DOE Office of Scientific and Technical Information (OSTI.GOV)
Dornsife, William P.; Kirk, J. Scott; Shaw, Chris G.
2012-07-01
This Performance Assessment (PA) submittal is an update to the original PA that was developed to support the licensing of the Waste Control Specialists LLC Low-Level Radioactive Waste (LLRW) disposal facility. This update includes both the Compact Waste Facility (CWF) and the Federal Waste Facility (FWF), in accordance with Radioactive Material License (RML) No. R04100, License Condition (LC) 87. While many of the baseline assumptions supporting the initial license application PA were incorporated in this update, a new transport code, GoldSim, and new deterministic groundwater flow codes, including HYDRUS and MODFLOWSURFACT{sup TM}, were employed to demonstrate compliance with the performancemore » objectives codified in the regulations and RML No. R04100, LC 87. A revised source term, provided by the Texas Commission on Environmental Quality staff, was used to match the initial 15 year license term. This updated PA clearly confirms and demonstrates the robustness of the characteristics of the site's geology and the advanced engineering design of the disposal units. Based on the simulations from fate and transport models, the radiation doses to members of the general public and site workers predicted in the initial and updated PA were a small fraction of the criterion doses of 0.25 mSv and 50 mSv, respectively. In a comparison between the results of the updated PA against the one developed in support of the initial license, both clearly demonstrated the robustness of the characteristics of the site's geology and engineering design of the disposal units. Based on the simulations from fate and transport models, the radiation doses to members of the general public predicted in the initial and updated PA were a fraction of the allowable 25 mrem/yr (0.25 m sievert/yr) dose standard for tens-of-thousands of years into the future. Draft Texas guidance on performance assessment (TCEQ, 2004) recommends a period of analysis equal to 1,000 years or until peak doses from the more mobile radionuclides occur. The EPA National Emissions Standards for Hazardous Air Pollutants limits radionuclide doses through the air pathway to 10 mrem/yr. Gaseous radionuclide doses from the CWF and the FWF, due to decomposition gases, are a small fraction of the dose limit. The radon flux from the CWF and FWF were compared to the flux limit of 20 pCi/m{sup 2}-s from 40 CFR 192. Because of the thick cover system, the calculated radon flux was a very small fraction of the limit. (authors)« less
This report updates the cancer dose-response assessment for PCBs and shows how information on toxicity, disposition, and environmental processes can be considered together to evaluate health risks from PCB mixtures in the environment.
PCBs: Cancer Dose-Response Assessment and Application to Environmental Mixtures (1996)
This report updates the cancer dose-response assessment for polychlorinated biphenyls (PCBs) and shows how information on toxicity, disposition, and environmental processes can be considered together to evaluate health risks from PCB mixtures in the environment. Processes that ch...
IRIS Toxicological Review of Tetrachloroethylene ...
EPA conducted a peer review of the scientific basis supporting the human health hazard and dose-response assessment of tetrachloroethylene that will appear on the Integrated Risk Information System (IRIS) database. Peer review is meant to ensure that science is used credibly and appropriately in derivation of the toxicological characterization and dose-response assessments. This draft health assessment addresses both non-cancer and cancer human health effects that may result from chronic exposure to tetrachloroethylene (also called Perchloroethylene or Perc) . This is an update of an existing assessment posted on IRIS in 1988. This draft Toxicological Review includes a chronic Reference Concentration (RfC) and carcinogenicity assessment, which are not currently available on IRIS, as well as an update of the 1988 IRIS Reference Dose (RfD). Tetrachloroethylene is a chemical solvent that is widely used for dry cleaning of fabrics, metal degreasing, and in making some consumer products and other chemicals.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hoover, M.D.; Farrell, R.F.; Newton, G.J.
1995-12-01
The recent 1995 WIPP Safety Analysis Report (SAR) Update provided detailed analyses of potential radiation doses to members of the public at the site boundary during postulated accident scenarios at the U.S. Department of Energy`s Waste Isolation Pilot Plant (WIPP). The SAR Update addressed the complete spectrum of potential accidents associated with handling and emplacing transuranic waste at WIPP, including damage to waste drums from fires, punctures, drops, and other disruptions. The report focused on the adequacy of the multiple layers of safety practice ({open_quotes}defense-in-depth{close_quotes}) at WIPP, which are designed to (1) reduce the likelihood of accidents and (2) limitmore » the consequences of those accidents. The safeguards which contribute to defense-in-depth at WIPP include a substantial array of inherent design features, engineered controls, and administrative procedures. The SAR Update confirmed that the defense-in-depth at WIPP is adequate to assure the protection of the public and environment. As a supplement to the 1995 SAR Update, we have conducted additional analyses to confirm that these controls will also provide adequate protection to workers at the WIPP. The approaches and results of the worker dose assessment are summarized here. In conformance with the guidance of DOE Standard 3009-94, we emphasize that use of these evaluation guidelines is not intended to imply that these numbers constitute acceptable limits for worker exposures under accident conditions. However, in conjunction with the extensive safety assessment in the 1995 SAR Update, these results indicate that the Carlsbad Area Office strategy for the assessment of hazards and accidents assures the protection of workers, members of the public, and the environment.« less
IRIS Toxicological Review of 1,4-Dioxane (with Inhalation Update) (External Review Draft)
EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of 1,4-Dioxane (with inhalation update) that when finalized will appear on the Integrated Risk Information System (IRIS) database.
Update the following IRIS chemical dose-response assessments: Barium (cancer, RfC), o-Cresol (RfD, cancer), carbon disulfied (RfD, RfC), 1,1-Dichloroethane (cancer), 2,4-Dimethylphenol (RfD), 1,4-Dibromobenzene (RfD), 1-chloro-1,1-difluroelfane (RfC, Acetyl chloride (cancer),2,4...
IRIS Toxicological Review of 1,4-Dioxane (with Inhalation Update) (Final Report)
The final IRIS Toxicological Review of 1,4-dioxane (with inhalation update) provides scientific support and rationale for the hazard and dose-response assessment pertaining to chronic exposure to 1,4-dioxane. Human health risk concerns for 1,4-dioxane are primarily relat...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Alkhatib, H; Oves, S
Purpose: To demonstrate a quick and comprehensive method verifying the accuracy of the updated dose model by recalculating dose distribution in an anthropomorphic phantom with a new version of the TPS and comparing the results to measured values. Methods: CT images and IMRT plan of an RPC anthropomorphic head phantom, previously calculated by Pinnacle 9.0, was re-computed using Pinnacle 9.2 and 9.6. The dosimeters within the phantom include four TLD capsules representing a primary PTV, two TLD capsules representing a secondary PTV, and two TLD capsules representing an organ at risk. Also included were three sheets of Gafchromic film. Performancemore » of the updated TPS version was assessed by recalculating point doses and dose profiles corresponding to TLD and film position respectively and then comparing the results to reported values by the RPC. Results: Comparing calculated doses to reported measured doses from the RPC yielded an average disagreement of 1.48%, 2.04% and 2.10% for versions 9.0, 9.2, 9.6 respectively. Computed doses points all meet the RPC's passing criteria with the exception of the point representing the superior organ at risk in version 9.6. However, qualitative analysis of the recalculated dose profiles showed improved agreement with those of the RPC, especially in the penumbra region. Conclusion: This work has demonstrated the calculation results of Pinnacle 9.2 and 9.6 vs 9.0 version. Additionally, this study illustrates a method for the user to gain confidence upgrade to a newer version of the treatment planning system.« less
Ketamine as an adjuvant to opioids for cancer pain.
Bell, Rae F; Eccleston, Christopher; Kalso, Eija A
2017-06-28
This is an update of a review first published in 2003 and updated in 2012.Ketamine is a commonly used anaesthetic agent, and in subanaesthetic doses is also given as an adjuvant to opioids for the treatment of refractory cancer pain, when opioids alone or in combination with appropriate adjuvant analgesics prove to be ineffective. Ketamine is known to have psychomimetic (including hallucinogenic), urological, and hepatic adverse effects. To determine the effectiveness and adverse effects of ketamine as an adjuvant to opioids for refractory cancer pain in adults. For this update, we searched MEDLINE (OVID) to December 2016. We searched CENTRAL (CRSO), Embase (OVID) and two clinical trial registries to January 2017. The intervention considered by this review was the addition of ketamine, given by any route of administration, in any dose, to pre-existing opioid treatment given by any route and in any dose, compared with placebo or active control. We included studies with a group size of at least 10 participants who completed the trial. Two review authors independently assessed the search results and performed 'Risk of bias' assessments. We aimed to extract data on patient-reported pain intensity, total opioid consumption over the study period; use of rescue medication; adverse events; measures of patient satisfaction/preference; function; and distress. We also assessed participant withdrawal (dropout) from trial. We assessed the quality of the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). One new study (185 participants) was identified by the updated search and included in the review. We included a total of three studies in this update.Two small studies, both with cross-over design, with 20 and 10 participants respectively, were eligible for inclusion in the original review. One study with 20 participants examined the addition of intrathecal ketamine to intrathecal morphine, compared with intrathecal morphine alone. The second study with 10 participants examined the addition of intravenous ketamine bolus in two different doses to ongoing morphine therapy, compared with placebo. Both of these studies reported reduction in pain intensity and reduction in morphine requirements when ketamine was added to opioid for refractory cancer pain. The new study identified by the updated search had a parallel group design and 185 participants. This placebo-controlled study examined rapid titration of subcutaneous ketamine to high dose (500 mg) in participants who were using different opioids. There were no differences between groups for patient-reported pain intensity.Pooling of the data from the three included trials was not appropriate because of clinical heterogeneity.The study examining intrathecal drug administration reported no adverse events related to ketamine. In the study using intravenous bolus administration, ketamine caused hallucinations in four of 10 participants. In the rapid dose escalation/high-dose subcutaneous ketamine study, there was almost twice the incidence of adverse events in the ketamine group, compared to the placebo group, with the most common adverse events being needle site irritation and cognitive disturbance. Two serious adverse events (bradyarrhythmia and cardiac arrest) thought to be related to ketamine were also reported in this trial.For all three studies there was an unclear risk of bias overall. Using GRADE, we judged the quality of the evidence to be very low due to study limitations and imprecision due to the small number of participants in all comparisons. Current evidence is insufficient to assess the benefits and harms of ketamine as an adjuvant to opioids for the relief of refractory cancer pain. The evidence was of very low quality, meaning that it does not provide a reliable indication of the likely effect, and the likelihood that the effect will be substantially different is high. Rapid dose escalation of ketamine to high dose (500 mg) does not appear to have clinical benefit and may be associated with serious adverse events. More randomised controlled trials (RCTs) examining specific low-dose ketamine clinical regimens in current use are needed.
IRIS Toxicological Review of 2,2',4,4'-Tetrabromodiphenyl ...
The U.S. EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessments of congeners of polybrominated diphenyl ethers (PDBEs), this review is about 2,2',4,4'-Tetrabromodiphenyl Ether, or commonly referred to as tetraBDE (BDE-47). Following the external peer review this assessment will appear in the Integrated Risk Information System (IRIS) database. Peer review will ensure that science is used credibly and appropriately in derivation of the dose-response assessments and toxicological characterization. EPA is updating the Integrated Risk Information System (IRIS) health assessments for the PBDEs.
Comparison of current recommended regimens of atropinization in organophosphate poisoning.
Connors, Nicholas J; Harnett, Zachary H; Hoffman, Robert S
2014-06-01
Atropine is the mainstay of therapy in organophosphate (OP) toxicity, though research and consensus on dosing is lacking. In 2004, as reported by Eddleston et al. (J Toxicol Clin Toxicol 42(6):865-75, 2004), they noted variation in recommended regimens. We assessed revisions of original references, additional citations, and electronic sources to determine the current variability in atropine dosing recommendations. Updated editions of references from Eddleston et al.'s work, texts of Internal and Emergency Medicine, and electronic resources were reviewed for atropine dosing recommendations. For comparison, recommendations were assessed using the same mean dose (23.4 mg) and the highest dose (75 mg) of atropine as used in the original paper. Recommendations were also compared with the dosing regimen from the World Health Organization (WHO). Thirteen of the original recommendations were updated and 15 additional references were added giving a convenience sample of 28. Sufficient information to calculate time to targeted dose was provided by 24 of these samples. Compared to 2004, current recommendations have greatly increased the speed of atropinization with 13/24 able to reach the mean and high atropine dose within 30 min compared to 1/36 in 2004. In 2004, there were 13 regimens where the maximum time to reach 75 mg was over 18 h, whereas now, there are 2. While only one recommendation called for doubling the dose for faster escalation in 2004, 15 of the 24 current works include dose doubling. In 2004, Eddleston et al. called for an evidence-based guideline for the treatment of OP poisoning that could be disseminated worldwide. Many current recommendations can adequately treat patients within 1 h. While the WHO recommendations remain slow to treat patients with OP poisoning, other authorities are close to a consensus on rapid atropinization.
Aylward, L L; Hays, S M
2015-12-01
Urinary biomonitoring data for 2,4-dichlorophenoxyacetic acid (2,4-D) reflect aggregate population exposures to trace 2,4-D residues in diet and the environment. These data can be interpreted in the context of current risk assessments by comparison to a Biomonitoring Equivalent (BE), which is an estimate of the average biomarker concentration consistent with an exposure guidance value such as the US EPA Reference Dose (RfD). BE values are updated here from previous published BE values to reflect a change in the US EPA RfD. The US EPA RfD has been updated to reflect a revised point of departure (POD) based on new information from additional toxicological studies and updated assessment of applicable uncertainty factors. In addition, new biomonitoring data from both the US National Health and Nutrition Examination Survey (NHANES) and the Canadian Health Measures Survey (CHMS) have been published. The updated US EPA chronic RfD of 0.21 mg/kg-d results in updated BE values of 10,500 and 7000 μg/L for adults and children, respectively. Comparison of the current population-representative data to these BE values shows that upper bound population biomarker concentrations are more than 5000-fold below BE values corresponding to the updated US EPA RfD. This biomonitoring-based risk assessment supports the conclusion that current use patterns in the US and Canada result in incidental exposures in the general population that can be considered negligible in the context of the current 2,4-D risk assessment. Copyright © 2015 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Jansen, Jan T. M.; Shrimpton, Paul C.
2016-07-01
The ImPACT (imaging performance assessment of CT scanners) CT patient dosimetry calculator is still used world-wide to estimate organ and effective doses (E) for computed tomography (CT) examinations, although the tool is based on Monte Carlo calculations reflecting practice in the early 1990’s. Subsequent developments in CT scanners, definitions of E, anthropomorphic phantoms, computers and radiation transport codes, have all fuelled an urgent need for updated organ dose conversion factors for contemporary CT. A new system for such simulations has been developed and satisfactorily tested. Benchmark comparisons of normalised organ doses presently derived for three old scanners (General Electric 9800, Philips Tomoscan LX and Siemens Somatom DRH) are within 5% of published values. Moreover, calculated normalised values of CT Dose Index for these scanners are in reasonable agreement (within measurement and computational uncertainties of ±6% and ±1%, respectively) with reported standard measurements. Organ dose coefficients calculated for a contemporary CT scanner (Siemens Somatom Sensation 16) demonstrate potential deviations by up to around 30% from the surrogate values presently assumed (through a scanner matching process) when using the ImPACT CT Dosimetry tool for newer scanners. Also, illustrative estimates of E for some typical examinations and a range of anthropomorphic phantoms demonstrate the significant differences (by some 10’s of percent) that can arise when changing from the previously adopted stylised mathematical phantom to the voxel phantoms presently recommended by the International Commission on Radiological Protection (ICRP), and when following the 2007 ICRP recommendations (updated from 1990) concerning tissue weighting factors. Further simulations with the validated dosimetry system will provide updated series of dose coefficients for a wide range of contemporary scanners.
A user friendly database for use in ALARA job dose assessment
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zodiates, A.M.; Willcock, A.
1995-03-01
The pressurized water reactor (PWR) design chosen for adoption by Nuclear Electric plc was based on the Westinghouse Standard Nuclear Unit Power Plant (SNUPPS). This design was developed to meet the United Kingdom requirements and these improvements are embodied in the Sizewell B plant which will start commercial operation in 1994. A user-friendly database was developed to assist the station in the dose and ALARP assessments of the work expected to be carried out during station operation and outage. The database stores the information in an easily accessible form and enables updating, editing, retrieval, and searches of the information. Themore » database contains job-related information such as job locations, number of workers required, job times, and the expected plant doserates. It also contains the means to flag job requirements such as requirements for temporary shielding, flushing, scaffolding, etc. Typical uses of the database are envisaged to be in the prediction of occupational doses, the identification of high collective and individual dose jobs, use in ALARP assessments, setting of dose targets, monitoring of dose control performance, and others.« less
Nanoparticle Exposure and Hormetic Dose–Responses: An Update
Leso, Veruscka; Fontana, Luca; Calabrese, Edward J.
2018-01-01
The concept of hormesis, as an adaptive response of biological systems to moderate environmental challenges, has raised considerable nano-toxicological interests in view of the rapid pace of production and application of even more innovative nanomaterials and the expected increasing likelihood of environmental and human exposure to low-dose concentrations. Therefore, the aim of this review is to provide an update of the current knowledge concerning the biphasic dose–responses induced by nanoparticle exposure. The evidence presented confirmed and extended our previous findings, showing that hormesis is a generalized adaptive response which may be further generalized to nanoscale xenobiotic challenges. Nanoparticle physico-chemical properties emerged as possible features affecting biphasic relationships, although the molecular mechanisms underlining such influences remain to be fully understood, especially in experimental settings resembling long-term and low-dose realistic environmental exposure scenarios. Further investigation is necessary to achieve helpful information for a suitable assessment of nanomaterial risks at the low-dose range for both the ecosystem function and the human health. PMID:29534471
The GENII System provides a state-of-the-art, fully documented set of programs for calculating radiation dose and risk from radionuclides released to the environment. The GENII-NESHAPs Edition can be utilized for assessing compliance with 40 CFR 61, Subparts H and I.
In support of the trichloroethylene (TCE) risk assessment for the Office of Air and Radiation, Office of Solid Waste and Emergency Response, and Office of Water, NERL and NCEA are developing an updated physiologically-based pharmacokinetic (PBPK) model. The PBPK modeling effort ...
In support of the trichloroethylene (TCE) risk assessment for the Office of Air and Radiation, Office of Solid Waste and Emergency Response, and Office of Water, NERL and NCEA are developing an updated physiologically-based pharmacokinetic (PBPK) model. The PBPK modeling effor...
NASA Astrophysics Data System (ADS)
Inaniwa, Taku; Kanematsu, Nobuyuki; Matsufuji, Naruhiro; Kanai, Tatsuaki; Shirai, Toshiyuki; Noda, Koji; Tsuji, Hiroshi; Kamada, Tadashi; Tsujii, Hirohiko
2015-04-01
At the National Institute of Radiological Sciences (NIRS), more than 8,000 patients have been treated for various tumors with carbon-ion (C-ion) radiotherapy in the past 20 years based on a radiobiologically defined clinical-dose system. Through clinical experience, including extensive dose escalation studies, optimum dose-fractionation protocols have been established for respective tumors, which may be considered as the standards in C-ion radiotherapy. Although the therapeutic appropriateness of the clinical-dose system has been widely demonstrated by clinical results, the system incorporates several oversimplifications such as dose-independent relative biological effectiveness (RBE), empirical nuclear fragmentation model, and use of dose-averaged linear energy transfer to represent the spectrum of particles. We took the opportunity to update the clinical-dose system at the time we started clinical treatment with pencil beam scanning, a new beam delivery method, in 2011. The requirements for the updated system were to correct the oversimplifications made in the original system, while harmonizing with the original system to maintain the established dose-fractionation protocols. In the updated system, the radiation quality of the therapeutic C-ion beam was derived with Monte Carlo simulations, and its biological effectiveness was predicted with a theoretical model. We selected the most used C-ion beam with αr = 0.764 Gy-1 and β = 0.0615 Gy-2 as reference radiation for RBE. The C-equivalent biological dose distribution is designed to allow the prescribed survival of tumor cells of the human salivary gland (HSG) in entire spread-out Bragg peak (SOBP) region, with consideration to the dose dependence of the RBE. This C-equivalent biological dose distribution is scaled to a clinical dose distribution to harmonize with our clinical experiences with C-ion radiotherapy. Treatment plans were made with the original and the updated clinical-dose systems, and both physical and clinical dose distributions were compared with regard to the prescribed dose level, beam energy, and SOBP width. Both systems provided uniform clinical dose distributions within the targets consistent with the prescriptions. The mean physical doses delivered to targets by the updated system agreed with the doses by the original system within ±1.5% for all tested conditions. The updated system reflects the physical and biological characteristics of the therapeutic C-ion beam more accurately than the original system, while at the same time allowing the continued use of the dose-fractionation protocols established with the original system at NIRS.
Staples, J Erin; Bocchini, Joseph A; Rubin, Lorry; Fischer, Marc
2015-06-19
On February 26, 2015, the Advisory Committee on Immunization Practices (ACIP) voted that a single primary dose of yellow fever vaccine provides long-lasting protection and is adequate for most travelers. ACIP also approved recommendations for at-risk laboratory personnel and certain travelers to receive additional doses of yellow fever vaccine (Box). The ACIP Japanese Encephalitis and Yellow Fever Vaccines Workgroup evaluated published and unpublished data on yellow fever vaccine immunogenicity and safety. The evidence for benefits and risks associated with yellow fever vaccine booster doses was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. This report summarizes the evidence considered by ACIP and provides the updated recommendations for yellow fever vaccine booster doses.
Soller, Jeffrey A; Eftim, Sorina E; Nappier, Sharon P
2018-01-01
Understanding pathogen risks is a critically important consideration in the design of water treatment, particularly for potable reuse projects. As an extension to our published microbial risk assessment methodology to estimate infection risks associated with Direct Potable Reuse (DPR) treatment train unit process combinations, herein, we (1) provide an updated compilation of pathogen density data in raw wastewater and dose-response models; (2) conduct a series of sensitivity analyses to consider potential risk implications using updated data; (3) evaluate the risks associated with log credit allocations in the United States; and (4) identify reference pathogen reductions needed to consistently meet currently applied benchmark risk levels. Sensitivity analyses illustrated changes in cumulative annual risks estimates, the significance of which depends on the pathogen group driving the risk for a given treatment train. For example, updates to norovirus (NoV) raw wastewater values and use of a NoV dose-response approach, capturing the full range of uncertainty, increased risks associated with one of the treatment trains evaluated, but not the other. Additionally, compared to traditional log-credit allocation approaches, our results indicate that the risk methodology provides more nuanced information about how consistently public health benchmarks are achieved. Our results indicate that viruses need to be reduced by 14 logs or more to consistently achieve currently applied benchmark levels of protection associated with DPR. The refined methodology, updated model inputs, and log credit allocation comparisons will be useful to regulators considering DPR projects and design engineers as they consider which unit treatment processes should be employed for particular projects. Published by Elsevier Ltd.
