neutron dose outside the shield boundary. To avoid these difficulties, the SOURCE and TALLYX user subroutines of MCNPX were developed for the study. The generated neutrons are banked, together with all related parameters, for a subsequent MCNPX calculation to obtain the neutron and secondary photon doses. The weight windows variance reduction technique is utilized for both neutron and photon dose calculations. Two shielding materials, i.e., heavy concrete and ordinary concrete, were considered for the shield design. The main goal is to maintain the total dose outside the shield boundary at less than 0.5-mrem/hr. The shield configuration and parameters of the accelerator building have been determined and are presented in this paper. (authors)« less

Blunted beta-adrenoceptor-mediated fat oxidation in overweight subjects: a role for the hormone-sensitive lipase gene.

PubMed

Jocken, Johan W E; Blaak, Ellen E; van der Kallen, Carla J H; van Baak, Marleen A; Saris, Wim H M

2008-03-01

Obesity is associated with blunted beta-adrenoceptor-mediated lipolysis and fat oxidation, which persist after weight reduction. We investigated whether dinucleotide (CA)(n) repeat polymorphisms in intron 6 (i6) or 7 (i7) and a C-60G promoter substitution of the hormone-sensitive lipase (HSL) gene are associated with a blunted in vivo beta-adrenoceptor-mediated increase in circulating fatty acids and glycerol (estimation of lipolytic response) and fat oxidation in overweight-obese subjects. A total of 103 overweight (25 kg/m(2) < or = body mass index < 30 kg/m(2)) and obese (body mass index > or =30 kg/m(2)) subjects (62 men, 41 women) were included. Energy expenditure, respiratory quotient (RQ), and circulating fatty acid and glycerol were determined after stepwise infusion of increasing doses of the nonselective beta-agonist isoprenaline. The i6, i7 (CA)(n) repeat polymorphisms were determined by size-resolved capillary electrophoresis; and a C-60G promoter substitution was determined by restriction enzyme digestion assay. Female noncarriers of allele 184 i7 (n = 18) and female carriers of allele 240 i6 (n = 12) showed an overall reduced fat oxidation (as indicated by changes in RQ) after beta-adrenoceptor-mediated stimulation, explaining, respectively, 6.9% and 20.8% of the variance in RQ. These effects were not seen in male subjects. In conclusion, our results suggest that variation in i7 and i6 of the HSL gene might be associated with a physiological effect on in vivo beta-adrenoceptor-mediated fat oxidation, at least in overweight-obese female subjects.

Patterns of patient specific dosimetry in total body irradiation

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

Akino, Yuichi; Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871; McMullen, Kevin P.

2013-04-15

Purpose: Total body irradiation (TBI) has been used for bone marrow transplant for hematologic and immune deficiency conditions. The goal of TBI is to deliver a homogeneous dose to the entire body, with a generally accepted range of dose uniformity being within {+-}10% of the prescribed dose. The moving table technique for TBI could make dose uniform in whole body by adjusting couch speed. However, it is difficult to accurately estimate the actual dose by calculation and hence in vivo dosimetry (IVD) is routinely performed. Here, the authors present patterns of patient-specific IVD in 161 TBI patients treated at ourmore » institution. Methods: Cobalt-60 teletherapy unit (Model C9 Cobalt-60 teletherapy unit, Picker X-ray Corporation) with customized moving bed (SITI Industrial Products, Inc., Fishers, IN) were used for TBI treatment. During treatment, OneDose{sup TM} (Sicel Technology, NC) Metal Oxide-silicon Semiconductor Field Effect Transistor detectors were placed at patient body surface; both entrance and exit side of the beam at patient head, neck, mediastinum, umbilicus, and knee to estimate midplane dose. When large differences (>10%) between the prescribed and measured dose were observed, dose delivery was corrected for subsequent fractions by the adjustment of couch speed and/or bolus placement. Under IRB exempt status, the authors retrospectively analyzed the treatment records of 161 patients who received TBI treatment between 2006 and 2011. Results: Across the entire cohort, the median {+-} SD (range) percent variance between calculated and measured dose for head, neck, mediastinum, umbilicus, and knee was -2.3 {+-} 10.2% (-66.2 to +35.3), 1.1 {+-} 11.5% (-62.2 to +40.3), -1.9 {+-} 9.5% (-66.4 to +46.6), -1.1 {+-} 7.2% (-35.2 to +42.9), and 3.4 {+-} 12.2% (-47.9 to +108.5), respectively. More than half of treatments were within {+-}10% of the prescribed dose for all anatomical regions. For 80% of treatments (10%-90%), dose at the umbilicus was within {+-}10%. However, some large differences greater than 35% were also found at several points. For one case, the knee received double the prescribed dose. When the dose differences for multiple fractions were averaged, compliance ({+-}10%) between the prescription and measured dose was improved compared to the dose difference of the first single fraction, for example, as at umbilicus, which improved from 83.9% to 98.5%. Conclusions: Actual dose measurement analysis of TBI patients revealed a potentially wide variance from the calculated dose. Based from their IVD method for TBI using Cobalt-60 irradiator and moving table, {+-}10% over entire body is hard to achieve. However, it can be significantly improved with immediate feedback after the first fraction prior to subsequent treatments.« less

PWR Facility Dose Modeling Using MCNP5 and the CADIS/ADVANTG Variance-Reduction Methodology

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

Blakeman, Edward D; Peplow, Douglas E.; Wagner, John C

2007-09-01

The feasibility of modeling a pressurized-water-reactor (PWR) facility and calculating dose rates at all locations within the containment and adjoining structures using MCNP5 with mesh tallies is presented. Calculations of dose rates resulting from neutron and photon sources from the reactor (operating and shut down for various periods) and the spent fuel pool, as well as for the photon source from the primary coolant loop, were all of interest. Identification of the PWR facility, development of the MCNP-based model and automation of the run process, calculation of the various sources, and development of methods for visually examining mesh tally filesmore » and extracting dose rates were all a significant part of the project. Advanced variance reduction, which was required because of the size of the model and the large amount of shielding, was performed via the CADIS/ADVANTG approach. This methodology uses an automatically generated three-dimensional discrete ordinates model to calculate adjoint fluxes from which MCNP weight windows and source bias parameters are generated. Investigative calculations were performed using a simple block model and a simplified full-scale model of the PWR containment, in which the adjoint source was placed in various regions. In general, it was shown that placement of the adjoint source on the periphery of the model provided adequate results for regions reasonably close to the source (e.g., within the containment structure for the reactor source). A modification to the CADIS/ADVANTG methodology was also studied in which a global adjoint source is weighted by the reciprocal of the dose response calculated by an earlier forward discrete ordinates calculation. This method showed improved results over those using the standard CADIS/ADVANTG approach, and its further investigation is recommended for future efforts.« less

Fundamental limits of image registration performance: Effects of image noise and resolution in CT-guided interventions.

PubMed

Ketcha, M D; de Silva, T; Han, R; Uneri, A; Goerres, J; Jacobson, M; Vogt, S; Kleinszig, G; Siewerdsen, J H

2017-02-11

In image-guided procedures, image acquisition is often performed primarily for the task of geometrically registering information from another image dataset, rather than detection / visualization of a particular feature. While the ability to detect a particular feature in an image has been studied extensively with respect to image quality characteristics (noise, resolution) and is an ongoing, active area of research, comparatively little has been accomplished to relate such image quality characteristics to registration performance. To establish such a framework, we derived Cramer-Rao lower bounds (CRLB) for registration accuracy, revealing the underlying dependencies on image variance and gradient strength. The CRLB was analyzed as a function of image quality factors (in particular, dose) for various similarity metrics and compared to registration accuracy using CT images of an anthropomorphic head phantom at various simulated dose levels. Performance was evaluated in terms of root mean square error (RMSE) of the registration parameters. Analysis of the CRLB shows two primary dependencies: 1) noise variance (related to dose); and 2) sum of squared image gradients (related to spatial resolution and image content). Comparison of the measured RMSE to the CRLB showed that the best registration method, RMSE achieved the CRLB to within an efficiency factor of 0.21, and optimal estimators followed the predicted inverse proportionality between registration performance and radiation dose. Analysis of the CRLB for image registration is an important step toward understanding and evaluating an intraoperative imaging system with respect to a registration task. While the CRLB is optimistic in absolute performance, it reveals a basis for relating the performance of registration estimators as a function of noise content and may be used to guide acquisition parameter selection (e.g., dose) for purposes of intraoperative registration.

Prospective memory deficits in illicit polydrug users are associated with the average long-term typical dose of ecstasy typically consumed in a single session.

PubMed

Gallagher, Denis T; Hadjiefthyvoulou, Florentia; Fisk, John E; Montgomery, Catharine; Robinson, Sarita J; Judge, Jeannie

2014-01-01

Neuroimaging evidence suggests that ecstasy-related reductions in SERT densities relate more closely to the number of tablets typically consumed per session rather than estimated total lifetime use. To better understand the basis of drug related deficits in prospective memory (p.m.) we explored the association between p.m. and average long-term typical dose and long-term frequency of use. Study 1: Sixty-five ecstasy/polydrug users and 85 nonecstasy users completed an event-based, a short-term and a long-term time-based p.m. task. Study 2: Study 1 data were merged with outcomes on the same p.m. measures from a previous study creating a combined sample of 103 ecstasy/polydrug users, 38 cannabis-only users, and 65 nonusers of illicit drugs. Study 1: Ecstasy/polydrug users had significant impairments on all p.m. outcomes compared with nonecstasy users. Study 2: Ecstasy/polydrug users were impaired in event-based p.m. compared with both other groups and in long-term time-based p.m. compared with nonillicit drug users. Both drug using groups did worse on the short-term time-based p.m. task compared with nonusers. Higher long-term average typical dose of ecstasy was associated with poorer performance on the event and short-term time-based p.m. tasks and accounted for unique variance in the two p.m. measures over and above the variance associated with cannabis and cocaine use. The typical ecstasy dose consumed in a single session is an important predictor of p.m. impairments with higher doses reflecting increasing tolerance giving rise to greater p.m. impairment.

Technical Note: Statistical dependences between channels in radiochromic film readings. Implications in multichannel dosimetry

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

González-López, Antonio, E-mail: antonio.gonzalez7@carm.es; Vera-Sánchez, Juan Antonio; Ruiz-Morales, Carmen

Purpose: This note studies the statistical relationships between color channels in radiochromic film readings with flatbed scanners. The same relationships are studied for noise. Finally, their implications for multichannel film dosimetry are discussed. Methods: Radiochromic films exposed to wedged fields of 6 MV energy were read in a flatbed scanner. The joint histograms of pairs of color channels were used to obtain the joint and conditional probability density functions between channels. Then, the conditional expectations and variances of one channel given another channel were obtained. Noise was extracted from film readings by means of a multiresolution analysis. Two different dosemore » ranges were analyzed, the first one ranging from 112 to 473 cGy and the second one from 52 to 1290 cGy. Results: For the smallest dose range, the conditional expectations of one channel given another channel can be approximated by linear functions, while the conditional variances are fairly constant. The slopes of the linear relationships between channels can be used to simplify the expression that estimates the dose by means of the multichannel method. The slopes of the linear relationships between each channel and the red one can also be interpreted as weights in the final contribution to dose estimation. However, for the largest dose range, the conditional expectations of one channel given another channel are no longer linear functions. Finally, noises in different channels were found to correlate weakly. Conclusions: Signals present in different channels of radiochromic film readings show a strong statistical dependence. By contrast, noise correlates weakly between channels. For the smallest dose range analyzed, the linear behavior between the conditional expectation of one channel given another channel can be used to simplify calculations in multichannel film dosimetry.« less

Development of a pharmacogenetic-guided warfarin dosing algorithm for Puerto Rican patients.

PubMed

Ramos, Alga S; Seip, Richard L; Rivera-Miranda, Giselle; Felici-Giovanini, Marcos E; Garcia-Berdecia, Rafael; Alejandro-Cowan, Yirelia; Kocherla, Mohan; Cruz, Iadelisse; Feliu, Juan F; Cadilla, Carmen L; Renta, Jessica Y; Gorowski, Krystyna; Vergara, Cunegundo; Ruaño, Gualberto; Duconge, Jorge

2012-12-01

This study was aimed at developing a pharmacogenetic-driven warfarin-dosing algorithm in 163 admixed Puerto Rican patients on stable warfarin therapy. A multiple linear-regression analysis was performed using log-transformed effective warfarin dose as the dependent variable, and combining CYP2C9 and VKORC1 genotyping with other relevant nongenetic clinical and demographic factors as independent predictors. The model explained more than two-thirds of the observed variance in the warfarin dose among Puerto Ricans, and also produced significantly better 'ideal dose' estimates than two pharmacogenetic models and clinical algorithms published previously, with the greatest benefit seen in patients ultimately requiring <7 mg/day. We also assessed the clinical validity of the model using an independent validation cohort of 55 Puerto Rican patients from Hartford, CT, USA (R(2) = 51%). Our findings provide the basis for planning prospective pharmacogenetic studies to demonstrate the clinical utility of genotyping warfarin-treated Puerto Rican patients.

Likelihood Ratio Tests for Relationships between Two Covariance Matrices.

DTIC Science & Technology

1982-11-01

mk+l+...+mp)/(p-k). Then, using the results on the asymptotic distribution of the functions of the roots mk+l,...,m p (see Fang and Krishnaiah , 1982...variances and co- variances of the variables in (6.1) is k , :i, 12 E( i- l,...,k (6.2) A B... B D (X) B A ... B (6.3) Krishnaiah and Lee (1974) and...P,R. Krishnaiah for reading the manuscript and making useful comments. 7. REFERENCES [1] Anderson, T.W. (1951). Estimating linear restrictions on

Monte Carlo method for calculating the radiation skyshine produced by electron accelerators

NASA Astrophysics Data System (ADS)

Kong, Chaocheng; Li, Quanfeng; Chen, Huaibi; Du, Taibin; Cheng, Cheng; Tang, Chuanxiang; Zhu, Li; Zhang, Hui; Pei, Zhigang; Ming, Shenjin

2005-06-01

Using the MCNP4C Monte Carlo code, the X-ray skyshine produced by 9 MeV, 15 MeV and 21 MeV electron linear accelerators were calculated respectively with a new two-step method combined with the split and roulette variance reduction technique. Results of the Monte Carlo simulation, the empirical formulas used for skyshine calculation and the dose measurements were analyzed and compared. In conclusion, the skyshine dose measurements agreed reasonably with the results computed by the Monte Carlo method, but deviated from computational results given by empirical formulas. The effect on skyshine dose caused by different structures of accelerator head is also discussed in this paper.

An Empirical Assessment of Defense Contractor Risk 1976-1984.

DTIC Science & Technology

1986-06-01

Model to evaluate the. Department of Defense contract pricing , financing, and profit policies . ’ D*’ ’ *NTV D? 7A’:: TA E *A l ..... -:- A-i SN 0102...defense con- tractor risk-return relationship is performed utilizing four methods: mean-variance analysis of rate of return, the Capital Asset Pricing Model ...relationship is performed utilizing four methods: mean- variance analysis of rate of return, the Capital Asset Pricing Model , mean-variance analysis of total

[Pharmacogenetic approaches to predicting the efficiency and safety of amlodipine in patients with arterial hypertension].

PubMed

Sychev, D A; Shih, N V; Kalle, E G; Ryzhikova, K A; Morozova, T E

2017-10-01

An open, non-comparative, prospective clinical study was conducted to evaluate the antihypertensive efficacy and tolerability of amlodipine, a calcium antagonist, in patients with arterial hypertension (AH) I-II stages, depending on the genotype for the polymorphic marker C3435T of the ABCB1 gene. The study included 100 patients with AH I-II stages, aged from 45 to 58 years. The initial dose of amlodipine was 5 mg, duration of treatment was 12 weeks. General clinical examination methods, office measurement and daily blood pressure monitoring, tolerance evaluation, and genotyping using the ABCB1 polymorphic marker C3435T by the PCR-RFLP method (polymerase chain reaction and restriction fragment length polymorphism) were used. The statistical analysis of results was carried out using the Mann-Whitney U test for quantitative variables, Kruskal-Wallis one-way analysis of variance (ANOVA) for three independent groups of quantitative data. Excellent antihypertensive efficacy with the CC genotype was found in 11.8% patients, with CT - 33.9%, with TT - 43.3%; good - 35.3%, 32.1%, and 33.3% respectively, satisfactory - 52.9%, 34,0% and 23.4% respectively. Six patients with the CT genotype and nine patients with the CC genotype required the increase in the dose to 10 mg. The number of patients with Adverse drug reactions (ADR) were found in 35.3% of patients with the CC genotype, 6.7% with the TT genotype and 11.3% with the CT genotype. The Kruskal-Wallis test revealed significant differences between CC and TT genotypes in the degree of decrease in SBP (p=0.02), antihypertensive efficacy parameter (p=0.02), an increase in dose requirements (p = 0.04) and the incidence of ADR(p=0.05). In AH patients (I-II stage) with the TT genotype of the C3435T gene polymorphism one can expect higher rates of antihypertensive efficacy of amlodipine in combination with a good safety profile and the lowest ADR percentage, while patients with the CC genotype more likely to develop ADR and lower antihypertensive responsiveness.

Robust LOD scores for variance component-based linkage analysis.

PubMed

Blangero, J; Williams, J T; Almasy, L

2000-01-01

The variance component method is now widely used for linkage analysis of quantitative traits. Although this approach offers many advantages, the importance of the underlying assumption of multivariate normality of the trait distribution within pedigrees has not been studied extensively. Simulation studies have shown that traits with leptokurtic distributions yield linkage test statistics that exhibit excessive Type I error when analyzed naively. We derive analytical formulae relating the deviation from the expected asymptotic distribution of the lod score to the kurtosis and total heritability of the quantitative trait. A simple correction constant yields a robust lod score for any deviation from normality and for any pedigree structure, and effectively eliminates the problem of inflated Type I error due to misspecification of the underlying probability model in variance component-based linkage analysis.

SU-E-QI-21: Iodinated Contrast Agent Time Course In Human Brain Metastasis: A Study For Stereotactic Synchrotron Radiotherapy Clinical Trials

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

Obeid, L; Esteve, F; Adam, J

2014-06-15

Purpose: Synchrotron stereotactic radiotherapy (SSRT) is an innovative treatment combining the selective accumulation of heavy elements in tumors with stereotactic irradiations using monochromatic medium energy x-rays from a synchrotron source. Phase I/II clinical trials on brain metastasis are underway using venous infusion of iodinated contrast agents. The radiation dose enhancement depends on the amount of iodine in the tumor and its time course. In the present study, the reproducibility of iodine concentrations between the CT planning scan day (Day 0) and the treatment day (Day 10) was assessed in order to predict dose errors. Methods: For each of days 0more » and 10, three patients received a biphasic intravenous injection of iodinated contrast agent (40 ml, 4 ml/s, followed by 160 ml, 0.5 ml/s) in order to ensure stable intra-tumoral amounts of iodine during the treatment. Two volumetric CT scans (before and after iodine injection) and a multi-slice dynamic CT of the brain were performed using conventional radiotherapy CT (Day 0) or quantitative synchrotron radiation CT (Day 10). A 3D rigid registration was processed between images. The absolute and relative differences of absolute iodine concentrations and their corresponding dose errors were evaluated in the GTV and PTV used for treatment planning. Results: The differences in iodine concentrations remained within the standard deviation limits. The 3D absolute differences followed a normal distribution centered at zero mg/ml with a variance (∼1 mg/ml) which is related to the image noise. Conclusion: The results suggest that dose errors depend only on the image noise. This study shows that stable amounts of iodine are achievable in brain metastasis for SSRT treatment in a 10 days interval.« less

Spatial and temporal variance in fatty acid and stable isotope signatures across trophic levels in large river systems

USGS Publications Warehouse

Fritts, Andrea; Knights, Brent C.; Lafrancois, Toben D.; Bartsch, Lynn; Vallazza, Jon; Bartsch, Michelle; Richardson, William B.; Karns, Byron N.; Bailey, Sean; Kreiling, Rebecca

2018-01-01

Fatty acid and stable isotope signatures allow researchers to better understand food webs, food sources, and trophic relationships. Research in marine and lentic systems has indicated that the variance of these biomarkers can exhibit substantial differences across spatial and temporal scales, but this type of analysis has not been completed for large river systems. Our objectives were to evaluate variance structures for fatty acids and stable isotopes (i.e. δ13C and δ15N) of seston, threeridge mussels, hydropsychid caddisflies, gizzard shad, and bluegill across spatial scales (10s-100s km) in large rivers of the Upper Mississippi River Basin, USA that were sampled annually for two years, and to evaluate the implications of this variance on the design and interpretation of trophic studies. The highest variance for both isotopes was present at the largest spatial scale for all taxa (except seston δ15N) indicating that these isotopic signatures are responding to factors at a larger geographic level rather than being influenced by local-scale alterations. Conversely, the highest variance for fatty acids was present at the smallest spatial scale (i.e. among individuals) for all taxa except caddisflies, indicating that the physiological and metabolic processes that influence fatty acid profiles can differ substantially between individuals at a given site. Our results highlight the need to consider the spatial partitioning of variance during sample design and analysis, as some taxa may not be suitable to assess ecological questions at larger spatial scales.

Investigations of interference between electromagnetic transponders and wireless MOSFET dosimeters: a phantom study.

PubMed

Su, Zhong; Zhang, Lisha; Ramakrishnan, V; Hagan, Michael; Anscher, Mitchell

2011-05-01

To evaluate both the Calypso Systems' (Calypso Medical Technologies, Inc., Seattle, WA) localization accuracy in the presence of wireless metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters of dose verification system (DVS, Sicel Technologies, Inc., Morrisville, NC) and the dosimeters' reading accuracy in the presence of wireless electromagnetic transponders inside a phantom. A custom-made, solid-water phantom was fabricated with space for transponders and dosimeters. Two inserts were machined with positioning grooves precisely matching the dimensions of the transponders and dosimeters and were arranged in orthogonal and parallel orientations, respectively. To test the transponder localization accuracy with/without presence of dosimeters (hypothesis 1), multivariate analyses were performed on transponder-derived localization data with and without dosimeters at each preset distance to detect statistically significant localization differences between the control and test sets. To test dosimeter dose-reading accuracy with/without presence of transponders (hypothesis 2), an approach of alternating the transponder presence in seven identical fraction dose (100 cGy) deliveries and measurements was implemented. Two-way analysis of variance was performed to examine statistically significant dose-reading differences between the two groups and the different fractions. A relative-dose analysis method was also used to evaluate transponder impact on dose-reading accuracy after dose-fading effect was removed by a second-order polynomial fit. Multivariate analysis indicated that hypothesis 1 was false; there was a statistically significant difference between the localization data from the control and test sets. However, the upper and lower bounds of the 95% confidence intervals of the localized positional differences between the control and test sets were less than 0.1 mm, which was significantly smaller than the minimum clinical localization resolution of 0.5 mm. For hypothesis 2, analysis of variance indicated that there was no statistically significant difference between the dosimeter readings with and without the presence of transponders. Both orthogonal and parallel configurations had difference of polynomial-fit dose to measured dose values within 1.75%. The phantom study indicated that the Calypso System's localization accuracy was not affected clinically due to the presence of DVS wireless MOSFET dosimeters and the dosimeter-measured doses were not affected by the presence of transponders. Thus, the same patients could be implanted with both transponders and dosimeters to benefit from improved accuracy of radiotherapy treatments offered by conjunctional use of the two systems.

40 CFR 142.306 - What are the responsibilities of the public water system, State and the Administrator in ensuring...

Code of Federal Regulations, 2010 CFR

2010-07-01

... meets the source water quality requirements for installing the small system variance technology...: (i) The quality of the source water for the public water system; and (ii) Removal efficiencies and expected useful life of the small system variance technology. ...

40 CFR 142.306 - What are the responsibilities of the public water system, State and the Administrator in ensuring...

Code of Federal Regulations, 2011 CFR

2011-07-01

... meets the source water quality requirements for installing the small system variance technology...: (i) The quality of the source water for the public water system; and (ii) Removal efficiencies and expected useful life of the small system variance technology. ...

40 CFR 142.307 - What terms and conditions must be included in a small system variance?

Code of Federal Regulations, 2010 CFR

2010-07-01

... that may affect proper and effective operation and maintenance of the technology; (2) Monitoring... effective installation, operation and maintenance of the applicable small system variance technology in... health, which may include: (i) Public education requirements; and (ii) Source water protection...

R package MVR for Joint Adaptive Mean-Variance Regularization and Variance Stabilization

PubMed Central

Dazard, Jean-Eudes; Xu, Hua; Rao, J. Sunil

2015-01-01

We present an implementation in the R language for statistical computing of our recent non-parametric joint adaptive mean-variance regularization and variance stabilization procedure. The method is specifically suited for handling difficult problems posed by high-dimensional multivariate datasets (p ≫ n paradigm), such as in ‘omics’-type data, among which are that the variance is often a function of the mean, variable-specific estimators of variances are not reliable, and tests statistics have low powers due to a lack of degrees of freedom. The implementation offers a complete set of features including: (i) normalization and/or variance stabilization function, (ii) computation of mean-variance-regularized t and F statistics, (iii) generation of diverse diagnostic plots, (iv) synthetic and real ‘omics’ test datasets, (v) computationally efficient implementation, using C interfacing, and an option for parallel computing, (vi) manual and documentation on how to setup a cluster. To make each feature as user-friendly as possible, only one subroutine per functionality is to be handled by the end-user. It is available as an R package, called MVR (‘Mean-Variance Regularization’), downloadable from the CRAN. PMID:26819572

Advanced Communication Processing Techniques Held in Ruidoso, New Mexico on 14-17 May 1989

DTIC Science & Technology

1990-01-01

Criteria: * Prob. of Detection and False Alarm * Variances of Parameter Estimators * Prob. of Correct Classiflcsation and Rejection 0 2 In the exposure...couple of criteria. The tell? [LAUGHTER] If it was anybody else, I standard Neyman-Pearson approach for de- wouldn’t say .... tection, variances for... VARIANCE AISJ11T UPPER AND0 LOWER PMIOUIESOES FEATUE---OELET!U FETUA1E----WW-4A140 TIME SEOLIENTIAL CORRELATION FEATUE -$-ESTIMATED INA FEATURE-ID--LOW

Robust optimization based upon statistical theory.

PubMed

Sobotta, B; Söhn, M; Alber, M

2010-08-01

Organ movement is still the biggest challenge in cancer treatment despite advances in online imaging. Due to the resulting geometric uncertainties, the delivered dose cannot be predicted precisely at treatment planning time. Consequently, all associated dose metrics (e.g., EUD and maxDose) are random variables with a patient-specific probability distribution. The method that the authors propose makes these distributions the basis of the optimization and evaluation process. The authors start from a model of motion derived from patient-specific imaging. On a multitude of geometry instances sampled from this model, a dose metric is evaluated. The resulting pdf of this dose metric is termed outcome distribution. The approach optimizes the shape of the outcome distribution based on its mean and variance. This is in contrast to the conventional optimization of a nominal value (e.g., PTV EUD) computed on a single geometry instance. The mean and variance allow for an estimate of the expected treatment outcome along with the residual uncertainty. Besides being applicable to the target, the proposed method also seamlessly includes the organs at risk (OARs). The likelihood that a given value of a metric is reached in the treatment is predicted quantitatively. This information reveals potential hazards that may occur during the course of the treatment, thus helping the expert to find the right balance between the risk of insufficient normal tissue sparing and the risk of insufficient tumor control. By feeding this information to the optimizer, outcome distributions can be obtained where the probability of exceeding a given OAR maximum and that of falling short of a given target goal can be minimized simultaneously. The method is applicable to any source of residual motion uncertainty in treatment delivery. Any model that quantifies organ movement and deformation in terms of probability distributions can be used as basis for the algorithm. Thus, it can generate dose distributions that are robust against interfraction and intrafraction motion alike, effectively removing the need for indiscriminate safety margins.

Balancing Radiation and Contrast Media Dose in Single-Pass Abdominal Multidetector CT: Prospective Evaluation of Image Quality.

PubMed

Camera, Luigi; Romano, Federica; Liccardo, Immacolata; Liuzzi, Raffaele; Imbriaco, Massimo; Mainenti, Pier Paolo; Pizzuti, Laura Micol; Segreto, Sabrina; Maurea, Simone; Brunetti, Arturo

2015-11-01

As both contrast and radiation dose affect the quality of CT images, a constant image quality in abdominal contrast-enhanced multidetector computed tomography (CE-MDCT) could be obtained balancing radiation and contrast media dose according to the age of the patients. Seventy-two (38 Men; 34 women; aged 20-83 years) patients underwent a single-pass abdominal CE-MDCT. Patients were divided into three different age groups: A (20-44 years); B (45-65 years); and C (>65 years). For each group, a different noise index (NI) and contrast media dose (370 mgI/mL) was selected as follows: A (NI, 15; 2.5 mL/kg), B (NI, 12.5; 2 mL/kg), and C (NI, 10; 1.5 mL/kg). Radiation exposure was reported as dose-length product (DLP) in mGy × cm. For quantitative analysis, signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated for both the liver (L) and the abdominal aorta (A). Statistical analysis was performed with a one-way analysis of variance. Standard imaging criteria were used for qualitative analysis. Although peak hepatic enhancement was 152 ± 16, 128 ± 12, and 101 ± 14 Hounsfield units (P < .001) for groups A, B, and C, respectively, no significant differences were observed in the corresponding SNRL with 9.2 ± 1.4, 9.1 ± 1.2, and 9.2 ± 3. Radiation (mGy × cm) and contrast media dose (mL) administered were 476 ± 147 and 155 ± 27 for group A, 926 ± 291 and 130 ± 16 for group B, and 1981 ± 451 and 106 ± 15 for group C, respectively (P < .001). None of the studies was graded as poor or inadequate by both readers, and the prevalence-adjusted bias-adjusted kappa ranged between 0.48 and 0.93 for all but one criteria. A constant image quality in CE-MDCT can be obtained balancing radiation and contrast media dose administered to patients of different age. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

Sexual selection in a lekking bird: the relative opportunity for selection by female choice and male competition.

PubMed

DuVal, Emily H; Kempenaers, Bart

2008-09-07

Leks are classic models for studies of sexual selection due to extreme variance in male reproductive success, but the relative influence of intrasexual competition and female mate choice in creating this skew is debatable. In the lekking lance-tailed manakin (Chiroxiphia lanceolata), these selective episodes are temporally separated into intrasexual competition for alpha status and female mate choice among alpha males that rarely interact. Variance in reproductive success between status classes of adult males (alpha versus non-alpha) can therefore be attributed to male-male competition whereas that within status largely reflects female mate choice. This provides an excellent opportunity for quantifying the relative contribution of each of these mechanisms of sexual selection to the overall opportunity for sexual selection on males (I males). To calculate variance in actual reproductive success, we assigned genetic paternity to 92.3% of 447 chicks sampled in seven years. Reproduction by non-alphas was rare and apparently reflected status misclassifications or opportunistic copulations en route to attaining alpha status rather than alternative mating strategies. On average 31% (range 7-44%, n=6 years) of the total I males was due to variance in reproductive success between alphas and non-alphas. Similarly, in a cohort of same-aged males followed for six years, 44-58% of the total I males was attributed to variance between males of different status. Thus, both intrasexual competition for status and female mate choice among lekking alpha males contribute substantially to the potential for sexual selection in this species.

Differences in Growth Reading Patterns for at-Risk Spanish-Monolingual Children as a Function of a Tier 2 Intervention.

PubMed

Crespo, Patricia; Jiménez, Juan E; Rodríguez, Cristina; Baker, Doris; Park, Yonghan

2018-03-09

The present study compares the patterns of growth of beginning reading skills (i.e., phonemic awareness, phonics, fluency, vocabulary and comprehension) of Spanish speaking monolingual students who received a Tier 2 reading intervention with students who did not receive the intervention. All the students in grades K-2 were screened at the beginning of the year to confirm their risk status. A quasi-experimental longitudinal design was used: the treatment group received a supplemental program in small groups of 3 to 5 students, for 30 minutes daily from November to June. The control group did not receive it. All students were assessed three times during the academic year. A hierarchical linear growth modeling was conducted and differences on growth rate were found in vocabulary in kindergarten (p < .001; variance explained = 77.0%), phonemic awareness in kindergarten (p < .001; variance explained = 43.7%) and first grade (p < .01; variance explained = 15.2%), and finally we also find significant growth differences for second grade in oral reading fluency (p < .05; variance explained = 15.1%) and retell task (p < .05; variance explained = 14.5%). Children at risk for reading disabilities in Spanish can improve their skills when they receive explicit instruction in the context of Response to Intervention (RtI). Findings are discussed for each skill in the context of implementing a Tier 2 small group intervention within an RtI approach. Implications for practice in the Spanish educational context are also discussed for children who are struggling with reading.

Radioiodine (1-131) Dose for the Treatment of Hyperthyroidism in Rajavithi Hospital.

PubMed

Kuanrakcharoen, Pichit

2016-02-01

The main cause of hyperthyroidism is diffuse toxic goiter (Graves' disease), and the treatment of choice after medical therapy failure is radioiodine (I-131). There are two common methods of determining the optimal I-131 dose: calculated dose or fixed dose. The calculated dose method is based on the following formula: 75-200 microcuri/gram of thyroid gland divided by the percentage of radioiodine uptake at 24 hours (24-hour RAIU). As this is quite complex, some centers use fixed doses, such as 5, 10 or 15 mCi because it is simpler. At Rajavithi Hospital, the applied dose of I-131 is determined based on the thyroid gland weight assessed by palpation and other clinical factors. To study the mean I-131 dose for the initial treatment of hyperthyroidism in Rajavithi Hospital, to find the clinical factors that correlate with I-131 treatment dose, and to devise a formula to predict the optimal I-131 treatment dose. This was a retrospective study of 510 patients with a diagnosis of hyperthyroidism who received initial I-131 treatment at the Department of Nuclear Medicine in Rajavithi Hospital between January 2014 and June 2015. Baseline characteristics including age, sex, age at diagnosis, duration of antithyroid drug (ATD) therapy, gland weight (g), 3-hour RAIU and I-131 treatment dose were reviewed from medical records. The mean age ± SD was 41.93 ± 14.11 years (range 14-81 years), and the male to female ratio was 4.1:1. The mean duration of ATD therapy was 3.54 ± 4.02 years (min-max, 0.8-40.6 years). The mean gland weight was 54.35 ± 32.95 grams, and the mean 3-hour RAIU was 55.5 ± 23.69%. The mean I-131 treatment dose was 14.84 ± 5.71 mCi (min-max, 7-30 mCi). There was no significant correlation between dose and age, age at diagnosis, duration of A TD therapy or 3-hour RAIU. The study showed a significant correlation between I-131 dose and gland size, r = 0.938 (p < 0.001), and the regression relationship equation was: 1-131 dose = 0.235 gland size, r = 0.938. I-131 is the treatment of choice for hyperthyroidism after medical therapy failure, and there are various techniques for determining the optimal dose. At Rajavithi Hospital, the I-131 dose (mean = 14.84 ± 5.71 mCi) is estimated based on the gland weight by palpation and other additional clinical factors. The present study provided a practical formula which is simple and practical for use in determining the I-131 dose for the treatment of hyperthyroidism: Dose of I-131 (mCi) = 0.235 x gland size (g).

Skin dose for head and neck cancer patients treated with intensity-modulated radiation therapy(IMRT)

NASA Astrophysics Data System (ADS)

Fu, Hsiao-Ju; Li, Chi-Wei; Tsai, Wei-Ta; Chang, Chih-Chia; Tsang, Yuk-Wah

2017-11-01

The reliability of thermoluminescent dosimeters (ultrathin TLD) and ISP Gafchromic EBT2 film to measure the surface dose in phantom and the skin dose in head-and-neck patients treated with intensity-modulated radiation therapy technique(IMRT) is the research focus. Seven-field treatment plans with prescribed dose of 180 cGy were performed on Eclipse treatment planning system which utilized pencil beam calculation algorithm(PBC). In calibration tests, the variance coefficient of the ultrathin TLDs were within 3%. The points on the calibration curve of the Gafchromic film was within 1% variation. Five measurements were taken on phantom using ultrathin TLD and EBT2 film respectively. The measured mean surface doses between ultrathin TLD or EBT2 film were within 5% deviation. Skin doses of 6 patients were measured for initial 5 fractions and the mean dose per-fraction was calculated. If the extrapolated doses for 30 fractions were below 4000 cGy, the skin reaction grading observed according to Radiation Therapy Oncology Group (RTOG) was either grade 1 or grade 2. If surface dose exceeded 5000 cGy in 32 fractions, then grade 3 skin reactions were observed.

SU-F-T-222: Dose of Fetus and Infant Following Accidental Intakes of I-131 by the Mother

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

Wang, Y; Hu, P

Purpose: To estimate the calculation of absorbed dose to the fetus and infants from intakes of I-131 by the mother. Thus provide some advice to the radioprotection of radioactive accident. Methods: In this clinical case, a staff of nuclear medicine accidently intake I-131 during (10–12 weeks) and after pregnancy. The infant was born at full term, but both lobes of the thyroid gland were found to be absent (bilobar thyroid agenesis). It was suspected that the fetal thyroid agenesis may be related with mother’s contamination of I-131 during pregnancy. Urine samples for 24h were collected at different times after administeredmore » and radioactivity were measured to calculate the dose of intake I-131. Calculate the intake I-131 by the results of personal TLD dosimeter. We adopted the mean of two calculated results as the I-131 intake. According to the dose of intake I-131 by the mother, effective dose and absorbed dose of thyroid for mother, fetus and infant were calculated. Results: The intake of I-131 was estimated for 8.18 mCi. I-131 intake was calculated for 7.9 mCi based on data of TLD dosimeter. We adopted the mean of two results as the I-131 intake. The final result was 8.0 mCi. Effective dose and absorbed dose of thyroid for mother were 7.3Sv and 164 Gy, effective dose and absorbed dose of thyroid for fetus were 2.035 Sv and 40.7 Gy, effective dose and absorbed dose of thyroid for infant were 16.25 Sv and 355Gy. Conclusion: The intake during pregnancy was about 1mCi. The absorbed dose of thyroid of the mother was 19.5Gy, whereas the effective of infant was estimated for 40.7Gy. The function of the mother’s thyroid was normal after diagnosis. But the infant was diagnosed as bilobar thyroid agenesis.« less

A Demonstration of the Analysis of Variance Using Physical Movement and Space

ERIC Educational Resources Information Center

Owen, William J.; Siakaluk, Paul D.

2011-01-01

Classroom demonstrations help students better understand challenging concepts. This article introduces an activity that demonstrates the basic concepts involved in analysis of variance (ANOVA). Students who physically participated in the activity had a better understanding of ANOVA concepts (i.e., higher scores on an exam question answered 2…

77 FR 50622 - Land Disposal Restrictions: Site-Specific Treatment Variance for Hazardous Selenium-Bearing Waste...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-22

... Restrictions: Site-Specific Treatment Variance for Hazardous Selenium-Bearing Waste Treated by U.S. Ecology... program, to U.S. Ecology Nevada in Beatty, Nevada for the treatment of a hazardous selenium- bearing waste.... Ecology Nevada located in Beatty, Nevada. B. Table of Contents I. Background [[Page 50623

Prediction of lethal/effective concentration/dose in the presence of multiple auxiliary covariates and components of variance

USGS Publications Warehouse

Gutreuter, S.; Boogaard, M.A.

2007-01-01

Predictors of the percentile lethal/effective concentration/dose are commonly used measures of efficacy and toxicity. Typically such quantal-response predictors (e.g., the exposure required to kill 50% of some population) are estimated from simple bioassays wherein organisms are exposed to a gradient of several concentrations of a single agent. The toxicity of an agent may be influenced by auxiliary covariates, however, and more complicated experimental designs may introduce multiple variance components. Prediction methods lag examples of those cases. A conventional two-stage approach consists of multiple bivariate predictions of, say, medial lethal concentration followed by regression of those predictions on the auxiliary covariates. We propose a more effective and parsimonious class of generalized nonlinear mixed-effects models for prediction of lethal/effective dose/concentration from auxiliary covariates. We demonstrate examples using data from a study regarding the effects of pH and additions of variable quantities 2???,5???-dichloro-4???- nitrosalicylanilide (niclosamide) on the toxicity of 3-trifluoromethyl-4- nitrophenol to larval sea lamprey (Petromyzon marinus). The new models yielded unbiased predictions and root-mean-squared errors (RMSEs) of prediction for the exposure required to kill 50 and 99.9% of some population that were 29 to 82% smaller, respectively, than those from the conventional two-stage procedure. The model class is flexible and easily implemented using commonly available software. ?? 2007 SETAC.

X-Band Rapid-Scan Electron Paramagnetic Resonance of Radiation-Induced Defects in Tooth Enamel

PubMed Central

Yu, Zhelin; Romanyukha, Alexander; Eaton, Sandra S.; Eaton, Gareth R.

2015-01-01

X-band rapid-scan electron paramagnetic resonance (EPR) spectra from tooth enamel samples irradiated with doses of 0.5, 1 and 10 Gy had substantially improved signal-to-noise relative to conventional continuous wave EPR. The radiation-induced signal in 60 mg of a tooth enamel sample irradiated with a 0.5 Gy dose was readily characterized in spectra recorded with 34 min data acquisition times. The coefficient of variance of the calculated dose for a 1 Gy irradiated sample, based on simulation of the first-derivative spectra for three replicates as the sum of native and radiation-induced signals, was 3.9% for continuous wave and 0.4% for rapid scan. PMID:26207683

Measuring kinetics of complex single ion channel data using mean-variance histograms.

PubMed

Patlak, J B

1993-07-01

The measurement of single ion channel kinetics is difficult when those channels exhibit subconductance events. When the kinetics are fast, and when the current magnitudes are small, as is the case for Na+, Ca2+, and some K+ channels, these difficulties can lead to serious errors in the estimation of channel kinetics. I present here a method, based on the construction and analysis of mean-variance histograms, that can overcome these problems. A mean-variance histogram is constructed by calculating the mean current and the current variance within a brief "window" (a set of N consecutive data samples) superimposed on the digitized raw channel data. Systematic movement of this window over the data produces large numbers of mean-variance pairs which can be assembled into a two-dimensional histogram. Defined current levels (open, closed, or sublevel) appear in such plots as low variance regions. The total number of events in such low variance regions is estimated by curve fitting and plotted as a function of window width. This function decreases with the same time constants as the original dwell time probability distribution for each of the regions. The method can therefore be used: 1) to present a qualitative summary of the single channel data from which the signal-to-noise ratio, open channel noise, steadiness of the baseline, and number of conductance levels can be quickly determined; 2) to quantify the dwell time distribution in each of the levels exhibited. In this paper I present the analysis of a Na+ channel recording that had a number of complexities. The signal-to-noise ratio was only about 8 for the main open state, open channel noise, and fast flickers to other states were present, as were a substantial number of subconductance states. "Standard" half-amplitude threshold analysis of these data produce open and closed time histograms that were well fitted by the sum of two exponentials, but with apparently erroneous time constants, whereas the mean-variance histogram technique provided a more credible analysis of the open, closed, and subconductance times for the patch. I also show that the method produces accurate results on simulated data in a wide variety of conditions, whereas the half-amplitude method, when applied to complex simulated data shows the same errors as were apparent in the real data. The utility and the limitations of this new method are discussed.

Effect of Laser Therapy on Chronic Osteoarthritis of the Knee in Older Subjects

PubMed Central

Youssef, Enas Fawzey; Muaidi, Qassim Ibrahim; Shanb, Alsayed Abdelhameed

2016-01-01

Introduction: Osteoarthritis (OA) is a common degenerative joint disease particularly in older subjects. It is usually associated with pain, restricted range of motion, muscle weakness, difficulties in daily living activities and impaired quality of life. To determine the effects of adding two different intensities of low-level laser therapy (LLLT) to exercise training program on pain severity, joint stiffness, physical function, isometric muscle strength, range of motion of the knee, and quality of life in older subjects with knee OA. Methods: Patients were randomly assigned into three groups. They received 16 sessions, 2 sessions/week for 8 weeks. Group-I: 18 patients were treated with a laser dose of 6 J/cm2 with a total dose of 48 J. Group-II: 18 patients were treated with a laser dose of 3 J/cm2 with a total dose of 27 J. Group-III: 15 patients were treated with laser without emission as a placebo. All patients received same exercise training program including stretching and strengthening exercises. Patients were evaluated before and after intervention by visual analogue scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index for quality of life, handheld dynamometer and universal goniometer. Results: T test revealed that there was a significant reduction in VAS and pain intensity, an increase in isometric muscle strength and range of motion of the knee as well as increase in physical functional ability in three treatment groups. Also analysis of variance (ANOVA) proved significant differences among them and the post hoc tests (LSD) test showed the best improvements for patients of the first group. Conclusion: It can be concluded that addition of LLLT to exercise training program is more effective than exercise training alone in the treatment of older patients with chronic knee OA and the rate of improvement may be dose dependent, as with 6 J/cm2 or 3 J/cm2. PMID:27330707

Hard beta and gamma emissions of 124I. Impact on occupational dose in PET/CT.

PubMed

Kemerink, G J; Franssen, R; Visser, M G W; Urbach, C J A; Halders, S G E A; Frantzen, M J; Brans, B; Teule, G J J; Mottaghy, F M

2011-01-01

The hard beta and gamma radiation of 124I can cause high doses to PET/CT workers. In this study we tried to quantify this occupational exposure and to optimize radioprotection. Thin MCP-Ns thermoluminescent dosimeters suitable for measuring beta and gamma radiation were used for extremity dosimetry, active personal dosimeters for whole-body dosimetry. Extremity doses were determined during dispensing of 124I and oral administration of the activity to the patient, the body dose during all phases of the PET/CT procedure. In addition, dose rates of vials and syringes as used in clinical practice were measured. The procedure for dispensing 124I was optimized using newly developed shielding. Skin dose rates up to 100 mSv/min were measured when in contact with the manufacturer's vial containing 370 MBq of 124I. For an unshielded 5 ml syringe the positron skin dose was about seven times the gamma dose. Before optimization of the preparation of 124I, using an already reasonably safe technique, the highest mean skin dose caused by handling 370 MBq was 1.9 mSv (max. 4.4 mSv). After optimization the skin dose was below 0.2 mSv. The highly energetic positrons emitted by 124I can cause high skin doses if radioprotection is poor. Under optimized conditions occupational doses are acceptable. Education of workers is of paramount importance.

Analysis of Radiation Transport Due to Activated Coolant in the ITER Neutral Beam Injection Cell

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

Royston, Katherine; Wilson, Stephen C.; Risner, Joel M.

Detailed spatial distributions of the biological dose rate due to a variety of sources are required for the design of the ITER tokamak facility to ensure that all radiological zoning limits are met. During operation, water in the Integrated loop of Blanket, Edge-localized mode and vertical stabilization coils, and Divertor (IBED) cooling system will be activated by plasma neutrons and will flow out of the bioshield through a complex system of pipes and heat exchangers. This paper discusses the methods used to characterize the biological dose rate outside the tokamak complex due to 16N gamma radiation emitted by the activatedmore » coolant in the Neutral Beam Injection (NBI) cell of the tokamak building. Activated coolant will enter the NBI cell through the IBED Primary Heat Transfer System (PHTS), and the NBI PHTS will also become activated due to radiation streaming through the NBI system. To properly characterize these gamma sources, the production of 16N, the decay of 16N, and the flow of activated water through the coolant loops were modeled. The impact of conservative approximations on the solution was also examined. Once the source due to activated coolant was calculated, the resulting biological dose rate outside the north wall of the NBI cell was determined through the use of sophisticated variance reduction techniques. The AutomateD VAriaNce reducTion Generator (ADVANTG) software implements methods developed specifically to provide highly effective variance reduction for complex radiation transport simulations such as those encountered with ITER. Using ADVANTG with the Monte Carlo N-particle (MCNP) radiation transport code, radiation responses were calculated on a fine spatial mesh with a high degree of statistical accuracy. In conclusion, advanced visualization tools were also developed and used to determine pipe cell connectivity, to facilitate model checking, and to post-process the transport simulation results.« less

Within- and between- subject variability in methadone pharmacokinetics and pharmacodynamics in methadone maintenance subjects

PubMed Central

Hanna, Julia; Foster, David JR; Salter, Amy; Somogyi, Andrew A; White, Jason M; Bochner, Felix

2005-01-01

Aims To investigate within- and between-subject variability of the pharmacodynamics and pharmacokinetics of (R)- and (S)-methadone in methadone maintenance subjects at steady-state. Methods Six non-holder subjects were studied on three occasions at 7–16 day intervals; doses (20–170 mg/day) remained unchanged. Blood samples and pharmacodynamic data were collected 10–12 times over a 24-h inter-dosing interval. All pharmacodynamic data were expressed as the area under the end-point versus time curve. Using analyses of variance with mixed effects, best estimates were made of the ratio of between- to within-subject variation, with corresponding 95% confidence intervals (CI) for within-subject variation at the average value. Results Subjects were relatively consistent between occasions, whereas there was much greater between-subject variability (P < 0.02) for all measures. Estimates of the ratio of between- to within-subject variation ranged from 2.2–12.8 for pharmacodynamic measures, and 1.3–7.9 for pharmacokinetic parameters. For pain, total mood disturbance, withdrawal, pupil size and respiration rate, 95% CI for within-subject measures ranged ≤2-fold, while this was greater for subjective direct opioid effects (4.2-fold). For CL/F of the active (R)-methadone, the variance ratio was 4.9 (P < 0.0003), with 95% CI for within-subject measures ranging ≤2-fold. (S)-methadone CL/F demonstrated greater within-subject variability (3.4-fold), possibly contributing to a smaller (2.7; P < 0.0003) ratio of between- to within-subject variance. Conclusions Non-holder methadone maintenance treatment participants appear to respond consistently with respect to pharmacokinetics and pharmacodynamics over a 1–2 month period. Such knowledge may help prescribers to determine whether alternative dosing regimens or treatments might be more appropriate in this population. PMID:16187972

Analysis of Radiation Transport Due to Activated Coolant in the ITER Neutral Beam Injection Cell

DOE PAGES

Royston, Katherine; Wilson, Stephen C.; Risner, Joel M.; ...

2017-07-26

Detailed spatial distributions of the biological dose rate due to a variety of sources are required for the design of the ITER tokamak facility to ensure that all radiological zoning limits are met. During operation, water in the Integrated loop of Blanket, Edge-localized mode and vertical stabilization coils, and Divertor (IBED) cooling system will be activated by plasma neutrons and will flow out of the bioshield through a complex system of pipes and heat exchangers. This paper discusses the methods used to characterize the biological dose rate outside the tokamak complex due to 16N gamma radiation emitted by the activatedmore » coolant in the Neutral Beam Injection (NBI) cell of the tokamak building. Activated coolant will enter the NBI cell through the IBED Primary Heat Transfer System (PHTS), and the NBI PHTS will also become activated due to radiation streaming through the NBI system. To properly characterize these gamma sources, the production of 16N, the decay of 16N, and the flow of activated water through the coolant loops were modeled. The impact of conservative approximations on the solution was also examined. Once the source due to activated coolant was calculated, the resulting biological dose rate outside the north wall of the NBI cell was determined through the use of sophisticated variance reduction techniques. The AutomateD VAriaNce reducTion Generator (ADVANTG) software implements methods developed specifically to provide highly effective variance reduction for complex radiation transport simulations such as those encountered with ITER. Using ADVANTG with the Monte Carlo N-particle (MCNP) radiation transport code, radiation responses were calculated on a fine spatial mesh with a high degree of statistical accuracy. In conclusion, advanced visualization tools were also developed and used to determine pipe cell connectivity, to facilitate model checking, and to post-process the transport simulation results.« less

Helicopter Control Energy Reduction Using Moving Horizontal Tail

PubMed Central

Oktay, Tugrul; Sal, Firat

2015-01-01

Helicopter moving horizontal tail (i.e., MHT) strategy is applied in order to save helicopter flight control system (i.e., FCS) energy. For this intention complex, physics-based, control-oriented nonlinear helicopter models are used. Equations of MHT are integrated into these models and they are together linearized around straight level flight condition. A specific variance constrained control strategy, namely, output variance constrained Control (i.e., OVC) is utilized for helicopter FCS. Control energy savings due to this MHT idea with respect to a conventional helicopter are calculated. Parameters of helicopter FCS and dimensions of MHT are simultaneously optimized using a stochastic optimization method, namely, simultaneous perturbation stochastic approximation (i.e., SPSA). In order to observe improvement in behaviors of classical controls closed loop analyses are done. PMID:26180841

Application of low-tube current with iterative model reconstruction on Philips Brilliance iCT Elite FHD in the accuracy of spinal QCT using a European spine phantom.

PubMed

Wu, Yan; Jiang, Yaojun; Han, Xueli; Wang, Mingyue; Gao, Jianbo

2018-02-01

To investigate the repeatability and accuracy of quantitative CT (QCT) measurement of bone mineral density (BMD) by low-mAs using iterative model reconstruction (IMR) technique based on phantom model. European spine phantom (ESP) was selected and measured on the Philips Brilliance iCT Elite FHD machine for 10 times. Data were transmitted to the QCT PRO workstation to measure BMD (mg/cm 3 ) of the ESP (L1, L2, L3). Scanning method: the voltage of X-ray tube is 120 kV, the electric current of X-ray tube output in five respective groups A-E were: 20, 30, 40, 50 and 60 mAs. Reconstruction: all data were reconstructed using filtered back projection (FBP), IR levels of hybrid iterative reconstruction (iDose 4 , levels 1, 2, 3, 4, 5, 6 were used) and IMR (levels 1, 2, 3 were used). ROIs were placed in the middle of L1, L2 and L3 spine phantom in each group. CT values, noise and contrast-to-noise ratio (CNR) were measured and calculated. One-way analysis of variance (ANOVA) was used to compare BMD values of different mAs and different IMR. Radiation dose [volume CT dose index (CTDI vol ) and dose length product (DLP)] was positively correlated with tube current. In L1 with low BMD, different mAs in FBP showed P<0.05, indicating statistically significant BMD in ESP. In other iterative algorithms, different mAs under same iterative algorithms showed P>0.05, indicating no difference in BMD. And P>0.05 was observed among BMD of spine phantom in L1, L2 and L3 under same mAs joined with varied iterative reconstruction. The BMD in L1 varied greatly during FBP reconstruction, and less variation was observed in reconstruction of IMR [1] and IMR [2]. The BMD of L2 changed more during FBP reconstruction, where less was observed in IMR [2]. The BMD of L3 varied greatly during FBP reconstruction, and was less varied in all levels of iDose 4 and reconstruction of IMR [2]. In addition, along with continuous mAs incensement, the CNRs in various algorithms continued to increase. Among them, CNR with the FBP algorithm is the lowest, and CNR of the IMR [3] algorithm is the highest. Repeated measurements of BMD with QCT in the ESP multicenter showed that BMD changes in L1-L3 are the least varied at IMR [2] algorithm. It is recommended to scan at 120 kV with 20 mAs combined with IMR [2] algorithm. In this way, the BMD of spine by QCT could be accurately measured, while radiation dosage significantly reduced and imaging quality improved at the same time.

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

Jans, H-S; Dept. of Oncology, University of Alberta, Edmonton, AB; Stypinski, D

Purpose: To compare the radiation dose to normal organs from the radio-iodinated, hypoxia-binding radiosensitizer iodoazomycin arabinoside (IAZA) for three different isotopes of iodine. Methods: Dosimety studies with normal volunteers had been carried out with [{sup 123}I]IAZA, a drug binding selectively to hypoxic sites. Two other isotopes of iodine, {sup 131}I and {sup 124}I, offer the opportunity to use IAZA as an agent for radioisotope therapy and as an imaging tracer for Positron Emission Tomography. Radioisotope dosimetry for {sup 131}I and {sup 124}I was performed by first deriving from the [{sup 123}I]IAZA studies biological uptake and excretion data. The cumulated activitiesmore » for {sup 131}I or {sup 124}I where obtained by including their half-lives when integrating the biological data and then extrapolating to infinite time points considering a) physical decay only or b) physical and biological excretion. Doses were calculated using the Medical Internal Radiation Dose (MIRD) schema (OLINDA1.1 code, Vanderbilt 2007). Results: Compared to {sup 123}I, organ doses were elevated on average by a factor 6 and 9 for {sup 131}I and {sup 124}I, respectively, if both physical decay and biological excretion were modeled. If only physical decay is considered, doses increase by a factor 18 ({sup 131}I) and 19 ({sup 124}I). Highest organ doses were observed in intestinal walls, urinary bladder and thyroid. Effective doses increased by a factor 11 and 14 for {sup 131}I and {sup 124}I, respectively, if biological and physical decay are present. Purely physical decay yields a 23-fold increase over {sup 123}I for both, {sup 131}I and {sup 124}I. Conclusion: Owing to the significant dose increase, caused by their longer half life and the approximately 10 times larger electronic dose deposited in tissue per nuclear decay, normal tissue doses of IAZA labeled with {sup 131}I and {sup 124}I need to be carefully considered when designing imaging and therapy protocols for clinical trials. Effective blocking of iodine uptake in the thyroid is essential. Alberta Innovates - Health Solutions (AIHS) and Canadian Institutes of Health Research (CIHR)« less

A prospective randomized study of the efficacy and cost-effectiveness of high and low dose regimens of I-131 treatment in hyperthyroidism.

PubMed

Pusuwan, Pawana; Tuntawiroon, Malulee; Sritongkul, Nopamol; Chaudakshetrin, Pachee; Nopmaneejumruslers, Cherdchai; Komoltri, Chulalak; Thepamongkhol, Kullathorn; Khiewvan, Benjapa; Tuchinda, Pongpija; Sriussadaporn, Sutin

2011-03-01

To compare the efficacy and cost-effectiveness of high and low dose regimens of I-131 treatment in patients with hyperthyroidism. One hundred fifty patients with proven hyperthyroidism were randomly allocated into the high (74 patients) and low (76 patients) dose regimen of I-131 treatment. Four patients of the high dose group and one patient of the low dose group were excluded because of lost follow-up. A gland-specific dosage was calculated on the estimated weight of thyroid gland and 24-hour I-131 uptake. The high and low I-131 dose regimens were 150 microCi/gm and 100 microCi/gm, respectively. The first mean radioiodine activity administered to the high and low dose group was 10.2 and 8 mCi, respectively. Repeated treatment was given to 25 patients of the high dose group and 40 patients of the low dose group. Clinical outcome and calculated costs for outpatient attendances, and laboratory tests together with initial and subsequent treatments were evaluated for one year after I-131 treatment. Elimination of hyperthyroidism that resulted in either euthyroidism or hypothyroidism was classified as therapeutic success. The cost effectiveness was also compared. At 6 months after treatment, 45 (64.3%) patients receiving high dose and 59 (78.7%) patients receiving low dose were hyperthyroidism. Clinical outcome at one year showed persistence of hyperthyroidism in 21 (30%) patients of the high dose regimen and 36 (48%) patients of the low dose regimen. At one year post treatment, it was demonstrated that the high dose regimen could eliminate hyperthyroidism in a significantly shorter time than the low dose regimen, i.e., 259.6 days and 305.5 days, respectively, p = 0.008). For the persistent hyperthyroid patients, the average total cost of treatment in the low dose group was significantly higher than that of the high dose group, i.e., 13,422.78 baht and 10,942.79 baht, respectively; p = 0.050). A high dose regimen of radioactive iodine treatment is more effective than the low dose regimen. The successful outcome of a high dose regimen occurred significantly earlier than that of the low dose regimen. For the persistent hyperthyroid patients, the average total cost in the low dose group was significantly higher than that of the high dose group.

Reduced Variance using ADVANTG in Monte Carlo Calculations of Dose Coefficients to Stylized Phantoms

NASA Astrophysics Data System (ADS)

Hiller, Mauritius; Bellamy, Michael; Eckerman, Keith; Hertel, Nolan

2017-09-01

The estimation of dose coefficients of external radiation sources to the organs in phantoms becomes increasingly difficult for lower photon source energies. This study focus on the estimation of photon emitters around the phantom. The computer time needed to calculate a result within a certain precision can be lowered by several orders of magnitude using ADVANTG compared to a standard run. Using ADVANTG which employs the DENOVO adjoint calculation package enables the user to create a fully populated set of weight windows and source biasing instructions for an MCNP calculation.

Shielding design of the Mayo Clinic Scottsdale cyclotron vault

NASA Astrophysics Data System (ADS)

Riper, Kenneth A. Van; Metzger, Robert L.; Nelson, Kevin

2017-09-01

Mayo Clinic Scottsdale (Scottsdale, Arizona) is building a cyclotron vault containing a cyclotron with adjacent targets and a beam line leading to an external target. The targets are irradiated by high energy (15 to 16.5 MeV) protons for the production of radioisotopes. We performed Monte Carlo radiation transport simulations to calculate the radiation dose outside of the vault during irradiation of the cyclotron and external targets. We present the Monte Carlo model including the geometry, sources, and variance reduction methods. Mesh tallies surrounding the vault show the external dose rate is within acceptable limits.

Analysis of liquid medication dose errors made by patients and caregivers using alternative measuring devices.

PubMed

Ryu, Gyeong Suk; Lee, Yu Jeung

2012-01-01

Patients use several types of devices to measure liquid medication. Using a criterion ranging from a 10% to 40% variation from a target 5 mL for a teaspoon dose, previous studies have found that a considerable proportion of patients or caregivers make errors when dosing liquid medication with measuring devices. To determine the rate and magnitude of liquid medication dose errors that occur with patient/caregiver use of various measuring devices in a community pharmacy. Liquid medication measurements by patients or caregivers were observed in a convenience sample of community pharmacy patrons in Korea during a 2-week period in March 2011. Participants included all patients or caregivers (N = 300) who came to the pharmacy to buy over-the-counter liquid medication or to have a liquid medication prescription filled during the study period. The participants were instructed by an investigator who was also a pharmacist to select their preferred measuring devices from 6 alternatives (etched-calibration dosing cup, printed-calibration dosing cup, dosing spoon, syringe, dispensing bottle, or spoon with a bottle adapter) and measure a 5 mL dose of Coben (chlorpheniramine maleate/phenylephrine HCl, Daewoo Pharm. Co., Ltd) syrup using the device of their choice. The investigator used an ISOLAB graduated cylinder (Germany, blue grad, 10 mL) to measure the amount of syrup dispensed by the study participants. Participant characteristics were recorded including gender, age, education level, and relationship to the person for whom the medication was intended. Of the 300 participants, 257 (85.7%) were female; 286 (95.3%) had at least a high school education; and 282 (94.0%) were caregivers (parent or grandparent) for the patient. The mean (SD) measured dose was 4.949 (0.378) mL for the 300 participants. In analysis of variance of the 6 measuring devices, the greatest difference from the 5 mL target was a mean 5.552 mL for 17 subjects who used the regular (etched) dosing cup and 4.660 mL for the dosing spoon (n = 10; P < 0.001). Doses were within 10% of the 5 mL target volume for 88.7% (n = 266) of the participant samples. Only 34 cases (11.3%) had dose errors greater than 10%, and only 6 cases (2.0%) had a variance of more than 20% from the 5 mL target volume. Dose errors greater than 10% of the target volume were more common for the etched dosing cup (47.1%, n = 8), the dosing spoon (50.0%, n = 5), and the printed dosing cup (30.8%, n = 4), but these 3 devices were used by only 13.3% of the study participants. Approximately 1 in 10 participants measured doses of liquid medication with a volume error greater than 10%, and these dose errors were more common with the etched dosing cup, the dosing spoon, and the printed dosing cup. Pharmacists have an opportunity to counsel patients or caregivers regarding the appropriate use of measuring devices for liquid medication.

Adaptive increase in force variance during fatigue in tasks with low redundancy.

PubMed

Singh, Tarkeshwar; S K M, Varadhan; Zatsiorsky, Vladimir M; Latash, Mark L

2010-11-26

We tested a hypothesis that fatigue of an element (a finger) leads to an adaptive neural strategy that involves an increase in force variability in the other finger(s) and an increase in co-variation of commands to fingers to keep total force variability relatively unchanged. We tested this hypothesis using a system with small redundancy (two fingers) and a marginally redundant system (with an additional constraint related to the total moment of force produced by the fingers, unstable condition). The subjects performed isometric accurate rhythmic force production tasks by the index (I) finger and two fingers (I and middle, M) pressing together before and after a fatiguing exercise by the I finger. Fatigue led to a large increase in force variance in the I-finger task and a smaller increase in the IM-task. We quantified two components of variance in the space of hypothetical commands to fingers, finger modes. Under both stable and unstable conditions, there was a large increase in the variance component that did not affect total force and a much smaller increase in the component that did. This resulted in an increase in an index of the force-stabilizing synergy. These results indicate that marginal redundancy is sufficient to allow the central nervous system to use adaptive increase in variability to shield important variables from effects of fatigue. We offer an interpretation of these results based on a recent development of the equilibrium-point hypothesis known as the referent configuration hypothesis. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Maximum dose rate is a determinant of hypothyroidism after 131I therapy of Graves' disease but the total thyroid absorbed dose is not.