Johnson, J A; Caudle, K E; Gong, L; Whirl-Carrillo, M; Stein, C M; Scott, S A; Lee, M T; Gage, B F; Kimmel, S E; Perera, M A; Anderson, J L; Pirmohamed, M; Klein, T E; Limdi, N A; Cavallari, L H; Wadelius, M
2017-09-01
This document is an update to the 2011 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and VKORC1 genotypes and warfarin dosing. Evidence from the published literature is presented for CYP2C9, VKORC1, CYP4F2, and rs12777823 genotype-guided warfarin dosing to achieve a target international normalized ratio of 2-3 when clinical genotype results are available. In addition, this updated guideline incorporates recommendations for adult and pediatric patients that are specific to continental ancestry. © 2017 American Society for Clinical Pharmacology and Therapeutics.
Bohm, Tim D; DeLuca, Paul M; DeWerd, Larry A
2003-04-01
Permanent implantation of low energy (20-40 keV) photon emitting radioactive seeds to treat prostate cancer is an important treatment option for patients. In order to produce accurate implant brachytherapy treatment plans, the dosimetry of a single source must be well characterized. Monte Carlo based transport calculations can be used for source characterization, but must have up to date cross section libraries to produce accurate dosimetry results. This work benchmarks the MCNP code and its photon cross section library for low energy photon brachytherapy applications. In particular, we calculate the emitted photon spectrum, air kerma, depth dose in water, and radial dose function for both 125I and 103Pd based seeds and compare to other published results. Our results show that MCNP's cross section library differs from recent data primarily in the photoelectric cross section for low energies and low atomic number materials. In water, differences as large as 10% in the photoelectric cross section and 6% in the total cross section occur at 125I and 103Pd photon energies. This leads to differences in the dose rate constant of 3% and 5%, and differences as large as 18% and 20% in the radial dose function for the 125I and 103Pd based seeds, respectively. Using a partially updated photon library, calculations of the dose rate constant and radial dose function agree with other published results. Further, the use of the updated photon library allows us to verify air kerma and depth dose in water calculations performed using MCNP's perturbation feature to simulate updated cross sections. We conclude that in order to most effectively use MCNP for low energy photon brachytherapy applications, we must update its cross section library. Following this update, the MCNP code system will be a very effective tool for low energy photon brachytherapy dosimetry applications.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gonzales, G.J.; Gallegos, A.F.; Foxx, T.S.
1998-02-01
In FY96 and FY97, preliminary assessments were conducted of the potential risk from legacy waste to the American peregrine falcon (Falco peregrimus), the bald eagle (Haliaeetus leucocephalus), and the Mexican spotted owl (Strix occidentalis lucida). Estimated doses were compared against toxicity reference values (TRVs) to generate hazard indices that included a measure of cumulative effects from multiple contaminants (radionuclides, metals, and organic chemicals). The tools used included a custom FORTRAN code ECORSK, and a geographic information system. The assessments originally included only the soil ingestion contaminant pathway. Since the initial assessments, a food consumption contaminant pathway has been added, bioaccumulationmore » and biomagnification of some contaminants have been factored into the food consumption pathway, and some of the TRVs against which estimated doses are compared have been changed to values which relate more closely to the Aves taxonomical class. With these and other more subtle improvements in model input parameters, ECORSK has been revised and the model has been re-executed for the owl and peregrine exposure units that originally generated the highest risk indices. This report contains the updated results. On average, results indicate a small potential for impact to the peregrine falcon, but no appreciable impact to the spotted owl nor the bald eagle. The original reports cited in this document should be consulted for details on methods.« less
CCl4 is a common environmental contaminant in water and superfund sites, and a model liver toxicant. One application of PBPK models used in risk assessment is simulation of internal dose for the metric involved with toxicity, particularly for different routes of exposure. Time-co...
Basis for the ICRP’s updated biokinetic model for carbon inhaled as CO 2
Leggett, Richard W.
2017-03-02
Here, the International Commission on Radiological Protection (ICRP) is updating its biokinetic and dosimetric models for occupational intake of radionuclides (OIR) in a series of reports called the OIR series. This paper describes the basis for the ICRP's updated biokinetic model for inhalation of radiocarbon as carbon dioxide (CO 2) gas. The updated model is based on biokinetic data for carbon isotopes inhaled as carbon dioxide or injected or ingested as bicarbonatemore » $$({{{\\rm{HCO}}}_{3}}^{-}).$$ The data from these studies are expected to apply equally to internally deposited (or internally produced) carbon dioxide and bicarbonate based on comparison of excretion rates for the two administered forms and the fact that carbon dioxide and bicarbonate are largely carried in a common form (CO 2–H$${{{\\rm{CO}}}_{3}}^{-})$$ in blood. Compared with dose estimates based on current ICRP biokinetic models for inhaled carbon dioxide or ingested carbon, the updated model will result in a somewhat higher dose estimate for 14C inhaled as CO 2 and a much lower dose estimate for 14C ingested as bicarbonate.« less
Basis for the ICRP’s updated biokinetic model for carbon inhaled as CO 2
DOE Office of Scientific and Technical Information (OSTI.GOV)
Leggett, Richard W.
Here, the International Commission on Radiological Protection (ICRP) is updating its biokinetic and dosimetric models for occupational intake of radionuclides (OIR) in a series of reports called the OIR series. This paper describes the basis for the ICRP's updated biokinetic model for inhalation of radiocarbon as carbon dioxide (CO 2) gas. The updated model is based on biokinetic data for carbon isotopes inhaled as carbon dioxide or injected or ingested as bicarbonatemore » $$({{{\\rm{HCO}}}_{3}}^{-}).$$ The data from these studies are expected to apply equally to internally deposited (or internally produced) carbon dioxide and bicarbonate based on comparison of excretion rates for the two administered forms and the fact that carbon dioxide and bicarbonate are largely carried in a common form (CO 2–H$${{{\\rm{CO}}}_{3}}^{-})$$ in blood. Compared with dose estimates based on current ICRP biokinetic models for inhaled carbon dioxide or ingested carbon, the updated model will result in a somewhat higher dose estimate for 14C inhaled as CO 2 and a much lower dose estimate for 14C ingested as bicarbonate.« less
IRIS Toxicological Review of 1,4-Dioxane (with Inhalation ...
EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of 1,4-Dioxane (with inhalation update) that when finalized will appear on the Integrated Risk Information System (IRIS) database. 1,4-Dioxane is commonly used as a solvent, cleaning agent, chemical stabilizer, surface coating, adhesive agent, and an ingredient in chemical manufacture.
Up-date on the NeoVitaA Trial: Obstacles, challenges, perspectives, and local experiences.
Meyer, Sascha; Gortner, Ludwig
2017-09-01
The aim of the NeoVitaA Trial is to assess the role of postnatal additional high-dose oral vitamin A supplementation for 28 days in reducing Bronchopulmonary dysplasia (BPD) or death in extremely low birth weight (ELBW) infants at 36 weeks postmenstrual age (PMA). All infants (both intervention and control group) will be provided with basic vitamin A (1000 IU/kg/day) in addition to trial intervention.In this short communication, we will give an up-date on obstacles, challenges as well as perspectives and potential solutions when putting into place a multicenter, double-blind, randomized trial in this cohort of extremely susceptible infants.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bryan, Charles R.; Weck, Philippe F.; Vaughn, Palmer
Report RWEV-REP-001, Analysis of Postclosure Groundwater Impacts for a Geologic Repository for the Disposal of Spent Nuclear Fuel and High Level Radioactive Waste at Yucca Mountain, Nye County, Nevada was issued by the DOE in 2009 and is currently being updated. Sandia National Laboratories (SNL) provided support for the original document, performing calculations and extracting data from the Yucca Mountain Performance Assessment Model that were used as inputs to the contaminant transport and dose calculations by Jason Associates Corporation, the primary developers of the DOE report. The inputs from SNL were documented in LSA-AR-037, Inputs to Jason Associates Corporation inmore » Support of the Postclosure Repository Supplemental Environmental Impact Statement. To support the updating of the original Groundwater Impacts document, SNL has reviewed the inputs provided in LSA-AR-037 to verify that they are current and appropriate for use. The results of that assessment are documented here.« less
Mielke, H; Strickland, J; Jacobs, M N; Mehta, J M
2017-10-01
A comprehensive biometrical assessment was conducted to compare the performance of multiple test designs for acute dermal systemic toxicity to support the animal welfare update to the original OECD Test Guideline (TG) 402 for acute dermal toxicity. The test designs evaluated included: (1) two, three, or five animals per dose group (2) evident toxicity or lethality endpoints and (3) absence or presence of a one-animal sighting study. The revision of TG 402 respected the 3R principles (replace, reduce, refine) of animal testing. The results demonstrate that the TG 402 test design can be optimised with reduced animal numbers per test group, such that a scenario of two animals per group following a sighting study at a starting dose of 200 mg/kg bw (unless further information is available to better define the starting dose) would provide a classification which in most cases is conservative, without compromising both the statistical ability of the study to assess dermal toxicity, or the relevant classification outcome. Copyright © 2017 Elsevier Inc. All rights reserved.
CONSULTATION ON UPDATED METHODOLOGY FOR ...
The National Academy of Sciences (NAS) expects to publish the Biological Effects of Ionizing Radiation (BEIR) committee's report (BEIR VII) on risks from ionizing radiation exposures in calendar year 2005. The committee is expected to have analyzed the most recent epidemiology from the important exposed cohorts and to have factored in any changes resulting from the updated analysis of dosimetry for the Japanese atomic bomb survivors. To the extent practical, the Committee will also consider any relevant radiobiological data, including those from the Department of Energy's low dose effects research program. Based on their evaluation of relevant information, the Committee is then expected to propose a set of models for estimating risks from low-dose ionizing radiation. ORIA will review the BEIR VII report and consider revisions to the Agency's methodology for estimating cancer risks from exposure to ionizing radiation in light of this report and other relevant information. This will be the subject of the Consultation. This project supports a major risk management initiative to improve the basis on which radiation risk decisions are made. This project, funded by several Federal Agencies, reflects an attempt to characterize risks where there are substantial uncertainties. The outcome will improve our ability to assess risks well into the future and will strengthen EPAs overall capability for assessing and managing radiation risks. the BEIR VII report is funde
IRIS TOXICOLOGICAL REVIEW AND SUMMARY ...
EPA's assessment of the noncancer health effects and carcinogenic potential of 1,2,3-trichloropropane (TCP) was added to the IRIS database in 1990. The IRIS program is updating the IRIS assessment for TCP. This update will incorporate health effects information published since the last assessment was prepared as well as new risk assessment methods. The IRIS assessment for TCP will consist of a Toxicological Review and IRIS Summary. The Toxicological Review is a critical review of the physicochemical and toxicokinetic properties of the chemical and its toxicity in humans and experimental systems. The assessment will present reference values for noncancer effects of TCP (RfD and RfC) and a cancer assessment. The Toxicological Review and IRIS Summary will be subject to internal peer consultation, Agency review, and external scientific peer review. The final products will constitute the Agency's opinion on the toxicity of TCP. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for 1,2,3-trichloropropane. IRIS is an EPA database containing the Agency's consensus scientific positions on potential adverse human effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment process, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in
van Hoek, Albert Jan; Melegaro, Alessia; Zagheni, Emelio; Edmunds, W John; Gay, Nigel
2011-03-16
This study updates previous work on modelling the incidence of varicella and Herpes Zoster (HZ) following the introduction of childhood vaccination. The updated model includes new data on age-specific contact patterns, as well as data on the efficacy of zoster vaccination in the elderly and allows for HZ among vaccinees. The current study also looks at two-dose varicella childhood programmes, and assesses the combined impact of varicella vaccination in childhood and zoster vaccination of the elderly. The results suggest that a two-dose schedule is likely to reduce the incidence of varicella to very low levels, provided first dose coverage is around 90% and second dose coverage is in excess of 70%. Single dose varicella vaccination programmes are expected to result in large numbers of breakthrough cases. Childhood vaccination is expected to increase the incidence of zoster for more than 40 years after introduction of the programme, the magnitude of this increase being influenced primarily by the duration of boosting following exposure to the varicella zoster virus. Though this increase in zoster incidence can be partly offset by vaccination of the elderly, the effectiveness of this combined strategy is limited, as much of the increase occurs in those adults too young to be vaccinated. Childhood vaccination at intermediate levels of coverage (70% and 60% for first and second dose coverage respectively) is expected to lead to an increase in adult varicella. At high coverage (90% and 80% coverage) this is unlikely to be the case. These results will be used to inform a cost-effectiveness analysis of combined varicella and zoster vaccination programmes. Copyright © 2011 Elsevier Ltd. All rights reserved.
Wu, Junfeng; Dai, Fang; Hu, Gang; Mou, Xuanqin
2018-04-18
Excessive radiation exposure in computed tomography (CT) scans increases the chance of developing cancer and has become a major clinical concern. Recently, statistical iterative reconstruction (SIR) with l0-norm dictionary learning regularization has been developed to reconstruct CT images from the low dose and few-view dataset in order to reduce radiation dose. Nonetheless, the sparse regularization term adopted in this approach is l0-norm, which cannot guarantee the global convergence of the proposed algorithm. To address this problem, in this study we introduced the l1-norm dictionary learning penalty into SIR framework for low dose CT image reconstruction, and developed an alternating minimization algorithm to minimize the associated objective function, which transforms CT image reconstruction problem into a sparse coding subproblem and an image updating subproblem. During the image updating process, an efficient model function approach based on balancing principle is applied to choose the regularization parameters. The proposed alternating minimization algorithm was evaluated first using real projection data of a sheep lung CT perfusion and then using numerical simulation based on sheep lung CT image and chest image. Both visual assessment and quantitative comparison using terms of root mean square error (RMSE) and structural similarity (SSIM) index demonstrated that the new image reconstruction algorithm yielded similar performance with l0-norm dictionary learning penalty and outperformed the conventional filtered backprojection (FBP) and total variation (TV) minimization algorithms.
Human papillomavirus vaccination coverage using two-dose or three-dose schedule criteria.
Lin, Xia; Rodgers, Loren; Zhu, Liping; Stokley, Shannon; Meites, Elissa; Markowitz, Lauri E
2017-10-13
In October 2016, the Advisory Committee on Immunization Practices (ACIP) updated the human papillomavirus (HPV) vaccination recommendation to include a 2-dose schedule for U.S. adolescents initiating the vaccine series before their 15th birthday. We analyzed records for >4million persons aged 9-17years receiving any HPV vaccine by the end of each quarter during January 1, 2014-September 30, 2016 from six Immunization Information Systems Sentinel Sites, and reclassified HPV vaccination up-to-date coverage according to the updated recommendations. Compared with HPV vaccination up-to-date coverage by the 3-dose schedule only, including criteria for either a 2-dose or 3-dose schedule increased up-to-date coverage in 11-12, 13-14, and 15-17 year-olds by 4.5-8.5 percentage points. The difference between 3-dose up-to-date coverage and 2- or 3-dose up-to-date coverage was greatest in late 2016. These data provide baseline HPV vaccination coverage using current ACIP recommendations. Published by Elsevier Ltd.
Ladtap XL Version 2017: A Spreadsheet For Estimating Dose Resulting From Aqueous Releases
DOE Office of Scientific and Technical Information (OSTI.GOV)
Minter, K.; Jannik, T.
LADTAP XL© is an EXCEL© spreadsheet used to estimate dose to offsite individuals and populations resulting from routine and accidental releases of radioactive materials to the Savannah River. LADTAP XL© contains two worksheets: LADTAP and IRRIDOSE. The LADTAP worksheet estimates dose for environmental pathways including external exposure resulting from recreational activities on the Savannah River and internal exposure resulting from ingestion of water, fish, and invertebrates originating from the Savannah River. IRRIDOSE estimates offsite dose to individuals and populations from irrigation of foodstuffs with contaminated water from the Savannah River. In 2004, a complete description of the LADTAP XL© codemore » and an associated user’s manual was documented in LADTAP XL©: A Spreadsheet for Estimating Dose Resulting from Aqueous Release (WSRC-TR-2004-00059) and revised input parameters, dose coefficients, and radionuclide decay constants were incorporated into LADTAP XL© Version 2013 (SRNL-STI-2011-00238). LADTAP XL© Version 2017 is a slight modification to Version 2013 with minor changes made for more user-friendly parameter inputs and organization, updates in the time conversion factors used within the dose calculations, and fixed an issue with the expected time build-up parameter referenced within the population shoreline dose calculations. This manual has been produced to update the code description, verification of the models, and provide an updated user’s manual. LADTAP XL© Version 2017 has been verified by Minter (2017) and is ready for use at the Savannah River Site (SRS).« less
Dose Matters: FDA's Guidance on Children's X-rays
... Consumers Home For Consumers Consumer Updates Dose Matters: FDA's Guidance on Children's X-rays Share Tweet Linkedin ... extra care to “child size” the radiation dose. FDA’s Role The FDA's Center for Devices and Radiological ...
The effects of black pepper on the intestinal absorption and hepatic metabolism of drugs.
Han, Hyo-Kyung
2011-06-01
There is currently a need for a better understanding of the mechanisms of food-drug interaction as well as the clinical implication to maximize the effectiveness and applicability of black pepper or its active component, piperine, as a bioavailability enhancer in the clinical arena. This review deals with the effects of black pepper and piperine on drug metabolizing enzymes as well as on intestinal drug absorption. The review provides the reader with a comprehensive update on the potential mechanisms and pharmacokinetic interactions of black pepper and piperine with co-administered medicines. The article also provides a comprehensive update on the current known issues with black pepper and piperine. The information provided is used to assess the clinical significance of black pepper and piperine and optimize their effectiveness as a bioavailability enhancer. For black pepper or piperine to be widely applicable in current medical practice, as a combination therapy, the clinical significance of food-drug interactions caused by concurrent use of black pepper or piperine should be carefully assessed with consideration for many compounding factors affecting the clinical outcome of pharmacokinetic interactions (e.g., dose, dosing regimen, genetic variation and species). Furthermore, the effective formulation strategy for the optimization of the pharmacokinetic characteristics of dietary components is crucial to improve their in vivo performance and ultimately maximize their effectiveness as a bioavailability enhancer.
NASA Astrophysics Data System (ADS)
Zhang, Guozhi; Liu, Qian; Zeng, Shaoqun; Luo, Qingming
2008-07-01
The voxel-based visible Chinese human (VCH) adult male phantom has offered a high-quality test bed for realistic Monte Carlo modeling in radiological dosimetry simulations. The phantom has been updated in recent effort by adding newly segmented organs, revising walled and smaller structures as well as recalibrating skeletal marrow distributions. The organ absorbed dose against external proton exposure was calculated at a voxel resolution of 2 × 2 × 2 mm3 using the MCNPX code for incident energies from 20 MeV to 10 GeV and for six idealized irradiation geometries: anterior-posterior (AP), posterior-anterior (PA), left-lateral (LLAT), right-lateral (RLAT), rotational (ROT) and isotropic (ISO), respectively. The effective dose on the VCH phantom was derived in compliance with the evaluation scheme for the reference male proposed in the 2007 recommendations of the International Commission on Radiological Protection (ICRP). Algorithm transitions from the revised radiation and tissue weighting factors are accountable for approximately 90% and 10% of effective dose discrepancies in proton dosimetry, respectively. Results are tabulated in terms of fluence-to-dose conversion coefficients for practical use and are compared with data from other models available in the literature. Anatomical variations between various computational phantoms lead to dose discrepancies ranging from a negligible level to 100% or more at proton energies below 200 MeV, corresponding to the spatial geometric locations of individual organs within the body. Doses show better agreement at higher energies and the deviations are mostly within 20%, to which the organ volume and mass differences should be of primary responsibility. The impact of body size on dose distributions was assessed by dosimetry of a scaled-up VCH phantom that was resized in accordance with the height and total mass of the ICRP reference man. The organ dose decreases with the directionally uniform enlargement of voxels. Potential pathways to improve the VCH phantom have also been briefly addressed. This work pertains to VCH-based systematic multi-particle dose investigations and will contribute to comparative dosimetry studies of ICRP standardized voxel phantoms in the near future.
Code of Federal Regulations, 2013 CFR
2013-10-01
... scientific elements underlying the dose reconstruction process? 82.33 Section 82.33 Public Health PUBLIC... RELATED ACTIVITIES METHODS FOR CONDUCTING DOSE RECONSTRUCTION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 Updating the Scientific Elements Underlying Dose Reconstructions...
Code of Federal Regulations, 2011 CFR
2011-10-01
... scientific elements underlying the dose reconstruction process? 82.33 Section 82.33 Public Health PUBLIC... RELATED ACTIVITIES METHODS FOR CONDUCTING DOSE RECONSTRUCTION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 Updating the Scientific Elements Underlying Dose Reconstructions...
Code of Federal Regulations, 2014 CFR
2014-10-01
... scientific elements underlying the dose reconstruction process? 82.33 Section 82.33 Public Health PUBLIC... RELATED ACTIVITIES METHODS FOR CONDUCTING DOSE RECONSTRUCTION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 Updating the Scientific Elements Underlying Dose Reconstructions...
Code of Federal Regulations, 2012 CFR
2012-10-01
... scientific elements underlying the dose reconstruction process? 82.33 Section 82.33 Public Health PUBLIC... RELATED ACTIVITIES METHODS FOR CONDUCTING DOSE RECONSTRUCTION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 Updating the Scientific Elements Underlying Dose Reconstructions...
Jones, Alison; Jones, Kelly; Holmes, Sheila; Ewers, Leon; Cabianca, Tiberio
2013-03-01
The aim of this work is to assess the possible radiological impact on the population of the United Kingdom (UK) from new nuclear power stations proposed for up to eight sites in England and Wales. The radiological impact was measured in terms of collective dose to the UK, European and world populations from a single year's discharge integrated to 500 and 100 000 years and the annual dose to an average member of the UK population (known as the per-caput dose). The doses were calculated for two reactor types, UK EPR™ and AP1000™, using the annual expected discharges estimated by the designers of the reactors and assuming two reactors per site. In addition, typical individual doses to adults living close to the sites were calculated on the basis of continuous discharges for 60 years (the assumed lifetime of the reactors). The dose to a representative person (previously known as the critical group) was not calculated, as this has been done elsewhere. The assessments were carried out using the software program PC-CREAM 08(®) which implements the updated European Commission methodology for assessing the radiological impact of routine releases of radionuclides to the environment. The collective dose truncated to 500 years to the UK population was estimated to be 0.5 manSv assuming UK EPR reactors on all sites and 0.6 manSv assuming AP1000s on three sites with UK EPRs on the other sites. The most significant contribution to the collective dose to the UK population is due to the global circulation of carbon-14 released to the atmosphere. The annual dose to an average member of the UK population from all sites was calculated to be around 10 nSv y(-1) and would therefore contribute little to an individual's total radiation dose. All the calculated doses to a typical adult living near the sites assuming continuous discharges for 60 years were found to be below 1 μSv y(-1).
Thiamine for prevention and treatment of Wernicke-Korsakoff Syndrome in people who abuse alcohol.
Day, Ed; Bentham, Peter W; Callaghan, Rhiannon; Kuruvilla, Tarun; George, Sanju
2013-07-01
Autopsy studies suggest that Wernicke-Korsakoff syndrome (WKS) is not a rare disorder, particularly in individuals who abuse alcohol. Thiamine has been established as the treatment of choice for over 50 years, but uncertainty remains about appropriate dosage and duration. Current practice guidelines are based on case reports and clinical experience. This is an update of a review first published in 2004 and last updated in 2008. • To assess the efficacy of thiamine in preventing and treating the manifestations of WKS due to excess alcohol consumption. • To determine the optimum form, dose and duration of thiamine treatment for this indication. ALOIS, the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS were searched on 6 September 2012 using the term thiamine OR aneurine. ALOIS contains records from all major health care databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many trial databases and grey literature sources. Any randomised trials comparing thiamine with alternative interventions or comparing different thiamine regimens (varying in formulation, dose or duration of administration). All abstracts were independently inspected by two reviewers (ED and PWB), and relevant articles were retrieved and assessed for methodological quality using criteria provided in the Cochrane Handbook for Systematic Reviews of Interventions. Two studies were identified that met the inclusion criteria, but only one contained sufficient data for quantitative analysis. Ambrose (2001) randomly assigned participants (n = 107) to one of five doses of intramuscular thiamine and measured outcomes after 2 days of treatment. We compared the lowest dose (5 mg/day) with each of the other four doses. A significant difference favoured 200 mg/day compared with the 5-mg/day dose in determining the number of trials needed to meet inclusion criteria on a delayed alternation test (mean difference (MD) -17.90, 95% confidence interval (CI) -35.4 to -0.40, P = 0.04). No significant differences emerged when the other doses were compared with 5 mg/day. The pattern of results did not reflect a simple dose-response relationship. The study had methodological shortcomings in design and in the presentation of results that limited further analysis. Evidence from randomised controlled clinical trials is insufficient to guide clinicians in determining the dose, frequency, route or duration of thiamine treatment for prophylaxis against or treatment of WKS due to alcohol abuse.
Beck, P; Latocha, M; Dorman, L; Pelliccioni, M; Rollet, S
2007-01-01
As required by the European Directive 96/29/Euratom, radiation exposure due to natural ionizing radiation has to be taken into account at workplaces if the effective dose could become more than 1 mSv per year. An example of workers concerned by this directive is aircraft crew due to cosmic radiation exposure in the atmosphere. Extensive measurement campaigns on board aircrafts have been carried out to assess ambient dose equivalent. A consortium of European dosimetry institutes within EURADOS WG5 summarized experimental data and results of calculations, together with detailed descriptions of the methods for measurements and calculations. The radiation protection quantity of interest is the effective dose, E (ISO). The comparison of results by measurements and calculations is done in terms of the operational quantity ambient dose equivalent, H(10). This paper gives an overview of the EURADOS Aircraft Crew In-Flight Database and it presents a new empirical model describing fitting functions for this data. Furthermore, it describes numerical simulations performed with the Monte Carlo code FLUKA-2005 using an updated version of the cosmic radiation primary spectra. The ratio between ambient dose equivalent and effective dose at commercial flight altitudes, calculated with FLUKA-2005, is discussed. Finally, it presents the aviation dosimetry model AVIDOS based on FLUKA-2005 simulations for routine dose assessment. The code has been developed by Austrian Research Centers (ARC) for the public usage (http://avidos.healthphysics.at).
Grant, Frederick D; Gelfand, Michael J; Drubach, Laura A; Treves, S Ted; Fahey, Frederic H
2015-04-01
Estimated radiation dose is important for assessing and communicating the risks and benefits of pediatric nuclear medicine studies. Radiation dose depends on the radiopharmaceutical, the administered activity, and patient factors such as age and size. Most radiation dose estimates for pediatric nuclear medicine have not been based on administered activities of radiopharmaceuticals recommended by established practice guidelines. The dosage card of the European Association of Nuclear Medicine (EANM) and the North American consensus guidelines each provide recommendations of administered activities of radiopharmaceuticals in children, but there are substantial differences between these two guidelines. For 12 commonly performed pediatric nuclear medicine studies, two established pediatric radiopharmaceutical administration guidelines were used to calculate updated radiation dose estimates and to compare the radiation exposure resulting from the recommendations of each of the guidelines. Estimated radiation doses were calculated for 12 common procedures in pediatric nuclear medicine using administered activities recommended by the dosage card of the EANM (version 1.5.2008) and the 2010 North American consensus guidelines for radiopharmaceutical administered activities in pediatrics. Based on standard models and nominal age-based weights, radiation dose was estimated for typical patients at ages 1, 5, 10 and 15 years and adult. The resulting effective doses were compared, with differences greater than 20% considered significant. Following either the EANM dosage card or the 2010 North American guidelines, the highest effective doses occur with radiopharmaceuticals labeled with fluorine-18 and iodine-123. In 24% of cases, following the North American consensus guidelines would result in a substantially higher radiation dose. The guidelines of the EANM dosage card would lead to a substantially higher radiation dose in 39% of all cases, and in 62% of cases in which patients were age 5 years or younger. For 12 commonly performed pediatric nuclear medicine studies, updated radiation dose estimates can guide efforts to reduce radiation exposure and provide current information for discussing radiation exposure and risk with referring physicians, patients and families. There can be substantial differences in radiation exposure for the same procedure, depending upon which of these two guidelines is followed. This discordance identifies opportunities for harmonization of the guidelines, which may lead to further reduction in nuclear medicine radiation doses in children.
INEEL AIR MODELING PROTOCOL ext
DOE Office of Scientific and Technical Information (OSTI.GOV)
C. S. Staley; M. L. Abbott; P. D. Ritter
2004-12-01
Various laws stemming from the Clean Air Act of 1970 and the Clean Air Act amendments of 1990 require air emissions modeling. Modeling is used to ensure that air emissions from new projects and from modifications to existing facilities do not exceed certain standards. For radionuclides, any new airborne release must be modeled to show that downwind receptors do not receive exposures exceeding the dose limits and to determine the requirements for emissions monitoring. For criteria and toxic pollutants, emissions usually must first exceed threshold values before modeling of downwind concentrations is required. This document was prepared to provide guidancemore » for performing environmental compliance-driven air modeling of emissions from Idaho National Engineering and Environmental Laboratory facilities. This document assumes that the user has experience in air modeling and dose and risk assessment. It is not intended to be a "cookbook," nor should all recommendations herein be construed as requirements. However, there are certain procedures that are required by law, and these are pointed out. It is also important to understand that air emissions modeling is a constantly evolving process. This document should, therefore, be reviewed periodically and revised as needed. The document is divided into two parts. Part A is the protocol for radiological assessments, and Part B is for nonradiological assessments. This document is an update of and supersedes document INEEL/INT-98-00236, Rev. 0, INEEL Air Modeling Protocol. This updated document incorporates changes in some of the rules, procedures, and air modeling codes that have occurred since the protocol was first published in 1998.« less
2018-01-01
Introduction: Clozapine is an atypical antipsychotic medication approved for treatment-resistant schizophrenia and suicidal behavior in schizophrenia or schizoaffective disorders. Despite its therapeutic efficacy, clozapine is associated with several adverse effects, including agranulocytosis. In late 2015, the Food and Drug Administration updated the risk evaluation and mitigation strategy (REMS) for clozapine with new requirements for monitoring, prescribing, and dispensing. The purpose of this study was to evaluate clozapine prescribing practices at a Kentucky state psychiatric hospital before and after the implementation of the updated REMS program. Methods: The primary outcome of this study was to evaluate clozapine prescribing practices by identifying the number of patients on clozapine therapy in the 6 months pre and post updated REMS implementation. Included in the study were patients at a Kentucky state psychiatric hospital on clozapine therapy for the 24 months before the updated REMS implementation and in the 6-month study period after the implementation. The secondary objective of this study examined psychiatrist comfort level of prescribing clozapine. Results: Since the implementation of the updated REMS program, there has been an increased percentage of patients that were prescribed clozapine at a Kentucky state psychiatric hospital. This increase was not statistically significant (P = .2610). Discussion: The prescribing practices of clozapine within this facility did not differ significantly comparing pre- and post-REMS change in terms of number of patients prescribed clozapine, patient's dose, and therapy duration. Data from this study contributes to the body of knowledge evaluating this new standard of practice under the updated REMS.
Radiation dose optimization in the decommissioning plan for Loviisa NPP
DOE Office of Scientific and Technical Information (OSTI.GOV)
Holmberg, R.; Eurajoki, T.
1995-03-01
Finnish rules for nuclear power require a detailed decommissioning plan to be made and kept up to date already during plant operation. The main reasons for this {open_quotes}premature{close_quotes} plan, is, firstly, the need to demonstrate the feasibility of decommissioning, and, secondly, to make realistic cost estimates in order to fund money for this future operation. The decomissioning for Lovissa Nuclear Power Plant (NPP) (2{times}445 MW, PWR) was issued in 1987. It must be updated about every five years. One important aspect of the plant is an estimate of radiation doses to the decomissioning workers. The doses were recently re-estimated becausemore » of a need to decrease the total collective dose estimate in the original plan, 23 manSv. In the update, the dose was reduced by one-third. Part of the reduction was due to changes in the protection and procedures, in which ALARA considerations were taken into account, and partly because of re-estimation of the doses.« less
An updated dose assessment for resettlement options at Bikini Atoll--a U.S. nuclear test site.
Robison, W L; Bogen, K T; Conrado, C L
1997-07-01
On 1 March 1954, a nuclear weapon test, code-named BRAVO, conducted at Bikini Atoll in the northern Marshall Islands contaminated the major residence island. There has been a continuing effort since 1977 to refine dose assessments for resettlement options at Bikini Atoll. Here we provide a radiological dose assessment for the main residence island, Bikini, using extensive radionuclide concentration data derived from analysis of food crops, ground water, cistern water, fish and other marine species, animals, air, and soil collected at Bikini Island as part of our continuing research and monitoring program that began in 1978. The unique composition of coral soil greatly alters the relative contribution of 137Cs and 90Sr to the total estimated dose relative to expectations based on North American and European soils. Without counter measures, 137Cs produces 96% of the estimated dose for returning residents, mostly through uptake from the soil to terrestrial food crops but also from external gamma exposure. The doses are calculated assuming a resettlement date of 1999. The estimated maximum annual effective dose for current island conditions is 4.0 mSv when imported foods, which are now an established part of the diet, are available. The 30-, 50-, and 70-y integral effective doses are 91 mSv, 130 mSv, and 150 mSv, respectively. A detailed uncertainty analysis for these dose estimates is presented in a companion paper in this issue. We have evaluated various countermeasures to reduce 137Cs in food crops. Treatment with potassium reduces the uptake of 137Cs into food crops, and therefore the ingestion dose, to about 5% of pretreatment levels and has essentially no negative environmental consequences. We have calculated the dose for the rehabilitation scenario where the top 40 cm of soil is removed in the housing and village area, and the rest of the island is treated with potassium fertilizer; the maximum annual effective dose is 0.41 mSv and the 30-, 50-, and 70-y integral effective doses are 9.8 mSv, 14 mSv, and 16 mSv, respectively.
High-dose neutron detector project update
DOE Office of Scientific and Technical Information (OSTI.GOV)
Menlove, Howard Olsen; Henzlova, Daniela
These are the slides for a progress review meeting by the sponsor. This is an update on the high-dose neutron detector project. In summary, improvements in both boron coating and signal amplification have been achieved; improved boron coating materials and procedures have increased efficiency by ~ 30-40% without the corresponding increase in the detector plate area; low dead-time via thin cell design (~ 4 mm gas gaps) and fast amplifiers; prototype PDT 8” pod has been received and testing is in progress; significant improvements in efficiency and stability have been verified; use commercial PDT 10B design and fabrication to obtainmore » a faster path from the research to practical high-dose neutron detector.« less
Vashishtha, Vipin M; Choudhury, Panna; Kalra, Ajay; Bose, Anuradha; Thacker, Naveen; Yewale, Vijay N; Bansal, C P; Mehta, Pravin J
2014-10-01
There is a need to review/revise recommendations about existing vaccines in light of recent developments in the field of vaccinology. Following an IAP ACVIP meeting on April 19 and 20, 2014, a draft of revised recommendations for the year 2014 and updates on certain vaccine formulations was prepared and circulated among the meeting participants to arrive at a consensus. To review and revise recommendations for 2014 Immunization timetable for pediatricians in office practice and issue statements on certain new and existing vaccine formulations. The major changes in the 2014 Immunization Timetable include two doses of MMR vaccine at 9 and 15 months of age, single dose recommendation for administration of live attenuated H2 strain hepatitis A vaccine, inclusion of two new situations in high-risk category of children in context with pre-exposure prophylaxis of rabies, creation of a new slot at 9-12 months of age for typhoid conjugate vaccine for primary immunization, and recommendation of two doses of human papilloma virus vaccines with a minimum interval of 6 months between doses for primary schedule of adolescent/preadolescent girls aged 9-14 years. There would not be any change to the committee's last year's (2013) recommendations on pertussis vaccination and administration schedule of monovalent human rotavirus vaccine. There is no need of providing additional doses of whole-cell pertussis vaccine to children who have earlier completed their primary schedule with acellular pertussis vaccine-containing products. A brief update on the new Indian Rotavirus vaccine, 116E is also provided. The committee has reviewed and offered its recommendations on the currently available pentavalent vaccine (DTwP+Hib+Hepatitis-B) combinations in Indian market. The comments and footnotes for several vaccines are also updated and revised.
IRIS Toxicological Review of Ammonia Noncancer Inhalation ...
EPA has finalized the Integrated Risk Information System (IRIS) Assessment of Ammonia (Noncancer Inhalation). This assessment addresses the potential noncancer human health effects from long-term inhalation exposure to ammonia. Now final, this assessment will update the current toxicological information on ammonia posted in 1991. EPA’s program and regional offices may use this assessment to inform decisions to protect human health. EPA completed the Integrated Risk Information System (IRIS) health assessment for ammonia. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment paradigm, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in combination with specific situational exposure assessment information to evaluate potential public health risk associated with environmental contaminants.
Red Meat and Colorectal Cancer: A Quantitative Update on the State of the Epidemiologic Science
Alexander, Dominik D.; Weed, Douglas L.; Miller, Paula E.; Mohamed, Muhima A.
2015-01-01
The potential relationship between red meat consumption and colorectal cancer (CRC) has been the subject of scientific debate. Given the high degree of resulting uncertainty, our objective was to update the state of the science by conducting a systematic quantitative assessment of the epidemiologic literature. Specifically, we updated and expanded our previous meta-analysis by integrating data from new prospective cohort studies and conducting a broader evaluation of the relative risk estimates by specific intake categories. Data from 27 independent prospective cohort studies were meta-analyzed using random-effects models, and sources of potential heterogeneity were examined through subgroup and sensitivity analyses. In addition, a comprehensive evaluation of potential dose-response patterns was conducted. In the meta-analysis of all cohorts, a weakly elevated summary relative risk was observed (1.11, 95% CI: 1.03–1.19); however, statistically significant heterogeneity was present. In general, summary associations were attenuated (closer to the null and less heterogeneous) in models that isolated fresh red meat (from processed meat), adjusted for more relevant factors, analyzed women only, and were conducted in countries outside of the United States. Furthermore, no clear patterns of dose-response were apparent. In conclusion, the state of the epidemiologic science on red meat consumption and CRC is best described in terms of weak associations, heterogeneity, an inability to disentangle effects from other dietary and lifestyle factors, lack of a clear dose-response effect, and weakening evidence over time. Key Teaching Points: •The role of red meat consumption in colorectal cancer risk has been widely contested among the scientific community.•In the current meta-analysis of red meat intake and colorectal cancer, we comprehensively examined associations by creating numerous sub-group stratifications, conducting extensive sensitivity analyses, and evaluating dose-response using several different methods.•Overall, all summary associations were weak in magnitude with no clear dose-response patterns.•Interpretation of findings from epidemiologic studies investigating diet and health outcomes involves numerous methodological considerations, such as accurately measuring food intake, dietary pattern differences across populations, food definitions, outcome classifications, bias and confounding, multicollinearity, biological mechanisms, genetic variation in metabolizing enzymes, and differences in analytical metrics and statistical testing parameters. PMID:25941850
Lanini, Juliana; Galduróz, José Carlos Fernandes; Pompéia, Sabine
2016-01-01
Caffeine is widely used, often consumed with food, and improves simple and complex/executive attention under fasting conditions. We investigated whether these cognitive effects are observed when personalized habitual doses of caffeine are ingested by caffeine consumers, whether they are influenced by nutriments and if various executive domains are susceptible to improvement. This was a double-blind, placebo-controlled study including 60 young, healthy, rested males randomly assigned to one of four treatments: placebo fasting, caffeine fasting, placebo meal and caffeine meal. Caffeine doses were individualized for each participant based on their self-reported caffeine consumption at the time of testing (morning). The test battery included measures of simple and sustained attention, executive domains (inhibiting, updating, shifting, dual tasking, planning and accessing long-term memory), control measures of subjective alterations, glucose and insulin levels, skin conductance, heart rate and pupil dilation. Regardless of meal intake, acute habitual doses of caffeine decreased fatigue, and improved simple and sustained attention and executive updating. This executive effect was not secondary to the habitual weekly dose consumed, changes in simple and sustained attention, mood, meal ingestion and increases in cognitive effort. We conclude that the morning caffeine "fix" has positive attentional effects and selectively improved executive updating whether or not caffeine is consumed with food. Copyright © 2015 John Wiley & Sons, Ltd.
Lougheed, M Diane; Lemiere, Catherine; Ducharme, Francine M; Licskai, Chris; Dell, Sharon D; Rowe, Brian H; FitzGerald, Mark; Leigh, Richard; Watson, Wade; Boulet, Louis-Philippe
2012-01-01
BACKGROUND: In 2010, the Canadian Thoracic Society (CTS) published a Consensus Summary for the diagnosis and management of asthma in children six years of age and older, and adults, including an updated Asthma Management Continuum. The CTS Asthma Clinical Assembly subsequently began a formal clinical practice guideline update process, focusing, in this first iteration, on topics of controversy and/or gaps in the previous guidelines. METHODS: Four clinical questions were identified as a focus for the updated guideline: the role of noninvasive measurements of airway inflammation for the adjustment of anti-inflammatory therapy; the initiation of adjunct therapy to inhaled corticosteroids (ICS) for uncontrolled asthma; the role of a single inhaler of an ICS/long-acting beta2-agonist combination as a reliever, and as a reliever and a controller; and the escalation of controller medication for acute loss of asthma control as part of a self-management action plan. The expert panel followed an adaptation process to identify and appraise existing guidelines on the specified topics. In addition, literature searches were performed to identify relevant systematic reviews and randomized controlled trials. The panel formally assessed and graded the evidence, and made 34 recommendations. RESULTS: The updated guideline recommendations outline a role for inclusion of assessment of sputum eosinophils, in addition to standard measures of asthma control, to guide adjustment of controller therapy in adults with moderate to severe asthma. Appraisal of the evidence regarding which adjunct controller therapy to add to ICS and at what ICS dose to begin adjunct therapy in children and adults with poor asthma control supported the 2010 CTS Consensus Summary recommendations. New recommendations for the adjustment of controller medication within written action plans are provided. Finally, priority areas for future research were identified. CONCLUSIONS: The present clinical practice guideline is the first update of the CTS Asthma Guidelines following the Canadian Respiratory Guidelines Committee’s new guideline development process. Tools and strategies to support guideline implementation will be developed and the CTS will continue to regularly provide updates reflecting new evidence. PMID:22536582
Estimates of internal-dose equivalent from inhalation and ingestion of selected radionuclides
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dunning, D.E.
1982-01-01
This report presents internal radiation dose conversion factors for radionuclides of interest in environmental assessments of nuclear fuel cycles. This volume provides an updated summary of estimates of committed dose equivalent for radionuclides considered in three previous Oak Ridge National Laboratory (ORNL) reports. Intakes by inhalation and ingestion are considered. The International Commission on Radiological Protection (ICRP) Task Group Lung Model has been used to simulate the deposition and retention of particulate matter in the respiratory tract. Results corresponding to activity median aerodynamic diameters (AMAD) of 0.3, 1.0, and 5.0 ..mu..m are given. The gastorintestinal (GI) tract has been representedmore » by a four-segment catenary model with exponential transfer of radioactivity from one segment to the next. Retention of radionuclides in systemic organs is characterized by linear combinations of decaying exponential functions, recommended in ICRP Publication 30. The first-year annual dose rate, maximum annual dose rate, and fifty-year dose commitment per microcurie intake of each radionuclide is given for selected target organs and the effective dose equivalent. These estimates include contributions from specified source organs plus the systemic activity residing in the rest of the body; cross irradiation due to penetrating radiations has been incorporated into these estimates. 15 references.« less
Poet, T S; Schlosser, P M; Rodriguez, C E; Parod, R J; Rodwell, D E; Kirman, C R
2016-04-01
The developmental effects of NMP are well studied in Sprague-Dawley rats following oral, inhalation, and dermal routes of exposure. Short-term and chronic occupational exposure limit (OEL) values were derived using an updated physiologically based pharmacokinetic (PBPK) model for NMP, along with benchmark dose modeling. Two suitable developmental endpoints were evaluated for human health risk assessment: (1) for acute exposures, the increased incidence of skeletal malformations, an effect noted only at oral doses that were toxic to the dam and fetus; and (2) for repeated exposures to NMP, changes in fetal/pup body weight. Where possible, data from multiple studies were pooled to increase the predictive power of the dose-response data sets. For the purposes of internal dose estimation, the window of susceptibility was estimated for each endpoint, and was used in the dose-response modeling. A point of departure value of 390 mg/L (in terms of peak NMP in blood) was calculated for skeletal malformations based on pooled data from oral and inhalation studies. Acceptable dose-response model fits were not obtained using the pooled data for fetal/pup body weight changes. These data sets were also assessed individually, from which the geometric mean value obtained from the inhalation studies (470 mg*hr/L), was used to derive the chronic OEL. A PBPK model for NMP in humans was used to calculate human equivalent concentrations corresponding to the internal dose point of departure values. Application of a net uncertainty factor of 20-21, which incorporates data-derived extrapolation factors, to the point of departure values yields short-term and chronic occupational exposure limit values of 86 and 24 ppm, respectively. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Marchiondo, A A; Holdsworth, P A; Fourie, L J; Rugg, D; Hellmann, K; Snyder, D E; Dryden, M W
2013-05-01
These second edition guidelines, updated from the 2007 version (Marchiondo et al., 2007), are intended to assist the planning and conduct of laboratory and clinical studies to assess the efficacy of ectoparasiticides applied to dogs or cats for the purpose of treating, preventing and controlling flea and tick infestations. Major revisions to this second edition include guidelines on the assessment of systemic flea and tick products, an update of the geographical distribution of the common fleas and ticks species on dogs and cats, determination of flea and tick efficacy based on geometric versus arithmetic means with respect to geographic regulatory agencies, modification of tick categorization in the assessment of efficacy, expanded guidelines on repellency and anti-feeding effects, enhanced practical field study guidance, and considerations on the ranges of flea and ticks for infestations in laboratory studies. The term ectoparasiticide includes insecticidal and acaricidal compounds, as well as insect growth regulators. The range of biological activities from animal treatment that are considered include: repellency and anti-feeding effects, knockdown, speed of kill, immediate and persistent lethal effects, and interference with egg fertility and subsequent development of off-host life cycle stages. Information is provided on the selection of animals, dose determination, dose confirmation and field studies, record keeping, interpretation of results and animal welfare. These guidelines are also intended to assist regulatory authorities involved in the approval and registration of new topical or systemic ectoparasiticides, and to facilitate the worldwide adoption of harmonized procedures.