PubMed

Krohn, Thomas; Hänscheid, Heribert; Müller, Berthold; Behrendt, Florian F; Heinzel, Alexander; Mottaghy, Felix M; Verburg, Frederik A

2014-11-01

The determinants of successful (131)I therapy of Graves' disease (GD) are unclear. To relate dosimetry parameters to outcome of therapy to identify significant determinants eu- and/or hypothyroidism after (131)I therapy in patients with GD. A retrospective study in which 206 Patients with GD treated in University Hospital between November 1999 and January 2011. All received (131)I therapy aiming at a total absorbed dose to the thyroid of 250 Gy based on pre-therapeutic dosimetry. Post-therapy dosimetric thyroid measurements were performed twice daily until discharge. From these measurements, thyroid (131)I half-life, the total thyroid absorbed dose, and the maximum dose rate after (131)I administration were calculated. In all, 48.5% of patients were hypothyroid and 28.6% of patients were euthyroid after (131)I therapy. In univariate analysis, nonhyperthyroid and hyperthyroid patients only differed by sex. A lower thyroid mass, a higher activity per gram thyroid tissue, a shorter effective thyroidal (131)I half-life, and a higher maximum dose rate, but not the total thyroid absorbed dose, were significantly associated with hypothyroidism. In multivariate analysis, the maximum dose rate remained the only significant determinant of hypothyroidism (P < .001). Maximum dose rates of 2.2 Gy/h and higher were associated with a 100% hypothyroidism rate. Not the total thyroid absorbed dose, but the maximum dose rate is a determinant of successfully achieving hypothyroidism in Graves' disease. Dosimetric concepts aiming at a specific total thyroid absorbed dose will therefore require reconsideration if our data are confirmed prospectively.

Calculations of individual doses for Techa River Cohort members exposed to atmospheric radioiodine from Mayak releases

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

Napier, Bruce A.; Eslinger, Paul W.; Tolstykh, Evgenia I.

Time-dependent thyroid doses were reconstructed for Techa River Cohort members living near the Mayak production facilities from 131I released to the atmosphere for all relevant exposure pathways. The calculational approach uses four general steps: 1) construct estimates of releases of 131I to the air from production facilities; 2) model the transport of 131I in the air and subsequent deposition on the ground and vegetation; 3) model the accumulation of 131I in soil, water, and food products (environmental media); and 4) calculate individual doses by matching appropriate lifestyle and consumption data for the individual to concentrations of 131I in environmental media.more » The dose calculations are implemented in a Monte Carlo framework that produces best estimates and confidence intervals of dose time-histories. The 131I contribution was 75-99% of the thyroid dose. The mean total thyroid dose for cohort members was 193 mGy and the median was 53 mGy. Thyroid doses for about 3% of cohort members were larger than 1 Gy. About 7% of children born in 1940-1950 had doses larger than 1 Gy. The uncertainty in the 131I dose estimates is low enough for this approach to be used in regional epidemiological studies.« less

DOSE-RESPONSE RELATIONSHIPS FOR MOLECULAR ALTERATIONS INDUCED BY B[ A ]P IN STRAIN A/J MOUSE LUNG

EPA Science Inventory

Benzo[a]pyrene (B[a]P) induces tumors in rodents at doses much higher than those found in the environment. Current cancer risk assessment of B[a]P assumes that the risk posed by low level exposure to B[a]P is linear with respect to dose. We have measur...

Modelling heterogeneity variances in multiple treatment comparison meta-analysis--are informative priors the better solution?

PubMed

Thorlund, Kristian; Thabane, Lehana; Mills, Edward J

2013-01-11

Multiple treatment comparison (MTC) meta-analyses are commonly modeled in a Bayesian framework, and weakly informative priors are typically preferred to mirror familiar data driven frequentist approaches. Random-effects MTCs have commonly modeled heterogeneity under the assumption that the between-trial variance for all involved treatment comparisons are equal (i.e., the 'common variance' assumption). This approach 'borrows strength' for heterogeneity estimation across treatment comparisons, and thus, ads valuable precision when data is sparse. The homogeneous variance assumption, however, is unrealistic and can severely bias variance estimates. Consequently 95% credible intervals may not retain nominal coverage, and treatment rank probabilities may become distorted. Relaxing the homogeneous variance assumption may be equally problematic due to reduced precision. To regain good precision, moderately informative variance priors or additional mathematical assumptions may be necessary. In this paper we describe four novel approaches to modeling heterogeneity variance - two novel model structures, and two approaches for use of moderately informative variance priors. We examine the relative performance of all approaches in two illustrative MTC data sets. We particularly compare between-study heterogeneity estimates and model fits, treatment effect estimates and 95% credible intervals, and treatment rank probabilities. In both data sets, use of moderately informative variance priors constructed from the pair wise meta-analysis data yielded the best model fit and narrower credible intervals. Imposing consistency equations on variance estimates, assuming variances to be exchangeable, or using empirically informed variance priors also yielded good model fits and narrow credible intervals. The homogeneous variance model yielded high precision at all times, but overall inadequate estimates of between-trial variances. Lastly, treatment rankings were similar among the novel approaches, but considerably different when compared with the homogenous variance approach. MTC models using a homogenous variance structure appear to perform sub-optimally when between-trial variances vary between comparisons. Using informative variance priors, assuming exchangeability or imposing consistency between heterogeneity variances can all ensure sufficiently reliable and realistic heterogeneity estimation, and thus more reliable MTC inferences. All four approaches should be viable candidates for replacing or supplementing the conventional homogeneous variance MTC model, which is currently the most widely used in practice.

Genetic Variance in Homophobia: Evidence from Self- and Peer Reports.

PubMed

Zapko-Willmes, Alexandra; Kandler, Christian

2018-01-01

The present twin study combined self- and peer assessments of twins' general homophobia targeting gay men in order to replicate previous behavior genetic findings across different rater perspectives and to disentangle self-rater-specific variance from common variance in self- and peer-reported homophobia (i.e., rater-consistent variance). We hypothesized rater-consistent variance in homophobia to be attributable to genetic and nonshared environmental effects, and self-rater-specific variance to be partially accounted for by genetic influences. A sample of 869 twins and 1329 peer raters completed a seven item scale containing cognitive, affective, and discriminatory homophobic tendencies. After correction for age and sex differences, we found most of the genetic contributions (62%) and significant nonshared environmental contributions (16%) to individual differences in self-reports on homophobia to be also reflected in peer-reported homophobia. A significant genetic component, however, was self-report-specific (38%), suggesting that self-assessments alone produce inflated heritability estimates to some degree. Different explanations are discussed.

Daily Goals Formulation and Enhanced Visualization of Mechanical Ventilation Variance Improves Mechanical Ventilation Score.

PubMed

Walsh, Brian K; Smallwood, Craig; Rettig, Jordan; Kacmarek, Robert M; Thompson, John; Arnold, John H

2017-03-01

The systematic implementation of evidence-based practice through the use of guidelines, checklists, and protocols mitigates the risks associated with mechanical ventilation, yet variation in practice remains prevalent. Recent advances in software and hardware have allowed for the development and deployment of an enhanced visualization tool that identifies mechanical ventilation goal variance. Our aim was to assess the utility of daily goal establishment and a computer-aided visualization of variance. This study was composed of 3 phases: a retrospective observational phase (baseline) followed by 2 prospective sequential interventions. Phase I intervention comprised daily goal establishment of mechanical ventilation. Phase II intervention was the setting and monitoring of daily goals of mechanical ventilation with a web-based data visualization system (T3). A single score of mechanical ventilation was developed to evaluate the outcome. The baseline phase evaluated 130 subjects, phase I enrolled 31 subjects, and phase II enrolled 36 subjects. There were no differences in demographic characteristics between cohorts. A total of 171 verbalizations of goals of mechanical ventilation were completed in phase I. The use of T3 increased by 87% from phase I. Mechanical ventilation score improved by 8.4% in phase I and 11.3% in phase II from baseline ( P = .032). The largest effect was in the low risk V T category, with a 40.3% improvement from baseline in phase I, which was maintained at 39% improvement from baseline in phase II ( P = .01). mechanical ventilation score was 9% higher on average in those who survived. Daily goal formation and computer-enhanced visualization of mechanical ventilation variance were associated with an improvement in goal attainment by evidence of an improved mechanical ventilation score. Further research is needed to determine whether improvements in mechanical ventilation score through a targeted, process-oriented intervention will lead to improved patient outcomes. (ClinicalTrials.gov registration NCT02184208.). Copyright © 2017 by Daedalus Enterprises.

A simplified analytical random walk model for proton dose calculation

NASA Astrophysics Data System (ADS)

Yao, Weiguang; Merchant, Thomas E.; Farr, Jonathan B.

2016-10-01

We propose an analytical random walk model for proton dose calculation in a laterally homogeneous medium. A formula for the spatial fluence distribution of primary protons is derived. The variance of the spatial distribution is in the form of a distance-squared law of the angular distribution. To improve the accuracy of dose calculation in the Bragg peak region, the energy spectrum of the protons is used. The accuracy is validated against Monte Carlo simulation in water phantoms with either air gaps or a slab of bone inserted. The algorithm accurately reflects the dose dependence on the depth of the bone and can deal with small-field dosimetry. We further applied the algorithm to patients’ cases in the highly heterogeneous head and pelvis sites and used a gamma test to show the reasonable accuracy of the algorithm in these sites. Our algorithm is fast for clinical use.

Estimation Of Organ Doses From Solar Particle Events For Future Space Exploration Missions

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee; Cucinotta, Francis A.

2006-01-01

Radiation protection practices define the effective dose as a weighted sum of equivalent dose over major organ sites for radiation cancer risks. Since a crew personnel dosimeter does not make direct measurement of the effective dose, it has been estimated with skin-dose measurements and radiation transport codes for ISS and STS missions. If sufficient protection is not provided near solar maximum, the radiation risk can be significant due to exposure to sporadic solar particle events (SPEs) as well as to the continuous galactic cosmic radiation (GCR) on future exploratory-class and long-duration missions. For accurate estimates of overall fatal cancer risks from SPEs, the specific doses at various blood forming organs (BFOs) were considered, because proton fluences and doses vary considerably across marrow regions. Previous estimates of BFO doses from SPEs have used an average body-shielding distribution for the bone marrow based on the computerized anatomical man model (CAM). With the development of an 82-point body-shielding distribution at BFOs, the mean and variance of SPE doses in the major active marrow regions (head and neck, chest, abdomen, pelvis and thighs) will be presented. Consideration of the detailed distribution of bone marrow sites is one of many requirements to improve the estimation of effective doses for radiation cancer risks.

Can contrast media increase organ doses in CT examinations? A clinical study.

PubMed

Amato, Ernesto; Salamone, Ignazio; Naso, Serena; Bottari, Antonio; Gaeta, Michele; Blandino, Alfredo

2013-06-01

The purpose of this article is to quantify the CT radiation dose increment in five organs resulting from the administration of iodinated contrast medium. Forty consecutive patients who underwent both un-enhanced and contrast-enhanced thoracoabdominal CT were included in our retrospective study. The dose increase between CT before and after contrast agent administration was evaluated in the portal phase for the thyroid, liver, spleen, pancreas, and kidneys by applying a previously validated method. An increase in radiation dose was noted in all organs studied. Average dose increments were 19% for liver, 71% for kidneys, 33% for spleen and pancreas, and 41% for thyroid. Kidneys exhibited the maximum dose increment, whereas the pancreas showed the widest variance because of the differences in fibro-fatty involution. Finally, thyroids with high attenuation values on unenhanced CT showed a lower Hounsfield unit increase and, thus, a smaller increment in the dose. Our study showed an increase in radiation dose in several parenchymatous tissues on contrast-enhanced CT. Our method allowed us to evaluate the dose increase from the change in attenuation measured in Hounsfield units. Because diagnostic protocols require multiple acquisitions after the contrast agent administration, such a dose increase should be considered when optimizing these protocols.

Upper Limits on the 21 cm Epoch of Reionization Power Spectrum from One Night with LOFAR

NASA Astrophysics Data System (ADS)

Patil, A. H.; Yatawatta, S.; Koopmans, L. V. E.; de Bruyn, A. G.; Brentjens, M. A.; Zaroubi, S.; Asad, K. M. B.; Hatef, M.; Jelić, V.; Mevius, M.; Offringa, A. R.; Pandey, V. N.; Vedantham, H.; Abdalla, F. B.; Brouw, W. N.; Chapman, E.; Ciardi, B.; Gehlot, B. K.; Ghosh, A.; Harker, G.; Iliev, I. T.; Kakiichi, K.; Majumdar, S.; Mellema, G.; Silva, M. B.; Schaye, J.; Vrbanec, D.; Wijnholds, S. J.

2017-03-01

We present the first limits on the Epoch of Reionization 21 cm H I power spectra, in the redshift range z = 7.9-10.6, using the Low-Frequency Array (LOFAR) High-Band Antenna (HBA). In total, 13.0 hr of data were used from observations centered on the North Celestial Pole. After subtraction of the sky model and the noise bias, we detect a non-zero {{{Δ }}}{{I}}2={(56+/- 13{mK})}2 (1-σ) excess variance and a best 2-σ upper limit of {{{Δ }}}212< {(79.6{mK})}2 at k = 0.053 h cMpc-1 in the range z = 9.6-10.6. The excess variance decreases when optimizing the smoothness of the direction- and frequency-dependent gain calibration, and with increasing the completeness of the sky model. It is likely caused by (I) residual side-lobe noise on calibration baselines, (II) leverage due to nonlinear effects, (III) noise and ionosphere-induced gain errors, or a combination thereof. Further analyses of the excess variance will be discussed in forthcoming publications.

Measuring the Relationship between Two Questionnaires: Appropriate Definitions of Intuitive Understandings

ERIC Educational Resources Information Center

Burt, Gordon

2005-01-01

A number of recent articles have claimed strong relationships--i.e., very high "proportions of shared variance"--between pairs of teaching and learning questionnaires. These claims have been the subject of debate and it has emerged that the proportion of shared variance is defined as the complement of Wilks' lambda. The present article argues that…

Teaching Principles of One-Way Analysis of Variance Using M&M's Candy

ERIC Educational Resources Information Center

Schwartz, Todd A.

2013-01-01

I present an active learning classroom exercise illustrating essential principles of one-way analysis of variance (ANOVA) methods. The exercise is easily conducted by the instructor and is instructive (as well as enjoyable) for the students. This is conducive for demonstrating many theoretical and practical issues related to ANOVA and lends itself…

An Investigation of the Raudenbush (1988) Test for Studying Variance Heterogeneity.

ERIC Educational Resources Information Center

Harwell, Michael

1997-01-01

The meta-analytic method proposed by S. W. Raudenbush (1988) for studying variance heterogeneity was studied. Results of a Monte Carlo study indicate that the Type I error rate of the test is sensitive to even modestly platykurtic score distributions and to the ratio of study sample size to the number of studies. (SLD)

Standard errors in forest area

Treesearch

Joseph McCollum

2002-01-01

I trace the development of standard error equations for forest area, beginning with the theory behind double sampling and the variance of a product. The discussion shifts to the particular problem of forest area - at which time the theory becomes relevant. There are subtle difficulties in figuring out which variance of a product equation should be used. The equations...

One Idea of Portfolio Risk Control Focusing on States of Correlation

NASA Astrophysics Data System (ADS)

Nishiyama, Noboru

2004-04-01

In the modern portfolio theory there are 2 major risk parameters that mean and variance. Correlations should be playing important role as well but variance is thought to be most important risk parameter for risk control in the theory. I focused on states of correlation to calculate eigen values as risk control parameter.

TH-AB-201-10: Portal Dosimetry with Elekta IViewDose:Performance of the Simplified Commissioning Approach Versus Full Commissioning

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

Kydonieos, M; Folgueras, A; Florescu, L

2016-06-15

Purpose: Elekta recently developed a solution for in-vivo EPID dosimetry (iViewDose, Elekta AB, Stockholm, Sweden) in conjunction with the Netherlands Cancer Institute (NKI). This uses a simplified commissioning approach via Template Commissioning Models (TCMs), consisting of a subset of linac-independent pre-defined parameters. This work compares the performance of iViewDose using a TCM commissioning approach with that corresponding to full commissioning. Additionally, the dose reconstruction based on the simplified commissioning approach is validated via independent dose measurements. Methods: Measurements were performed at the NKI on a VersaHD™ (Elekta AB, Stockholm, Sweden). Treatment plans were generated with Pinnacle 9.8 (Philips Medical Systems,more » Eindhoven, The Netherlands). A farmer chamber dose measurement and two EPID images were used to create a linac-specific commissioning model based on a TCM. A complete set of commissioning measurements was collected and a full commissioning model was created.The performance of iViewDose based on the two commissioning approaches was compared via a series of set-to-work tests in a slab phantom. In these tests, iViewDose reconstructs and compares EPID to TPS dose for square fields, IMRT and VMAT plans via global gamma analysis and isocentre dose difference. A clinical VMAT plan was delivered to a homogeneous Octavius 4D phantom (PTW, Freiburg, Germany). Dose was measured with the Octavius 1500 array and VeriSoft software was used for 3D dose reconstruction. EPID images were acquired. TCM-based iViewDose and 3D Octavius dose distributions were compared against the TPS. Results: For both the TCM-based and the full commissioning approaches, the pass rate, mean γ and dose difference were >97%, <0.5 and <2.5%, respectively. Equivalent gamma analysis results were obtained for iViewDose (TCM approach) and Octavius for a VMAT plan. Conclusion: iViewDose produces similar results with the simplified and full commissioning approaches. Good agreement is obtained between iViewDose (simplified approach) and the independent measurement tool. This research is funded by Elekta Limited.« less

Consumption of Yogurt and the Incident Risk of Cardiovascular Disease: A Meta-Analysis of Nine Cohort Studies

PubMed Central

Wu, Lei; Sun, Dali

2017-01-01

Previous systematic reviews and meta-analyses have evaluated the association of dairy consumption and the risk of cardiovascular disease (CVD). However, the findings were inconsistent. No quantitative analysis has specifically assessed the effect of yogurt intake on the incident risk of CVD. We searched the PubMed and the Embase databases from inception to 10 January 2017. A generic inverse-variance method was used to pool the fully-adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs) with a random-effects model. A generalized least squares trend estimation model was used to calculate the specific slopes in the dose-response analysis. The present systematic review and meta-analysis identified nine prospective cohort articles involving a total of 291,236 participants. Compared with the lowest category, highest category of yogurt consumption was not significantly related with the incident risk of CVD, and the RR (95% CI) was 1.01 (0.95, 1.08) with an evidence of significant heterogeneity (I2 = 52%). However, intake of ≥200 g/day yogurt was significantly associated with a lower risk of CVD in the subgroup analysis. There was a trend that a higher level of yogurt consumption was associated with a lower incident risk of CVD in the dose-response analysis. A daily dose of ≥200 g yogurt intake might be associated with a lower incident risk of CVD. Further cohort studies and randomized controlled trials are still demanded to establish and confirm the observed association in populations with different characteristics. PMID:28327514

Calculations of individual doses for Techa River Cohort members exposed to atmospheric radioiodine from Mayak releases.

PubMed

Napier, Bruce A; Eslinger, Paul W; Tolstykh, Evgenia I; Vorobiova, Marina I; Tokareva, Elena E; Akhramenko, Boris N; Krivoschapov, Victor A; Degteva, Marina O

2017-11-01

Time-dependent thyroid doses were reconstructed for over 29,000 Techa River Cohort members living near the Mayak production facilities from 131 I released to the atmosphere for all relevant exposure pathways. The calculational approach uses four general steps: 1) construct estimates of releases of 131 I to the air from production facilities; 2) model the transport of 131 I in the air and subsequent deposition on the ground and vegetation; 3) model the accumulation of 131 I in environmental media; and 4) calculate individualized doses. The dose calculations are implemented in a Monte Carlo framework that produces best estimates and confidence intervals of dose time-histories. Other radionuclide contributors to thyroid dose were evaluated. The 131 I contribution was 75-99% of the thyroid dose. The mean total thyroid dose for cohort members was 193 mGy and the median was 53 mGy. Thyroid doses for about 3% of cohort members were larger than 1 Gy. About 7% of children born in 1940-1950 had doses larger than 1 Gy. The uncertainty in the 131 I dose estimates is low enough for this approach to be used in regional epidemiological studies. Copyright © 2017. Published by Elsevier Ltd.

Warfarin sensitivity genotyping: a review of the literature and summary of patient experience.

PubMed

Moyer, Thomas P; O'Kane, Dennis J; Baudhuin, Linnea M; Wiley, Carmen L; Fortini, Alexandre; Fisher, Pamela K; Dupras, Denise M; Chaudhry, Rajeev; Thapa, Prabin; Zinsmeister, Alan R; Heit, John A

2009-12-01

The antithrombotic benefits of warfarin are countered by a narrow therapeutic index that contributes to excessive bleeding or cerebrovascular clotting and stroke in some patients. This article reviews the current literature describing warfarin sensitivity genotyping and compares the results of that review to the findings of our study in 189 patients at Mayo Clinic conducted between June 2001 and April 2003. For the review of the literature, we identified relevant peer-reviewed articles by searching the Web of Knowledge using key word warfarin-related adverse event. For the 189 Mayo Clinic patients initiating warfarin therapy to achieve a target international normalized ratio (INR) in the range of 2.0 to 3.5, we analyzed the CYP2C9 (cytochrome P450 2C9) and VKORC1 (vitamin K epoxide reductase complex, subunit 1) genetic loci to study the relationship among the initial warfarin dose, steady-state dose, time to achieve steady-state dose, variations in INR, and allelic variance. Results were compared with those previously reported in the literature for 637 patients. The relationships between allelic variants and warfarin sensitivity found in our study of Mayo Clinic patients are fundamentally the same as in those reported by others. The Mayo Clinic population is predominantly white and shows considerable allelic variability in CYP2C9 and VKORC1. Certain of these alleles are associated with increased sensitivity to warfarin. Polymorphisms in CYP2C9 and VKORC1 have a considerable effect on warfarin dose in white people. A correlation between steady-state warfarin dose and allelic variants of CYP2C9 and VKORC1 has been demonstrated by many previous reports and is reconfirmed in this report. The allelic variants found to most affect warfarin sensitivity are CYP2C9*1*1-VKORC1BB (less warfarin sensitivity than typical); CYP2C9*1*1-VKORC1AA (considerable variance in INR throughout initiation); CYP2C9*1*2-VKORC1AB (more sensitivity to warfarin than typical); CYP2C9*1*3-VKORC1AB (much more sensitivity to warfarin than typical); CYP2C9*1*2-VKORC1AB (much more sensitivity to warfarin than typical); CYP2C9*1*3-VKORC1AA (much more sensitivity to warfarin than typical); and CYP2C9*2*2-VKORC1AB (much more sensitivity to warfarin than typical). Although we were unable to show an association between allelic variants and initial warfarin dose or dose escalation, an association was seen between allelic variant and steady-state warfarin dose. White people show considerable variance in CYP2C9 allele types, whereas people of Asian or African descent infrequently carry CYP2C9 allelic variants. The VKORC1AA allele associated with high warfarin sensitivity predominates in those of Asian descent, whereas white people and those of African descent show diversity, carrying either the VKORC1BB, an allele associated with low warfarin sensitivity, or VKORC1AB or VKORC1AA, alleles associated with moderate and high warfarin sensitivity, respectively.

A simple low-cost of liquid I-131 dispenser for routine radiopharmaceutical dispensing at nuclear medicine department, Institut Kanser Negara

NASA Astrophysics Data System (ADS)

Said, M. A.; Ashhar, Z. N.; Suhaimi, N. E. F.; Zainon, R.

2016-01-01

In routine radiopharmaceutical Iodine-131 (131I) dispensing, the amount of radiation dose received by the personnel depends on the distance between the personnel and the source, the time spent manipulating the source and the amount of shielding used to reduce the dose rate from the source. The novel iRAD-I131 dispenser using recycle 131I liquid lead pot will lead into low cost production, less maintenance and low dose received by the personnel that prepared the 131I. The new fabricated of low cost 131I dispenser was tested and the dose received by personnel were evaluated. The body of lead material is made from 2.5 cm lead shielded coated with epoxy paint to absorb the radiation dose up to 7.4 GBq of 131 I. The lead pot was supported with two stainless steel rod. The Optically Stimulated Luminescence (OSL) nanodot was used in this study to measure the dose rate at both extremities for every personnel who prepared the 131I. Each OSL nanodot was attached at the fingertip. Three different personnel (experienced between one to ten years above in preparing the radiopharmaceuticals) were participated in this study. The average equivalent dose at right and left hand were 122.694 ± 121.637 µSv/GBq and 77.281 ± 62.146 µSv/GBq respectively. This study found that the dose exposure received using iRAD-I131 was less up to seven times compared to the conventional method. The comparison of experimental data using iRAD-I131 and established radiopharmaceutical dispenser was also discussed. The innovation of 131I dispenser is highly recommended in a small radiopharmaceutical facility with limited budget. The novel iRAD-I131 enables implementation of higher output liquid dispensing with low radiation dose to the personnel.

A simple low-cost of liquid I-131 dispenser for routine radiopharmaceutical dispensing at nuclear medicine department, Institut Kanser Negara

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

Said, M. A.; Suhaimi, N. E. F.; Ashhar, Z. N., E-mail: aminhpj@gmail.com

In routine radiopharmaceutical Iodine-131 ({sup 131}I) dispensing, the amount of radiation dose received by the personnel depends on the distance between the personnel and the source, the time spent manipulating the source and the amount of shielding used to reduce the dose rate from the source. The novel iRAD-I131 dispenser using recycle {sup 131}I liquid lead pot will lead into low cost production, less maintenance and low dose received by the personnel that prepared the {sup 131}I. The new fabricated of low cost {sup 131}I dispenser was tested and the dose received by personnel were evaluated. The body of leadmore » material is made from 2.5 cm lead shielded coated with epoxy paint to absorb the radiation dose up to 7.4 GBq of {sup 131} I. The lead pot was supported with two stainless steel rod. The Optically Stimulated Luminescence (OSL) nanodot was used in this study to measure the dose rate at both extremities for every personnel who prepared the {sup 131}I. Each OSL nanodot was attached at the fingertip. Three different personnel (experienced between one to ten years above in preparing the radiopharmaceuticals) were participated in this study. The average equivalent dose at right and left hand were 122.694 ± 121.637 µSv/GBq and 77.281 ± 62.146 µSv/GBq respectively. This study found that the dose exposure received using iRAD-I131 was less up to seven times compared to the conventional method. The comparison of experimental data using iRAD-I131 and established radiopharmaceutical dispenser was also discussed. The innovation of {sup 131}I dispenser is highly recommended in a small radiopharmaceutical facility with limited budget. The novel iRAD-I131 enables implementation of higher output liquid dispensing with low radiation dose to the personnel.« less

What is the danger of the anomaly zone for empirical phylogenetics?

PubMed

Huang, Huateng; Knowles, L Lacey

2009-10-01

The increasing number of observations of gene trees with discordant topologies in phylogenetic studies has raised awareness about the problems of incongruence between species trees and gene trees. Moreover, theoretical treatments focusing on the impact of coalescent variance on phylogenetic study have also identified situations where the most probable gene trees are ones that do not match the underlying species tree (i.e., anomalous gene trees [AGTs]). However, although the theoretical proof of the existence of AGTs is alarming, the actual risk that AGTs pose to empirical phylogenetic study is far from clear. Establishing the conditions (i.e., the branch lengths in a species tree) for which AGTs are possible does not address the critical issue of how prevalent they might be. Furthermore, theoretical characterization of the species trees for which AGTs may pose a problem (i.e., the anomaly zone or the species histories for which AGTs are theoretically possible) is based on consideration of just one source of variance that contributes to species tree and gene tree discord-gene lineage coalescence. Yet, empirical data contain another important stochastic component-mutational variance. Estimated gene trees will differ from the underlying gene trees (i.e., the actual genealogy) because of the random process of mutation. Here, we take a simulation approach to investigate the prevalence of AGTs, among estimated gene trees, thereby characterizing the boundaries of the anomaly zone taking into account both coalescent and mutational variances. We also determine the frequency of realized AGTs, which is critical to putting the theoretical work on AGTs into a realistic biological context. Two salient results emerge from this investigation. First, our results show that mutational variance can indeed expand the parameter space (i.e., the relative branch lengths in a species tree) where AGTs might be observed in empirical data. By exploring the underlying cause for the expanded anomaly zone, we identify aspects of empirical data relevant to avoiding the problems that AGTs pose for species tree inference from multilocus data. Second, for the empirical species histories where AGTs are possible, unresolved trees-not AGTs-predominate the pool of estimated gene trees. This result suggests that the risk of AGTs, while they exist in theory, may rarely be realized in practice. By considering the biological realities of both mutational and coalescent variances, the study has refined, and redefined, what the actual challenges are for empirical phylogenetic study of recently diverged taxa that have speciated rapidly-AGTs themselves are unlikely to pose a significant danger to empirical phylogenetic study.

Experimental and Monte Carlo evaluation of Eclipse treatment planning system for effects on dose distribution of the hip prostheses

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

Çatlı, Serap, E-mail: serapcatli@hotmail.com; Tanır, Güneş

2013-10-01

The present study aimed to investigate the effects of titanium, titanium alloy, and stainless steel hip prostheses on dose distribution based on the Monte Carlo simulation method, as well as the accuracy of the Eclipse treatment planning system (TPS) at 6 and 18 MV photon energies. In the present study the pencil beam convolution (PBC) method implemented in the Eclipse TPS was compared to the Monte Carlo method and ionization chamber measurements. The present findings show that if high-Z material is used in prosthesis, large dose changes can occur due to scattering. The variance in dose observed in the presentmore » study was dependent on material type, density, and atomic number, as well as photon energy; as photon energy increased back scattering decreased. The dose perturbation effect of hip prostheses was significant and could not be predicted accurately by the PBC method for hip prostheses. The findings show that for accurate dose calculation the Monte Carlo-based TPS should be used in patients with hip prostheses.« less

Investigations of interference between electromagnetic transponders and wireless MOSFET dosimeters: A phantom study

PubMed Central

Su, Zhong; Zhang, Lisha; Ramakrishnan, V.; Hagan, Michael; Anscher, Mitchell

2011-01-01

Purpose: To evaluate both the Calypso Systems’ (Calypso Medical Technologies, Inc., Seattle, WA) localization accuracy in the presence of wireless metal–oxide–semiconductor field-effect transistor (MOSFET) dosimeters of dose verification system (DVS, Sicel Technologies, Inc., Morrisville, NC) and the dosimeters’ reading accuracy in the presence of wireless electromagnetic transponders inside a phantom.Methods: A custom-made, solid-water phantom was fabricated with space for transponders and dosimeters. Two inserts were machined with positioning grooves precisely matching the dimensions of the transponders and dosimeters and were arranged in orthogonal and parallel orientations, respectively. To test the transponder localization accuracy with∕without presence of dosimeters (hypothesis 1), multivariate analyses were performed on transponder-derived localization data with and without dosimeters at each preset distance to detect statistically significant localization differences between the control and test sets. To test dosimeter dose-reading accuracy with∕without presence of transponders (hypothesis 2), an approach of alternating the transponder presence in seven identical fraction dose (100 cGy) deliveries and measurements was implemented. Two-way analysis of variance was performed to examine statistically significant dose-reading differences between the two groups and the different fractions. A relative-dose analysis method was also used to evaluate transponder impact on dose-reading accuracy after dose-fading effect was removed by a second-order polynomial fit.Results: Multivariate analysis indicated that hypothesis 1 was false; there was a statistically significant difference between the localization data from the control and test sets. However, the upper and lower bounds of the 95% confidence intervals of the localized positional differences between the control and test sets were less than 0.1 mm, which was significantly smaller than the minimum clinical localization resolution of 0.5 mm. For hypothesis 2, analysis of variance indicated that there was no statistically significant difference between the dosimeter readings with and without the presence of transponders. Both orthogonal and parallel configurations had difference of polynomial-fit dose to measured dose values within 1.75%.Conclusions: The phantom study indicated that the Calypso System’s localization accuracy was not affected clinically due to the presence of DVS wireless MOSFET dosimeters and the dosimeter-measured doses were not affected by the presence of transponders. Thus, the same patients could be implanted with both transponders and dosimeters to benefit from improved accuracy of radiotherapy treatments offered by conjunctional use of the two systems. PMID:21776780

FW-CADIS Method for Global and Semi-Global Variance Reduction of Monte Carlo Radiation Transport Calculations

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

Wagner, John C; Peplow, Douglas E.; Mosher, Scott W

2014-01-01

This paper presents a new hybrid (Monte Carlo/deterministic) method for increasing the efficiency of Monte Carlo calculations of distributions, such as flux or dose rate distributions (e.g., mesh tallies), as well as responses at multiple localized detectors and spectra. This method, referred to as Forward-Weighted CADIS (FW-CADIS), is an extension of the Consistent Adjoint Driven Importance Sampling (CADIS) method, which has been used for more than a decade to very effectively improve the efficiency of Monte Carlo calculations of localized quantities, e.g., flux, dose, or reaction rate at a specific location. The basis of this method is the development ofmore » an importance function that represents the importance of particles to the objective of uniform Monte Carlo particle density in the desired tally regions. Implementation of this method utilizes the results from a forward deterministic calculation to develop a forward-weighted source for a deterministic adjoint calculation. The resulting adjoint function is then used to generate consistent space- and energy-dependent source biasing parameters and weight windows that are used in a forward Monte Carlo calculation to obtain more uniform statistical uncertainties in the desired tally regions. The FW-CADIS method has been implemented and demonstrated within the MAVRIC sequence of SCALE and the ADVANTG/MCNP framework. Application of the method to representative, real-world problems, including calculation of dose rate and energy dependent flux throughout the problem space, dose rates in specific areas, and energy spectra at multiple detectors, is presented and discussed. Results of the FW-CADIS method and other recently developed global variance reduction approaches are also compared, and the FW-CADIS method outperformed the other methods in all cases considered.« less

Improved accuracy of ultrasound-guided therapies using electromagnetic tracking: in-vivo speed of sound measurements

NASA Astrophysics Data System (ADS)

Samboju, Vishal; Adams, Matthew; Salgaonkar, Vasant; Diederich, Chris J.; Cunha, J. Adam M.

2017-02-01

The speed of sound (SOS) for ultrasound devices used for imaging soft tissue is often calibrated to water, 1540 m/s1 , despite in-vivo soft tissue SOS varying from 1450 to 1613 m/s2 . Images acquired with 1540 m/s and used in conjunction with stereotactic external coordinate systems can thus result in displacement errors of several millimeters. Ultrasound imaging systems are routinely used to guide interventional thermal ablation and cryoablation devices, or radiation sources for brachytherapy3 . Brachytherapy uses small radioactive pellets, inserted interstitially with needles under ultrasound guidance, to eradicate cancerous tissue4 . Since the radiation dose diminishes with distance from the pellet as 1/r2 , imaging uncertainty of a few millimeters can result in significant erroneous dose delivery5,6. Likewise, modeling of power deposition and thermal dose accumulations from ablative sources are also prone to errors due to placement offsets from SOS errors7 . This work presents a method of mitigating needle placement error due to SOS variances without the need of ionizing radiation2,8. We demonstrate the effects of changes in dosimetry in a prostate brachytherapy environment due to patientspecific SOS variances and the ability to mitigate dose delivery uncertainty. Electromagnetic (EM) sensors embedded in the brachytherapy ultrasound system provide information regarding 3D position and orientation of the ultrasound array. Algorithms using data from these two modalities are used to correct bmode images to account for SOS errors. While ultrasound localization resulted in >3 mm displacements, EM resolution was verified to <1 mm precision using custom-built phantoms with various SOS, showing 1% accuracy in SOS measurement.

Reducing statistical uncertainties in simulated organ doses of phantoms immersed in water

DOE PAGES

Hiller, Mauritius M.; Veinot, Kenneth G.; Easterly, Clay E.; ...

2016-08-13

In this study, methods are addressed to reduce the computational time to compute organ-dose rate coefficients using Monte Carlo techniques. Several variance reduction techniques are compared including the reciprocity method, importance sampling, weight windows and the use of the ADVANTG software package. For low-energy photons, the runtime was reduced by a factor of 10 5 when using the reciprocity method for kerma computation for immersion of a phantom in contaminated water. This is particularly significant since impractically long simulation times are required to achieve reasonable statistical uncertainties in organ dose for low-energy photons in this source medium and geometry. Althoughmore » the MCNP Monte Carlo code is used in this paper, the reciprocity technique can be used equally well with other Monte Carlo codes.« less

Second Cancers After Fractionated Radiotherapy: Stochastic Population Dynamics Effects

NASA Technical Reports Server (NTRS)

Sachs, Rainer K.; Shuryak, Igor; Brenner, David; Fakir, Hatim; Hahnfeldt, Philip

2007-01-01

When ionizing radiation is used in cancer therapy it can induce second cancers in nearby organs. Mainly due to longer patient survival times, these second cancers have become of increasing concern. Estimating the risk of solid second cancers involves modeling: because of long latency times, available data is usually for older, obsolescent treatment regimens. Moreover, modeling second cancers gives unique insights into human carcinogenesis, since the therapy involves administering well characterized doses of a well studied carcinogen, followed by long-term monitoring. In addition to putative radiation initiation that produces pre-malignant cells, inactivation (i.e. cell killing), and subsequent cell repopulation by proliferation can be important at the doses relevant to second cancer situations. A recent initiation/inactivation/proliferation (IIP) model characterized quantitatively the observed occurrence of second breast and lung cancers, using a deterministic cell population dynamics approach. To analyze ifradiation-initiated pre-malignant clones become extinct before full repopulation can occur, we here give a stochastic version of this I I model. Combining Monte Carlo simulations with standard solutions for time-inhomogeneous birth-death equations, we show that repeated cycles of inactivation and repopulation, as occur during fractionated radiation therapy, can lead to distributions of pre-malignant cells per patient with variance >> mean, even when pre-malignant clones are Poisson-distributed. Thus fewer patients would be affected, but with a higher probability, than a deterministic model, tracking average pre-malignant cell numbers, would predict. Our results are applied to data on breast cancers after radiotherapy for Hodgkin disease. The stochastic IIP analysis, unlike the deterministic one, indicates: a) initiated, pre-malignant cells can have a growth advantage during repopulation, not just during the longer tumor latency period that follows; b) weekend treatment gaps during radiotherapy, apart from decreasing the probability of eradicating the primary cancer, substantially increase the risk of later second cancers.

Distribution of a low dose compound within pharmaceutical tablet by using multivariate curve resolution on Raman hyperspectral images.

PubMed

Boiret, Mathieu; de Juan, Anna; Gorretta, Nathalie; Ginot, Yves-Michel; Roger, Jean-Michel

2015-01-25

In this work, Raman hyperspectral images and multivariate curve resolution-alternating least squares (MCR-ALS) are used to study the distribution of actives and excipients within a pharmaceutical drug product. This article is mainly focused on the distribution of a low dose constituent. Different approaches are compared, using initially filtered or non-filtered data, or using a column-wise augmented dataset before starting the MCR-ALS iterative process including appended information on the low dose component. In the studied formulation, magnesium stearate is used as a lubricant to improve powder flowability. With a theoretical concentration of 0.5% (w/w) in the drug product, the spectral variance contained in the data is weak. By using a principal component analysis (PCA) filtered dataset as a first step of the MCR-ALS approach, the lubricant information is lost in the non-explained variance and its associated distribution in the tablet cannot be highlighted. A sufficient number of components to generate the PCA noise-filtered matrix has to be used in order to keep the lubricant variability within the data set analyzed or, otherwise, work with the raw non-filtered data. Different models are built using an increasing number of components to perform the PCA reduction. It is shown that the magnesium stearate information can be extracted from a PCA model using a minimum of 20 components. In the last part, a column-wise augmented matrix, including a reference spectrum of the lubricant, is used before starting MCR-ALS process. PCA reduction is performed on the augmented matrix, so the magnesium stearate contribution is included within the MCR-ALS calculations. By using an appropriate PCA reduction, with a sufficient number of components, or by using an augmented dataset including appended information on the low dose component, the distribution of the two actives, the two main excipients and the low dose lubricant are correctly recovered. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluation and recommendation of sensitivity analysis methods for application to Stochastic Human Exposure and Dose Simulation models.

PubMed

Mokhtari, Amirhossein; Christopher Frey, H; Zheng, Junyu

2006-11-01

Sensitivity analyses of exposure or risk models can help identify the most significant factors to aid in risk management or to prioritize additional research to reduce uncertainty in the estimates. However, sensitivity analysis is challenged by non-linearity, interactions between inputs, and multiple days or time scales. Selected sensitivity analysis methods are evaluated with respect to their applicability to human exposure models with such features using a testbed. The testbed is a simplified version of a US Environmental Protection Agency's Stochastic Human Exposure and Dose Simulation (SHEDS) model. The methods evaluated include the Pearson and Spearman correlation, sample and rank regression, analysis of variance, Fourier amplitude sensitivity test (FAST), and Sobol's method. The first five methods are known as "sampling-based" techniques, wheras the latter two methods are known as "variance-based" techniques. The main objective of the test cases was to identify the main and total contributions of individual inputs to the output variance. Sobol's method and FAST directly quantified these measures of sensitivity. Results show that sensitivity of an input typically changed when evaluated under different time scales (e.g., daily versus monthly). All methods provided similar insights regarding less important inputs; however, Sobol's method and FAST provided more robust insights with respect to sensitivity of important inputs compared to the sampling-based techniques. Thus, the sampling-based methods can be used in a screening step to identify unimportant inputs, followed by application of more computationally intensive refined methods to a smaller set of inputs. The implications of time variation in sensitivity results for risk management are briefly discussed.

Bioequivalence evaluation of two brands of amoxicillin/clavulanic acid 250/125 mg combination tablets in healthy human volunteers: use of replicate design approach.

PubMed

Idkaidek, Nasir M; Al-Ghazawi, Ahmad; Najib, Naji M

2004-12-01

The purpose of this study was to apply a replicate design approach to a bioequivalence study of amoxicillin/clavulanic acid combination following a 250/125 mg oral dose to 23 subjects, and to compare the analysis of individual bioequivalence with average bioequivalence. This was conducted as a 2-treatment 2-sequence 4-period crossover study. Average bioequivalence was shown, while the results from the individual bioequivalence approach had no success in showing bioequivalence. In conclusion, the individual bioequivalence approach is a strong statistical tool to test for intra-subject variances and also subject-by-formulation interaction variance compared with the average bioequivalence approach. copyright (c) 2004 John Wiley & Sons, Ltd.

Dopamine D1 Sensitivity in the Prefrontal Cortex Predicts General Cognitive Abilities and is Modulated by Working Memory Training

ERIC Educational Resources Information Center

Wass, Christopher; Pizzo, Alessandro; Sauce, Bruno; Kawasumi, Yushi; Sturzoiu, Tudor; Ree, Fred; Otto, Tim; Matzel, Louis D.

2013-01-01

A common source of variance (i.e., "general intelligence") underlies an individual's performance across diverse tests of cognitive ability, and evidence indicates that the processing efficacy of working memory may serve as one such source of common variance. One component of working memory, selective attention, has been reported to…

A Negative Binomial Regression Model for Accuracy Tests

ERIC Educational Resources Information Center

Hung, Lai-Fa

2012-01-01

Rasch used a Poisson model to analyze errors and speed in reading tests. An important property of the Poisson distribution is that the mean and variance are equal. However, in social science research, it is very common for the variance to be greater than the mean (i.e., the data are overdispersed). This study embeds the Rasch model within an…

Applications of multiscale change point detections to monthly stream flow and rainfall in Xijiang River in southern China, part I: correlation and variance

NASA Astrophysics Data System (ADS)

Zhu, Yuxiang; Jiang, Jianmin; Huang, Changxing; Chen, Yongqin David; Zhang, Qiang

2018-04-01

This article, as part I, introduces three algorithms and applies them to both series of the monthly stream flow and rainfall in Xijiang River, southern China. The three algorithms include (1) normalization of probability distribution, (2) scanning U test for change points in correlation between two time series, and (3) scanning F-test for change points in variances. The normalization algorithm adopts the quantile method to normalize data from a non-normal into the normal probability distribution. The scanning U test and F-test have three common features: grafting the classical statistics onto the wavelet algorithm, adding corrections for independence into each statistic criteria at given confidence respectively, and being almost objective and automatic detection on multiscale time scales. In addition, the coherency analyses between two series are also carried out for changes in variance. The application results show that the changes of the monthly discharge are still controlled by natural precipitation variations in Xijiang's fluvial system. Human activities disturbed the ecological balance perhaps in certain content and in shorter spells but did not violate the natural relationships of correlation and variance changes so far.

Meta-analysis with missing study-level sample variance data.

PubMed

Chowdhry, Amit K; Dworkin, Robert H; McDermott, Michael P

2016-07-30

We consider a study-level meta-analysis with a normally distributed outcome variable and possibly unequal study-level variances, where the object of inference is the difference in means between a treatment and control group. A common complication in such an analysis is missing sample variances for some studies. A frequently used approach is to impute the weighted (by sample size) mean of the observed variances (mean imputation). Another approach is to include only those studies with variances reported (complete case analysis). Both mean imputation and complete case analysis are only valid under the missing-completely-at-random assumption, and even then the inverse variance weights produced are not necessarily optimal. We propose a multiple imputation method employing gamma meta-regression to impute the missing sample variances. Our method takes advantage of study-level covariates that may be used to provide information about the missing data. Through simulation studies, we show that multiple imputation, when the imputation model is correctly specified, is superior to competing methods in terms of confidence interval coverage probability and type I error probability when testing a specified group difference. Finally, we describe a similar approach to handling missing variances in cross-over studies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A General Definition of the Heritable Variation That Determines the Potential of a Population to Respond to Selection

PubMed Central

Bijma, Piter

2011-01-01

Genetic selection is a major force shaping life on earth. In classical genetic theory, response to selection is the product of the strength of selection and the additive genetic variance in a trait. The additive genetic variance reflects a population’s intrinsic potential to respond to selection. The ordinary additive genetic variance, however, ignores the social organization of life. With social interactions among individuals, individual trait values may depend on genes in others, a phenomenon known as indirect genetic effects. Models accounting for indirect genetic effects, however, lack a general definition of heritable variation. Here I propose a general definition of the heritable variation that determines the potential of a population to respond to selection. This generalizes the concept of heritable variance to any inheritance model and level of organization. The result shows that heritable variance determining potential response to selection is the variance among individuals in the heritable quantity that determines the population mean trait value, rather than the usual additive genetic component of phenotypic variance. It follows, therefore, that heritable variance may exceed phenotypic variance among individuals, which is impossible in classical theory. This work also provides a measure of the utilization of heritable variation for response to selection and integrates two well-known models of maternal genetic effects. The result shows that relatedness between the focal individual and the individuals affecting its fitness is a key determinant of the utilization of heritable variance for response to selection. PMID:21926298

A general definition of the heritable variation that determines the potential of a population to respond to selection.

PubMed

Bijma, Piter

2011-12-01

Genetic selection is a major force shaping life on earth. In classical genetic theory, response to selection is the product of the strength of selection and the additive genetic variance in a trait. The additive genetic variance reflects a population's intrinsic potential to respond to selection. The ordinary additive genetic variance, however, ignores the social organization of life. With social interactions among individuals, individual trait values may depend on genes in others, a phenomenon known as indirect genetic effects. Models accounting for indirect genetic effects, however, lack a general definition of heritable variation. Here I propose a general definition of the heritable variation that determines the potential of a population to respond to selection. This generalizes the concept of heritable variance to any inheritance model and level of organization. The result shows that heritable variance determining potential response to selection is the variance among individuals in the heritable quantity that determines the population mean trait value, rather than the usual additive genetic component of phenotypic variance. It follows, therefore, that heritable variance may exceed phenotypic variance among individuals, which is impossible in classical theory. This work also provides a measure of the utilization of heritable variation for response to selection and integrates two well-known models of maternal genetic effects. The result shows that relatedness between the focal individual and the individuals affecting its fitness is a key determinant of the utilization of heritable variance for response to selection.

Optimization of hybrid iterative reconstruction level in pediatric body CT.

PubMed

Karmazyn, Boaz; Liang, Yun; Ai, Huisi; Eckert, George J; Cohen, Mervyn D; Wanner, Matthew R; Jennings, S Gregory

2014-02-01

The objective of our study was to attempt to optimize the level of hybrid iterative reconstruction (HIR) in pediatric body CT. One hundred consecutive chest or abdominal CT examinations were selected. For each examination, six series were obtained: one filtered back projection (FBP) and five HIR series (iDose(4)) levels 2-6. Two pediatric radiologists, blinded to noise measurements, independently chose the optimal HIR level and then rated series quality. We measured CT number (mean in Hounsfield units) and noise (SD in Hounsfield units) changes by placing regions of interest in the liver, muscles, subcutaneous fat, and aorta. A mixed-model analysis-of-variance test was used to analyze correlation of noise reduction with the optimal HIR level compared with baseline FBP noise. One hundred CT examinations were performed of 88 patients (52 females and 36 males) with a mean age of 8.5 years (range, 19 days-18 years); 12 patients had both chest and abdominal CT studies. Radiologists agreed to within one level of HIR in 92 of 100 studies. The mean quality rating was significantly higher for HIR than FBP (3.6 vs 3.3, respectively; p < 0.01). HIR caused minimal (0-0.2%) change in CT numbers. Noise reduction varied among structures and patients. Liver noise reduction positively correlated with baseline noise when the optimal HIR level was used (p < 0.01). HIR levels were significantly correlated with body weight and effective diameter of the upper abdomen (p < 0.01). HIR, such as iDose(4), improves the quality of body CT scans of pediatric patients by decreasing noise; HIR level 3 or 4 is optimal for most studies. The optimal HIR level was less effective in reducing liver noise in children with lower baseline noise.

Is There a Common Summary Statistical Process for Representing the Mean and Variance? A Study Using Illustrations of Familiar Items.

PubMed

Yang, Yi; Tokita, Midori; Ishiguchi, Akira

2018-01-01

A number of studies revealed that our visual system can extract different types of summary statistics, such as the mean and variance, from sets of items. Although the extraction of such summary statistics has been studied well in isolation, the relationship between these statistics remains unclear. In this study, we explored this issue using an individual differences approach. Observers viewed illustrations of strawberries and lollypops varying in size or orientation and performed four tasks in a within-subject design, namely mean and variance discrimination tasks with size and orientation domains. We found that the performances in the mean and variance discrimination tasks were not correlated with each other and demonstrated that extractions of the mean and variance are mediated by different representation mechanisms. In addition, we tested the relationship between performances in size and orientation domains for each summary statistic (i.e. mean and variance) and examined whether each summary statistic has distinct processes across perceptual domains. The results illustrated that statistical summary representations of size and orientation may share a common mechanism for representing the mean and possibly for representing variance. Introspections for each observer performing the tasks were also examined and discussed.

Measuring kinetics of complex single ion channel data using mean-variance histograms.

PubMed Central

Patlak, J B

1993-01-01

The measurement of single ion channel kinetics is difficult when those channels exhibit subconductance events. When the kinetics are fast, and when the current magnitudes are small, as is the case for Na+, Ca2+, and some K+ channels, these difficulties can lead to serious errors in the estimation of channel kinetics. I present here a method, based on the construction and analysis of mean-variance histograms, that can overcome these problems. A mean-variance histogram is constructed by calculating the mean current and the current variance within a brief "window" (a set of N consecutive data samples) superimposed on the digitized raw channel data. Systematic movement of this window over the data produces large numbers of mean-variance pairs which can be assembled into a two-dimensional histogram. Defined current levels (open, closed, or sublevel) appear in such plots as low variance regions. The total number of events in such low variance regions is estimated by curve fitting and plotted as a function of window width. This function decreases with the same time constants as the original dwell time probability distribution for each of the regions. The method can therefore be used: 1) to present a qualitative summary of the single channel data from which the signal-to-noise ratio, open channel noise, steadiness of the baseline, and number of conductance levels can be quickly determined; 2) to quantify the dwell time distribution in each of the levels exhibited. In this paper I present the analysis of a Na+ channel recording that had a number of complexities. The signal-to-noise ratio was only about 8 for the main open state, open channel noise, and fast flickers to other states were present, as were a substantial number of subconductance states. "Standard" half-amplitude threshold analysis of these data produce open and closed time histograms that were well fitted by the sum of two exponentials, but with apparently erroneous time constants, whereas the mean-variance histogram technique provided a more credible analysis of the open, closed, and subconductance times for the patch. I also show that the method produces accurate results on simulated data in a wide variety of conditions, whereas the half-amplitude method, when applied to complex simulated data shows the same errors as were apparent in the real data. The utility and the limitations of this new method are discussed. Images FIGURE 2 FIGURE 4 FIGURE 8 FIGURE 9 PMID:7690261

Bioavailability and Preliminary Clinical Efficacy of Intrarectal Artesunate in Ghanaian Children with Moderate Malaria

PubMed Central

Krishna, Sanjeev; Planche, Tim; Agbenyega, Tsiri; Woodrow, Charles; Agranoff, Dan; Bedu-Addo, George; Owusu-Ofori, Alex K.; Appiah, John Adabie; Ramanathan, Surash; Mansor, Sharif M.; Navaratnam, Visweswaran

2001-01-01

We report the first detailed pharmacokinetic assessment of intrarectal (i.r.) artesunate (ARS) in African children. Artesunate was given intravenously (i.v.; 2.4 mg/kg of body weight) and i.r. (10 or 20 mg/kg formulated as 50- or 200-mg suppositories [Rectocaps]) in a crossover study design to 34 Ghanaian children with moderate falciparum malaria. The median relative bioavailability of dihydroartemisinin (DHA), the active antimalarial metabolite of ARS, was higher in the low-dose i.r. group (10 mg/kg) than in the high-dose i.r. group (20 mg/kg) (58 versus 23%; P = 0.018). There was wide interpatient variation in the area under the concentration-time curve after i.r. ARS administration (up to 9-fold in the high-dose group and 20-fold in the low-dose group). i.r. administered ARS was more rapidly absorbed in the low-dose group than the high-dose group (median [range] absorption half-lives, 0.7 h [0.3 to 1.24 h] versus 1.1 h [0.6 to 2.7 h] [P = 0.023]. i.r. administered ARS was eliminated with a median (range) half-life of 0.8 h (0.4 to 2.7 h) (low-dose group and 0.9 h (0.1 to 2.5 h) (high-dose group) (P = 1). The fractional clearances of DHA were 3.9, 2.6, and 1.5 liters/kg/h for the 20-mg/kg, 10-mg/kg and i.v. groups, respectively (P = 0.001 and P = 0.06 for the high-and low-dose i.r. groups compared with the i.v. groups, respectively). The median volumes of distribution for DHA were 1.5 liters kg (20 mg/kg, i.r. group), 1.8 liters/kg (10 mg/kg, i.r. group), and 0.6 liters/kg (i.v. group) (P < 0.05 for both i.r. groups compared with the i.v. group). Parasite clearance kinetics were comparable in all treatment groups. i.r. administered ARS may be a useful alternative to parenterally administered ARS in the management of moderate childhood malaria and should be studied further. PMID:11158748

The role of cortisol and psychopathy in the cycle of violence

PubMed Central

Green, Charles E.; Alcorn, Joseph L.; Swann, Alan C.; Moeller, F. Gerard; Lane, Scott D.

2016-01-01

Rationale Child abuse and neglect are universal risk factors for delinquency, violence, and aggression; this phenomenon is known as the cycle of violence. Additional factors—psychopathy, impulsiveness, and disruptions in the hypothalamic–pituitary–adrenal (HPA) axis—play a role in aggressive behavior but have rarely been examined in the same conceptual and experimental framework. Objectives We sought to examine the above-mentioned risk factors for aggression in a prospective study employing psychopharmacologic and psychometric techniques. Methods Sixty-seven adult participants were given an acute dose of 20 mg cortisol in a placebo-controlled, within-subject, counter-balanced dosing design. Salivary cortisol was measured at baseline and at regular intervals across a 5 h testing period. Following dosing, state-aggressive behavior was measured by a laboratory task, the Point-Subtraction Aggression Paradigm. History of child abuse/−neglect, psychopathy, impulsivity, and a trait measure of aggression were assessed through self-report questionnaires. Results Using multiple regression, a model including abuse/neglect, psychopathy, impulsivity, and baseline cortisol explained 58 % of the variance in trait aggression and 26 % of the variance in state aggression. Abuse/neglect predicted diminished HPA-axis reactivity and HPA-axis reactivity showed a trend toward predicting state and trait aggression, although it was not a significant mediating variable between abuse/neglect and aggression. Conclusions The results indicate that child maltreatment, psychopathy and HPA-axis reactivity interact to provide a confluence over aggressive behavior, and intervention efforts need to consider all these factors. PMID:23371492

Human Platelet Lipidomics: Variance, Visualization, Flux, and Fuel.

PubMed

FitzGerald, Garret A

2016-05-10

The cardioprotection afforded by low-dose aspirin reflects the biological importance of the platelet lipid thromboxane A2. In this issue of Cell Metabolism, Slatter et al. (2016) illuminate the breadth, complexity, and variability of the human platelet lipidome under conditions of thrombin activation and aspirin suppression, potentially facilitating the pursuit of precision medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

Variability of Photodynamic Killing in Escherichia coli and Avoidance of Variability with Agar

PubMed Central

O'Bryan, Corliss; Harrison, Arthur P.

1971-01-01

Photodynamic killing of Escherichia coli in acridine orange is influenced by the composition of the containing vessel, and after high kill the variance between replicate suspensions is greater than attributable solely to sampling and plating. Addition of agar minimizes both phenomena, but a higher illumination dose is required to produce the same degree of killing. PMID:4934057

Improved delivery of fenoterol plus ipratropium bromide using Respimat compared with a conventional metered dose inhaler.

PubMed

Goldberg, J; Freund, E; Beckers, B; Hinzmann, R

2001-02-01

Asthma can be effectively treated by the use of bronchodilator therapies administered by inhalation. The objective of this study was to describe the dose-response relationship of combined doses of fenoterol hydrobromide (F) and ipratropium bromide (I) (F/I) delivered via Respimat, a soft mist inhaler, and to establish the Respimat dose which is as efficacious and as safe as the standard marketed dose of F/I (100/40 microg) which is delivered via a conventional metered dose inhaler (MDI). In a double-blind (within device) cross-over study with a balanced incomplete block design, 62 patients with stable bronchial asthma (mean forced expiratory volume in one second (FEV1) 63% predicted) were randomized at five study centres to receive five out of eight possible treatments: placebo, F/I 12.5/5, 25/10, 50/20, 100/40 or 200/80 microg delivered via Respimat; F/I 50/20 or 100/40 microg delivered via MDI. Pulmonary function results were based on the per-protocol dataset, comprising 47 patients. All F/I doses produced greater increases in FEV1 than placebo. A log-linear dose-response was obtained for the average increase in FEV1 up to 6 h (AUC0-6 h) and peak FEV1 across the dose range administered by Respimat. Statistically, therapeutic equivalence was not demonstrated between any F/I dose administered by Respimat compared with the MDI. However 12.5/5 and 25/10 microg F/I administered via Respimat were closest (slightly superior) to the F/I dose of 100/40 microg delivered via MDI. Pharmacokinetic data from 34 patients indicated a two-fold greater systemic availability of both drugs following inhalation by Respimat compared to MDI. In general, the active treatments were well tolerated and safe with regard to vital signs, electrocardiography, laboratory parameters and adverse events. In conclusion, combined administration of fenoterol hydrobromide and ipratropium bromide via Respimat, is as effective and as safe as higher doses given via a metered dose inhaler.

A Multilevel AR(1) Model: Allowing for Inter-Individual Differences in Trait-Scores, Inertia, and Innovation Variance.

PubMed

Jongerling, Joran; Laurenceau, Jean-Philippe; Hamaker, Ellen L

2015-01-01

In this article we consider a multilevel first-order autoregressive [AR(1)] model with random intercepts, random autoregression, and random innovation variance (i.e., the level 1 residual variance). Including random innovation variance is an important extension of the multilevel AR(1) model for two reasons. First, between-person differences in innovation variance are important from a substantive point of view, in that they capture differences in sensitivity and/or exposure to unmeasured internal and external factors that influence the process. Second, using simulation methods we show that modeling the innovation variance as fixed across individuals, when it should be modeled as a random effect, leads to biased parameter estimates. Additionally, we use simulation methods to compare maximum likelihood estimation to Bayesian estimation of the multilevel AR(1) model and investigate the trade-off between the number of individuals and the number of time points. We provide an empirical illustration by applying the extended multilevel AR(1) model to daily positive affect ratings from 89 married women over the course of 42 consecutive days.

Variance in direct exposure measures of typing force and wrist kinematics across hours and days among office computer workers.

PubMed

Asundi, Krishna; Johnson, Peter W; Dennerlein, Jack T

2012-01-01

To determine the number of direct measurements needed to obtain a representative estimate of typing force and wrist kinematics, continuous measures of keyboard reaction force and wrist joint angle were collected at the workstation of 22 office workers while they completed their own work over three days, six hours per day. Typing force and wrist kinematics during keyboard, mouse and idle activities were calculated for each hour of measurement along with variance in measurements between subjects and between day and hour within subjects. Variance in measurements between subjects was significantly greater than variance in measurements between days and hours within subjects. Therefore, we concluded a single, one-hour period of continuous measures is sufficient to identify differences in typing force and wrist kinematics between subjects. Within subjects, day and hour of measurement had a significant effect on some measures and thus should be accounted for when comparing measures within a subject. The dose response relationship between exposure to computer related biomechanical risk factors and musculoskeletal disorders is poorly understood due to the difficulty and cost of direct measures. This study demonstrates a single hour of direct continuous measures is sufficient to identify differences in wrist kinematics and typing force between individuals.

Modelling heterogeneity variances in multiple treatment comparison meta-analysis – Are informative priors the better solution?

PubMed Central

2013-01-01

Background Multiple treatment comparison (MTC) meta-analyses are commonly modeled in a Bayesian framework, and weakly informative priors are typically preferred to mirror familiar data driven frequentist approaches. Random-effects MTCs have commonly modeled heterogeneity under the assumption that the between-trial variance for all involved treatment comparisons are equal (i.e., the ‘common variance’ assumption). This approach ‘borrows strength’ for heterogeneity estimation across treatment comparisons, and thus, ads valuable precision when data is sparse. The homogeneous variance assumption, however, is unrealistic and can severely bias variance estimates. Consequently 95% credible intervals may not retain nominal coverage, and treatment rank probabilities may become distorted. Relaxing the homogeneous variance assumption may be equally problematic due to reduced precision. To regain good precision, moderately informative variance priors or additional mathematical assumptions may be necessary. Methods In this paper we describe four novel approaches to modeling heterogeneity variance - two novel model structures, and two approaches for use of moderately informative variance priors. We examine the relative performance of all approaches in two illustrative MTC data sets. We particularly compare between-study heterogeneity estimates and model fits, treatment effect estimates and 95% credible intervals, and treatment rank probabilities. Results In both data sets, use of moderately informative variance priors constructed from the pair wise meta-analysis data yielded the best model fit and narrower credible intervals. Imposing consistency equations on variance estimates, assuming variances to be exchangeable, or using empirically informed variance priors also yielded good model fits and narrow credible intervals. The homogeneous variance model yielded high precision at all times, but overall inadequate estimates of between-trial variances. Lastly, treatment rankings were similar among the novel approaches, but considerably different when compared with the homogenous variance approach. Conclusions MTC models using a homogenous variance structure appear to perform sub-optimally when between-trial variances vary between comparisons. Using informative variance priors, assuming exchangeability or imposing consistency between heterogeneity variances can all ensure sufficiently reliable and realistic heterogeneity estimation, and thus more reliable MTC inferences. All four approaches should be viable candidates for replacing or supplementing the conventional homogeneous variance MTC model, which is currently the most widely used in practice. PMID:23311298

Dose Calculations for [131I] Meta-Iodobenzylguanidine-Induced Bystander Effects

PubMed Central

Gow, M. D.; Seymour, C. B.; Boyd, M.; Mairs, R. J.; Prestiwch, W. V.; Mothersill, C. E.

2014-01-01

Targeted radiotherapy is a potentially useful treatment for some cancers and may be potentiated by bystander effects. However, without estimation of absorbed dose, it is difficult to compare the effects with conventional external radiation treatment. Methods: Using the Vynckier – Wambersie dose point kernel, a model for dose rate evaluation was created allowing for calculation of absorbed dose values to two cell lines transfected with the noradrenaline transporter (NAT) gene and treated with [131I]MIBG. Results: The mean doses required to decrease surviving fractions of UVW/NAT and EJ138/NAT cells, which received medium from [131I]MIBG-treated cells, to 25 – 30% were 1.6 and 1.7 Gy respectively. The maximum mean dose rates achieved during [131I]MIBG treatment were 0.09 – 0.75 Gy/h for UVW/NAT and 0.07 – 0.78 Gy/h for EJ138/NAT. These were significantly lower than the external beam gamma radiation dose rate of 15 Gy/h. In the case of control lines which were incapable of [131I]MIBG uptake the mean absorbed doses following radiopharmaceutical were 0.03 – 0.23 Gy for UVW and 0.03 – 0.32 Gy for EJ138. Conclusion: [131I]MIBG treatment for ICCM production elicited a bystander dose-response profile similar to that generated by external beam gamma irradiation but with significantly greater cell death. PMID:24659931

Dose response of fish oil versus safflower oil on graft arteriosclerosis in rabbit heterotopic cardiac allografts.