Drug therapy for symptoms associated with anxiety in adult palliative care patients.
Salt, Susan; Mulvaney, Caroline A; Preston, Nancy J
2017-05-18
This is an update of a Cochrane Review first published in 2004 (Issue 1) and previously updated in 2012 (Issue 10). Anxiety is common in palliative care patients. It can be a natural response to the complex uncertainty of having a life-limiting illness or impending death, but it may represent a clinically significant issue in its own right. To assess the effectiveness of drug therapy for treating symptoms of anxiety in adults with a progressive life-limiting illness who are thought to be in their last year of life. We ran the searches for this update to May 2016. We searched the CENTRAL, MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO), PsychLIT (Silver Platter) and PsycINFO (Ovid). We searched seven trials registers and seven pharmaceutical industry trials registers. We handsearched the conference abstracts of the European Association of Palliative Care. Randomised controlled trials which examined the effect of drug therapy for the treatment of symptoms of anxiety in adult palliative care patients, that is, people with a known progressive life-limiting illness that is no longer responsive to curative treatment, including advanced heart, respiratory and neurological diseases (including dementia). Comparator treatments included placebo; another drug therapy or different dose schedule; or a non-drug intervention such as counselling, cognitive behaviour therapies or relaxation therapies. Two review authors independently screened titles and abstracts to identify potentially relevant papers for inclusion in the review. We sought full-text reports for all papers retained at this stage and two reviews authors independently assessed these for inclusion in the review. We planned to assess risk of bias and extract data including information on adverse events. We planned to assess the evidence using GRADE and to create a 'Summary of findings' table. In this update, we identified 707 potentially relevant papers and of these we sought the full-text reports of 10 papers. On examination of these full-text reports, we excluded eight and two are awaiting classification as we have insufficient information to make a decision. Thus, in this update, we found no studies which met our inclusion criteria. For the original review, we identified, and then excluded, the full-text reports of six potentially relevant studies. For the 2012 update, we sought, and excluded, two full-text reports. Thus, we found no studies that assessed the effectiveness of drugs to treat symptoms of anxiety in palliative care patients. There is a lack of evidence to draw a conclusion about the effectiveness of drug therapy for symptoms of anxiety in adult palliative care patients. To date, we have found no studies that meet the inclusion criteria for this review. We are awaiting further information for two studies which may be included in a future update. Randomised controlled trials which assess management of anxiety as a primary endpoint are required to establish the benefits and harms of drug therapy for the treatment of anxiety in palliative care.
Etard, Cécile; Bigand, Emeline; Salvat, Cécile; Vidal, Vincent; Beregi, Jean Paul; Hornbeck, Amaury; Greffier, Joël
2017-10-01
A national retrospective survey on patient doses was performed by the French Society of Medical physicists to assess reference levels (RLs) in interventional radiology as required by the European Directive 2013/59/Euratom. Fifteen interventional procedures in neuroradiology, vascular radiology and osteoarticular procedures were analysed. Kerma area product (KAP), fluoroscopy time (FT), reference air kerma and number of images were recorded for 10 to 30 patients per procedure. RLs were calculated as the 3rd quartiles of the distributions. Results on 4600 procedures from 36 departments confirmed the large variability in patient dose for the same procedure. RLs were proposed for the four dosimetric estimators and the 15 procedures. RLs in terms of KAP and FT were 90 Gm.cm 2 and 11 mins for cerebral angiography, 35 Gy.cm 2 and 16 mins for biliary drainage, 75 Gy.cm 2 and 6 mins for lower limbs arteriography and 70 Gy.cm 2 and 11 mins for vertebroplasty. For these four procedures, RLs were defined according to the complexity of the procedure. For all the procedures, the results were lower than most of those already published. This study reports RLs in interventional radiology based on a national survey. Continual evolution of practices and technologies requires regular updates of RLs. • Delivered dose in interventional radiology depends on procedure, practice and patient. • National RLs are proposed for 15 interventional procedures. • Reference levels (RLs) are useful to benchmark practices and optimize protocols. • RLs are proposed for kerma area product, air kerma, fluoroscopy time and number of images. • RLs should be adapted to the procedure complexity and updated regularly.
NASA Astrophysics Data System (ADS)
Nagai, Haruyasu; Terada, Hiroaki; Tsuduki, Katsunori; Katata, Genki; Ota, Masakazu; Furuno, Akiko; Akari, Shusaku
2017-09-01
In order to assess the radiological dose to the public resulting from the Fukushima Daiichi Nuclear Power Station (FDNPS) accident in Japan, especially for the early phase of the accident when no measured data are available for that purpose, the spatial and temporal distribution of radioactive materials in the environment are reconstructed by computer simulations. In this study, by refining the source term of radioactive materials discharged into the atmosphere and modifying the atmospheric transport, dispersion and deposition model (ATDM), the atmospheric dispersion simulation of radioactive materials is improved. Then, a database of spatiotemporal distribution of radioactive materials in the air and on the ground surface is developed from the output of the simulation. This database is used in other studies for the dose assessment by coupling with the behavioral pattern of evacuees from the FDNPS accident. By the improvement of the ATDM simulation to use a new meteorological model and sophisticated deposition scheme, the ATDM simulations reproduced well the 137Cs and 131I deposition patterns. For the better reproducibility of dispersion processes, further refinement of the source term was carried out by optimizing it to the improved ATDM simulation by using new monitoring data.
Paracetamol/acetaminophen (single administration) for perineal pain in the early postpartum period.
Chou, Doris; Abalos, Edgardo; Gyte, Gillian M L; Gülmezoglu, A Metin
2013-01-31
Perineal pain is a common but poorly studied adverse outcome following childbirth. Pain may result from perineal trauma due to bruising, spontaneous tears, surgical incisions (episiotomies), or in association with operative births (ventouse or forceps assisted births). To determine the efficacy of a single administration of paracetamol (acetaminophen) systemic drugs used in the relief of acute postpartum perineal pain We updated the search of the Cochrane Pregnancy and Childbirth Group's Trials Register on 6 November 2012. Randomised controlled trials (RCTs) assessing paracetamol (acetaminophen) in a single dose compared with placebo for women with early postpartum perineal pain. We excluded quasi-RCTs and cross-over studies. Two review authors assessed each paper for inclusion and extracted data. One review author reviewed the decisions and confirmed calculations for pain relief scores. We did not identify any new trials from the updated search so the results remain unchanged as follows.We have included 10 studies describing two dosages of paracetamol. Of these, five studies (526 women) assessed 500 mg to 650 mg and six studies (841 women) assessed 1000 mg of paracetamol. We chose to use random-effects meta-analyses because of the heterogeneity in dosage used. Studies were from the 1970s to the early 1990s, and there was insufficient information to assess the risk of bias adequately, hence the findings need to be interpreted within this context.More women experienced pain relief with paracetamol compared with placebo (average risk ratio (RR) 2.14, 95% confidence interval (CI) 1.59 to 2.89, 10 studies, 1279 women). In addition, there were significantly fewer women having additional pain relief with paracetamol compared with placebo (RR 0.34, 95% CI 0.21 to 0.55, eight studies, 1132 women). Both the 500 mg to 650 mg and 1000 mg doses were effective in providing more pain relief than placebo.Maternal and neonatal potential adverse drug effects were not assessed in any of the included studies. Indeed few secondary outcomes were assessed. More women experienced pain relief, and fewer had additional pain relief, with paracetamol compared with placebo, although potential adverse effects were not assessed and generally the quality of studies was unclear.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jannik, Tim; Hartman, Larry
During the operational history of Savannah River Site, many different radionuclides have been released from site facilities. However, as shown in this analysis, only a relatively small number of the released radionuclides have been significant contributors to doses to the offsite public. This report is an update to the 2011 analysis, Critical Radionuclide and Pathway Analysis for the Savannah River Site. SRS-based Performance Assessments for E-Area, Saltstone, F-Tank Farm, H-Tank Farm, and a Comprehensive SRS Composite Analysis have been completed. The critical radionuclides and pathways identified in those extensive reports are also detailed and included in this analysis.
Venom immunotherapy: an updated review.
Antolín-Amérigo, Darío; Moreno Aguilar, Carmen; Vega, Arantza; Alvarez-Mon, Melchor
2014-07-01
Venom immunotherapy (VIT) is the most effective form of specific immunotherapy to date. Hitherto, several relevant queries remain unanswered, namely optimal doses, duration, and means of assessment. Important progress has been lately made in terms of diagnosis by means of component-resolved diagnosis. Moreover, basophil activation test results in patients with negative serum immunoglobulin E (IgE) and skin prick test confer this technique a promising future, although these outcomes shall be considered with caution. This review aims to unravel the important advances made on diagnosis, management, and prognosis and also focuses on several undetermined aspects of VIT.
Doripenem Treatment during Continuous Renal Replacement Therapy
Wenisch, J. M.; Maier-Salamon, A.; Fritsch, A.; Saria, K.; Zuba, C.; Jilch, S.; Lemmerer, R.; Unger, M.; Jaehde, U.; Jäger, W.; Thalhammer, F.
2015-01-01
Doripenem is a broad-spectrum parenteral carbapenem with enhanced activity against Pseudomonas aeruginosa. While the initial dosing recommendation for renally competent patients and patients undergoing continuous renal replacement therapy (cRRT) was 500 mg every 8 h (q8h), the dose for renally competent patients was updated to 1 g q8h in June 2012. There are no updated data for the dosing of patients on continuous renal replacement therapy. The original dosing regimen for cRRT patients was based on nonseptic patients, while newer publications chose comparatively low target concentrations for a carbapenem. Thus, there is an urgent need for updated recommendations for dosing during cRRT. In the trial presented here, we included 13 oliguric septic patients undergoing cRRT in an intensive care setting. Five patients each were treated with hemodiafiltration or hemodialysis, while three patients received hemofiltration treatment. All patients received 1 g doripenem every 8 h. Doripenem concentrations in the plasma and ultrafiltrate were measured over 48 h. The mean hemofilter clearance was 36.53 ml/min, and the mean volume of distribution was 59.26 liters. The steady-state trough levels were found at 8.5 mg/liter, with no considerable accumulation. Based on pharmacokinetic and pharmacodynamic considerations, we propose a regimen of 1 g q8h, which may be combined with a loading dose of 1.5 to 2 g for critically ill patients. (This study has been registered with EudraCT under registration no. 2009-018010-18 and at ClinicalTrials.gov under registration no. NCT02018939.) PMID:26711775
Ketamine as an adjuvant to opioids for cancer pain.
Bell, Rae F; Eccleston, Christopher; Kalso, Eija A
2012-11-14
This is an update of the original review published in Issue 1, 2003. Ketamine is a commonly used anaesthetic agent, and in subanaesthetic doses is also given as an adjuvant to opioids for the treatment of cancer pain, particularly when opioids alone prove to be ineffective. Ketamine is known to have psychotomimetic (including hallucinogenic), urological and hepatic adverse effects. To determine the effectiveness and adverse effects of ketamine as an adjuvant to opioids in the treatment of cancer pain. Studies were originally identified from MEDLINE (1966 to 2002), EMBASE (1980 to 2002), CancerLit (1966 to 2002), The Cochrane Library (Issue 1, 2001); by handsearching reference lists from review articles, trials, and chapters from standard textbooks on pain and palliative care. The manufacturer of ketamine (Pfizer Parke-Davis) provided search results from their in-house database, PARDLARS.An improved and updated search of the following was performed in May 2012: CENTRAL, MEDLINE & OVID MEDLINE R, EMBASE. Randomized controlled trials (RCTs) of adult patients with cancer and pain being treated with an opioid, and receiving either ketamine (any dose and any route of administration) or placebo or an active control. Studies having a group size of at least 10 participants who completed the trial. Two independent review authors identified four RCTs for possible inclusion in the review, and 32 case studies/case series reports. Quality and validity assessment was performed by three independent review authors, and two RCTs were excluded because of inappropriate study design. Patient-reported pain intensity and pain relief was assessed using visual analogue scales (VAS), verbal rating scales or other validated scales, and adverse effects data were collated. For the update three RCTs were identified for possible inclusion in the review. Three new studies were identified by the updated search. All three were excluded from the review. Two studies were eligible for inclusion in the original review and both concluded that ketamine improves the effectiveness of morphine in the treatment of cancer pain. However, pooling of the data was not appropriate because of the small total number of participants (30), and the presence of clinical heterogeneity. Some patients experienced hallucinations on both ketamine plus morphine and morphine alone and were treated successfully with diazepam. No other serious adverse effects were reported. Since the last version of this review three new studies were identified but excluded from the review. Current evidence is insufficient to assess the benefits and harms of ketamine as an adjuvant to opioids for the relief of cancer pain. More RCTs are needed.
MO-G-18A-01: Radiation Dose Reducing Strategies in CT, Fluoroscopy and Radiography
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mahesh, M; Gingold, E; Jones, A
2014-06-15
Advances in medical x-ray imaging have provided significant benefits to patient care. According to NCRP 160, there are more than 400 million x-ray procedures performed annually in the United States alone that contributes to nearly half of all the radiation exposure to the US population. Similar growth trends in medical x-ray imaging are observed worldwide. Apparent increase in number of medical x-ray imaging procedures, new protocols and the associated radiation dose and risk has drawn considerable attention. This has led to a number of technological innovations such as tube current modulation, iterative reconstruction algorithms, dose alerts, dose displays, flat panelmore » digital detectors, high efficient digital detectors, storage phosphor radiography, variable filters, etc. that are enabling users to acquire medical x-ray images at a much lower radiation dose. Along with these, there are number of radiation dose optimization strategies that users can adapt to effectively lower radiation dose in medical x-ray procedures. The main objectives of this SAM course are to provide information and how to implement the various radiation dose optimization strategies in CT, Fluoroscopy and Radiography. Learning Objectives: To update impact of technological advances on dose optimization in medical imaging. To identify radiation optimization strategies in computed tomography. To describe strategies for configuring fluoroscopic equipment that yields optimal images at reasonable radiation dose. To assess ways to configure digital radiography systems and recommend ways to improve image quality at optimal dose.« less
Federal Guidance Report No. 14 provides federal facilities that use diagnostic and interventional x-ray equipment with updated recommendations for keeping doses as low as reasonably achievable without compromising the quality of patient care, This guidance is an update of Federal...
The 1998 Australian external beam radiotherapy survey and IAEA/WHO TLD postal dose quality audit.
Huntley, R; Izewska, J
2000-03-01
The results of an updated Australian survey of external beam radiotherapy centres are presented. Most of the centres provided most of the requested information. The relative caseloads of various linear accelerator photon and electron beams have not changed significantly since the previous survey in 1995. The mean age of Australian LINACs is 7.1 years and that of other radiotherapy machines is 14.7 years. Every Australian radiotherapy centre participated in a special run of the IAEA/WHO TLD postal dose quality audit program, which was provided for Australian centres by the IAEA and WHO in May 1998. The dose quoted by the centres was in nearly every case within 1.5% of the dose assessed by the IAEA. This is within the combined standard uncertainty of the IAEA TLD service (1.8%). The results confirm the accuracy and precision of radiotherapy dosimetry in Australia and the adequate dissemination of the Australian standards from ARL (now ARPANSA) to the centres. The Australian standards have recently been shown to agree with those of other countries to within 0.25% by comparison with the BIPM.
PROBABILISTIC SAFETY ASSESSMENT OF OPERATIONAL ACCIDENTS AT THE WASTE ISOLATION PILOT PLANT
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rucker, D.F.
2000-09-01
This report presents a probabilistic safety assessment of radioactive doses as consequences from accident scenarios to complement the deterministic assessment presented in the Waste Isolation Pilot Plant (WIPP) Safety Analysis Report (SAR). The International Council of Radiation Protection (ICRP) recommends both assessments be conducted to ensure that ''an adequate level of safety has been achieved and that no major contributors to risk are overlooked'' (ICRP 1993). To that end, the probabilistic assessment for the WIPP accident scenarios addresses the wide range of assumptions, e.g. the range of values representing the radioactive source of an accident, that could possibly have beenmore » overlooked by the SAR. Routine releases of radionuclides from the WIPP repository to the environment during the waste emplacement operations are expected to be essentially zero. In contrast, potential accidental releases from postulated accident scenarios during waste handling and emplacement could be substantial, which necessitates the need for radiological air monitoring and confinement barriers (DOE 1999). The WIPP Safety Analysis Report (SAR) calculated doses from accidental releases to the on-site (at 100 m from the source) and off-site (at the Exclusive Use Boundary and Site Boundary) public by a deterministic approach. This approach, as demonstrated in the SAR, uses single-point values of key parameters to assess the 50-year, whole-body committed effective dose equivalent (CEDE). The basic assumptions used in the SAR to formulate the CEDE are retained for this report's probabilistic assessment. However, for the probabilistic assessment, single-point parameter values were replaced with probability density functions (PDF) and were sampled over an expected range. Monte Carlo simulations were run, in which 10,000 iterations were performed by randomly selecting one value for each parameter and calculating the dose. Statistical information was then derived from the 10,000 iteration batch, which included 5%, 50%, and 95% dose likelihood, and the sensitivity of each assumption to the calculated doses. As one would intuitively expect, the doses from the probabilistic assessment for most scenarios were found to be much less than the deterministic assessment. The lower dose of the probabilistic assessment can be attributed to a ''smearing'' of values from the high and low end of the PDF spectrum of the various input parameters. The analysis also found a potential weakness in the deterministic analysis used in the SAR, a detail on drum loading was not taken into consideration. Waste emplacement operations thus far have handled drums from each shipment as a single unit, i.e. drums from each shipment are kept together. Shipments typically come from a single waste stream, and therefore the curie loading of each drum can be considered nearly identical to that of its neighbor. Calculations show that if there are large numbers of drums used in the accident scenario assessment, e.g. 28 drums in the waste hoist failure scenario (CH5), then the probabilistic dose assessment calculations will diverge from the deterministically determined doses. As it is currently calculated, the deterministic dose assessment assumes one drum loaded to the maximum allowable (80 PE-Ci), and the remaining are 10% of the maximum. The effective average of drum curie content is therefore less in the deterministic assessment than the probabilistic assessment for a large number of drums. EEG recommends that the WIPP SAR calculations be revisited and updated to include a probabilistic safety assessment.« less
Schoretsanitis, Georgios; Paulzen, Michael; Unterecker, Stefan; Schwarz, Markus; Conca, Andreas; Zernig, Gerald; Gründer, Gerhard; Haen, Ekkerhard; Baumann, Pierre; Bergemann, Niels; Clement, Hans Willi; Domschke, Katharina; Eckermann, Gabriel; Egberts, Karin; Gerlach, Manfred; Greiner, Christine; Havemann-Reinecke, Ursula; Hefner, Gudrun; Helmer, Renate; Janssen, Ger; Jaquenoud-Sirot, Eveline; Laux, Gerd; Messer, Thomas; Mössner, Rainald; Müller, Matthias J; Pfuhlmann, Bruno; Riederer, Peter; Saria, Alois; Schoppek, Bernd; Silva Gracia, Margarete; Stegmann, Benedikt; Steimer, Werner; Stingl, Julia C; Uhr, Manfred; Ulrich, Sven; Waschgler, Roland; Zurek, Gabriela; Hiemke, Christoph
2018-04-01
Therapeutic drug monitoring (TDM) combines the quantification of drug concentrations in blood, pharmacological interpretation and treatment guidance. TDM introduces a precision medicine tool in times of increasing awareness of the need for personalized treatment. In neurology and psychiatry, TDM can guide pharmacotherapy for patient subgroups such as children, adolescents, pregnant women, elderly patients, patients with intellectual disabilities, patients with substance use disorders, individuals with pharmacokinetic peculiarities and forensic patients. Clear indications for TDM include lack of clinical response in the therapeutic dose range, assessment of drug adherence, tolerability issues and drug-drug interactions. Based upon existing literature, recommended therapeutic reference ranges, laboratory alert levels, and levels of recommendation to use TDM for dosage optimization without specific indications, conversion factors, factors for calculation of dose-related drug concentrations and metabolite-to-parent ratios were calculated. This summary of the updated consensus guidelines by the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie offers the practical and theoretical knowledge for the integration of TDM as part of pharmacotherapy with neuropsychiatric agents into clinical routine. The present guidelines for TDM application for neuropsychiatric agents aim to assist clinicians in enhancing safety and efficacy of treatment.
Code of Federal Regulations, 2011 CFR
2011-10-01
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Code of Federal Regulations, 2012 CFR
2012-10-01
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Code of Federal Regulations, 2013 CFR
2013-10-01
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Code of Federal Regulations, 2014 CFR
2014-10-01
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Evans, M V; Chiu, W A; Okino, M S; Caldwell, J C
2009-05-01
Trichloroethylene (TCE) is a lipophilic solvent rapidly absorbed and metabolized via oxidation and conjugation to a variety of metabolites that cause toxicity to several internal targets. Increases in liver weight (hepatomegaly) have been reported to occur quickly in rodents after TCE exposure, with liver tumor induction reported in mice after long-term exposure. An integrated dataset for gavage and inhalation TCE exposure and oral data for exposure to two of its oxidative metabolites (TCA and DCA) was used, in combination with an updated and more accurate physiologically-based pharmacokinetic (PBPK) model, to examine the question as to whether the presence of TCA in the liver is responsible for TCE-induced hepatomegaly in mice. The updated PBPK model was used to help discern the quantitative contribution of metabolites to this effect. The update of the model was based on a detailed evaluation of predictions from previously published models and additional preliminary analyses based on gas uptake inhalation data in mice. The parameters of the updated model were calibrated using Bayesian methods with an expanded pharmacokinetic database consisting of oral, inhalation, and iv studies of TCE administration as well as studies of TCE metabolites in mice. The dose-response relationships for hepatomegaly derived from the multi-study database showed that the proportionality of dose to response for TCE- and DCA-induced hepatomegaly is not observed for administered doses of TCA in the studied range. The updated PBPK model was used to make a quantitative comparison of internal dose of metabolized and administered TCA. While the internal dose of TCA predicted by modeling of TCE exposure (i.e., mg TCA/kg-d) showed a linear relationship with hepatomegaly, the slope of the relationship was much greater than that for directly administered TCA. Thus, the degree of hepatomegaly induced per unit of TCA produced through TCE oxidation is greater than that expected per unit of TCA administered directly, which is inconsistent with the hypothesis that TCA alone accounts for TCE-induced hepatomegaly. In addition, TCE-induced hepatomegaly showed a much more consistent relationship with PBPK model predictions of total oxidative metabolism than with predictions of TCE area-under-the-curve in blood, consistent with toxicity being induced by oxidative metabolites rather than the parent compound. Therefore, these results strongly suggest that oxidative metabolites in addition to TCA are necessary contributors to TCE-induced liver weight changes in mice.
Risk Assessment in the 21st Century | Science Inventory | US ...
For the past ~50 years, risk assessment depended almost exclusively on animal testing for hazard identification and dose-response assessment. Originally sound and effective, with increasing dependence on chemical tools and the number of chemicals in commerce, this traditional approach is no longer adequate. This presentation provides an update on current progress in achieving the goals outlined in the NAS report on Toxicology Testing in the 21st Century, highlighting many of the advances lead by the EPA. Topics covered include the evolution of the mode of action framework into a chemically agnostic, adverse outcome pathway (AOP), a systems-based data framework that facilitates integration of modifiable factors (e.g., genetic variation, life stages), and an understanding of networks, and mixtures. Further, the EDSP pivot is used to illustrate how AOPs drive development of predictive models for risk assessment based on assembly of high throughput assays representing AOP key elements. The birth of computational exposure science, capable of large-scale predictive exposure models, is reviewed. Although still in its infancy, development of non-targeted analysis to begin addressing exposome also is presented. Finally, the systems-based AEP is described that integrates exposure, toxicokinetics and AOPs into a comprehensive framework. For the past ~50 years, risk assessment depended almost exclusively on animal testing for hazard identification and dose-response as
DOE Office of Scientific and Technical Information (OSTI.GOV)
Park, C; Zhang, H; Chen, Y
Purpose: Recently, compressed sensing (CS) based iterative reconstruction (IR) method is receiving attentions to reconstruct high quality cone beam computed tomography (CBCT) images using sparsely sampled or noisy projections. The aim of this study is to develop a novel baseline algorithm called Mask Guided Image Reconstruction (MGIR), which can provide superior image quality for both low-dose 3DCBCT and 4DCBCT under single mathematical framework. Methods: In MGIR, the unknown CBCT volume was mathematically modeled as a combination of two regions where anatomical structures are 1) within the priori-defined mask and 2) outside the mask. Then we update each part of imagesmore » alternatively thorough solving minimization problems based on CS type IR. For low-dose 3DCBCT, the former region is defined as the anatomically complex region where it is focused to preserve edge information while latter region is defined as contrast uniform, and hence aggressively updated to remove noise/artifact. In 4DCBCT, the regions are separated as the common static part and moving part. Then, static volume and moving volumes were updated with global and phase sorted projection respectively, to optimize the image quality of both moving and static part simultaneously. Results: Examination of MGIR algorithm showed that high quality of both low-dose 3DCBCT and 4DCBCT images can be reconstructed without compromising the image resolution and imaging dose or scanning time respectively. For low-dose 3DCBCT, a clinical viable and high resolution head-and-neck image can be obtained while cutting the dose by 83%. In 4DCBCT, excellent quality 4DCBCT images could be reconstructed while requiring no more projection data and imaging dose than a typical clinical 3DCBCT scan. Conclusion: The results shown that the image quality of MGIR was superior compared to other published CS based IR algorithms for both 4DCBCT and low-dose 3DCBCT. This makes our MGIR algorithm potentially useful in various on-line clinical applications. Provisional Patent: UF#15476; WGS Ref. No. U1198.70067US00.« less
Banholzer, Maria Longauer; Wandel, Christoph; Barrow, Paul; Mannino, Marie; Schmitt, Georg; Guérard, Melanie; Müller, Lutz; Greig, Gerard; Amemiya, Kenjie; Peck, Richard; Singer, Thomas; Doessegger, Lucette
2016-12-01
This is an update to our 2012 publication on clinical trial considerations on male contraception and collection of pregnancy information from female partner, after critical review of recent (draft) guidances released by the International Council for Harmonisation [ICH] the Clinical Trial Facilitation Group [CTFG] and the US Food & Drug Administration [FDA]. Relevant aspects of the new guidance documents are discussed in the context of male contraception and pregnancy reporting from female partner in clinical trials and the approach is updated accordingly. Genotoxicity The concept of a threshold is introduced using acceptable daily intake/permissible daily exposure to define genotoxicity requirements, hence highly effective contraception in order to avoid conception. The duration for highly effective contraception has been extended from 74 to 90 days from the end of relevant systemic exposure. Teratogenicity Pharmacokinetic considerations to estimate safety margins have been contextualized with regard to over- and underestimation of the risk of teratogenicity transmitted by a vaginal dose. The duration of male contraception after the last dose takes into account the end of relevant systemic exposure if measured, or a default period of five half-lives after last dose for small molecules and two half-lives for immunoglobulins (mAbs). Measures to prevent exposure of the conceptus via a vaginal dose apply to reproductively competent or vasectomized men, unless measurements fail to detect the compound in seminal fluid. Critical review of new guidance documents provides a comparison across approaches and resulted in an update of our previous publication. Separate algorithms for small molecules and monoclonal antibodies are proposed to guide the recommendations for contraception for male trial participants and pregnancy reporting from female partners. No male contraception is required if the dose is below a defined threshold for genotoxic concern applicable to small molecules. For men treated with teratogenic mAbs, condom use to prevent exposure of a potentially pregnant partner is unlikely to be recommended because of the minimal female exposure anticipated following a vaginal dose. The proposed safety margins for teratogenicity may evolve with further knowledge.
Marchetti, C; De Felice, F; Di Pinto, A; D'Oria, O; Aleksa, N; Musella, A; Palaia, I; Muzii, L; Tombolini, V; Benedetti Panici, P
2018-05-01
The use of dose-dense weekly chemotherapy in the management of advanced ovarian cancer (OC) remains controversial. The aim of this meta-analysis was to evaluate the efficacy of dose-dense regimen to improve clinical outcomes in OC patients with the inclusion of new trials. For this updated meta-analysis, PubMed Medline and Scopus databases and meeting proceedings were searched for eligible studies with the limitation of randomized controlled trials, comparing dose-dense chemotherapy versus standard treatment. Trials were grouped in two types of dose-dense chemotherapy: weekly dose-dense (both paclitaxel and carboplatin weekly administration) and semi-weekly dose-dense (weekly paclitaxel and three weekly carboplatin administration). Data were extracted independently and were analyzed using RevMan statistical software version 5.3 (http://www.cochrane.org). Primary end-point was progression-free survival (PFS). Four randomized controlled trials comprising 3698 patients were identified as eligible. Dose-dense chemotherapy had not a significant benefit on PFS (HR 0.92, 95% CI 0.81-1.04, p = 0.20). When the analysis was restricted to both weekly and semi-weekly dose-dense data, a no significant interaction between dose-dense and standard regimen was confirmed (HR 1.01, 95% CI 0.93-1.10 and HR 0.82, 95% CI 0.63-1.08, respectively). In the absence of PFS superiority of dose-dense schedule, three weekly schedule should remain the standard of care for advanced OC. Copyright © 2018 Elsevier B.V. All rights reserved.
Efficacy of interventions to combat tobacco addiction: Cochrane update of 2012 reviews.
Hartmann-Boyce, Jamie; Stead, Lindsay F; Cahill, Kate; Lancaster, Tim
2013-10-01
The Cochrane Collaboration is an international not-for-profit organization which produces and disseminates systematic reviews of health-care interventions. This paper is the first in a series of annual updates of Cochrane reviews on tobacco addiction interventions. It also provides an up-to-date overview of review findings in this area to date and summary statistics for cessation reviews in which meta-analyses were conducted. In 2012, the Group published seven new reviews and updated 13 others. This update summarizes and comments on these reviews. It also summarizes key findings from all the other reviews in this area. New reviews in 2012 found that in smokers using pharmacotherapy, behavioural support improves success rates [risk ratio (RR) 1.16, 95% confidence interval (CI) = 1.09-1.24], and that combining behavioural support and pharmacotherapy aids cessation (RR 1.82, 95% CI = 1.66-2.00). Updated reviews established mobile phones as potentially helpful in aiding cessation (RR 1.71, 95% CI = 1.47-1.99), found that cytisine (RR 3.98, 95% CI = 2.01-7.87) and low-dose varenicline (RR 2.09, 95% CI = 1.56-2.78) aid smoking cessation, and found that training health professionals in smoking cessation improves patient cessation rates (RR 1.60, 95% CI = 1.26-2.03). The updated reviews confirmed the benefits of nicotine replacement therapy, standard dose varenicline and providing cessation treatment free of charge. Lack of demonstrated efficacy remained for partner support, expired-air carbon monoxide feedback and lung function feedback. Cochrane systematic review evidence for the first time establishes the efficacy of behavioural support over and above pharmacotherapy, as well as the efficacy of cytisine, mobile phone technology, low-dose varenicline and health professional training in promoting smoking cessation. © 2013 Society for the Study of Addiction.
Single dose oral aspirin for acute postoperative pain in adults.
Derry, Sheena; Moore, R Andrew
2012-04-18
This review is an update of a previously published review in the Cochrane Database of Systematic Reviews on 'Single dose oral aspirin for acute pain'. Aspirin has been known for many years to be an effective analgesic for many different pain conditions. Although its use as an analgesic is now limited in developed countries, it is widely available, inexpensive, and remains commonly used throughout the world. To assess the analgesic efficacy and associated adverse events of single dose oral aspirin in acute postoperative pain. For the earlier review, we identified randomised trials by searching CENTRAL (The Cochrane Library) (1998, Issue 1), MEDLINE (1966 to March 1998), EMBASE (1980 to January 1998), and the Oxford Pain Relief Database (1950 to 1994). We updated searches of CENTRAL, MEDLINE, and EMBASE to January 2012. Single oral dose, randomised, double-blind, placebo-controlled trials of aspirin for relief of established moderate to severe postoperative pain in adults. We assessed studies for methodological quality and two review authors extracted the data independently. We used summed total pain relief (TOTPAR) over four to six hours to calculate the number of participants achieving at least 50% pain relief. We used these derived results to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over four to six hours. We sought numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, as additional measures of efficacy. We collected information on adverse events and withdrawals. We included 68 studies in which aspirin was used at doses from 300 mg to 1200 mg, but the vast majority of participants received either 600/650 mg (2409 participants, 64 studies) or 990/1000 mg (380 participants, eight studies). There was only one new study.Studies were overwhelmingly of adequate or good methodological quality. NNTs for at least 50% pain relief over four to six hours were 4.2 (3.9 to 4.8), 3.8 (3.0 to 5.1), and 2.7 (2.0 to 3.8) for 600/650 mg, 900/1000 mg, and 1200 mg respectively, compared with placebo. Type of pain model had no significant impact on the results. Lower doses were not significantly different from placebo. These results do not differ from those of the earlier review.Fewer participants required rescue medication with aspirin than with placebo over four to eight hours postdose, but by 12 hours there was no difference. The number of participants experiencing adverse events was not significantly different from placebo for 600/650 mg aspirin, but for 900/1000 mg the number needed to treat to harm was 7.5 (4.8 to 17). The most commonly reported events were dizziness, drowsiness, gastric irritation, nausea, and vomiting, nearly all of which were of mild to moderate severity. Aspirin is an effective analgesic for acute pain of moderate to severe intensity. High doses are more effective, but are associated with increased adverse events, including drowsiness and gastric irritation. The pain relief achieved with aspirin was very similar milligram for milligram to that seen with paracetamol. There was no change to the conclusions in this update.
Bernetich, Matthew; Oliai, Caspian; Lanciano, Rachelle; Hanlon, Alexandra; Lamond, John; Arrigo, Stephen; Yang, Jun; Good, Michael; Feng, Jing; Brown, Royce; Garber, Bruce; Mooreville, Michael; Brady, Luther W
2014-01-01
To report an update of our previous experience using stereotactic body radiation therapy (SBRT) for the primary treatment of prostate cancer, risk stratified by the updated National Comprehensive Cancer Network (NCCN) version 2.2014, reporting efficacy and toxicity in a community hospital setting. From 2007 to 2012, 142 localized prostate cancer patients were treated with SBRT using CyberKnife. NCCN guidelines Version 2.2014 risk groups analyzed included very low (20%), low (23%), intermediate (35%), and high (22%) risk. To further explore group heterogeneity and to comply with new guidelines, we separated our prior intermediate risk group into favorable intermediate and unfavorable intermediate groups depending on how many intermediate risk factors were present (one vs. > one). The unfavorable intermediate group was further analyzed in combination with the high risk group as per NCCN guidelines Version 2.2014. Various dose levels were used over the years of treatment, and have been categorized into low dose (35 Gy, n = 5 or 36.25 Gy, n = 107) and high dose (37.5 Gy, n = 30). All treatments were delivered in five fractions. Toxicity was assessed using radiation therapy oncology group criteria. Five-year actuarial freedom from biochemical failure (FFBF) was 100, 91.7, 95.2, 90.0, and 86.7% for very low, low, intermediate and high risk patients, respectively. A significant difference in 5 year FFBF was noted for patients with Gleason score (GS) ≥8 vs. 7 vs. 5/6 (p = 0.03) and low vs. high dose (p = 0.05). T-stage, pretreatment PSA, age, risk stratification group, and use of ADT did not affect 5-year FFBF. Multivariate analysis revealed GS and dose to be the most predictive factors for 5-year FFBF. Our experience with SBRT for the primary treatment of localized prostate cancer demonstrates favorable efficacy and toxicity comparable to the results reported for IMRT in literature. GS remains the single most important pretreatment predictor of outcome.
NASA Astrophysics Data System (ADS)
Borot de Battisti, M.; de Senneville, B. Denis; Hautvast, G.; Binnekamp, D.; Lagendijk, J. J. W.; Maenhout, M.; Moerland, M. A.
2017-05-01
MR-guided high-dose-rate (HDR) brachytherapy has gained increasing interest as a treatment for patients with localized prostate cancer because of the superior value of MRI for tumor and surrounding tissues localization. To enable needle insertion into the prostate with the patient in the MR bore, a single needle MR-compatible robotic system involving needle-by-needle dose delivery has been developed at our institution. Throughout the intervention, dose delivery may be impaired by: (1) sub-optimal needle positioning caused by e.g. needle bending, (2) intra-operative internal organ motion such as prostate rotations or swelling, or intra-procedural rectum or bladder filling. This may result in failure to reach clinical constraints. To assess the first aforementioned challenge, a recent study from our research group demonstrated that the deposited dose may be greatly improved by real-time adaptive planning with feedback on the actual needle positioning. However, the needle insertion sequence is left to the doctor and therefore, this may result in sub-optimal dose delivery. In this manuscript, a new method is proposed to determine and update automatically the needle insertion sequence. This strategy is based on the determination of the most sensitive needle track. The sensitivity of a needle track is defined as its impact on the dose distribution in case of sub-optimal positioning. A stochastic criterion is thus presented to determine each needle track sensitivity based on needle insertion simulations. To assess the proposed sequencing strategy, HDR prostate brachytherapy was simulated on 11 patients with varying number of needle insertions. Sub-optimal needle positioning was simulated at each insertion (modeled by typical random angulation errors). In 91% of the scenarios, the dose distribution improved when the needle was inserted into the most compared to the least sensitive needle track. The computation time for sequencing was less than 6 s per needle track. The proposed needle insertion sequencing can therefore assist in delivering an optimal dose in HDR prostate brachytherapy.
NASA Astrophysics Data System (ADS)
Duluc, Matthieu; Bardelay, Aurélie; Celik, Cihangir; Heinrichs, Dave; Hopper, Calvin; Jones, Richard; Kim, Soon; Miller, Thomas; Troisne, Marc; Wilson, Chris
2017-09-01
AWE (UK), IRSN (France), LLNL (USA) and ORNL (USA) began a long term collaboration effort in 2015 to update the nuclear criticality Slide Rule for the emergency response to a nuclear criticality accident. This document, published almost 20 years ago, gives order of magnitude estimates of key parameters, such as number of fissions and doses (neutron and gamma), useful for emergency response teams and public authorities. This paper will present, firstly the motivation and the long term objectives for this update, then the overview of the initial configurations for updated calculations and preliminary results obtained with modern 3D codes.
Megestrol acetate for treatment of anorexia-cachexia syndrome.
Ruiz Garcia, Vicente; López-Briz, Eduardo; Carbonell Sanchis, Rafael; Gonzalvez Perales, Jose Luis; Bort-Marti, Sylvia
2013-03-28
This is an updated version of a previously published review in The Cochrane Library (2005, Issue 2) on 'Megestrol acetate for the treatment of anorexia-cachexia syndrome'. Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993, MA was approved by the US Food and Drug Administration for the treatment of anorexia, cachexia or unexplained weight loss in patients with AIDS. The mechanism by which MA increases appetite is unknown and its effectiveness for anorexia and cachexia in neoplastic and AIDS (acquired immunodeficiency syndrome) patients is under investigation. To evaluate the efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and other underlying pathologies. We sought studies through an extensive search of electronic databases, journals, reference lists, contact with investigators and other search strategies outlined in the methods. The most recent search for this update was carried out in May 2012. Studies were included in the review if they assessed MA compared to placebo or other drug treatments in randomised controlled trials of patients with a clinical diagnosis of anorexia-cachexia syndrome related to cancer, AIDS or any other underlying pathology. Two independent review authors conducted data extraction and evaluated methodological quality. We performed quantitative analyses using appetite and quality of life as a dichotomous variable, and analysed weight gain as continuous and dichotomous variables. We included 35 trials in this update, the same number but not the same trials as in the previous version of the review. The trials comprised 3963 patients for effectiveness and 3180 for safety. Sixteen trials compared MA at different doses with placebo, seven trials compared different doses of MA with other drug treatments and 10 trials compared different doses of MA. Meta-analysis showed a benefit of MA compared with placebo, particularly with regard to appetite improvement and weight gain in cancer, AIDS and other underlying conditions, and lack of benefit in the same patients when MA was compared to other drugs. There was insufficient information to define the optimal dose of MA, but higher doses were more related to weight improvement than lower doses. Quality of life improvement in patients was seen only when comparing MA versus placebo but not other drugs in both subcategories: cancer and AIDS. Oedema, thromboembolic phenomena and deaths were more frequent in the patients treated with MA. More than 40 side effects were studied. This review shows that MA improves appetite and is associated with slight weight gain in cancer, AIDS and in patients with other underlying pathology. Despite the fact that these patients are receiving palliative care they should be informed of the risks involved in taking MA.
Editorial: ERCP-Related Radiation Cataractogenesis: Is It Time to Be Concerned?
Mekaroonkamol, Parit; Keilin, Steven
2017-05-01
With the growing number of fluoroscopic guided endoscopic procedures, radiation-related risk needs to be further assessed. Recent evidence indicates that radiation cataractogenesis occurs at a lower dose threshold than previously believed. While body aprons and thyroid shields are well-established standard protection during fluoroscopy, ocular safety and the use of protective eyewear are not as well defined. This prospective study answered two important questions: Does the standard body dosimeter provide an accurate ocular dosimetry? And what is the time of fluoroscopy needed to warrant using lens protection? It also raises the question whether current guidelines need to be updated.
DOE Office of Scientific and Technical Information (OSTI.GOV)
McCafferty, Ian, E-mail: ian.mccafferty@uhb.nhs.uk
This review article aims to give an overview of the current state of imaging, patient selection, agents and techniques used in the management of low-flow vascular malformations. The review includes the current classifications for low-flow vascular malformations including the 2014 updates. Clinical presentation and assessment is covered with a detailed section on the common sclerosant agents used to treat low-flow vascular malformations, including dosing and common complications. Imaging is described with a guide to a simple stratification of the use of imaging for diagnosis and interventional techniques.