PubMed Central

Yun, K L; Fann, J I; Sokoloff, M H; Fong, L G; Sarris, G E; Billingham, M E; Miller, D C

1991-01-01

With the advent of cyclosporin A, accelerated coronary arteriosclerosis has become the major impediment to the long-term survival of heart transplant recipients. Due to epidemiologic reports suggesting a salutary effect of fish oil, the dose response of fish oil on graft coronary arteriosclerosis in a rabbit heterotopic cardiac allograft model was assessed using safflower oil as a caloric control. Seven groups of New Zealand White rabbits (n = 10/group) received heterotropic heart transplants from Dutch-Belted donors and were immunosuppressed with low-dose cyclosporin A (7.5 mg/kg/day). Group 1 animals were fed a normal diet and served as control. Group 2, 3, and 4 animals received a daily supplement of low- (0.25 mL/kg/day), medium- (0.75 mL/kg/day), and high- (1.5 mL/kg/day) dose fish oil (116 mg n-3 polyunsaturated fatty acid/mL), respectively. Group 5, 6, and 7 animals were supplemented with equivalent dose of safflower oil (i.e., 0.25, 0.75, and 1.5 mL/kg/day). Oil-supplemented rabbits were pretreated for 3 weeks before transplantation and maintained on the same diet for 6 weeks after operation. The extent of graft coronary arteriosclerosis was quantified using computer-assisted, morphometric planimetry. When the animals were killed, cyclosporin A was associated with elevated plasma total cholesterol and triglyceride levels in the control group. While safflower oil prevented the increase in plasma lipids at all dosages, fish oil ameliorated the cyclosporin-induced increase in total cholesterol only with high doses. Compared to control animals, there was a trend for more graft vessel disease with increasing fish oil dose, as assessed by mean luminal occlusion and intimal thickness. A steeper trend was observed for increasing doses of safflower oil; compared to the high-dose safflower oil group, animals supplemented with low-dose safflower oil had less mean luminal occlusion (16.3% +/- 5.9% versus 41.4% +/- 7.6%, p less than 0.017) and intimal thickness (7.9 +/- 1.9 microns versus 34.0 +/- 13.0 microns, analysis of variance: p = 0.054). Low-dose safflower oil also had a slight, but nonsignificant, beneficial effect on graft vessel disease when compared to control rabbits. The same trends were observed in the degree of histologic rejection (0 = none to 3 = severe) in fish oil- and safflower oil-treated animals. Rejection score correlated weakly but significantly (p = 0.0001) with mean luminal occlusion (r = 0.52) and intimal thickness (r = 0.46). Therefore allograft coronary disease in this model appeared to exhibit an unfavorable, direct-dose response to fish oil and safflower oil, independent of effects on plasma lipids.(ABSTRACT TRUNCATED AT 400 WORDS) Images Fig. 2. PMID:1867523

A Novel Admixture-Based Pharmacogenetic Approach to Refine Warfarin Dosing in Caribbean Hispanics.

PubMed

Duconge, Jorge; Ramos, Alga S; Claudio-Campos, Karla; Rivera-Miranda, Giselle; Bermúdez-Bosch, Luis; Renta, Jessicca Y; Cadilla, Carmen L; Cruz, Iadelisse; Feliu, Juan F; Vergara, Cunegundo; Ruaño, Gualberto

2016-01-01

This study is aimed at developing a novel admixture-adjusted pharmacogenomic approach to individually refine warfarin dosing in Caribbean Hispanic patients. A multiple linear regression analysis of effective warfarin doses versus relevant genotypes, admixture, clinical and demographic factors was performed in 255 patients and further validated externally in another cohort of 55 individuals. The admixture-adjusted, genotype-guided warfarin dosing refinement algorithm developed in Caribbean Hispanics showed better predictability (R2 = 0.70, MAE = 0.72mg/day) than a clinical algorithm that excluded genotypes and admixture (R2 = 0.60, MAE = 0.99mg/day), and outperformed two prior pharmacogenetic algorithms in predicting effective dose in this population. For patients at the highest risk of adverse events, 45.5% of the dose predictions using the developed pharmacogenetic model resulted in ideal dose as compared with only 29% when using the clinical non-genetic algorithm (p<0.001). The admixture-driven pharmacogenetic algorithm predicted 58% of warfarin dose variance when externally validated in 55 individuals from an independent validation cohort (MAE = 0.89 mg/day, 24% mean bias). Results supported our rationale to incorporate individual's genotypes and unique admixture metrics into pharmacogenetic refinement models in order to increase predictability when expanding them to admixed populations like Caribbean Hispanics. ClinicalTrials.gov NCT01318057.

Antithetic proportional-integral feedback for reduced variance and improved control performance of stochastic reaction networks.

PubMed

Briat, Corentin; Gupta, Ankit; Khammash, Mustafa

2018-06-01

The ability of a cell to regulate and adapt its internal state in response to unpredictable environmental changes is called homeostasis and this ability is crucial for the cell's survival and proper functioning. Understanding how cells can achieve homeostasis, despite the intrinsic noise or randomness in their dynamics, is fundamentally important for both systems and synthetic biology. In this context, a significant development is the proposed antithetic integral feedback (AIF) motif, which is found in natural systems, and is known to ensure robust perfect adaptation for the mean dynamics of a given molecular species involved in a complex stochastic biomolecular reaction network. From the standpoint of applications, one drawback of this motif is that it often leads to an increased cell-to-cell heterogeneity or variance when compared to a constitutive (i.e. open-loop) control strategy. Our goal in this paper is to show that this performance deterioration can be countered by combining the AIF motif and a negative feedback strategy. Using a tailored moment closure method, we derive approximate expressions for the stationary variance for the controlled network that demonstrate that increasing the strength of the negative feedback can indeed decrease the variance, sometimes even below its constitutive level. Numerical results verify the accuracy of these results and we illustrate them by considering three biomolecular networks with two types of negative feedback strategies. Our computational analysis indicates that there is a trade-off between the speed of the settling-time of the mean trajectories and the stationary variance of the controlled species; i.e. smaller variance is associated with larger settling-time. © 2018 The Author(s).

Ovulation-inducing factor: a protein component of llama seminal plasma

PubMed Central

2010-01-01

Background Previously, we documented the presence of ovulation-inducing factor (OIF) in the seminal plasma of llamas and alpacas. The purpose of the study was to define the biochemical characteristics of the molecule(s) in seminal plasma responsible for inducing ovulation. Methods In Experiment 1, llama seminal plasma was centrifuged using filtration devices with nominal molecular mass cut-offs of 30, 10 and 5 kDa. Female llamas (n = 9 per group) were treated i.m. with whole seminal plasma (positive control), phosphate-buffered saline (negative control), or the fraction of seminal plasma equal or higher than 30 kDa, 10 to 30 kDa, 5 to 10 kDa, or < 5 kDa. In Experiment 2, female llamas (n = 7 per group) were given an i.m. dose of seminal plasma treated previously by: 1) enzymatic digestion with proteinase-K, 2) incubation with charcoal-dextran, 3) heating to 65°C, or 4) untreated (control). In Experiment 3, female llamas (n = 10 per group) were given an i.m. dose of pronase-treated or non-treated (control) seminal plasma. In all experiments, llamas were examined by transrectal ultrasonography to detect ovulation and CL formation. Ovulation rate was compared among groups by Fisher's exact test and follicle and CL diameters were compared among groups by analyses of variance or student's t-tests. Results In Experiment 1, all llamas in the equal or higher than 30 kDa and positive control groups ovulated (9/9 in each), but none ovulated in the other groups (P < 0.001). In Experiment 2, ovulations were detected in all llamas in each treatment group; i.e., respective treatments of seminal plasma failed to inactivate the ovulation-inducing factor. In Experiment 3, ovulations were detected in 0/10 llamas given pronase-treated seminal plasma and in 9/10 controls (P < 0.01). Conclusions We conclude that ovulation-inducing factor (OIF) in llama seminal plasma is a protein molecule that is resistant to heat and enzymatic digestion with proteinase K, and has a molecular mass of approximately equal or higher than 30 kDa. PMID:20462434

Assessment of levothyroxine sodium bioavailability: recommendations for an improved methodology based on the pooled analysis of eight identically designed trials with 396 drug exposures.

PubMed

Walter-Sack, Ingeborg; Clanget, Christof; Ding, Reinhard; Goeggelmann, Christoph; Hinke, Vera; Lang, Matthias; Pfeilschifter, Johannes; Tayrouz, Yorki; Wegscheider, Karl

2004-01-01

Assessment of dosage form performance in delivering endogenous compounds, such as hormones, in vivo requires a specific approach. Assessment of relative bioavailability of levothyroxine sodium (L-T4) from eight solid preparations, compared with a liquid formulation, by using pharmacological doses, and critical evaluation of trial methodology based on the pooled analysis of individual data. Eight open-label, randomised, single-dose, crossover phase I studies using eight solid L-T4 dosage forms (25, 50, 75, 100, 125, 150, 175, 200 microg per tablet; administered total doses 600, 625 or 700 microg) and a liquid formulation; assessment of relative bioavailability by 90% confidence intervals for the relative area under the concentration-time curve (AUC) of total thyroxine (TT4), i.e. protein-bound plus free thyroxine, calculated by using the recommended log AUC four-way analysis of variance models for crossover designs. For the pooled analysis, general linear models were applied to assess the validity of model assumptions, to identify potential sources of effect modification, to discuss alternative modelling approaches with respect to endogenous hormone secretion and to give recommendations for future designs and sample sizes. One hundred and sixty-nine healthy males; 29 of these individuals participating in two studies. Single oral doses of L-T4 tablets and the liquid formulation administered after fasting, separated by at least 6 weeks; a total of 396 drug exposures. TT4 AUC from 0 to 48 hours and peak plasma concentration with and without baseline correction. Each study demonstrated equivalence of the tablets to the drinking solution, independent of the chosen analysis model. Sequence effects that could devalidate the chosen crossover approach were not found. Period effects with changing directions that could best be explained by seasonal variation were detected. While the pre-specified method of baseline correction of simply subtracting individual time-zero TT4 values was disadvantageous, the analysis of total AUC could be improved considerably by covariate adjustment for baseline TT4. With this approach, sample sizes could have been substantially reduced or, alternatively, the recommended equivalence ranges could be reduced to +/-6%. Using a single pharmacological dose of L-T4 in two-period crossover designs is a safe and reliable procedure to assess L-T4 dosage form performance. With an adequate statistical modelling approach, the design is efficient and allows general conclusions with moderate sample sizes.

A Monte Carlo Study of Levene's Test of Homogeneity of Variance: Empirical Frequencies of Type I Error in Normal Distributions.

ERIC Educational Resources Information Center

Neel, John H.; Stallings, William M.

An influential statistics test recommends a Levene text for homogeneity of variance. A recent note suggests that Levene's test is upwardly biased for small samples. Another report shows inflated Alpha estimates and low power. Neither study utilized more than two sample sizes. This Monte Carlo study involved sampling from a normal population for…

Variance in Broad Reading Accounted for by Measures of Reading Speed Embedded within Maze and Comprehension Rate Measures

ERIC Educational Resources Information Center

Hale, Andrea D.; Skinner, Christopher H.; Wilhoit, Brian; Ciancio, Dennis; Morrow, Jennifer A.

2012-01-01

Maze and reading comprehension rate measures are calculated by using measures of reading speed and measures of accuracy (i.e., correctly selected words or answers). In sixth- and seventh-grade samples, we found that the measures of reading speed embedded within our Maze measures accounted for 50% and 39% of broad reading score (BRS) variance,…

The microcomputer scientific software series 3: general linear model--analysis of variance.

Treesearch

Harold M. Rauscher

1985-01-01

A BASIC language set of programs, designed for use on microcomputers, is presented. This set of programs will perform the analysis of variance for any statistical model describing either balanced or unbalanced designs. The program computes and displays the degrees of freedom, Type I sum of squares, and the mean square for the overall model, the error, and each factor...

Warfarin Anticoagulation Therapy in Caribbean Hispanics of Puerto Rico: A Candidate Gene Association Study.

PubMed

Claudio-Campos, Karla; Labastida, Aurora; Ramos, Alga; Gaedigk, Andrea; Renta-Torres, Jessicca; Padilla, Dariana; Rivera-Miranda, Giselle; Scott, Stuart A; Ruaño, Gualberto; Cadilla, Carmen L; Duconge-Soler, Jorge

2017-01-01

Existing algorithms account for ~50% of observed variance in warfarin dose requirements after including common polymorphisms. However, they do not perform as well in populations other than Caucasians, in part because some ethno-specific genetic variants are overlooked. The objective of the present study was to identify genetic polymorphisms that can explain variability in warfarin dose requirements among Caribbean Hispanics of Puerto Rico. Next-Generation Sequencing of candidate genes CYP2C9 and VKORC1 and genotyping by DMET® Plus Assay of cardiovascular patients were performed. We also aimed at characterizing the genomic structure and admixture pattern of this study cohort. Our study used the Extreme Discordant Phenotype approach to perform a case-control association analysis. The CYP2C9 variant rs2860905, which was found in all the major haplotypes occurring in the Puerto Rican population, showed stronger association with warfarin sensitivity (<4 mg/day) than common variants CYP2C9 * 2 and CYP2C9 * 3 . Although, CYP2C9 * 2 and CYP2C9 * 3 are separately contained within two of the haplotypes, 10 subjects with the sensitive phenotype were carriers of only the CYP2C9 rs2860905 variant. Other polymorphisms in CES2 and ABCB1 were found to be associated with warfarin resistance. Incorporation of rs 2860905 in a regression model ( R 2 = 0.63, MSE = 0.37) that also includes additional genetics (i.e., VKORC1 -1639 G>A; CYP2C9 rs1856908; ABCB1 c.IVS9-44A>G/ rs10276036; CES2 c.269-965A>G/ rs4783745) and non-genetic factors (i.e., hypertension, diabetes and age) showed better prediction of warfarin dose requirements than CYP2C9 * 2 and CYP2C9 * 3 combined (partial R 2 = 0.132 vs. 0.023 and 0.007, respectively, p < 0.001). The genetic background of Puerto Ricans in the study cohort showed a tri-hybrid admixture pattern, with a slightly higher than expected contribution of Native American ancestry (25%). The genomic diversity of Puerto Ricans is highlighted by the presence of four different major haplotype blocks in the CYP2C9 locus. Although, our findings need further replication, this study contributes to the field by identifying novel genetic variants that increase predictability of stable warfarin dosing among Caribbean Hispanics.

Interstitial rotating shield brachytherapy for prostate cancer.

PubMed

Adams, Quentin E; Xu, Jinghzu; Breitbach, Elizabeth K; Li, Xing; Enger, Shirin A; Rockey, William R; Kim, Yusung; Wu, Xiaodong; Flynn, Ryan T

2014-05-01

To present a novel needle, catheter, and radiation source system for interstitial rotating shield brachytherapy (I-RSBT) of the prostate. I-RSBT is a promising technique for reducing urethra, rectum, and bladder dose relative to conventional interstitial high-dose-rate brachytherapy (HDR-BT). A wire-mounted 62 GBq(153)Gd source is proposed with an encapsulated diameter of 0.59 mm, active diameter of 0.44 mm, and active length of 10 mm. A concept model I-RSBT needle/catheter pair was constructed using concentric 50 and 75 μm thick nickel-titanium alloy (nitinol) tubes. The needle is 16-gauge (1.651 mm) in outer diameter and the catheter contains a 535 μm thick platinum shield. I-RSBT and conventional HDR-BT treatment plans for a prostate cancer patient were generated based on Monte Carlo dose calculations. In order to minimize urethral dose, urethral dose gradient volumes within 0-5 mm of the urethra surface were allowed to receive doses less than the prescribed dose of 100%. The platinum shield reduced the dose rate on the shielded side of the source at 1 cm off-axis to 6.4% of the dose rate on the unshielded side. For the case considered, for the same minimum dose to the hottest 98% of the clinical target volume (D(98%)), I-RSBT reduced urethral D(0.1cc) below that of conventional HDR-BT by 29%, 33%, 38%, and 44% for urethral dose gradient volumes within 0, 1, 3, and 5 mm of the urethra surface, respectively. Percentages are expressed relative to the prescription dose of 100%. For the case considered, for the same urethral dose gradient volumes, rectum D(1cc) was reduced by 7%, 6%, 6%, and 6%, respectively, and bladder D(1cc) was reduced by 4%, 5%, 5%, and 6%, respectively. Treatment time to deliver 20 Gy with I-RSBT was 154 min with ten 62 GBq (153)Gd sources. For the case considered, the proposed(153)Gd-based I-RSBT system has the potential to lower the urethral dose relative to HDR-BT by 29%-44% if the clinician allows a urethral dose gradient volume of 0-5 mm around the urethra to receive a dose below the prescription. A multisource approach is necessary in order to deliver the proposed (153)Gd-based I-RSBT technique in reasonable treatment times.

Recommendations for choosing an analysis method that controls Type I error for unbalanced cluster sample designs with Gaussian outcomes.

PubMed

Johnson, Jacqueline L; Kreidler, Sarah M; Catellier, Diane J; Murray, David M; Muller, Keith E; Glueck, Deborah H

2015-11-30

We used theoretical and simulation-based approaches to study Type I error rates for one-stage and two-stage analytic methods for cluster-randomized designs. The one-stage approach uses the observed data as outcomes and accounts for within-cluster correlation using a general linear mixed model. The two-stage model uses the cluster specific means as the outcomes in a general linear univariate model. We demonstrate analytically that both one-stage and two-stage models achieve exact Type I error rates when cluster sizes are equal. With unbalanced data, an exact size α test does not exist, and Type I error inflation may occur. Via simulation, we compare the Type I error rates for four one-stage and six two-stage hypothesis testing approaches for unbalanced data. With unbalanced data, the two-stage model, weighted by the inverse of the estimated theoretical variance of the cluster means, and with variance constrained to be positive, provided the best Type I error control for studies having at least six clusters per arm. The one-stage model with Kenward-Roger degrees of freedom and unconstrained variance performed well for studies having at least 14 clusters per arm. The popular analytic method of using a one-stage model with denominator degrees of freedom appropriate for balanced data performed poorly for small sample sizes and low intracluster correlation. Because small sample sizes and low intracluster correlation are common features of cluster-randomized trials, the Kenward-Roger method is the preferred one-stage approach. Copyright © 2015 John Wiley & Sons, Ltd.

Stochastic variation in avian survival rates: Life-history predictions, population consequences, and the potential responses to human perturbations and climate change

USGS Publications Warehouse

Schmutz, Joel A.; Thomson, David L.; Cooch, Evan G.; Conroy, Michael J.

2009-01-01

Stochastic variation in survival rates is expected to decrease long-term population growth rates. This expectation influences both life-history theory and the conservation of species. From this expectation, Pfister (1998) developed the important life-history prediction that natural selection will have minimized variability in those elements of the annual life cycle (such as adult survival rate) with high sensitivity. This prediction has not been rigorously evaluated for bird populations, in part due to statistical difficulties related to variance estimation. I here overcome these difficulties, and in an analysis of 62 populations, I confirm her prediction by showing a negative relationship between the proportional sensitivity (elasticity) of adult survival and the proportional variance (CV) of adult survival. However, several species deviated significantly from this expectation, with more process variance in survival than predicted. For instance, projecting the magnitude of process variance in annual survival for American redstarts (Setophaga ruticilla) for 25 years resulted in a 44% decline in abundance without assuming any change in mean survival rate. For most of these species with high process variance, recent changes in harvest, habitats, or changes in climate patterns are the likely sources of environmental variability causing this variability in survival. Because of climate change, environmental variability is increasing on regional and global scales, which is expected to increase stochasticity in vital rates of species. Increased stochasticity in survival will depress population growth rates, and this result will magnify the conservation challenges we face.

Epigenetic Variance, Performing Cooperative Structure with Genetics, Is Associated with Leaf Shape Traits in Widely Distributed Populations of Ornamental Tree Prunus mume.

PubMed

Ma, Kaifeng; Sun, Lidan; Cheng, Tangren; Pan, Huitang; Wang, Jia; Zhang, Qixiang

2018-01-01

Increasing evidence shows that epigenetics plays an important role in phenotypic variance. However, little is known about epigenetic variation in the important ornamental tree Prunus mume . We used amplified fragment length polymorphism (AFLP) and methylation-sensitive amplified polymorphism (MSAP) techniques, and association analysis and sequencing to investigate epigenetic variation and its relationships with genetic variance, environment factors, and traits. By performing leaf sampling, the relative total methylation level (29.80%) was detected in 96 accessions of P . mume . And the relative hemi-methylation level (15.77%) was higher than the relative full methylation level (14.03%). The epigenetic diversity ( I ∗ = 0.575, h ∗ = 0.393) was higher than the genetic diversity ( I = 0.484, h = 0.319). The cultivated population displayed greater epigenetic diversity than the wild populations in both southwest and southeast China. We found that epigenetic variance and genetic variance, and environmental factors performed cooperative structures, respectively. In particular, leaf length, width and area were positively correlated with relative full methylation level and total methylation level, indicating that the DNA methylation level played a role in trait variation. In total, 203 AFLP and 423 MSAP associated markers were detected and 68 of them were sequenced. Homologous analysis and functional prediction suggested that the candidate marker-linked genes were essential for leaf morphology development and metabolism, implying that these markers play critical roles in the establishment of leaf length, width, area, and ratio of length to width.

A diffusion-based approach to stochastic individual growth and energy budget, with consequences to life-history optimization and population dynamics.

PubMed

Filin, I

2009-06-01

Using diffusion processes, I model stochastic individual growth, given exogenous hazards and starvation risk. By maximizing survival to final size, optimal life histories (e.g. switching size for habitat/dietary shift) are determined by two ratios: mean growth rate over growth variance (diffusion coefficient) and mortality rate over mean growth rate; all are size dependent. For example, switching size decreases with either ratio, if both are positive. I provide examples and compare with previous work on risk-sensitive foraging and the energy-predation trade-off. I then decompose individual size into reversibly and irreversibly growing components, e.g. reserves and structure. I provide a general expression for optimal structural growth, when reserves grow stochastically. I conclude that increased growth variance of reserves delays structural growth (raises threshold size for its commencement) but may eventually lead to larger structures. The effect depends on whether the structural trait is related to foraging or defence. Implications for population dynamics are discussed.

SLR precision analysis for LAGEOS I and II

NASA Astrophysics Data System (ADS)

Kizilsu, Gaye; Sahin, Muhammed

2000-10-01

This paper deals with the problem of properly weighting satellite observations which are non-uniform in quality. The technique, the variance component estimation method developed by Helmert, was first applied to the 1987 LAGEOS I SLR data by Sahin et al. (1992). This paper investigates the performance of the globally distributed SLR stations using the Helmert type variance component estimation. As well as LAGEOS I data, LAGEOS II data were analysed, in order to compare with the previously analysed 1987 LAGEOS I data. The LAGEOS I and II data used in this research were obtained from the NASA Crustal Dynamics Data Information System (CDDIS), which archives data acquired from stations operated by NASA and by other U.S. and international organizations. The data covers the years 1994, 1995 and 1996. The analysis is based on "full-rate" laser observations, which consist of hundreds to thousands of ranges per satellite pass. The software used is based on the SATAN package (SATellite ANalysis) developed at the Royal Greenwich Observatory in the UK.

An internal pilot design for prospective cancer screening trials with unknown disease prevalence.

PubMed

Brinton, John T; Ringham, Brandy M; Glueck, Deborah H

2015-10-13

For studies that compare the diagnostic accuracy of two screening tests, the sample size depends on the prevalence of disease in the study population, and on the variance of the outcome. Both parameters may be unknown during the design stage, which makes finding an accurate sample size difficult. To solve this problem, we propose adapting an internal pilot design. In this adapted design, researchers will accrue some percentage of the planned sample size, then estimate both the disease prevalence and the variances of the screening tests. The updated estimates of the disease prevalence and variance are used to conduct a more accurate power and sample size calculation. We demonstrate that in large samples, the adapted internal pilot design produces no Type I inflation. For small samples (N less than 50), we introduce a novel adjustment of the critical value to control the Type I error rate. We apply the method to two proposed prospective cancer screening studies: 1) a small oral cancer screening study in individuals with Fanconi anemia and 2) a large oral cancer screening trial. Conducting an internal pilot study without adjusting the critical value can cause Type I error rate inflation in small samples, but not in large samples. An internal pilot approach usually achieves goal power and, for most studies with sample size greater than 50, requires no Type I error correction. Further, we have provided a flexible and accurate approach to bound Type I error below a goal level for studies with small sample size.

The impact of inter-fraction dose variations on biological equivalent dose (BED): the concept of equivalent constant dose.

PubMed

Zavgorodni, S

2004-12-07

Inter-fraction dose fluctuations, which appear as a result of setup errors, organ motion and treatment machine output variations, may influence the radiobiological effect of the treatment even when the total delivered physical dose remains constant. The effect of these inter-fraction dose fluctuations on the biological effective dose (BED) has been investigated. Analytical expressions for the BED accounting for the dose fluctuations have been derived. The concept of biological effective constant dose (BECD) has been introduced. The equivalent constant dose (ECD), representing the constant physical dose that provides the same cell survival fraction as the fluctuating dose, has also been introduced. The dose fluctuations with Gaussian as well as exponential probability density functions were investigated. The values of BECD and ECD calculated analytically were compared with those derived from Monte Carlo modelling. The agreement between Monte Carlo modelled and analytical values was excellent (within 1%) for a range of dose standard deviations (0-100% of the dose) and the number of fractions (2 to 37) used in the comparison. The ECDs have also been calculated for conventional radiotherapy fields. The analytical expression for the BECD shows that BECD increases linearly with the variance of the dose. The effect is relatively small, and in the flat regions of the field it results in less than 1% increase of ECD. In the penumbra region of the 6 MV single radiotherapy beam the ECD exceeded the physical dose by up to 35%, when the standard deviation of combined patient setup/organ motion uncertainty was 5 mm. Equivalently, the ECD field was approximately 2 mm wider than the physical dose field. The difference between ECD and the physical dose is greater for normal tissues than for tumours.

Characterization of adaptive statistical iterative reconstruction algorithm for dose reduction in CT: A pediatric oncology perspective

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

Brady, S. L.; Yee, B. S.; Kaufman, R. A.

Purpose: This study demonstrates a means of implementing an adaptive statistical iterative reconstruction (ASiR Trade-Mark-Sign ) technique for dose reduction in computed tomography (CT) while maintaining similar noise levels in the reconstructed image. The effects of image quality and noise texture were assessed at all implementation levels of ASiR Trade-Mark-Sign . Empirically derived dose reduction limits were established for ASiR Trade-Mark-Sign for imaging of the trunk for a pediatric oncology population ranging from 1 yr old through adolescence/adulthood. Methods: Image quality was assessed using metrics established by the American College of Radiology (ACR) CT accreditation program. Each image quality metricmore » was tested using the ACR CT phantom with 0%-100% ASiR Trade-Mark-Sign blended with filtered back projection (FBP) reconstructed images. Additionally, the noise power spectrum (NPS) was calculated for three common reconstruction filters of the trunk. The empirically derived limitations on ASiR Trade-Mark-Sign implementation for dose reduction were assessed using (1, 5, 10) yr old and adolescent/adult anthropomorphic phantoms. To assess dose reduction limits, the phantoms were scanned in increments of increased noise index (decrementing mA using automatic tube current modulation) balanced with ASiR Trade-Mark-Sign reconstruction to maintain noise equivalence of the 0% ASiR Trade-Mark-Sign image. Results: The ASiR Trade-Mark-Sign algorithm did not produce any unfavorable effects on image quality as assessed by ACR criteria. Conversely, low-contrast resolution was found to improve due to the reduction of noise in the reconstructed images. NPS calculations demonstrated that images with lower frequency noise had lower noise variance and coarser graininess at progressively higher percentages of ASiR Trade-Mark-Sign reconstruction; and in spite of the similar magnitudes of noise, the image reconstructed with 50% or more ASiR Trade-Mark-Sign presented a more smoothed appearance than the pre-ASiR Trade-Mark-Sign 100% FBP image. Finally, relative to non-ASiR Trade-Mark-Sign images with 100% of standard dose across the pediatric phantom age spectrum, similar noise levels were obtained in the images at a dose reduction of 48% with 40% ASIR Trade-Mark-Sign and a dose reduction of 82% with 100% ASIR Trade-Mark-Sign . Conclusions: The authors' work was conducted to identify the dose reduction limits of ASiR Trade-Mark-Sign for a pediatric oncology population using automatic tube current modulation. Improvements in noise levels from ASiR Trade-Mark-Sign reconstruction were adapted to provide lower radiation exposure (i.e., lower mA) instead of improved image quality. We have demonstrated for the image quality standards required at our institution, a maximum dose reduction of 82% can be achieved using 100% ASiR Trade-Mark-Sign ; however, to negate changes in the appearance of reconstructed images using ASiR Trade-Mark-Sign with a medium to low frequency noise preserving reconstruction filter (i.e., standard), 40% ASiR Trade-Mark-Sign was implemented in our clinic for 42%-48% dose reduction at all pediatric ages without a visually perceptible change in image quality or image noise.« less

Understanding and comparisons of different sampling approaches for the Fourier Amplitudes Sensitivity Test (FAST)

PubMed Central

Xu, Chonggang; Gertner, George

2013-01-01

Fourier Amplitude Sensitivity Test (FAST) is one of the most popular uncertainty and sensitivity analysis techniques. It uses a periodic sampling approach and a Fourier transformation to decompose the variance of a model output into partial variances contributed by different model parameters. Until now, the FAST analysis is mainly confined to the estimation of partial variances contributed by the main effects of model parameters, but does not allow for those contributed by specific interactions among parameters. In this paper, we theoretically show that FAST analysis can be used to estimate partial variances contributed by both main effects and interaction effects of model parameters using different sampling approaches (i.e., traditional search-curve based sampling, simple random sampling and random balance design sampling). We also analytically calculate the potential errors and biases in the estimation of partial variances. Hypothesis tests are constructed to reduce the effect of sampling errors on the estimation of partial variances. Our results show that compared to simple random sampling and random balance design sampling, sensitivity indices (ratios of partial variances to variance of a specific model output) estimated by search-curve based sampling generally have higher precision but larger underestimations. Compared to simple random sampling, random balance design sampling generally provides higher estimation precision for partial variances contributed by the main effects of parameters. The theoretical derivation of partial variances contributed by higher-order interactions and the calculation of their corresponding estimation errors in different sampling schemes can help us better understand the FAST method and provide a fundamental basis for FAST applications and further improvements. PMID:24143037

Understanding and comparisons of different sampling approaches for the Fourier Amplitudes Sensitivity Test (FAST).

PubMed

Xu, Chonggang; Gertner, George

2011-01-01

Fourier Amplitude Sensitivity Test (FAST) is one of the most popular uncertainty and sensitivity analysis techniques. It uses a periodic sampling approach and a Fourier transformation to decompose the variance of a model output into partial variances contributed by different model parameters. Until now, the FAST analysis is mainly confined to the estimation of partial variances contributed by the main effects of model parameters, but does not allow for those contributed by specific interactions among parameters. In this paper, we theoretically show that FAST analysis can be used to estimate partial variances contributed by both main effects and interaction effects of model parameters using different sampling approaches (i.e., traditional search-curve based sampling, simple random sampling and random balance design sampling). We also analytically calculate the potential errors and biases in the estimation of partial variances. Hypothesis tests are constructed to reduce the effect of sampling errors on the estimation of partial variances. Our results show that compared to simple random sampling and random balance design sampling, sensitivity indices (ratios of partial variances to variance of a specific model output) estimated by search-curve based sampling generally have higher precision but larger underestimations. Compared to simple random sampling, random balance design sampling generally provides higher estimation precision for partial variances contributed by the main effects of parameters. The theoretical derivation of partial variances contributed by higher-order interactions and the calculation of their corresponding estimation errors in different sampling schemes can help us better understand the FAST method and provide a fundamental basis for FAST applications and further improvements.

Trait and State Variance in Oppositional Defiant Disorder Symptoms: A Multi-Source Investigation with Spanish Children

PubMed Central

Preszler, Jonathan; Burns, G. Leonard; Litson, Kaylee; Geiser, Christian; Servera, Mateu

2016-01-01

The objective was to determine and compare the trait and state components of oppositional defiant disorder (ODD) symptom reports across multiple informants. Mothers, fathers, primary teachers, and secondary teachers rated the occurrence of the ODD symptoms in 810 Spanish children (55% boys) on two occasions (end first and second grades). Single source latent state-trait (LST) analyses revealed that ODD symptom ratings from all four sources showed more trait (M = 63%) than state residual (M = 37%) variance. A multiple source LST analysis revealed substantial convergent validity of mothers’ and fathers’ trait variance components (M = 68%) and modest convergent validity of state residual variance components (M = 35%). In contrast, primary and secondary teachers showed low convergent validity relative to mothers for trait variance (Ms = 31%, 32%, respectively) and essentially zero convergent validity relative to mothers for state residual variance (Ms = 1%, 3%, respectively). Although ODD symptom ratings reflected slightly more trait- than state-like constructs within each of the four sources separately across occasions, strong convergent validity for the trait variance only occurred within settings (i.e., mothers with fathers; primary with secondary teachers) with the convergent validity of the trait and state residual variance components being low to non-existent across settings. These results suggest that ODD symptom reports are trait-like across time for individual sources with this trait variance, however, only having convergent validity within settings. Implications for assessment of ODD are discussed. PMID:27148784

Examination of Variables That May Affect the Relationship Between Cognition and Functional Status in Individuals with Mild Cognitive Impairment: A Meta-Analysis

PubMed Central

Mcalister, Courtney; Schmitter-Edgecombe, Maureen; Lamb, Richard

2016-01-01

The objective of this meta-analysis was to improve understanding of the heterogeneity in the relationship between cognition and functional status in individuals with mild cognitive impairment (MCI). Demographic, clinical, and methodological moderators were examined. Cognition explained an average of 23% of the variance in functional outcomes. Executive function measures explained the largest amount of variance (37%), whereas global cognitive status and processing speed measures explained the least (20%). Short- and long-delayed memory measures accounted for more variance (35% and 31%) than immediate memory measures (18%), and the relationship between cognition and functional outcomes was stronger when assessed with informant-report (28%) compared with self-report (21%). Demographics, sample characteristics, and type of everyday functioning measures (i.e., questionnaire, performance-based) explained relatively little variance compared with cognition. Executive functioning, particularly measured by Trails B, was a strong predictor of everyday functioning in individuals with MCI. A large proportion of variance remained unexplained by cognition. PMID:26743326

Finding meaning in loss: the mediating role of social support between personality and two construals of meaning.

PubMed

Boyraz, Güler; Horne, Sharon G; Sayger, Thomas V

2012-07-01

Dimensions of personality may shape an individual's response to loss both directly and indirectly through its effects on other variables such as an individual's ability to seek social support. The mediating effect of social support on the relationship between personality (i.e., extraversion and neuroticism) and 2 construals of meaning (i.e., sense-making and benefit-finding) among 325 bereaved individuals was explored using path analysis. Supporting our hypotheses, social support mediated the relationship between personality and construals of meaning. Neuroticism was negatively and indirectly associated with both sense-making and benefit-finding through social support. Extraversion had a significant positive relationship to social support, which, in turn, mediated the impact of extraversion on both sense-making and benefit finding. The model explained 35% of the variance in social support, 19% of the variance in sense-making, and 25% of the variance in benefit-finding. Implications are discussed in light of existing theories of bereavement and loss.

Maintaining evolvability.

PubMed

Crow, James F

2008-12-01

Although molecular methods, such as QTL mapping, have revealed a number of loci with large effects, it is still likely that the bulk of quantitative variability is due to multiple factors, each with small effect. Typically, these have a large additive component. Conventional wisdom argues that selection, natural or artificial, uses up additive variance and thus depletes its supply. Over time, the variance should be reduced, and at equilibrium be near zero. This is especially expected for fitness and traits highly correlated with it. Yet, populations typically have a great deal of additive variance, and do not seem to run out of genetic variability even after many generations of directional selection. Long-term selection experiments show that populations continue to retain seemingly undiminished additive variance despite large changes in the mean value. I propose that there are several reasons for this. (i) The environment is continually changing so that what was formerly most fit no longer is. (ii) There is an input of genetic variance from mutation, and sometimes from migration. (iii) As intermediate-frequency alleles increase in frequency towards one, producing less variance (as p --> 1, p(1 - p) --> 0), others that were originally near zero become more common and increase the variance. Thus, a roughly constant variance is maintained. (iv) There is always selection for fitness and for characters closely related to it. To the extent that the trait is heritable, later generations inherit a disproportionate number of genes acting additively on the trait, thus increasing genetic variance. For these reasons a selected population retains its ability to evolve. Of course, genes with large effect are also important. Conspicuous examples are the small number of loci that changed teosinte to maize, and major phylogenetic changes in the animal kingdom. The relative importance of these along with duplications, chromosome rearrangements, horizontal transmission and polyploidy is yet to be determined. It is likely that only a case-by-case analysis will provide the answers. Despite the difficulties that complex interactions cause for evolution in Mendelian populations, such populations nevertheless evolve very well. Longlasting species must have evolved mechanisms for coping with such problems. Since such difficulties do not arise in asexual populations, a comparison of epistatic patterns in closely related sexual and asexual species might provide some important insights.

Server-side Log Data Analytics for I/O Workload Characterization and Coordination on Large Shared Storage Systems

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

Liu, Y.; Gunasekaran, Raghul; Ma, Xiaosong

2016-01-01

Inter-application I/O contention and performance interference have been recognized as severe problems. In this work, we demonstrate, through measurement from Titan (world s No. 3 supercomputer), that high I/O variance co-exists with the fact that individual storage units remain under-utilized for the majority of the time. This motivates us to propose AID, a system that performs automatic application I/O characterization and I/O-aware job scheduling. AID analyzes existing I/O traffic and batch job history logs, without any prior knowledge on applications or user/developer involvement. It identifies the small set of I/O-intensive candidates among all applications running on a supercomputer and subsequentlymore » mines their I/O patterns, using more detailed per-I/O-node traffic logs. Based on such auto- extracted information, AID provides online I/O-aware scheduling recommendations to steer I/O-intensive applications away from heavy ongoing I/O activities. We evaluate AID on Titan, using both real applications (with extracted I/O patterns validated by contacting users) and our own pseudo-applications. Our results confirm that AID is able to (1) identify I/O-intensive applications and their detailed I/O characteristics, and (2) significantly reduce these applications I/O performance degradation/variance by jointly evaluating out- standing applications I/O pattern and real-time system l/O load.« less

Positron Emission Tomography-Guided, Focal-Dose Escalation Using Intensity-Modulated Radiotherapy for Head and Neck Cancer

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

Madani, Indira; Duthoy, Wim; Derie, Cristina R.N.

2007-05-01

Purpose: To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided dose escalation, and to determine the maximum tolerated dose in head and neck cancer. Methods and Materials: A Phase I clinical trial was designed to escalate the dose limited to the [{sup 18}-F]fluoro-2-deoxy-D-glucose positron emission tomography ({sup 18}F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two dose levels were planned: 25 Gy (level I) and 30 Gy (level II), delivered in 10 fractions. Standard IMRT was appliedmore » for the remaining 22 fractions of 2.16 Gy. Results: Between 2003 and 2005, 41 patients were enrolled, with 23 at dose level I, and 18 at dose level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of dose-limiting toxicity occurred at dose level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at dose level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at dose levels I and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and 87% (p n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at dose levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted {sup 18}F-FDG-PET-delineated region. Conclusions: For head and neck cancer, PET-guided dose escalation appears to be well-tolerated. The maximum tolerated dose was not reached at the investigated dose levels.« less

Contrast discrimination: Second responses reveal the relationship between the mean and variance of visual signals

PubMed Central

Solomon, Joshua A.

2007-01-01

To explain the relationship between first- and second-response accuracies in a detection experiment, Swets, Tanner, and Birdsall [Swets, J., Tanner, W. P., Jr., & Birdsall, T. G. (1961). Decision processes in perception. Psychological Review, 68, 301–340] proposed that the variance of visual signals increased with their means. However, both a low threshold and intrinsic uncertainty produce similar relationships. I measured the relationship between first- and second-response accuracies for suprathreshold contrast discrimination, which is thought to be unaffected by sensory thresholds and intrinsic uncertainty. The results are consistent with a slowly increasing variance. PMID:17961625

Efficacy of Low-dose (2 millicurie) versus Standard-dose (4 millicurie) Radioiodine Treatment for Cats with Mild-to-Moderate Hyperthyroidism.

PubMed

Lucy, J M; Peterson, M E; Randolph, J F; Scrivani, P V; Rishniw, M; Davignon, D L; Thompson, M S; Scarlett, J M

2017-03-01

Radioiodine ( 131 I) is effective treatment for hyperthyroidism in cats, but optimal dose to restore euthyroidism without inducing hypothyroidism is unclear. Treatment-induced hypothyroidism can lead to azotemia and reduced duration of survival. To compare efficacy and short-term outcomes of low-dose 131 I versus higher, standard-dose 131 I as treatment for hyperthyroidism. A total of 189 client-owned cats undergoing 131 I treatment for mild-to-moderate hyperthyroidism (serum T 4 ≥ 4.0 μg/dL and <13.0 μg/dL). Prospective, nonrandomized, cohort study comparing treatment with either low-dose (2 mCi, n = 150) or standard-dose (4 mCi, n = 39) 131 I. Serum T 4 , thyroid-stimulating hormone (TSH), and creatinine concentrations were measured after 1, 3, and 6 months to determine persistent hyperthyroidism, overt hypothyroidism (low T 4 , high TSH), subclinical hypothyroidism (normal T 4 , high TSH), and azotemia. There was no significant difference in prevalence of cats with persistent hyperthyroidism between standard- and low-dose treatment groups at 3 (0% versus 5.3%; P = .34) and 6 (0% versus 3.3%; P = .51) months. Overt (18% versus 1%; P = .0005) or subclinical (46% versus 21%; P = .004) hypothyroidism was more common in cats at 6 months after standard-dose 131 I. No difference in incidence of azotemia existed between groups, but cats treated with standard-dose 131 I had higher creatinine concentrations (P < .05) and higher percent rises in creatinine (P < .0001). Low-dose 131 I is safe and effective for cats with mild-to-moderate hyperthyroidism, as evidenced by a cure rate of >95% with reduced frequency of iatrogenic hypothyroidism and azotemia. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

The application of drug dose equivalence in the quantitative analysis of receptor occupation and drug combinations

PubMed Central

Tallarida, Ronald J.; Raffa, Robert B.

2014-01-01

In this review we show that the concept of dose equivalence for two drugs, the theoretical basis of the isobologram, has a wider use in the analysis of pharmacological data derived from single and combination drug use. In both its application to drug combination analysis with isoboles and certain other actions, listed below, the determination of doses, or receptor occupancies, that yield equal effects provide useful metrics that can be used to obtain quantitative information on drug actions without postulating any intimate mechanism of action. These other drug actions discussed here include (1) combinations of agonists that produce opposite effects, (2) analysis of inverted U-shaped dose effect curves of single agents, (3) analysis on the effect scale as an alternative to isoboles and (4) the use of occupation isoboles to examine competitive antagonism in the dual receptor case. New formulas derived to assess the statistical variance for additive combinations are included, and the more detailed mathematical topics are included in the appendix. PMID:20546783

Hypercholesterolemia: a look at low-cost treatment and treatment adherence.

PubMed

Flannery, J; Raulerson, A

2000-11-01

To determine whether a positive cholesterol-lowering effect could be achieved with a psyllium dose of 6 grams per day instead of the usual 10 grams per day as advocated by other researchers. Randomized trial of 46 males and females with hypercholesterolemia; multivariate analysis of variance with repeated measures on 1 factor done on 28 subjects (18 in treatment group, 10 in control group) remaining after 16 weeks of treatment. Lipoprotein analysis at 2, 8, and 16 weeks indicated that a daily dose of 6 grams of psyllium hydrophilic mucilloid did not significantly affect serum total cholesterol nor low-density lipoproteins in either men or women with hypercholesterolemia. The effects of psyllium on hypercholesterolemia appear to be dose dependent. Although it is a low cost option, the addition of psyllium to the diet has unpleasant side-effects, including abdominal distention, flatulence, and discomfort. Because these side effects are troublesome, the lowest effective dose of psyllium may be an important factor in improving treatment adherence.

Development of a pharmacogenetic-guided warfarin dosing algorithm for Puerto Rican patients

PubMed Central

Ramos, Alga S; Seip, Richard L; Rivera-Miranda, Giselle; Felici-Giovanini, Marcos E; Garcia-Berdecia, Rafael; Alejandro-Cowan, Yirelia; Kocherla, Mohan; Cruz, Iadelisse; Feliu, Juan F; Cadilla, Carmen L; Renta, Jessica Y; Gorowski, Krystyna; Vergara, Cunegundo; Ruaño, Gualberto; Duconge, Jorge

2012-01-01

Aim This study was aimed at developing a pharmacogenetic-driven warfarin-dosing algorithm in 163 admixed Puerto Rican patients on stable warfarin therapy. Patients & methods A multiple linear-regression analysis was performed using log-transformed effective warfarin dose as the dependent variable, and combining CYP2C9 and VKORC1 genotyping with other relevant nongenetic clinical and demographic factors as independent predictors. Results The model explained more than two-thirds of the observed variance in the warfarin dose among Puerto Ricans, and also produced significantly better ‘ideal dose’ estimates than two pharmacogenetic models and clinical algorithms published previously, with the greatest benefit seen in patients ultimately requiring <7 mg/day. We also assessed the clinical validity of the model using an independent validation cohort of 55 Puerto Rican patients from Hartford, CT, USA (R2 = 51%). Conclusion Our findings provide the basis for planning prospective pharmacogenetic studies to demonstrate the clinical utility of genotyping warfarin-treated Puerto Rican patients. PMID:23215886

Terrestrial gamma radiation dose (TGRD) levels in northern zone of Jos Plateau, Nigeria: Statistical relationship between dose rates and geological formations

NASA Astrophysics Data System (ADS)

Abba, Habu Tela; Hassan, Wan Muhamad Saridan Wan; Saleh, Muneer Aziz; Aliyu, Abubakar Sadiq; Ramli, Ahmad Termizi

2017-11-01

In- situ measurement of terrestrial gamma radiation dose rates (TGRD) was conducted in northern zone of Jos Plateau and a statistical relationship between the TGRD and the underlying geological formations was investigated. The TGRD rates in all the measurements ranged from 40 to 1265 nGy h-1 with a mean value of 250 nGy h-1. The maximum TGDR was recorded on geological type G8 (Younger Granites) at Bisitchi, and the lowest TGDR was recorded on G6 (Basaltic rocks) at Gabia. One way analysis of variance (ANOVA) statistical test was used to compared the data. Significantly, the results of this study inferred a strong relationship between TGRD levels with geological structures of a place. An isodose map was plotted to represent exposure rates due to TGRD. The results of this investigation could be useful for multiple public interest such as evaluating public dose for the area.

Effect of Genetic Variants, Especially CYP2C9 and VKORC1, on the Pharmacology of Warfarin

PubMed Central

Fung, Erik; Patsopoulos, Nikolaos A.; Belknap, Steven M.; O’Rourke, Daniel J.; Robb, John F.; Anderson, Jeffrey L.; Shworak, Nicholas W.; Moore, Jason H.

2014-01-01

The genes encoding the cytochrome P450 2C9 enzyme (CYP2C9) and vitamin K-epoxide reductase complex unit 1 (VKORC1) are major determinants of anticoagulant response to warfarin. Together with patient demographics and clinical information, they account for approximately one-half of the warfarin dose variance in individuals of European descent. Recent prospective and randomized controlled trial data support pharmacogenetic guidance with their use in warfarin dose initiation and titration. Benefits from pharmacogenetics-guided warfarin dosing have been reported to extend beyond the period of initial dosing, with supportive data indicating benefits to at least 3 months. The genetic effects of VKORC1 and CYP2C9 in African and Asian populations are concordant with those in individuals of European ancestry; however, frequency distribution of allelic variants can vary considerably between major populations. Future randomized controlled trials in multiethnic settings using population-specific dosing algorithms will allow us to further ascertain the generalizability and cost-effectiveness of pharmacogenetics-guided warfarin therapy. Additional genome-wide association studies may help us to improve and refine dosing algorithms and potentially identify novel biological pathways. PMID:23041981

Effect of palm oil (Elaeis guineensis) tocotrienols on mesenteric adipose tissue deposition and the expression of 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1) in adrenalectomized rats treated with dexamethasone.

PubMed

Azwan, K; Farihah, H S; Fairus, A; Elvy, M R

2015-01-01

A study was done to investigate the effect of palm oil (Elaeis guineensis) tocotrienols on (1) rats mesenteric adipose tissue deposition (2) and 11β-HSD1 enzyme expression in mesenteric adipocyte. There is a necessity to find an inhibitor for the 11β-HSD1 enzyme which enhances the proliferation of mesenteric adipocyte tissue therefore curbing the onset of metabolic syndrome. A total of 35 male Spraque Dawley rats were divided into 5 different groups, i.e., a baseline control group (n=7), a sham operated group (n=7) and three experimental adrenalectomised groups (ADR) (n=21). Each of the experimental ADR group was given intramuscular dexamethasone (Dexa) with a dose of 120 μg/kg after 2 weeks post adrenalectomy and were divided into adrenalectomised control (n=7), Glycyrrhizic acid (GCA) treated (dose=120 mg/kg/day; n=7) and Palm Tocotrienol treated (dose=60 mg/kg/day; n=7) groups. These various treatments were given 6 days a week for 8 weeks via gastric gavage (following 2 weeks of adrenalectomy). Data is expressed as mean ± standard error mean (SEM), compared to each other using one-way analysis-of-variance (ANOVA) followed by Tukey's post hoc test and then a t-test. The results show that palm tocotrienol tend to slightly increase mesenteric adipose tissue deposition in rats. However, palm tocotrienol was also found to have potential in inhibiting the expression of 11β-HSD1 enzyme in mesenteric adipocytes. This study suggests palm tocotrienol inhibits 11β-HSD1 enzyme expression and activity.

[The effect of high-dose ultraviolet irradiation on sodium, calcium and aldosterone in the blood of calves].

PubMed

Broucek, J; Gajdosík, D; Letkovicová, M; Kovalcik, K

1992-07-01

Five Holstein-Friesian calves, from one sire, with prevalent black hair coat pigmentation were used in the experiment. The mean age was 33 days and the mean live weight 51 kg. The animals were exposed free running without interruption for 12 hours to an artificial ultraviolet light in the range of 280-320 nm. The mean doses of radiation was 179.10(-10) J/h/m. One-spot high-pressure mercury discharge lamps Tesla RVK 400 W were used as a radiation source. The dose rate was estimated from measurements by a spectral photometer with filter UG 2 for absorbtion of visible light located at the height of the back of standing calf. Blood samples were collected immediately before the beginning of treatment and after 5, 12, 24, 48 and 72 hours. The blood plasma aldosterone was measured by radioimmunoassays, the levels of sodium, potassium and calcium in blood plasma by flame spectrophotometry. Double classification variance analysis and evaluation according to the Snedecor F-test, the contrast effect test according to Duncan and regression analysis were used for statistical evaluation. Compared to the first sampling, sodium increased significantly after 5 and 12 hours of exposure (Tab. I) to 138.1 and 138.3 mmol/l, respectively. In the subsequent samplings this trend continued up to 72 hours from the beginning of irradiation (140.5 mmol/l). The potassium level did not change statistically significantly. Owing to an excessive irradiation, the calcium concentration increased significantly. The greatest increase occurred after 12 hours of irradiation (from 2.29 mmol/l to 2.61 mmol/l) and after 36 hours from the end of irradiation (2.70 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal-by-environment but not genotype-by-environment interactions in a fish without parental care.

PubMed

Vega-Trejo, Regina; Head, Megan L; Jennions, Michael D; Kruuk, Loeske E B

2018-01-01

The impact of environmental conditions on the expression of genetic variance and on maternal effects variance remains an important question in evolutionary quantitative genetics. We investigate here the effects of early environment on variation in seven adult life history, morphological, and secondary sexual traits (including sperm characteristics) in a viviparous poeciliid fish, the mosquitofish Gambusia holbrooki. Specifically, we manipulated food availability during early development and then assessed additive genetic and maternal effects contributions to the overall phenotypic variance in adults. We found higher heritability for female than male traits, but maternal effects variance for traits in both sexes. An interaction between maternal effects variance and rearing environment affected two adult traits (female age at maturity and male size at maturity), but there was no evidence of trade-offs in maternal effects across environments. Our results illustrate (i) the potential for pre-natal maternal effects to interact with offspring environment during development, potentially affecting traits through to adulthood and (ii) that genotype-by-environment interactions might be overestimated if maternal-by-environment interactions are not accounted for, similar to heritability being overestimated if maternal effects are ignored. We also discuss the potential for dominance genetic variance to contribute to the estimate of maternal effects variance.

A fully-stochasticized, age-structured population model for population viability analysis of fish: Lower Missouri River endangered pallid sturgeon example

USGS Publications Warehouse

Wildhaber, Mark L.; Albers, Janice; Green, Nicholas; Moran, Edward H.

2017-01-01

We develop a fully-stochasticized, age-structured population model suitable for population viability analysis (PVA) of fish and demonstrate its use with the endangered pallid sturgeon (Scaphirhynchus albus) of the Lower Missouri River as an example. The model incorporates three levels of variance: parameter variance (uncertainty about the value of a parameter itself) applied at the iteration level, temporal variance (uncertainty caused by random environmental fluctuations over time) applied at the time-step level, and implicit individual variance (uncertainty caused by differences between individuals) applied within the time-step level. We found that population dynamics were most sensitive to survival rates, particularly age-2+ survival, and to fecundity-at-length. The inclusion of variance (unpartitioned or partitioned), stocking, or both generally decreased the influence of individual parameters on population growth rate. The partitioning of variance into parameter and temporal components had a strong influence on the importance of individual parameters, uncertainty of model predictions, and quasiextinction risk (i.e., pallid sturgeon population size falling below 50 age-1+ individuals). Our findings show that appropriately applying variance in PVA is important when evaluating the relative importance of parameters, and reinforce the need for better and more precise estimates of crucial life-history parameters for pallid sturgeon.

Is There a Common Summary Statistical Process for Representing the Mean and Variance? A Study Using Illustrations of Familiar Items

PubMed Central

Yang, Yi; Tokita, Midori; Ishiguchi, Akira

2018-01-01

A number of studies revealed that our visual system can extract different types of summary statistics, such as the mean and variance, from sets of items. Although the extraction of such summary statistics has been studied well in isolation, the relationship between these statistics remains unclear. In this study, we explored this issue using an individual differences approach. Observers viewed illustrations of strawberries and lollypops varying in size or orientation and performed four tasks in a within-subject design, namely mean and variance discrimination tasks with size and orientation domains. We found that the performances in the mean and variance discrimination tasks were not correlated with each other and demonstrated that extractions of the mean and variance are mediated by different representation mechanisms. In addition, we tested the relationship between performances in size and orientation domains for each summary statistic (i.e. mean and variance) and examined whether each summary statistic has distinct processes across perceptual domains. The results illustrated that statistical summary representations of size and orientation may share a common mechanism for representing the mean and possibly for representing variance. Introspections for each observer performing the tasks were also examined and discussed. PMID:29399318

Results from the Evaluation of the Massachusetts Nursing Home Connection Program

DTIC Science & Technology

1989-10-01

pn nDosage 2 f. Numberof Doses 193L II mg LI9I g, prn Dosage 3. h. Numberof Doses; Was the following medication admfnistered Haldol ( Haloperidol ) [Dse...Dosage 3 h. Number of Doses I F 9i W mg 58F[17 22 Was the lollowing medication administered Haldol ( Haloperidol )" [Dose range. 0.5 mg to 5 0 ri1g] 1 E YES

Monte Carlo Simulations Comparing Fisher Exact Test and Unequal Variances t Test for Analysis of Differences Between Groups in Brief Hospital Lengths of Stay.

PubMed

Dexter, Franklin; Bayman, Emine O; Dexter, Elisabeth U

2017-12-01

We examined type I and II error rates for analysis of (1) mean hospital length of stay (LOS) versus (2) percentage of hospital LOS that are overnight. These 2 end points are suitable for when LOS is treated as a secondary economic end point. We repeatedly resampled LOS for 5052 discharges of thoracoscopic wedge resections and lung lobectomy at 26 hospitals. Unequal variances t test (Welch method) and Fisher exact test both were conservative (ie, type I error rate less than nominal level). The Wilcoxon rank sum test was included as a comparator; the type I error rates did not differ from the nominal level of 0.05 or 0.01. Fisher exact test was more powerful than the unequal variances t test at detecting differences among hospitals; estimated odds ratio for obtaining P < .05 with Fisher exact test versus unequal variances t test = 1.94, with 95% confidence interval, 1.31-3.01. Fisher exact test and Wilcoxon-Mann-Whitney had comparable statistical power in terms of differentiating LOS between hospitals. For studies with LOS to be used as a secondary end point of economic interest, there is currently considerable interest in the planned analysis being for the percentage of patients suitable for ambulatory surgery (ie, hospital LOS equals 0 or 1 midnight). Our results show that there need not be a loss of statistical power when groups are compared using this binary end point, as compared with either Welch method or Wilcoxon rank sum test.

Human breast milk excretion of iodine-131 following diagnostic and therapeutic administration to a lactating patient with Graves' disease

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

Dydek, G.J.; Blue, P.W.

Previous reports on the excretion of /sup 131/I into human breast milk have recommended discontinuance of breast feeding from 1 to 12 days following diagnostic tracer doses of /sup 131/I. Recent excretion models have calculated that breast feeding could safely resume 56 days following a 5 microCi (0.185 MBq) /sup 131/I maternal tracer dose. We studied a postpartum patient with Graves' disease following first an uptake dose of 8.6 microCi (0.317 MBq) and then for 38 days following a 9.6 mCi (355 MBq) therapy dose of Na/sup 131/I. We calculated from our data that although nursing could not be safelymore » resumed for 46 days following the 8.6-microCi uptake dose, nursing could resume in this patient 8 days after a 100-nCi (3.7 KBq) dose. Extrapolating this data to impure /sup 123/I (p, 2n or p, 5n) we feel that standard 100-microCi (3.7 MBq) doses of either /sup 123/I preparation is not suitable if nursing is to be resumed.« less

Physiologic variability at the verge of systemic inflammation: multiscale entropy of heart rate variability is affected by very low doses of endotoxin.

PubMed

Herlitz, Georg N; Arlow, Renee L; Cheung, Nora H; Coyle, Susette M; Griffel, Benjamin; Macor, Marie A; Lowry, Stephen F; Calvano, Steve E; Gale, Stephen C

2015-02-01

Human injury or infection induces systemic inflammation with characteristic neuroendocrine responses. Fluctuations in autonomic function during inflammation are reflected by beat-to-beat variation in heart rate, termed heart rate variability (HRV). In the present study, we determine threshold doses of endotoxin needed to induce observable changes in markers of systemic inflammation, investigate whether metrics of HRV exhibit a differing threshold dose from other inflammatory markers, and investigate the size of data sets required for meaningful use of multiscale entropy (MSE) analysis of HRV. Healthy human volunteers (n = 25) were randomized to receive placebo (normal saline) or endotoxin/lipopolysaccharide (LPS): 0.1, 0.25, 0.5, 1.0, or 2.0 ng/kg administered intravenously. Vital signs were recorded every 30 min for 6 h and then at 9, 12, and 24 h after LPS. Blood samples were drawn at specific time points for cytokine measurements. Heart rate variability analysis was performed using electrocardiogram epochs of 5 min. Multiscale entropy for HRV was calculated for all dose groups to scale factor 40. The lowest significant threshold dose was noted in core temperature at 0.25 ng/kg. Endogenous tumor necrosis factor α and interleukin 6 were significantly responsive at the next dosage level (0.5 ng/kg) along with elevations in circulating leukocytes and heart rate. Responses were exaggerated at higher doses (1 and 2 ng/kg). Time domain and frequency domain HRV metrics similarly suggested a threshold dose, differing from placebo at 1.0 and 2.0 ng/kg, below which no clear pattern in response was evident. By applying repeated-measures analysis of variance across scale factors, a significant decrease in MSE was seen at 1.0 and 2.0 ng/kg by 2 h after exposure to LPS. Although not statistically significant below 1.0 ng/kg, MSE unexpectedly decreased across all groups in an orderly dose-response pattern not seen in the other outcomes. By using repeated-measures analysis of variance across scale factors, MSE can detect autonomic change after LPS challenge in a group of 25 subjects using electrocardiogram epochs of only 5 min and entropy analysis to scale factor of only 40, potentially facilitating MSE's wider use as a research tool or bedside monitor. Traditional markers of inflammation generally exhibit threshold dose behavior. In contrast, MSE's apparent continuous dose-response pattern, although not statistically verifiable in this study, suggests a potential subclinical harbinger of infectious or other insult. The possible derangement of autonomic complexity prior to or independent of the cytokine surge cannot be ruled out. Future investigation should focus on confirmation of overt inflammation following observed decreases in MSE in a clinical setting.

Gender, body weight, disease activity, and previous radiotherapy influence the response to pegvisomant.

PubMed

Parkinson, Craig; Burman, Pia; Messig, Michael; Trainer, Peter J

2007-01-01

To effectively normalize IGF-I in patients with acromegaly, various covariates may affect dosing and plasma concentrations of pegvisomant. We assessed whether sex, age, weight, and previous radiotherapy influence dosing of pegvisomant in patients with active disease. Data from 69 men and 49 women participating in multicenter, open-label trials of pegvisomant were retrospectively evaluated using multiple regression techniques. Sixty-nine subjects (39 men, 30 women) had undergone external beam pituitary radiotherapy. Serum IGF-I was at least 30% above age-related upper limit of normal in all patients at study entry. After a loading dose of pegvisomant (80 mg), patients were commenced on 10 mg/d. Pegvisomant dose was adjusted by 5 mg every eighth week until serum IGF-I was normalized. At baseline, men had significantly higher mean serum IGF-I levels than women despite similar GH levels. After treatment with pegvisomant, IGF-I levels were similar in men and women. A significant correlation between baseline GH, IGF-I, body weight, and the dose of pegvisomant required to normalize serum IGF-I was observed (all P < 0.001). Women required an average of 0.04 mg/kg more pegvisomant than men and a mean weight-corrected dose of 19.2 mg/d to normalize serum IGF-I [14.5 mg/d (men); P < 0.001]. Patients treated with radiotherapy required less pegvisomant to normalize serum IGF-I despite similar baseline GH/IGF-I levels (15.2 vs. 18.5 mg/d for no previous radiotherapy; P = 0.002). Sex, body weight, previous radiotherapy, and baseline GH/IGF-I influence the dose of pegvisomant required to normalize serum IGF-I in patients with active acromegaly.

Keeping an eye on the ring: COMS plaque loading optimization for improved dose conformity and homogeneity.

PubMed

Gagne, Nolan L; Cutright, Daniel R; Rivard, Mark J

2012-09-01

To improve tumor dose conformity and homogeneity for COMS plaque brachytherapy by investigating the dosimetric effects of varying component source ring radionuclides and source strengths. The MCNP5 Monte Carlo (MC) radiation transport code was used to simulate plaque heterogeneity-corrected dose distributions for individually-activated source rings of 14, 16 and 18 mm diameter COMS plaques, populated with (103)Pd, (125)I and (131)Cs sources. Ellipsoidal tumors were contoured for each plaque size and MATLAB programming was developed to generate tumor dose distributions for all possible ring weighting and radionuclide permutations for a given plaque size and source strength resolution, assuming a 75 Gy apical prescription dose. These dose distributions were analyzed for conformity and homogeneity and compared to reference dose distributions from uniformly-loaded (125)I plaques. The most conformal and homogeneous dose distributions were reproduced within a reference eye environment to assess organ-at-risk (OAR) doses in the Pinnacle(3) treatment planning system (TPS). The gamma-index analysis method was used to quantitatively compare MC and TPS-generated dose distributions. Concentrating > 97% of the total source strength in a single or pair of central (103)Pd seeds produced the most conformal dose distributions, with tumor basal doses a factor of 2-3 higher and OAR doses a factor of 2-3 lower than those of corresponding uniformly-loaded (125)I plaques. Concentrating 82-86% of the total source strength in peripherally-loaded (131)Cs seeds produced the most homogeneous dose distributions, with tumor basal doses 17-25% lower and OAR doses typically 20% higher than those of corresponding uniformly-loaded (125)I plaques. Gamma-index analysis found > 99% agreement between MC and TPS dose distributions. A method was developed to select intra-plaque ring radionuclide compositions and source strengths to deliver more conformal and homogeneous tumor dose distributions than uniformly-loaded (125)I plaques. This method may support coordinated investigations of an appropriate clinical target for eye plaque brachytherapy.

An evaluation of evaluative personality terms: a comparison of the big seven and five-factor model in predicting psychopathology.

PubMed

Durrett, Christine; Trull, Timothy J

2005-09-01

Two personality models are compared regarding their relationship with personality disorder (PD) symptom counts and with lifetime Axis I diagnoses. These models share 5 similar domains, and the Big 7 model also includes 2 domains assessing self-evaluation: positive and negative valence. The Big 7 model accounted for more variance in PDs than the 5-factor model, primarily because of the association of negative valence with most PDs. Although low-positive valence was associated with most Axis I diagnoses, the 5-factor model generally accounted for more variance in Axis I diagnoses than the Big 7 model. Some predicted associations between self-evaluation and psychopathology were not found, and unanticipated associations emerged. These findings are discussed regarding the utility of evaluative terms in clinical assessment.

Examining Radiation-Induced In Vivo and In Vitro Gene Expression Changes of the Peripheral Blood in Different Laboratories for Biodosimetry Purposes: First RENEB Gene Expression Study.