2007-03-01
time. This is a very powerful tool in determining fine spatial resolution , as boundary conditions are not only updated at every timestep, but the ...HIGH RESOLUTION MESOSCALE WEATHER DATA IMPROVEMENT TO SPATIAL EFFECTS FOR DOSE-RATE CONTOUR PLOT PREDICTIONS THESIS Christopher P...11 1 HIGH RESOLUTION MESOSCALE WEATHER DATA IMPROVEMENT TO SPATIAL EFFECTS FOR DOSE-RATE CONTOUR PLOT
Thilander-Klang, Anne; Ylhan, Betȕl; Lofthag-Hansen, Sara; Ekestubbe, Annika
2016-01-01
Objective: During dental radiography, the salivary and thyroid glands are at radiation risk. In 2007, the International Commission on Radiological Protection (ICRP) updated the methodology for determining the effective dose, and the salivary glands were assigned tissue-specific weighting factors for the first time. The aims of this study were to determine the absorbed dose to the organs and to calculate, applying the ICRP publication 103 tissue-weighting factors, the effective doses delivered during digital intraoral and panoramic radiography. Methods: Thermoluminescent dosemeter measurements were performed on an anthropomorphic head and neck phantom. The organ-absorbed doses were measured at 30 locations, representing different radiosensitive organs in the head and neck, and the effective dose was calculated according to the ICRP recommendations. Results: The salivary glands and the oral mucosa received the highest absorbed doses from both intraoral and panoramic radiography. The effective dose from a full-mouth intraoral examination was 15 μSv and for panoramic radiography, the effective dose was in the range of 19–75 μSv, depending on the panoramic equipment used. Conclusion: The effective dose from a full-mouth intraoral examination is lower and that from panoramic radiography is higher than previously reported. Clinicians should be aware of the higher effective dose delivered during panoramic radiography and the risk–benefit profile of this technique must be assessed for the individual patient. Advances in knowledge: The effective dose of radiation from panoramic radiography is higher than previously reported and there is large variability in the delivered radiation dosage among the different types of equipment used. PMID:27452261
2006-01-01
The Commission intended that its revised recommendations should be based on a simple, but widely applicable, system of protection that would clarify its objectives and provide a basis for the more formal systems needed by operating managers and regulators. The recommendations would establish quantified constraints, or limits, on individual dose from specified sources. These dose constraints apply to actual or representative people who encounter occupational, medical, and public exposures. This report updates the previous guidance for estimating dose to the public. Dose to the public cannot be measured directly and, in some cases, it cannot be measured at all. Therefore, for the purpose of protection of the public, it is necessary to characterise an individual, either hypothetical or specific, whose dose can be used for determining compliance with the relevant dose constraint. This individual is defined as the 'representative person'. The Commission's goal of protection of the public is achieved if the relevant dose constraint for this individual for a single source is met and radiological protection is optimised. This report explains the process of estimating annual dose and recognises that a number of different methods are available for this purpose. These methods range from deterministic calculations to more complex probabilistic techniques. In addition, a mixture of these techniques may be applied. In selecting characteristics of the representative person, three important concepts should be borne in mind: reasonableness, sustainability, and homogeneity. Each concept is explained and examples are provided to illustrate their roles. Doses to the public are prospective (may occur in the future) or retrospective (occurred in the past). Prospective doses are for hypothetical individuals who may or may not exist in the future, while retrospective doses are generally calculated for specific individuals. The Commission recognises that the level of detail afforded by its provision of dose coefficients for six age categories is not necessary in making prospective assessments of dose, given the inherent uncertainties usually associated with estimating dose to the public and with identification of the representative person. It now recommends the use of three age categories for estimating annual dose to the representative person for prospective assessments. These categories are 0-5 years (infant), 6-15 years (child), and 16-70 years (adult). For practical implementation of this recommendation, dose coefficients and habit data for a 1-year-old infant, a 10-year-old child, and an adult should be used to represent the three age categories. In a probabilistic assessment of dose, whether from a planned facility or an existing situation, the Commission recommends that the representative person should be defined such that the probability is less than about 5% that a person drawn at random from the population will receive a greater dose. If such an assessment indicates that a few tens of people or more could receive doses above the relevant constraint, the characteristics of these people need to be explored. If, following further analysis, it is shown that doses to a few tens of people are indeed likely to exceed the relevant dose constraint, actions to modify the exposure should be considered. The Commission recognises the role that stakeholders can play in identifying characteristics of the representative person. Involvement of stakeholders can significantly improve the quality, understanding, and acceptability of the characteristics of the representative person and the resulting estimated dose.
Single dose oral paracetamol (acetaminophen) with codeine for postoperative pain in adults
Toms, Laurence; Derry, Sheena; Moore, R Andrew; McQuay, Henry J
2014-01-01
Background This is an updated version of the Cochrane review published in Issue 4, 1998. Combining drugs from different classes with different modes of action may offer opportunity to optimise efficacy and tolerability, using lower doses of each drug to achieve the same degree of pain relief. Previously we concluded that addition of codeine to paracetamol provided additional pain relief, but at expense of additional adverse events. New studies have been published since. This review sought to evaluate efficacy and safety of paracetamol plus codeine using current data, and compare findings with other analgesics evaluated similarly. Objectives Assess efficacy of single dose oral paracetamol plus codeine in acute postoperative pain, increase in efficacy due to the codeine component, and associated adverse events. Search methods We searched CENTRAL, MEDLINE, EMBASE, the Oxford Pain Relief Database in October 2008 for this update. Selection criteria Randomised, double-blind, placebo-controlled trials of paracetamol plus codeine, compared with placebo or the same dose of paracetamol alone, for relief of acute postoperative pain in adults. Data collection and analysis Two authors assessed trial quality and extracted data. The area under the “pain relief versus time” curve was used to derive proportion of participants with paracetamol plus codeine and placebo or paracetamol alone experiencing least 50% pain relief over four-to-six hours, using validated equations. Number-needed-to-treat-to-benefit (NNT) was calculated using 95% confidence intervals (CIs). Proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results Twenty-six studies, with 2295 participants, were included comparing paracetamol plus codeine with placebo. Significant dose response was seen for the outcome of at least 50% pain relief over four-to-six hours, with NNTs of 2.2 (95% CI 1.8 to 2.9) for 800 to 1000 mg paracetamol plus 60 mg codeine, 3.9 (2.9 to 4.5) for 600 to 650 mg paracetamol plus 60 mg codeine, and 6.9 (4.8 to 12) for 300 mg paracetamol plus 30 mg codeine. Time to use of rescue medication was over four hours with paracetamol plus codeine and two hours with placebo. The NNT to prevent remedication was 5.6 (4.0 to 9.0) for 600 mg paracetamol plus 60 mg codeine over four to six hours. Adverse events increased of mainly mild to moderate severity with paracetamol plus codeine than placebo. Fourteen studies, with 926 participants, were included in the comparison of paracetamol plus codeine with the same dose of paracetamol alone. Addition of codeine increased proportion of participants achieving at least 50% pain relief over four-to-six hours by 10 to 15%, increased time to use of rescue medication by about one hour, and reduced proportion of participants needing rescue medication by about 15% (NNT to prevent remedication 6.9 (4.2 to 19). Adverse events were mainly mild to moderate in severity and incidence did not differ between groups. Authors’ conclusions This update confirms previous findings that combining paracetamol with codeine provided clinically useful levels of pain relief in about 50% of patients with moderate to severe postoperative pain, compared with under 20% with placebo. New information for remedication shows that the combination extended the duration of analgesia by about one hour compared to treatment with the same dose of paracetamol alone. At higher doses, more participants experienced adequate pain relief, but the amount of information available for the 1000 mg paracetamol plus 60 mg codeine dose was small, and based on limited information. PMID:19160199
DOE Office of Scientific and Technical Information (OSTI.GOV)
McLaughlin, David A; Schwahn, Scott O
2011-01-01
While inhalation dose coefficients are provided for about 800 radionuclides in International Commission on Radiological Protection (ICRP) Publication 68, many radionuclides of practical dosimetric interest for facilities such as high-energy proton accelerators are not specifically addressed, nor are organ-specific dose coefficients tabulated. The ICRP Publication 68 methodology is used, along with updated radiological decay data and metabolic data, to identify committed equivalent dose coefficients [hT(50)] and committed effective dose coefficients [e(50)] for radionuclides produced at the Oak Ridge National Laboratory s Spallation Neutron Source.
Nelson, Noele P
2017-09-15
GamaSTAN S/D (Grifols Therapeutics, Inc., Research Triangle Park, North Carolina) is a sterile, preservative-free solution of immune globulin (IG) for intramuscular administration and is used for prophylaxis against disease caused by infection with hepatitis A, measles, varicella, and rubella viruses (1). GamaSTAN S/D is the only IG product approved by the Food and Drug Administration for hepatitis A virus (HAV) prophylaxis. In July 2017, GamaSTAN S/D prescribing information was updated with changes to the dosing instructions for hepatitis A preexposure and postexposure prophylaxis indications. These changes were made because of concerns about decreased HAV immunoglobulin G antibody (anti-HAV IgG) potency, likely resulting from decreasing prevalence of previous HAV infection among plasma donors, leading to declining anti-HAV antibody levels in donor plasma (2). No changes in dosing instructions were made for measles, varicella, or rubella preexposure or postexposure prophylaxis.
Updates from the MSL-RAD Experiment on the Mars Curiosity Rover
NASA Technical Reports Server (NTRS)
Zeitlin, Cary
2015-01-01
The MSL-RAD instrument continues to operate flawlessly on Mars. As of this writing, some 1040 sols (Martian days) of data have been successfully acquired. Several improvements have been made to the instrument's configuration, particularly aimed at enabling the analysis of neutral-particle data. The dose rate since MSL's landing in August 2012 has remained remarkably stable, reflecting the unusual and very weak solar maximum of Cycle 24. Only a few small SEP events have been observed by RAD, which is shielded by the Martian atmosphere. Gale Crater, where Curiosity landed, is 4.4 km below the mean surface of Mars, and the column depth of atmosphere above is approximately 20 g/sq cm, which provides significant attenuation of GCR heavy ions and SEPs. Recent analysis results will be presented, including updated estimates of the neutron contributions to dose and dose equivalent in cruise and on the surface of Mars.
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.
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
23 CFR 1335.12 - Contents of application.
Code of Federal Regulations, 2011 CFR
2011-04-01
... coordinating committee; (2) Certify that the State has conducted or updated an assessment within the last five years, and submit a copy of the assessment and any updates of the assessment; and (3) Certify that the...) Certify that the State has conducted or updated an assessment within the last five years, and submit a...
23 CFR 1335.12 - Contents of application.
Code of Federal Regulations, 2012 CFR
2012-04-01
... coordinating committee; (2) Certify that the State has conducted or updated an assessment within the last five years, and submit a copy of the assessment and any updates of the assessment; and (3) Certify that the...) Certify that the State has conducted or updated an assessment within the last five years, and submit a...
23 CFR 1335.12 - Contents of application.
Code of Federal Regulations, 2010 CFR
2010-04-01
... coordinating committee; (2) Certify that the State has conducted or updated an assessment within the last five years, and submit a copy of the assessment and any updates of the assessment; and (3) Certify that the...) Certify that the State has conducted or updated an assessment within the last five years, and submit a...
International Space Station (ISS) Plasma Contactor Unit (PCU) Utilization Plan Assessment Update
NASA Technical Reports Server (NTRS)
Hernandez-Pellerano, Amri; Iannello, Christopher J.; Wollack, Edward J.; Wright, Kenneth H.; Garrett, Henry B.; Ging, Andrew T.; Katz, Ira; Keith, R. Lloyd; Minow, Joseph I.; Willis, Emily M.;
2014-01-01
The NASA Engineering and Safety Center (NESC) received a request to support the Assessment of the International Space Station (ISS) Plasma Contactor Unit (PCU) Utilization Update. The NESC conducted an earlier assessment of the use of the PCU in 2009. This document contains the outcome of the assessment update.
Federal Register 2010, 2011, 2012, 2013, 2014
2010-08-24
... evaluates potential datasets and recommends which datasets are appropriate for assessment analyses. The... points to datasets incorporated in the original SEDAR benchmark assessment and run the benchmark... Webinar II November 22, 2010; 10 a.m. - 1 p.m.; SEDAR Update Assessment Webinar III Using updated datasets...
Deepwater BP Oil Spill Natural Resource Damage Assessment Update | NOAA
Publications Press Releases Story Archive Home Deepwater BP Oil Spill Natural Resource Damage Assessment Update Deepwater BP Oil Spill Natural Resource Damage Assessment Update share Posted on July 7, 2011 | Assessment and Early Restoration Restoration Area Title: Deepwater BP Oil Spill Natural Resource Damage
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jannik, G. Tim; Hartman, Larry; Stagich, Brooke
Operations at the Savannah River Site (SRS) result in releases of small amounts of radioactive materials to the atmosphere and to the Savannah River. For regulatory compliance purposes, potential offsite radiological doses are estimated annually using computer models that follow U.S. Nuclear Regulatory Commission (NRC) regulatory guides. Within the regulatory guides, default values are provided for many of the dose model parameters, but the use of applicant site-specific values is encouraged. Detailed surveys of land-use and water-use parameters were conducted in 1991 and 2010. They are being updated in this report. These parameters include local characteristics of meat, milk andmore » vegetable production; river recreational activities; and meat, milk and vegetable consumption rates, as well as other human usage parameters required in the SRS dosimetry models. In addition, the preferred elemental bioaccumulation factors and transfer factors (to be used in human health exposure calculations at SRS) are documented. The intent of this report is to establish a standardized source for these parameters that is up to date with existing data, and that is maintained via review of future-issued national references (to evaluate the need for changes as new information is released). These reviews will continue to be added to this document by revision.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jannik, T.; Stagich, B.
Operations at the Savannah River Site (SRS) result in releases of relatively small amounts of radioactive materials to the atmosphere and to the Savannah River. For regulatory compliance purposes, potential offsite radiological doses are estimated annually using computer models that follow U.S. Nuclear Regulatory Commission (NRC) regulatory guides. Within the regulatory guides, default values are provided for many of the dose model parameters, but the use of site-specific values is encouraged. Detailed surveys of land-use and water-use parameters were conducted in 1991, 2008, 2010, and 2016 and are being concurred with or updated in this report. These parameters include localmore » characteristics of meat, milk, and vegetable production; river recreational activities; and meat, milk, and vegetable consumption rates, as well as other human usage parameters required in the SRS dosimetry models. In addition, the preferred elemental bioaccumulation factors and transfer factors (to be used in human health exposure calculations at SRS) are documented. The intent of this report is to establish a standardized source for these parameters that is up to date with existing data, and that is maintained via review of future-issued national references (to evaluate the need for changes as new information is released). These reviews will continue to be added to this document by revision.« less
EURADOS strategic research agenda: vision for dosimetry of ionising radiation
Rühm, W.; Fantuzzi, E.; Harrison, R.; Schuhmacher, H.; Vanhavere, F.; Alves, J.; Bottollier Depois, J. F.; Fattibene, P.; Knežević, Ž.; Lopez, M. A.; Mayer, S.; Miljanić, S.; Neumaier, S.; Olko, P.; Stadtmann, H.; Tanner, R.; Woda, C.
2016-01-01
Since autumn 2012, the European Radiation Dosimetry Group (EURADOS) has been developing its Strategic Research Agenda (SRA), which is intended to contribute to the identification of future research needs in radiation dosimetry in Europe. The present article summarises—based on input from EURADOS Working Groups (WGs) and Voting Members—five visions in dosimetry and defines key issues in dosimetry research that are considered important for the next decades. The five visions include scientific developments required towards (a) updated fundamental dose concepts and quantities, (b) improved radiation risk estimates deduced from epidemiological cohorts, (c) efficient dose assessment for radiological emergencies, (d) integrated personalised dosimetry in medical applications and (e) improved radiation protection of workers and the public. The SRA of EURADOS will be used as a guideline for future activities of the EURADOS WGs. A detailed version of the SRA can be downloaded as a EURADOS report from the EURADOS website (www.eurados.org). PMID:25752758
Owusu-Boateng, Ivy; Anto, Francis
2017-08-10
Malaria in pregnancy poses a great risk to both mother and fetus. In Ghana, malaria accounts for 3.4% of deaths and 16.8% of all hospital admissions in pregnant women. In 2014, Ghana updated her policy on intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) to reflect the updated policy of the WHO. This study determined the level of uptake of sulfadoxine pyrimethamine (SP) to serve as baseline for monitoring progress and also reviewed stock levels of SP, a key factor in the programme implementation. A cross-sectional hospital-based study was carried out among nursing mothers who had delivered within 12 weeks and were seeking postnatal care at Osu Government Maternity Home in Accra. Antenatal record books of the mothers were reviewed and data collected on number of visits and receipt of IPTp-SP. Mothers were interviewed and data collected on their background characteristics and obstetric history. Data on SP stock levels for the past 6 months were also reviewed. Logistic regression analysis was carried out to determine antenatal indicators on uptake of IPTp-SP using Stata version 12. The proportion of uptake of three-five doses of SP were: IPT3 (87.5%), IPT4 (55.7%) and IPT5 (14.5%). The proportion of women who received the first dose of SP at 16 weeks of gestation was 21.3%. Women who made ≥4 visits were more likely to receive ≥3 doses of SP than those who made <4 visits (AOR = 4.57, 95% CI 1.15-18.16, p < 0.05). Women receiving the first dose of SP in the third trimester were less likely to receive ≥3 doses of SP than those who received the drug in the second trimester (AOR = 0.04, 95% CI 0.01-0.16, p < 0.05). Stock levels of SP were adequate to meet the demands by the pregnant women at the Maternity Home for the period under review. The uptake of ≥3 doses of SP was high in the study area. Frequent visits to the antenatal clinic and early uptake of the first dose of SP by pregnant women are necessary to achieve the new target of five or more doses of SP.
Dose conversion coefficients for neutron exposure to the lens of the human eye.
Manger, R P; Bellamy, M B; Eckerman, K F
2012-03-01
Dose conversion coefficients for the lens of the human eye have been calculated for neutron exposure at energies from 1 × 10(-9) to 20 MeV and several standard orientations: anterior-to-posterior, rotational and right lateral. MCNPX version 2.6.0, a Monte Carlo-based particle transport package, was used to determine the energy deposited in the lens of the eye. The human eyeball model was updated by partitioning the lens into sensitive and insensitive volumes as the anterior portion (sensitive volume) of the lens being more radiosensitive and prone to cataract formation. The updated eye model was used with the adult UF-ORNL mathematical phantom in the MCNPX transport calculations.
Fish consumption and CHD mortality: an updated meta-analysis of seventeen cohort studies.
Zheng, Jusheng; Huang, Tao; Yu, Yinghua; Hu, Xiaojie; Yang, Bin; Li, Duo
2012-04-01
Results of studies on fish consumption and CHD mortality are inconsistent. The present updated meta-analysis was conducted to investigate the up-to-date pooling effects. A random-effects model was used to pool the risk estimates. Generalized least-squares regression and restricted cubic splines were used to assess the possible dose-response relationship. Subgroup analyses were conducted to examine the sources of heterogeneity. PubMed and ISI Web of Science databases up to September 2010 were searched and secondary referencing qualified for inclusion in the study. Seventeen cohorts with 315,812 participants and average follow-up period of 15·9 years were identified. Compared with the lowest fish intake (<1 serving/month or 1-3 servings/month), the pooled relative risk (RR) of fish intake on CHD mortality was 0·84 (95% CI 0·75, 0·95) for low fish intake (1 serving/week), 0·79 (95% CI 0·67, 0·92) for moderate fish intake (2-4 servings/week) and 0·83 (95% CI 0·68, 1·01) for high fish intake (>5 servings/week). The dose-response analysis indicated that every 15 g/d increment of fish intake decreased the risk of CHD mortality by 6% (RR = 0·94; 95% CI 0·90, 0·98). The method of dietary assessment, gender and energy adjustment affected the results remarkably. Our results indicate that either low (1 serving/week) or moderate fish consumption (2-4 servings/week) has a significantly beneficial effect on the prevention of CHD mortality. High fish consumption (>5 servings/week) possesses only a marginally protective effect on CHD mortality, possibly due to the limited studies included in this group.
Zhao, Li-Na; Li, Jie-Yao; Yu, Tao; Chen, Guang-Cheng; Yuan, Yu-Hong; Chen, Qi-Kui
2014-01-01
Background Although the chemopreventive effect of 5-aminosalicylates on patients with ulcerative colitis has been extensively studied, the results remain controversial. This updated review included more recent studies and evaluated the effectiveness of 5-aminosalicylates use on colorectal neoplasia prevention in patients with ulcerative colitis. Methods Up to July 2013, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant observational studies (case-control and cohort) about the effect of 5-aminosalicylates on the risk of colorectal neoplasia among patients with ulcerative colitis. The Newcastle-Ottawa Scale was used to assess the quality of studies. Adjusted odds ratios (ORs) were extracted from each study. A random-effects model was used to generate pooled ORs and 95% confidence intervals (95%CI). Publication bias and heterogeneity were assessed. Results Seventeen studies containing 1,508 cases of colorectal neoplasia and a total of 20,193 subjects published from 1994 to 2012 were analyzed. 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis (OR 0.63; 95%CI 0.48–0.84). Pooled OR of a higher average daily dose of 5-aminosalicylates (sulfasalazine ≥ 2.0 g/d, mesalamine ≥ 1.2 g/d) was 0.51 [0.35–0.75]. Pooled OR of 5-aminosalicylates use in patients with extensive ulcerative colitis was 1.00 [0.53–1.89]. Conclusion Our pooled results indicated that 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis, especially in the cases with a higher average daily dose of 5-aminosalicylates use. However, the chemopreventive benefit of 5-aminosalicylates use in patients with extensive ulcerative colitis was limited. PMID:24710620
Zhao, Li-Na; Li, Jie-Yao; Yu, Tao; Chen, Guang-Cheng; Yuan, Yu-Hong; Chen, Qi-Kui
2014-01-01
Although the chemopreventive effect of 5-aminosalicylates on patients with ulcerative colitis has been extensively studied, the results remain controversial. This updated review included more recent studies and evaluated the effectiveness of 5-aminosalicylates use on colorectal neoplasia prevention in patients with ulcerative colitis. Up to July 2013, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant observational studies (case-control and cohort) about the effect of 5-aminosalicylates on the risk of colorectal neoplasia among patients with ulcerative colitis. The Newcastle-Ottawa Scale was used to assess the quality of studies. Adjusted odds ratios (ORs) were extracted from each study. A random-effects model was used to generate pooled ORs and 95% confidence intervals (95%CI). Publication bias and heterogeneity were assessed. Seventeen studies containing 1,508 cases of colorectal neoplasia and a total of 20,193 subjects published from 1994 to 2012 were analyzed. 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis (OR 0.63; 95%CI 0.48-0.84). Pooled OR of a higher average daily dose of 5-aminosalicylates (sulfasalazine ≥ 2.0 g/d, mesalamine ≥ 1.2 g/d) was 0.51 [0.35-0.75]. Pooled OR of 5-aminosalicylates use in patients with extensive ulcerative colitis was 1.00 [0.53-1.89]. Our pooled results indicated that 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis, especially in the cases with a higher average daily dose of 5-aminosalicylates use. However, the chemopreventive benefit of 5-aminosalicylates use in patients with extensive ulcerative colitis was limited.
Federal Register 2010, 2011, 2012, 2013, 2014
2010-10-06
... of SEDAR spiny lobster update assessment review. SUMMARY: SEDAR will hold a meeting of the spiny lobster update assessment review panel. The meeting will be held in Key West, FL. See SUPPLEMENTARY... review of the updated spiny lobster assessment. They will develop stock status and fishing level...
Improvements to the Ionizing Radiation Risk Assessment Program for NASA Astronauts
NASA Technical Reports Server (NTRS)
Semones, E. J.; Bahadori, A. A.; Picco, C. E.; Shavers, M. R.; Flores-McLaughlin, J.
2011-01-01
To perform dosimetry and risk assessment, NASA collects astronaut ionizing radiation exposure data from space flight, medical imaging and therapy, aviation training activities and prior occupational exposure histories. Career risk of exposure induced death (REID) from radiation is limited to 3 percent at a 95 percent confidence level. The Radiation Health Office at Johnson Space Center (JSC) is implementing a program to integrate the gathering, storage, analysis and reporting of astronaut ionizing radiation dose and risk data and records. This work has several motivations, including more efficient analyses and greater flexibility in testing and adopting new methods for evaluating risks. The foundation for these improvements is a set of software tools called the Astronaut Radiation Exposure Analysis System (AREAS). AREAS is a series of MATLAB(Registered TradeMark)-based dose and risk analysis modules that interface with an enterprise level SQL Server database by means of a secure web service. It communicates with other JSC medical and space weather databases to maintain data integrity and consistency across systems. AREAS is part of a larger NASA Space Medicine effort, the Mission Medical Integration Strategy, with the goal of collecting accurate, high-quality and detailed astronaut health data, and then securely, timely and reliably presenting it to medical support personnel. The modular approach to the AREAS design accommodates past, current, and future sources of data from active and passive detectors, space radiation transport algorithms, computational phantoms and cancer risk models. Revisions of the cancer risk model, new radiation detection equipment and improved anthropomorphic computational phantoms can be incorporated. Notable hardware updates include the Radiation Environment Monitor (which uses Medipix technology to report real-time, on-board dosimetry measurements), an updated Tissue-Equivalent Proportional Counter, and the Southwest Research Institute Radiation Assessment Detector. Also, the University of Florida hybrid phantoms, which are flexible in morphometry and positioning, are being explored as alternatives to the current NASA computational phantoms.
Jiang, Wenjie; Wu, Yili; Jiang, Xiubo
2013-06-01
We conducted an updated meta-analysis to summarize the evidence from published studies regarding the association of coffee and caffeine intake with breast cancer risk. Pertinent studies were identified by a search of PubMed and by reviewing the reference lists of retrieved articles. The fixed or random effect model was used based on heterogeneity test. The dose-response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression. 37 published articles, involving 59,018 breast cancer cases and 966,263 participants, were included in the meta-analysis. No significant association was found between breast cancer risk and coffee (RR=0.97, P=0.09), decaffeinated coffee (RR=0.98, P=0.55) and caffeine (RR=0.99, P=0.73), respectively. And the association was still not significant when combining coffee and caffeine (coffee/caffeine) (RR=0.97, P=0.09). However, an inverse association of coffee/caffeine with breast cancer risk was found for postmenopausal women (RR=0.94, P=0.02), and a strong and significant association of coffee with breast cancer risk was found for BRCA1 mutation carriers (RR=0.69, P<0.01). A linear dose-response relationship was found for breast cancer risk with coffee and caffeine, and the risk of breast cancer decreased by 2% (P=0.05) for every 2 cups/day increment in coffee intake, and 1% (P=0.52) for every 200mg/day increment in caffeine intake, respectively. Findings from this meta-analysis suggested that coffee/caffeine might be weakly associated with breast cancer risk for postmenopausal women, and the association for BRCA1 mutation carriers deserves further investigation. Copyright © 2013 Elsevier Inc. All rights reserved.
Vardeny, Orly; Claggett, Brian; Packer, Milton; Zile, Michael R; Rouleau, Jean; Swedberg, Karl; Teerlink, John R; Desai, Akshay S; Lefkowitz, Martin; Shi, Victor; McMurray, John J V; Solomon, Scott D
2016-10-01
In this analysis, we utilized data from PARADIGM-HF to test the hypothesis that participants who exhibited any dose reduction during the trial would have similar benefits from lower doses of sacubitril/valsartan relative to lower doses of enalapril. In a post-hoc analysis from PARADIGM-HF, we characterized patients by whether they received the maximal dose (200 mg sacubitril/valsartan or 10 mg enalapril twice daily) throughout the trial or had any dose reduction to lower doses (100/50/0 mg sacubitril/valsartan or 5/2.5/0 mg enalapril twice daily). The treatment effect for the primary outcome was estimated, stratified by dose level using time-updated Cox regression models. In the two treatment arms, participants with a dose reduction (43% of those randomized to enalapril and 42% of those randomized to sacubitril/valsartan) had similar baseline characteristics and similar baseline predictors of the need for dose reduction. In a time-updated analysis, any dose reduction was associated with a higher subsequent risk of the primary event [hazard ratio (HR) 2.5, 95% confidence interval (CI) 2.2-2.7]. However, the treatment benefit of sacubitril/valsartan over enalapril following a dose reduction was similar (HR 0.80, 95% CI 0.70-0.93, P < 0.001) to that observed in patients who had not experienced any dose reduction (HR 0.79, 95% CI 0.71-0.88, P < 0.001). In PARADIGM-HF, study medication dose reduction identified patients at higher risk of a major cardiovascular event. The magnitude of benefit for patients on lower doses of sacubitril/valsartan relative to those on lower doses of enalapril was similar to that of patients who remained on target doses of both drugs. © 2016 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hay, Tristan R.; Rishel, Jeremy P.
2013-09-30
The Air Pollutant Graphical Environmental Monitoring System (APGEMS) is used by the Hanford Emergency Operation Center (EOC) to provide refined plume modeling of releases involving radionuclides. The dose conversion factors (DCFs) used by APGEMS to convert air concentration to dose are stored in a file called HUDUFACT.dat; the DCFs are based primarily on ICRP 30 compiled in the late 1980’s. This report updates the DCFs using more recent values reported in the Environmental Protection Agencies (EPAs) Federal Guidance Report (FGR) 12 and 13. FGR 12 provides external exposure (air submersion) DCFs for radionuclides in air; FGR 13 provides DCFs formore » radionuclides from inhalation. DCFs were updated for only those radionuclides listed in the original HUDUFACT.dat file. Since FGR 13 provides inhalation dose conversion factors as a function of age, revised DCF files were created for APGEMS for each age group. The “adult” DCF file is the most relevant to compare to the original DCF file being used in APGEMS; these DCF values are compared in this report.« less
Single dose dipyrone for acute postoperative pain
Derry, Sheena; Faura, Clara; Edwards, Jayne; McQuay, Henry J; Moore, R Andrew
2014-01-01
Background Dipyrone (metamizole) is a non-steroidal anti-inflammatory drug used in some countries to treat pain (postoperative, colic, cancer, and migraine); it is banned in others because of an association with life-threatening blood agranulocytosis. This review updates a 2001 Cochrane review, and no relevant new studies were identified, but additional outcomes were sought. Objectives To assess the efficacy and adverse events of single dose dipyrone in acute postoperative pain. Search methods The earlier review searched CENTRAL, MEDLINE, EMBASE, LILACS and the Oxford Pain Relief Database to December 1999. For the update we searched CENTRAL, MEDLINE,EMBASE and LILACS to February 2010. Selection criteria Single dose, randomised, double-blind, placebo or active controlled trials of dipyrone for relief of established moderate to severe postoperative pain in adults. We included oral, rectal, intramuscular or intravenous administration of study drugs. Data collection and analysis Studies were assessed for methodological quality and data extracted by two review authors independently. Summed total pain relief over six hours (TOTPAR) was used to calculate the number of participants achieving at least 50% pain relief. Derived results were used to calculate, with 95% confidence intervals, relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over six hours. Use and time to use of rescue medication were additional measures of efficacy. Information on adverse events and withdrawals was collected. Main results Fifteen studies tested mainly 500 mg oral dipyrone (173 participants), 2.5 g intravenous dipyrone (101), 2.5 g intramuscular dipyrone (99); fewer than 60 participants received any other dose. All studies used active controls (ibuprofen, paracetamol, aspirin, flurbiprofen, ketoprofen, dexketoprofen, ketorolac, pethidine, tramadol, suprofen); eight used placebo controls. Over 70% of participants experienced at least 50% pain relief over 4 to 6 hours with oral dipyrone 500 mg compared to 30% with placebo in five studies (288 participants; NNT 2.4 (1.9 to 3.2)). Fewer participants needed rescue medication with dipyrone (7%) than with placebo (34%; four studies, 248 participants). There was no difference in participants experiencing at least 50% pain relief with 2.5 g intravenous dipyrone and 100 mg intravenous tramadol (70% vs 65%; two studies, 200 participants). No serious adverse events were reported. Authors’ conclusions Based on very limited information, single dose dipyrone 500 mg provides good pain relief to 70% of patients. For every five individuals given dipyrone 500 mg, two would experience this level of pain relief who would not have done with placebo, and fewer would need rescue medication, over 4 to 6 hours. PMID:20824835
Krauer, Fabienne; Riesen, Maurane; Reveiz, Ludovic; Oladapo, Olufemi T; Martínez-Vega, Ruth; Porgo, Teegwendé V; Haefliger, Anina; Broutet, Nathalie J; Low, Nicola
2017-01-01
The World Health Organization (WHO) stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain-Barré syndrome (GBS) and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b) GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality. The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose-response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose-response relationship and specificity), we found that more than half the relevant studies supported a causal association with Zika virus infection. For GBS, we included 36 items, of which more than half the relevant studies supported a causal association in seven of ten dimensions (all except dose-response relationship, specificity, and animal experimental evidence). Articles identified nonsystematically from May 30 to July 29, 2016 strengthened the review findings. The expert panel concluded that (a) the most likely explanation of available evidence from outbreaks of Zika virus infection and clusters of microcephaly is that Zika virus infection during pregnancy is a cause of congenital brain abnormalities including microcephaly, and (b) the most likely explanation of available evidence from outbreaks of Zika virus infection and GBS is that Zika virus infection is a trigger of GBS. The expert panel recognised that Zika virus alone may not be sufficient to cause either congenital brain abnormalities or GBS but agreed that the evidence was sufficient to recommend increased public health measures. Weaknesses are the limited assessment of the role of dengue virus and other possible cofactors, the small number of comparative epidemiological studies, and the difficulty in keeping the review up to date with the pace of publication of new research. Rapid and systematic reviews with frequent updating and open dissemination are now needed both for appraisal of the evidence about Zika virus infection and for the next public health threats that will emerge. This systematic review found sufficient evidence to say that Zika virus is a cause of congenital abnormalities and is a trigger of GBS.
IRIS Toxicological Review of 1,4-Dioxane (with Inhalation ...
On September 9, 2011, the Toxicological Review of 1,4-Dioxane (inhalation) (External Review Draft) was posted for external peer review and public comment. Subsequently, the Toxicological Review and IRIS Summary were reviewed internally by EPA and by other federal agencies and Executive Office of the President before final public release. Based on the 2009 IRIS assessment development process, all written comments on IRIS assessments submitted by other federal agencies and the Executive Office of the President will be made publicly available. Accordingly, interagency comments with EPA's response and the interagency science discussion draft of the IRIS Toxicological Review of 1,4-dioxane (with inhalation update) and the draft IRIS Summary are posted on this site. The Toxicological Review of 1,4-dioxane provides scientific support and rationale for the hazard and dose-response assessment pertaining to chronic exposure to 1,4-dioxane.
MutAIT: an online genetic toxicology data portal and analysis tools.
Avancini, Daniele; Menzies, Georgina E; Morgan, Claire; Wills, John; Johnson, George E; White, Paul A; Lewis, Paul D
2016-05-01
Assessment of genetic toxicity and/or carcinogenic activity is an essential element of chemical screening programs employed to protect human health. Dose-response and gene mutation data are frequently analysed by industry, academia and governmental agencies for regulatory evaluations and decision making. Over the years, a number of efforts at different institutions have led to the creation and curation of databases to house genetic toxicology data, largely, with the aim of providing public access to facilitate research and regulatory assessments. This article provides a brief introduction to a new genetic toxicology portal called Mutation Analysis Informatics Tools (MutAIT) (www.mutait.org) that provides easy access to two of the largest genetic toxicology databases, the Mammalian Gene Mutation Database (MGMD) and TransgenicDB. TransgenicDB is a comprehensive collection of transgenic rodent mutation data initially compiled and collated by Health Canada. The updated MGMD contains approximately 50 000 individual mutation spectral records from the published literature. The portal not only gives access to an enormous quantity of genetic toxicology data, but also provides statistical tools for dose-response analysis and calculation of benchmark dose. Two important R packages for dose-response analysis are provided as web-distributed applications with user-friendly graphical interfaces. The 'drsmooth' package performs dose-response shape analysis and determines various points of departure (PoD) metrics and the 'PROAST' package provides algorithms for dose-response modelling. The MutAIT statistical tools, which are currently being enhanced, provide users with an efficient and comprehensive platform to conduct quantitative dose-response analyses and determine PoD values that can then be used to calculate human exposure limits or margins of exposure. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Palache, Abraham; Oriol-Mathieu, Valerie; Fino, Mireli; Xydia-Charmanta, Margarita
2015-10-13
Seasonal influenza is an important disease which results in 250,000-500,000 annual deaths worldwide. Global targets for vaccination coverage rates (VCRs) in high-risk groups are at least 75% in adults ≥65 years and increased coverage in other risk groups. The International Federation of Pharmaceutical Manufacturers and Associations Influenza Vaccine Supply (IFPMA IVS) International Task Force developed a survey methodology in 2008, to assess the global distribution of influenza vaccine doses as a proxy for VCRs. This paper updates the previous survey results on absolute numbers of influenza vaccine doses distributed between 2004 and 2013 inclusive, and dose distribution rates per 1000 population, and provides a qualitative assessment of the principal enablers and barriers to seasonal influenza vaccination. The two main findings from the quantitative portion of the survey are the continued negative trend for dose distribution in the EURO region and the perpetuation of appreciable differences in scale of dose distribution between WHO regions, with no observed convergence in the rates of doses distributed per 1000 population over time. The main findings from the qualitative portion of the survey were that actively managing the vaccination program in real-time and ensuring political commitment to vaccination are important enablers of vaccination, whereas insufficient access to vaccination and lack of political commitment to seasonal influenza vaccination programs are likely contributing to vaccination target failures. In all regions of the world, seasonal influenza vaccination is underutilized as a public health tool. The survey provides evidence of lost opportunity to protect populations against potentially serious influenza-associated disease. We call on the national and international public health communities to re-evaluate their political commitment to the prevention of the annual influenza disease burden and to develop a systematic approach to improve vaccine distribution equitably. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Updated recommendations on the use of hydroxychloroquine in dermatologic practice.
Fernandez, Anthony P
2017-06-01
Hydroxychloroquine has unique immunomodulatory properties and an attractive adverse effect profile. Over the past 10 years, research has led to significant updates in clinical recommendations concerning the optimal use of hydroxychloroquine and monitoring of patients taking it. We discuss updated recommendations concerning hydroxychloroquine daily dosing, retinopathy screening, serologic monitoring, use in smokers, use in pregnant women, and adverse effect risk and monitoring. This review can hopefully serve as an aid to dermatologists and help ensure they continue using hydroxychloroquine safely and effectively. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Single dose oral paracetamol (acetaminophen) for postoperative pain in adults
Toms, Laurence; McQuay, Henry J; Derry, Sheena; Moore, R Andrew
2014-01-01
Background This is an updated version of the original Cochrane review published in Issue 1, 2004 - this original review had been split from a previous title on ‘Single dose paracetamol (acetaminophen) with and without codeine for postoperative pain’. The last version of this review concluded that paracetamol is an effective analgesic for postoperative pain, but additional trials have since been published. This review sought to evaluate the efficacy and safety of paracetamol using current data, and to compare the findings with other analgesics evaluated in the same way. Objectives To assess the efficacy of single dose oral paracetamol for the treatment of acute postoperative pain. Search methods We searched The Cochrane Library, MEDLINE, EMBASE, the Oxford Pain Relief Database and reference lists of articles to update an existing version of the review in July 2008. Selection criteria Randomised, double-blind, placebo-controlled clinical trials of paracetamol for acute postoperative pain in adults. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Area under the “pain relief versus time” curve was used to derive the proportion of participants with paracetamol or placebo experiencing at least 50% pain relief over four to six hours, using validated equations. Number-needed-to-treat-to-benefit (NNT) was calculated, with 95% confidence intervals (CI). The proportion of participants using rescue analgesia over a specified time period, and time to use, were sought as measures of duration of analgesia. Information on adverse events and withdrawals was also collected. Main results Fifty-one studies, with 5762 participants, were included: 3277 participants were treated with a single oral dose of paracetamol and 2425 with placebo. About half of participants treated with paracetamol at standard doses achieved at least 50% pain relief over four to six hours, compared with about 20% treated with placebo. NNTs for at least 50% pain relief over four to six hours following a single dose of paracetamol were as follows: 500 mg NNT 3.5 (2.7 to 4.8); 600 to 650 mg NNT 4.6 (3.9 to 5.5); 975 to 1000 mg NNT 3.6 (3.4 to 4.0). There was no dose response. Sensitivity analysis showed no significant effect of trial size or quality on this outcome. About half of participants needed additional analgesia over four to six hours, compared with about 70% with placebo. Five people would need to be treated with 1000 mg paracetamol, the most commonly used dose, to prevent one needing rescue medication over four to six hours, who would have needed it with placebo. Adverse event reporting was inconsistent and often incomplete. Reported adverse events were mainly mild and transient, and occurred at similar rates with 1000 mg paracetamol and placebo. No serious adverse events were reported. Withdrawals due to adverse events were uncommon and occurred in both paracetamol and placebo treatment arms. Authors’ conclusions A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events. PMID:18843665
Dose conversion coefficients for neutron exposure to the lens of the human eye
DOE Office of Scientific and Technical Information (OSTI.GOV)
Manger, Ryan P; Bellamy, Michael B; Eckerman, Keith F
Dose conversion coefficients for the lens of the human eye have been calculated for neutron exposure at energies from 1 x 10{sup -9} to 20 MeV and several standard orientations: anterior-to-posterior, rotational and right lateral. MCNPX version 2.6.0, a Monte Carlo-based particle transport package, was used to determine the energy deposited in the lens of the eye. The human eyeball model was updated by partitioning the lens into sensitive and insensitive volumes as the anterior portion (sensitive volume) of the lens being more radiosensitive and prone to cataract formation. The updated eye model was used with the adult UF-ORNL mathematicalmore » phantom in the MCNPX transport calculations.« less
Airliner Cabin Ozone: An Updated Review
1989-12-01
authorized Airliner Cabin Ozone: An Updated Review INTRODUCTION Prior to 1980 , there was a great deal of concern about the adverse effects of ozone on the...and by flight planning to avoid known areas of high atmospheric ozone concentration. Since the final rule was published in 1980 , few reports have...pointed out in 1980 (4), that ozone concentration is the predominant factor in determining the effective dose. These latter studies indicate that
Wang, Zhi-Quan; Zhang, Rui; Zhang, Peng-Pai; Liu, Xiao-Hong; Sun, Jian; Wang, Jun; Feng, Xiang-Fei; Lu, Qiu-Fen; Li, Yi-Gang
2015-04-01
Warfarin is yet the most widely used oral anticoagulant for thromboembolic diseases, despite the recently emerged novel anticoagulants. However, difficulty in maintaining stable dose within the therapeutic range and subsequent serious adverse effects markedly limited its use in clinical practice. Pharmacogenetics-based warfarin dosing algorithm is a recently emerged strategy to predict the initial and maintaining dose of warfarin. However, whether this algorithm is superior over conventional clinically guided dosing algorithm remains controversial. We made a comparison of pharmacogenetics-based versus clinically guided dosing algorithm by an updated meta-analysis. We searched OVID MEDLINE, EMBASE, and the Cochrane Library for relevant citations. The primary outcome was the percentage of time in therapeutic range. The secondary outcomes were time to stable therapeutic dose and the risks of adverse events including all-cause mortality, thromboembolic events, total bleedings, and major bleedings. Eleven randomized controlled trials with 2639 participants were included. Our pooled estimates indicated that pharmacogenetics-based dosing algorithm did not improve percentage of time in therapeutic range [weighted mean difference, 4.26; 95% confidence interval (CI), -0.50 to 9.01; P = 0.08], but it significantly shortened the time to stable therapeutic dose (weighted mean difference, -8.67; 95% CI, -11.86 to -5.49; P < 0.00001). Additionally, pharmacogenetics-based algorithm significantly reduced the risk of major bleedings (odds ratio, 0.48; 95% CI, 0.23 to 0.98; P = 0.04), but it did not reduce the risks of all-cause mortality, total bleedings, or thromboembolic events. Our results suggest that pharmacogenetics-based warfarin dosing algorithm significantly improves the efficiency of International Normalized Ratio correction and reduces the risk of major hemorrhage.
The updated billion-ton resource assessment
Anthony Turhollow; Robert Perlack; Laurence Eaton; Matthew Langholtz; Craig Brandt; Mark Downing; Lynn Wright; Kenneth Skog; Chad Hellwinckel; Bryce Stokes; Patricia Lebow
2014-01-01
This paper summarizes the results of an update to a resource assessment, published in 2005, commonly referred to as the Billion-Ton Study (BTS). The updated results are consistent with the 2005 BTS in terms of overall magnitude. The 2005 BTS projected between 860 and 1240 Tg of biomass available in the 2050 timeframe, while the Billion-Ton Update (BT2), for a price of...
Palache, A; Abelin, A; Hollingsworth, R; Cracknell, W; Jacobs, C; Tsai, T; Barbosa, P
2017-08-24
There is no global monitoring system for influenza vaccination coverage, making it difficult to assess progress towards the 2003 World Health Assembly (WHA) vaccination coverage target. In 2008, the IFPMA Influenza Vaccine Supply International Task Force (IVS) developed a survey method to assess the global distribution of influenza vaccine doses as a proxy for vaccination coverage rates. The latest dose distribution data for 2014 and 2015 was used to update previous analyses. Data were confidentially collected and aggregated by the IFPMA Secretariat, and combined with previous IFPMA IVS survey data (2004-2013). Data were available from 201 countries over the 2004-2015 period. A "hurdle" rate was defined as the number of doses required to reach 15.9% of the population in 2008. Overall, the number of distributed doses progressively increased between 2004 and 2011, driven by a 150% increase in AMRO, then plateaued. One percent fewer doses were distributed in 2015 than in 2011. Twenty-three countries were above the hurdle rate in 2015, compared to 15 in 2004, but distribution was highly uneven in and across all WHO regions. Three WHO regions (AMRO, EURO and WPRO) accounted for about 95% of doses distributed. But in EURO and WPRO, distribution rates in 2015 were only marginally higher than in 2004, and in EURO there was an overall downward trend in dose distribution. The vast majority of countries cannot meet the 2003WHA coverage targets and are inadequately prepared for a global influenza pandemic. With only 5% of influenza vaccine doses being distributed to 50% of the world's population, there is urgency to redress the gross inequities in disease prevention and in pandemic preparedness. The 2003WHA resolution must be reviewed and revised and a call issued for the renewed commitment of Member States to influenza vaccination coverage targets. Copyright © 2017. Published by Elsevier Ltd.
An update to the toxicological profile for water-soluble and sparingly soluble tungsten substances
Lemus, Ranulfo; Venezia, Carmen F.