PubMed

Abend, M; Badie, C; Quintens, R; Kriehuber, R; Manning, G; Macaeva, E; Njima, M; Oskamp, D; Strunz, S; Moertl, S; Doucha-Senf, S; Dahlke, S; Menzel, J; Port, M

2016-02-01

The risk of a large-scale event leading to acute radiation exposure necessitates the development of high-throughput methods for providing rapid individual dose estimates. Our work addresses three goals, which align with the directive of the European Union's Realizing the European Network of Biodosimetry project (EU-RENB): 1. To examine the suitability of different gene expression platforms for biodosimetry purposes; 2. To perform this examination using blood samples collected from prostate cancer patients (in vivo) and from healthy donors (in vitro); and 3. To compare radiation-induced gene expression changes of the in vivo with in vitro blood samples. For the in vitro part of this study, EDTA-treated whole blood was irradiated immediately after venipuncture using single X-ray doses (1 Gy/min(-1) dose rate, 100 keV). Blood samples used to generate calibration curves as well as 10 coded (blinded) samples (0-4 Gy dose range) were incubated for 24 h in vitro, lysed and shipped on wet ice. For the in vivo part of the study PAXgene tubes were used and peripheral blood (2.5 ml) was collected from prostate cancer patients before and 24 h after the first fractionated 2 Gy dose of localized radiotherapy to the pelvis [linear accelerator (LINAC), 580 MU/min, exposure 1-1.5 min]. Assays were run in each laboratory according to locally established protocols using either microarray platforms (2 laboratories) or qRT-PCR (2 laboratories). Report times on dose estimates were documented. The mean absolute difference of estimated doses relative to the true doses (Gy) were calculated. Doses were also merged into binary categories reflecting aspects of clinical/diagnostic relevance. For the in vitro part of the study, the earliest report time on dose estimates was 7 h for qRT-PCR and 35 h for microarrays. Methodological variance of gene expression measurements (CV ≤10% for technical replicates) and interindividual variance (≤twofold for all genes) were low. Dose estimates based on one gene, ferredoxin reductase (FDXR), using qRT-PCR were as precise as dose estimates based on multiple genes using microarrays, but the precision decreased at doses ≥2 Gy. Binary dose categories comprising, for example, unexposed compared with exposed samples, could be completely discriminated with most of our methods. Exposed prostate cancer blood samples (n = 4) could be completely discriminated from unexposed blood samples (n = 4, P < 0.03, two-sided Fisher's exact test) without individual controls. This could be performed by introducing an in vitro-to-in vivo correction factor of FDXR, which varied among the laboratories. After that the in vitro-constructed calibration curves could be used for dose estimation of the in vivo exposed prostate cancer blood samples within an accuracy window of ±0.5 Gy in both contributing qRT-PCR laboratories. In conclusion, early and precise dose estimates can be performed, in particular at doses ≤2 Gy in vitro. Blood samples of prostate cancer patients exposed to 0.09-0.017 Gy could be completely discriminated from pre-exposure blood samples with the doses successfully estimated using adjusted in vitro-constructed calibration curves.

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.

Neutron track length estimator for GATE Monte Carlo dose calculation in radiotherapy.

PubMed

Elazhar, H; Deschler, T; Létang, J M; Nourreddine, A; Arbor, N

2018-06-20

The out-of-field dose in radiation therapy is a growing concern in regards to the late side-effects and secondary cancer induction. In high-energy x-ray therapy, the secondary neutrons generated through photonuclear reactions in the accelerator are part of this secondary dose. The neutron dose is currently not estimated by the treatment planning system while it appears to be preponderant for distances greater than 50 cm from the isocenter. Monte Carlo simulation has become the gold standard for accurately calculating the neutron dose under specific treatment conditions but the method is also known for having a slow statistical convergence, which makes it difficult to be used on a clinical basis. The neutron track length estimator, a neutron variance reduction technique inspired by the track length estimator method has thus been developped for the first time in the Monte Carlo code GATE to allow a fast computation of the neutron dose in radiotherapy. The details of its implementation, as well as the comparison of its performances against the analog MC method, are presented here. A gain of time from 15 to 400 can be obtained by our method, with a mean difference in the dose calculation of about 1% in comparison with the analog MC method.

Interstitial rotating shield brachytherapy for prostate cancer

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

Adams, Quentin E., E-mail: quentin-adams@uiowa.edu; Xu, Jinghzu; Breitbach, Elizabeth K.

Purpose: To present a novel needle, catheter, and radiation source system for interstitial rotating shield brachytherapy (I-RSBT) of the prostate. I-RSBT is a promising technique for reducing urethra, rectum, and bladder dose relative to conventional interstitial high-dose-rate brachytherapy (HDR-BT). Methods: A wire-mounted 62 GBq{sup 153}Gd source is proposed with an encapsulated diameter of 0.59 mm, active diameter of 0.44 mm, and active length of 10 mm. A concept model I-RSBT needle/catheter pair was constructed using concentric 50 and 75 μm thick nickel-titanium alloy (nitinol) tubes. The needle is 16-gauge (1.651 mm) in outer diameter and the catheter contains a 535more » μm thick platinum shield. I-RSBT and conventional HDR-BT treatment plans for a prostate cancer patient were generated based on Monte Carlo dose calculations. In order to minimize urethral dose, urethral dose gradient volumes within 0–5 mm of the urethra surface were allowed to receive doses less than the prescribed dose of 100%. Results: The platinum shield reduced the dose rate on the shielded side of the source at 1 cm off-axis to 6.4% of the dose rate on the unshielded side. For the case considered, for the same minimum dose to the hottest 98% of the clinical target volume (D{sub 98%}), I-RSBT reduced urethral D{sub 0.1cc} below that of conventional HDR-BT by 29%, 33%, 38%, and 44% for urethral dose gradient volumes within 0, 1, 3, and 5 mm of the urethra surface, respectively. Percentages are expressed relative to the prescription dose of 100%. For the case considered, for the same urethral dose gradient volumes, rectum D{sub 1cc} was reduced by 7%, 6%, 6%, and 6%, respectively, and bladder D{sub 1cc} was reduced by 4%, 5%, 5%, and 6%, respectively. Treatment time to deliver 20 Gy with I-RSBT was 154 min with ten 62 GBq {sup 153}Gd sources. Conclusions: For the case considered, the proposed{sup 153}Gd-based I-RSBT system has the potential to lower the urethral dose relative to HDR-BT by 29%–44% if the clinician allows a urethral dose gradient volume of 0–5 mm around the urethra to receive a dose below the prescription. A multisource approach is necessary in order to deliver the proposed {sup 153}Gd-based I-RSBT technique in reasonable treatment times.« less

The direct biologic effects of radioactive 125I seeds on pancreatic cancer cells PANC-1, at continuous low-dose rates.

PubMed

Wang, Jidong; Wang, Junjie; Liao, Anyan; Zhuang, Hongqing; Zhao, Yong

2009-08-01

The relative biologic effectiveness of model 6711 125I seeds (Ningbo Junan Pharmaceutical Technology Company,Ningbo, China) and their effects on growth, cell cycle, and apoptosis in human pancreatic cancer cell line PANC-1 were examined in the present study. PANC-1 cells were exposed to the absorbed doses of 1, 2, 4, 6, 8, and 10 Gyeither with 125I seeds (initial dose rate, 2.59 cGy=h) or with 60Co g-ray irradiation (dose rate, 221 cGy=min),respectively. Significantly greater numbers of apoptotic PANC-1 cells were detected following the continuouslow-dose-rate (CLDR) irradiation of 125I seeds, compared with cells irradiated with identical doses of 60Co g-ray. The D(0) for 60Co g-ray and 125I seed irradiation were 2.30 and 1.66, respectively. The survival fraction after 125Iseed irradiation was significantly lower than that of 60Co g-ray, with a relative biologic effectiveness of 1.39.PANC-1 cells were dose dependently arrested in the S-phase by 60Co g-rays and in the G2=M phase by 125I seeds,24 hour after irradiation. CLDR irradiation by 125I seeds was more effective in inducing cell apoptosis in PANC-1cells than acute high-dose-rate 60Co g irradiation. Interestingly, CLDR irradiation by 125I seeds can cause PANC-1cell-cycle arrest at the G2=M phase and induce apoptosis, which may be an important mechanism underlying 125Iseed-induced PANC-1 cell inhibition.

Comparison of Aerosol Delivery by Face Mask and Tracheostomy Collar.

PubMed

Bugis, Alaa A; Sheard, Meryl M; Fink, James B; Harwood, Robert J; Ari, Arzu

2015-09-01

The purpose of this study was to compare the performance of a tracheostomy collar, Wright mask, and aerosol mask attached to a jet nebulizer in facilitating aerosolized medication delivery to the lungs. We also compared albuterol delivery with open versus closed fenestration and determined the effect of inspiratory-expiratory ratio (I:E) on aerosol delivery. Albuterol (2.5 mg/3 mL) was administered to an in vitro model consisting of an adult teaching mannequin extrathoracic and upper airway with stoma intubated with an 8-mm fenestrated tracheostomy tube. The cuff was deflated. A collecting filter at the level of the bronchi was connected to a breathing simulator at a tidal volume of 400 mL, breathing frequency of 20 breaths/min, and I:E of 2:1 and 1:2. A jet nebulizer was operated with O2 at 8 L/min. Each interface was tested in triplicate. The flow was discontinued at the end of nebulization. For each test, the nebulizer was attached to a tracheostomy collar with the fenestration open or closed, a Wright mask, or an aerosol mask. Drug was analyzed by spectrophotometry (276 nm). A paired t test and analysis of variance were performed (P < .05). The mean ± SD percent albuterol dose delivered distal to the bronchi was greater with the tracheostomy collar with a closed fenestration (9.4 ± 1.5%) compared with an open fenestration (7.0 ± 0.8%). The doses delivered with the Wright mask (4.1 ± 0.6%) and aerosol mask (3.5 ± 0.04%) were both less than with the tracheostomy collar under either condition (P < .05). Increasing the I:E from 1:2 to 2:1 increased aerosol delivery by 2.5-4%, with significance for the tracheostomy collar with an open fenestration (11.6 ± 1.4%), Wright mask (7.2 ± 0.6%), and aerosol mask (6.1 ± 0.5%). In an adult tracheostomy model, the tracheostomy collar delivered more aerosol to the bronchi than the Wright or aerosol mask. An I:E of 2:1 caused greater aerosol deposition compared with an I:E of 1:2. During aerosol administration via a tracheostomy collar, closing the fenestration improved aerosol delivery. Copyright © 2015 by Daedalus Enterprises.

Risk analysis in cohort studies with heterogeneous strata. A global chi2-test for dose-response relationship, generalizing the Mantel-Haenszel procedure.

PubMed

Ahlborn, W; Tuz, H J; Uberla, K

1990-03-01

In cohort studies the Mantel-Haenszel estimator ORMH is computed from sample data and is used as a point estimator of relative risk. Test-based confidence intervals are estimated with the help of the asymptotic chi-squared distributed MH-statistic chi 2MHS. The Mantel-extension-chi-squared is used as a test statistic for a dose-response relationship. Both test statistics--the Mantel-Haenszel-chi as well as the Mantel-extension-chi--assume homogeneity of risk across strata, which is rarely present. Also an extended nonparametric statistic, proposed by Terpstra, which is based on the Mann-Whitney-statistics assumes homogeneity of risk across strata. We have earlier defined four risk measures RRkj (k = 1,2,...,4) in the population and considered their estimates and the corresponding asymptotic distributions. In order to overcome the homogeneity assumption we use the delta-method to get "test-based" confidence intervals. Because the four risk measures RRkj are presented as functions of four weights gik we give, consequently, the asymptotic variances of these risk estimators also as functions of the weights gik in a closed form. Approximations to these variances are given. For testing a dose-response relationship we propose a new class of chi 2(1)-distributed global measures Gk and the corresponding global chi 2-test. In contrast to the Mantel-extension-chi homogeneity of risk across strata must not be assumed. These global test statistics are of the Wald type for composite hypotheses.(ABSTRACT TRUNCATED AT 250 WORDS)

Planning additional drilling campaign using two-space genetic algorithm: A game theoretical approach

NASA Astrophysics Data System (ADS)

Kumral, Mustafa; Ozer, Umit

2013-03-01

Grade and tonnage are the most important technical uncertainties in mining ventures because of the use of estimations/simulations, which are mostly generated from drill data. Open pit mines are planned and designed on the basis of the blocks representing the entire orebody. Each block has different estimation/simulation variance reflecting uncertainty to some extent. The estimation/simulation realizations are submitted to mine production scheduling process. However, the use of a block model with varying estimation/simulation variances will lead to serious risk in the scheduling. In the medium of multiple simulations, the dispersion variances of blocks can be thought to regard technical uncertainties. However, the dispersion variance cannot handle uncertainty associated with varying estimation/simulation variances of blocks. This paper proposes an approach that generates the configuration of the best additional drilling campaign to generate more homogenous estimation/simulation variances of blocks. In other words, the objective is to find the best drilling configuration in such a way as to minimize grade uncertainty under budget constraint. Uncertainty measure of the optimization process in this paper is interpolation variance, which considers data locations and grades. The problem is expressed as a minmax problem, which focuses on finding the best worst-case performance i.e., minimizing interpolation variance of the block generating maximum interpolation variance. Since the optimization model requires computing the interpolation variances of blocks being simulated/estimated in each iteration, the problem cannot be solved by standard optimization tools. This motivates to use two-space genetic algorithm (GA) approach to solve the problem. The technique has two spaces: feasible drill hole configuration with minimization of interpolation variance and drill hole simulations with maximization of interpolation variance. Two-space interacts to find a minmax solution iteratively. A case study was conducted to demonstrate the performance of approach. The findings showed that the approach could be used to plan a new drilling campaign.

Evaluation of the Protective Role of Glycine max Seed Extract (Soybean Oil) in Drug-Induced Nephrotoxicity in Experimental Rats.

PubMed

Ramasamy, Anand; Jothivel, Nandhakumar; Das, Saibal; Swapna, A; Albert, Alice Padmini; Barnwal, Preeti; Babu, Dinesh

2017-09-28

This study was conducted to evaluate the nephroprotective effect of Glycine max seed extract (soybean oil) against gentamicin- and rifampicin-induced nephrotoxicity in Sprague-Dawley rats and to compare its effects with those of vitamin E, which has well-established antioxidant and nephroprotective effects. Sixty male Sprague-Dawley rats (body weight 150-210 g) were divided into 10 groups. The first five groups were treated for 14 consecutive days with normal saline (5 ml/kg, by mouth [p.o.]); gentamicin (80 mg/kg intraperitoneally [i.p.]); gentamicin (80 mg/kg, i.p.) + vitamin E (250 mg/kg p.o.); gentamicin (80 mg/kg i.p.) + soybean oil (2.5 ml/kg p.o.); and gentamicin (80 mg/kg, i.p.) + soybean oil (5 ml/kg p.o.), respectively. For the next five groups, the same group allocation was done, but gentamicin was replaced with rifampicin (1 g/kg i.p.). Various biomarkers for nephrotoxicity in serum and urine were evaluated along with histopathological examination of kidneys. Analysis of variance (ANOVA) was done following Tukey's multiple comparison test; p < .05 was considered significant. Soybean oil in both doses significantly (p < .005) decreased serum blood urea nitrogen, creatinine, urea, uric acid and urine volume, kidney weight, urinary sodium, urinary potassium, and total protein and significantly (p < .005) increased serum total protein and urine creatinine in gentamicin- and rifampicin-treated animals, exhibiting nephroprotective effects. Soybean oil also showed strong antioxidant effects, causing significant (p < .005) increase in kidney homogenate catalases, glutathione peroxidase, and superoxide dismutase and significant (p < .005) decrease in lipid peroxidase in gentamicin- and rifampicin-treated animals. Soybean oil demonstrated good nephroprotective activity due to antioxidant effects.

Chernobyl accident: reconstruction of thyroid dose for inhabitants of the Republic of Belarus.

PubMed

Gavrilin, Y I; Khrouch, V T; Shinkarev, S M; Krysenko, N A; Skryabin, A M; Bouville, A; Anspaugh, L R

1999-02-01

The Chernobyl accident in April 1986 resulted in widespread contamination of the environment with radioactive materials, including (131)I and other radioiodines. This environmental contamination led to substantial radiation doses in the thyroids of many inhabitants of the Republic of Belarus. The reconstruction of thyroid doses received by Belarussians is based primarily on exposure rates measured against the neck of more than 200,000 people in the more contaminated territories; these measurements were carried out within a few weeks after the accident and before the decay of (131)I to negligible levels. Preliminary estimates of thyroid dose have been divided into 3 classes: Class 1 ("measured" doses), Class 2 (doses "derived by affinity"), and Class 3 ("empirically-derived" doses). Class 1 doses are estimated directly from the measured thyroidal (131)I content of the person considered, plus information on lifestyle and dietary habits. Such estimates are available for about 130,000 individuals from the contaminated areas of the Gomel and Mogilev Oblasts and from the city of Minsk. Maximum individual doses are estimated to range up to about 60 Gy. For every village with a sufficient number of residents with Class 1 doses, individual thyroid dose distributions are determined for several age groups and levels of milk consumption. These data are used to derive Class 2 thyroid dose estimates for unmeasured inhabitants of these villages. For any village where the number of residents with Class 1 thyroid doses is small or equal to zero, individual thyroid doses of Class 3 are derived from the relationship obtained between the mean adult thyroid dose and the deposition density of (131)I or 137Cs in villages with Class 2 thyroid doses presenting characteristics similar to those of the village considered. In order to improve the reliability of the Class 3 thyroid doses, an extensive program of measurement of (129)I in soils is envisaged.

WE-D-BRE-07: Variance-Based Sensitivity Analysis to Quantify the Impact of Biological Uncertainties in Particle Therapy

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

Kamp, F.; Brueningk, S.C.; Wilkens, J.J.

Purpose: In particle therapy, treatment planning and evaluation are frequently based on biological models to estimate the relative biological effectiveness (RBE) or the equivalent dose in 2 Gy fractions (EQD2). In the context of the linear-quadratic model, these quantities depend on biological parameters (α, β) for ions as well as for the reference radiation and on the dose per fraction. The needed biological parameters as well as their dependency on ion species and ion energy typically are subject to large (relative) uncertainties of up to 20–40% or even more. Therefore it is necessary to estimate the resulting uncertainties in e.g.more » RBE or EQD2 caused by the uncertainties of the relevant input parameters. Methods: We use a variance-based sensitivity analysis (SA) approach, in which uncertainties in input parameters are modeled by random number distributions. The evaluated function is executed 10{sup 4} to 10{sup 6} times, each run with a different set of input parameters, randomly varied according to their assigned distribution. The sensitivity S is a variance-based ranking (from S = 0, no impact, to S = 1, only influential part) of the impact of input uncertainties. The SA approach is implemented for carbon ion treatment plans on 3D patient data, providing information about variations (and their origin) in RBE and EQD2. Results: The quantification enables 3D sensitivity maps, showing dependencies of RBE and EQD2 on different input uncertainties. The high number of runs allows displaying the interplay between different input uncertainties. The SA identifies input parameter combinations which result in extreme deviations of the result and the input parameter for which an uncertainty reduction is the most rewarding. Conclusion: The presented variance-based SA provides advantageous properties in terms of visualization and quantification of (biological) uncertainties and their impact. The method is very flexible, model independent, and enables a broad assessment of uncertainties. Supported by DFG grant WI 3745/1-1 and DFG cluster of excellence: Munich-Centre for Advanced Photonics.« less

Effect of combined oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models.

PubMed

Rock, Erin M; Connolly, Cassidy; Limebeer, Cheryl L; Parker, Linda A

2016-09-01

The purpose of this study was to evaluate the potential of oral combined cannabis constituents to reduce nausea. The objective of this study was to determine the effect of combining subthreshold oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models of conditioned gaping. The potential of intragastric (i.g.) administration of THC, CBDA, or combined doses, to interfere with acute nausea-induced conditioned gaping (acute nausea) or the expression of contextually elicited conditioned gaping (anticipatory nausea), was evaluated. For acute nausea, i.g. administration of subthreshold doses of THC (0.5 and 1 mg/kg) or CBDA (0.5 and 1 μg/kg) significantly suppressed acute nausea-induced gaping, whereas higher individual doses of both THC and CBDA were maximally effective. Combined i.g. administration of higher doses of THC and CBDA (2.5 mg/kg THC-2.5 μg/kg CBDA; 10 mg/kg THC-10 μg/kg CBDA; 20 mg/kg THC-20 μg/kg CBDA) also enhanced positive hedonic reactions elicited by saccharin solution during conditioning. For anticipatory nausea, combined subthreshold i.g. doses of THC (0.1 mg/kg) and CBDA (0.1 μg/kg) suppressed contextually elicited conditioned gaping. When administered i.g., THC was effective on its own at doses ranging from 1 to 10 mg/kg, but CBDA was only effective at 10 μg/kg. THC alone was equally effective by intraperitoneal (i.p.) and i.g. administration, whereas CBDA alone was more effective by i.p. administration (Rock et al. in Psychopharmacol (Berl) 232:4445-4454, 2015) than by i.g. administration. Oral administration of subthreshold doses of THC and CBDA may be an effective new treatment for acute nausea and anticipatory nausea and appetite enhancement in chemotherapy patients.

Estimating Required Contingency Funds for Construction Projects using Multiple Linear Regression

DTIC Science & Technology

2006-03-01

Breusch - Pagan test , in which the null hypothesis states that the residuals have constant variance. The alternate hypothesis is that the residuals do not...variance, the Breusch - Pagan test provides statistical evidence that the assumption is justified. For the proposed model, the p-value is 0.173...entire test sample. v Acknowledgments First, I would like to acknowledge the influence and help of Greg Hoffman. His work served as the

A Novel Admixture-Based Pharmacogenetic Approach to Refine Warfarin Dosing in Caribbean Hispanics

PubMed Central

Claudio-Campos, Karla; Rivera-Miranda, Giselle; Bermúdez-Bosch, Luis; Renta, Jessicca Y.; Cadilla, Carmen L.; Cruz, Iadelisse; Feliu, Juan F.; Vergara, Cunegundo; Ruaño, Gualberto

2016-01-01

Aim This study is aimed at developing a novel admixture-adjusted pharmacogenomic approach to individually refine warfarin dosing in Caribbean Hispanic patients. Patients & Methods A multiple linear regression analysis of effective warfarin doses versus relevant genotypes, admixture, clinical and demographic factors was performed in 255 patients and further validated externally in another cohort of 55 individuals. Results The admixture-adjusted, genotype-guided warfarin dosing refinement algorithm developed in Caribbean Hispanics showed better predictability (R2 = 0.70, MAE = 0.72mg/day) than a clinical algorithm that excluded genotypes and admixture (R2 = 0.60, MAE = 0.99mg/day), and outperformed two prior pharmacogenetic algorithms in predicting effective dose in this population. For patients at the highest risk of adverse events, 45.5% of the dose predictions using the developed pharmacogenetic model resulted in ideal dose as compared with only 29% when using the clinical non-genetic algorithm (p<0.001). The admixture-driven pharmacogenetic algorithm predicted 58% of warfarin dose variance when externally validated in 55 individuals from an independent validation cohort (MAE = 0.89 mg/day, 24% mean bias). Conclusions Results supported our rationale to incorporate individual’s genotypes and unique admixture metrics into pharmacogenetic refinement models in order to increase predictability when expanding them to admixed populations like Caribbean Hispanics. Trial Registration ClinicalTrials.gov NCT01318057 PMID:26745506

Pharmacokinetics of theophylline: a dose-range study.

PubMed Central

Rovei, V; Chanoine, F; Strolin Benedetti, M

1982-01-01

1 Pharmacokinetics of theophylline were investigated in a group of healthy adult volunteers (non smokers and on xanthine-free diet) following single oral administration of 125, 250, 375 and 500 mg doses as tablets (Theodel). 2 Absorption of theophylline was rapid and followed first-order kinetics. Plasma curves were fitted according to a one compartment open model. 3 There was a linear relationship (P less than 0.001) between plasma Cmax or AUCx values and the administered dose. The analysis of variance showed that the pharmacokinetic parameters of theophylline (t1/2 abs, tmax, t1/2 beta, CL, CLR, Vd and F) were not modified at any dose. 4 Absorption of the drug was complete since the recovery in urine of theophylline (13.7 to 16.8% of the dose) and its major metabolites, 1,3-dimethyluric acid (35 to 42%), 1-methyluric acid (21.3 to 26.7%) and 3-methylxanthine (11.5 to 13.7%), accounted for the administered dose. Some impairment of demethylation to 3-methylxanthine was observed in two subjects, however the percentage of theophylline and its major metabolites excreted in urine was constant for all the four doses. 5 On the basis of these results, after single oral administration, elimination of theophylline followed first-order kinetics in the range of doses investigated (1.62 to 10.42 mg/kg). PMID:7150456

40 CFR 52.720 - Identification of plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 2, Parts I, II and III were submitted May 4, 1972, by the Governor. (3) A document describing the... and the final rulemaking action: (i)-(iii) [Reserved] (iv) The new materials in Section 4.11 of the... boilers a variance from the requirements of IPCB (A), Rule 203(g)(1)(C)(i) and/or Rule 203(g)(1)(D) which...

Dose reduction assessment in dynamic CT myocardial perfusion imaging in a porcine balloon-induced-ischemia model

NASA Astrophysics Data System (ADS)

Fahmi, Rachid; Eck, Brendan L.; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.

2014-03-01

We investigated the use of an advanced hybrid iterative reconstruction (IR) technique (iDose4, Philips Health- care) for low dose dynamic myocardial CT perfusion (CTP) imaging. A porcine model was created to mimic coronary stenosis through partial occlusion of the left anterior descending (LAD) artery with a balloon catheter. The severity of LAD occlusion was adjusted with FFR measurements. Dynamic CT images were acquired at end-systole (45% R-R) using a multi-detector CT (MDCT) scanner. Various corrections were applied to the acquired scans to reduce motion and imaging artifacts. Absolute myocardial blood flow (MBF) was computed with a deconvolution-based approach using singular value decomposition (SVD). We compared a high and a low dose radiation protocol corresponding to two different tube-voltage/tube-current combinations (80kV p/100mAs and 120kV p/150mAs). The corresponding radiation doses for these protocols are 7.8mSv and 34.3mSV , respectively. The images were reconstructed using conventional FBP and three noise-reduction strengths of the IR method, iDose. Flow contrast-to-noise ratio, CNRf, as obtained from MBF maps, was used to quantitatively evaluate the effect of reconstruction on contrast between normal and ischemic myocardial tissue. Preliminary results showed that the use of iDose to reconstruct low dose images provide better or comparable CNRf to that of high dose images reconstructed with FBP, suggesting significant dose savings. CNRf was improved with the three used levels of iDose compared to FBP for both protocols. When using the entire 4D dynamic sequence for MBF computation, a 77% dose reduction was achieved, while considering only half the scans (i.e., every other heart cycle) allowed even further dose reduction while maintaining relatively higher CNRf.

Studies on fate and toxicity of nanoalumina in male albino rats: Lethality, bioaccumulation and genotoxicity.

PubMed

Morsy, Gamal M; El-Ala, Kawther S Abou; Ali, Atef A

2016-02-01

The purpose of this study is to follow-up the distribution, lethality percentile doses (LDs) and bioaccumulation of aluminium oxide nanoparticles (Al2O3-NPs, average diameter 9.83 ± 1.61 nm) in some tissues of male albino rats, and to evaluate its genotoxicity to the brain tissues, during acute and sublethal experiments. The LDs of Al2O3-NPs, including median lethal dose (LD50), were estimated after intraperitoneal injection. The computed LD50 at 24 and 48 h were 15.10 and 12.88 g/kg body weight (b.w.), respectively. For acute experiments, the bioaccumulation of aluminium (Al) in the brain, liver, kidneys, intestine and spleen was estimated after 48 h of injection with a single acute dose (3.9, 6.4 and 8.5 g/kg b.w.), while for sublethal experiments it was after 1, 3, 7, 14 and 28 days of injection with 1.3 g/kg b.w. once in 2 days. Multi-way analysis of variance affirmed that Al uptake, in acute experiments, was significantly affected by the injected doses, organs (brain, liver, kidneys, intestine and spleen) and their interactions, while for sublethal experiments an altogether effect based on time (1, 3, 7, 14, 28 days), doses (0 and 1.3 g), organs and their interactions was reported. In addition, Al accumulated in the brain, liver, kidney, intestine and spleen of rats administered with Al2O3-NPs were significantly higher than the corresponding controls, during acute and sublethal experiments. The uptake of Al by the spleen of rats injected with acute doses was greater than that accumulated by kidney>brain>intestine>liver, whereas the brain of rats injected with sublethal dose accumulated lesser amount of Al followed by the kidney

Chlorophyll a and inorganic suspended solids in backwaters of the upper Mississippi River system: Backwater lake effects and their associations with selected environmental predictors

USGS Publications Warehouse

Rogala, James T.; Gray, Brian R.

2006-01-01

The Long Term Resource Monitoring Program (LTRMP) uses a stratified random sampling design to obtain water quality statistics within selected study reaches of the Upper Mississippi River System (UMRS). LTRMP sampling strata are based on aquatic area types generally found in large rivers (e.g., main channel, side channel, backwater, and impounded areas). For hydrologically well-mixed strata (i.e., main channel), variance associated with spatial scales smaller than the strata scale is a relatively minor issue for many water quality parameters. However, analysis of LTRMP water quality data has shown that within-strata variability at the strata scale is high in off-channel areas (i.e., backwaters). A portion of that variability may be associated with differences among individual backwater lakes (i.e., small and large backwater regions separated by channels) that cumulatively make up the backwater stratum. The objective of the statistical modeling presented here is to determine if differences among backwater lakes account for a large portion of the variance observed in the backwater stratum for selected parameters. If variance associated with backwater lakes is high, then inclusion of backwater lake effects within statistical models is warranted. Further, lakes themselves may represent natural experimental units where associations of interest to management may be estimated.

Genetic and environmental variance in content dimensions of the MMPI.

PubMed

Rose, R J

1988-08-01

To evaluate genetic and environmental variance in the Minnesota Multiphasic Personality Inventory (MMPI), I studied nine factor scales identified in the first item factor analysis of normal adult MMPIs in a sample of 820 adolescent and young adult co-twins. Conventional twin comparisons documented heritable variance in six of the nine MMPI factors (Neuroticism, Psychoticism, Extraversion, Somatic Complaints, Inadequacy, and Cynicism), whereas significant influence from shared environmental experience was found for four factors (Masculinity versus Femininity, Extraversion, Religious Orthodoxy, and Intellectual Interests). Genetic variance in the nine factors was more evident in results from twin sisters than those of twin brothers, and a developmental-genetic analysis, using hierarchical multiple regressions of double-entry matrixes of the twins' raw data, revealed that in four MMPI factor scales, genetic effects were significantly modulated by age or gender or their interaction during the developmental period from early adolescence to early adulthood.

Adaptive Dose Painting by Numbers for Head-and-Neck Cancer

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

Duprez, Frederic, E-mail: frederic.duprez@ugent.be; De Neve, Wilfried; De Gersem, Werner

Purpose: To investigate the feasibility of adaptive intensity-modulated radiation therapy (IMRT) using dose painting by numbers (DPBN) for head-and-neck cancer. Methods and Materials: Each patient's treatment used three separate treatment plans: fractions 1-10 used a DPBN ([{sup 18}-F]fluoro-2-deoxy-D-glucose positron emission tomography [{sup 18}F-FDG-PET]) voxel intensity-based IMRT plan based on a pretreatment {sup 18}F-FDG-PET/computed tomography (CT) scan; fractions 11-20 used a DPBN plan based on a {sup 18}F-FDG-PET/CT scan acquired after the eighth fraction; and fractions 21-32 used a conventional (uniform dose) IMRT plan. In a Phase I trial, two dose prescription levels were tested: a median dose of 80.9 Gymore » to the high-dose clinical target volume (CTV{sub highdose}) (dose level I) and a median dose of 85.9 Gy to the gross tumor volume (GTV) (dose level II). Between February 2007 and August 2009, 7 patients at dose level I and 14 patients at dose level II were enrolled. Results: All patients finished treatment without a break, and no Grade 4 acute toxicity was observed. Treatment adaptation (i.e., plans based on the second {sup 18}F-FDG-PET/CT scan) reduced the volumes for the GTV (41%, p = 0.01), CTV{sub highdose} (18%, p = 0.01), high-dose planning target volume (14%, p = 0.02), and parotids (9-12%, p < 0.05). Because the GTV was much smaller than the CTV{sub highdose} and target adaptation, further dose escalation at dose level II resulted in less severe toxicity than that observed at dose level I. Conclusion: To our knowledge, this represents the first clinical study that combines adaptive treatments with dose painting by numbers. Treatment as described above is feasible.« less

Pediatric chest HRCT using the iDose4 Hybrid Iterative Reconstruction Algorithm: Which iDose level to choose?

NASA Astrophysics Data System (ADS)

Smarda, M.; Alexopoulou, E.; Mazioti, A.; Kordolaimi, S.; Ploussi, A.; Priftis, K.; Efstathopoulos, E.

2015-09-01

Purpose of the study is to determine the appropriate iterative reconstruction (IR) algorithm level that combines image quality and diagnostic confidence, for pediatric patients undergoing high-resolution computed tomography (HRCT). During the last 2 years, a total number of 20 children up to 10 years old with a clinical presentation of chronic bronchitis underwent HRCT in our department's 64-detector row CT scanner using the iDose IR algorithm, with almost similar image settings (80kVp, 40-50 mAs). CT images were reconstructed with all iDose levels (level 1 to 7) as well as with filtered-back projection (FBP) algorithm. Subjective image quality was evaluated by 2 experienced radiologists in terms of image noise, sharpness, contrast and diagnostic acceptability using a 5-point scale (1=excellent image, 5=non-acceptable image). Artifacts existance was also pointed out. All mean scores from both radiologists corresponded to satisfactory image quality (score ≤3), even with the FBP algorithm use. Almost excellent (score <2) overall image quality was achieved with iDose levels 5 to 7, but oversmoothing artifacts appearing with iDose levels 6 and 7 affected the diagnostic confidence. In conclusion, the use of iDose level 5 enables almost excellent image quality without considerable artifacts affecting the diagnosis. Further evaluation is needed in order to draw more precise conclusions.

Effect of Ion Flux (Dose Rate) in Source-Drain Extension Ion Implantation for 10-nm Node FinFET and Beyond on 300/450mm Platforms

NASA Astrophysics Data System (ADS)

Shen, Ming-Yi

The improvement of wafer equipment productivity has been a continuous effort of the semiconductor industry. Higher productivity implies lower product price, which economically drives more demand from the market. This is desired by the semiconductor manufacturing industry. By raising the ion beam current of the ion implanter for 300/450mm platforms, it is possible to increase the throughput of the ion implanter. The resulting dose rate can be comparable to the performance of conventional ion implanters or higher, depending on beam current and beam size. Thus, effects caused by higher dose rate must be investigated further. One of the major applications of ion implantation (I/I) is source-drain extension (SDE) I/I for the silicon FinFET device. This study investigated the dose rate effects on the material properties and device performance of the 10-nm node silicon FinFET. In order to gain better understanding of the dose rate effects, the dose rate study is based on Synopsys Technology CAD (TCAD) process and device simulations that are calibrated and validated using available structural silicon fin samples. We have successfully shown that the kinetic monte carlo (KMC) I/I simulation can precisely model both the silicon amorphization and the arsenic distribution in the fin by comparing the KMC simulation results with TEM images. The results of the KMC I/I simulation show that at high dose rate more activated arsenic dopants were in the source-drain extension (SDE) region. This finding matches with the increased silicon amorphization caused by the high dose-rate I/I, given that the arsenic atoms could be more easily activated by the solid phase epitaxial regrowth process. This increased silicon amorphization led to not only higher arsenic activation near the spacer edge, but also less arsenic atoms straggling into the channel. Hence, it is possible to improve the throughput of the ion implanter when the dopants are implanted at high dose rate if the same doping level with a lower wafer dose can be achieved. In addition, the leakage current might also be reduced due to less undesired dopants in the channel. However, the twin defects from the problematic Si{111} recrystallization is well-known to cause excessive leakage current to the FinFET. This drawback can offset the benefits of the high dose rate I/I mentioned above. This work produced the first attempt at simulating the electrical impact of twin defects on advanced-node (10 nm) FinFET device performance. It was found that the high dose-rate I/I causes more twin defects in the silicon fin, and the physical locations of these defects were close to the channel. The defects undesirably induced trap-assisted band-to-band tunneling near the drain, which increased the leakage current. This issue could be mitigated by using asymmetrical gate overlap/underlap design or thicker spacer for SDE I/I so that the twin defects are not located in the depletion region near the drain.

Plasma concentrations, behavioural and physiological effects following intravenous and intramuscular detomidine in horses.

PubMed

Mama, K R; Grimsrud, K; Snell, T; Stanley, S

2009-11-01

Detomidine hydrochloride is used to provide sedation, muscle relaxation and analgesia in horses, but a lack of information pertaining to plasma concentration has limited the ability to correlate drug concentration with effect. To build on previous information and assess detomidine for i.v. and i.m. use in horses by simultaneously assessing plasma drug concentrations, physiological parameters and behavioural characteristics. Systemic effects would be seen following i.m. and i.v. detomidine administration and these effects would be positively correlated with plasma drug concentrations. Behavioural (e.g. head position) and physiological (e.g. heart rate) responses were recorded at fixed time points from 4 min to 24 h after i.m. or i.v. detomidine (30 microg/kg bwt) administration to 8 horses. Route of administration was assigned using a balanced crossover design. Blood was sampled at predetermined time points from 0.5 min to 48 h post administration for subsequent detomidine concentration measurements using liquid chromatography-mass spectrometry. Data were summarised as mean +/- s.d. for subsequent analysis of variance for repeated measures. Plasma detomidine concentration peaked earlier (1.5 min vs. 1.5 h) and was significantly higher (105.4 +/- 71.6 ng/ml vs. 6.9 +/- 1.4 ng/ml) after i.v. vs. i.m. administration. Physiological and behavioural changes were of a greater magnitude and observed at earlier time points for i.v. vs. i.m. groups. For example, head position decreased from an average of 116 cm in both groups to a low value 35 +/- 23 cm from the ground 10 min following i.v. detomidine and to 64 +/- 24 cm 60 min after i.m. detomidine. Changes in heart rate followed a similar pattern; low value of 17 beats/min 10 min after i.v. administration and 29 beats/min 30 min after i.m. administration. Plasma drug concentration and measured effects were correlated positively and varied with route of administration following a single dose of detomidine. Results support a significant influence of route of administration on desirable and undesirable drug effects that influence case management.

Dose-specific transcriptional responses in thyroid tissue in mice after (131)I administration.

PubMed

Rudqvist, Nils; Schüler, Emil; Parris, Toshima Z; Langen, Britta; Helou, Khalil; Forssell-Aronsson, Eva

2015-03-01

In the present investigation, microarray analysis was used to monitor transcriptional activity in thyroids in mice 24 h after (131)I exposure. The aims of this study were to 1) assess the transcriptional patterns associated with (131)I exposure in normal mouse thyroid tissue and 2) propose biomarkers for (131)I exposure of the thyroid. Adult BALB/c nude mice were i.v. injected with 13, 130 or 260 kBq of (131)I and killed 24h after injection (absorbed dose to thyroid: 0.85, 8.5, or 17 Gy). Mock-treated mice were used as controls. Total RNA was extracted from thyroids and processed using the Illumina platform. In total, 497, 546, and 90 transcripts were regulated (fold change ≥1.5) in the thyroid after 0.85, 8.5, and 17 Gy, respectively. These were involved in several biological functions, e.g. oxygen access, inflammation and immune response, and apoptosis/anti-apoptosis. Approximately 50% of the involved transcripts at each absorbed dose level were dose-specific, and 18 transcripts were commonly detected at all absorbed dose levels. The Agpat9, Plau, Prf1, and S100a8 gene expression displayed a monotone decrease in regulation with absorbed dose, and further studies need to be performed to evaluate if they may be useful as dose-related biomarkers for 131I exposure. Distinct and substantial differences in gene expression and affected biological functions were detected at the different absorbed dose levels. The transcriptional profiles were specific for the different absorbed dose levels. We propose that the Agpat9, Plau, Prf1, and S100a8 genes might be novel potential absorbed dose-related biomarkers to (131)I exposure of thyroid. During the recent years, genomic techniques have been developed; however, they have not been fully utilized in nuclear medicine and radiation biology. We have used RNA microarrays to investigate genome-wide transcriptional regulations in thyroid tissue in mice after low, intermediate, and high absorbed doses from (131)I exposure in vivo. Using this approach, we have identified novel biological responses and potential absorbed dose-related biomarkers to (131)I exposure. Our research shows the importance of embracing technological advances and multi-disciplinary collaboration in order to apply them in radiation therapy, nuclear medicine, and radiation biology. This work may contribute with new knowledge of potential normal tissue effects or complications that may occur after exposure to ionizing radiation in diagnostic and therapeutic nuclear medicine, and due to radioactive fallout or accident with radionuclide spread. Copyright © 2014 Elsevier Inc. All rights reserved.

Distributed, Collaborative Human-Robotic Networks for Outdoor Experiments in Search, Identify and Track

DTIC Science & Technology

2011-01-11

and its variance σ2Ûi are determined. Ûi = ûi + Pu,EN (PEN )−1 [( Ejc Njc ) − ( êi n̂i )] (15) σ2 Ûi = Pui − P u,EN i ( PENi )−1 PEN,ui (16) where...screen; the operator can click a robot’s camera view to select it as the Focus Robot. The Focus Robot’s camera stream is enlarged and displayed in the

A reproducible radiation delivery method for unanesthetized rodents during periods of hind limb unloading

NASA Astrophysics Data System (ADS)

Walb, M. C.; Black, P. J.; Payne, V. S.; Munley, M. T.; Willey, J. S.

2015-07-01

Exposure to the spaceflight environment has long been known to be a health challenge concerning many body systems. Both microgravity and/or ionizing radiation can cause acute and chronic effects in multiple body systems. The hind limb unloaded (HLU) rodent model is a ground-based analogue for microgravity that can be used to simulate and study the combined biologic effects of reduced loading with spaceflight radiation exposure. However, studies delivering radiation to rodents during periods of HLU are rare. Herein we report the development of an irradiation protocol using a clinical linear accelerator that can be used with hind limb unloaded, unanesthetized rodents that is capable of being performed at most academic medical centers. A 30.5 cm × 30.5 cm × 40.6 cm rectangular chamber was constructed out of polymethyl methacrylate (PMMA) sheets (0.64 cm thickness). Five centimeters of water-equivalent material were placed outside of two PMMA inserts on either side of the rodent that permitted the desired radiation dose buildup (electronic equilibrium) and helped to achieve a flatter dose profile. Perforated aluminum strips permitted the suspension dowel to be placed at varying heights depending on the rodent size. Radiation was delivered using a medical linear accelerator at an accelerating potential of 10 MV. A calibrated PTW Farmer ionization chamber, wrapped in appropriately thick tissue-equivalent bolus material to simulate the volume of the rodent, was used to verify a uniform dose distribution at various regions of the chamber. The dosimetry measurements confirmed variances typically within 3%, with maximum variance <10% indicated through optically stimulated luminescent dosimeter (OSLD) measurements, thus delivering reliable spaceflight-relevant total body doses and ensuring a uniform dose regardless of its location within the chamber. Due to the relative abundance of LINACs at academic medical centers and the reliability of their dosimetry properties, this method may find great utility in the implementation of future ground-based studies that examine the combined spaceflight challenges of reduced loading and radiation while using the HLU rodent model.

Pediatric 131I-MIBG Therapy for Neuroblastoma: Whole-Body 131I-MIBG Clearance, Radiation Doses to Patients, Family Caregivers, Medical Staff, and Radiation Safety Measures.

PubMed

Willegaignon, José; Crema, Karin Paola; Oliveira, Nathaliê Canhameiro; Pelissoni, Rogério Alexandre; Coura-Filho, George Barberio; Sapienza, Marcelo Tatit; Buchpiguel, Carlos Alberto

2018-06-19

I-metaiodobenzylguanidine (I-MIBG) has been used in the diagnosis and therapy of neuroblastoma in adult and pediatric patients for many years. In this study, we evaluated whole-body I-MIBG clearance and radiation doses received by patients, family caregivers, and medical staff to establish appropriate radiation safety measures to be used in therapy applications. Research was focused on 23 children and adolescents with metastatic neuroblastoma, with ages ranging from 1.8 to 13 years, being treated with I-MIBG. Based on measured external dose rates from patients, dosimetric data to patients, family members, and others were calculated. The mean ± SD I-MIBG activity administered was 8.55 ± 1.69 GBq. Percent whole-body retention rates of I-MIBG at 24, 48, and 72 hours after administration were 48% ± 7%, 23% ± 7%, and 12% ± 6%, with a whole-body I-MIBG effective half-life of 23 ± 5 hours for all patients. The mean doses for patients were 0.234 ± 0.096 mGy·MBq to red-marrow and 0.251 ± 0.101 mGy·MBq to whole body. The maximum potential radiation doses transmitted by patients to others at 1.0 m was estimated to be 11.9 ± 3.4 mSv, with 97% of this dose occurring over 120 hours after therapy administration. Measured mean dose received by the 22 family caregivers was 1.88 ± 1.85 mSv, and that received by the 19 pediatric physicians was 43 ± 51 μSv. In this study, we evaluated the whole-body clearance of I-MIBG in 23 pediatric patients, and the radiation doses received by family caregivers and medical staff during these therapy procedures, thus facilitating the establishment of radiation safety measures to be applied in pediatric therapy.

Computer modeling of airway deposition distribution of Foster(®) NEXThaler(®) and Seretide(®) Diskus(®) dry powder combination drugs.

PubMed

Jókay, Ágnes; Farkas, Árpád; Füri, Péter; Horváth, Alpár; Tomisa, Gábor; Balásházy, Imre

2016-06-10

Asthma is a serious global health problem with rising prevalence and treatment costs. Due to the growing number of different types of inhalation devices and aerosol drugs, physicians often face difficulties in choosing the right medication for their patients. The main objectives of this study are (i) to elucidate the possibility and the advantages of the application of numerical modeling techniques in aerosol drug and device selection, and (ii) to demonstrate the possibility of the optimization of inhalation modes in asthma therapy with a numerical lung model by simulating patient-specific drug deposition distributions. In this study we measured inhalation parameter values of 25 healthy adult volunteers when using Foster(®) NEXThaler(®) and Seretide(®) Diskus(®). Relationships between emitted doses and patient-specific inhalation flow rates were established. Furthermore, individualized emitted particle size distributions were determined applying size distributions at measured flow rates. Based on the measured breathing parameter values, we calculated patient-specific drug deposition distributions for the active components (steroid and bronchodilator) of both drugs by the help of a validated aerosol lung deposition model adapted to therapeutic aerosols. Deposited dose fractions and deposition densities have been computed in the entire respiratory tract, in distinct anatomical regions of the airways and at the level of airway generations. We found that Foster(®) NEXThaler(®) deposits more efficiently in the lungs (average deposited steroid dose: 42.32±5.76% of the nominal emitted dose) than Seretide(®) Diskus(®) (average deposited steroid dose: 24.33±2.83% of the nominal emitted dose), but the variance of the deposition values of different individuals in the lung is significant. In addition, there are differences in the required minimal flow rates, therefore at certain patients Seretide(®) Diskus(®) or pMDIs could be a better choice. Our results show that validated computer deposition models could be useful tools in providing valuable deposition data and assisting health professionals in the personalized drug selection and delivery optimization. Patient-specific modeling could open a new horizon in the treatment of asthma towards a more effective personalized medicine in the future. Copyright © 2016 Elsevier B.V. All rights reserved.

Validation of CT dose-reduction simulation

PubMed Central

Massoumzadeh, Parinaz; Don, Steven; Hildebolt, Charles F.; Bae, Kyongtae T.; Whiting, Bruce R.

2009-01-01

The objective of this research was to develop and validate a custom computed tomography dose-reduction simulation technique for producing images that have an appearance consistent with the same scan performed at a lower mAs (with fixed kVp, rotation time, and collimation). Synthetic noise is added to projection (sinogram) data, incorporating a stochastic noise model that includes energy-integrating detectors, tube-current modulation, bowtie beam filtering, and electronic system noise. Experimental methods were developed to determine the parameters required for each component of the noise model. As a validation, the outputs of the simulations were compared to measurements with cadavers in the image domain and with phantoms in both the sinogram and image domain, using an unbiased root-mean-square relative error metric to quantify agreement in noise processes. Four-alternative forced-choice (4AFC) observer studies were conducted to confirm the realistic appearance of simulated noise, and the effects of various system model components on visual noise were studied. The “just noticeable difference (JND)” in noise levels was analyzed to determine the sensitivity of observers to changes in noise level. Individual detector measurements were shown to be normally distributed (p>0.54), justifying the use of a Gaussian random noise generator for simulations. Phantom tests showed the ability to match original and simulated noise variance in the sinogram domain to within 5.6%±1.6% (standard deviation), which was then propagated into the image domain with errors less than 4.1%±1.6%. Cadaver measurements indicated that image noise was matched to within 2.6%±2.0%. More importantly, the 4AFC observer studies indicated that the simulated images were realistic, i.e., no detectable difference between simulated and original images (p=0.86) was observed. JND studies indicated that observers’ sensitivity to change in noise levels corresponded to a 25% difference in dose, which is far larger than the noise accuracy achieved by simulation. In summary, the dose-reduction simulation tool demonstrated excellent accuracy in providing realistic images. The methodology promises to be a useful tool for researchers and radiologists to explore dose reduction protocols in an effort to produce diagnostic images with radiation dose “as low as reasonably achievable.” PMID:19235386

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.

Examination of Variables That May Affect the Relationship Between Cognition and Functional Status in Individuals with Mild Cognitive Impairment: A Meta-Analysis.

PubMed

Mcalister, Courtney; Schmitter-Edgecombe, Maureen; Lamb, Richard

2016-03-01

The objective of this meta-analysis was to improve understanding of the heterogeneity in the relationship between cognition and functional status in individuals with mild cognitive impairment (MCI). Demographic, clinical, and methodological moderators were examined. Cognition explained an average of 23% of the variance in functional outcomes. Executive function measures explained the largest amount of variance (37%), whereas global cognitive status and processing speed measures explained the least (20%). Short- and long-delayed memory measures accounted for more variance (35% and 31%) than immediate memory measures (18%), and the relationship between cognition and functional outcomes was stronger when assessed with informant-report (28%) compared with self-report (21%). Demographics, sample characteristics, and type of everyday functioning measures (i.e., questionnaire, performance-based) explained relatively little variance compared with cognition. Executive functioning, particularly measured by Trails B, was a strong predictor of everyday functioning in individuals with MCI. A large proportion of variance remained unexplained by cognition. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A multiscale filter for noise reduction of low-dose cone beam projections.

PubMed

Yao, Weiguang; Farr, Jonathan B

2015-08-21

The Poisson or compound Poisson process governs the randomness of photon fluence in cone beam computed tomography (CBCT) imaging systems. The probability density function depends on the mean (noiseless) of the fluence at a certain detector. This dependence indicates the natural requirement of multiscale filters to smooth noise while preserving structures of the imaged object on the low-dose cone beam projection. In this work, we used a Gaussian filter, exp(-x2/2σ(2)(f)) as the multiscale filter to de-noise the low-dose cone beam projections. We analytically obtained the expression of σ(f), which represents the scale of the filter, by minimizing local noise-to-signal ratio. We analytically derived the variance of residual noise from the Poisson or compound Poisson processes after Gaussian filtering. From the derived analytical form of the variance of residual noise, optimal σ(2)(f)) is proved to be proportional to the noiseless fluence and modulated by local structure strength expressed as the linear fitting error of the structure. A strategy was used to obtain the reliable linear fitting error: smoothing the projection along the longitudinal direction to calculate the linear fitting error along the lateral direction and vice versa. The performance of our multiscale filter was examined on low-dose cone beam projections of a Catphan phantom and a head-and-neck patient. After performing the filter on the Catphan phantom projections scanned with pulse time 4 ms, the number of visible line pairs was similar to that scanned with 16 ms, and the contrast-to-noise ratio of the inserts was higher than that scanned with 16 ms about 64% in average. For the simulated head-and-neck patient projections with pulse time 4 ms, the visibility of soft tissue structures in the patient was comparable to that scanned with 20 ms. The image processing took less than 0.5 s per projection with 1024   ×   768 pixels.

SU-E-T-41: Analysis of GI Dose Variability Due to Intrafraction Setup Variance

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

Phillips, J; Wolfgang, J

2014-06-01

Purpose: Proton SBRT (stereotactic body radiation therapy) can be an effective modality for treatment of gastrointestinal tumors, but limited in practice due to sensitivity with respect to variation in the RPL (radiological path length). Small, intrafractional shifts in patient anatomy can lead to significant changes in the dose distribution. This study describes a tool designed to visualize uncertainties in radiological depth in patient CT's and aid in treatment plan design. Methods: This project utilizes the Shadie toolkit, a GPU-based framework that allows for real-time interactive calculations for volume visualization. Current SBRT simulation practice consists of a serial CT acquisition formore » the assessment of inter- and intra-fractional motion utilizing patient specific immobilization systems. Shadie was used to visualize potential uncertainties, including RPL variance and changes in gastric content. Input for this procedure consisted of two patient CT sets, contours of the desired organ, and a pre-calculated dose. In this study, we performed rigid registrations between sets of 4DCT's obtained from a patient with varying setup conditions. Custom visualizations are written by the user in Shadie, permitting one to create color-coded displays derived from a calculation along each ray. Results: Serial CT data acquired on subsequent days was analyzed for variation in RPB and gastric content. Specific shaders were created to visualize clinically relevant features, including RPL (radiological path length) integrated up to organs of interest. Using pre-calculated dose distributions and utilizing segmentation masks as additional input allowed us to further refine the display output from Shadie and create tools suitable for clinical usage. Conclusion: We have demonstrated a method to visualize potential uncertainty for intrafractional proton radiotherapy. We believe this software could prove a useful tool to guide those looking to design treatment plans least insensitive to motion for patients undergoing proton SBRT in the GI tract.« less

Controlling on-demand gastric acidity in obese subjects: a randomized, controlled trial comparing a single dose of 20 mg rabeprazole and 20 mg omeprazole.

PubMed

Belhocine, Kafia; Vavasseur, Fabienne; Volteau, Christelle; Flet, Laurent; Touchefeu, Yann; Bruley des Varannes, Stanislas

2014-07-15

Obesity is associated with a risk of gastroesophageal reflux disease. The pharmacodynamic efficacy of proton pump inhibitors has not been specifically evaluated in obese subjects. The aim of this study was to compare the antisecretory response to a single oral dose of 20 mg rabeprazole, 20 mg omeprazole and placebo in obese subjects. Gastric pH was monitored for 24 hours on three separate occasions in eighteen H. pylori-negative, asymptomatic obese subjects. Subjects were given omeprazole, rabeprazole or placebo in a randomized order and in a double-blind fashion. The main analysis criterion was 24-h percent of time post dose with intragastric pH above 3; secondary criteria were percentage of time above pH 4, median pH, [H+] concentrations and nocturnal acid breakthrough (NAB). Results were analyzed using linear mixed models and Wilks test comparing variances. 24-h median [IQ] percentages of time with gastric pH above 3 and 4 were higher with rabeprazole than omeprazole (46 [37-55] vs. 30 [15-55] %, 9 [5-11] % for placebo) but the differences did not reach statistical significance (p = 0.11 and 0.24, respectively). Median acid concentrations were significantly lower with rabeprazole than with omeprazole and placebo (22 [14-53] vs. 54 [19-130] and 95 [73-170] mmoles/l, p < 0.01) for all periods. The number of NAB was significantly lower with rabeprazole than with omeprazole (median 1 [1,2] vs. 2 [1-3], p = 0.04). Variances of 24-h data (pH above 3 and 4, median pH, [H+] concentrations) were significantly lower with rabeprazole than with omeprazole (p < 0.0001). In asymptomatic obese subjects the gastric antisecretory response to a single dose of rabeprazole and omeprazole was strong and not significantly different between drugs despite a significantly more homogeneous response with rabeprazole. ClinicalTrial.gov: NCT01136317.

Smoothing of the bivariate LOD score for non-normal quantitative traits.

PubMed

Buil, Alfonso; Dyer, Thomas D; Almasy, Laura; Blangero, John

2005-12-30

Variance component analysis provides an efficient method for performing linkage analysis for quantitative traits. However, type I error of variance components-based likelihood ratio testing may be affected when phenotypic data are non-normally distributed (especially with high values of kurtosis). This results in inflated LOD scores when the normality assumption does not hold. Even though different solutions have been proposed to deal with this problem with univariate phenotypes, little work has been done in the multivariate case. We present an empirical approach to adjust the inflated LOD scores obtained from a bivariate phenotype that violates the assumption of normality. Using the Collaborative Study on the Genetics of Alcoholism data available for the Genetic Analysis Workshop 14, we show how bivariate linkage analysis with leptokurtotic traits gives an inflated type I error. We perform a novel correction that achieves acceptable levels of type I error.

SU-F-T-02: Estimation of Radiobiological Doses (BED and EQD2) of Single Fraction Electronic Brachytherapy That Equivalent to I-125 Eye Plaque: By Using Linear-Quadratic and Universal Survival Curve Models

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

Kim, Y; Waldron, T; Pennington, E

Purpose: To test the radiobiological impact of hypofractionated choroidal melanoma brachytherapy, we calculated single fraction equivalent doses (SFED) of the tumor that equivalent to 85 Gy of I125-BT for 20 patients. Corresponding organs-at-risks (OARs) doses were estimated. Methods: Twenty patients treated with I125-BT were retrospectively examined. The tumor SFED values were calculated from tumor BED using a conventional linear-quadratic (L-Q) model and an universal survival curve (USC). The opposite retina (α/β = 2.58), macula (2.58), optic disc (1.75), and lens (1.2) were examined. The % doses of OARs over tumor doses were assumed to be the same as for amore » single fraction delivery. The OAR SFED values were converted into BED and equivalent dose in 2 Gy fraction (EQD2) by using both L-Q and USC models, then compared to I125-BT. Results: The USC-based BED and EQD2 doses of the macula, optic disc, and the lens were on average 118 ± 46% (p < 0.0527), 126 ± 43% (p < 0.0354), and 112 ± 32% (p < 0.0265) higher than those of I125-BT, respectively. The BED and EQD2 doses of the opposite retina were 52 ± 9% lower than I125-BT. The tumor SFED values were 25.2 ± 3.3 Gy and 29.1 ± 2.5 Gy when using USC and LQ models which can be delivered within 1 hour. All BED and EQD2 values using L-Q model were significantly larger when compared to the USC model (p < 0.0274) due to its large single fraction size (> 14 Gy). Conclusion: The estimated single fraction doses were feasible to be delivered within 1 hour using a high dose rate source such as electronic brachytherapy (eBT). However, the estimated OAR doses using eBT were 112 ∼ 118% higher than when using the I125-BT technique. Continued exploration of alternative dose rate or fractionation schedules should be followed.« less

Approximate distribution of dose among foetal organs for radioiodine uptake via placenta transfer

NASA Astrophysics Data System (ADS)

Millard, R. K.; Saunders, M.; Palmer, A. M.; Preece, A. W.

2001-11-01

Absorbed radiation doses to internal foetal organs were calculated according to the medical internal radiation dose (MIRD) technique in this study. Anthropomorphic phantoms of the pregnant female as in MIRDOSE3 enabled estimation of absorbed dose to the whole foetus at two stages of gestation. Some foetal organ self-doses could have been estimated by invoking simple spherical models for thyroid, liver, etc, but we investigated the use of the MIRDOSE3 new-born phantom as a surrogate for the stage 3 foetus, scaled to be compatible with total foetal body mean absorbed dose/cumulated activity. We illustrate the method for obtaining approximate dose distribution in the foetus near term following intake of 1 MBq of 123I, 124I, 125I or 131I as sodium iodide by the mother using in vivo biodistribution data examples from a good model of placenta transfer. Doses to the foetal thyroid of up to 1.85 Gy MBq-1 were predicted from the 131I uptake data. Activity in the foetal thyroid was the largest contributor to absorbed dose in the foetal body, brain, heart and thymus. Average total doses to the whole foetus ranged from 0.16 to 1.2 mGy MBq-1 for stages 1 and 3 of pregnancy using the MIRDOSE3 program, and were considerably higher than those predicted from the maternal contributions alone. Doses to the foetal thymus and stomach were similar, around 2-3 mGy MBq-1. Some foetal organ doses from the radioiodides were ten times higher than to the corresponding organs of the mother, and up to 100 times higher to the thyroid. The fraction of activity uptakes in foetal organs were distributed similarly to the maternal ones.

Dose escalation methods in phase I cancer clinical trials.

PubMed

Le Tourneau, Christophe; Lee, J Jack; Siu, Lillian L

2009-05-20

Phase I clinical trials are an essential step in the development of anticancer drugs. The main goal of these studies is to establish the recommended dose and/or schedule of new drugs or drug combinations for phase II trials. The guiding principle for dose escalation in phase I trials is to avoid exposing too many patients to subtherapeutic doses while preserving safety and maintaining rapid accrual. Here we review dose escalation methods for phase I trials, including the rule-based and model-based dose escalation methods that have been developed to evaluate new anticancer agents. Toxicity has traditionally been the primary endpoint for phase I trials involving cytotoxic agents. However, with the emergence of molecularly targeted anticancer agents, potential alternative endpoints to delineate optimal biological activity, such as plasma drug concentration and target inhibition in tumor or surrogate tissues, have been proposed along with new trial designs. We also describe specific methods for drug combinations as well as methods that use a time-to-event endpoint or both toxicity and efficacy as endpoints. Finally, we present the advantages and drawbacks of the various dose escalation methods and discuss specific applications of the methods in developmental oncotherapeutics.

Bed load transport over a broad range of timescales: Determination of three regimes of fluctuations

NASA Astrophysics Data System (ADS)

Ma, Hongbo; Heyman, Joris; Fu, Xudong; Mettra, Francois; Ancey, Christophe; Parker, Gary

2014-12-01

This paper describes the relationship between the statistics of bed load transport flux and the timescale over which it is sampled. A stochastic formulation is developed for the probability distribution function of bed load transport flux, based on the Ancey et al. (2008) theory. An analytical solution for the variance of bed load transport flux over differing sampling timescales is presented. The solution demonstrates that the timescale dependence of the variance of bed load transport flux reduces to a three-regime relation demarcated by an intermittency timescale (tI) and a memory timescale (tc). As the sampling timescale increases, this variance passes through an intermittent stage (≪tI), an invariant stage (tI < t < tc), and a memoryless stage (≫ tc). We propose a dimensionless number (Ra) to represent the relative strength of fluctuation, which provides a common ground for comparison of fluctuation strength among different experiments, as well as different sampling timescales for each experiment. Our analysis indicates that correlated motion and the discrete nature of bed load particles are responsible for this three-regime behavior. We use the data from three experiments with high temporal resolution of bed load transport flux to validate the proposed three-regime behavior. The theoretical solution for the variance agrees well with all three sets of experimental data. Our findings contribute to the understanding of the observed fluctuations of bed load transport flux over monosize/multiple-size grain beds, to the characterization of an inherent connection between short-term measurements and long-term statistics, and to the design of appropriate sampling strategies for bed load transport flux.

Extending i-line capabilities through variance characterization and tool enhancement

NASA Astrophysics Data System (ADS)

Miller, Dan; Salinas, Adrian; Peterson, Joel; Vickers, David; Williams, Dan

2006-03-01

Continuous economic pressures have moved a large percent of integrated device manufacturing (IDM) operations either overseas or to foundry operations over the last 10 years. These pressures have left the IDM fabs in the U.S. with required COO improvements in order to maintain operations domestically. While the assets of many of these factories are at a very favorable point in the depreciation life cycle, the equipment and processes are constrained to the quality of the equipment in its original state and the degradation over its installed life. With the objective to enhance output and improve process performance, this factory and their primary lithography process tool supplier have been able to extend the usable life of the existing process tools, increase the output of the tool base, and improve the distribution of the CDs on the product produced. Texas Instruments Incorporated lead an investigation with the POLARIS ® Systems & Services business of FSI International to determine the sources of variance in the i-line processing of a wide array of IC device types. Data from the sources of variance were investigated such as PEB temp, PEB delay time, develop recipe, develop time, and develop programming. While PEB processes are a primary driver of acid catalyzed resists, the develop mode is shown in this work to have an overwhelming impact on the wafer to wafer and across wafer CD performance of these i-line processes. These changes have been able to improve the wafer to wafer CD distribution by more than 80 %, and the within wafer CD distribution by more than 50 % while enabling a greater than 50 % increase in lithography cluster throughput. The paper will discuss the contribution from each of the sources of variance and their importance in overall system performance.

Inter-operator Reliability of Magnetic Resonance Image-Based Computational Fluid Dynamics Prediction of Cerebrospinal Fluid Motion in the Cervical Spine.

PubMed

Martin, Bryn A; Yiallourou, Theresia I; Pahlavian, Soroush Heidari; Thyagaraj, Suraj; Bunck, Alexander C; Loth, Francis; Sheffer, Daniel B; Kröger, Jan Robert; Stergiopulos, Nikolaos

2016-05-01

For the first time, inter-operator dependence of MRI based computational fluid dynamics (CFD) modeling of cerebrospinal fluid (CSF) in the cervical spinal subarachnoid space (SSS) is evaluated. In vivo MRI flow measurements and anatomy MRI images were obtained at the cervico-medullary junction of a healthy subject and a Chiari I malformation patient. 3D anatomies of the SSS were reconstructed by manual segmentation by four independent operators for both cases. CFD results were compared at nine axial locations along the SSS in terms of hydrodynamic and geometric parameters. Intraclass correlation (ICC) assessed the inter-operator agreement for each parameter over the axial locations and coefficient of variance (CV) compared the percentage of variance for each parameter between the operators. Greater operator dependence was found for the patient (0.19 < ICC < 0.99) near the craniovertebral junction compared to the healthy subject (ICC > 0.78). For the healthy subject, hydraulic diameter and Womersley number had the least variance (CV = ~2%). For the patient, peak diastolic velocity and Reynolds number had the smallest variance (CV = ~3%). These results show a high degree of inter-operator reliability for MRI-based CFD simulations of CSF flow in the cervical spine for healthy subjects and a lower degree of reliability for patients with Type I Chiari malformation.

Inter-Operator Dependence of Magnetic Resonance Image-Based Computational Fluid Dynamics Prediction of Cerebrospinal Fluid Motion in the Cervical Spine

PubMed Central

Martin, Bryn A.; Yiallourou, Theresia I.; Pahlavian, Soroush Heidari; Thyagaraj, Suraj; Bunck, Alexander C.; Loth, Francis; Sheffer, Daniel B.; Kröger, Jan Robert; Stergiopulos, Nikolaos

2015-01-01

For the first time, inter-operator dependence of MRI based computational fluid dynamics (CFD) modeling of cerebrospinal fluid (CSF) in the cervical spinal subarachnoid space (SSS) is evaluated. In vivo MRI flow measurements and anatomy MRI images were obtained at the cervico-medullary junction of a healthy subject and a Chiari I malformation patient. 3D anatomies of the SSS were reconstructed by manual segmentation by four independent operators for both cases. CFD results were compared at nine axial locations along the SSS in terms of hydrodynamic and geometric parameters. Intraclass correlation (ICC) assessed the inter-operator agreement for each parameter over the axial locations and coefficient of variance (CV) compared the percentage of variance for each parameter between the operators. Greater operator dependence was found for the patient (0.19 0.78). For the healthy subject, hydraulic diameter and Womersley number had the least variance (CV= ~2%). For the patient, peak diastolic velocity and Reynolds number had the smallest variance (CV= ~3%). These results show a high degree of inter-operator reliability for MRI-based CFD simulations of CSF flow in the cervical spine for healthy subjects and a lower degree of reliability for patients with Type I Chiari malformation. PMID:26446009

Bootstrap-based methods for estimating standard errors in Cox's regression analyses of clustered event times.

PubMed

Xiao, Yongling; Abrahamowicz, Michal

2010-03-30

We propose two bootstrap-based methods to correct the standard errors (SEs) from Cox's model for within-cluster correlation of right-censored event times. The cluster-bootstrap method resamples, with replacement, only the clusters, whereas the two-step bootstrap method resamples (i) the clusters, and (ii) individuals within each selected cluster, with replacement. In simulations, we evaluate both methods and compare them with the existing robust variance estimator and the shared gamma frailty model, which are available in statistical software packages. We simulate clustered event time data, with latent cluster-level random effects, which are ignored in the conventional Cox's model. For cluster-level covariates, both proposed bootstrap methods yield accurate SEs, and type I error rates, and acceptable coverage rates, regardless of the true random effects distribution, and avoid serious variance under-estimation by conventional Cox-based standard errors. However, the two-step bootstrap method over-estimates the variance for individual-level covariates. We also apply the proposed bootstrap methods to obtain confidence bands around flexible estimates of time-dependent effects in a real-life analysis of cluster event times.

Pharmacokinetics, Safety, and Efficacy of Posaconazole in Patients with Persistent Febrile Neutropenia or Refractory Invasive Fungal Infection

PubMed Central

Ullmann, A. J.; Cornely, O. A.; Burchardt, A.; Hachem, R.; Kontoyiannis, D. P.; Töpelt, K.; Courtney, R.; Wexler, D.; Krishna, G.; Martinho, M.; Corcoran, G.; Raad, I.

2006-01-01

The pharmacokinetic profiles, safety, and efficacies of different dosing schedules of posaconazole oral suspension in patients with possible, probable, and proven refractory invasive fungal infection (rIFI) or febrile neutropenia (FN) were evaluated in a multicenter, open-label, parallel-group study. Sixty-six patients with FN and 32 patients with rIFI were randomly assigned to one of three posaconazole regimens: 200 mg four times a day (q.i.d.) for nine doses, followed by 400 mg twice a day (b.i.d.); 400 mg q.i.d. for nine doses, followed by 600 mg b.i.d.; or 800 mg b.i.d. for five doses, followed by 800 mg once a day (q.d.). Therapy was continued for up to 6 months in patients with rIFI or until neutrophil recovery occurred in patients with FN. The 400-mg-b.i.d. dose provided the highest overall mean exposure, with 135% (P = 0.0004) and 182% (P < 0.0001) greater exposure than the 600-mg-b.i.d. and 800-mg-q.d. doses, respectively. However, exposure in allogeneic bone marrow transplant (BMT) recipients (n = 12) was 52% lower than in non-BMT patients. Treatment-related adverse events (occurring in 24% of patients) were mostly gastrointestinal in nature. Twenty-four percent of patients had adverse events leading to premature discontinuation (none were treatment related). In efficacy-evaluable patients, successful clinical response was observed in 43% with rIFI (56% of patients receiving 400 mg b.i.d., 17% receiving 600 mg b.i.d., and 50% receiving 800 mg q.d.) and 77% with FN (74% receiving 400 mg b.i.d., 78% receiving 600 mg b.i.d., and 81% receiving 800 mg q.d.). Posaconazole is well tolerated and absorbed. Divided doses of 800 mg (400 mg b.i.d.) provide the greatest posaconazole exposure. PMID:16436724

Rocuronium duration of action under sevoflurane, desflurane or propofol anaesthesia.

PubMed

Maidatsi, P G; Zaralidou, A Th; Gorgias, N K; Amaniti, E N; Karakoulas, K A; Giala, M M

2004-10-01

We conducted a prospective randomized study to evaluate whether the duration of action of a single bolus dose of rocuronium is influenced by maintenance of anaesthesia with sevoflurane, desflurane or propofol infusion. Fifty-seven ASA I-II patients undergoing elective abdominal surgery were enrolled in this study. Anaesthesia was induced with thiopental 3-5 mg kg(-1) or propofol 2.5 mg kg(-1) and fentanyl 5 microg kg(-1) and tracheal intubation was facilitated with rocuronium 0.9 mg kg(-1). Thereafter patients were randomly allocated to three different groups to receive sevoflurane, desflurane or propofol for maintenance of anaesthesia. Recovery of neuromuscular function was monitored by single twitch stimulation of the ulnar nerve and by recording the adductor pollicis response using accelerometry. Intergroup recovery times to 5% of control value of single twitch were analysed using analysis of variance with Bonferroni correction. The mean (95% confidence interval) recovery time to 5% of control value of single twitch during desflurane anaesthesia was 90.18 (86.11-94.25) min. Significantly shorter recovery times were observed during sevoflurane or propofol anaesthesia, 58.86 (54.73-62.99) min and 51.11 (45.47-56.74) min, respectively (P < 0.001). There were also significant differences in the recovery time between groups receiving desflurane vs. sevoflurane (P < 0.001) and desflurane vs. propofol (P < 0.001). Desflurane anaesthesia significantly prolongs the duration of action of rocuronium at 0.9 mg kg(-1) single bolus dose, compared to sevoflurane or propofol anaesthesia maintenance regimens.

A Posteriori Correction of Forecast and Observation Error Variances

NASA Technical Reports Server (NTRS)

Rukhovets, Leonid

2005-01-01

Proposed method of total observation and forecast error variance correction is based on the assumption about normal distribution of "observed-minus-forecast" residuals (O-F), where O is an observed value and F is usually a short-term model forecast. This assumption can be accepted for several types of observations (except humidity) which are not grossly in error. Degree of nearness to normal distribution can be estimated by the symmetry or skewness (luck of symmetry) a(sub 3) = mu(sub 3)/sigma(sup 3) and kurtosis a(sub 4) = mu(sub 4)/sigma(sup 4) - 3 Here mu(sub i) = i-order moment, sigma is a standard deviation. It is well known that for normal distribution a(sub 3) = a(sub 4) = 0.

Model-based Iterative Reconstruction: Effect on Patient Radiation Dose and Image Quality in Pediatric Body CT

PubMed Central

Dillman, Jonathan R.; Goodsitt, Mitchell M.; Christodoulou, Emmanuel G.; Keshavarzi, Nahid; Strouse, Peter J.

2014-01-01

Purpose To retrospectively compare image quality and radiation dose between a reduced-dose computed tomographic (CT) protocol that uses model-based iterative reconstruction (MBIR) and a standard-dose CT protocol that uses 30% adaptive statistical iterative reconstruction (ASIR) with filtered back projection. Materials and Methods Institutional review board approval was obtained. Clinical CT images of the chest, abdomen, and pelvis obtained with a reduced-dose protocol were identified. Images were reconstructed with two algorithms: MBIR and 100% ASIR. All subjects had undergone standard-dose CT within the prior year, and the images were reconstructed with 30% ASIR. Reduced- and standard-dose images were evaluated objectively and subjectively. Reduced-dose images were evaluated for lesion detectability. Spatial resolution was assessed in a phantom. Radiation dose was estimated by using volumetric CT dose index (CTDIvol) and calculated size-specific dose estimates (SSDE). A combination of descriptive statistics, analysis of variance, and t tests was used for statistical analysis. Results In the 25 patients who underwent the reduced-dose protocol, mean decrease in CTDIvol was 46% (range, 19%–65%) and mean decrease in SSDE was 44% (range, 19%–64%). Reduced-dose MBIR images had less noise (P > .004). Spatial resolution was superior for reduced-dose MBIR images. Reduced-dose MBIR images were equivalent to standard-dose images for lungs and soft tissues (P > .05) but were inferior for bones (P = .004). Reduced-dose 100% ASIR images were inferior for soft tissues (P < .002), lungs (P < .001), and bones (P < .001). By using the same reduced-dose acquisition, lesion detectability was better (38% [32 of 84 rated lesions]) or the same (62% [52 of 84 rated lesions]) with MBIR as compared with 100% ASIR. Conclusion CT performed with a reduced-dose protocol and MBIR is feasible in the pediatric population, and it maintains diagnostic quality. © RSNA, 2013 Online supplemental material is available for this article. PMID:24091359

Antibiotic Dosing in Continuous Renal Replacement Therapy.

PubMed

Shaw, Alexander R; Mueller, Bruce A

2017-07-01

Appropriate antibiotic dosing is critical to improve outcomes in critically ill patients with sepsis. The addition of continuous renal replacement therapy makes achieving appropriate antibiotic dosing more difficult. The lack of continuous renal replacement therapy standardization results in treatment variability between patients and may influence whether appropriate antibiotic exposure is achieved. The aim of this study was to determine if continuous renal replacement therapy effluent flow rate impacts attaining appropriate antibiotic concentrations when conventional continuous renal replacement therapy antibiotic doses were used. This study used Monte Carlo simulations to evaluate the effect of effluent flow rate variance on pharmacodynamic target attainment for cefepime, ceftazidime, levofloxacin, meropenem, piperacillin, and tazobactam. Published demographic and pharmacokinetic parameters for each antibiotic were used to develop a pharmacokinetic model. Monte Carlo simulations of 5000 patients were evaluated for each antibiotic dosing regimen at the extremes of Kidney Disease: Improving Global Outcomes guidelines recommended effluent flow rates (20 and 35 mL/kg/h). The probability of target attainment was calculated using antibiotic-specific pharmacodynamic targets assessed over the first 72 hours of therapy. Most conventional published antibiotic dosing recommendations, except for levofloxacin, reach acceptable probability of target attainment rates when effluent rates of 20 or 35 mL/kg/h are used. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Evaluation of material heterogeneity dosimetric effects using radiochromic film for COMS eye plaques loaded with {sup 125}I seeds (model I25.S16)

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

Acar, Hilal; Chiu-Tsao, Sou-Tung; Oezbay, Ismail

Purpose: (1) To measure absolute dose distributions in eye phantom for COMS eye plaques with {sup 125}I seeds (model I25.S16) using radiochromic EBT film dosimetry. (2) To determine the dose correction function for calculations involving the TG-43 formalism to account for the presence of the COMS eye plaque using Monte Carlo (MC) method specific to this seed model. (3) To test the heterogeneous dose calculation accuracy of the new version of Plaque Simulator (v5.3.9) against the EBT film data for this seed model. Methods: Using EBT film, absolute doses were measured for {sup 125}I seeds (model I25.S16) in COMS eyemore » plaques (1) along the plaque's central axis for (a) uniformly loaded plaques (14-20 mm in diameter) and (b) a 20 mm plaque with single seed, and (2) in off-axis direction at depths of 5 and 12 mm for all four plaque sizes. The EBT film calibration was performed at {sup 125}I photon energy. MC calculations using MCNP5 code for a single seed at the center of a 20 mm plaque in homogeneous water and polystyrene medium were performed. The heterogeneity dose correction function was determined from the MC calculations. These function values at various depths were entered into PS software (v5.3.9) to calculate the heterogeneous dose distributions for the uniformly loaded plaques (of all four sizes). The dose distributions with homogeneous water assumptions were also calculated using PS for comparison. The EBT film measured absolute dose rate values (film) were compared with those calculated using PS with homogeneous assumption (PS Homo) and heterogeneity correction (PS Hetero). The values of dose ratio (film/PS Homo) and (film/PS Hetero) were obtained. Results: The central axis depth dose rate values for a single seed in 20 mm plaque measured using EBT film and calculated with MCNP5 code (both in ploystyrene phantom) were compared, and agreement within 9% was found. The dose ratio (film/PS Homo) values were substantially lower than unity (mostly between 0.8 and 0.9) for all four plaque sizes, indicating dose reduction by COMS plaque compared with homogeneous assumption. The dose ratio (film/PS Hetero) values were close to unity, indicating the PS Hetero calculations agree with those from the film study. Conclusions: Substantial heterogeneity effect on the {sup 125}I dose distributions in an eye phantom for COMS plaques was verified using radiochromic EBT film dosimetry. The calculated doses for uniformly loaded plaques using PS with heterogeneity correction option enabled were corroborated by the EBT film measurement data. Radiochromic EBT film dosimetry is feasible in measuring absolute dose distributions in eye phantom for COMS eye plaques loaded with single or multiple {sup 125}I seeds. Plaque Simulator is a viable tool for the calculation of dose distributions if one understands its limitations and uses the proper heterogeneity correction feature.« less

Technical and biological variance structure in mRNA-Seq data: life in the real world

PubMed Central

2012-01-01

Background mRNA expression data from next generation sequencing platforms is obtained in the form of counts per gene or exon. Counts have classically been assumed to follow a Poisson distribution in which the variance is equal to the mean. The Negative Binomial distribution which allows for over-dispersion, i.e., for the variance to be greater than the mean, is commonly used to model count data as well. Results In mRNA-Seq data from 25 subjects, we found technical variation to generally follow a Poisson distribution as has been reported previously and biological variability was over-dispersed relative to the Poisson model. The mean-variance relationship across all genes was quadratic, in keeping with a Negative Binomial (NB) distribution. Over-dispersed Poisson and NB distributional assumptions demonstrated marked improvements in goodness-of-fit (GOF) over the standard Poisson model assumptions, but with evidence of over-fitting in some genes. Modeling of experimental effects improved GOF for high variance genes but increased the over-fitting problem. Conclusions These conclusions will guide development of analytical strategies for accurate modeling of variance structure in these data and sample size determination which in turn will aid in the identification of true biological signals that inform our understanding of biological systems. PMID:22769017

Behavioral and Biological Effects of Prenatal Stress and Social Enrichment: Relevance to Heart Disease

DTIC Science & Technology

2009-08-17

Weight: Repeated Measures (Between-Subjects Effects ) Body Weight: Analysis of Variance (ANOVA) - Males Only Body Weight: Last Measurement Corticosterone ...also decreased the effects of stress on freezing behavior and corticosterone levels in mice (Benaroya-Milshtein et aI., 2004). Summary of Social...rats (e.g., Faradayet aI., 2005; Kalinichev et aI., 2002; Kant et aI., 1987; Hayley et aI., 2001). 22 Corticosterone responses to stressors are

Jackknife Variance Estimator for Two Sample Linear Rank Statistics

DTIC Science & Technology

1988-11-01

Accesion For - - ,NTIS GPA&I "TIC TAB Unann c, nc .. [d Keywords: strong consistency; linear rank test’ influence function . i , at L By S- )Distribut...reverse if necessary and identify by block number) FIELD IGROUP SUB-GROUP Strong consistency; linear rank test; influence function . 19. ABSTRACT

Observed Score Linear Equating with Covariates

ERIC Educational Resources Information Center

Branberg, Kenny; Wiberg, Marie

2011-01-01

This paper examined observed score linear equating in two different data collection designs, the equivalent groups design and the nonequivalent groups design, when information from covariates (i.e., background variables correlated with the test scores) was included. The main purpose of the study was to examine the effect (i.e., bias, variance, and…

Comparison of organ dose and dose equivalent using ray tracing of male and female Voxel phantoms to space flight phantom torso data

NASA Astrophysics Data System (ADS)

Kim, Myung-Hee; Qualls, Garry; Slaba, Tony; Cucinotta, Francis A.

Phantom torso experiments have been flown on the space shuttle and International Space Station (ISS) providing validation data for radiation transport models of organ dose and dose equivalents. We describe results for space radiation organ doses using a new human geometry model based on detailed Voxel phantoms models denoted for males and females as MAX (Male Adult voXel) and Fax (Female Adult voXel), respectively. These models represent the human body with much higher fidelity than the CAMERA model currently used at NASA. The MAX and FAX models were implemented for the evaluation of directional body shielding mass for over 1500 target points of major organs. Radiation exposure to solar particle events (SPE), trapped protons, and galactic cosmic rays (GCR) were assessed at each specific site in the human body by coupling space radiation transport models with the detailed body shielding mass of MAX/FAX phantom. The development of multiple-point body-shielding distributions at each organ site made it possible to estimate the mean and variance of space dose equivalents at the specific organ. For the estimate of doses to the blood forming organs (BFOs), active marrow distributions in adult were accounted at bone marrow sites over the human body. We compared the current model results to space shuttle and ISS phantom torso experiments and to calculations using the CAMERA model.

Comparison of Organ Dose and Dose Equivalent Using Ray Tracing of Male and Female Voxel Phantoms to Space Flight Phantom Torso Data

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee Y.; Qualls, Garry D.; Cucinotta, Francis A.

2008-01-01

Phantom torso experiments have been flown on the space shuttle and International Space Station (ISS) providing validation data for radiation transport models of organ dose and dose equivalents. We describe results for space radiation organ doses using a new human geometry model based on detailed Voxel phantoms models denoted for males and females as MAX (Male Adult voXel) and Fax (Female Adult voXel), respectively. These models represent the human body with much higher fidelity than the CAMERA model currently used at NASA. The MAX and FAX models were implemented for the evaluation of directional body shielding mass for over 1500 target points of major organs. Radiation exposure to solar particle events (SPE), trapped protons, and galactic cosmic rays (GCR) were assessed at each specific site in the human body by coupling space radiation transport models with the detailed body shielding mass of MAX/FAX phantom. The development of multiple-point body-shielding distributions at each organ site made it possible to estimate the mean and variance of space dose equivalents at the specific organ. For the estimate of doses to the blood forming organs (BFOs), active marrow distributions in adult were accounted at bone marrow sites over the human body. We compared the current model results to space shuttle and ISS phantom torso experiments and to calculations using the CAMERA model.

High-precision dosimetry for radiotherapy using the optically stimulated luminescence technique and thin Al2O3:C dosimeters.

PubMed

Yukihara, E G; Yoshimura, E M; Lindstrom, T D; Ahmad, S; Taylor, K K; Mardirossian, G

2005-12-07

The potential of using the optically stimulated luminescence (OSL) technique with aluminium oxide (Al(2)O(3):C) dosimeters for a precise and accurate estimation of absorbed doses delivered by high-energy photon beams was investigated. This study demonstrates the high reproducibility of the OSL measurements and presents a preliminary determination of the depth-dose curve in water for a 6 MV photon beam from a linear accelerator. The uncertainty of a single OSL measurement, estimated from the variance of a large sample of dosimeters irradiated with the same dose, was 0.7%. In the depth-dose curve obtained using the OSL technique, the difference between the measured and expected doses was < or =0.7% for depths between 1.5 and 10 cm, and 1.1% for a depth of 15 cm. The readout procedure includes a normalization of the response of the dosimeter with respect to a reference dose in order to eliminate variations in the dosimeter mass, dosimeter sensitivity, and the reader's sensitivity. This may be relevant for quality assurance programmes, since it simplifies the requirements in terms of personnel training to achieve the precision and accuracy necessary for radiotherapy applications. We concluded that the OSL technique has the potential to be reliably incorporated in quality assurance programmes and dose verification.

Incidence of hypothyroidism following small doses of /sup 131/I in the treatment of Graves' disease

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

McCullagh, F.P.; Jelden, G.L.; Rodriguez-Antunez, A.

1976-09-01

In a group of 147 patients treated with /sup 131/I in doses of 3.0 millicuries or less for Graves' disease, the incidence of hypothyroidism was calculated 10 to 17 years after treatment. This paper emphasizes the frequency of hypothyroidism after treatment with /sup 131/I in small doses, if sufficient time lapse is considered.

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

Behavioral effects of ketamine and toxic interactions with psychostimulants

PubMed Central

Hayase, Tamaki; Yamamoto, Yoshiko; Yamamoto, Keiichi

2006-01-01

Background The anesthetic drug ketamine (KT) has been reported to be an abused drug and fatal cases have been observed in polydrug users. In the present study, considering the possibility of KT-enhanced toxic effects of other drugs, and KT-induced promotion of an overdose without making the subject aware of the danger due to the attenuation of several painful subjective symptoms, the intraperitoneal (i.p.) KT-induced alterations in behaviors and toxic interactions with popular co-abused drugs, the psychostimulants cocaine (COC) and methamphetamine (MA), were examined in ICR mice. Results A single dose of KT caused hyperlocomotion in a low (30 mg/kg, i.p.) dose group, and hypolocomotion followed by hyperlocomotion in a high (100 mg/kg, i.p.) dose group. However, no behavioral alterations derived from enhanced stress-related depression or anxiety were observed in the forced swimming or the elevated plus-maze test. A single non-fatal dose of COC (30 mg/kg, i.p.) or MA (4 mg/kg, i.p.) caused hyperlocomotion, stress-related depression in swimming behaviors in the forced swimming test, and anxiety-related behavioral changes (preference for closed arms) in the elevated plus-maze test. For the COC (30 mg/kg) or MA (4 mg/kg) groups of mice simultaneously co-treated with KT, the psychostimulant-induced hyperlocomotion was suppressed by the high dose KT, and the psychostimulant-induced behavioral alterations in the above tests were reversed by both low and high doses of KT. For the toxic dose COC (70 mg/kg, i.p.)- or MA (15 mg/kg, i.p.)-only group, mortality and severe seizures were observed in some animals. In the toxic dose psychostimulant-KT groups, KT attenuated the severity of seizures dose-dependently. Nevertheless, the mortality rate was significantly increased by co-treatment with the high dose KT. Conclusion Our results demonstrated that, in spite of the absence of stress-related depressive and anxiety-related behavioral alterations following a single dose of KT treatment, and in spite of the KT-induced anticonvulsant effects and attenuation of stress- and anxiety-related behaviors caused by COC or MA, the lethal effects of these psychostimulants were increased by KT. PMID:16542420

Relative biologic effectiveness in terms of tumor response of {sup 125}I implants compared with {sup 60}Co gamma rays

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

Lehnert, Shirley; Reniers, Brigitte; Verhaegen, Frank

2005-09-01

Purpose: To measure the relative biologic effectiveness (RBE) for {sup 125}I seeds compared with external beam radiotherapy using a clinically relevant in vivo system. Methods and Materials: Photon emission from a detailed source model was simulated using the Monte Carlo code MCNP4C, sampling from a {sup 125}I spectrum. The mouse RIF-1 tumor was treated with either temporary implant of an {sup 125}I seed or with {sup 60}Co gamma rays. The tumors were always the same size at the initiation of treatment, and the endpoint was growth inhibition. Results: The dose-response curve for both modalities was close to linear and wasmore » independent of the initial {sup 125}I activity (dose rate) for the range investigated. Calculation of the RBE for tumor response requires assigning a unique value for the tumor dose that is not homogenous but depends on the distance from the {sup 125}I source. Because tumor regrowth will depend on the subpopulation of cells that have the greatest probability of survival (i.e., those at the greatest distance from the {sup 125}I source), one approach is to use the dose to this population. On this basis, the RBE for {sup 125}I compared with {sup 60}Co gamma rays is 1.5. If the {sup 125}I dose is computed as the average dose to the tumor, corrected for the dose that is wasted as overkill in the cell population closest to the center of the {sup 125}I seed, the RBE is 1.4. Conclusion: The result, an RBE of 1.4-1.5 is similar to findings obtained by other methods, supporting the validity of this approach to derive an RBE with validity in a clinical context.« less

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

Hiller, Mauritius M.; Veinot, Kenneth G.; Easterly, Clay E.

In this study, methods are addressed to reduce the computational time to compute organ-dose rate coefficients using Monte Carlo techniques. Several variance reduction techniques are compared including the reciprocity method, importance sampling, weight windows and the use of the ADVANTG software package. For low-energy photons, the runtime was reduced by a factor of 10 5 when using the reciprocity method for kerma computation for immersion of a phantom in contaminated water. This is particularly significant since impractically long simulation times are required to achieve reasonable statistical uncertainties in organ dose for low-energy photons in this source medium and geometry. Althoughmore » the MCNP Monte Carlo code is used in this paper, the reciprocity technique can be used equally well with other Monte Carlo codes.« less

Statistical optimization of process parameters for the simultaneous adsorption of Cr(VI) and phenol onto Fe-treated tea waste biomass

NASA Astrophysics Data System (ADS)

Gupta, Ankur; Balomajumder, Chandrajit

2017-12-01

In this study, simultaneous removal of Cr(VI) and phenol from binary solution was carried out using Fe-treated tea waste biomass. The effect of process parameters such as adsorbent dose, pH, initial concentration of Cr(VI) (mg/L), and initial concentration of phenol (mg/L) was optimized. The analysis of variance of the quadratic model demonstrates that the experimental results are in good agreement with the predicted values. Based on experimental design at an initial concentration of 55 mg/L of Cr(VI), 27.50 mg/L of phenol, pH 2.0, 15 g/L adsorbent dose, 99.99% removal of Cr(VI), and phenol was achieved.

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.

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

Radiation Dose-rate Reduction Pattern in Well-differentiated Thyroid Cancer Treated with I-131.

PubMed

Khan, Shahbaz Ahmad; Khan, Muhammad Saqib; Arif, Muhammad; Durr-e-Sabih; Rahim, Muhammad Kashif; Ahmad, Israr

2015-07-01

To determine the patterns of dose rate reduction in single and multiple radioiodine (I-131) therapies in cases of well differentiated thyroid cancer patients. Analytical series. Department of Nuclear Medicine and Radiation Physics, Multan Institute of Nuclear Medicine and Radiotherapy (MINAR), Multan, Pakistan, from December 2006 to December 2013. Ninety three patients (167 therapies) with well differentiated thyroid cancer treated with different doses of I-131 as an in-patient were inducted. Fifty four patients were given only single I-131 therapy dose ranging from 70 mCi (2590 MBq) to 150 mCi (5550 MBq). Thirty nine patients were treated with multiple I-131 radioisotope therapy doses ranging from 80 mCi (2960 MBq) to 250 mCi (9250 MBq). T-test was applied on the sample data showed statistically significant difference between the two groups with p-value (p < 0.01) less than 0.05 taken as significant. There were 68 females and 25 males with an age range of 15 to 80 years. Mean age of the patients were 36 years. Among the 93 cases of first time Radio Active Iodine (RAI) therapy, 59 cases (63%) were discharged after 48 hours. Among 39 patients who received RAI therapy second time or more, most were discharged earlier after achieving acceptable discharge dose rate i.e 25 µSv/hour; 2 out of 39 (5%) were discharged after 48 hours. In 58% patients, given single I-131 therapy dose, majority of these were discharged after 48 hours without any major complications. For well differentiated thyroid cancer patients, rapid dose rate reduction is seen in patients receiving second or subsequent radioiodine (RAI) therapy, as compared to first time receiving RAI therapy.

Estimation of maximum tolerated dose for long-term bioassays from acute lethal dose and structure by QSAR

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

Gombar, V.K.; Enslein, K.; Hart, J.B.

1991-09-01

A quantitative structure-activity relationship (QSAR) model has been developed to estimate maximum tolerated doses (MTD) from structural features of chemicals and the corresponding oral acute lethal doses (LD50) as determined in male rats. The model is based on a set of 269 diverse chemicals which have been tested under the National Cancer Institute/National Toxicology Program (NCI/NTP) protocols. The rat oral LD50 value was the strongest predictor. Additionally, 22 structural descriptors comprising nine substructural MOLSTAC(c) keys, three molecular connectivity indices, and sigma charges on 10 molecular fragments were identified as endpoint predictors. The model explains 76% of the variance and ismore » significant (F = 35.7) at p less than 0.0001 with a standard error of the estimate of 0.40 in the log (1/mol) units used in Hansch-type equations. Cross-validation showed that the difference between the average deleted residual square (0.179) and the model residual square (0.160) was not significant (t = 0.98).« less

Development of CER-001: Preclinical Dose Selection Through to Phase I Clinical Findings.

PubMed

Keyserling, Constance H; Barbaras, Ronald; Benghozi, Renee; Dasseux, Jean-Louis

2017-05-01

CER-001 comprises recombinant human apolipoprotein A-I complexed with phospholipids that mimics natural, nascent, pre-β high-density lipoprotein (HDL). We present animal model data showing dose-dependent increases in cholesterol efflux with CER-001 and its subsequent elimination by reverse lipid transport, together with inhibition of atherosclerotic plaque progression. We report the first phase I study results with CER-001 in humans, starting at 0.25 mg/kg, which is 1/80th of the safe dose (20 mg/kg) established in 4-week multiple-dose animal studies dosed every second day. Healthy volunteers, 18-55 years old with a low-density lipoprotein-cholesterol:HDL-cholesterol ratio greater than 3.0, received single intravenous escalating doses of CER-001 (0.25-45.0 mg/kg) and placebo in a double-blind randomised cross-over fashion. Subjects were followed up for 3 weeks post-dose. Assessments included adverse event monitoring, blood sampling, and clinical laboratory measurements. Thirty-two subjects were enrolled. All CER-001 doses (0.25-45 mg/kg) were safe and well tolerated, with an adverse event profile similar to placebo. Effects on clinical chemistry, haematology and coagulation parameters were comparable to placebo. No adverse effects of CER-001 on electrocardiograms were observed. No antibodies to apolipoprotein A-I were detected following single-dose administration of CER-001. Plasma apolipoprotein A-I levels increased in a dose-related manner and returned to baseline by 24 h post-dose for doses up to 10 mg/kg but remained in circulation for >72 h post-dose for doses >10 mg/kg. CER-001 caused elevations in plasma cholesterol and total and unesterified cholesterol in the HDL fraction. Mobilisation of unesterified cholesterol in the HDL fraction was seen with CER-001 at doses as low as 2 mg/kg. CER-001 is well tolerated when administered to humans as single doses up to 45 mg/kg and mobilises and eliminates cholesterol via reverse lipid transport.

Quantifying cosmic variance

NASA Astrophysics Data System (ADS)

Driver, Simon P.; Robotham, Aaron S. G.

2010-10-01

We determine an expression for the cosmic variance of any `normal' galaxy survey based on examination of M* +/- 1 mag galaxies in the Sloan Digital Sky Survey (SDSS) Data Release 7 (DR7) data cube. We find that cosmic variance will depend on a number of factors principally: total survey volume, survey aspect ratio and whether the area surveyed is contiguous or comprising independent sightlines. As a rule of thumb cosmic variance falls below 10 per cent once a volume of 107h-30.7Mpc3 is surveyed for a single contiguous region with a 1:1 aspect ratio. Cosmic variance will be lower for higher aspect ratios and/or non-contiguous surveys. Extrapolating outside our test region we infer that cosmic variance in the entire SDSS DR7 main survey region is ~7 per cent to z < 0.1. The equation obtained from the SDSS DR7 region can be generalized to estimate the cosmic variance for any density measurement determined from normal galaxies (e.g. luminosity densities, stellar mass densities and cosmic star formation rates) within the volume range 103-107h-30.7Mpc3. We apply our equation to show that two sightlines are required to ensure that cosmic variance is <10 per cent in any ASKAP galaxy survey (divided into Δ z ~ 0.1 intervals, i.e. ~1Gyr intervals for z < 0.5). Likewise 10 MeerKAT sightlines will be required to meet the same conditions. GAMA, VVDS and zCOSMOS all suffer less than 10 per cent cosmic variance (~3-8 per cent) in Δ z intervals of 0.1, 0.25 and 0.5, respectively. Finally we show that cosmic variance is potentially at the 50-70 per cent level, or greater, in the Hubble Space Telescope (HST) Ultra Deep Field depending on assumptions as to the evolution of clustering. 100 or 10 independent sightlines will be required to reduce cosmic variance to a manageable level (<10 per cent) for HST ACS or HST WFC3 surveys, respectively (in Δ z ~ 1 intervals). Cosmic variance is therefore a significant factor in the z > 6 HST studies currently underway.

Temporal Lobe Reactions After Carbon Ion Radiation Therapy: Comparison of Relative Biological Effectiveness–Weighted Tolerance Doses Predicted by Local Effect Models I and IV

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

Gillmann, Clarissa, E-mail: clarissa.gillmann@med.uni-heidelberg.de; Jäkel, Oliver; Heidelberg Ion Beam Therapy Center

2014-04-01

Purpose: To compare the relative biological effectiveness (RBE)–weighted tolerance doses for temporal lobe reactions after carbon ion radiation therapy using 2 different versions of the local effect model (LEM I vs LEM IV) for the same patient collective under identical conditions. Methods and Materials: In a previous study, 59 patients were investigated, of whom 10 experienced temporal lobe reactions (TLR) after carbon ion radiation therapy for low-grade skull-base chordoma and chondrosarcoma at Helmholtzzentrum für Schwerionenforschung (GSI) in Darmstadt, Germany in 2002 and 2003. TLR were detected as visible contrast enhancements on T1-weighted MRI images within a median follow-up time ofmore » 2.5 years. Although the derived RBE-weighted temporal lobe doses were based on the clinically applied LEM I, we have now recalculated the RBE-weighted dose distributions using LEM IV and derived dose-response curves with Dmax,V-1 cm³ (the RBE-weighted maximum dose in the remaining temporal lobe volume, excluding the volume of 1 cm³ with the highest dose) as an independent dosimetric variable. The resulting RBE-weighted tolerance doses were compared with those of the previous study to assess the clinical impact of LEM IV relative to LEM I. Results: The dose-response curve of LEM IV is shifted toward higher values compared to that of LEM I. The RBE-weighted tolerance dose for a 5% complication probability (TD{sub 5}) increases from 68.8 ± 3.3 to 78.3 ± 4.3 Gy (RBE) for LEM IV as compared to LEM I. Conclusions: LEM IV predicts a clinically significant increase of the RBE-weighted tolerance doses for the temporal lobe as compared to the currently applied LEM I. The limited available photon data do not allow a final conclusion as to whether RBE predictions of LEM I or LEM IV better fit better clinical experience in photon therapy. The decision about a future clinical application of LEM IV therefore requires additional analysis of temporal lobe reactions in a comparable photon-treated collective using the same dosimetric variable as in the present study.« less

Incorporation of Differential Global Positioning System Measurements Using an Extended Kalman Filter for Improved Reference System Performance

DTIC Science & Technology

1991-12-01

Kalman filtering. As GPS usage expands throughout the military and civilian communities, I hope this thesis provides a small contribution in this area...of the measurement’equation. In this thesis, some of the INS states not part of a measurement equation need a small amount of added noise to...estimating the state, but the variance often goes negative. A small amount of added noise in the filter keeps the variance of the state positive and does not

PTSD Symptom Increases in Iraq-Deployed Soldiers: Comparison with NonDeployed Soldiers and Associations with Baseline Symptoms, Deployment Experiences, and Postdeployment Stress

DTIC Science & Technology

2010-02-01

Findings also highlighl the impact of homefront and poSl-deploymentlife events in addition to war -zone stress exposures, and emphasize the imponance of...additional 20% of the variance; Wlr-7.0ne stTessors and perceived war -zone threat together contributed an additional 19% of the variance; and homefront ...in the types of noncombat (i.e., post battle) war -zone events experienced by the two groups. Homefront concerns experienced during deployment were

Institute for the Study of Human Capabilities

DTIC Science & Technology

1994-05-31

Catholic Univ. James Reason Univ. of Manchester,UK Earl Hunt Univ. of Washington Barry Kantowitz Battelle Res. Center Colin Drury SUNY at Buffalo, NY Andrew...score variance accounted for were obtained in the elderly subjects by including various measures of auditory processing. 0 I 10I I I MAldling the...frequency could be discriminated. This analysis will now be extended to account for the detailed differences in thresholds3 observed for female (Kewley-Port

Persistence of antibody to hepatitis B surface antigen after low-dose, intradermal hepatitis B immunization and response to a booster dose.

PubMed

Bryan, J P; Sjogren, M H; Macarthy, P; Cox, E; Legters, L J; Perine, P L

1992-01-01

To determine the duration of antibody after low-dose, intradermal (i.d.), plasma-derived hepatitis B vaccination and the response to a booster dose, we studied two classes of medical students who were immunized with 2 micrograms doses i.d. In one class, 73/88 (85%) who had been immunized by skilled personnel at 0, 1 and 6 months, had protective concentrations (greater than or equal to 10 mIU ml-1) of anti-HBs at 20 months after the first dose. Twelve (92%) out of 13 students who received only two doses at 0 and 1 months also had protective concentrations at month 20. At month 27, 11/16 (69%) with antibody less than or equal to 10 mIU ml-1 responded to a fourth dose of 2 micrograms i.d. with protective concentrations of anti-HBs. In the second class, after three doses of vaccine at 0, 1, and 6 months, protective concentrations of anti-HBs were present in 90/93 (97%) at 14 months and in 71/80 (89%) at 25 months. In those who received only two doses, protective concentrations were found in 24/31 (74%) at 14 months and 9/16 (56%) at 25 months. After a booster dose of 2 micrograms i.d. at month 25, anti-HBs concentrations rose from a geometric mean of 78 to 1198 mIU ml-1 in 60 subjects previously immunized with three doses and from 18 to 1054 mIU ml-1 in 16 students previously immunized with only two doses. Overall, 73/76 (96%) of students in the second group had protective concentrations of antibody after the booster dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of heparin and related polysaccharides

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

Boneu, B.; Dol, F.; Caranobe, C.

1989-01-01

The pharmacodynamic profile of standard heparin (SH), a low molecular weight derivative (CY 216) and of dermatan sulfate (DS), a new potential antithrombotic drug, was investigated in the rabbit over a large range of doses. After bolus i.v. injection of low doses, the biological activity of SH disappeared exponentially; however, its half-life was prolonged when the dose injected increased, and over 158 micrograms/kg (100 anti-factor Xa U/kg) the biological activity disappeared as a concave-convex curve. CY 216 disappeared more slowly than SH at low doses but faster than SH at higher doses. More than 90% of the DS biological activitymore » present 1 minute after the i.v. injection disappeared exponentially without dose-dependent effects. Increasing doses of the three drugs were then delivered for 5 h under continuous infusions. Below 500 micrograms/kg/h the DS and CY 216 plateau concentrations were higher than that of SH while above this dose the SH concentration was higher than that of DS and CY 216. These observations may be explained by the results of pharmacokinetics experiments where /sup 125/I-labeled compounds were delivered by bolus i.v. injection in association with increasing doses of their unlabeled counterparts. For SH there was a 10-fold difference between the half-life of the lower dose (32 micrograms/kg or 5 anti-factor Xa U/kg) and that of the higher dose (3200 micrograms/kg); it was demonstrated that the half-life of SH continuously shortened as its plasma concentration decreased. In contrast the CY 216 and DS half-lives were very close, independent of the dose delivered, and therefore longer than that of SH at low doses and shorter than that of SH at higher doses.« less

Heterogeneous Multi-Robot Multi-Sensor Platform for Intruder Detection

DTIC Science & Technology

2009-09-15

propagation model, with variance τi: si ~ N(b0i + b1i *logDi, τ i). The initial parameters (b0i, b1i, τ i ) of the model are unknown, and the training...that the advantage of MOO-learned mode would become more significant over time compared with the other mode. 1 2 3 4 5 6 7 0 0.05 0.1 0.15 0.2...nondominated sorting genetic algorithm for multi-objective optimization: NSGA-II,” in Parallel Problem Solving from Nature (PPSN VI), M. Schoenauer

The threshold vs LNT showdown: Dose rate findings exposed flaws in the LNT model part 2. How a mistake led BEIR I to adopt LNT

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

Calabrese, Edward J., E-mail: edwardc@schoolph.uma

This paper reveals that nearly 25 years after the used Russell's dose-rate data to support the adoption of the linear-no-threshold (LNT) dose response model for genetic and cancer risk assessment, Russell acknowledged a significant under-reporting of the mutation rate of the historical control group. This error, which was unknown to BEIR I, had profound implications, leading it to incorrectly adopt the LNT model, which was a decision that profoundly changed the course of risk assessment for radiation and chemicals to the present. -- Highlights: • The BEAR I Genetics Panel made an error in denying dose rate for mutation. •more » The BEIR I Genetics Subcommittee attempted to correct this dose rate error. • The control group used for risk assessment by BEIR I is now known to be in error. • Correcting this error contradicts the LNT, supporting a threshold model.« less

Neuroticism explains unwanted variance in Implicit Association Tests of personality: possible evidence for an affective valence confound.

PubMed

Fleischhauer, Monika; Enge, Sören; Miller, Robert; Strobel, Alexander; Strobel, Anja

2013-01-01

Meta-analytic data highlight the value of the Implicit Association Test (IAT) as an indirect measure of personality. Based on evidence suggesting that confounding factors such as cognitive abilities contribute to the IAT effect, this study provides a first investigation of whether basic personality traits explain unwanted variance in the IAT. In a gender-balanced sample of 204 volunteers, the Big-Five dimensions were assessed via self-report, peer-report, and IAT. By means of structural equation modeling (SEM), latent Big-Five personality factors (based on self- and peer-report) were estimated and their predictive value for unwanted variance in the IAT was examined. In a first analysis, unwanted variance was defined in the sense of method-specific variance which may result from differences in task demands between the two IAT block conditions and which can be mirrored by the absolute size of the IAT effects. In a second analysis, unwanted variance was examined in a broader sense defined as those systematic variance components in the raw IAT scores that are not explained by the latent implicit personality factors. In contrast to the absolute IAT scores, this also considers biases associated with the direction of IAT effects (i.e., whether they are positive or negative in sign), biases that might result, for example, from the IAT's stimulus or category features. None of the explicit Big-Five factors was predictive for method-specific variance in the IATs (first analysis). However, when considering unwanted variance that goes beyond pure method-specific variance (second analysis), a substantial effect of neuroticism occurred that may have been driven by the affective valence of IAT attribute categories and the facilitated processing of negative stimuli, typically associated with neuroticism. The findings thus point to the necessity of using attribute category labels and stimuli of similar affective valence in personality IATs to avoid confounding due to recoding.

Jackknife variance of the partial area under the empirical receiver operating characteristic curve.

PubMed

Bandos, Andriy I; Guo, Ben; Gur, David

2017-04-01

Receiver operating characteristic analysis provides an important methodology for assessing traditional (e.g., imaging technologies and clinical practices) and new (e.g., genomic studies, biomarker development) diagnostic problems. The area under the clinically/practically relevant part of the receiver operating characteristic curve (partial area or partial area under the receiver operating characteristic curve) is an important performance index summarizing diagnostic accuracy at multiple operating points (decision thresholds) that are relevant to actual clinical practice. A robust estimate of the partial area under the receiver operating characteristic curve is provided by the area under the corresponding part of the empirical receiver operating characteristic curve. We derive a closed-form expression for the jackknife variance of the partial area under the empirical receiver operating characteristic curve. Using the derived analytical expression, we investigate the differences between the jackknife variance and a conventional variance estimator. The relative properties in finite samples are demonstrated in a simulation study. The developed formula enables an easy way to estimate the variance of the empirical partial area under the receiver operating characteristic curve, thereby substantially reducing the computation burden, and provides important insight into the structure of the variability. We demonstrate that when compared with the conventional approach, the jackknife variance has substantially smaller bias, and leads to a more appropriate type I error rate of the Wald-type test. The use of the jackknife variance is illustrated in the analysis of a data set from a diagnostic imaging study.

Repeatability and reproducibility of ribotyping and its computer interpretation.

PubMed

Lefresne, Gwénola; Latrille, Eric; Irlinger, Françoise; Grimont, Patrick A D

2004-04-01

Many molecular typing methods are difficult to interpret because their repeatability (within-laboratory variance) and reproducibility (between-laboratory variance) have not been thoroughly studied. In the present work, ribotyping of coryneform bacteria was the basis of a study involving within-gel and between-gel repeatability and between-laboratory reproducibility (two laboratories involved). The effect of different technical protocols, different algorithms, and different software for fragment size determination was studied. Analysis of variance (ANOVA) showed, within a laboratory, that there was no significant added variance between gels. However, between-laboratory variance was significantly higher than within-laboratory variance. This may be due to the use of different protocols. An experimental function was calculated to transform the data and make them compatible (i.e., erase the between-laboratory variance). The use of different interpolation algorithms (spline, Schaffer and Sederoff) was a significant source of variation in one laboratory only. The use of either Taxotron (Institut Pasteur) or GelCompar (Applied Maths) was not a significant source of added variation when the same algorithm (spline) was used. However, the use of Bio-Gene (Vilber Lourmat) dramatically increased the error (within laboratory, within gel) in one laboratory, while decreasing the error in the other laboratory; this might be due to automatic normalization attempts. These results were taken into account for building a database and performing automatic pattern identification using Taxotron. Conversion of the data considerably improved the identification of patterns irrespective of the laboratory in which the data were obtained.

Warfarin Anticoagulation Therapy in Caribbean Hispanics of Puerto Rico: A Candidate Gene Association Study

PubMed Central

Claudio-Campos, Karla; Labastida, Aurora; Ramos, Alga; Gaedigk, Andrea; Renta-Torres, Jessicca; Padilla, Dariana; Rivera-Miranda, Giselle; Scott, Stuart A.; Ruaño, Gualberto; Cadilla, Carmen L.; Duconge-Soler, Jorge

2017-01-01

Existing algorithms account for ~50% of observed variance in warfarin dose requirements after including common polymorphisms. However, they do not perform as well in populations other than Caucasians, in part because some ethno-specific genetic variants are overlooked. The objective of the present study was to identify genetic polymorphisms that can explain variability in warfarin dose requirements among Caribbean Hispanics of Puerto Rico. Next-Generation Sequencing of candidate genes CYP2C9 and VKORC1 and genotyping by DMET® Plus Assay of cardiovascular patients were performed. We also aimed at characterizing the genomic structure and admixture pattern of this study cohort. Our study used the Extreme Discordant Phenotype approach to perform a case-control association analysis. The CYP2C9 variant rs2860905, which was found in all the major haplotypes occurring in the Puerto Rican population, showed stronger association with warfarin sensitivity (<4 mg/day) than common variants CYP2C9*2 and CYP2C9*3. Although, CYP2C9*2 and CYP2C9*3 are separately contained within two of the haplotypes, 10 subjects with the sensitive phenotype were carriers of only the CYP2C9 rs2860905 variant. Other polymorphisms in CES2 and ABCB1 were found to be associated with warfarin resistance. Incorporation of rs2860905 in a regression model (R2 = 0.63, MSE = 0.37) that also includes additional genetics (i.e., VKORC1-1639 G>A; CYP2C9 rs1856908; ABCB1 c.IVS9-44A>G/ rs10276036; CES2 c.269-965A>G/ rs4783745) and non-genetic factors (i.e., hypertension, diabetes and age) showed better prediction of warfarin dose requirements than CYP2C9*2 and CYP2C9*3 combined (partial R2 = 0.132 vs. 0.023 and 0.007, respectively, p < 0.001). The genetic background of Puerto Ricans in the study cohort showed a tri-hybrid admixture pattern, with a slightly higher than expected contribution of Native American ancestry (25%). The genomic diversity of Puerto Ricans is highlighted by the presence of four different major haplotype blocks in the CYP2C9 locus. Although, our findings need further replication, this study contributes to the field by identifying novel genetic variants that increase predictability of stable warfarin dosing among Caribbean Hispanics. PMID:28638342

RET/PTC and PAX8/PPARγ chromosomal rearrangements in post-Chernobyl thyroid cancer and their association with I-131 radiation dose and other characteristics

PubMed Central

Leeman-Neill, Rebecca J.; Brenner, Alina V.; Little, Mark P.; Bogdanova, Tetiana I.; Hatch, Maureen; Zurnadzy, Liudmyla Y.; Mabuchi, Kiyohiko; Tronko, Mykola D.; Nikiforov, Yuri E.

2012-01-01

Background Childhood exposure to I-131 from the 1986 Chernobyl accident led to a sharp increase in papillary thyroid carcinoma (PTC) incidence in regions surrounding the reactor. Data concerning the association between genetic mutations in PTCs and individual radiation doses are limited. Methods We performed mutational analysis of 62 PTCs diagnosed in a Ukrainian cohort of patients who were <18 y.o. in 1986 and received 0.008-8.6 Gy of I-131 to the thyroid and explored associations between mutation types and I-131 dose and other characteristics. Results RET/PTC rearrangements were most common (35%), followed by BRAF (15%) and RAS (8%) point mutations. Two tumors carrying PAX8/PPARγ rearrangement were identified. We found a significant negative association with I-131 dose for BRAF and RAS point mutations and a significant concave association with I-131 dose, with an inflection point at 1.6 Gy and odds ratio 2.1, based on a linear-quadratic model for RET/PTC and PAX8/PPARγ rearrangements. The trends with dose were significantly different between tumors with point mutations and rearrangements. Compared to point mutations, rearrangements were associated with residence in the relatively iodine deficient Zhytomyr region, younger age at exposure or surgery, and male gender. Conclusions Our results provide the first demonstration of PAX8/PPARγ rearrangements in post-Chernobyl tumors and show different associations for point mutations and chromosomal rearrangements with I-131 dose and other factors. These data support the relationship between chromosomal rearrangements, but not point mutations, and I-131 exposure and point to a possible role of iodine deficiency in generation of RET/PTC rearrangements in these patients. PMID:23436219

All Data Collection and Analysis Methods Have Limitations: Reply to Rabbitt (2011) and Raz and Lindenberger (2011)

ERIC Educational Resources Information Center

Salthouse, Timothy A.

2011-01-01

The commentaries on my article contain a number of points with which I disagree but also several with which I agree. For example, I continue to believe that the existence of many cases in which between-person variability does not increase with age indicates that greater variance with increased age is not inevitable among healthy individuals up to…

Dose Effect of Rhenium (I)-diselenoether as Anticancer Drug in Resistant Breast Tumor-bearing Mice After Repeated Administrations.

PubMed

Collery, Philippe; Santoni, François; Ciccolini, Joseph; Tran, Thi Ngoc Nga; Mohsen, Ahmed; Desmaele, Didier

2016-11-01

Rhenium (I)-diselenoether has shown promising antiproliferative efficacy in both in vitro and in vivo models. However, the maximal tolerated dose and dose-effect relationships have not been fully addressed for this compound. Here, we evaluated the tolerance and efficacy of three dose-levels (namely 10, 40 and 100 mg/kg) intraperitoneally administered daily over 28 days in mice bearing the resistant MDA-MB231 breast cancer cell line. The upper dose was found to be toxic and was reduced to 60 mg/kg. The 10 mg/kg dose well tolerated, whereas 40 mg/kg was associated with 10% mortality (LD 10 ). Both 10 and 40 mg/kg dosing achieved a significantly similar regression of tumor growth compared with untreated animals. This study suggests that 10 mg/kg daily is the recommended dose for rhenium (I) diselenoether. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

The Effect of Diagnostic Absorbed Doses from 131I on Human Thyrocytes in Vitro.

PubMed

Adamczewski, Zbigniew; Stasiołek, Mariusz; Karwowski, Bolesław; Dedecjus, Marek; Orszulak-Michalak, Daria; Merecz, Anna; Śliwka, Przemysław W; Puła, Bartosz; Lewiński, Andrzej

2015-06-29

Administration of diagnostic activities of 131I, performed in order to detect thyroid remnants after surgery and/or thyroid cancer recurrence/metastases, may lead to reduction of iodine uptake. This phenomenon is called "thyroid stunning". We estimated radiation absorbed dose-dependent changes in genetic material, in particular in sodium iodide symporter (NIS) gene promoter, and NIS protein level in human thyrocytes (HT). We used unmodified HT isolated from patients subjected to thyroidectomy exposed to 131I in culture. The different 131I activities applied were calculated to result in absorbed doses of 5, 10, and 20 Gy. According to flow cytometry analysis and comet assay, 131I did not influence the HT viability in culture. Temporary increase of 8-oxo-dG concentration in HT directly after 24 h (p < 0.05) and increase in the number of AP-sites 72 h after termination of exposition to 20 Gy dose (p < 0.0001) were observed. The signs of dose-dependent DNA damage were not associated with essential changes in the NIS expression on mRNA and protein levels. Our observation constitutes a first attempt to evaluate the effect of the absorbed dose of 131I on HT. The results have not confirmed the theory that the "thyroid stunning" reduces the NIS protein synthesis.

Bayesian model of categorical effects in L1 and L2 speech perception

NASA Astrophysics Data System (ADS)

Kronrod, Yakov

In this dissertation I present a model that captures categorical effects in both first language (L1) and second language (L2) speech perception. In L1 perception, categorical effects range between extremely strong for consonants to nearly continuous perception of vowels. I treat the problem of speech perception as a statistical inference problem and by quantifying categoricity I obtain a unified model of both strong and weak categorical effects. In this optimal inference mechanism, the listener uses their knowledge of categories and the acoustics of the signal to infer the intended productions of the speaker. The model splits up speech variability into meaningful category variance and perceptual noise variance. The ratio of these two variances, which I call Tau, directly correlates with the degree of categorical effects for a given phoneme or continuum. By fitting the model to behavioral data from different phonemes, I show how a single parametric quantitative variation can lead to the different degrees of categorical effects seen in perception experiments with different phonemes. In L2 perception, L1 categories have been shown to exert an effect on how L2 sounds are identified and how well the listener is able to discriminate them. Various models have been developed to relate the state of L1 categories with both the initial and eventual ability to process the L2. These models largely lacked a formalized metric to measure perceptual distance, a means of making a-priori predictions of behavior for a new contrast, and a way of describing non-discrete gradient effects. In the second part of my dissertation, I apply the same computational model that I used to unify L1 categorical effects to examining L2 perception. I show that we can use the model to make the same type of predictions as other SLA models, but also provide a quantitative framework while formalizing all measures of similarity and bias. Further, I show how using this model to consider L2 learners at different stages of development we can track specific parameters of categories as they change over time, giving us a look into the actual process of L2 category development.

Phase I study of olaparib plus gemcitabine in patients with advanced solid tumours and comparison with gemcitabine alone in patients with locally advanced/metastatic pancreatic cancer.

PubMed

Bendell, J; O'Reilly, E M; Middleton, M R; Chau, I; Hochster, H; Fielding, A; Burke, W; Burris, H

2015-04-01

Olaparib (Lynparza) is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor that induces synthetic lethality in cancers with homologous recombination defects. In this phase I, dose-escalation trial, patients with advanced solid tumours received olaparib (50-200 mg capsules b.i.d.) continuously or intermittently (days 1-14, per 28-day cycle) plus gemcitabine [i.v. 600-800 mg/m(2); days 1, 8, 15, and 22 (cycle 1), days 1, 8, and 15 (subsequent cycles)] to establish the maximum tolerated dose. A separate dose-escalation phase evaluated olaparib in tablet formulation (100 mg o.d./b.i.d.; days 1-14) plus gemcitabine (600 mg/m(2)). In an expansion phase, patients with genetically unselected locally advanced or metastatic pancreatic cancer were randomised 2 : 1 to the tolerated olaparib capsule combination dose or gemcitabine alone (1000 mg/m(2)). Sixty-six patients were treated [dose-escalation phase, n = 44 (tablet cohort, n = 12); dose-expansion phase, n = 22 (olaparib plus gemcitabine, n = 15; gemcitabine alone, n = 7)]. In the dose-escalation phase, four patients (6%) experienced dose-limiting toxicities (raised alanine aminotransferase, n = 2; neutropenia, n = 1; febrile neutropenia, n = 1). Grade ≥3 adverse events were reported in 38/47 patients (81%) treated with olaparib capsules plus gemcitabine; most common were haematological toxicities (55%). Tolerated combinations were olaparib 100 mg b.i.d. capsule (intermittently, days 1-14) plus gemcitabine 600 mg/m(2) and olaparib 100 mg o.d. tablet (intermittently, days 1-14) plus gemcitabine 600 mg/m(2). There were no differences in efficacy observed during the dose-expansion phase. Olaparib 100 mg b.i.d. (intermittent dosing; capsules) plus gemcitabine 600 mg/m(2) is tolerated in advanced solid tumour patients, with no unmanageable/unexpected toxicities. Continuous dosing of olaparib or combination with gemcitabine at doses >600 mg/m(2) was not considered to have an acceptable tolerability profile for further study. NCT00515866. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Chemical Characterization of HC Smoke Pot Residue.

DTIC Science & Technology

1988-01-01

vvv.twwii, ,- 11111 I.U . ". I III 140 2.0 1~~.25 111111. J_____1.6 ’."Ik ~ w MICROCOP RESOLUTION TEST CHART ii O.i S S • S • S S S • 0 0 S • S 0...conditions. Two trials were conducted: the first examined the spatial distribultion of organic and inorganic compounds in the smoke pot residue, and...27 4 Results of Nested Analysis of Variance - Trial I ................... 28 - 5 Major Organic Compounds Found in Trial I Smokepot

Knowledge-based iterative model reconstruction: comparative image quality and radiation dose with a pediatric computed tomography phantom.

PubMed

Ryu, Young Jin; Choi, Young Hun; Cheon, Jung-Eun; Ha, Seongmin; Kim, Woo Sun; Kim, In-One

2016-03-01

CT of pediatric phantoms can provide useful guidance to the optimization of knowledge-based iterative reconstruction CT. To compare radiation dose and image quality of CT images obtained at different radiation doses reconstructed with knowledge-based iterative reconstruction, hybrid iterative reconstruction and filtered back-projection. We scanned a 5-year anthropomorphic phantom at seven levels of radiation. We then reconstructed CT data with knowledge-based iterative reconstruction (iterative model reconstruction [IMR] levels 1, 2 and 3; Philips Healthcare, Andover, MA), hybrid iterative reconstruction (iDose(4), levels 3 and 7; Philips Healthcare, Andover, MA) and filtered back-projection. The noise, signal-to-noise ratio and contrast-to-noise ratio were calculated. We evaluated low-contrast resolutions and detectability by low-contrast targets and subjective and objective spatial resolutions by the line pairs and wire. With radiation at 100 peak kVp and 100 mAs (3.64 mSv), the relative doses ranged from 5% (0.19 mSv) to 150% (5.46 mSv). Lower noise and higher signal-to-noise, contrast-to-noise and objective spatial resolution were generally achieved in ascending order of filtered back-projection, iDose(4) levels 3 and 7, and IMR levels 1, 2 and 3, at all radiation dose levels. Compared with filtered back-projection at 100% dose, similar noise levels were obtained on IMR level 2 images at 24% dose and iDose(4) level 3 images at 50% dose, respectively. Regarding low-contrast resolution, low-contrast detectability and objective spatial resolution, IMR level 2 images at 24% dose showed comparable image quality with filtered back-projection at 100% dose. Subjective spatial resolution was not greatly affected by reconstruction algorithm. Reduced-dose IMR obtained at 0.92 mSv (24%) showed similar image quality to routine-dose filtered back-projection obtained at 3.64 mSv (100%), and half-dose iDose(4) obtained at 1.81 mSv.

Nonclinical and clinical pharmacological characterization of the potent and selective cathepsin K inhibitor MIV-711.

PubMed

Lindström, Erik; Rizoska, Biljana; Henderson, Ian; Terelius, Ylva; Jerling, Markus; Edenius, Charlotte; Grabowska, Urszula

2018-05-09

Cathepsin K is an attractive therapeutic target for diseases in which bone resorption is excessive such as osteoporosis and osteoarthritis (OA). The current paper characterized the pharmacological profile of the potent and selective cathepsin K inhibitor, MIV-711, in vitro and in cynomolgus monkeys, and assessed translation to human based on a single dose clinical study in man. The potency and selectivity of MIV-711 were assessed in vitro using recombinant enzyme assays and differentiated human osteoclasts. MIV-711 was administered to healthy cynomolgus monkeys (3-30 µmol/kg, p.o.). Plasma levels of MIV-711 and the bone resorption biomarker CTX-I were measured after single dose experiments, and urine levels of CTX-I, NTX-I and CTX-II biomarkers were measured after repeat dose experiments. The safety, pharmacokinetics and pharmacodynamics (serum CTX-I) of MIV-711 were assessed in human healthy subjects after single ascending doses from 20 to 600 mg. MIV-711 was a potent inhibitor of human cathepsin K (K i : 0.98 nmol/L) with > 1300-fold selectivity towards other human cathepsins. MIV-711 inhibited human osteoclast-mediated bone resorption with an IC 50 value of 43 nmol/L. Single oral doses of MIV-711 to monkeys reduced plasma levels of CTX-I in a dose-dependent fashion by up to 57% at trough. The effect on CTX-I was linearly correlated to the plasma exposure of MIV-711, while the efficacy duration outlasted plasma exposure. Repeat oral dosing with MIV-711 also reduced urinary levels of the bone resorption biomarkers CTX-I (by 93%) and NTX-I (by 71%) and the cartilage degradation biomarker CTX-II (by 71%). MIV-711 was safe and well-tolerated when given as single ascending doses to healthy subjects. MIV-711 reduced serum CTX-I levels in a dose-dependent manner by up to 79% at trough. The relationship between MIV-711 exposure and effects on these biomarkers in humans was virtually identical when compared to the corresponding monkey data. MIV-711 is a potent and selective cathepsin K inhibitor with dose-dependent effects on biomarkers of bone and cartilage degradation in monkey and human. Taken together, MIV-711 shows promise for the treatment of bone and cartilage related disorders in humans, such as OA. Trial Registration EudraCT number 2011-003024-12, registered on June 22nd 2011.

Range and trend of expected toxicity level (ETL) in standard A + B designs: a report from the Children's Oncology Group.

PubMed

Chen, Zhengjia; Krailo, Mark D; Sun, Junfeng; Azen, Stanley P

2009-03-01

The traditional algorithm-based 3+3 designs are most widely used for their practical simplicity in phase I clinical trials. At early stage, a common belief was that the expected toxicity level (ETL) at the maximum tolerated dose (MTD) should be 33% [Storer, B. Design and analysis of phase I clinical trials. Biometrics 1989;45;925-937, Gorden, N., Willson, J. Using toxicity grades in the design and analysis of cancer phase I clinical trials. Statistics in Medicine 1992; 11: 2063-2075, Mick, R. Phase I Clinical Trial Design. In Schilsky, R., Milano, G., Ratain, M., eds. Principles of Antineoplastic Drug Development and Pharmacology New York, NY: Marcel Dekker, 1996; 29-36]. Recently, Kang and Ahn [Kang, S., Ahn, C. The expected toxicity rate at the maximum tolerated dose in the standard phase I cancer clinical trial design. Drug Information Journal 2001; 35:1189-1199, Kang, S., Ahn, C. An investigation of the traditional algorithm-based designs for phase I cancer clinical trials. Drug Information Journal 2002; 36:865-873] found that the ETL is between 17% and 21% and He et al [He, W., Liu, J., Binkowitz, B., Quan, H. A model-based approach in the estimation of the maximum tolerated dose in phase I cancer clinical trials. Statistics in Medicine 2006; 25(12):2027-42] further reported that the ETL ranges from 19% to 24%. However they only investigated designs where the number of dose levels was at most 20. It has practical significance in designing and conducting phase I clinical trial to definitely assess the full range and trend of ETL by all possible number of tested dose levels in traditional algorithm-based A+B designs, especially 3+3 designs. In this simulation study, we originally find that the ETL decreases monotonically from about 30% to 0% as the number of dose levels increase from 3 to infinity, which will correct the inaccuracy in the common belief among phase I trial investigators. To help better design and conduct phase I trials, we create a table as a reference for the association between ETL and number of dose levels considered in a design when the exact shape of the dose-toxicity relationship is not well understood. We conclude that the number of specified dose levels is an important factor affecting substantially the ETL at MTD and recommend that fewer than 20 dose levels be designated.

Location tests for biomarker studies: a comparison using simulations for the two-sample case.

PubMed

Scheinhardt, M O; Ziegler, A

2013-01-01

Gene, protein, or metabolite expression levels are often non-normally distributed, heavy tailed and contain outliers. Standard statistical approaches may fail as location tests in this situation. In three Monte-Carlo simulation studies, we aimed at comparing the type I error levels and empirical power of standard location tests and three adaptive tests [O'Gorman, Can J Stat 1997; 25: 269 -279; Keselman et al., Brit J Math Stat Psychol 2007; 60: 267- 293; Szymczak et al., Stat Med 2013; 32: 524 - 537] for a wide range of distributions. We simulated two-sample scenarios using the g-and-k-distribution family to systematically vary tail length and skewness with identical and varying variability between groups. All tests kept the type I error level when groups did not vary in their variability. The standard non-parametric U-test performed well in all simulated scenarios. It was outperformed by the two non-parametric adaptive methods in case of heavy tails or large skewness. Most tests did not keep the type I error level for skewed data in the case of heterogeneous variances. The standard U-test was a powerful and robust location test for most of the simulated scenarios except for very heavy tailed or heavy skewed data, and it is thus to be recommended except for these cases. The non-parametric adaptive tests were powerful for both normal and non-normal distributions under sample variance homogeneity. But when sample variances differed, they did not keep the type I error level. The parametric adaptive test lacks power for skewed and heavy tailed distributions.

Improvements to image quality using hybrid and model-based iterative reconstructions: a phantom study.

PubMed

Aurumskjöld, Marie-Louise; Ydström, Kristina; Tingberg, Anders; Söderberg, Marcus

2017-01-01

The number of computed tomography (CT) examinations is increasing and leading to an increase in total patient exposure. It is therefore important to optimize CT scan imaging conditions in order to reduce the radiation dose. The introduction of iterative reconstruction methods has enabled an improvement in image quality and a reduction in radiation dose. To investigate how image quality depends on reconstruction method and to discuss patient dose reduction resulting from the use of hybrid and model-based iterative reconstruction. An image quality phantom (Catphan® 600) and an anthropomorphic torso phantom were examined on a Philips Brilliance iCT. The image quality was evaluated in terms of CT numbers, noise, noise power spectra (NPS), contrast-to-noise ratio (CNR), low-contrast resolution, and spatial resolution for different scan parameters and dose levels. The images were reconstructed using filtered back projection (FBP) and different settings of hybrid (iDose 4 ) and model-based (IMR) iterative reconstruction methods. iDose 4 decreased the noise by 15-45% compared with FBP depending on the level of iDose 4 . The IMR reduced the noise even further, by 60-75% compared to FBP. The results are independent of dose. The NPS showed changes in the noise distribution for different reconstruction methods. The low-contrast resolution and CNR were improved with iDose 4 , and the improvement was even greater with IMR. There is great potential to reduce noise and thereby improve image quality by using hybrid or, in particular, model-based iterative reconstruction methods, or to lower radiation dose and maintain image quality. © The Foundation Acta Radiologica 2016.

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

Vega-Carrillo, Hector Rene; Manzanares-Acuna, Eduardo; Hernandez-Davila, Victor Martin

The use of 131I is widely used in diagnostic and treatment of patients. If the patient is pregnant the 131I presence in the thyroid it becomes a source of constant exposition to other organs and the fetus. In this study the absorbed dose in the uterus of a 3 months pregnant woman with 131I in her thyroid gland has been calculated. The dose was determined using Monte Carlo methods in which a detailed model of the woman has been developed. The dose was also calculated using a simple procedure that was refined including the photons' attenuation in the woman organsmore » and body. To verify these results an experiment was carried out using a neck phantom with 131I. Comparing the results it was found that the simple calculation tend to overestimate the absorbed dose, by doing the corrections due to body and organs photon attenuation the dose is 0.14 times the Monte Carlo estimation.« less

ACB-PCR MEASUREMENT OF K-RAS CODON 12 MUTATION IN A/J MOUSE LUNG EXPOSED TO BENZO[A]PYRENE: A DOSE-RESPONSE ASSESSMENT

EPA Science Inventory

Benzo[a]pyrene (B[a]P) is a known human carcinogen and environmental contaminant. The direct measurement of K-Ras mutant fraction (MF) was developed as a metric with which to examine the default assumption of low dose linearity in the mutational response to B...

Dose escalation in permanent brachytherapy for prostate cancer: dosimetric and biological considerations

NASA Astrophysics Data System (ADS)

Li, X. Allen; Wang, Jian Z.; Stewart, Robert D.; Di Biase, Steven J.

2003-09-01

No prospective dose escalation study for prostate brachytherapy (PB) with permanent implants has been reported. In this work, we have performed a dosimetric and biological analysis to explore the implications of dose escalation in PB using 125I and 103Pd implants. The concept of equivalent uniform dose (EUD), proposed originally for external-beam radiotherapy (EBRT), is applied to low dose rate brachytherapy. For a given 125I or 103Pd PB, the EUD for tumour that corresponds to a dose distribution delivered by EBRT is calculated based on the linear quadratic model. The EUD calculation is based on the dose volume histogram (DVH) obtained retrospectively from representative actual patient data. Tumour control probabilities (TCPs) are also determined in order to compare the relative effectiveness of different dose levels. The EUD for normal tissue is computed using the Lyman model. A commercial inverse treatment planning algorithm is used to investigate the feasibility of escalating the dose to prostate with acceptable dose increases in the rectum and urethra. The dosimetric calculation is performed for five representative patients with different prostate sizes. A series of PB dose levels are considered for each patient using 125I and 103Pd seeds. It is found that the PB prescribed doses (minimum peripheral dose) that give an equivalent EBRT dose of 64.8, 70.2, 75.6 and 81 Gy with a fraction size of 1.8 Gy are 129, 139, 150 and 161 Gy for 125I and 103, 112, 122 and 132 Gy for 103Pd implants, respectively. Estimates of the EUD and TCP for a series of possible prescribed dose levels (e.g., 145, 160, 170 and 180 Gy for 125I and 125, 135, 145 and 155 for 103Pd implants) are tabulated. The EUD calculation was found to depend strongly on DVHs and radiobiological parameters. The dosimetric calculations suggest that the dose to prostate can be escalated without a substantial increase in both rectal and urethral dose. For example, increasing the PB prescribed dose from 145 to 180 Gy increases EUD for the rectum by only 3%. Our studies indicate that the dose to urethra can be kept within 100-120% of the prescription dose for all the dose levels studied. In conclusion, dose escalation in permanent implant for localized prostate cancer may be advantageous. It is dosimetrically possible to increase dose to prostate without a substantial increase in the dose to the rectum and urethra. Based on the results of our studies, a prospective dose escalation trial for prostate permanent implants has been initiated at our institution.

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

Ader, M.; Bergman, R.N.

Insulin may suppress hepatic glucose production directly, or indirectly via suppression of release of gluconeogenic substrates from extrasplanchnic tissues. To compare these mechanisms, we performed insulin dose-response experiments in conscious dogs at euglycemia, during somatostatin infusion, and intraportal glucagon replacement. Insulin was sequentially infused either intraportally (0.05, 0.20, 0.40, 1.0, 1.4, and/or 3.0; protocol I) or systemically at half the intraportal rate (0.025, 0.10, 0.20, 0.50, 0.70, and/or 1.5 mU.min-1.kg-1; protocol II). Exogenous glucose infused during clamps was labeled with 3-(3H)glucose (2 microCi/g) to prevent a fall in plasma specific activity (P greater than 0.2) that may have contributed tomore » previous underestimations of hepatic glucose output (HGO). Portal insulins were up to threefold higher during intraportal infusion, but peripheral insulin levels were not different between the intraportal and systemic protocols (7 +/- 5 vs. 9 +/- 1, 12 +/- 4 vs. 13 +/- 6, 16 +/- 3 vs. 27 +/- 5, 70 +/- 23 vs. 48 +/- 8, 83 +/- 3 vs. 86 +/- 21, and 128 vs. 120 +/- 14 microU/ml for paired insulin doses; P greater than 0.06 by analysis of variance (ANOVA)). Despite higher portal insulin levels in protocol I, HGO suppression was equivalent in the two protocols when systemic insulin was matched, from 3.3 +/- 0.1 to near-total suppression at 0.3 mg.min-1.kg-1 at the highest insulin infusion rate (3.0 mU.min-1.kg-1; P less than 0.0001) with intraportal insulin, from 2.9 +/- 0.8 to -0.8 +/- 0.2 mg.min-1.kg-1 in protocol II (P less than 0.001). Suppression of HGO was similar at matched systemic insulin, regardless of portal insulin, suggesting the primacy of insulin's action on the periphery in its restraint of hepatic glucose production.« less

The effect of Amifostine (Ethyol) on intestinal anastomosis in rats with radiation enteritis.

PubMed

Ozdemir, C S; Burgazli, K M; Beken-Ozdemir, E; Akdere, H; Mericliler, M; Ozcelik, M F

2013-05-01

Preoperative radiotherapy in colorectal cancers is being used as an adjuvant therapy with increasing frequency. Postoperative complications in early and late periods in various ratios are reported. It has also been shown that radiation has a delaying effect on wound healing and this effect is dose-dependent. This study investigated the effects of the Amifostine on healing of the irradiated colonic anastomosis. 30 female Wistar rats were divided randomly into three groups equally (n=10). Colonic anastomosis were performed to all rats. Group I served as a control. 800 rad abdominopelvic irradiation on the 5th day of preoperation was given to group II and III. Rats in the group III, prior to radiation, were given Amifostine at a dose of 200 mg/kg. On the 5th postoperative day all the rats were sacrificed and the healing of anastomosis was measured with bursting pressure, hydroxyproline levels and histopathological evaluations. Statistical analyses were expressed by analysis of variance (ANOVA) test and p < 0.05 was regarded as significant. In group II, all parameters were found lower compared with control group and Amifostine+Radiation group. As compared with hydroxyproline values and the anastomotic wound healing scores, except group II, no significantly difference were determined between the two other groups. In bursting pressure levels, Group I and III were higher than group II, but not statistically significant (p > 0.05). In group III (Amifostine+Radiation group), the hydroxyproline levels and anastomotic wound healing scores were found significantly higher than group II (p < 0.05), and no significant difference were found between the control group. It is determined that radiation given on the 5th preoperative day has a negative effect on anastomotic wound healing and administered Amifostine prevent this negative effect. In the light of these data, the Amifostine may have a positive effect on preoperative irradiated colonic anastomosis and may play an important role in future on the supporting of the colonic anastomosis.

Effects of 5-HT5A receptor blockade on amnesia or forgetting.

PubMed

Aparicio-Nava, L; Márquez-García, L A; Meneses, A

2018-01-09

Previously the effects (0.01-3.0 mg/kg) of post-training SB-699551 (a 5-HT 5A receptor antagonist) were reported in the associative learning task of autoshaping, showing that SB-699551 (0.1 mg/kg) decreased lever-press conditioned responses (CR) during short-term (STM; 1.5-h) or (3.0 mg/kg) long-term memory (LTM; 24-h); relative to the vehicle animals. Moreover, as pro-cognitive efficacy of SB-699551 was reported in the ketamine-model of schizophrenia. Hence, firstly aiming improving performance (conditioned response, CR), in this work autoshaping lever-press vs. nose-poke response was compared; secondly, new set of animals were randomly assigned to SB-699551 plus forgetting or amnesia protocols. Results show that the nose-poke operandum reduced inter-individual variance, increased CR and produced a progressive CR until 48-h. After one week of no training/testing sessions (i.e., interruption of 216 h), the forgetting was observed; i.e., the CR% of control-saline group significantly decreased. In contrast, SB-699551 at 0.3 and 3.0 mg/kg prevents forgetting. Additionally, as previously reported the non-competitive NMDA receptor antagonist dizocilpine (0.2 mg/kg) or the non-selective cholinergic antagonist scopolamine (0.3 mg/kg) decreased CR in STM. SB-699551 (0.3 mg/kg) alone also produced amnesia-like effect. Co-administration of SB-699551-dizocilpine or SB-699551-scopolamine reversed the SB-699551 induced-amnesic effects in LTM (24-h). Nose-poke seems to be a reliable operandum. The anti-amnesic and anti-forgetting mechanisms of amnesic SB-699551-dose remain unclear. The present findings are consistent with the notion that low doses of 5-HT 5A receptor antagonists might be useful for reversing memory deficits associated to forgetting and amnesia. Of course, further experiments are necessary. Copyright © 2018 Elsevier B.V. All rights reserved.

12 CFR 1263.17 - Rebuttable presumptions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... from the rating required by § 1263.11(b)(3)(i), or a variance from a performance trend criterion... any criminal, civil or administrative proceedings reflecting upon creditworthiness, business judgment...

Variance adaptation in navigational decision making

NASA Astrophysics Data System (ADS)

Gershow, Marc; Gepner, Ruben; Wolk, Jason; Wadekar, Digvijay

Drosophila larvae navigate their environments using a biased random walk strategy. A key component of this strategy is the decision to initiate a turn (change direction) in response to declining conditions. We modeled this decision as the output of a Linear-Nonlinear-Poisson cascade and used reverse correlation with visual and fictive olfactory stimuli to find the parameters of this model. Because the larva responds to changes in stimulus intensity, we used stimuli with uncorrelated normally distributed intensity derivatives, i.e. Brownian processes, and took the stimulus derivative as the input to our LNP cascade. In this way, we were able to present stimuli with 0 mean and controlled variance. We found that the nonlinear rate function depended on the variance in the stimulus input, allowing larvae to respond more strongly to small changes in low-noise compared to high-noise environments. We measured the rate at which the larva adapted its behavior following changes in stimulus variance, and found that larvae adapted more quickly to increases in variance than to decreases, consistent with the behavior of an optimal Bayes estimator. Supported by NIH Grant 1DP2EB022359 and NSF Grant PHY-1455015.

Estimating means and variances: The comparative efficiency of composite and grab samples.

PubMed

Brumelle, S; Nemetz, P; Casey, D

1984-03-01

This paper compares the efficiencies of two sampling techniques for estimating a population mean and variance. One procedure, called grab sampling, consists of collecting and analyzing one sample per period. The second procedure, called composite sampling, collectsn samples per period which are then pooled and analyzed as a single sample. We review the well known fact that composite sampling provides a superior estimate of the mean. However, it is somewhat surprising that composite sampling does not always generate a more efficient estimate of the variance. For populations with platykurtic distributions, grab sampling gives a more efficient estimate of the variance, whereas composite sampling is better for leptokurtic distributions. These conditions on kurtosis can be related to peakedness and skewness. For example, a necessary condition for composite sampling to provide a more efficient estimate of the variance is that the population density function evaluated at the mean (i.e.f(μ)) be greater than[Formula: see text]. If[Formula: see text], then a grab sample is more efficient. In spite of this result, however, composite sampling does provide a smaller estimate of standard error than does grab sampling in the context of estimating population means.

Estimated dose rates to members of the public from external exposure to patients with 131I thyroid treatment

DOE PAGES

Dewji, S.; Bellamy, M.; Hertel, N.; ...

2015-03-25

The purpose of this study is to estimate dose rates that may result from exposure to patients who had been administered iodine-131 ( 131I) as part of medical therapy were calculated. These effective dose rate estimates were compared with simplified assumptions under United States Nuclear Regulatory Commission Regulatory Guide 8.39, which does not consider body tissue attenuation nor time-dependent redistribution and excretion of the administered 131I. Methods: Dose rates were estimated for members of the public potentially exposed to external irradiation from patients recently treated with 131I. Tissue attenuation and iodine biokinetics were considered in the patient in a largermore » comprehensive effort to improve external dose rate estimates. The external dose rate estimates are based on Monte Carlo simulations using the Phantom with Movable Arms and Legs (PIMAL), previously developed by Oak Ridge National Laboratory and the United States Nuclear Regulatory Commission. PIMAL was employed to model the relative positions of the 131I patient and members of the public in three exposure scenarios: (1) traveling on a bus in a total of six seated or standing permutations, (2) two nursing home cases where a caregiver is seated at 30 cm from the patient’s bedside and a nursing home resident seated 250 cm away from the patient in an adjacent bed, and (3) two hotel cases where the patient and a guest are in adjacent rooms with beds on opposite sides of the common wall, with the patient and guest both in bed and either seated back-to-back or lying head to head. The biokinetic model predictions of the retention and distribution of 131I in the patient assumed a single voiding of urinary bladder contents that occurred during the trip at 2, 4, or 8 h after 131I administration for the public transportation cases, continuous first-order voiding for the nursing home cases, and regular periodic voiding at 4, 8, or 12 h after administration for the hotel room cases. Organ specific activities of 131I in the thyroid, bladder, and combined remaining tissues were calculated as a function of time after administration. Exposures to members of the public were considered for 131I patients with normal thyroid uptake (peak thyroid uptake of ~27% of administered 131I), differentiated thyroid cancer (DTC, 5% uptake), and hyperthyroidism (80% uptake). Results: The scenario with the patient seated behind the member of the public yielded the highest dose rate estimate of seated public transportation exposure cases. The dose rate to the adjacent room guest was highest for the exposure scenario in which the hotel guest and patient are seated by a factor of ~4 for the normal and differentiated thyroid cancer uptake cases and by a factor of ~3 for the hyperthyroid case. Conclusions: It was determined that for all modeled cases, the DTC case yielded the lowest external dose rates, whereas the hyperthyroid case yielded the highest dose rates. In estimating external dose to members of the public from patients with 131I therapy, consideration must be given to (patient- and case-specific) administered 131I activities and duration of exposure for a more complete estimate. The method implemented here included a detailed calculation model, which provides a means to determine dose rate estimates for a range of scenarios. Finally, the method was demonstrated for variations of three scenarios, showing how dose rates are expected to vary with uptake, voiding pattern, and patient location.« less

Estimated dose rates to members of the public from external exposure to patients with 131I thyroid treatment

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

Dewji, S.; Bellamy, M.; Hertel, N.

The purpose of this study is to estimate dose rates that may result from exposure to patients who had been administered iodine-131 ( 131I) as part of medical therapy were calculated. These effective dose rate estimates were compared with simplified assumptions under United States Nuclear Regulatory Commission Regulatory Guide 8.39, which does not consider body tissue attenuation nor time-dependent redistribution and excretion of the administered 131I. Methods: Dose rates were estimated for members of the public potentially exposed to external irradiation from patients recently treated with 131I. Tissue attenuation and iodine biokinetics were considered in the patient in a largermore » comprehensive effort to improve external dose rate estimates. The external dose rate estimates are based on Monte Carlo simulations using the Phantom with Movable Arms and Legs (PIMAL), previously developed by Oak Ridge National Laboratory and the United States Nuclear Regulatory Commission. PIMAL was employed to model the relative positions of the 131I patient and members of the public in three exposure scenarios: (1) traveling on a bus in a total of six seated or standing permutations, (2) two nursing home cases where a caregiver is seated at 30 cm from the patient’s bedside and a nursing home resident seated 250 cm away from the patient in an adjacent bed, and (3) two hotel cases where the patient and a guest are in adjacent rooms with beds on opposite sides of the common wall, with the patient and guest both in bed and either seated back-to-back or lying head to head. The biokinetic model predictions of the retention and distribution of 131I in the patient assumed a single voiding of urinary bladder contents that occurred during the trip at 2, 4, or 8 h after 131I administration for the public transportation cases, continuous first-order voiding for the nursing home cases, and regular periodic voiding at 4, 8, or 12 h after administration for the hotel room cases. Organ specific activities of 131I in the thyroid, bladder, and combined remaining tissues were calculated as a function of time after administration. Exposures to members of the public were considered for 131I patients with normal thyroid uptake (peak thyroid uptake of ~27% of administered 131I), differentiated thyroid cancer (DTC, 5% uptake), and hyperthyroidism (80% uptake). Results: The scenario with the patient seated behind the member of the public yielded the highest dose rate estimate of seated public transportation exposure cases. The dose rate to the adjacent room guest was highest for the exposure scenario in which the hotel guest and patient are seated by a factor of ~4 for the normal and differentiated thyroid cancer uptake cases and by a factor of ~3 for the hyperthyroid case. Conclusions: It was determined that for all modeled cases, the DTC case yielded the lowest external dose rates, whereas the hyperthyroid case yielded the highest dose rates. In estimating external dose to members of the public from patients with 131I therapy, consideration must be given to (patient- and case-specific) administered 131I activities and duration of exposure for a more complete estimate. The method implemented here included a detailed calculation model, which provides a means to determine dose rate estimates for a range of scenarios. Finally, the method was demonstrated for variations of three scenarios, showing how dose rates are expected to vary with uptake, voiding pattern, and patient location.« less

Lateral topography for reducing effective dose in low-dose chest CT.

PubMed

Bang, Dong-Ho; Lim, Daekeon; Hwang, Wi-Sub; Park, Seong-Hoon; Jeong, Ok-man; Kang, Kyung Wook; Kang, Hohyung

2013-06-01

The purposes of this study were to assess radiation exposure during low-dose chest CT by using lateral topography and to compare the lateral topographic findings with findings obtained with anteroposterior topography alone and anteroposterior and lateral topography combined. From November 2011 to February 2012, 210 male subjects were enrolled in the study. Age, weight, and height of the men were recorded. All subjects were placed into one of three subgroups based on the type of topographic image obtained: anteroposterior topography, lateral topography, and both anteroposterior and lateral topography. Imaging was performed with a 128-MDCT scanner. CT, except for topography, was the same for all subjects. A radiologist analyzed each image, recorded scan length, checked for any insufficiencies in the FOV, and calculated the effective radiation dose. One-way analysis of variance and multiple comparisons were used to compare the effective radiation exposure and scan length between groups. The mean scan length in the anteroposterior topography group was significantly greater than that of the lateral topography group and the combined anteroposterior and lateral topography group (p < 0.001). The mean effective radiation dose for the lateral topography group (0.735 ± 0.033 mSv) was significantly lower than that for the anteroposterior topography group (0.763 ± 0.038 mSv) and the combined anteroposterior and lateral topography group (0.773 ± 0.038) (p < 0.001). Lateral topographic low-dose CT was associated with a lower effective radiation dose and scan length than either anteroposterior topographic low-dose chest CT or low-dose chest CT with both anteroposterior and lateral topograms.

Assessment of phase based dose modulation for improved dose efficiency in cardiac CT on an anthropomorphic motion phantom

NASA Astrophysics Data System (ADS)

Budde, Adam; Nilsen, Roy; Nett, Brian

2014-03-01

State of the art automatic exposure control modulates the tube current across view angle and Z based on patient anatomy for use in axial full scan reconstructions. Cardiac CT, however, uses a fundamentally different image reconstruction that applies a temporal weighting to reduce motion artifacts. This paper describes a phase based mA modulation that goes beyond axial and ECG modulation; it uses knowledge of the temporal view weighting applied within the reconstruction algorithm to improve dose efficiency in cardiac CT scanning. Using physical phantoms and synthetic noise emulation, we measure how knowledge of sinogram temporal weighting and the prescribed cardiac phase can be used to improve dose efficiency. First, we validated that a synthetic CT noise emulation method produced realistic image noise. Next, we used the CT noise emulation method to simulate mA modulation on scans of a physical anthropomorphic phantom where a motion profile corresponding to a heart rate of 60 beats per minute was used. The CT noise emulation method matched noise to lower dose scans across the image within 1.5% relative error. Using this noise emulation method to simulate modulating the mA while keeping the total dose constant, the image variance was reduced by an average of 11.9% on a scan with 50 msec padding, demonstrating improved dose efficiency. Radiation dose reduction in cardiac CT can be achieved while maintaining the same level of image noise through phase based dose modulation that incorporates knowledge of the cardiac reconstruction algorithm.

RISK ASSESSMENT FOR CRYPTOSPORIDIUM: A HIERARCHICAL BAYESIAN ANALYSIS OF HUMAN DOSE-RESPONSE DATA. (R828035)

EPA Science Inventory

Three dose_¯response studies were conducted with healthy volunteers using different Cryptosporidium parvum isolates (IOWA, TAMU, and UCP). The study data were previously analyzed for median infectious dose (ID₅₀) using a simple cumulative perce...

Cost effectiveness analysis of elementary school-located vaccination against influenza--results from a randomized controlled trial.

PubMed

Yoo, Byung-Kwang; Humiston, Sharon G; Szilagyi, Peter G; Schaffer, Stanley J; Long, Christine; Kolasa, Maureen

2013-04-19

School-located vaccination against influenza (SLV-I) has been suggested to help meet the need for annual vaccination of large numbers of school-aged children with seasonal influenza vaccine. However, little is known about the cost and cost-effectiveness of SLV-I. We conducted a cost-analysis and a cost-effectiveness analysis based on a randomized controlled trial (RCT) of an SLV-I program implemented in Monroe County, New York during the 2009-2010 vaccination season. We hypothesized that SLV-I is more cost effective, or less-costly, compared to a conventional, office-located influenza vaccination delivery. First and second SLV-I clinics were offered in 21 intervention elementary schools (n=9027 children) with standard of care (no SLV-I) in 11 control schools (n=4534 children). The direct costs, to purchase and administer vaccines, were estimated from our RCT. The effectiveness measure, receipt of ≥1 dose of influenza vaccine, was 13.2 percentage points higher in SLV-I schools than control schools. The school costs ($9.16/dose in 2009 dollars) plus project costs ($23.00/dose) plus vendor costs excluding vaccine purchase ($19.89/dose) was higher in direct costs ($52.05/dose) than the previously reported mean/median cost [$38.23/$21.44 per dose] for providing influenza vaccination in pediatric practices. However SLV-I averted parent costs to visit medical practices ($35.08 per vaccine). Combining direct and averted costs through Monte Carlo Simulation, SLV-I costs were $19.26/dose in net costs, which is below practice-based influenza vaccination costs. The incremental cost-effectiveness ratio (ICER) was estimated to be $92.50 or $38.59 (also including averted parent costs). When additionally accounting for the costs averted by disease prevention (i.e., both reduced disease transmission to household members and reduced loss of productivity from caring for a sick child), the SLV-I model appears to be cost-saving to society, compared to "no vaccination". Our findings support the expanded implementation of SLV-I, but also the need to focus on efficient delivery to reduce direct costs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Characterization of Two Ton NaI Scintillator

NASA Astrophysics Data System (ADS)

Maier, Alleta; Coherent Collaboration

2017-09-01

The COHERENT collaboration is dedicated to measuring Coherent Elastic Neutrino-Nucleus Scattering (CE νNS), an interaction predicted by the standard model that ultimately serves as a background floor for dark matter detection. In the pursuit of observing the N2 scaling predicted, COHERENT is deploying two tons of NaI[Tl] detector to observe CE νNS recoils of sodium nuclei. Before the two tons of this NaI[Tl] scintillator are deployed, however, all crystals and PMTs must be characterized to understand the individual properties vital to precision in the measurement of CE νNS. This detector is also expected to allow COHERENT to observe charged current and CE νNS interactions with 127I. A standard operating procedure is developed to characterize each detector based on seven properties relevant to precision in the measurement of CE νNS: energy scale, energy resolution, low-energy light yield non-linearity, decay time energy dependence, position variance, time variance, and background levels. Crystals will be tested and characterized for these properties in the context of a ton-scale NaI[Tl] detector. Preliminary development of the SOP has allowed for greater understanding of optimization methods needed for characterization for the ton scale detector. TUNL, NSF, Duke University.

Differences in the effective population sizes of males and females do not require differences in their distribution of offspring number.

PubMed

Mendez, Fernando L

2017-04-01

Difference in male and female effective population sizes has, at times, been attributed to both sexes having unequal variance in their number of offspring. Such difference is paralleled by the relative effective sizes of autosomes, sex chromosomes, and mitochondrial DNA. I develop a simple framework to calculate the inbreeding effective population sizes for loci with different modes of inheritance. In this framework, I separate the effects due to mating strategy and those due to genetic transmission. I then show that, in addition to differences in the variance in offspring number, skew in the male/female effective sizes can also be caused by family composition. This approach can be used to illustrate the effect of induced behaviors on the relative male and female effective population sizes. In particular, I show the impact of the one-child policy formerly implemented in the People's Republic of China on the relative male and female effective population sizes. Furthermore, I argue that, under some strong constraints on family structure, the concepts of male and female effective population sizes are invalid. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Advanced Variance Reduction Strategies for Optimizing Mesh Tallies in MAVRIC

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

Peplow, Douglas E.; Blakeman, Edward D; Wagner, John C

2007-01-01

More often than in the past, Monte Carlo methods are being used to compute fluxes or doses over large areas using mesh tallies (a set of region tallies defined on a mesh that overlays the geometry). For problems that demand that the uncertainty in each mesh cell be less than some set maximum, computation time is controlled by the cell with the largest uncertainty. This issue becomes quite troublesome in deep-penetration problems, and advanced variance reduction techniques are required to obtain reasonable uncertainties over large areas. The CADIS (Consistent Adjoint Driven Importance Sampling) methodology has been shown to very efficientlymore » optimize the calculation of a response (flux or dose) for a single point or a small region using weight windows and a biased source based on the adjoint of that response. This has been incorporated into codes such as ADVANTG (based on MCNP) and the new sequence MAVRIC, which will be available in the next release of SCALE. In an effort to compute lower uncertainties everywhere in the problem, Larsen's group has also developed several methods to help distribute particles more evenly, based on forward estimates of flux. This paper focuses on the use of a forward estimate to weight the placement of the source in the adjoint calculation used by CADIS, which we refer to as a forward-weighted CADIS (FW-CADIS).« less

Assessment of the point-source method for estimating dose rates to members of the public from exposure to patients with 131I thyroid treatment

DOE PAGES

Dewji, Shaheen Azim; Bellamy, Michael B.; Hertel, Nolan E.; ...

2015-09-01

The U.S. Nuclear Regulatory Commission (USNRC) initiated a contract with Oak Ridge National Laboratory (ORNL) to calculate radiation dose rates to members of the public that may result from exposure to patients recently administered iodine-131 ( 131I) as part of medical therapy. The main purpose was to compare dose rate estimates based on a point source and target with values derived from more realistic simulations that considered the time-dependent distribution of 131I in the patient and attenuation of emitted photons by the patient’s tissues. The external dose rate estimates were derived using Monte Carlo methods and two representations of themore » Phantom with Movable Arms and Legs, previously developed by ORNL and the USNRC, to model the patient and a nearby member of the public. Dose rates to tissues and effective dose rates were calculated for distances ranging from 10 to 300 cm between the phantoms and compared to estimates based on the point-source method, as well as to results of previous studies that estimated exposure from 131I patients. The point-source method overestimates dose rates to members of the public in very close proximity to an 131I patient but is a broadly accurate method of dose rate estimation at separation distances of 300 cm or more at times closer to administration.« less

Probabilistic assessment method of the non-monotonic dose-responses-Part I: Methodological approach.

PubMed

Chevillotte, Grégoire; Bernard, Audrey; Varret, Clémence; Ballet, Pascal; Bodin, Laurent; Roudot, Alain-Claude

2017-08-01

More and more studies aim to characterize non-monotonic dose response curves (NMDRCs). The greatest difficulty is to assess the statistical plausibility of NMDRCs from previously conducted dose response studies. This difficulty is linked to the fact that these studies present (i) few doses tested, (ii) a low sample size per dose, and (iii) the absence of any raw data. In this study, we propose a new methodological approach to probabilistically characterize NMDRCs. The methodology is composed of three main steps: (i) sampling from summary data to cover all the possibilities that may be presented by the responses measured by dose and to obtain a new raw database, (ii) statistical analysis of each sampled dose-response curve to characterize the slopes and their signs, and (iii) characterization of these dose-response curves according to the variation of the sign in the slope. This method allows characterizing all types of dose-response curves and can be applied both to continuous data and to discrete data. The aim of this study is to present the general principle of this probabilistic method which allows to assess the non-monotonic dose responses curves, and to present some results. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preclinical Toxicological Evaluation of IDM01: The Botanical Composition of 4-Hydroxyisoleucine- and Trigonelline-based Standardized Fenugreek Seed Extract.

PubMed

Deshpande, Pallavi O; Mohan, Vishwaraman; Thakurdesai, Prasad Arvind

2017-01-01

To evaluate acute oral toxicity (AOT), subchronic (90-day repeated dose) toxicity, mutagenicity, and genotoxicity potential of IDM01, the botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek ( Trigonella foenum-graecum L) seed extract in laboratory rats. The AOT and subchronic (90-day repeated dose) toxicity were evaluated using Sprague-Dawley rats as per the Organisation for Economic Co-operation and Development (OECD) guidelines No. 423 and No. 408, respectively. During the subchronic study, the effects on body weight, food and water consumption, organ weights with hematology, clinical biochemistry, and histology were studied. The mutagenicity and genotoxicity of IDM01 were evaluated by reverse mutation assay (Ames test, OECD guideline No. 471) and chromosome aberration test (OECD guideline No. 473), respectively. The IDM01 did not show mortality or treatment-related adverse signs during acute (limit dose of 2000 mg/kg) and subchronic (90-day repeated dose of 250, 500, and 1000 mg/kg with 28 days of recovery period) administration. The IDM01 showed oral median lethal dose (LD50) >2000 mg/kg during AOT study. The no-observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg. IDM01 did not show mutagenicity up to a concentration of 5000 μg/plate during Ames test and did not induce structural chromosomal aberrations up to 50 mg/culture. IDM01 was found safe during preclinical acute and subchronic (90-day repeated dose) toxicity in rats without mutagenicity or genotoxicity. Acute oral toxicity, subchronic (90-day) oral toxicity, mutagenicity and genotoxicity of IDM01 (4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract) was evaluated.The median lethal dose, LD50, of IDM01 was more than 2000 mg/kg of body weight in rats.No observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg of body weight in rats.IDM01 was found safe during acute and subchronic oral toxicity studies in rats without mutagenicity or genotoxicity potetial. Abbreviations Used: 2-AA: 2-aminoanthracene; 2-AF: 2-aminofluorene; 4 NQNO: 4-nitroquinolene-N-oxide; 4HI: 4-hydroxyisoleucine; ANOVA: Analysis of variance; AOT: Acute oral toxicity; DM: Diabetes mellitus; IDM01: The Botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract; LD50: Median lethal dose; MMS: Methyl methanesulfonate; NAD: No abnormality detected; OECD: Organisation for Economic Co-operation and Development; SD: Standard deviation; UV: Ultraviolet; VC: Vehicle control. 2-AA: 2-aminoanthracene; 2-AF: 2-aminofluorene; 4 NQNO: 4-nitroquinolene-N-oxide; 4HI: 4-hydroxyisoleucine; ANOVA: Analysis of variance; AOT: Acute oral toxicity; DM: Diabetes mellitus; IDM01: The Botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract; LD50: Median lethal dose; MMS: Methyl methanesulfonate; NAD: No abnormality detected; OECD: Organisation for Economic Co-operation and Development; SD: Standard deviation; UV: Ultraviolet; VC: Vehicle control.

Preclinical Toxicological Evaluation of IDM01: The Botanical Composition of 4-Hydroxyisoleucine- and Trigonelline-based Standardized Fenugreek Seed Extract

PubMed Central

Deshpande, Pallavi O.; Mohan, Vishwaraman; Thakurdesai, Prasad Arvind

2017-01-01

Objective: To evaluate acute oral toxicity (AOT), subchronic (90-day repeated dose) toxicity, mutagenicity, and genotoxicity potential of IDM01, the botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek (Trigonella foenum-graecum L) seed extract in laboratory rats. Materials and Methods: The AOT and subchronic (90-day repeated dose) toxicity were evaluated using Sprague-Dawley rats as per the Organisation for Economic Co-operation and Development (OECD) guidelines No. 423 and No. 408, respectively. During the subchronic study, the effects on body weight, food and water consumption, organ weights with hematology, clinical biochemistry, and histology were studied. The mutagenicity and genotoxicity of IDM01 were evaluated by reverse mutation assay (Ames test, OECD guideline No. 471) and chromosome aberration test (OECD guideline No. 473), respectively. Results: The IDM01 did not show mortality or treatment-related adverse signs during acute (limit dose of 2000 mg/kg) and subchronic (90-day repeated dose of 250, 500, and 1000 mg/kg with 28 days of recovery period) administration. The IDM01 showed oral median lethal dose (LD50) >2000 mg/kg during AOT study. The no-observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg. IDM01 did not show mutagenicity up to a concentration of 5000 μg/plate during Ames test and did not induce structural chromosomal aberrations up to 50 mg/culture. Conclusions: IDM01 was found safe during preclinical acute and subchronic (90-day repeated dose) toxicity in rats without mutagenicity or genotoxicity. SUMMARY Acute oral toxicity, subchronic (90-day) oral toxicity, mutagenicity and genotoxicity of IDM01 (4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract) was evaluated.The median lethal dose, LD50, of IDM01 was more than 2000 mg/kg of body weight in rats.No observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg of body weight in rats.IDM01 was found safe during acute and subchronic oral toxicity studies in rats without mutagenicity or genotoxicity potetial. Abbreviations Used: 2-AA: 2-aminoanthracene; 2-AF: 2-aminofluorene; 4 NQNO: 4-nitroquinolene-N-oxide; 4HI: 4-hydroxyisoleucine; ANOVA: Analysis of variance; AOT: Acute oral toxicity; DM: Diabetes mellitus; IDM01: The Botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract; LD50: Median lethal dose; MMS: Methyl methanesulfonate; NAD: No abnormality detected; OECD: Organisation for Economic Co-operation and Development; SD: Standard deviation; UV: Ultraviolet; VC: Vehicle control. 2-AA: 2-aminoanthracene; 2-AF: 2-aminofluorene; 4 NQNO: 4-nitroquinolene-N-oxide; 4HI: 4-hydroxyisoleucine; ANOVA: Analysis of variance; AOT: Acute oral toxicity; DM: Diabetes mellitus; IDM01: The Botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract; LD50: Median lethal dose; MMS: Methyl methanesulfonate; NAD: No abnormality detected; OECD: Organisation for Economic Co-operation and Development; SD: Standard deviation; UV: Ultraviolet; VC: Vehicle control PMID:28539737

Feasibility of online IMPT adaptation using fast, automatic and robust dose restoration

NASA Astrophysics Data System (ADS)

Bernatowicz, Kinga; Geets, Xavier; Barragan, Ana; Janssens, Guillaume; Souris, Kevin; Sterpin, Edmond

2018-04-01

Intensity-modulated proton therapy (IMPT) offers excellent dose conformity and healthy tissue sparing, but it can be substantially compromised in the presence of anatomical changes. A major dosimetric effect is caused by density changes, which alter the planned proton range in the patient. Three different methods, which automatically restore an IMPT plan dose on a daily CT image were implemented and compared: (1) simple dose restoration (DR) using optimization objectives of the initial plan, (2) voxel-wise dose restoration (vDR), and (3) isodose volume dose restoration (iDR). Dose restorations were calculated for three different clinical cases, selected to test different capabilities of the restoration methods: large range adaptation, complex dose distributions and robust re-optimization. All dose restorations were obtained in less than 5 min, without manual adjustments of the optimization settings. The evaluation of initial plans on repeated CTs showed large dose distortions, which were substantially reduced after restoration. In general, all dose restoration methods improved DVH-based scores in propagated target volumes and OARs. Analysis of local dose differences showed that, although all dose restorations performed similarly in high dose regions, iDR restored the initial dose with higher precision and accuracy in the whole patient anatomy. Median dose errors decreased from 13.55 Gy in distorted plan to 9.75 Gy (vDR), 6.2 Gy (DR) and 4.3 Gy (iDR). High quality dose restoration is essential to minimize or eventually by-pass the physician approval of the restored plan, as long as dose stability can be assumed. Motion (as well as setup and range uncertainties) can be taken into account by including robust optimization in the dose restoration. Restoring clinically-approved dose distribution on repeated CTs does not require new ROI segmentation and is compatible with an online adaptive workflow.

The piecewise-linear dynamic attenuator reduces the impact of count rate loss with photon-counting detectors

NASA Astrophysics Data System (ADS)

Hsieh, Scott S.; Pelc, Norbert J.

2014-06-01

Photon counting x-ray detectors (PCXDs) offer several advantages compared to standard energy-integrating x-ray detectors, but also face significant challenges. One key challenge is the high count rates required in CT. At high count rates, PCXDs exhibit count rate loss and show reduced detective quantum efficiency in signal-rich (or high flux) measurements. In order to reduce count rate requirements, a dynamic beam-shaping filter can be used to redistribute flux incident on the patient. We study the piecewise-linear attenuator in conjunction with PCXDs without energy discrimination capabilities. We examined three detector models: the classic nonparalyzable and paralyzable detector models, and a ‘hybrid’ detector model which is a weighted average of the two which approximates an existing, real detector (Taguchi et al 2011 Med. Phys. 38 1089-102 ). We derive analytic expressions for the variance of the CT measurements for these detectors. These expressions are used with raw data estimated from DICOM image files of an abdomen and a thorax to estimate variance in reconstructed images for both the dynamic attenuator and a static beam-shaping (‘bowtie’) filter. By redistributing flux, the dynamic attenuator reduces dose by 40% without increasing peak variance for the ideal detector. For non-ideal PCXDs, the impact of count rate loss is also reduced. The nonparalyzable detector shows little impact from count rate loss, but with the paralyzable model, count rate loss leads to noise streaks that can be controlled with the dynamic attenuator. With the hybrid model, the characteristic count rates required before noise streaks dominate the reconstruction are reduced by a factor of 2 to 3. We conclude that the piecewise-linear attenuator can reduce the count rate requirements of the PCXD in addition to improving dose efficiency. The magnitude of this reduction depends on the detector, with paralyzable detectors showing much greater benefit than nonparalyzable detectors.

Gini estimation under infinite variance

NASA Astrophysics Data System (ADS)

Fontanari, Andrea; Taleb, Nassim Nicholas; Cirillo, Pasquale

2018-07-01

We study the problems related to the estimation of the Gini index in presence of a fat-tailed data generating process, i.e. one in the stable distribution class with finite mean but infinite variance (i.e. with tail index α ∈(1 , 2)). We show that, in such a case, the Gini coefficient cannot be reliably estimated using conventional nonparametric methods, because of a downward bias that emerges under fat tails. This has important implications for the ongoing discussion about economic inequality. We start by discussing how the nonparametric estimator of the Gini index undergoes a phase transition in the symmetry structure of its asymptotic distribution, as the data distribution shifts from the domain of attraction of a light-tailed distribution to that of a fat-tailed one, especially in the case of infinite variance. We also show how the nonparametric Gini bias increases with lower values of α. We then prove that maximum likelihood estimation outperforms nonparametric methods, requiring a much smaller sample size to reach efficiency. Finally, for fat-tailed data, we provide a simple correction mechanism to the small sample bias of the nonparametric estimator based on the distance between the mode and the mean of its asymptotic distribution.

Entropy vs. energy waveform processing: A comparison based on the heat equation

DOE PAGES

Hughes, Michael S.; McCarthy, John E.; Bruillard, Paul J.; ...

2015-05-25

Virtually all modern imaging devices collect electromagnetic or acoustic waves and use the energy carried by these waves to determine pixel values to create what is basically an “energy” picture. However, waves also carry “information”, as quantified by some form of entropy, and this may also be used to produce an “information” image. Numerous published studies have demonstrated the advantages of entropy, or “information imaging”, over conventional methods. The most sensitive information measure appears to be the joint entropy of the collected wave and a reference signal. The sensitivity of repeated experimental observations of a slowly-changing quantity may be definedmore » as the mean variation (i.e., observed change) divided by mean variance (i.e., noise). Wiener integration permits computation of the required mean values and variances as solutions to the heat equation, permitting estimation of their relative magnitudes. There always exists a reference, such that joint entropy has larger variation and smaller variance than the corresponding quantities for signal energy, matching observations of several studies. Moreover, a general prescription for finding an “optimal” reference for the joint entropy emerges, which also has been validated in several studies.« less

Two Topics in Seasonal Streamflow Forecasting: Soil Moisture Initialization Error and Precipitation Downscaling

NASA Technical Reports Server (NTRS)

Koster, Randal; Walker, Greg; Mahanama, Sarith; Reichle, Rolf

2012-01-01

Continental-scale offline simulations with a land surface model are used to address two important issues in the forecasting of large-scale seasonal streamflow: (i) the extent to which errors in soil moisture initialization degrade streamflow forecasts, and (ii) the extent to which the downscaling of seasonal precipitation forecasts, if it could be done accurately, would improve streamflow forecasts. The reduction in streamflow forecast skill (with forecasted streamflow measured against observations) associated with adding noise to a soil moisture field is found to be, to first order, proportional to the average reduction in the accuracy of the soil moisture field itself. This result has implications for streamflow forecast improvement under satellite-based soil moisture measurement programs. In the second and more idealized ("perfect model") analysis, precipitation downscaling is found to have an impact on large-scale streamflow forecasts only if two conditions are met: (i) evaporation variance is significant relative to the precipitation variance, and (ii) the subgrid spatial variance of precipitation is adequately large. In the large-scale continental region studied (the conterminous United States), these two conditions are met in only a somewhat limited area.

An accelerated dose escalation with a grass pollen allergoid is safe and well-tolerated: a randomized open label phase II trial.

PubMed

Chaker, A M; Al-Kadah, B; Luther, U; Neumann, U; Wagenmann, M

2015-01-01

The number of injections in the dose escalation of subcutaneous immunotherapy (SCIT) is small for some currently used hypoallergenic allergoids, but can still be inconvenient to patients and can impair compliance. The aim of this trial was to compare safety and tolerability of an accelerated to the conventional dose escalation scheme of a grass pollen allergoid. In an open label phase II trial, 122 patients were 1:1 randomized for SCIT using a grass pollen allergoid with an accelerated dose escalation comprising only 4 weekly injections (Group I) or a conventional dose escalation including 7 weekly injections (Group II). Safety determination included the occurrence of local and systemic adverse events. Tolerability was assessed by patients and physicians. Treatment-related adverse events were observed in 22 (36.1 %) patients in Group I and 15 (24.6 %) in Group II. Local reactions were reported by 18 patients in Group I and 11 in Group II. Five Grade 1 systemic reactions (WAO classification) were observed in Group I and 2 in Group II. Grade 2 reactions occurred 3 times in Group I and 2 times in Group II. Tolerability was rated as "good" or "very good" by 53 (86.9 %) patients in Group I and 59 (100 %) in Group II by investigators. Forty-eight patients in Group I (80.0 %) and 54 in Group II (91.5 %) rated tolerability as "good" or "very good". The dose escalation of a grass pollen allergoid can be accelerated with safety and tolerability profiles comparable to the conventional dose escalation.

Exploring the relationship between socioeconomic status, control beliefs and exercise behavior: a multiple mediator model.

PubMed

Murray, Terra C; Rodgers, Wendy M; Fraser, Shawn N

2012-02-01

The purpose of this study was to examine the relationship between control beliefs, socioeconomic status and exercise intentions and behavior. Specifically, we examined whether distal and proximal control beliefs mediated the association between socioeconomic status and exercise intentions and behavior. A one time, cross sectional mail out survey (N = 350) was conducted in a large urban Canadian city. Distal (i.e., personal constraints) and proximal (i.e., scheduling self-efficacy) control beliefs mediated the association between socioeconomic status and exercise, explaining approximately 30% of the variance. Proximal control beliefs (i.e., scheduling self-efficacy) partially mediated the association between socioeconomic status and intentions, with the models explaining approximately 50% of the variance. Compared to individuals with lower socioeconomic status, individuals with higher socioeconomic status reported more exercise and stronger intentions to exercise. This was at least partly because higher socioeconomic status respondents reported fewer barriers in their lives, and were more confident to cope with the scheduling demands of exercise.

Interspecies Extrapolations of Halocarbon Respiratory and Tissue Kinetics: Applications to Predicting Toxicity in Different Species

DTIC Science & Technology

1993-09-01

both routes of administration and for both po doses. Bioavailability, peak blood levels and the area-under-the-blood-concentration-time curves were also...Absorption of TET following oral administration was very rapid in rats and dogs, with peak blood levels achieved in both species and at both doses...I I I I [ I I I I I I I ournial ni ( Ilirioiainrtirphi . 0~ 12 00 A’ 1 199 󈧌 Elsevier Scienc~e Publishers BA.V. Anisterdamn CHROM 111. cooof

Effect of low-dose atropine administration on dobutamine dose requirement in horses anesthetized with detomidine and halothane.

PubMed

Weil, A B; Keegan, R D; Greene, S A

1997-12-01

To determine whether a low dose of atropine is associated with decreased requirement for cardiovascular supportive treatment in horses given detomidine prior to maintenance of general anesthesia with halothane. 3 groups of 10 healthy horses. Detomidine (20 micrograms/kg of body weight, i.m.) was administered to all 30 horses. Then, 10 horses received atropine (0.006 mg/kg, i.v.) 1 hour after detomidine administration, 10 horses received atropine (0.012 mg/kg, i.m.) at the time of detomidine administration, and 10 horses served as a control group. Heart rate was measured prior to detomidine administration and at fixed intervals throughout anesthesia. The dobutamine infusion rate necessary to maintain mean arterial blood pressure between 70 and 80 mm of Hg was recorded. Systemic blood pressures, end-tidal halothane, end-tidal CO2, and arterial blood gas tensions were measured at fixed intervals. Mean heart rate was higher among horses receiving atropine i.v. or i.m., compared with that in control horses. Horses that received atropine i.v. had higher systemic arterial blood pressure and required a lower dobutamine infusion rate than did horses of the other groups. Detomidine-treated, halothane-anesthetized horses given atropine i.v. required less dobutamine, compared with horses receiving or not receiving atropine i.m. Complications, such as colic and dysrhythmias, from use of higher doses of atropine, were not observed at this lower dose of atropine. i.v. administration of a low dose of atropine prior to induction of general anesthesia may result in improved blood pressure in horses that have received detomidine before anesthesia with halothane.

The Effect of Diagnostic Absorbed Doses from 131I on Human Thyrocytes in Vitro

PubMed Central

Adamczewski, Zbigniew; Stasiołek, Mariusz; Karwowski, Bolesław; Dedecjus, Marek; Orszulak-Michalak, Daria; Merecz, Anna; Śliwka, Przemysław W.; Puła, Bartosz; Lewiński, Andrzej

2015-01-01

Background: Administration of diagnostic activities of 131I, performed in order to detect thyroid remnants after surgery and/or thyroid cancer recurrence/metastases, may lead to reduction of iodine uptake. This phenomenon is called “thyroid stunning”. We estimated radiation absorbed dose-dependent changes in genetic material, in particular in sodium iodide symporter (NIS) gene promoter, and NIS protein level in human thyrocytes (HT). Materials and Methods: We used unmodified HT isolated from patients subjected to thyroidectomy exposed to 131I in culture. The different 131I activities applied were calculated to result in absorbed doses of 5, 10, and 20 Gy. Results: According to flow cytometry analysis and comet assay, 131I did not influence the HT viability in culture. Temporary increase of 8-oxo-dG concentration in HT directly after 24 h (p < 0.05) and increase in the number of AP-sites 72 h after termination of exposition to 20 Gy dose (p < 0.0001) were observed. The signs of dose-dependent DNA damage were not associated with essential changes in the NIS expression on mRNA and protein levels. Conclusions: Our observation constitutes a first attempt to evaluate the effect of the absorbed dose of 131I on HT. The results have not confirmed the theory that the “thyroid stunning” reduces the NIS protein synthesis. PMID:26132566

From total empiricism to a rational design of metronomic chemotherapy phase I dosing trials.

PubMed

Lam, Thomas; Hetherington, John W; Greenman, John; Maraveyas, Anthony

2006-02-01

'Metronomic chemotherapy' represents a novel anti-angiogenic strategy whereby low-dose chemotherapy is utilized in a continuous fashion in order to target tumor endothelium. There are many potential advantages of this strategy and clinical trials are already underway. However, although the scheduling of metronomic chemotherapy is relatively unequivocal, metronomic dosing principles are at present poorly defined. Arbitrarily, 10-33% of the maximum tolerated dose comprises 'the dose range'. We argue that this is too empirical and propose a set of phase I metronomic chemotherapy dosing strategies based on a principled approach which may help to reduce the problem of empiricism in dosing for metronomic chemotherapy trials.

Assessment of intake and internal dose from iodine-131 for exposed workers handling radiopharmaceutical products.

PubMed

Bitar, A; Maghrabi, M; Doubal, A W

2013-12-01

Two methods for determination of internal dose due to (131)I intake during the preparation and handling of iodine radiopharmaceutical products have been compared. The first method was based on the measurement of (131)I in 24-hour urine samples while the second method was based on the measurement in vivo of (131)I in thyroid. The results have shown that urine analysis method can be used as a screening test but not for internal dose assessment of exposed workers. Thyroid monitoring method was found to be more reliable and accurate method for assessing internal dose from (131)I intake. In addition, the assessed internal dose showed that the annual internal effective dose for some workers was below 1 mSv with no risk classification, whereas the results of other group of workers were between 1 and 6 mSv with low risk classification. Only one worker reached 7.66 mSv with high risk classification; and this worker must be monitored individually. © 2013 Elsevier Ltd. All rights reserved.

Impact of the Lok-bar for High-precision Radiotherapy with Tomotherapy.

PubMed

Hirata, Makoto; Monzen, Hajime; Tamura, Mikoto; Kubo, Kazuki; Matsumoto, Kenji; Hanaoka, Kohei; Okumura, Masahiko; Nishimura, Yasumasa

2018-05-01

Patient immobilization systems are used to establish a reproducible patient position relative to the couch. In this study, the impact of conventional lok-bars for CT-simulation (CIVCO-bar) and treatment (iBEAM-bar) were compared with a novel lok-bar (mHM-bar) in tomotherapy. Verification was obtained as follows: i. artifacts in CT images; ii. dose attenuation rate of lok-bar, compared to without lok-bar; and iii. dose differences between the calculated and measured absorbed doses. With the CIVCO-bar, there were obvious metal artifacts, while there were nearly no artifacts with the mHM-bar. The mean dose attenuation rates with the mHM-bar and iBEAM-bar were 1.31% and 2.28%, and the mean dose difference was 1.55% and 1.66% for mHM-bar and iBEAM-bar. Using the mHM-bar reduced artifacts on the CT image and improved dose attenuation are obtained. The lok-bar needs to be inserted as a structure set in treatment planning with tomotherapy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Assessing the uncertainty in a normal tissue complication probability difference (∆NTCP): radiation-induced liver disease (RILD) in liver tumour patients treated with proton vs X-ray therapy

PubMed Central

Kobashi, Keiji; Kimoto, Takuya; Toramatsu, Chie; Dekura, Yasuhiro; Katoh, Norio; Shimizu, Shinichi; Ito, Yoichi M; Shirato, Hiroki

2018-01-01

Abstract Modern radiotherapy technologies such as proton beam therapy (PBT) permit dose escalation to the tumour and minimize unnecessary doses to normal tissues. To achieve appropriate patient selection for PBT, a normal tissue complication probability (NTCP) model can be applied to estimate the risk of treatment-related toxicity relative to X-ray therapy (XRT). A methodology for estimating the difference in NTCP (∆NTCP), including its uncertainty as a function of dose to normal tissue, is described in this study using the Delta method, a statistical method for evaluating the variance of functions, considering the variance–covariance matrix. We used a virtual individual patient dataset of radiation-induced liver disease (RILD) in liver tumour patients who were treated with XRT as a study model. As an alternative option for individual patient data, dose-bin data, which consists of the number of patients who developed toxicity in each dose level/bin and the total number of patients in that dose level/bin, are useful for multi-institutional data sharing. It provides comparable accuracy with individual patient data when using the Delta method. With reliable NTCP models, the ∆NTCP with uncertainty might potentially guide the use of PBT; however, clinical validation and a cost-effectiveness study are needed to determine the appropriate ∆NTCP threshold. PMID:29538699

Nonclinical pharmacokinetic and pharmacodynamic characterisation of somapacitan: A reversible non-covalent albumin-binding growth hormone.

PubMed

Thygesen, Peter; Andersen, Henrik Sune; Behrens, Carsten; Fels, Johannes Josef; Nørskov-Lauritsen, Leif; Rischel, Christian; Johansen, Nils Langeland

2017-08-01

Somapacitan is an albumin-binding growth hormone derivative intended for once weekly administration, currently in clinical development for treatment of adult as well as juvenile GH deficiency. Nonclinical in vivo pharmacological characterisation of somapacitan was performed to support the clinical trials. Here we present the pharmacokinetic and pharmacodynamic effects of somapacitan in rats, minipigs, and cynomolgus monkeys. Pharmacokinetic studies investigating exposure, absorption, clearance, and bioavailability after single intravenous (i.v.) and subcutaneous (s.c.) administration were performed in all species. A dose-response study with five dose levels and a multiple dose pharmacodynamic study with four once weekly doses was performed in hypophysectomised rats to evaluate the effect of somapacitan on growth and IGF-I production. Pharmacokinetic profiles indicated first order absorption from the subcutaneous tissue after s.c. injections for somapacitan in all three species. Apparent terminal half-lives were 5-6h in rats, 10-12h in minipigs, and 17-20h in monkeys. Somapacitan induced a dose-dependent growth in hypophysectomised rats (p<0.001) and an increase in plasma IGF-I levels in rats (p<0.01), minipigs (p<0.01), and cynomolgus monkeys (p<0.05) after single dose administration. Multiple once weekly dosing of somapacitan in hypophysectomised rats induced a step-wise increase in body weight with an initial linear phase the first 3-4days in each dosing interval (p<0.001). The nonclinical pharmacokinetic and pharmacodynamic studies of somapacitan showed similar pharmacokinetic properties, with no absorption-limited elimination, increased clearance and increased and sustained levels of IGF-I in plasma for up to 10days after a single dose administration in all three species. Somapacitan induced a dose-dependent increase in body weight and IGF-I levels in hypophysectomised rats. Multiple dosing of somapacitan in hypophysectomised rats suggested a linear growth for the first 3-4days in each weekly dosing interval, whereas daily hGH dosing showed linear growth for approximately two weeks before reaching a plateau level. Copyright © 2017 Elsevier Ltd. All rights reserved.

No effect on QT intervals of mipomersen, a 2'-O-methoxyethyl modified antisense oligonucleotide targeting ApoB-100 mRNA, in a phase I dose escalation placebo-controlled study, and confirmed by a thorough QT (tQT) study, in healthy subjects.

PubMed

Yu, Rosie Z; Gunawan, Rudy; Li, Zhaoyang; Mittleman, Robert S; Mahmood, Asif; Grundy, John S; Singleton, Walter; Geary, Richard; Wang, Yanfeng

2016-03-01

The aim of this study to evaluate the effect of mipomersen on QT intervals in a phase I dose escalation, placebo-controlled study, and a thorough QT (tQT) study in healthy subjects. In the initial phase I study, 29 healthy subjects received either single or multiple (for 4 weeks) ascending doses of mipomersen (50-400 mg) administered subcutaneously (SC) or via a 2-h intravenous (IV) infusion, and 7 subjects received placebo. In the confirmative tQT study, 58 healthy subjects received placebo, 400 mg IV moxifloxacin, 200 mg SC, or 200 mg IV of mipomersen in a double-blind, 4-way crossover design with a minimum 5-day washout between treatments. ECG measurements were performed at baseline and selected time points (including Tmax). The correlation between QTcF intervals corrected for baseline and time-matched placebo when available with PK plasma exposure was evaluated by linear regression analysis. In the phase I study, no positive correlation between the PK exposure and ∆QTcF or ∆∆QTcF was observed within the wide dose or exposure range tested. Similar results were observed in the tQT study, where the predicted ΔΔQTcF and its upper bound of the 90% CI at Cmax of therapeutic and supratherapeutic dose were approximately -1.7 and 2.9 ms, respectively. Mipomersen showed no effect on QT intervals in both the phase I dose escalation study and the tQT study. These results support the proposal that QT assessment can be made in a phase I dose escalation study, and no tQT study may be necessary if the phase I dose escalation study showed a negative QT effect.

Detecting structural variances of Co 3O 4 catalysts by controlling beam-induced sample alterations in the vacuum of a transmission electron microscope

DOE PAGES

Kisielowski, C.; Frei, H.; Specht, P.; ...

2016-11-02

This article summarizes core aspects of beam-sample interactions in research that aims at exploiting the ability to detect single atoms at atomic resolution by mid-voltage transmission electron microscopy. Investigating the atomic structure of catalytic Co 3O 4 nanocrystals underscores how indispensable it is to rigorously control electron dose rates and total doses to understand native material properties on this scale. We apply in-line holography with variable dose rates to achieve this goal. Genuine object structures can be maintained if dose rates below ~100 e/Å 2s are used and the contrast required for detection of single atoms is generated by capturing largemore » image series. Threshold doses for the detection of single atoms are estimated. An increase of electron dose rates and total doses to common values for high resolution imaging of solids stimulates object excitations that restructure surfaces, interfaces, and defects and cause grain reorientation or growth. We observe a variety of previously unknown atom configurations in surface proximity of the Co 3O 4 spinel structure. These are hidden behind broadened diffraction patterns in reciprocal space but become visible in real space by solving the phase problem. Finallly, an exposure of the Co 3O 4 spinel structure to water vapor or other gases induces drastic structure alterations that can be captured in this manner.« less

A comparison study on various low energy sources in interstitial prostate brachytherapy

PubMed Central

Bakhshabadi, Mahdi; Ghorbani, Mahdi; Knaup, Courtney; Meigooni, Ali S.

2016-01-01

Purpose Low energy sources are routinely used in prostate brachytherapy. 125I is one of the most commonly used sources. Low energy 131Cs source was introduced recently as a brachytherapy source. The aim of this study is to compare dose distributions of 125I, 103Pd, and 131Cs sources in interstitial brachytherapy of prostate. Material and methods ProstaSeed 125I brachytherapy source was simulated using MCNPX Monte Carlo code. Additionally, two hypothetical sources of 103Pd and 131Cs were simulated with the same geometry as the ProstaSeed 125I source, while having their specific emitted gamma spectra. These brachytherapy sources were simulated with distribution of forty-eight seeds in a phantom including prostate. The prostate was considered as a sphere with radius of 1.5 cm. Absolute and relative dose rates were obtained in various distances from the source along the transverse and longitudinal axes inside and outside the tumor. Furthermore, isodose curves were plotted around the sources. Results Analyzing the initial dose profiles for various sources indicated that with the same time duration and air kerma strength, 131Cs delivers higher dose to tumor. However, relative dose rate inside the tumor is higher and outside the tumor is lower for the 103Pd source. Conclusions The higher initial absolute dose in cGy/(h.U) of 131Cs brachytherapy source is an advantage of this source over the others. The higher relative dose inside the tumor and lower relative dose outside the tumor for the 103Pd source are advantages of this later brachytherapy source. Based on the total dose the 125I source has advantage over the others due to its longer half-life. PMID:26985200

A comparison study on various low energy sources in interstitial prostate brachytherapy.

PubMed

Bakhshabadi, Mahdi; Ghorbani, Mahdi; Khosroabadi, Mohsen; Knaup, Courtney; Meigooni, Ali S

2016-02-01

Low energy sources are routinely used in prostate brachytherapy. (125)I is one of the most commonly used sources. Low energy (131)Cs source was introduced recently as a brachytherapy source. The aim of this study is to compare dose distributions of (125)I, (103)Pd, and (131)Cs sources in interstitial brachytherapy of prostate. ProstaSeed (125)I brachytherapy source was simulated using MCNPX Monte Carlo code. Additionally, two hypothetical sources of (103)Pd and (131)Cs were simulated with the same geometry as the ProstaSeed (125)I source, while having their specific emitted gamma spectra. These brachytherapy sources were simulated with distribution of forty-eight seeds in a phantom including prostate. The prostate was considered as a sphere with radius of 1.5 cm. Absolute and relative dose rates were obtained in various distances from the source along the transverse and longitudinal axes inside and outside the tumor. Furthermore, isodose curves were plotted around the sources. Analyzing the initial dose profiles for various sources indicated that with the same time duration and air kerma strength, (131)Cs delivers higher dose to tumor. However, relative dose rate inside the tumor is higher and outside the tumor is lower for the (103)Pd source. The higher initial absolute dose in cGy/(h.U) of (131)Cs brachytherapy source is an advantage of this source over the others. The higher relative dose inside the tumor and lower relative dose outside the tumor for the (103)Pd source are advantages of this later brachytherapy source. Based on the total dose the (125)I source has advantage over the others due to its longer half-life.

Simultaneously optimizing dose and schedule of a new cytotoxic agent.

PubMed

Braun, Thomas M; Thall, Peter F; Nguyen, Hoang; de Lima, Marcos

2007-01-01

Traditionally, phase I clinical trial designs are based upon one predefined course of treatment while varying among patients the dose given at each administration. In actual medical practice, patients receive a schedule comprised of several courses of treatment, and some patients may receive one or more dose reductions or delays during treatment. Consequently, the overall risk of toxicity for each patient is a function of both actual schedule of treatment and the differing doses used at each adminstration. Our goal is to provide a practical phase I clinical trial design that more accurately reflects actual medical practice by accounting for both dose per administration and schedule. We propose an outcome-adaptive Bayesian design that simultaneously optimizes both dose and schedule in terms of the overall risk of toxicity, based on time-to-toxicity outcomes. We use computer simulation as a tool to calibrate design parameters. We describe a phase I trial in allogeneic bone marrow transplantation that was designed and is currently being conducted using our new method. Our computer simulations demonstrate that our method outperforms any method that searches for an optimal dose but does not allow schedule to vary, both in terms of the probability of identifying optimal (dose, schedule) combinations, and the numbers of patients assigned to those combinations in the trial. Our design requires greater sample sizes than those seen in traditional phase I studies due to the larger number of treatment combinations examined. Our design also assumes that the effects of multiple administrations are independent of each other and that the hazard of toxicity is the same for all administrations. Our design is the first for phase I clinical trials that is sufficiently flexible and practical to truly reflect clinical practice by varying both dose and the timing and number of administrations given to each patient.

Somapacitan, a once-weekly reversible albumin-binding GH derivative, in children with GH deficiency: A randomized dose-escalation trial.

PubMed

Battelino, Tadej; Rasmussen, Michael Højby; De Schepper, Jean; Zuckerman-Levin, Nehama; Gucev, Zoran; Sävendahl, Lars

2017-10-01

To evaluate the safety, local tolerability, pharmacodynamics and pharmacokinetics of escalating single doses of once-weekly somapacitan, a reversible, albumin-binding GH derivative, vs once-daily GH in children with GH deficiency (GHD). Phase 1, randomized, open-label, active-controlled, dose-escalation trial (NCT01973244). Thirty-two prepubertal GH-treated children with GHD were sequentially randomized 3:1 within each of four cohorts to a single dose of somapacitan (0.02, 0.04, 0.08 and 0.16 mg/kg; n=6 each), or once-daily Norditropin ® SimpleXx ® (0.03 mg/kg; n=2 each) for 7 days. Pharmacokinetic and pharmacodynamic profiles were assessed. Adverse events were all mild, and there were no apparent treatment-dependent patterns in type or frequency. Four mild transient injection site reactions were reported in three of 24 children treated with somapacitan. No antisomapacitan/anti-human growth hormone (hGH) antibodies were detected. Mean serum concentrations of somapacitan increased in a dose-dependent but nonlinear manner: maximum concentration ranged from 21.8 ng/mL (0.02 mg/kg dose) to 458.4 ng/mL (0.16 mg/kg dose). IGF-I and IGFBP-3, and change from baseline in IGF-I standard deviation score (SDS) and IGFBP-3 SDS, increased dose dependently; greatest changes in SDS values were seen for 0.16 mg/kg. IGF-I SDS values were between -2 and +2 SDS, except for peak IGF-I SDS with 0.08 mg/kg somapacitan. Postdosing, IGF-I SDS remained above baseline levels for at least 1 week. Single doses of once-weekly somapacitan (0.02-0.16 mg/kg) were well tolerated in children with GHD, with IGF-I profiles supporting a once-weekly treatment profile. No clinically significant safety/tolerability signals or immunogenicity concerns were identified. © 2017 The Authors. Clinical Endocrinology Published by John Wiley & Sons Ltd.

Phase I North Central Cancer Treatment Group Trial-N9923 of escalating doses of twice-daily thoracic radiation therapy with amifostine and with alternating chemotherapy in limited stage small-cell lung cancer

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

Garces, Yolanda I.; Okuno, Scott H.; Schild, Steven E.

Purpose: The primary goal was to identify the maximum tolerable dose (MTD) of thoracic radiation therapy (TRT) that can be given with chemotherapy and amifostine for patients with limited-stage small-cell lung cancer (LSCLC). Methods and Materials: Treatment began with two cycles of topotecan (1 mg/m{sup 2}) Days 1 to 5 and paclitaxel (175 mg/m{sup 2}) Day 5 (every 3 weeks) given before and after TRT. The TRT began at 6 weeks. The TRT was given in 120 cGy fractions b.i.d. and the dose escalation (from 4,800 cGy, dose level 1, to 6,600 cGy, dose level 4) followed the standard 'cohortsmore » of 3' design. The etoposide (E) (50 mg/day) and cisplatin (C) (3 mg/m{sup 2}) were given i.v. before the morning TRT and amifostine (500 mg/day) was given before the afternoon RT. This was followed by prophylactic cranial irradiation (PCI). The dose-limiting toxicities (DLTs) were defined as Grade {>=}4 hematologic, febrile neutropenia, esophagitis, or other nonhematologic toxicity, Grade {>=}3 dyspnea, or Grade {>=}2 pneumonitis. Results: Fifteen patients were evaluable for the Phase I portion of the trial. No DLTs were seen at dose levels 1 and 2. Two patients on dose level 4 experienced DLTs: 1 patient had a Grade 4 pneumonitis, dyspnea, fatigue, hypokalemia, and anorexia, and 1 patient had a Grade 5 hypoxia attributable to TRT. One of 6 patients on dose level 3 had a DLT, Grade 3 esophagitis. The Grade {>=}3 toxicities seen in at least 10% of patients during TRT were esophagitis (53%), leukopenia (33%), dehydration (20%), neutropenia (13%), and fatigue (13%). The median survival was 14.5 months. Conclusion: The MTD of b.i.d. TRT was 6000 cGy (120 cGy b.i.d.) with EP and amifostine.« less

Joint Adaptive Mean-Variance Regularization and Variance Stabilization of High Dimensional Data.

PubMed

Dazard, Jean-Eudes; Rao, J Sunil

2012-07-01

The paper addresses a common problem in the analysis of high-dimensional high-throughput "omics" data, which is parameter estimation across multiple variables in a set of data where the number of variables is much larger than the sample size. Among the problems posed by this type of data are that variable-specific estimators of variances are not reliable and variable-wise tests statistics have low power, both due to a lack of degrees of freedom. In addition, it has been observed in this type of data that the variance increases as a function of the mean. We introduce a non-parametric adaptive regularization procedure that is innovative in that : (i) it employs a novel "similarity statistic"-based clustering technique to generate local-pooled or regularized shrinkage estimators of population parameters, (ii) the regularization is done jointly on population moments, benefiting from C. Stein's result on inadmissibility, which implies that usual sample variance estimator is improved by a shrinkage estimator using information contained in the sample mean. From these joint regularized shrinkage estimators, we derived regularized t-like statistics and show in simulation studies that they offer more statistical power in hypothesis testing than their standard sample counterparts, or regular common value-shrinkage estimators, or when the information contained in the sample mean is simply ignored. Finally, we show that these estimators feature interesting properties of variance stabilization and normalization that can be used for preprocessing high-dimensional multivariate data. The method is available as an R package, called 'MVR' ('Mean-Variance Regularization'), downloadable from the CRAN website.

Joint Adaptive Mean-Variance Regularization and Variance Stabilization of High Dimensional Data

PubMed Central

Dazard, Jean-Eudes; Rao, J. Sunil

2012-01-01

The paper addresses a common problem in the analysis of high-dimensional high-throughput “omics” data, which is parameter estimation across multiple variables in a set of data where the number of variables is much larger than the sample size. Among the problems posed by this type of data are that variable-specific estimators of variances are not reliable and variable-wise tests statistics have low power, both due to a lack of degrees of freedom. In addition, it has been observed in this type of data that the variance increases as a function of the mean. We introduce a non-parametric adaptive regularization procedure that is innovative in that : (i) it employs a novel “similarity statistic”-based clustering technique to generate local-pooled or regularized shrinkage estimators of population parameters, (ii) the regularization is done jointly on population moments, benefiting from C. Stein's result on inadmissibility, which implies that usual sample variance estimator is improved by a shrinkage estimator using information contained in the sample mean. From these joint regularized shrinkage estimators, we derived regularized t-like statistics and show in simulation studies that they offer more statistical power in hypothesis testing than their standard sample counterparts, or regular common value-shrinkage estimators, or when the information contained in the sample mean is simply ignored. Finally, we show that these estimators feature interesting properties of variance stabilization and normalization that can be used for preprocessing high-dimensional multivariate data. The method is available as an R package, called ‘MVR’ (‘Mean-Variance Regularization’), downloadable from the CRAN website. PMID:22711950

Three different up-titration regimens of ponesimod, an S1P1 receptor modulator, in healthy subjects.

PubMed

Scherz, Michael W; Brossard, Patrick; D'Ambrosio, Daniele; Ipek, Murat; Dingemanse, Jasper

2015-06-01

Ponesimod is a selective S1P1 receptor modulator, and induces dose-dependent reduction of circulating lymphocytes upon oral dosing. Previous studies showed that single doses up to 75 mg or multiple doses up to 40 mg once daily are well tolerated, and heart rate (HR) reduction and atrio-ventricular conduction delays upon treatment initiation are reduced by gradual up-titration to the maintenance dose. This single-center, open-label, randomized, multiple-dose, 3-treatment, 3-way crossover study compared the tolerability, safety, pharmacokinetics, cardiodynamics, and effects on lymphocytes of 3 different up-titration regimens of ponesimod in healthy male and female subjects. Up-titration regimens comprised escalating periods of b.i.d. dosing (2.5 or 5 mg) and q.d. dosing (10 or 20 mg or both). After the third up-titration period a variable-duration washout period of 1-3 days was followed by re-challenge with a single 20-mg dose of ponesimod. Adverse events were transient and mild to moderate in intensity, not different between regimens. HR decrease after the first dose was greater than after all subsequent doses, including up-titration doses. Little or no HR change was observed with morning doses of b.i.d. regimens, suggesting that 2.5 and 5 mg b.i.d. are sufficient to sustain cardiac desensitization for the 12-hours dosing interval. © 2015, The American College of Clinical Pharmacology.

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

Morrison, H; Menon, G; Sloboda, R

The purpose of this study was to investigate the accuracy of radiochromic film calibration procedures used in external beam radiotherapy when applied to I-125 brachytherapy sources delivering higher doses, and to determine any necessary modifications to achieve similar accuracy in absolute dose measurements. GafChromic EBT3 film was used to measure radiation doses upwards of 35 Gy from 6 MV, 75 kVp and (∼28 keV) I-125 photon sources. A custom phantom was used for the I-125 irradiations to obtain a larger film area with nearly constant dose to reduce the effects of film heterogeneities on the optical density (OD) measurements. RGBmore » transmission images were obtained with an Epson 10000XL flatbed scanner, and calibration curves relating OD and dose using a rational function were determined for each colour channel and at each energy using a non-linear least square minimization method. Differences found between the 6 MV calibration curve and those for the lower energy sources are large enough that 6 MV beams should not be used to calibrate film for low-energy sources. However, differences between the 75 kVp and I-125 calibration curves were quite small; indicating that 75 kVp is a good choice. Compared with I-125 irradiation, this gives the advantages of lower type B uncertainties and markedly reduced irradiation time. To obtain high accuracy calibration for the dose range up to 35 Gy, two-segment piece-wise fitting was required. This yielded absolute dose measurement accuracy above 1 Gy of ∼2% for 75 kVp and ∼5% for I-125 seed exposures.« less

The effect of different bleaching wavelengths on the sensitivity of Al{sub 2}O{sub 3}:C optically stimulated luminescence detectors (OSLDs) exposed to 6 MV photon beams

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

Omotayo, Azeez A.; Cygler, Joanna E.; Sawakuchi, Gabriel O.

2012-09-15

Purpose: To determine the effect of different bleaching wavelengths on the response of Al{sub 2}O{sub 3}:C optically stimulated luminescence detectors (OSLDs) exposed to accumulated doses of 6 MV photon beams. Methods: In this study the authors used nanoDot OSLDs readout with a MicroStar reader. The authors first characterized the dose-response, fading, and OSL signal loss of OSLDs exposed to doses from 0.5 to 10 Gy. To determine the effect of different bleaching wavelengths on the OSLDs' response, the authors optically treated the OSLDs with 26 W fluorescent lamps in two modes: (i) directly under the lamps for 10, 120, andmore » 600 min and (ii) with a long-pass filter for 55, 600, and 2000 min. Changes in the OSLDs' sensitivity were determined for an irradiation-readout-bleaching-readout cycle after irradiations with 1 and 10 Gy dose fractions. Results: The OSLDs presented supralinearity for doses of 2 Gy and above. The signal loss rates for sequential readouts were (0.287 {+-} 0.007)% per readout in the reader's strong-stimulation mode, and (0.019 {+-} 0.002)% and (0.035 {+-} 0.007)% per readout for doses of 0.2 and 10 Gy, respectively, in the reader's weak-stimulation mode. Fading half-life values ranged from (0.98 {+-} 0.14) min to (1.77 {+-} 0.24) min and fading showed dose dependence for the first 10-min interval. For 10 and 55 min bleaching using modes (i) and (ii), the OSL signal increased 14% for an accumulated dose of 7 Gy (1 Gy fractions). For OSLDs exposed to 10 Gy fractions, the OSL signal increased 30% and 25% for bleaching modes (i) and (ii) and accumulated dose of 70 Gy, respectively. For 120 and 600 min bleaching using modes (i) and (ii), the OSL signal increased 2.7% and 1.5% for an accumulated dose of 7 Gy (1 Gy fractions), respectively. For 10 Gy fractions, the signal increased 14% for bleaching mode (i) (120 min bleaching) and decreased 1.3% for bleaching mode (ii) (600 min bleaching) for an accumulated dose of 70 Gy. For 600 and 2000 min bleaching using modes (i) and (ii), the signal increased 2.3% and 1.8% for an accumulated dose of 7 Gy (1 Gy fractions), respectively. For 10 Gy fractions, the signal increased 10% for mode (i) (600 min bleaching) and decreased 2.5% for mode (ii) (2000 min bleaching) for an accumulated dose of 70 Gy. Conclusions: The dose-response of nanoDot OSLDs read using the MicroStar reader presented supralinearity for doses of 2 Gy and above. The signal loss as a function of sequential readouts depended on dose. Fading also depended on dose for the first 10-min interval. For dose fractions of 1 and 10 Gy, OSLDs may be reused within 3% and 5% accuracies up to the maximum accumulated dose of 7 and 70 Gy investigated in this study, respectively. These accuracies were obtained after the OSLDs were bleached with a light source with wavelengths above about 495 nm. The authors also concluded that changes in sensitivity of OSLDs depended on bleaching time, accumulated dose, and wavelength spectrum of the bleaching source.« less

Efficient production of therapeutic doses of [131I]-metaiodobenzylguanidine for clinical use.

PubMed

Prabhakar, G; Mathur, Anupam; Shunmugam, G; Teje, Y D; Sachdev, S S; Sivaprasad, N

2011-01-01

[(131)I]-metaiodobenzylguanidine (mIBG) is a known radiopharmaceutical used for the treatment of neuroendocrine tumors. The development of therapeutic [(131)I]-mIBG doses at production level is highly challenging due to rapid product degradation and high radiation exposures to the production plant personnel. In the present work, a working module for the production of 10 doses (100 mCi each) in a single operation was developed following copper (I) assisted isotope exchange. The labeled product complies with the pharmaceutical specifications suitable for in-vivo patient use. Copyright © 2010 Elsevier Ltd. All rights reserved.

A prospective, within-patient, crossover study of continuous intravenous and subcutaneous morphine for chronic cancer pain.

PubMed

Nelson, K A; Glare, P A; Walsh, D; Groh, E S

1997-05-01

The dose, efficacy, and side effects of continuous intravenous infusion (CIVI) of morphine were compared with continuous subcutaneous infusion (CSCI) of morphine in patients with chronic cancer pain. Eligible patients were referred to the Palliative Care Program and were receiving a stable dose of CIVI of morphine. The design was a within-patient, one-way crossover; in which each patient provided data before and after a switch from CIVI to CSCI of morphine. "Rescue" doses were 50% of the hourly dose given every 2 hours as needed. Morphine was infused intravenously (i.v.) and subcutaneously (s.c.) via a McGaw/AccuPro Volumetric Infusion Pump. After baseline data, including side effects and pain assessment, were obtained, patients were evaluated twice daily for toxicity and analgesic efficacy. Those who had a stable CIVI dose for 48 consecutive hr were crossed over to the CSCI at the same dose as the intravenous (i.v.) phase. A stable dose was defined as no dose change, four or less rescue doses in the previous 24 hr, and a pain rating of none or mild. CIVI was considered equal to CSCI if these criteria were maintained for 96 consecutive hr. Fifty-seven patients were entered, and 40 were evaluable (15 women and 25 men). The median age was 67 (range 30-83 years). All 40 participants, after maintaining a stable dose throughout the i.v. phase, crossed to the s.c. phase and remained on s.c. for at least 48 hr. Thirty-two patients maintained a stable dose throughout the i.v. and s.c. phases. The mean stable i.v. dose (day 2) was 5.05 mg/hr, and the mean stable s.c. dose (day 4) was 5.7 mg/hr (P = 0.01). The mean number of rescue doses on day 2 was 0.83 per 24 hr versus 0.80 per 24 hours on day 4 (P = 0.6). The mean categorical pain score on day 2 was 0.83, and on day 4, 0.85 (P = 0.7). The mean visual analogue scale (VAS) on day 2 was 22.9 mm versus 17.6 mm on day 4 (P = 0.1). The mean incidence of side effects on day 2 was 1.7, and on day 4, 2.0 (P = 0.2). No patient was withdrawn or had a dose reduction due to unacceptable toxicity. There were two reports of local toxicity (mild erythema) at the SC needle insertion point, which required a site change. All of our 40 patients had adequate pain control with CIVI and CSCI morphine. Of the eight participants who were not maintained on the same i.v. and s.c. dose, all had adequate pain control and a similar side-effect profile on a higher s.c. morphine dose. These data suggest that the i.v. and s.c. routes are equianalgesic for most patients when administered as a continuous infusion. Pain control and side-effect profiles are quite similar and acceptable. s.c. morphine is an excellent alternative to i.v. morphine in both inpatients and outpatients requiring parenteral morphine for pain.

A Phase I study of bizelesin (NSC 615291) in patients with advanced solid tumors.

PubMed

Pitot, Henry C; Reid, Joel M; Sloan, Jeff A; Ames, Matthew M; Adjei, Alex A; Rubin, Joseph; Bagniewski, Pamela G; Atherton, Pamela; Rayson, Daniel; Goldberg, Richard M; Erlichman, Charles

2002-03-01

To evaluate the toxicities, characterize the pharmacokinetics, and determine the maximum-tolerated dose of bizelesin administered once every 4 weeks. Patients with advanced solid tumors received escalating doses of bizelesin as an i.v. push every 4 weeks. Pharmacokinetic studies were performed with the first treatment cycle. Nineteen eligible patients received a total of 54 courses of bizelesin at doses ranging from 0.1 to 1 microg/m(2). Dose-limiting toxicity of neutropenia was seen in 2 of 4 patients treated at the 1 microg/m(2) dose level. Nonhematological toxicity was generally mild with maximum toxicity being

Multiple Choice Test Bias Uncovered by Use of an "I Don't Know" Alternative.

ERIC Educational Resources Information Center

Sherman, Susan W.

The multiple-choice science exercises used by the National Assessment of Educational Progress include an "I Don't Know" (IDK) alternative to estimate more accurately knowledge of groups of respondents. Group percentages of IDK responses were examined and compared with correct responses to see if the IDK introduces bias. Variance common…

43 CFR 3279.10 - When may I request a variance from BLM requirements pertaining to utilization operations?

Code of Federal Regulations, 2014 CFR

2014-10-01

... Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) GEOTHERMAL RESOURCE LEASING Utilization Relief and Appeals § 3279.10 When may I request a... request must include enough information to explain: (1) Why you cannot comply with the requirements; and...

Robust Algorithms for Detecting a Change in a Stochastic Process with Infinite Memory

DTIC Science & Technology

1988-03-01

breakdown point and the additional assumption of 0-mixing on the nominal meas- influence function . The structure of the optimal algorithm ures. Then Huber’s...are i.i.d. sequences of Gaus- For the breakdown point and the influence function sian random variables, with identical variance o2 . Let we will use...algebraic sign for i=0,1. Here z will be chosen such = f nthat it leads to worst case or earliest breakdown. i (14) Next, the influence function measures

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

A Long-Acting Human Growth Hormone With Delayed Clearance (VRS-317): Results of a Double-Blind, Placebo-Controlled, Single Ascending Dose Study in Growth Hormone–Deficient Adults

PubMed Central

Yuen, Kevin C. J.; Conway, Gerard S.; Popovic, Vera; Merriam, George R.; Bailey, Timothy; Hamrahian, Amir H.; Biller, Beverly M. K.; Kipnes, Mark; Moore, Jerome A.; Humphriss, Eric; Cleland, Jeffrey L.

2013-01-01

Background: Administration of daily recombinant human GH (rhGH) poses a considerable challenge to patient compliance. Reduced dosing frequency may improve treatment adherence and potentially overall treatment outcomes. Objectives: This study assessed the safety and tolerability and the potential for achieving IGF-I levels within the target range in adults with GH deficiency after a single dose of the long-acting rhGH analog, VRS-317. Design: This was a randomized, double-blind, placebo-controlled, single ascending dose study. Patients: Fifty adults with growth hormone deficiency (mean age, 45 years) were studied in 5 treatment groups of 10 subjects each (8 active drug and 2 placebo). Setting: The study was conducted in 17 adult endocrinology centers in North America and Europe. Main Outcome Measures: Adverse events, laboratory safety assessments, and VRS-317 pharmacokinetics and pharmacodynamics (IGF-I and IGF binding protein-3) were analyzed. Results: At 0.80 mg/kg, VRS-317 had a mean terminal elimination half-life of 131 hours. Single VRS-317 doses of 0.05, 0.10, 0.20, 0.40, and 0.80 mg/kg (approximately equivalent to daily rhGH doses of 0.3–5.0 μg/kg over 30 d) safely increased the amplitude and duration of IGF-I responses in a dose-dependent manner. After a single 0.80 mg/kg dose, serum IGF-I was maintained in the normal range between −1.5 and 1.5 SD values for a mean of 3 weeks. No unexpected or serious adverse events were observed. Conclusions: The elimination half-life for VRS-317 is 30- to 60-fold longer and stimulates more durable IGF-I responses than previously studied rhGH products. Prolonged IGF-I responses do not come at the expense of overexposure to high IGF-I levels. The pharmacokinetics and pharmacodynamics combined with the observed safety profile indicate the potential for safe and effective monthly dosing. PMID:23585663

Pharmacokinetics of Imipenem/Cilastatin Burn Intensive Care Unit Patients Undergoing High-Dose Continuous Venovenous Hemofiltration.

PubMed

Boucher, Bradley A; Hudson, Joanna Q; Hill, David M; Swanson, Joseph M; Wood, G Christopher; Laizure, S Casey; Arnold-Ross, Angela; Hu, Zhe-Yi; Hickerson, William L

2016-12-01

High-dose continuous venovenous hemofiltration (CVVH) is a continuous renal replacement therapy (CRRT) used frequently in patients with burns. However, antibiotic dosing is based on inference from studies assessing substantially different methods of CRRT. To address this knowledge gap for imipenem/cilastatin (I/C), we evaluated the systemic and extracorporeal clearances (CLs) of I/C in patients with burns undergoing high-dose CVVH. Prospective clinical pharmacokinetic study. Ten adult patients with burns receiving I/C for a documented infection and requiring high-dose CVVH were studied. Blood and effluent samples for analysis of I/C concentrations were collected for up to 6 hours after the I/C infusion for calculation of I/C total CL (CL T otal ), CL by CVVH (CL HF ), half-life during CVVH, volume of distribution at steady state (Vd ss ), and the percentage of drug eliminated by CVVH. In this patient sample, the mean age was 50 ± 17 years, total body surface area burns was 23 ± 27%, and 80% were male. Nine patients were treated with high-dose CVVH for acute kidney injury and one patient for sepsis. The mean delivered CVVH dose was 52 ± 14 ml/kg/hour (range 32-74 ml/kg/hr). The imipenem CL HF was 3.27 ± 0.48 L/hour, which accounted for 23 ± 4% of the CL T otal (14.74 ± 4.75 L/hr). Cilastatin CL HF was 1.98 ± 0.56 L/hour, which accounted for 45 ± 19% of the CL T otal (5.16 + 2.44 L/hr). The imipenem and cilastatin half-lives were 1.77 ± 0.38 hours and 4.21 ± 2.31 hours, respectively. Imipenem and cilastatin Vd ss were 35.1 ± 10.3 and 32.8 ± 13.8 L, respectively. Efficient removal of I/C by high-dose CVVH, a high overall clearance, and a high volume of distribution in burn intensive care unit patients undergoing this CRRT method warrant aggressive dosing to treat serious infections effectively depending on the infection site and/or pathogen. © 2016 Pharmacotherapy Publications, Inc.

Alternative chitosan-based EPR dosimeter applicable for a relatively wide range of gamma radiation doses

NASA Astrophysics Data System (ADS)

Piroonpan, Thananchai; Katemake, Pichayada; Panritdam, Eagkapong; Pasanphan, Wanvimol

2017-12-01

Chitosan biopolymer is proposed as an alternative EPR dosimeter. Its ability to be EPR dosimeter was studied in comparison with the conventional alanine, sugars (i.e., glucose and sucrose), formate derivatives (i.e., lithium (Li), magnesium (Mg), and calcium (Ca) formate). Ethylene vinyl acetate (EVA) and paraffin were used as binder for the preparation of composite EPR dosimeter. Dose responses of all materials were investigated in a wide dose range of radiation doses, i.e., low-level (0-1 kGy), medium-level (1-10 kGy) and high-level (10-100 kGy). The EPR dosimeter properties were studied under different parameters, i.e., microwave power, materials contents, absorbed doses, storage conditions and post-irradiation effects. Li-formate showed a simple EPR spectrum and exhibited superior radiation response for low-dose range; whereas chitosan and sucrose exhibited linear dose response in all studied dose ranges. The EPR signals of chitosan exhibited similar stability as glucose, Li-formate and alanine at ambient temperature after irradiation as long as a year. All EPR signals of the studied materials were affected post-irradiation temperature and humidity after gamma irradiation. The EPR signal of chitosan exhibited long-term stability and it was not sensitive to high storage temperatures and humidity values after irradiation. Chitosan has a good merit as the alternative bio-based material for a stable EPR dosimeter in a wide range of radiation-absorbed doses.

Virosomal hepatitis a vaccine: comparing intradermal and subcutaneous with intramuscular administration.

PubMed

Frösner, Gert; Steffen, Robert; Herzog, Christian

2009-01-01

Vaccination against hepatitis A virus (HAV) is unaffordable to many developing countries. Substantial reductions in cost occur when vaccines are administered intradermally at low doses. Aluminum-free HAV vaccines are considered more suitable for intradermal use than traditional vaccines which can cause long-lasting local reactions. Thus, we compared the immunogenicity and safety of an aluminum-free virosomal HAV vaccine (Epaxal) administered by different routes: intradermal (i.d.), subcutaneous (s.c.), and intramuscular (i.m.). Two open pilot studies were conducted as sub-studies of a large lot consistency trial. Healthy subjects aged 18 to 45 were enrolled. Study 1 compared two i.d. regimens of a lower dose of Epaxal [0.1 mL (4.8 IU), one or two injection sites] with i.m. administration of the standard dose [0.5 mL (24 IU)]. Study 2 compared the s.c. with the i.m. administration of the standard dose. At month 12, subjects in study 1 received a booster dose of 0.1 mL i.d. or 0.5 mL i.m.; subjects in study 2 received 0.5 mL via the respective route (s.c. or i.m.). Serum was tested for antibodies at baseline, 2 weeks (study 1), and 1 and 6 months after the primary vaccination as well as prior and 1 month after the booster dose. Incidences of solicited and unsolicited adverse events were recorded. Seroprotection rates (anti-HAV geometric mean concentration of > or =20 mIU/mL) after 1 month ranged from 93.2% to 100% in all groups and remained high until month 12 (range 85.2&-90.2%). Complete (100%) seroprotection was achieved by all subjects in all groups after booster vaccination. All routes of administration were well tolerated. Local reactions were more common in subjects vaccinated i.d. and s.c. than i.m. The aluminum-free virosomal HAV vaccine Epaxal is highly immunogenic and well tolerated when administered either via i.d., s.c., or i.m. Vaccination via the i.d. route may confer significant cost savings over the conventional i.m. route.

Comparative occupational radiation exposure between fixed and mobile imaging systems.

PubMed

Kendrick, Daniel E; Miller, Claire P; Moorehead, Pamela A; Kim, Ann H; Baele, Henry R; Wong, Virginia L; Jordan, David W; Kashyap, Vikram S

2016-01-01

Endovascular intervention exposes surgical staff to scattered radiation, which varies according to procedure and imaging equipment. The purpose of this study was to determine differences in occupational exposure between procedures performed with fixed imaging (FI) in an endovascular suite compared with conventional mobile imaging (MI) in a standard operating room. A series of 116 endovascular cases were performed over a 4-month interval in a dedicated endovascular suite with FI and conventional operating room with MI. All cases were performed at a single institution and radiation dose was recorded using real-time dosimetry badges from Unfors RaySafe (Hopkinton, Mass). A dosimeter was mounted in each room to establish a radiation baseline. Staff dose was recorded using individual badges worn on the torso lead. Total mean air kerma (Kar; mGy, patient dose) and mean case dose (mSv, scattered radiation) were compared between rooms and across all staff positions for cases of varying complexity. Statistical analyses for all continuous variables were performed using t test and analysis of variance where appropriate. A total of 43 cases with MI and 73 cases with FI were performed by four vascular surgeons. Total mean Kar, and case dose were significantly higher with FI compared with MI. (mean ± standard error of the mean, 523 ± 49 mGy vs 98 ± 19 mGy; P < .00001; 0.77 ± 0.03 mSv vs 0.16 ± 0.08 mSv, P < .00001). Exposure for the primary surgeon and assistant was significantly higher with FI compared with MI. Mean exposure for all cases using either imaging modality, was significantly higher for the primary surgeon and assistant than for support staff (ie, nurse, radiology technologist) beyond 6 feet from the X-ray source, indicated according to one-way analysis of variance (MI: P < .00001; FI: P < .00001). Support staff exposure was negligible and did not differ between FI and MI. Room dose stratified according to case complexity (Kar) showed statistically significantly higher scattered radiation in FI vs MI across all quartiles. The scattered radiation is several-fold higher with FI than MI across all levels of case complexity. Radiation exposure decreases with distance from the radiation source, and is negligible outside of a 6-foot radius. Modern endovascular suites allow high-fidelity imaging, yet additional strategies to minimize exposure and occupational risk are needed. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

RECONSTRUCTION OF RADIATION DOSES IN A CASE-CONTROL STUDY OF THYROID CANCER FOLLOWING THE CHERNOBYL ACCIDENT

PubMed Central

Drozdovitch, Vladimir; Khrouch, Valeri; Maceika, Evaldas; Zvonova, Irina; Vlasov, Oleg; Bratilova, Angelica; Gavrilin, Yury; Goulko, Guennadi; Hoshi, Masaharu; Kesminiene, Ausrele; Shinkarev, Sergey; Tenet, Vanessa; Cardis, Elisabeth; Bouville, Andre

2010-01-01

A population-based case-control study of thyroid cancer was carried out in contaminated regions of Belarus and Russia among persons who were exposed during childhood and adolescence to fallout from the Chernobyl accident. For each study subject, individual thyroid doses were reconstructed for the following pathways of exposure: (1) intake of 131I via inhalation and ingestion; (2) intake of short-lived radioiodines (132I, 133I, and 135I) and radiotelluriums (131mTe, 132Te) via inhalation and ingestion; (3) external dose from radionuclides deposited on the ground; and (4) ingestion of 134Cs and 137Cs. A series of intercomparison exercises validated the models used for reconstruction of average doses to populations of specific age groups as well as of individual doses. Median thyroid doses from all factors for study subjects were estimated to be 0.37 and 0.034 Gy in Belarus and Russia, respectively. The highest individual thyroid doses among the subjects were 10.2 Gy in Belarus and 5.3 Gy in Russia. Iodine-131 intake was the main pathway for thyroid exposure. Estimated doses from short-lived radioiodines and radiotelluriums ranged up to 0.53 Gy. Reconstructed individual thyroid doses from external exposure ranged up to 0.1 Gy, while those from internal exposure due to ingested cesium did not exceed 0.05 Gy. The uncertainty of the reconstructed individual thyroid doses, characterized by the geometric standard deviation, varies from 1.7 to 4.0 with a median of 2.2. PMID:20539120

Platform for Rapid Delivery of Biologics and Drugs to Ocular Cells and Tissues Following Combat Associated Trauma

DTIC Science & Technology

2016-09-01

by DOD to further develop and test protein delivery for the retina. Ongoing Research Support W81XWH-16-1-0650 09/30/16-09/29/19 U.S...Medical Research Institute to test small molecules for inhibition of MAC in laser induced choroidal neovascularization PI Robert Liddington; No...streptavidin594 conjugation and dosing studies. Bonferroni’s multiple comparison tests were used for Post hoc analysis. One-way analysis of variance

76 FR 9786 - NIOSH Dose Reconstruction Program Ten-Year Review-Phase I Report on Customer Service; Request for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-22

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention NIOSH Dose Reconstruction Program Ten-Year Review--Phase I Report on Customer Service; Request for Public Review and Comment... requests public review and comment on the draft publication, ``NIOSH Dose Reconstruction Program Ten-Year...

12 CFR 925.17 - Rebuttable presumptions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... rating required by § 925.11(b)(3)(i) of this part, or a variance from a performance trend criterion... creditworthiness, business judgment, or moral turpitude since the most recent regulatory examination report, the...

Monte Carlo calculated doses to treatment volumes and organs at risk for permanent implant lung brachytherapy

NASA Astrophysics Data System (ADS)

Sutherland, J. G. H.; Furutani, K. M.; Thomson, R. M.

2013-10-01

Iodine-125 (125I) and Caesium-131 (131Cs) brachytherapy have been used with sublobar resection to treat stage I non-small cell lung cancer and other radionuclides, 169Yb and 103Pd, are considered for these treatments. This work investigates the dosimetry of permanent implant lung brachytherapy for a range of source energies and various implant sites in the lung. Monte Carlo calculated doses are calculated in a patient CT-derived computational phantom using the EGsnrc user-code BrachyDose. Calculations are performed for 103Pd, 125I, 131Cs seeds and 50 and 100 keV point sources for 17 implant positions. Doses to treatment volumes, ipsilateral lung, aorta, and heart are determined and compared to those determined using the TG-43 approach. Considerable variation with source energy and differences between model-based and TG-43 doses are found for both treatment volumes and organs. Doses to the heart and aorta generally increase with increasing source energy. TG-43 underestimates the dose to the heart and aorta for all implants except those nearest to these organs where the dose is overestimated. Results suggest that model-based dose calculations are crucial for selecting prescription doses, comparing clinical endpoints, and studying radiobiological effects for permanent implant lung brachytherapy.

Activation calculation for the dismantling and decommissioning of a light water reactor using MCNP™ with ADVANTG and ORIGEN-S

NASA Astrophysics Data System (ADS)

Schlömer, Luc; Phlippen, Peter-W.; Lukas, Bernard

2017-09-01

The decommissioning of a light water reactor (LWR), which is licensed under § 7 of the German Atomic Energy Act, following the post-operational phase requires a comprehensive licensing procedure including in particular radiation protection aspects and possible impacts to the environment. Decommissioning includes essential changes in requirements for the systems and components and will mainly lead to the direct dismantling. In this context, neutron induced activation calculations for the structural components have to be carried out to predict activities in structures and to estimate future costs for conditioning and packaging. To avoid an overestimation of the radioactive inventory and to calculate the expenses for decommissioning as accurate as possible, modern state-of-the-art Monte-Carlo-Techniques (MCNP™) are applied and coupled with present-day activation and decay codes (ORIGEN-S). In this context ADVANTG is used as weight window generator for MCNP™ i. e. as variance reduction tool to speed up the calculation in deep penetration problems. In this paper the calculation procedure is described and the obtained results are presented with a validation along with measured activities and photon dose rates measured in the post-operational phase. The validation shows that the applied calculation procedure is suitable for the determination of the radioactive inventory of a nuclear power plant. Even the measured gamma dose rates in the post-operational phase at different positions in the reactor building agree within a factor of 2 to 3 with the calculation results. The obtained results are accurate and suitable to support effectively the decommissioning planning process.

Phase I/II adaptive design for drug combination oncology trials

PubMed Central

Wages, Nolan A.; Conaway, Mark R.

2014-01-01

Existing statistical methodology on dose finding for combination chemotherapies has focused on toxicity considerations alone in finding a maximum tolerated dose combination to recommend for further testing of efficacy in a phase II setting. Recently, there has been increasing interest in integrating phase I and phase II trials in order to facilitate drug development. In this article, we propose a new adaptive phase I/II method for dual-agent combinations that takes into account both toxicity and efficacy after each cohort inclusion. The primary objective, both within and at the conclusion of the trial, becomes finding a single dose combination with an acceptable level of toxicity that maximizes efficacious response. We assume that there exist monotone dose–toxicity and dose–efficacy relationships among doses of one agent when the dose of other agent is fixed. We perform extensive simulation studies that demonstrate the operating characteristics of our proposed approach, and we compare simulated results to existing methodology in phase I/II design for combinations of agents. PMID:24470329

Phase I clinical and pharmacokinetic study of kahalalide F administered weekly as a 1-hour infusion to patients with advanced solid tumors.

PubMed

Pardo, Beatriz; Paz-Ares, Luis; Tabernero, Josep; Ciruelos, Eva; García, Margarita; Salazar, Ramón; López, Ana; Blanco, María; Nieto, Antonio; Jimeno, José; Izquierdo, Miguel Angel; Trigo, José Manuel

2008-02-15

A dose-escalation, phase I study evaluated the safety, pharmacokinetics, and efficacy of a weekly 1-h regimen of kahalalide F, a cyclic depsipeptide isolated from the marine mollusk Elysia rufescens, in adult patients with advanced solid tumors and no standard treatment available. Patients received an i.v. 1-h infusion of kahalalide F once weekly until disease progression or unacceptable toxicity. The starting kahalalide F dose was 266 microg/m(2), and dose escalation proceeded based on the worst toxicity found in the previous cohort. Thirty-eight patients were enrolled at three Spanish institutions and received once-weekly kahalalide F 1-h infusions at doses between 266 and 1,200 microg/m(2). Dose-limiting toxicities consisted of transient grade 3/4 increases in transaminase blood levels. The maximum tolerated dose for this kahalalide F schedule was 800 microg/m(2), and the recommended dose for phase II studies was 650 microg/m(2). No accumulated toxicity was found. One patient with malignant melanoma had unconfirmed partial response, one patient with metastatic lung adenocarcinoma had minor response, and six patients with different types of metastatic solid tumors had stable disease for 2.8 to 12.7 months. The noncompartmental pharmacokinetics of this kahalalide F schedule was linear and showed a narrow distribution and short body residence. The transaminitis associated with kahalalide F was dose dependent. The maximum tolerated dose was 800 microg/m(2). Dose-limiting toxicities with weekly kahalalide F 1-h i.v. infusions were transient grade 3/4 increases in blood transaminase levels, and 650 microg/m(2) was declared the recommended dose for phase II studies. This schedule showed a favorable safety profile and hints of antitumor activity.

Comparing treatment effects of oral THC on simulated and on-the-road driving performance: testing the validity of driving simulator drug research.

PubMed

Veldstra, J L; Bosker, W M; de Waard, D; Ramaekers, J G; Brookhuis, K A

2015-08-01

The driving simulator provides a safe and controlled environment for testing driving behaviour efficiently. The question is whether it is sensitive to detect drug-induced effects. The primary aim of the current study was to investigate the sensitivity of the driving simulator for detecting drug effects. As a case in point, we investigated the dose-related effects of oral ∆(9)-tetrahydrocannabinol (THC), i.e. dronabinol, on simulator and on-the-road driving performance in equally demanding driving tasks. Twenty-four experienced driver participants were treated with dronabinol (Marinol®; 10 and 20 mg) and placebo. Dose-related effects of the drug on the ability to keep a vehicle in lane (weaving) and to follow the speed changes of a lead car (car following) were compared within subjects for on-the-road versus in-simulator driving. Additionally, the outcomes of equivalence testing to alcohol-induced effects were investigated. Treatment effects found on weaving when driving in the simulator were comparable to treatment effects found when driving on the road. The effect after 10 mg dronabinol was however less strong in the simulator than on the road and inter-individual variance seemed higher in the simulator. There was, however, a differential treatment effect of dronabinol on reactions to speed changes of a lead car (car following) when driving on the road versus when driving in the simulator. The driving simulator was proven to be sensitive for demonstrating dronabinol-induced effects particularly at higher doses. Treatment effects of dronabinol on weaving were comparable with driving on the road but inter-individual variability seemed higher in the simulator than on the road which may have potential effects on the clinical inferences made from simulator driving. Car following on the road and in the simulator were, however, not comparable.

Antioxidant and gastric cytoprotective prostaglandins properties of Cassia sieberiana roots bark extract as an anti-ulcerogenic agent.

PubMed

Nartey, Edmund T; Ofosuhene, Mark; Kudzi, William; Agbale, Caleb M

2012-05-20

Cassia sieberiana is a savannah tree with a wide phytotherapeutic application including the use of its roots in the management of various stomach disorders including gastric ulcer, stomach pains and indigestion. The aim of the study is to evaluate the antioxidant, gastric cytoprotective prostaglandins, secretory phospholipase A2, phytochemical and acute toxicity properties of Cassia sieberiana roots bark extract in a bid to justify its phytotherapeutic applications in gastric ulcer. Antioxidant and radical scavenging activities of the roots bark extract of Cassia sieberiana were assayed. Serum secretory phospholipase A2 (sPLA2) concentration and activity and the formation of gastric mucosal prostaglandins E2 (PGE2) and I2 (PGI2) were also assessed. Comparisons between means were performed using analysis of variance (ANOVA) followed by Students Standard Newman-Keuls post hoc analysis to determine statistical significance. P < 0.05 was considered significant. The extract was found to possess significant ferric reducing antioxidant power and can scavenge hydroxyl radicals. The extract also possesses DPPH scavenging activity, can chelate ferrous ion and a dose-dependent protective effect against lipid peroxidation and free radical generation. Prostaglandin studies showed that the roots bark extract dose dependently increased gastric mucosal PGE2 and PGI2 levels and also decreased serum sPLA2 activity. Phytochemical analyses suggest that the roots extract contains polyhydroxyl/phenolic substances. Acute toxicity test showed no sign of toxicity up to a dose level of 2000 mg/kg body weight p.o. C. sieberiana roots extract possesses significant antioxidant and gastric cytoprotective prostaglandin properties as well as serum secretory phospholipase A2 inhibitory activity which could be due to its content of polyhydroxy and/or phenolic substances. This may justify its use as an anti-ulcerogenic agent in traditional medicine in West Africa.

Do all patients in the phase I oncology trials need to be hospitalized? Domestic but outstanding issues for globalization of drug development in Japan.

PubMed

Shimomura, Akihiko; Kondo, Shunsuke; Kobayashi, Noriko; Iwasa, Satoru; Kitano, Shigehisa; Tamura, Kenji; Fujiwara, Yutaka; Yamamoto, Noboru

2017-08-01

Most trials investigating new drugs around the world, including phase I trials, are conducted in outpatient clinics. However, in Japan, regulatory authority requirements and traditional domestic guidelines often require hospitalization of phase I study participants. Patients participating in single-agent phase I clinical trials at National Cancer Center Hospital between December 1996 and August 2014 were monitored. Toxicity requiring hospitalization is defined as toxicity that needs intensive treatment. Study designs were classified into three types: first-in-human (FIH) study, dose-escalation study (conventional dose-escalation study to determine maximum tolerated dose (MTD) in Japanese patients), and dose-finding study (to assess safety and pharmacokinetic profiles up to the MTD previously determined in the West). A total of 945 patients who participated in a variety of single-agent phase I clinical trials between December 1996 and August 2014 were included in this study. Patients participated in one of three study types: dose-escalation (n = 582, 62%), first-in-human (n = 129, 14%), or dose-finding (n = 234, 25%). A total of 76 study drugs were evaluated as part of this pool of phase I studies. Subdivided by mechanism of action, 20 (26%) were cytotoxic, 50 (66%) were molecularly targeted, and 6 (8%) were immune checkpoint inhibitor. Thirty-six patients (3.8%) had severe toxicities requiring hospitalization during the first cycle. The overall number of toxicities requiring hospitalization and/or grade 4 toxicities during any cycle was 5.0%. The frequency of severe toxicity that needs to be hospitalized was unexpectedly low. The data did not demonstrate the need for hospitalization in the phase I trials, suggesting that phase I trials in Japan could be conducted in outpatient settings.

[Application of the elliptic fourier functions to the description of avian egg shape].

PubMed

Ávila, Dennis Denis

2014-12-01

Egg shape is difficult to quantify due to the lack of an exact formula to describe its geometry. Here I described a simple algorithm to characterize and compare egg shapes using Fourier functions. These functions can delineate any closed contour and had been previously applied to describe several biological objects. I described, step by step, the process of data acquisition, processing and the use of the SHAPE software to extract function coefficients in a study case. I compared egg shapes in three birds' species representing different reproductive strategies: Cuban Parakeet (Aratinga euops), Royal Tern (Thalasseus maximus) and Cuban Blackbird (Dives atroviolaceus). Using 73 digital pictures of eggs kept in Cuban scientific collections, I calculated Fourier descriptors with 4, 6, 8, 16 and 20 harmonics. Descriptors were reduced by a Principal Component Analysis and the scores of the eigen-values that account for 90% of variance were used in a Lineal Discriminant Function to analyze the possibility to differentiate eggs according to its shapes. Using four harmonics, the first five component accounted for 97% of shape variances; more harmonics diluted the variance increasing to eight the number of components needed to explain most of the variation. Convex polygons in the discriminant space showed a clear separation between species, allowing trustful discrimination (classification errors between 7-15%). Misclassifications were related to specific egg shape variability between species. In the study case, A. euops eggs were perfectly classified, but for the other species, errors ranged from 5 to 29% of misclassifications, in relation to the numbers or harmonics and components used. The proposed algorithm, despite its apparent mathematical complexity, showed many advantages to describe eggs shape allowing a deeper understanding of factors related to this variable.

Evaluation of an iterative model-based CT reconstruction algorithm by intra-patient comparison of standard and ultra-low-dose examinations.

PubMed

Noël, Peter B; Engels, Stephan; Köhler, Thomas; Muenzel, Daniela; Franz, Daniela; Rasper, Michael; Rummeny, Ernst J; Dobritz, Martin; Fingerle, Alexander A

2018-01-01

Background The explosive growth of computer tomography (CT) has led to a growing public health concern about patient and population radiation dose. A recently introduced technique for dose reduction, which can be combined with tube-current modulation, over-beam reduction, and organ-specific dose reduction, is iterative reconstruction (IR). Purpose To evaluate the quality, at different radiation dose levels, of three reconstruction algorithms for diagnostics of patients with proven liver metastases under tumor follow-up. Material and Methods A total of 40 thorax-abdomen-pelvis CT examinations acquired from 20 patients in a tumor follow-up were included. All patients were imaged using the standard-dose and a specific low-dose CT protocol. Reconstructed slices were generated by using three different reconstruction algorithms: a classical filtered back projection (FBP); a first-generation iterative noise-reduction algorithm (iDose4); and a next generation model-based IR algorithm (IMR). Results The overall detection of liver lesions tended to be higher with the IMR algorithm than with FBP or iDose4. The IMR dataset at standard dose yielded the highest overall detectability, while the low-dose FBP dataset showed the lowest detectability. For the low-dose protocols, a significantly improved detectability of the liver lesion can be reported compared to FBP or iDose 4 ( P = 0.01). The radiation dose decreased by an approximate factor of 5 between the standard-dose and the low-dose protocol. Conclusion The latest generation of IR algorithms significantly improved the diagnostic image quality and provided virtually noise-free images for ultra-low-dose CT imaging.

[Comparation study of incidental irradiation dose to the internal mammary chain during postmastectomy radiotherapy for patients treated with different irradiation techniques].

PubMed

Wang, W; Meng, Y T; Song, Y F; Sun, T; Xu, M; Shao, Q; Zhang, Y J; Li, J B

2018-05-23

Objective: To evaluated the unplanned coverage dose to the internal mammary chain (IMC) in patient treated with postmastectomy radiotherapy (PMRT). Methods: One hundred and thirty eight patients with breast cancer receiving radiotherapy (RT) in our hospital were retrospectively analyzed. Patients were divided into three groups: three-dimensional conformal radiotherapy (3D-CRT) group, forward intensity-modulated radiotherapy (F-IMRT) group and inverse IMRT (I-IMRT) group. The IMC were contoured according to Radiation Therapy Oncology Group (RTOG) consensus, and were not include into the planning target volume (PTV). The incidental irradiation dose to IMC among the three groups and the first three intercostal spaces IMC (ICS-IMC 1-3) were all compared, and explored the relationship between the mean doses (Dmean) of IMC and the OARs (ipsilateral lung and heart). Results: The dose delivered to IMC showed no difference in CRT, F-IMRT and I-IMRT(33.80 Gy, 29.65 Gy and 32.95 Gy). And 10.42%, 2.04%, and 9.76% patients achieved ≥45 Gy when treated with CRT, F-IMRT and I-IMRT. For the IMC dose in the first three intercostal spaces (ICS1-3), there was no difference to the three treatment plannings. The Dmean, V(20), V(30), V(40) and V(50) of the ICS-IMC2 and ICS-IMC3 were all obviously superior than ICS-IMC1 for all these three plannings. Moderate positive correlation was founded between Dmean for IMC and Dmean for heart for left breast cancer patients underwent CRT ( r =0.338, P =0.01). Whereas for F-IMRT and I-IMRT groups, positive correlation were founded between Dmean for IMC and Dmean and V(20) for ipsilateral lung for all patients (F-IMRT: r =0.366, P =0.010; r =0.318, P =0.026; I-IMRT: r =0.427, P =0.005; r =0.411, P =0.008). Conclusions: In 3D-CRT, F-IMRT and I-IMRT planning methods, partial patients get IMC irradiated doses that could achieve therapeutic doses. Compared with 3D-CRT, F-IMRT and I-IMRT further reduced the dose of irradiated organs. However, there is no difference in the dose coverage of IMC for the three planned approaches when the IMC made an unplanned target.

Low-dose priming before vaccination with the phase I chloroform-methanol residue vaccine against Q fever enhances humoral and cellular immune responses to Coxiella burnetii.

PubMed

Waag, David M; England, Marilyn J; Bolt, Christopher R; Williams, Jim C

2008-10-01

Although the phase I Coxiella burnetii cellular vaccine is completely efficacious in humans, adverse local and systemic reactions may develop if immune individuals are inadvertently vaccinated. The phase I chloroform-methanol residue (CMRI) vaccine was developed as a potentially safer alternative. Human volunteers with no evidence of previous exposure to C. burnetii received a subcutaneous vaccination with the CMRI vaccine in phase I studies under protocol IND 3516 to evaluate the safety and immunogenicity of the vaccine. This clinical trial tested escalating doses of the CMRI vaccine, ranging from 0.3 to 60 microg, followed by a booster dose of 30 microg, in a placebo-controlled study. Although priming doses of the CMRI vaccine did not induce a specific antibody detectable by enzyme-linked immunosorbent assay, booster vaccination stimulated the production of significant levels of anti-C. burnetii antibody. Peripheral blood cells (PBCs) of vaccinees responded to C. burnetii cellular antigen in vitro in a vaccine dose-dependent manner. After the booster dose, PBCs were activated by recall antigen in vitro, regardless of the priming dose. These findings suggest that vaccination with the CMRI vaccine can effectively prime the immune system to mount significant anamnestic responses after infection.

Low-Dose Priming before Vaccination with the Phase I Chloroform-Methanol Residue Vaccine against Q Fever Enhances Humoral and Cellular Immune Responses to Coxiella burnetii▿

PubMed Central

Waag, David M.; England, Marilyn J.; Bolt, Christopher R.; Williams, Jim C.

2008-01-01

Although the phase I Coxiella burnetii cellular vaccine is completely efficacious in humans, adverse local and systemic reactions may develop if immune individuals are inadvertently vaccinated. The phase I chloroform-methanol residue (CMRI) vaccine was developed as a potentially safer alternative. Human volunteers with no evidence of previous exposure to C. burnetii received a subcutaneous vaccination with the CMRI vaccine in phase I studies under protocol IND 3516 to evaluate the safety and immunogenicity of the vaccine. This clinical trial tested escalating doses of the CMRI vaccine, ranging from 0.3 to 60 μg, followed by a booster dose of 30 μg, in a placebo-controlled study. Although priming doses of the CMRI vaccine did not induce a specific antibody detectable by enzyme-linked immunosorbent assay, booster vaccination stimulated the production of significant levels of anti-C. burnetii antibody. Peripheral blood cells (PBCs) of vaccinees responded to C. burnetii cellular antigen in vitro in a vaccine dose-dependent manner. After the booster dose, PBCs were activated by recall antigen in vitro, regardless of the priming dose. These findings suggest that vaccination with the CMRI vaccine can effectively prime the immune system to mount significant anamnestic responses after infection. PMID:18701647

Anticlastogenic activity exhibited by botryosphaeran, a new exopolysaccharide produced by Botryosphaeria rhodina MAMB-05.

PubMed

Miranda, Carolina C B O; Dekker, Robert F H; Serpeloni, Juliana M; Fonseca, Eveline A I; Cólus, Ilce M S; Barbosa, Aneli M

2008-03-01

Biopolymers such as exopolysaccharides (EPS) are produced by microbial species and possess unusual properties known to modify biological responses, among them are antimutagenicity and immunomodulation. Botryosphaeran, a newly described fungal (1-->3; 1-->6)-beta-d-glucan produced by Botryosphaeria rhodina MAMB-05, was administered by gavage to mice at three doses (7.5, 15 and 30mg/kgb.w.per day) over 15 days, and found to be non-genotoxic by the micronucleus test in peripheral blood and bone marrow. Botryosphaeran administered at doses of 15 and 30mg EPS/kgb.w. decreased significantly (p<0.001) the clastogenic effect of cyclophosphamide-induced micronucleus formation resulting in a reduction of the frequency of micronucleated cells of 78 and 82% in polychromatic erythrocytes of bone marrow, and reticulocytes in peripheral blood, respectively. The protective effect was dose-dependent, and strong anticlastogenic activity was exerted at low EPS doses. Variance analysis (ANOVA) showed no significant differences (p<0.05) among the median body weights of the groups of mice treated with botryosphaeran during experiments evaluating genotoxic and protective activities of botryosphaeran. This is the first report on the biological activity attributed to botryosphaeran.

Radiation Doses to Members of the U.S. Population from Ubiquitous Radionuclides in the Body: Part 3, Results, Variability, and Uncertainty

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

Watson, David J.; Strom, Daniel J.

This paper is part three of a three-part series investigating annual effective doses to residents of the United States from intakes of ubiquitous radionuclides, including radionuclides occurring naturally, radionuclides whose concentrations are technologically enhanced, and anthropogenic radionuclides. The radionuclides of interest are the 238U series (14 nuclides), the actinium series (headed by 235U; 11 nuclides), and the 232Th series (11 nuclides); primordial radionuclides 87Rb and 40K; cosmogenic and fallout radionuclides 14C and 3H; and purely anthropogenic radionuclides 137Cs-137mBa, 129I and 90Sr-90Y. This series of papers explicitly excludes intakes from inhaling 222Rn, 220Rn, and their short-lived decay products; it also excludesmore » intakes of radionuclides in occupational and medical settings. Part one reviewed, summarized, characterized, and grouped all published and some unpublished data for U.S. residents on ubiquitous radionuclide concentrations in tissues and organs. Part two described the methods used to organize the data collected in part one and segregate it into the ages and genders defined by the study, imputed missing values from the existing data, apportioned activity in bone, and imputed activity in hollow organ contents and the remainder of the body. This paper estimates equivalent doses to target tissues from source regions and maps target tissues to lists of tissues with International Commission on Radiation Protection (ICRP) tissue-weighting factors or to surrogate tissue regions when there is no direct match. Effective doses, using ICRP tissue-weighting factors recommended in 1977, 1990, and 2007, are then calculated, and an upper bound of variability of the effective dose is estimated by calculating the average coefficients of variation (CV), assuming all variance is due to variability. Most of the data were for adult males, whose average annual effective dose is estimated to be 337 μSv (CV = 0.65, geometric mean = 283 μSv, geometric standard deviation sG = 1.81) using 2007 ICRP tissue-weighting factors. This result is between the National Council on Radiation Protection & Measurements’ 1987 estimate of 390 μSv (using 1977 wTs) and its 2009 estimate of 285 μSv (using 2007 wTs) and is higher than the United Nations Scientific Committee on the Effects of Atomic Radiation’s 2000 estimate of 310 μSv (using 1990 wTs). The methods and software developed for this project are sufficiently detailed and sufficiently general to be usable with autopsy data from any or all countries.« less

Measuring radiation dose in computed tomography using elliptic phantom and free-in-air, and evaluating iterative metal artifact reduction algorithm

NASA Astrophysics Data System (ADS)

Morgan, Ashraf

The need for an accurate and reliable way for measuring patient dose in multi-row detector computed tomography (MDCT) has increased significantly. This research was focusing on the possibility of measuring CT dose in air to estimate Computed Tomography Dose Index (CTDI) for routine quality control purposes. New elliptic CTDI phantom that better represent human geometry was manufactured for investigating the effect of the subject shape on measured CTDI. Monte Carlo simulation was utilized in order to determine the dose distribution in comparison to the traditional cylindrical CTDI phantom. This research also investigated the effect of Siemens health care newly developed iMAR (iterative metal artifact reduction) algorithm, arthroplasty phantom was designed and manufactured that purpose. The design of new phantoms was part of the research as they mimic the human geometry more than the existing CTDI phantom. The standard CTDI phantom is a right cylinder that does not adequately represent the geometry of the majority of the patient population. Any dose reduction algorithm that is used during patient scan will not be utilized when scanning the CTDI phantom, so a better-designed phantom will allow the use of dose reduction algorithms when measuring dose, which leads to better dose estimation and/or better understanding of dose delivery. Doses from a standard CTDI phantom and the newly-designed phantoms were compared to doses measured in air. Iterative reconstruction is a promising technique in MDCT dose reduction and artifacts correction. Iterative reconstruction algorithms have been developed to address specific imaging tasks as is the case with Iterative Metal Artifact Reduction or iMAR which was developed by Siemens and is to be in use with the companys future computed tomography platform. The goal of iMAR is to reduce metal artifact when imaging patients with metal implants and recover CT number of tissues adjacent to the implant. This research evaluated iMAR capability of recovering CT numbers and reducing noise. Also, the use of iMAR should allow using lower tube voltage instead of 140 KVp which is used frequently to image patients with shoulder implants. The evaluations of image quality and dose reduction were carried out using an arthroplasty phantom.

A multiscale filter for noise reduction of low-dose cone beam projections

NASA Astrophysics Data System (ADS)

Yao, Weiguang; Farr, Jonathan B.

2015-08-01

The Poisson or compound Poisson process governs the randomness of photon fluence in cone beam computed tomography (CBCT) imaging systems. The probability density function depends on the mean (noiseless) of the fluence at a certain detector. This dependence indicates the natural requirement of multiscale filters to smooth noise while preserving structures of the imaged object on the low-dose cone beam projection. In this work, we used a Gaussian filter, \\text{exp}≤ft(-{{x}2}/2σ f2\\right) as the multiscale filter to de-noise the low-dose cone beam projections. We analytically obtained the expression of {σf} , which represents the scale of the filter, by minimizing local noise-to-signal ratio. We analytically derived the variance of residual noise from the Poisson or compound Poisson processes after Gaussian filtering. From the derived analytical form of the variance of residual noise, optimal σ f2 is proved to be proportional to the noiseless fluence and modulated by local structure strength expressed as the linear fitting error of the structure. A strategy was used to obtain the reliable linear fitting error: smoothing the projection along the longitudinal direction to calculate the linear fitting error along the lateral direction and vice versa. The performance of our multiscale filter was examined on low-dose cone beam projections of a Catphan phantom and a head-and-neck patient. After performing the filter on the Catphan phantom projections scanned with pulse time 4 ms, the number of visible line pairs was similar to that scanned with 16 ms, and the contrast-to-noise ratio of the inserts was higher than that scanned with 16 ms about 64% in average. For the simulated head-and-neck patient projections with pulse time 4 ms, the visibility of soft tissue structures in the patient was comparable to that scanned with 20 ms. The image processing took less than 0.5 s per projection with 1024   ×   768 pixels.

Controlling on-demand gastric acidity in obese subjects: a randomized, controlled trial comparing a single dose of 20 mg rabeprazole and 20 mg omeprazole

PubMed Central

2014-01-01

Background Obesity is associated with a risk of gastroesophageal reflux disease. The pharmacodynamic efficacy of proton pump inhibitors has not been specifically evaluated in obese subjects. The aim of this study was to compare the antisecretory response to a single oral dose of 20 mg rabeprazole, 20 mg omeprazole and placebo in obese subjects. Methods Gastric pH was monitored for 24 hours on three separate occasions in eighteen H. pylori-negative, asymptomatic obese subjects. Subjects were given omeprazole, rabeprazole or placebo in a randomized order and in a double-blind fashion. The main analysis criterion was 24-h percent of time post dose with intragastric pH above 3; secondary criteria were percentage of time above pH 4, median pH, [H+] concentrations and nocturnal acid breakthrough (NAB). Results were analyzed using linear mixed models and Wilks test comparing variances. Results 24-h median [IQ] percentages of time with gastric pH above 3 and 4 were higher with rabeprazole than omeprazole (46 [37–55] vs. 30 [15–55] %, 9 [5-11] % for placebo) but the differences did not reach statistical significance (p = 0.11 and 0.24, respectively). Median acid concentrations were significantly lower with rabeprazole than with omeprazole and placebo (22 [14–53] vs. 54 [19–130] and 95 [73–170] mmoles/l, p < 0.01) for all periods. The number of NAB was significantly lower with rabeprazole than with omeprazole (median 1 [1,2] vs. 2 [1-3], p = 0.04). Variances of 24-h data (pH above 3 and 4, median pH, [H+] concentrations) were significantly lower with rabeprazole than with omeprazole (p < 0.0001). Conclusions In asymptomatic obese subjects the gastric antisecretory response to a single dose of rabeprazole and omeprazole was strong and not significantly different between drugs despite a significantly more homogeneous response with rabeprazole. Trial registration ClinicalTrial.gov: NCT01136317 PMID:25027286

Distribution of kriging errors, the implications and how to communicate them

NASA Astrophysics Data System (ADS)

Li, Hong Yi; Milne, Alice; Webster, Richard

2016-04-01

Kriging in one form or another has become perhaps the most popular method for spatial prediction in environmental science. Each prediction is unbiased and of minimum variance, which itself is estimated. The kriging variances depend on the mathematical model chosen to describe the spatial variation; different models, however plausible, give rise to different minimized variances. Practitioners often compare models by so-called cross-validation before finally choosing the most appropriate for their kriging. One proceeds as follows. One removes a unit (a sampling point) from the whole set, kriges the value there and compares the kriged value with the value observed to obtain the deviation or error. One repeats the process for each and every point in turn and for all plausible models. One then computes the mean errors (MEs) and the mean of the squared errors (MSEs). Ideally a squared error should equal the corresponding kriging variance (σK2), and so one is advised to choose the model for which on average the squared errors most nearly equal the kriging variances, i.e. the ratio MSDR = MSE/σK2 ≈ 1. Maximum likelihood estimation of models almost guarantees that the MSDR equals 1, and so the kriging variances are unbiased predictors of the squared error across the region. The method is based on the assumption that the errors have a normal distribution. The squared deviation ratio (SDR) should therefore be distributed as χ2 with one degree of freedom with a median of 0.455. We have found that often the median of the SDR (MedSDR) is less, in some instances much less, than 0.455 even though the mean of the SDR is close to 1. It seems that in these cases the distributions of the errors are leptokurtic, i.e. they have an excess of predictions close to the true values, excesses near the extremes and a dearth of predictions in between. In these cases the kriging variances are poor measures of the uncertainty at individual sites. The uncertainty is typically under-estimated for the extreme observations and compensated for by over estimating for other observations. Statisticians must tell users when they present maps of predictions. We illustrate the situation with results from mapping salinity in land reclaimed from the Yangtze delta in the Gulf of Hangzhou, China. There the apparent electrical conductivity (ECa) of the topsoil was measured at 525 points in a field of 2.3 ha. The marginal distribution of the observations was strongly positively skewed, and so the observed ECas were transformed to their logarithms to give an approximately symmetric distribution. That distribution was strongly platykurtic with short tails and no evident outliers. The logarithms were analysed as a mixed model of quadratic drift plus correlated random residuals with a spherical variogram. The kriged predictions that deviated from their true values with an MSDR of 0.993, but with a medSDR=0.324. The coefficient of kurtosis of the deviations was 1.45, i.e. substantially larger than 0 for a normal distribution. The reasons for this behaviour are being sought. The most likely explanation is that there are spatial outliers, i.e. points at which the observed values that differ markedly from those at their their closest neighbours.

Distribution of kriging errors, the implications and how to communicate them

NASA Astrophysics Data System (ADS)

Li, HongYi; Milne, Alice; Webster, Richard

2015-04-01

Kriging in one form or another has become perhaps the most popular method for spatial prediction in environmental science. Each prediction is unbiased and of minimum variance, which itself is estimated. The kriging variances depend on the mathematical model chosen to describe the spatial variation; different models, however plausible, give rise to different minimized variances. Practitioners often compare models by so-called cross-validation before finally choosing the most appropriate for their kriging. One proceeds as follows. One removes a unit (a sampling point) from the whole set, kriges the value there and compares the kriged value with the value observed to obtain the deviation or error. One repeats the process for each and every point in turn and for all plausible models. One then computes the mean errors (MEs) and the mean of the squared errors (MSEs). Ideally a squared error should equal the corresponding kriging variance (σ_K^2), and so one is advised to choose the model for which on average the squared errors most nearly equal the kriging variances, i.e. the ratio MSDR=MSE/ σ_K2 ≈1. Maximum likelihood estimation of models almost guarantees that the MSDR equals 1, and so the kriging variances are unbiased predictors of the squared error across the region. The method is based on the assumption that the errors have a normal distribution. The squared deviation ratio (SDR) should therefore be distributed as χ2 with one degree of freedom with a median of 0.455. We have found that often the median of the SDR (MedSDR) is less, in some instances much less, than 0.455 even though the mean of the SDR is close to 1. It seems that in these cases the distributions of the errors are leptokurtic, i.e. they have an excess of predictions close to the true values, excesses near the extremes and a dearth of predictions in between. In these cases the kriging variances are poor measures of the uncertainty at individual sites. The uncertainty is typically under-estimated for the extreme observations and compensated for by over estimating for other observations. Statisticians must tell users when they present maps of predictions. We illustrate the situation with results from mapping salinity in land reclaimed from the Yangtze delta in the Gulf of Hangzhou, China. There the apparent electrical conductivity (EC_a) of the topsoil was measured at 525 points in a field of 2.3~ha. The marginal distribution of the observations was strongly positively skewed, and so the observed EC_as were transformed to their logarithms to give an approximately symmetric distribution. That distribution was strongly platykurtic with short tails and no evident outliers. The logarithms were analysed as a mixed model of quadratic drift plus correlated random residuals with a spherical variogram. The kriged predictions that deviated from their true values with an MSDR of 0.993, but with a medSDR=0.324. The coefficient of kurtosis of the deviations was 1.45, i.e. substantially larger than 0 for a normal distribution. The reasons for this behaviour are being sought. The most likely explanation is that there are spatial outliers, i.e. points at which the observed values that differ markedly from those at their their closest neighbours.

Low dose dynamic myocardial CT perfusion using advanced iterative reconstruction

NASA Astrophysics Data System (ADS)

Eck, Brendan L.; Fahmi, Rachid; Fuqua, Christopher; Vembar, Mani; Dhanantwari, Amar; Bezerra, Hiram G.; Wilson, David L.

2015-03-01

Dynamic myocardial CT perfusion (CTP) can provide quantitative functional information for the assessment of coronary artery disease. However, x-ray dose in dynamic CTP is high, typically from 10mSv to >20mSv. We compared the dose reduction potential of advanced iterative reconstruction, Iterative Model Reconstruction (IMR, Philips Healthcare, Cleveland, Ohio) to hybrid iterative reconstruction (iDose4) and filtered back projection (FBP). Dynamic CTP scans were obtained using a porcine model with balloon-induced ischemia in the left anterior descending coronary artery to prescribed fractional flow reserve values. High dose dynamic CTP scans were acquired at 100kVp/100mAs with effective dose of 23mSv. Low dose scans at 75mAs, 50mAs, and 25mAs were simulated by adding x-ray quantum noise and detector electronic noise to the projection space data. Images were reconstructed with FBP, iDose4, and IMR at each dose level. Image quality in static CTP images was assessed by SNR and CNR. Blood flow was obtained using a dynamic CTP analysis pipeline and blood flow image quality was assessed using flow-SNR and flow-CNR. IMR showed highest static image quality according to SNR and CNR. Blood flow in FBP was increasingly over-estimated at reduced dose. Flow was more consistent for iDose4 from 100mAs to 50mAs, but was over-estimated at 25mAs. IMR was most consistent from 100mAs to 25mAs. Static images and flow maps for 100mAs FBP, 50mAs iDose4, and 25mAs IMR showed comparable, clear ischemia, CNR, and flow-CNR values. These results suggest that IMR can enable dynamic CTP at significantly reduced dose, at 5.8mSv or 25% of the comparable 23mSv FBP protocol.

Simultaneous oral therapeutic and intravenous 14C‐microdoses to determine the absolute oral bioavailability of saxagliptin and dapagliflozin

PubMed Central

Boulton, David W.; Kasichayanula, Sreeneeranj; Keung, Chi Fung (Anther); Arnold, Mark E.; Christopher, Lisa J.; Xu, Xiaohui (Sophia); LaCreta, Frank

2013-01-01

Aim To determine the absolute oral bioavailability (Fp.o.) of saxagliptin and dapagliflozin using simultaneous intravenous 14C‐microdose/therapeutic oral dosing (i.v.micro + oraltherap). Methods The Fp.o. values of saxagliptin and dapagliflozin were determined in healthy subjects (n = 7 and 8, respectively) following the concomitant administration of single i.v. micro doses with unlabelled oraltherap doses. Accelerator mass spectrometry and liquid chromatography‐tandem mass spectrometry were used to quantify the labelled and unlabelled drug, respectively. Results The geometric mean point estimates (90% confidence interval) Fp.o. values for saxagliptin and dapagliflozin were 50% (48, 53%) and 78% (73, 83%), respectively. The i.v.micro had similar pharmacokinetics to oraltherap. Conclusions Simultaneous i.v.micro + oraltherap dosing is a valuable tool to assess human absolute bioavailability. PMID:22823746

Individualized texting for adherence building (iTAB): improving antiretroviral dose timing among HIV-infected persons with co-occurring bipolar disorder.

PubMed

Moore, David J; Poquette, Amelia; Casaletto, Kaitlin B; Gouaux, Ben; Montoya, Jessica L; Posada, Carolina; Rooney, Alexandra S; Badiee, Jayraan; Deutsch, Reena; Letendre, Scott L; Depp, Colin A; Grant, Igor; Atkinson, J Hampton

2015-03-01

HIV+ persons with co-occurring bipolar disorder (HIV+/BD+) have elevated rates of medication nonadherence. We conducted a 30-day randomized controlled trial of a two-way, text messaging system, iTAB (n = 25), compared to an active comparison (CTRL) (n = 25) to improve antiretroviral (ARV) and psychotropic (PSY) adherence and dose timing. Both groups received medication adherence psychoeducation and daily texts assessing mood. The iTAB group additionally received personalized medication reminder texts. Participants responded to over 90 % of the mood and adherence text messages. Mean adherence, as assessed via electronic monitoring caps, was high and comparable between groups for both ARV (iTAB 86.2 % vs. CTRL 84.8 %; p = 0.95, Cliff's d = 0.01) and PSY (iTAB 78.9 % vs. CTRL 77.3 %; p = 0.43, Cliff's d = -0.13) medications. However, iTAB participants took ARVs significantly closer to their intended dosing time than CTRL participants (iTAB: 27.8 vs. CTRL: 77.0 min from target time; p = 0.02, Cliff's d = 0.37). There was no group difference on PSY dose timing. Text messaging interventions may represent a low-burden approach to improving timeliness of medication-taking behaviors among difficult-to-treat populations. The benefits of improved dose timing for long-term medication adherence require additional investigation.

Individualized Texting for Adherence Building (iTAB): Improving Antiretroviral Dose Timing Among HIV-Infected Persons with Co-occurring Bipolar Disorder

PubMed Central

Poquette, Amelia; Casaletto, Kaitlin B.; Gouaux, Ben; Montoya, Jessica L.; Posada, Carolina; Rooney, Alexandra S.; Badiee, Jayraan; Deutsch, Reena; Letendre, Scott L.; Depp, Colin A.; Grant, Igor; Atkinson, J. Hampton

2015-01-01

HIV+ persons with co-occurring bipolar disorder (HIV+/BD+) have elevated rates of medication nonadherence. We conducted a 30-day randomized controlled trial of a two-way, text messaging system, iTAB (n = 25), compared to an active comparison (CTRL) (n = 25) to improve antiretroviral (ARV) and psychotropic (PSY) adherence and dose timing. Both groups received medication adherence psychoeducation and daily texts assessing mood. The iTAB group additionally received personalized medication reminder texts. Participants responded to over 90 % of the mood and adherence text messages. Mean adherence, as assessed via electronic monitoring caps, was high and comparable between groups for both ARV (iTAB 86.2 % vs. CTRL 84.8 %; p = 0.95, Cliff’s d = 0.01) and PSY (iTAB 78.9 % vs. CTRL 77.3 %; p = 0.43, Cliff’s d = −0.13) medications. However, iTAB participants took ARVs significantly closer to their intended dosing time than CTRL participants (iTAB: 27.8 vs. CTRL: 77.0 min from target time; p = 0.02, Cliff’s d = 0.37). There was no group difference on PSY dose timing. Text messaging interventions may represent a low-burden approach to improving timeliness of medication-taking behaviors among difficult-to-treat populations. The benefits of improved dose timing for long-term medication adherence require additional investigation. PMID:25504449

Analysis of stimulus-related activity in rat auditory cortex using complex spectral coefficients

PubMed Central

Krause, Bryan M.

2013-01-01

The neural mechanisms of sensory responses recorded from the scalp or cortical surface remain controversial. Evoked vs. induced response components (i.e., changes in mean vs. variance) are associated with bottom-up vs. top-down processing, but trial-by-trial response variability can confound this interpretation. Phase reset of ongoing oscillations has also been postulated to contribute to sensory responses. In this article, we present evidence that responses under passive listening conditions are dominated by variable evoked response components. We measured the mean, variance, and phase of complex time-frequency coefficients of epidurally recorded responses to acoustic stimuli in rats. During the stimulus, changes in mean, variance, and phase tended to co-occur. After the stimulus, there was a small, low-frequency offset response in the mean and modest, prolonged desynchronization in the alpha band. Simulations showed that trial-by-trial variability in the mean can account for most of the variance and phase changes observed during the stimulus. This variability was state dependent, with smallest variability during periods of greatest arousal. Our data suggest that cortical responses to auditory stimuli reflect variable inputs to the cortical network. These analyses suggest that caution should be exercised when interpreting variance and phase changes in terms of top-down cortical processing. PMID:23657279

Phase I trial of S-1 every other day in combination with gemcitabine/cisplatin for inoperable biliary tract cancer.

PubMed

Uwagawa, Tadashi; Sakamoto, Taro; Abe, Kyohei; Okui, Norimitsu; Hata, Daigo; Shiba, Hiroaki; Futagawa, Yasuro; Aiba, Keisuke; Yanaga, Katsuhiko

2015-01-01

To date, gemcitabine-based or fluoropyrimidine-based regimens are recommended for unresectable advanced biliary tract cancer. Then, we conducted a phase I study of gemcitabine/cisplatin and S-1 that is an oral fluoropyrimidine. The aim of this study was to determine the dose-limiting toxicity (DLT), maximum-tolerated dose, and a recommended phase II dose of S-1. Response was assessed as a secondary endpoint. Patients who have been diagnosed with unresectable or postoperative recurrent biliary tract cancer received cisplatin (25 mg/m² i.v. for 120 min) followed by gemcitabine (1,000 mg/m² i.v. for 30 min) on days 1 and 8, and oral S-1 on alternate days; this regimen was repeated at 21-day intervals. A standard '3 + 3' phase I dose-escalation design was adopted. This study was registered with University hospital Medical Information Network (UMIN) Center in Japan, number UMIN000008415. Twelve patients were evaluable in this study. No patients developed DLTs. Recommended dose of S-1 was 80 (<1.25 m²), 100 (1.25 ≤ 1.5 m²), and 120 mg (1.5 m²≥) per day. One patient could achieve conversion to curative surgery. This phase I study was performed safely and demonstrated encouraging response.

Safety of an i.v. β-adrenergic blockade protocol for heart rate optimization before coronary CT angiography.

PubMed

Kassamali, Rahil H; Kim, Daniel H; Patel, Hiten; Raichura, Nitin; Hoey, Edward T D; Hodson, James; Hussain, Shahid

2014-10-01

The purpose of this study was to assess the safety of heart rate optimization by use of β-adrenergic blockade solely by the i.v. route before coronary CT angiography. The records of 679 patients undergoing CT coronary angiography after receiving i.v. β-adrenergic blockade were retrospectively analyzed. Health screening was completed before scanning, and heart rate was optimized by administration of i.v. metoprolol titrated to a maximum of 70 mg to achieve a heart rate less than 65 beats/min. The median i.v. dose was 20 mg (range, 5-70 mg). The 679 patients analyzed had a total of 10 complications (1.47%). Major complications, defined as not resolving with observation and analgesia alone, occurred in only three patients (0.44%). These complications included a second-degree atrioventricular block. A total of 299 patients (44.0%) needed more than 20 mg of i.v. metoprolol to achieve target heart rate. Only three patients needed the maximum i.v. dose of 70 mg metoprolol. Target heart rate was reached successfully in 666 patients (98.1%) with doses of less than 70 mg. This study did not show a statistically significant association between increasing complication frequency and increasing dose. This study showed that high doses of i.v. metoprolol can be used effectively and with a low rate of major complications to control heart rate before coronary CT angiography in correctly screened patients.

In Search of Effective Scales for Stream Management: Does Agroecoregion, Watershed, or Their Intersection Best Explain the Variance in Stream Macroinvertebrate Communities?

NASA Astrophysics Data System (ADS)

Dovciak, A. L.; Perry, J. A.

2002-09-01

Our lack of understanding of relationships between stream biotic communities and surrounding landscape conditions makes it difficult to determine the spatial scale at which management practices are best assessed. We investigated these relationships in the Minnesota River Basin, which is divided into major watersheds and agroecoregions which are based on soil type, geologic parent material, landscape slope steepness, and climatic factors affecting crop productivity. We collected macroinvertebrate and stream habitat data from 68 tributaries among three major watersheds and two agroecoregions. We tested the effectiveness of the two landscape classification systems (i.e., watershed, agroecoregion) in explaining variance in habitat and macroinvertebrate metrics, and analyzed the relative influence on macroinvertebrates of local habitat versus regional characteristics. Macroinvertebrate community composition was most strongly influenced by local habitat; the variance in habitat conditions was best explained at the scale of intersection of major watershed and agroecoregion (i.e., stream habitat conditions were most homogeneous within the physical regions of intersection of these two landscape classification systems). Our results are consistent with findings of other authors that most variation in macroinvertebrate community data from large agricultural catchments is attributable to local physical conditions. Our results are the first to test the hypothesis and demonstrate that the scale of intersection best explains these variances. The results suggest that management practices adjusted for both watershed and ecoregion characteristics, with the goal of improving physical habitat characteristics of local streams, may lead to better basin-wide water quality conditions and stream biological integrity.

Different dose-dependent effects of ebselen in sciatic nerve ischemia-reperfusion injury in rats.

PubMed

Ozyigit, Filiz; Kucuk, Aysegul; Akcer, Sezer; Tosun, Murat; Kocak, Fatma Emel; Kocak, Cengiz; Kocak, Ahmet; Metineren, Hasan; Genc, Osman

2015-08-26

Ebselen is an organoselenium compound which has strong antioxidant and anti-inflammatory effects. We investigated the neuroprotective role of ebselen pretreatment in rats with experimental sciatic nerve ischemia-reperfusion (I/R) injury. Adult male Sprague Dawley rats were divided into four groups (N = 7 in each group). Before sciatic nerve I/R was induced, ebselen was injected intraperitoneally at doses of 15 and 30 mg/kg. After a 2 h ischemia and a 3 h reperfusion period, sciatic nerve tissues were excised. Tissue levels of malondialdehyde (MDA) and nitric oxide (NO), and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured. Sciatic nerve tissues were also examined histopathologically. The 15 mg/kg dose of ebselen reduced sciatic nerve damage and apoptosis (p<0.01), levels of MDA, NO, and inducible nitric oxide synthase (iNOS) positive cells (p<0.01, p<0.05, respectively), and increased SOD, GPx, and CAT activities (p<0.001, p<0.01, p<0.05, respectively) compared with the I/R group that did not receive ebselen. Conversely, the 30 mg/kg dose of ebselen increased sciatic nerve damage, apoptosis, iNOS positive cells (p<0.01, p<0.05, p<0.001) and MDA and NO levels (p<0.05, p<0.01) and decreased SOD, GPx, and CAT activities (p<0.05) compared with the sham group. The results of this study suggest that ebselen may cause different effects depending on the dose employed. Ebselen may be protective against sciatic nerve I/R injury via antioxidant and antiapoptotic activities at a 15 mg/kg dose, conversely higher doses may cause detrimental effects.

Prediction of iodine-131 biokinetics and radiation doses from therapy on the basis of tracer studies: an important question for therapy planning in nuclear medicine.

PubMed

Willegaignon, José; Pelissoni, Rogério A; Lima, Beatriz C G D; Sapienza, Marcelo T; Coura-Filho, George B; Buchpiguel, Carlos A

2016-05-01

This study aimed to present a comparison of iodine-131 (I) biokinetics and radiation doses to red-marrow (rm) and whole-body (wb), following the administration of tracer and therapeutic activities, as a means of confirming whether I clearance and radiation doses for therapy procedures can be predicted by tracer activities. Eleven differentiated thyroid cancer patients were followed after receiving tracer and therapeutic I activity. Whole-body I clearance was estimated using radiation detectors and OLINDA/EXM software was used to calculate radiation doses to rm and wb. Tracer I activity of 86 (±14) MBq and therapeutic activity of 8.04 (±1.18) GBq were administered to patients, thereby producing an average wb I effective half-time and residence time of, respectively, 13.51 (±4.05) and 23.13 (±5.98) h for tracer activities and 13.32 (±3.38) and 19.63 (±4.77) h for therapy. Radiation doses to rm and wb were, respectively, 0.0467 (±0.0208) and 0.0589 (±0.0207) mGy/MBq in tracer studies and 0.0396 (±0.0169) and 0.0500 (±0.0163) mGy/MBq in therapy. Although the differences were not considered statistically significant between averages, those between the values of effective half-times (P=0.906), residence times (P=0.145), and radiation doses to rm (P=0.393) and to wb (P=0.272), from tracer and therapy procedures, large differences of up to 80% in wb I clearance, and up to 50% in radiation doses were observed when patients were analyzed individually, thus impacting on the total amount of I activity calculated to be safe for application in individual therapy. I biokinetics and radiation doses to rm and wb in therapy procedures are well predicted by diagnostic activities when average values of a group of patients are compared. Nonetheless, when patients are analyzed individually, significant differences may be encountered, thus implying that nuclear medicine therapy-planning requires due consideration of changes in individual patient-body status from initial tracer to final therapy procedures to thus provide appropriate adjustments in therapeutic activities.

The outcome of clinical parameters in adults with severe Type I Gaucher disease using very low dose enzyme replacement therapy.

PubMed

Wilson, Callum; Spearing, Ruth; Teague, Lochie; Robertson, Patsy; Blacklock, Hilary

2007-01-01

Enzyme replacement therapy is now well established as the treatment of choice in Type I Gaucher disease. Historically higher dosage regimens have been used in preference to lower doses despite the little clinical evidence in the way of large controlled clinical trials to support this. Moreover, the extraordinary cost of therapy means that not all eligible patients are able to be treated at the higher dose. Twelve type I adult patients with relatively severe disease were commenced on a very low dose of 7.5U of alglucerase/imiglucerase per kg every two weeks (initially given thrice weekly and later weekly). Follow-up 5 year data reveal a good visceral and haematological response with outcomes consistent with recently published treatment guidelines. Satisfactory clinical and radiological skeletal improvement was also demonstrated in most patients. Three patients had an inadequate overall skeletal response to therapy. Biomarkers also steadily improved although perhaps not quite at the same rate as that seen in higher doses. Very low dose enzyme replacement therapy may be appropriate for adult type I Gaucher patients with mild-moderate skeletal disease.

10 CFR 835.702 - Individual monitoring records.

Code of Federal Regulations, 2010 CFR

2010-01-01

... emergency exposures. (b) Recording of the non-uniform equivalent dose to the skin is not required if the... internal dose (committed effective dose or committed equivalent dose) is not required for any monitoring...: (i) The effective dose from external sources of radiation (equivalent dose to the whole body may be...

10 CFR 835.702 - Individual monitoring records.

Code of Federal Regulations, 2011 CFR

2011-01-01

... emergency exposures. (b) Recording of the non-uniform equivalent dose to the skin is not required if the... internal dose (committed effective dose or committed equivalent dose) is not required for any monitoring...: (i) The effective dose from external sources of radiation (equivalent dose to the whole body may be...

10 CFR 835.702 - Individual monitoring records.

Code of Federal Regulations, 2014 CFR

2014-01-01

... emergency exposures. (b) Recording of the non-uniform equivalent dose to the skin is not required if the... internal dose (committed effective dose or committed equivalent dose) is not required for any monitoring...: (i) The effective dose from external sources of radiation (equivalent dose to the whole body may be...

10 CFR 835.702 - Individual monitoring records.

Code of Federal Regulations, 2013 CFR

2013-01-01

... emergency exposures. (b) Recording of the non-uniform equivalent dose to the skin is not required if the... internal dose (committed effective dose or committed equivalent dose) is not required for any monitoring...: (i) The effective dose from external sources of radiation (equivalent dose to the whole body may be...

10 CFR 835.702 - Individual monitoring records.

Code of Federal Regulations, 2012 CFR

2012-01-01

... emergency exposures. (b) Recording of the non-uniform equivalent dose to the skin is not required if the... internal dose (committed effective dose or committed equivalent dose) is not required for any monitoring...: (i) The effective dose from external sources of radiation (equivalent dose to the whole body may be...

Absorbed radiation dose in adults from iodine-131 and iodine-123 orthoiodohippurate and technetium-99m DTPA renography

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

Carlsen, O.

1988-03-01

A mathematic model for evaluation of absorbed dose in radionuclide renography has been developed and programmed for automatic calculation in the computer. Input data to the model are readily available from the results of the renography and, hence, the method described is suitable for individual dose determinations in adults. Apart from the situation with very considerable outflow obstructions (/sup 131/I)OIH single probe renography involves a 15-20 times smaller dose to radiation sensitive organs than (/sup 123/I)OIH gamma camera renography. Further, the latter examination results in a 2-10 times smaller dose than (/sup 99m/Tc)DTPA gamma camera renography under normal outflow conditions.more » Absorbed renal dose is large, approximately 70 mGy, in the three renographies in the borderline case with total outflow obstructions. For comparison, i.v. pyelography, which is the x-ray examination often used instead of radionuclide renography, involves an absorbed dose to ovaries 10-1000 times larger than in radionuclide renography« less

Mutagenicity of diagnostic and therapeutical doses of radiopharmaceutical iodine-131 in Wistar rats.

PubMed

Düsman, Elisângela; Berti, Alessandra Paim; Mariucci, Rosinete Gonçalves; Lopes, Nilson Benedito; Vicentini, Veronica Elisa Pimenta

2011-11-01

Iodine-131 ((131)I) is a radioisotope used for the diagnosis and treatment of thyroidal disorders such as hyperthyroidism and cancer. During its decay, (131)I emits beta particles and gamma rays; its physical half-life is 8 days, and it is accumulated preferentially in the thyroid tissue. This study aimed to evaluate the cytotoxicity and mutagenicity of diagnostic and therapeutic doses of (131)I using bone marrow cells of rats treated in vivo in a test system with a single dose by gavage. Concentrations of 5, 25, 50 and 250 μCi in 1 ml of water were used, and after 24 h, the animals were killed. Also, a concentration of 25 μCi/ml of water was used, and the animals were killed after 5 days. The results showed that no concentration of (131)I was cytotoxic and that all concentrations were mutagenic. As a result, there was no statistically significant difference detected by the χ(2) test in the induction of chromosomal aberrations between the different doses. Thus, the present study demonstrated a significant increase in chromosomal aberration in bone marrow cells exposed to (131)I regardless of the dose or the treatment time.

Estimated dose rates to members of the public from external exposure to patients with {sup 131}I thyroid treatment

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

Dewji, S., E-mail: dewjisa@ornl.gov; Bellamy, M.; Leggett, R.

Purpose: Estimated dose rates that may result from exposure to patients who had been administered iodine-131 ({sup 131}I) as part of medical therapy were calculated. These effective dose rate estimates were compared with simplified assumptions under United States Nuclear Regulatory Commission Regulatory Guide 8.39, which does not consider body tissue attenuation nor time-dependent redistribution and excretion of the administered {sup 131}I. Methods: Dose rates were estimated for members of the public potentially exposed to external irradiation from patients recently treated with {sup 131}I. Tissue attenuation and iodine biokinetics were considered in the patient in a larger comprehensive effort to improvemore » external dose rate estimates. The external dose rate estimates are based on Monte Carlo simulations using the Phantom with Movable Arms and Legs (PIMAL), previously developed by Oak Ridge National Laboratory and the United States Nuclear Regulatory Commission. PIMAL was employed to model the relative positions of the {sup 131}I patient and members of the public in three exposure scenarios: (1) traveling on a bus in a total of six seated or standing permutations, (2) two nursing home cases where a caregiver is seated at 30 cm from the patient’s bedside and a nursing home resident seated 250 cm away from the patient in an adjacent bed, and (3) two hotel cases where the patient and a guest are in adjacent rooms with beds on opposite sides of the common wall, with the patient and guest both in bed and either seated back-to-back or lying head to head. The biokinetic model predictions of the retention and distribution of {sup 131}I in the patient assumed a single voiding of urinary bladder contents that occurred during the trip at 2, 4, or 8 h after {sup 131}I administration for the public transportation cases, continuous first-order voiding for the nursing home cases, and regular periodic voiding at 4, 8, or 12 h after administration for the hotel room cases. Organ specific activities of {sup 131}I in the thyroid, bladder, and combined remaining tissues were calculated as a function of time after administration. Exposures to members of the public were considered for {sup 131}I patients with normal thyroid uptake (peak thyroid uptake of ∼27% of administered {sup 131}I), differentiated thyroid cancer (DTC, 5% uptake), and hyperthyroidism (80% uptake). Results: The scenario with the patient seated behind the member of the public yielded the highest dose rate estimate of seated public transportation exposure cases. The dose rate to the adjacent room guest was highest for the exposure scenario in which the hotel guest and patient are seated by a factor of ∼4 for the normal and differentiated thyroid cancer uptake cases and by a factor of ∼3 for the hyperthyroid case. Conclusions: It was determined that for all modeled cases, the DTC case yielded the lowest external dose rates, whereas the hyperthyroid case yielded the highest dose rates. In estimating external dose to members of the public from patients with {sup 131}I therapy, consideration must be given to (patient- and case-specific) administered {sup 131}I activities and duration of exposure for a more complete estimate. The method implemented here included a detailed calculation model, which provides a means to determine dose rate estimates for a range of scenarios. The method was demonstrated for variations of three scenarios, showing how dose rates are expected to vary with uptake, voiding pattern, and patient location.« less

Feasibility of Administering High-Dose 131I-MIBG Therapy to Children with High-Risk Neuroblastoma without Lead-Lined Rooms

PubMed Central

Chu, Bae P.; Horan, Christopher; Basu, Ellen; Dauer, Lawrence; Williamson, Matthew; Carrasquillo, Jorge A.; Pandit-Taskar, Neeta; Modak, Shakeel

2015-01-01

Background Although 131I-metaiodobenzylguanidine therapy (131I-MIBG) is increasingly used for children with high-risk neuroblastoma, a paucity of lead-lined rooms limits its wider use. We implemented radiation safety procedures to comply with New York City Department of Health and Mental Hygiene regulations for therapeutic radioisotopes and administered 131I-MIBG using rolling lead shields. Procedure Patients received 0.67GBq (18mCi)/kg/dose 131I-MIBG on an IRB-approved protocol (NCT00107289). Radiation safety procedures included private room with installation of rolling lead shields to maintain area dose rates ≤0.02mSv/h outside the room, patient isolation until dose rate <0.07mSv/h at 1m and retention of a urinary catheter with collection of urine in lead boxes. Parents were permitted in the patient’s room behind lead shields, trained in radiation safety principles and given real-time radiation monitors. Results Records on 16 131I-MIBG infusions among 10 patients (age 2–11 years) were reviewed. Mean ± standard deviation 131I-MIBG administered was 17.67±11.14 (range: 6.11–40.59) GBq. Mean maximum dose rates outside treatment rooms were 0.013±0.008 mSv/hr. Median time-to-discharge was 3 days post-131I-MIBG. Exposure of medical staff and parents was below regulatory limits. Cumulative whole-body dose received by the physician, nurse and radiation safety officer during treatment was 0.098±0.058, 0.056±0.045, 0.055±0.050 mSv respectively. Cumulative exposure to parents was 0.978±0.579mSv. Estimated annual radiation exposure for inpatient nurses was 0.096±0.034mSv/nurse. Thyroid bioassay scans on all medical personnel were

Communicating and understanding the purpose of pediatric phase I cancer trials.

PubMed

Cousino, Melissa K; Zyzanski, Stephen J; Yamokoski, Amy D; Hazen, Rebecca A; Baker, Justin N; Noll, Robert B; Rheingold, Susan R; Geyer, J Russell; Alexander, Stewart C; Drotar, Dennis; Kodish, Eric D

2012-12-10

Quality informed consent should provide a clear understanding of the purpose of the research. Given the ethical challenges of pediatric phase I cancer trials, it is important to investigate physician-parent communication during informed consent conferences (ICCs) and parental understanding of the purpose of these studies. In the multisite Informed Consent in Pediatric Phase I Cancer Trials study, 85 ICCs for phase I research between June 2008 and May 2011 were directly observed, and 60 parents were subsequently interviewed. The scientific purpose was defined as composite understanding of drug safety, dose finding, and dose escalation. We determined the frequency with which physicians explained these and other phase I-related concepts during the ICC. Parent interviews were analyzed to determine understanding. The child was present at 83 of 85 ICCs. Only 32% of parents demonstrated substantial understanding of the scientific purpose of phase I cancer trials; 35% demonstrated little or no understanding. Parents of higher socioeconomic status and racial majority status were more likely to understand the scientific purpose. Factors associated with understanding included physician explanation of the goal of the applicable phase I protocol offered (explained in 85% of ICCs) and explanation of the dose cohorts (explained in 43% of ICCs). Physicians explained drug safety in 23% of ICCs, dose finding in 52% of ICCs, and dose escalation in 53% of ICCs. Many parents of children participating in phase I trials do not understand the purpose of these trials. Physician-parent communication about the purpose of phase I research is lacking during ICCs.

Suppression of experimental autoimmune diseases and prolongation of allograft survival by treatment of animals with low doses of heparins.

PubMed

Lider, O; Baharav, E; Mekori, Y A; Miller, T; Naparstek, Y; Vlodavsky, I; Cohen, I R

1989-03-01

The ability of activated T lymphocytes to penetrate the extracellular matrix and migrate to target tissues was found to be related to expression of a heparanase enzyme (Naparstek, Y., I. R. Cohen, Z. Fuks, and I. Vlodavsky. 1984. Nature (Lond.). 310:241-243; Savion, N., Z. Fuks, and I. Vlodavsky. 1984. J. Cell. Physiol. 118:169-176; Fridman, R., O. Lider, Y. Naparstek, Z. Fuks, I. Vlodavsky, and I. R. Cohen. 1987. J. Cell. Physiol. 130:85-92; Lider, O., J. Mekori, I. Vlodavsky, E. Baharav, Y. Naparstek, and I. R. Cohen, manuscript submitted for publication). We found previously that heparin molecules inhibited expression of T lymphocyte heparanase activity in vitro and in vivo, and administration of a low dose of heparin in mice inhibited lymphocyte traffic and delayed-type hypersensitivity reactions (Lider, O., J. Mekori, I. Vlodavsky, E. Baharav, Y. Naparstek, and I. R. Cohen, manuscript submitted for publication). We now report that treatment with commercial or chemically modified heparins at relatively low doses once daily (5 micrograms for mice and 20 micrograms for rats) led to inhibition of allograft rejection and the experimental autoimmune diseases adjuvant arthritis and experimental autoimmune encephalomyelitis. Higher doses of the heparins were less effective. The ability of chemically modified heparins to inhibit these immune reactions was associated with their ability to inhibit expression of T lymphocyte heparanase. There was no relationship to anticoagulant activity. Thus heparins devoid of anticoagulant activity can be effective in regulating immune reactions when used at appropriate doses.

Is Writing Performance Related to Keyboard Type? An Investigation from Examinees' Perspectives on the TOEFL IBT

ERIC Educational Resources Information Center

Ling, Guangming

2017-01-01

To investigate whether the type of keyboard used in exams introduces any construct-irrelevant variance to the TOEFL iBT Writing scores, we surveyed 17,040 TOEFL iBT examinees from 24 countries on their keyboard-related perceptions and preferences and analyzed the survey responses together with their test scores. Results suggest that controlling…

Digital Media for Low-Income Preschoolers' Effective Science Learning: A Study of iPad Instructions with a Social Development Approach

ERIC Educational Resources Information Center

Lee, Lena; Tu, Xintian

2016-01-01

As digital media devices have been increasingly used in early childhood educational settings, this study examined whether the iPad with a Vygotskian social development approach--namely, More Knowledgeable Other--can be integrated into low-income preschool classrooms to improve science learning. An analysis of variance was used to examine the…

A phase I, pharmacokinetic, and pharmacodynamic study of two schedules of vorinostat in combination with 5-fluorouracil and leucovorin in patients with refractory solid tumors.

PubMed

Fakih, Marwan G; Fetterly, Gerald; Egorin, Merrill J; Muindi, Josephia R; Espinoza-Delgado, Igor; Zwiebel, James A; Litwin, Alan; Holleran, Julianne L; Wang, Kangsheng; Diasio, Robert B

2010-07-15

We conducted a phase I clinical trial to determine the maximum tolerated dose (MTD) of daily or twice daily vorinostat x 3 days when combined with fixed doses of 5-fluorouracil (FU) and leucovorin every 2 weeks. Vorinostat doses were escalated in a standard 3 x 3 phase I design. FU/leucovorin was started on day 2 of vorinostat and consisted of leucovorin 400 mg/m(2) i.v. over 2 hours followed by FU 400 mg/m(2) i.v. bolus and 2,400 mg/m(2) over 46 hours (sLV5FU2). Forty-three patients were enrolled. Grade 3 fatigue, and hand and foot syndrome were the dose-limiting toxicities (DLT) at the 2,000 mg vorinostat once-daily dose level. Grade 3 fatigue and mucositis were DLTs at the 800 mg vorinostat twice-daily dose level. None of six patients at the 1,700 mg once daily or six patients at the 600 mg twice daily dose levels had a DLT; those dose levels represent the MTD. Twenty-one of 38 patients with FU-refractory colorectal cancer had stable disease, and one had a partial response. Vorinostat maximum serum concentrations at the MTD exceeded concentrations associated with thymidylate synthase downregulation in vitro. No pharmacokinetic interactions were noted between vorinostat and FU. The MTD of vorinostat in combination with sLV5FU2 is 1,700 mg orally once daily x 3 or 600 mg orally twice daily x 3 days every 2 weeks. Clinical activity in refractory colorectal cancer supports further clinical development of this combination. Copyrighth 2010 AACR.

A Phase I, Pharmacokinetic, and Pharmacodynamic Study of Two Schedules of Vorinostat in Combination with 5-Fluorouracil and Leucovorin in Patients with Refractory Solid Tumors

PubMed Central

Fakih, Marwan G.; Fetterly, Gerald; Egorin, Merrill J.; Muindi, Josephia R.; Espinoza-Delgado, Igor; Zwiebel, James A.; Litwin, Alan; Holleran, Julianne L.; Wang, Kangsheng; Diasio, Robert B.

2010-01-01

Purpose We conducted a phase I clinical trial to determine the maximum tolerated dose (MTD) of daily or twice daily vorinostat × 3 days when combined with fixed doses of 5-fluorouracil (FU) and leucovorin every 2 weeks. Experimental Design Vorinostat doses were escalated in a standard 3 × 3 phase I design. FU/leucovorin was started on day 2 of vorinostat and consisted of leucovorin 400 mg/m2 i.v. over 2 hours followed by FU 400 mg/m2 i.v. bolus and 2,400 mg/m2 over 46 hours (sLV5FU2). Results Forty-three patients were enrolled. Grade 3 fatigue, and hand and foot syndrome were the dose-limiting toxicities (DLT) at the 2,000 mg vorinostat once-daily dose level. Grade 3 fatigue and mucositis were DLTs at the 800 mg vorinostat twice-daily dose level. None of six patients at the 1,700 mg once daily or six patients at the 600 mg twice daily dose levels had a DLT; those dose levels represent the MTD. Twenty-one of 38 patients with FU-refractory colorectal cancer had stable disease, and one had a partial response. Vorinostat maximum serum concentrations at the MTD exceeded concentrations associated with thymidylate synthase downregulation in vitro. No pharmacokinetic interactions were noted between vorinostat and FU. Conclusions The MTD of vorinostat in combination with sLV5FU2 is 1,700 mg orally once daily × 3 or 600 mg orally twice daily × 3 days every 2 weeks. Clinical activity in refractory colorectal cancer supports further clinical development of this combination. PMID:20463088

An investigation into the selectivity of a novel series of benzoquinolizines for alpha 2-adrenoceptors in vivo.

PubMed Central

Paciorek, P. M.; Pierce, V.; Shepperson, N. B.; Waterfall, J. F.

1984-01-01

The potencies and selectivities of a novel series of benzoquinolizines for the alpha 2-adrenoceptor have been investigated in the rat in comparison with yohimbine and indoramin. Peripheral postjunctional alpha 2- and alpha 1-adrenoceptor blockade was measured as the reversal of B-HT 933 and methoxamine-induced pressor responses, respectively, in the pithed rat. Peripheral prejunctional alpha 2-adrenoceptor blockade was measured as the reversal of B-HT 933-induced inhibition of an electrically evoked tachycardia in the pithed rat. Central alpha 2-adrenoceptor blockade was measured as a reversal of the hypotension induced in anaesthetized rats by central (i.c.v.) administration of clonidine. Wy 25309, Wy 26392, Wy 26703 and yohimbine (0.3-3 mg kg-1 i.v.) evoked dose-dependent shifts to the right of the dose-response curves to B-HT 933 whilst having minimal effects on the methoxamine dose-response curve. The selectivity for alpha 2-adrenoceptors increased with the dose of antagonist administered. In general, the order of selectivity was Wy 25309 greater than Wy 26392 greater than Wy 26703 greater than yohimbine. Indoramin (1 mg kg-1 i.v.) shifted the methoxamine pressor dose-response curve to the right without affecting the B-HT 933 dose-response curves, confirming its selective alpha 1-antagonist activity. Peripheral administration of all three benzoquinolizines (1-100 micrograms kg-1 i.v.) led to a dose-dependent reversal of the hypotension evoked by central administration of clonidine (500 ng i.c.v.). The reversal was incomplete, higher doses causing a further decrease in blood pressure. (ABSTRACT TRUNCATED AT 250 WORDS) PMID:6329385

Comparative Effectiveness of Mesalamine, Sulfasalazine, Corticosteroids, and Budesonide for the Induction of Remission in Crohn's Disease: A Bayesian Network Meta-analysis.

PubMed

Coward, Stephanie; Kuenzig, M Ellen; Hazlewood, Glen; Clement, Fiona; McBrien, Kerry; Holmes, Rebecca; Panaccione, Remo; Ghosh, Subrata; Seow, Cynthia H; Rezaie, Ali; Kaplan, Gilaad G

2017-03-01

Induction treatment of mild-to-moderate Crohn's disease is controversial. To compare the induction of remission between different doses of mesalamine, sulfasalazine, corticosteroids, and budesonide for active Crohn's disease. We identified randomized controlled trials from existing Cochrane reviews and an updated literature search in Medline, EMBASE, and CENTRAL to November 2015. We included randomized controlled trials (n = 22) in adult patients with Crohn's disease that compared budesonide, sulfasalazine, mesalamine, or corticosteroids with placebo or each other, for the induction of remission (8-17 wks). Mesalamine (above and below 2.4 g/d) and budesonide (above and below 6 mg/d) were stratified into low and high doses. Our primary outcome was remission, defined as a Crohn's Disease Activity Index score <150. A Bayesian random-effects network meta-analysis was performed on the proportion in remission. Corticosteroids (odds ratio [OR] = 3.80; 95% credible interval [CrI]: 2.48-5.66), high-dose budesonide (OR = 2.96; 95% CrI: 2.06-4.30), and high-dose mesalamine (OR = 2.29; 95% CrI: 1.58-3.33) were superior to placebo. Corticosteroids were similar to high-dose budesonide (OR = 1.21; 95% CrI: 0.84-1.76), but more effective than high-dose mesalamine (OR = 1.83; 95% CrI: 1.16-2.88). Sulfasalazine was not significantly superior to any therapy including placebo. Randomized controlled trials that use a strict definition of induction of remission and disease severity at enrollment to assess effectiveness in treating mild-to-moderate Crohn's disease are limited. Corticosteroids and high-dose budesonide were effective treatments for inducing remission in mild-to-moderate Crohn's disease. High-dose mesalamine is an option among patients preferring to avoid steroids.

Between-Batch Pharmacokinetic Variability Inflates Type I Error Rate in Conventional Bioequivalence Trials: A Randomized Advair Diskus Clinical Trial.

PubMed

Burmeister Getz, E; Carroll, K J; Mielke, J; Benet, L Z; Jones, B

2017-03-01

We previously demonstrated pharmacokinetic differences among manufacturing batches of a US Food and Drug Administration (FDA)-approved dry powder inhalation product (Advair Diskus 100/50) large enough to establish between-batch bio-inequivalence. Here, we provide independent confirmation of pharmacokinetic bio-inequivalence among Advair Diskus 100/50 batches, and quantify residual and between-batch variance component magnitudes. These variance estimates are used to consider the type I error rate of the FDA's current two-way crossover design recommendation. When between-batch pharmacokinetic variability is substantial, the conventional two-way crossover design cannot accomplish the objectives of FDA's statistical bioequivalence test (i.e., cannot accurately estimate the test/reference ratio and associated confidence interval). The two-way crossover, which ignores between-batch pharmacokinetic variability, yields an artificially narrow confidence interval on the product comparison. The unavoidable consequence is type I error rate inflation, to ∼25%, when between-batch pharmacokinetic variability is nonzero. This risk of a false bioequivalence conclusion is substantially higher than asserted by regulators as acceptable consumer risk (5%). © 2016 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of The American Society for Clinical Pharmacology and Therapeutics.

SU-F-T-46: The Effect of Inter-Seed Attenuation and Tissue Composition in Prostate 125I Brachytherapy Dose Calculations

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

Tamura, K; Araki, F; Ohno, T

Purpose: To investigate the difference of dose distributions with/without the effect of inter-seed attenuation and tissue compositions in prostate {sup 125}I brachytherapy dose calculations, using Monte Carlo simulations of Particle and Heavy Ion Transport code System (PHITS). Methods: The dose distributions in {sup 125}I prostate brachytherapy were calculated using PHITS for non-simultaneous and simultaneous alignments of STM1251 sources in water or prostate phantom for six patients. The PHITS input file was created from DICOM-RT file which includes source coordinates and structures for clinical target volume (CTV) and organs at risk (OARs) of urethra and rectum, using in-house Matlab software. Photonmore » and electron cutoff energies were set to 1 keV and 100 MeV, respectively. The dose distributions were calculated with the kerma approximation and the voxel size of 1 × 1 × 1 mm{sup 3}. The number of incident photon was set to be the statistical uncertainty (1σ) of less than 1%. The effect of inter-seed attenuation and prostate tissue compositions was evaluated from dose volume histograms (DVHs) for each structure, by comparing to results of the AAPM TG-43 dose calculation (without the effect of inter-seed attenuation and prostate tissue compositions). Results: The dose reduction due to the inter-seed attenuation by source capsules was approximately 2% for CTV and OARs compared to those of TG-43. In additions, by considering prostate tissue composition, the D{sub 90} and V{sub 100} of CTV reduced by 6% and 1%, respectively. Conclusion: It needs to consider the dose reduction due to the inter-seed attenuation and tissue composition in prostate {sup 125}I brachytherapy dose calculations.« less

Batch versus column modes for the adsorption of radioactive metal onto rice husk waste: conditions optimization through response surface methodology.

PubMed

Kausar, Abida; Bhatti, Haq Nawaz; Iqbal, Munawar; Ashraf, Aisha

2017-09-01

Batch and column adsorption modes were compared for the adsorption of U(VI) ions using rice husk waste biomass (RHWB). Response surface methodology was employed for the optimization of process variables, i.e., (pH (A), adsorbent dose (B), initial ion concentration (C)) in batch mode. The B, C and C 2 affected the U(VI) adsorption significantly in batch mode. The developed quadratic model was found to be validated on the basis of regression coefficient as well as analysis of variance. The predicted and actual values were found to be correlated well, with negligible residual value, and B, C and C 2 were significant terms. The column study was performed considering bed height, flow rate and initial metal ion concentration, and adsorption efficiency was evaluated through breakthrough curves and bed depth service time and Thomas models. Adsorption was found to be dependent on bed height and initial U(VI) ion concentration, and flow rate decreased the adsorption capacity. Thomas models fitted well to the U(VI) adsorption onto RHWB. Results revealed that RHWB has potential to remove U(VI) ions and batch adsorption was found to be efficient versus column mode.

Attachment style and treatment completion among psychiatric inpatients with substance use disorders.

PubMed

Fowler, James Christopher; Groat, Michael; Ulanday, Mike

2013-01-01

A strong dose-response relationship exists for psychosocial treatments for co-morbid substance abuse disorders; yet rates of attrition are exceedingly high for those seeking treatment in residential and hospital settings. This study examined patient characteristics, including attachment style as predictors of completing 42 contiguous days of inpatient dual-diagnosis treatment among patients with substance use disorders. Baseline characteristics were assessed in 187 consecutively admitted patients with research diagnosis of substance use disorders. Hierarchical logistic regression analysis was used to examine predictors of treatment retention. Results indicated a two-variable model consisting of total number of co-occurring Axis I and II disorders, and pre-occupied attachment style, accounting for 17% of the variance. Attachment status predicted retention above and beyond psychiatric co-morbid disorders, demonstrating incremental predictive validity. Moderator analyses failed to detect an interaction. Among inpatients with substance abuse disorders, anxious-preoccupied attachment style predicted treatment retention, reflecting the importance of interpersonal components of treatment relationships in completing treatment. This study adds to a growing body of evidence linking attachment style with treatment adherence. Further research is needed to examine possible mechanisms associated with this relationship. Copyright © American Academy of Addiction Psychiatry.

Successful treatment of solitary toxic thyroid nodules with relatively low-dose iodine-131, with low prevalence of hypothyroidism

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

Ross, D.S.; Ridgway, E.C.; Daniels, G.H.

1984-10-01

Forty-five patients with solitary toxic thyroid adenomas received 131I (mean dose, 10.3 mCi) for treatment of hyperthyroidism and were followed for 4.9 +/- 3.2 years (range, 0.5 to 13.5). Seventy-seven percent were euthyroid by 2 months, 91% by 6 months, and 93% by 1 year. Only 3 patients did not respond to a single dose of 131I, but all responded to multiple doses. Late recurrent hyperthyroidism occurred in 3 patients at 4.5, 6, and 10 years after treatment with a single dose of 131I. No patient developed clinical hypothyroidism, and none had a low serum thyroxine level associated with anmore » elevated serum thyrotrophin level. Three patients developed minimal elevations in serum thyrotrophin levels: 1, 4, and 7.5 years after 131I treatment, their thyrotrophin levels were 8.4, 6.2, and 9.6 microU/mL, respectively. All 3 had normal serum thyroxine levels and were clinically euthyroid. Mean serum thyroxine concentrations of all patients were unchanged between 1 and more than 9 years of follow-up. These data suggest that solitary toxic adenomas may be treated with relatively low doses of 131I (5 to 15 mCi), and that post-treatment hypothyroidism is very unusual.« less

Sampling design optimisation for rainfall prediction using a non-stationary geostatistical model

NASA Astrophysics Data System (ADS)

Wadoux, Alexandre M. J.-C.; Brus, Dick J.; Rico-Ramirez, Miguel A.; Heuvelink, Gerard B. M.

2017-09-01

The accuracy of spatial predictions of rainfall by merging rain-gauge and radar data is partly determined by the sampling design of the rain-gauge network. Optimising the locations of the rain-gauges may increase the accuracy of the predictions. Existing spatial sampling design optimisation methods are based on minimisation of the spatially averaged prediction error variance under the assumption of intrinsic stationarity. Over the past years, substantial progress has been made to deal with non-stationary spatial processes in kriging. Various well-documented geostatistical models relax the assumption of stationarity in the mean, while recent studies show the importance of considering non-stationarity in the variance for environmental processes occurring in complex landscapes. We optimised the sampling locations of rain-gauges using an extension of the Kriging with External Drift (KED) model for prediction of rainfall fields. The model incorporates both non-stationarity in the mean and in the variance, which are modelled as functions of external covariates such as radar imagery, distance to radar station and radar beam blockage. Spatial predictions are made repeatedly over time, each time recalibrating the model. The space-time averaged KED variance was minimised by Spatial Simulated Annealing (SSA). The methodology was tested using a case study predicting daily rainfall in the north of England for a one-year period. Results show that (i) the proposed non-stationary variance model outperforms the stationary variance model, and (ii) a small but significant decrease of the rainfall prediction error variance is obtained with the optimised rain-gauge network. In particular, it pays off to place rain-gauges at locations where the radar imagery is inaccurate, while keeping the distribution over the study area sufficiently uniform.

Blinded sample size re-estimation in three-arm trials with 'gold standard' design.

PubMed

Mütze, Tobias; Friede, Tim

2017-10-15

In this article, we study blinded sample size re-estimation in the 'gold standard' design with internal pilot study for normally distributed outcomes. The 'gold standard' design is a three-arm clinical trial design that includes an active and a placebo control in addition to an experimental treatment. We focus on the absolute margin approach to hypothesis testing in three-arm trials at which the non-inferiority of the experimental treatment and the assay sensitivity are assessed by pairwise comparisons. We compare several blinded sample size re-estimation procedures in a simulation study assessing operating characteristics including power and type I error. We find that sample size re-estimation based on the popular one-sample variance estimator results in overpowered trials. Moreover, sample size re-estimation based on unbiased variance estimators such as the Xing-Ganju variance estimator results in underpowered trials, as it is expected because an overestimation of the variance and thus the sample size is in general required for the re-estimation procedure to eventually meet the target power. To overcome this problem, we propose an inflation factor for the sample size re-estimation with the Xing-Ganju variance estimator and show that this approach results in adequately powered trials. Because of favorable features of the Xing-Ganju variance estimator such as unbiasedness and a distribution independent of the group means, the inflation factor does not depend on the nuisance parameter and, therefore, can be calculated prior to a trial. Moreover, we prove that the sample size re-estimation based on the Xing-Ganju variance estimator does not bias the effect estimate. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Variance estimation when using inverse probability of treatment weighting (IPTW) with survival analysis.

PubMed

Austin, Peter C

2016-12-30

Propensity score methods are used to reduce the effects of observed confounding when using observational data to estimate the effects of treatments or exposures. A popular method of using the propensity score is inverse probability of treatment weighting (IPTW). When using this method, a weight is calculated for each subject that is equal to the inverse of the probability of receiving the treatment that was actually received. These weights are then incorporated into the analyses to minimize the effects of observed confounding. Previous research has found that these methods result in unbiased estimation when estimating the effect of treatment on survival outcomes. However, conventional methods of variance estimation were shown to result in biased estimates of standard error. In this study, we conducted an extensive set of Monte Carlo simulations to examine different methods of variance estimation when using a weighted Cox proportional hazards model to estimate the effect of treatment. We considered three variance estimation methods: (i) a naïve model-based variance estimator; (ii) a robust sandwich-type variance estimator; and (iii) a bootstrap variance estimator. We considered estimation of both the average treatment effect and the average treatment effect in the treated. We found that the use of a bootstrap estimator resulted in approximately correct estimates of standard errors and confidence intervals with the correct coverage rates. The other estimators resulted in biased estimates of standard errors and confidence intervals with incorrect coverage rates. Our simulations were informed by a case study examining the effect of statin prescribing on mortality. © 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.

Dose-dependent effects of β-phenylglutamic acid hydrochloride (RGPU-135, neuroglutam) on animal behavior.

PubMed

Tyurenkov, I N; Bagmetova, V V; Chernyshova, Yu V; Merkushenkova, O V

2014-12-01

β-Phenylglutamic acid hydrochloride (RGPU-135, neuroglutam) in doses of 13-650 mg/kg suppressed depressive behavior of animals in the Porsolt test (i.e. produced antidepressant properties), reduced anxiety in the open-field, elevated plus maze, and Vogel conflict tests (i.e. produced anxiolytic effects). RGPU-135 in doses of 26-130 mg/kg exhibited more pronounced antidepressant action and in doses of 26 and 52 mg/kg had more pronounced anxiolytic effects. RGPU-135 in doses of 13-78 mg/kg increased locomotor and exploratory activity of animals in the open-field test. Activating effects of this agent decreased with increasing the dose. RGPU-135 in the subtoxic dose (650 mg/kg) suppressed locomotor activity of animals (produced sedative effect).

Designing a compact high performance brain PET scanner—simulation study

NASA Astrophysics Data System (ADS)

Gong, Kuang; Majewski, Stan; Kinahan, Paul E.; Harrison, Robert L.; Elston, Brian F.; Manjeshwar, Ravindra; Dolinsky, Sergei; Stolin, Alexander V.; Brefczynski-Lewis, Julie A.; Qi, Jinyi

2016-05-01

The desire to understand normal and disordered human brain function of upright, moving persons in natural environments motivates the development of the ambulatory micro-dose brain PET imager (AMPET). An ideal system would be light weight but with high sensitivity and spatial resolution, although these requirements are often in conflict with each other. One potential approach to meet the design goals is a compact brain-only imaging device with a head-sized aperture. However, a compact geometry increases parallax error in peripheral lines of response, which increases bias and variance in region of interest (ROI) quantification. Therefore, we performed simulation studies to search for the optimal system configuration and to evaluate the potential improvement in quantification performance over existing scanners. We used the Cramér-Rao variance bound to compare the performance for ROI quantification using different scanner geometries. The results show that while a smaller ring diameter can increase photon detection sensitivity and hence reduce the variance at the center of the field of view, it can also result in higher variance in peripheral regions when the length of detector crystal is 15 mm or more. This variance can be substantially reduced by adding depth-of-interaction (DOI) measurement capability to the detector modules. Our simulation study also shows that the relative performance depends on the size of the ROI, and a large ROI favors a compact geometry even without DOI information. Based on these results, we propose a compact ‘helmet’ design using detectors with DOI capability. Monte Carlo simulations show the helmet design can achieve four-fold higher sensitivity and resolve smaller features than existing cylindrical brain PET scanners. The simulations also suggest that improving TOF timing resolution from 400 ps to 200 ps also results in noticeable improvement in image quality, indicating better timing resolution is desirable for brain imaging.

Designing a compact high performance brain PET scanner—simulation study

PubMed Central

Gong, Kuang; Majewski, Stan; Kinahan, Paul E; Harrison, Robert L; Elston, Brian F; Manjeshwar, Ravindra; Dolinsky, Sergei; Stolin, Alexander V; Brefczynski-Lewis, Julie A; Qi, Jinyi

2016-01-01

The desire to understand normal and disordered human brain function of upright, moving persons in natural environments motivates the development of the ambulatory micro-dose brain PET imager (AMPET). An ideal system would be light weight but with high sensitivity and spatial resolution, although these requirements are often in conflict with each other. One potential approach to meet the design goals is a compact brain-only imaging device with a head-sized aperture. However, a compact geometry increases parallax error in peripheral lines of response, which increases bias and variance in region of interest (ROI) quantification. Therefore, we performed simulation studies to search for the optimal system configuration and to evaluate the potential improvement in quantification performance over existing scanners. We used the Cramér–Rao variance bound to compare the performance for ROI quantification using different scanner geometries. The results show that while a smaller ring diameter can increase photon detection sensitivity and hence reduce the variance at the center of the field of view, it can also result in higher variance in peripheral regions when the length of detector crystal is 15 mm or more. This variance can be substantially reduced by adding depth-of- interaction (DOI) measurement capability to the detector modules. Our simulation study also shows that the relative performance depends on the size of the ROI, and a large ROI favors a compact geometry even without DOI information. Based on these results, we propose a compact ‘helmet’ design using detectors with DOI capability. Monte Carlo simulations show the helmet design can achieve four-fold higher sensitivity and resolve smaller features than existing cylindrical brain PET scanners. The simulations also suggest that improving TOF timing resolution from 400 ps to 200 ps also results in noticeable improvement in image quality, indicating better timing resolution is desirable for brain imaging. PMID:27081753

Cramer-Rao Bound, MUSIC, and Maximum Likelihood. Effects of Temporal Phase Difference

DTIC Science & Technology

1990-11-01

Technical Report 1373 November 1990 Cramer-Rao Bound, MUSIC , And Maximum Likelihood Effects of Temporal Phase o Difference C. V. TranI OTIC Approved... MUSIC , and Maximum Likelihood (ML) asymptotic variances corresponding to the two-source direction-of-arrival estimation where sources were modeled as...1pI = 1.00, SNR = 20 dB ..................................... 27 2. MUSIC for two equipowered signals impinging on a 5-element ULA (a) IpI = 0.50, SNR

Testing prediction capabilities of an 131I terrestrial transport model by using measurements collected at the Hanford nuclear facility.

PubMed

Apostoaei, A Iulian

2005-05-01

A model describing transport of 131I in the environment was developed by SENES Oak Ridge, Inc., for assessment of radiation doses and excess lifetime risk from 131I atmospheric releases from Oak Ridge Reservation in Oak Ridge, Tennessee, and from Idaho National Engineering and Environmental Laboratory in southeast Idaho. This paper describes the results of an exercise designed to test the reliability of this model and to identify the main sources of uncertainty in doses and risks estimated by this model. The testing of the model was based on materials published by the International Atomic Energy Agency BIOMASS program, specifically environmental data collected after the release into atmosphere of 63 curies of 131I during 2-5 September 1963, after an accident at the Hanford PUREX Chemical Separations Plant, in Hanford, Washington. Measurements of activity in air, vegetation, and milk were collected in nine counties around Hanford during the first couple of months after the accident. The activity of 131I in the thyroid glands of two children was measured 47 d after the accident. The model developed by SENES Oak Ridge, Inc., was used to estimate concentrations of 131I in environmental media, thyroid doses for the general population, and the activity of 131I in thyroid glands of the two children. Predicted concentrations of 131I in pasture grass and milk and thyroid doses were compared with similar estimates produced by other modelers. The SENES model was also used to estimate excess lifetime risk of thyroid cancer due to the September 1963 releases of 131I from Hanford. The SENES model was first calibrated and then applied to all locations of interest around Hanford without fitting the model parameters to a given location. Predictions showed that the SENES model reproduces satisfactorily the time-dependent and the time-integrated measured concentrations in vegetation and milk, and provides reliable estimates of 131I activity in thyroids of children. SENES model generated concentrations of 131I closer to observed concentrations, as compared to the predictions produced with other models. The inter-model comparison showed that variation of thyroid doses among all participating models (SENES model included) was a factor of 3 for the general population, but a factor of 10 for the two studied children. As opposed to other models, SENES model allows a complete analysis of uncertainties in every predicted quantity, including estimated thyroid doses and risk of thyroid cancer. The uncertainties in the risk-per-unit-dose and the dose-per-unit-intake coefficients are major contributors to the uncertainty in the estimated lifetime risk and thyroid dose, respectively. The largest contributors to the uncertainty in the estimated concentration in milk are the feed-to-milk transfer factor (F(m)), the dry deposition velocity (V(d)), and the mass interception factor (r/Y)dry for the elemental form of iodine (I2). Exposure to the 1963 PUREX/Hanford accident produced low doses and risks for people living at the studied locations. The upper 97.5th percentile of the excess lifetime risk of thyroid cancer for the most extreme situations is about 10(-4). Measurements in pasture grass and milk at all locations around Hanford indicate a very low transfer of 131I from pasture to cow's milk (e.g., a feed-to-milk transfer coefficient, F(m), for commercial cows of about 0.0022 d L(-1)). These values are towards the low end of F(m) values measured elsewhere and they are low compared to the F(m) values used in other dose reconstruction studies, including the Hanford Environmental Dose Reconstruction.

Overexpression of variant PNPLA3 gene at I148M position causes malignant transformation of hepatocytes via IL-6-JAK2/STAT3 pathway in low dose free fatty acid exposure: a laboratory investigation in vitro and in vivo

PubMed Central

Liu, Zhengtao; Chen, Tianchi; Lu, Xiaoxiao; Xie, Haiyang; Zhou, Lin; Zheng, Shusen

2016-01-01

Epidemiological survey identified that the variant patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene at I148M position exerts direct effect in promoting hepatocellular carcinoma (HCC) under extraneous oxidative stress by interaction with obesity. However, the mechanism is still unknown. HepG2 cells were overexpressed by transinfection of PNPLA3 with wild-type 148I (PNPLA3WT) and mutant 148M (PNPLA3I148M), respectively. Variation in metabolic indicators, hepatic steatosis, biological behaviors and signaling molecules related to cancer promotion was measured in hepatocytes using low-dose free fatty acid (FFA) exposure. Effect of PNPLA3I148M on xenograft biology and its interaction with dietary obesity were also evaluated in animal study. Cells overexpresssing PNPLA3I148M in low-dose FFA incubation showed more proliferation, migration, invasion, and less apoptosis (P<0.05). Low-dose FFA specifically activated JAK2/STAT3 phosphorylation of PNPLA3I148M cells via upregulation of interleukin-6. Animal study showed high-fat diet accelerated growth of xenografts derived from PNPLA3I148M cells incubated in low-dose FFA. In low oxidative stress, PNPLA3I148M initiated the hepatocyte malignant transformation through the activation of inflammation-mediated JAK/STAT pathway. Dietary obesity amplified the growth of tumor from PNPLA3I148M cells by interaction with local FFA incubation. Anti-inflammation and weight loss might be potential approaches for preventing HCC in high-risk population carrying PNPLA3 variant. PMID:27186262

Overexpression of variant PNPLA3 gene at I148M position causes malignant transformation of hepatocytes via IL-6-JAK2/STAT3 pathway in low dose free fatty acid exposure: a laboratory investigation in vitro and in vivo.

PubMed

Liu, Zhengtao; Chen, Tianchi; Lu, Xiaoxiao; Xie, Haiyang; Zhou, Lin; Zheng, Shusen

2016-01-01

Epidemiological survey identified that the variant patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene at I148M position exerts direct effect in promoting hepatocellular carcinoma (HCC) under extraneous oxidative stress by interaction with obesity. However, the mechanism is still unknown. HepG2 cells were overexpressed by transinfection of PNPLA3 with wild-type 148I (PNPLA3(WT)) and mutant 148M (PNPLA3(I148M)), respectively. Variation in metabolic indicators, hepatic steatosis, biological behaviors and signaling molecules related to cancer promotion was measured in hepatocytes using low-dose free fatty acid (FFA) exposure. Effect of PNPLA3(I148M) on xenograft biology and its interaction with dietary obesity were also evaluated in animal study. Cells overexpresssing PNPLA3(I148M) in low-dose FFA incubation showed more proliferation, migration, invasion, and less apoptosis (P<0.05). Low-dose FFA specifically activated JAK2/STAT3 phosphorylation of PNPLA3(I148M) cells via upregulation of interleukin-6. Animal study showed high-fat diet accelerated growth of xenografts derived from PNPLA3(I148M) cells incubated in low-dose FFA. In low oxidative stress, PNPLA3(I148M) initiated the hepatocyte malignant transformation through the activation of inflammation-mediated JAK/STAT pathway. Dietary obesity amplified the growth of tumor from PNPLA3(I148M) cells by interaction with local FFA incubation. Anti-inflammation and weight loss might be potential approaches for preventing HCC in high-risk population carrying PNPLA3 variant.

The effect of peptidase inhibitors on bradykinin-induced bronchoconstriction in guinea-pigs in vivo.

PubMed Central

Ichinose, M.; Barnes, P. J.

1990-01-01

1. Bradykinin (BK) instilled directly into the airway lumen caused bronchoconstriction in anaesthetized, mechanically ventilated guinea-pigs in the presence of propranolol (1 mg kg-1 i.v.). The geometric mean dose of BK required to produce 100% increase in airway opening pressure (PD100) was 22.9 nmol (95% c.i. 11.7-44.6 nmol). 2. The dose-response curve for the effect of instilled BK was significantly shifted to the left by the angiotensin converting enzyme (ACE) inhibitor, captopril (5 and 50 nmol instillation, PD100 = 3.0, 95% c.i. 0.98-8.9, and 2.0 nmol, 95% c.i. 0.65-6.2 nmol, respectively). 3. The neutral endopeptidase (NEP) inhibitor, phosphoramidon (5 and 50 nmol instillation) also shifted the dose-response curve for the effect of instilled BK; the PD100 values = 2.2 (95% c.i. 0.40-11.7) and 1.8 nmol (95% c.i. 0.87-3.5 nmol), respectively. 4. After pretreatment with captopril (50 nmol) and phosphoramidon (50 nmol) in combination, the dose-response curve for the effect of instilled BK (PD100 = 1.1 nmol, 95% c.i. 0.37-3.2 nmol) was similar to that obtained in the presence of each inhibitor used alone. 5. The kinase I inhibitor, DL-2-mercaptomethyl-3-guanidinoethylthiopropionic acid (50 nmol instillation) failed to alter the dose-response curve to instilled BK (PD100 = 14.6 nmol, 95% c.i. 6.7-32.0 nmol). 6. These data suggest that both ACE and NEP degrade BK in the airway lumen, but that kininase I is not involved. PMID:2282470

A robust two-stage design identifying the optimal biological dose for phase I/II clinical trials.

PubMed

Zang, Yong; Lee, J Jack

2017-01-15

We propose a robust two-stage design to identify the optimal biological dose for phase I/II clinical trials evaluating both toxicity and efficacy outcomes. In the first stage of dose finding, we use the Bayesian model averaging continual reassessment method to monitor the toxicity outcomes and adopt an isotonic regression method based on the efficacy outcomes to guide dose escalation. When the first stage ends, we use the Dirichlet-multinomial distribution to jointly model the toxicity and efficacy outcomes and pick the candidate doses based on a three-dimensional volume ratio. The selected candidate doses are then seamlessly advanced to the second stage for dose validation. Both toxicity and efficacy outcomes are continuously monitored so that any overly toxic and/or less efficacious dose can be dropped from the study as the trial continues. When the phase I/II trial ends, we select the optimal biological dose as the dose obtaining the minimal value of the volume ratio within the candidate set. An advantage of the proposed design is that it does not impose a monotonically increasing assumption on the shape of the dose-efficacy curve. We conduct extensive simulation studies to examine the operating characteristics of the proposed design. The simulation results show that the proposed design has desirable operating characteristics across different shapes of the underlying true dose-toxicity and dose-efficacy curves. The software to implement the proposed design is available upon request. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

DNA Topoisomerase IB as a Potential Ionizing Radiation Exposure and Dose Biomarker.

PubMed

Daudee, Rotem; Gonen, Rafi; German, Uzi; Orion, Itzhak; Alfassi, Zeev B; Priel, Esther

2018-06-01

In radiation exposure scenarios where physical dosimetry is absent or inefficient, dose estimation must rely on biological markers. A reliable biomarker is of utmost importance in correlating biological system changes with radiation exposure. Human DNA topoisomerase ІB (topo І) is a ubiquitous nuclear enzyme, which is involved in essential cellular processes, including transcription, DNA replication and DNA repair, and is the target of anti-cancer drugs. It has been shown that the cellular activity of this enzyme is significantly sensitive to various DNA lesions, including radiation-induced DNA damages. Therefore, we investigated the potential of topo I as a biomarker of radiation exposure and dose. We examined the effect of exposure of different human cells to beta, X-ray and gamma radiation on the cellular catalytic activity of topo I. The results demonstrate a significant reduction in the DNA relaxation activity of topo I after irradiation and the level of the reduction was correlated with radiation dose. In normal human peripheral blood lymphocytes, exposure for 3 h to an integral dose of 0.065 mGy from tritium reduced the enzyme activity to less than 25%. In MG-63 osteoblast-like cells and in human pulmonary fibroblast (HPF) cells exposed to gamma radiation from a 60 Co source (up to 2 Gy) or to X rays (up to 2.8 Gy), a significant decrease in topo I catalytic activity was also observed. We observed that the enzyme-protein level was not altered but was partially posttranslational modified by ADP-ribosylation of the enzyme protein that is known to reduce topo I activity. The results of this study suggest that the decrease in the cellular topo I catalytic activity after low-dose exposure to different radiation types may be considered as a novel biomarker of ionizing radiation exposure and dose. For this purpose, a suitable ELISA-based method for large-scale analysis of radiation-induced topo I modification is under development.