2015-01-01
Abstract Tungsten is a relatively rare metal with numerous applications, most notably in machine tools, catalysts, and superalloys. In 2003, tungsten was nominated for study under the National Toxicology Program, and in 2011, it was nominated for human health assessment under the US Environmental Protection Agency's (EPA) Integrated Risk Information System. In 2005, the Agency for Toxic Substances and Disease Registry (ATSDR) issued a toxicological profile for tungsten, identifying several data gaps in the hazard assessment of tungsten. By filling the data gaps identified by the ATSDR, this review serves as an update to the toxicological profile for tungsten and tungsten substances. A PubMed literature search was conducted to identify reports published during the period 2004–2014, in order to gather relevant information related to tungsten toxicity. Additional information was also obtained directly from unpublished studies from within the tungsten industry. A systematic approach to evaluate the quality of data was conducted according to published criteria. This comprehensive review has gathered new toxicokinetic information and summarizes the details of acute and repeated-exposure studies that include reproductive, developmental, neurotoxicological, and immunotoxicological endpoints. Such new evidence involves several relevant studies that must be considered when regulators estimate and propose a tungsten reference or concentration dose. PMID:25695728
Fetal and maternal dose assessment for diagnostic scans during pregnancy
NASA Astrophysics Data System (ADS)
Rafat Motavalli, Laleh; Miri Hakimabad, Hashem; Hoseinian Azghadi, Elie
2016-05-01
Despite the concerns about prenatal exposure to ionizing radiation, the number of nuclear medicine examinations performed for pregnant women increased in the past decade. This study attempts to better quantify radiation doses due to diagnostic nuclear medicine procedures during pregnancy with the help of our recently developed 3, 6, and 9 month pregnant hybrid phantoms. The reference pregnant models represent the adult female international commission on radiological protection (ICRP) reference phantom as a base template with a fetus in her gravid uterus. Six diagnostic scintigraphy scans using different radiopharmaceuticals were selected as typical diagnostic nuclear medicine procedures. Furthermore, the biokinetic data of radioiodine was updated in this study. A compartment representing iodide in fetal thyroid was addressed explicitly in the biokinetic model. Calculations were performed using the Monte Carlo transport method. Tabulated dose coefficients for both maternal and fetal organs are provided. The comparison was made with the previously published fetal doses calculated for stylized pregnant female phantoms. In general, the fetal dose in previous studies suffers from an underestimation of up to 100% compared to fetal dose at organ level in this study. A maximum of difference in dose was observed for the fetal thyroid compared to the previous studies, in which the traditional models did not contain the fetal thyroid. Cumulated activities of major source organs are primarily responsible for the discrepancies in the organ doses. The differences in fetal dose depend on several other factors including chord length distribution between fetal organs and maternal major source organs, and anatomical differences according to gestation periods. Finally, considering the results of this study, which was based on the realistic pregnant female phantoms, a more informed evaluation of the risks and benefits of the different procedures could be made.
Rizzo, J Douglas; Brouwers, Melissa; Hurley, Patricia; Seidenfeld, Jerome; Arcasoy, Murat O; Spivak, Jerry L; Bennett, Charles L; Bohlius, Julia; Evanchuk, Darren; Goode, Matthew J; Jakubowski, Ann A; Regan, David H; Somerfield, Mark R
2010-11-18
To update American Society of Hematology/American Society of Clinical Oncology recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer. An Update Committee reviewed data published between January 2007 and January 2010. MEDLINE and the Cochrane Library were searched. The literature search yielded one new individual patient data analysis and four literature-based meta-analyses, two systematic reviews, and 13 publications reporting new results from randomized controlled trials not included in prior or new reviews. For patients undergoing myelosuppressive chemotherapy who have a hemoglobin (Hb) level less than 10 g/dL, the Update Committee recommends that clinicians discuss potential harms (eg, thromboembolism, shorter survival) and benefits (eg, decreased transfusions) of ESAs and compare these with potential harms (eg, serious infections, immune-mediated adverse reactions) and benefits (eg, rapid Hb improvement) of RBC transfusions. Individual preferences for assumed risk should contribute to shared decisions on managing chemotherapy-induced anemia. The Committee cautions against ESA use under other circumstances. If used, ESAs should be administered at the lowest dose possible and should increase Hb to the lowest concentration possible to avoid transfusions. Available evidence does not identify Hb levels ≥ 10 g/dL either as thresholds for initiating treatment or as targets for ESA therapy. Starting doses and dose modifications after response or nonresponse should follow US Food and Drug Administration-approved labeling. ESAs should be discontinued after 6 to 8 weeks in nonresponders. ESAs should be avoided in patients with cancer not receiving concurrent chemotherapy, except for those with lower risk myelodysplastic syndromes. Caution should be exercised when using ESAs with chemotherapeutic agents in diseases associated with increased risk of thromboembolic complications. Table 1 lists detailed recommendations.
Rizzo, J Douglas; Brouwers, Melissa; Hurley, Patricia; Seidenfeld, Jerome; Arcasoy, Murat O; Spivak, Jerry L; Bennett, Charles L; Bohlius, Julia; Evanchuk, Darren; Goode, Matthew J; Jakubowski, Ann A; Regan, David H; Somerfield, Mark R
2010-11-20
To update American Society of Clinical Oncology/American Society of Hematology recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer. An Update Committee reviewed data published between January 2007 and January 2010. MEDLINE and the Cochrane Library were searched. The literature search yielded one new individual patient data analysis and four literature-based meta-analyses, two systematic reviews, and 13 publications reporting new results from randomized controlled trials not included in prior or new reviews. For patients undergoing myelosuppressive chemotherapy who have a hemoglobin (Hb) level less than 10 g/dL, the Update Committee recommends that clinicians discuss potential harms (eg, thromboembolism, shorter survival) and benefits (eg, decreased transfusions) of ESAs and compare these with potential harms (eg, serious infections, immune-mediated adverse reactions) and benefits (eg, rapid Hb improvement) of RBC transfusions. Individual preferences for assumed risk should contribute to shared decisions on managing chemotherapy-induced anemia. The Committee cautions against ESA use under other circumstances. If used, ESAs should be administered at the lowest dose possible and should increase Hb to the lowest concentration possible to avoid transfusions. Available evidence does not identify Hb levels ≥ 10 g/dL either as thresholds for initiating treatment or as targets for ESA therapy. Starting doses and dose modifications after response or nonresponse should follow US Food and Drug Administration-approved labeling. ESAs should be discontinued after 6 to 8 weeks in nonresponders. ESAs should be avoided in patients with cancer not receiving concurrent chemotherapy, except for those with lower risk myelodysplastic syndromes. Caution should be exercised when using ESAs with chemotherapeutic agents in diseases associated with increased risk of thromboembolic complications. Table 1 lists detailed recommendations.
NASA Astrophysics Data System (ADS)
Robinson, Alexandra R.
An updated global survey of radioisotope production and distribution was completed and subjected to a revised "down-selection methodology" to determine those radioisotopes that should be classified as potential national security risks based on availability and key physical characteristics that could be exploited in a hypothetical radiological dispersion device. The potential at-risk radioisotopes then were used in a modeling software suite known as Turbo FRMAC, developed by Sandia National Laboratories, to characterize plausible contamination maps known as Protective Action Guideline Zone Maps. This software also was used to calculate the whole body dose equivalent for exposed individuals based on various dispersion parameters and scenarios. Derived Response Levels then were determined for each radioisotope using: 1) target doses to members of the public provided by the U.S. EPA, and 2) occupational dose limits provided by the U.S. Nuclear Regulatory Commission. The limiting Derived Response Level for each radioisotope also was determined.
Air Pathway Dose Modeling for the E-Area Low-Level Waste Facility
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dixon, K. L.; Minter, K. M.
2017-09-06
Dose-release factors (DRFs) were calculated for potential atmospheric releases of several radionuclides from the E-Area Low-Level Waste Facility (ELLWF). The ELLWF receives solid low-level radioactive waste from across the Savannah River Site (SRS) and offsite for disposal. These factors represent the maximum dose a receptor would receive if standing at either 100 m or 11,410 m (Site Boundary) from the edge of an ELLWF disposal unit which are points of assessment (POA) for Department of Energy (DOE) Order 435.1 performance assessments (PA). The DRFs were calculated for 1 Ci of the specified radionuclide being released from the ground surface tomore » the atmosphere (mrem per curie released). The calculation conservatively represented the ELLWF as a point source, and conservatively assumed the receptor was positioned at the center of the contaminant plume and continuously exposed for a period of one year. These DRFs can be refined to take into consideration disposal unit size, proximity and timing of peak dose to establish less conservative radionuclide specific disposal limits. DRFs were calculated for H-3 and C-14 in Revision 0 of this report. H-3 as HTO and C-14 as CO 2 were identified as volatile radionuclides of potential concern in earlier radionuclide screening studies. In Revision 1, DRFs were calculated for eight additional radionuclides identified by an updated screening analysis as potentially important volatile radionuclides. These include Ar-37, Ar-39, Ar-42, Hg-194, Hg- 203, Kr-81, Kr-85, and Xe-127.« less
ICRP Publication 137: Occupational Intakes of Radionuclides: Part 3.
Paquet, F; Bailey, M R; Leggett, R W; Lipsztein, J; Marsh, J; Fell, T P; Smith, T; Nosske, D; Eckerman, K F; Berkovski, V; Blanchardon, E; Gregoratto, D; Harrison, J D
2017-12-01
The 2007 Recommendations of the International Commission on Radiological Protection (ICRP, 2007) introduced changes that affect the calculation of effective dose, and implied a revision of the dose coefficients for internal exposure, published previously in the Publication 30 series (ICRP, 1979, 1980, 1981, 1988) and Publication 68 (ICRP, 1994). In addition, new data are now available that support an update of the radionuclide-specific information given in Publications 54 and 78 (ICRP, 1988a, 1997b) for the design of monitoring programmes and retrospective assessment of occupational internal doses. Provision of new biokinetic models, dose coefficients, monitoring methods, and bioassay data was performed by Committee 2, Task Group 21 on Internal Dosimetry, and Task Group 4 on Dose Calculations. A new series, the Occupational Intakes of Radionuclides (OIR) series, will replace the Publication 30 series and Publications 54, 68, and 78. OIR Part 1 has been issued (ICRP, 2015), and describes the assessment of internal occupational exposure to radionuclides, biokinetic and dosimetric models, methods of individual and workplace monitoring, and general aspects of retrospective dose assessment. OIR Part 2 (ICRP, 2016), this current publication and upcoming publications in the OIR series (Parts 4 and 5) provide data on individual elements and their radioisotopes, including information on chemical forms encountered in the workplace; a list of principal radioisotopes and their physical half-lives and decay modes; the parameter values of the reference biokinetic model; and data on monitoring techniques for the radioisotopes encountered most commonly in workplaces. Reviews of data on inhalation, ingestion, and systemic biokinetics are also provided for most of the elements. Dosimetric data provided in the printed publications of the OIR series include tables of committed effective dose per intake (Sv Bq−1 intake) for inhalation and ingestion, tables of committed effective dose per content (Sv Bq−1 measurement) for inhalation, and graphs of retention and excretion data per Bq intake for inhalation. These data are provided for all absorption types and for the most common isotope(s) of each element. The electronic annex that accompanies the OIR series of publications contains a comprehensive set of committed effective and equivalent dose coefficients, committed effective dose per content functions, and reference bioassay functions. Data are provided for inhalation, ingestion, and direct input to blood. This third publication in the series provides the above data for the following elements: ruthenium (Ru), antimony (Sb), tellurium (Te), iodine (I), caesium (Cs), barium (Ba), iridium (Ir), lead (Pb), bismuth (Bi), polonium (Po), radon (Rn), radium (Ra), thorium (Th), and uranium (U).
ICRP Publication 134: Occupational Intakes of Radionuclides: Part 2.
Paquet, F; Bailey, M R; Leggett, R W; Lipsztein, J; Fell, T P; Smith, T; Nosske, D; Eckerman, K F; Berkovski, V; Ansoborlo, E; Giussani, A; Bolch, W E; Harrison, J D
2016-12-01
The 2007 Recommendations of the International Commission on Radiological Protection (ICRP, 2007) introduced changes that affect the calculation of effective dose, and implied a revision of the dose coefficients for internal exposure, published previously in the Publication 30 series (ICRP, 1979, 1980, 1981, 1988b) and Publication 68 (ICRP, 1994b). In addition, new data are available that support an update of the radionuclide-specific information given in Publications 54 and 78 (ICRP, 1988a, 1997b) for the design of monitoring programmes and retrospective assessment of occupational internal doses. Provision of new biokinetic models, dose coefficients, monitoring methods, and bioassay data was performed by Committee 2, Task Group 21 on Internal Dosimetry, and Task Group 4 on Dose Calculations. A new series, the Occupational Intakes of Radionuclides (OIR) series, will replace the Publication 30 series and Publications 54, 68, and 78. Part 1 of the OIR series has been issued (ICRP, 2015), and describes the assessment of internal occupational exposure to radionuclides, biokinetic and dosimetric models, methods of individual and workplace monitoring, and general aspects of retrospective dose assessment. The following publications in the OIR series (Parts 2–5) will provide data on individual elements and their radioisotopes, including information on chemical forms encountered in the workplace; a list of principal radioisotopes and their physical half-lives and decay modes; the parameter values of the reference biokinetic model; and data on monitoring techniques for the radioisotopes encountered most commonly in workplaces. Reviews of data on inhalation, ingestion, and systemic biokinetics are also provided for most of the elements. Dosimetric data provided in the printed publications of the OIR series include tables of committed effective dose per intake (Sv per Bq intake) for inhalation and ingestion, tables of committed effective dose per content (Sv per Bq measurement) for inhalation, and graphs of retention and excretion data per Bq intake for inhalation. These data are provided for all absorption types and for the most common isotope(s) of each element. The electronic annex that accompanies the OIR series of reports contains a comprehensive set of committed effective and equivalent dose coefficients, committed effective dose per content functions, and reference bioassay functions. Data are provided for inhalation, ingestion, and direct input to blood. The present publication provides the above data for the following elements: hydrogen (H), carbon (C), phosphorus (P), sulphur (S), calcium (Ca), iron (Fe), cobalt (Co), zinc (Zn), strontium (Sr), yttrium (Y), zirconium (Zr), niobium (Nb), molybdenum (Mo), and technetium (Tc).
NASA Astrophysics Data System (ADS)
Xie, Tianwu; Zaidi, Habib
2014-03-01
PET uses specific molecules labelled with positron-emitting radionuclides to provide valuable biochemical and physiological information. However, the administration of radiotracers to patients exposes them to low-dose ionizing radiation, which is a concern in the paediatric population since children are at a higher cancer risk from radiation exposure than adults. Therefore, radiation dosimety calculations for commonly used positron-emitting radiotracers in the paediatric population are highly desired. We evaluate the absorbed dose and effective dose for 19 positron-emitting labelled radiotracers in anthropomorphic paediatric models including the newborn, 1-, 5-, 10- and 15-year-old male and female. This is achieved using pre-calculated S-values of positron-emitting radionuclides of UF-NCI paediatric phantoms and published biokinetic data for various radiotracers. The influence of the type of anthropomorphic model, tissue weight factors and direct human- versus mouse-derived biokinetic data on the effective dose for paediatric phantoms was also evaluated. In the case of 18F-FDG, dosimetry calculations of reference paediatric patients from various dose regimens were also calculated. Among the considered radiotracers, 18F-FBPA and 15O-water resulted in the highest and lowest effective dose in the paediatric phantoms, respectively. The ICRP 103 updated tissue-weighting factors decrease the effective dose in most cases. Substantial differences of radiation dose were observed between direct human- versus mouse-derived biokinetic data. Moreover, the effect of using voxel- versus MIRD-type models on the calculation of the effective dose was also studied. The generated database of absorbed organ dose and effective dose for various positron-emitting labelled radiotracers using new generation computational models and the new ICRP tissue-weighting factors can be used for the assessment of radiation risks to paediatric patients in clinical practice. This work also contributes to a better understanding of the factors influencing patient-specific radiation dose calculation.
Parsai, E Ishmael; Zhang, Zhengdong; Feldmeier, John J
2009-01-01
The commercially available brachytherapy treatment-planning systems today, usually neglects the attenuation effect from stainless steel (SS) tube when Fletcher-Suit-Delclos (FSD) is used in treatment of cervical and endometrial cancers. This could lead to potential inaccuracies in computing dwell times and dose distribution. A more accurate analysis quantifying the level of attenuation for high-dose-rate (HDR) iridium 192 radionuclide ((192)Ir) source is presented through Monte Carlo simulation verified by measurement. In this investigation a general Monte Carlo N-Particles (MCNP) transport code was used to construct a typical geometry of FSD through simulation and compare the doses delivered to point A in Manchester System with and without the SS tubing. A quantitative assessment of inaccuracies in delivered dose vs. the computed dose is presented. In addition, this investigation expanded to examine the attenuation-corrected radial and anisotropy dose functions in a form parallel to the updated AAPM Task Group No. 43 Report (AAPM TG-43) formalism. This will delineate quantitatively the inaccuracies in dose distributions in three-dimensional space. The changes in dose deposition and distribution caused by increased attenuation coefficient resulted from presence of SS are quantified using MCNP Monte Carlo simulations in coupled photon/electron transport. The source geometry was that of the Vari Source wire model VS2000. The FSD was that of the Varian medical system. In this model, the bending angles of tandem and colpostats are 15 degrees and 120 degrees , respectively. We assigned 10 dwell positions to the tandem and 4 dwell positions to right and left colpostats or ovoids to represent a typical treatment case. Typical dose delivered to point A was determined according to Manchester dosimetry system. Based on our computations, the reduction of dose to point A was shown to be at least 3%. So this effect presented by SS-FSD systems on patient dose is of concern.
Adverse effects of levamisole in cocaine users: a review and risk assessment.
Brunt, Tibor Markus; van den Berg, Jorrit; Pennings, Ed; Venhuis, Bastiaan
2017-06-01
The immunomodulatory adjuvant and antihelminth levamisole is increasingly used as an adulterant in cocaine worldwide. An accumulating body of clinical and toxicological literature has appeared since 2010 describing neutropenia, agranulocytosis, leukoencephalopathy and vasculitis in cases associated with levamisole-adulterated cocaine. Mostly, neutropenia and agranulocytosis were reported, characterized by a decimation of neutrophils. A large proportion of cases also involved vasculopathy, characterized by pronounced black and purple skin purpura with cutaneous necrosis. Females are more susceptible for both agranulocytosis and vasculitis. Another complication reported with levamisole-adulterated cocaine is leukoencephalopathy, a disabling and potentially fatal neurological disorder caused by cerebral demyelination. In this review, all adverse effects associated with therapeutic levamisole and levamisole-adulterated cocaine are described. In addition, this review provides an update of the pharmacology of levamisole, its metabolism, including toxic metabolites and metabolites that are relevant for levamisole's addition to cocaine. Special emphasis is put on the immunopathology and the dose-effect relationship of chronic levamisole exposure. Finally, a risk assessment is provided based on the current level of levamisole adulteration in street cocaine, the dose range calculated per gram and the pattern of chronic exposure in heavy or dependent users.
Das, Subinoy; Maeso, Patricia A; Figueroa, Ramon E; Senior, Brent A; Delgaudio, John M; Sillers, Michael J; Schlosser, Rod J; Kountakis, Stilianos E
2008-01-01
This study was performed to assess the feasibility of using intraoperative computed tomography (CT) to provide real-time updates to image guidance systems (IGSs) during surgery. The xCAT ENT portable intraoperative CT scanner (Xoran Technologies, Ann Arbor, MI) was used to acquire scans before, midway, and at the end of six cadaver dissections during the Southern States Rhinology Course, Augusta, GA, in October 2006. These scans were used to recalibrate three different IGSs used during the dissection. Time measurements were recorded and dosimetry was obtained from the cornea, sphenoid sinus (near the optic chiasm), and from the operative field during acquisition of the images. IGS accuracy was determined at the skull base and lamina papyracea. Surgeons were interviewed on benefits of real-time updates to the IGS after completion of dissections. The xCAT ENT scanner was compatible with all three IGS platforms. The average time to update the IGS was 13 minutes. Radiation doses to the cornea were 620 mrad per scan, and optic chiasm was 800 mrad/scan. The accuracy at the anterior skull base improved from 1.58 to 0.62 mm (p=0.026). The accuracy at the posterior skull base improved from 1.46 to 0.71 mm (p=0.014). The accuracy at the lamina was not significantly changed. Intraoperative portable CT scanning with real-time IGS updates is feasible and likely would add little additional time. Accuracy is improved at the skull base. Prospective studies on actual patients are warranted.
IRIS Toxicological Review of 1,4-Dioxane (Interagency ...
On September 9, 2011, the Toxicological Review of 1,4-Dioxane (with inhalation update) (External Review Draft) was posted for external peer review and public comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and White House Offices before public release. In the new IRIS process, introduced by the EPA Administrator, all written comments on IRIS assessments submitted by other federal agencies and White House Offices will be made publicly available. Accordingly, interagency comments with EPA's response and the interagency science consultation draft of the IRIS Toxicological Review of 1,4-dioxane and the charge to external peer reviewers are posted on this site. The Toxicological Review of 1,4-dioxane provides scientific support and rationale for the hazard and dose-response assessment pertaining to chronic exposure to 1,4-dioxane.
Biphasic Dose Response in Low Level Light Therapy – An Update
Huang, Ying-Ying; Sharma, Sulbha K; Carroll, James; Hamblin, Michael R
2011-01-01
Low-level laser (light) therapy (LLLT) has been known since 1967 but still remains controversial due to incomplete understanding of the basic mechanisms and the selection of inappropriate dosimetric parameters that led to negative studies. The biphasic dose-response or Arndt-Schulz curve in LLLT has been shown both in vitro studies and in animal experiments. This review will provide an update to our previous (Huang et al. 2009) coverage of this topic. In vitro mediators of LLLT such as adenosine triphosphate (ATP) and mitochondrial membrane potential show biphasic patterns, while others such as mitochondrial reactive oxygen species show a triphasic dose-response with two distinct peaks. The Janus nature of reactive oxygen species (ROS) that may act as a beneficial signaling molecule at low concentrations and a harmful cytotoxic agent at high concentrations, may partly explain the observed responses in vivo. Transcranial LLLT for traumatic brain injury (TBI) in mice shows a distinct biphasic pattern with peaks in beneficial neurological effects observed when the number of treatments is varied, and when the energy density of an individual treatment is varied. Further understanding of the extent to which biphasic dose responses apply in LLLT will be necessary to optimize clinical treatments. PMID:22461763
Metered dose inhaler use - slideshow
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Scofield, Patricia A.; Smith, Linda Lenell; Johnson, David N.
2017-07-01
The U.S. Environmental Protection Agency promulgated national emission standards for emissions of radionuclides other than radon from US Department of Energy facilities in Chapter 40 of the Code of Federal Regulations (CFR) 61, Subpart H. This regulatory standard limits the annual effective dose that any member of the public can receive from Department of Energy facilities to 0.1 mSv. As defined in the preamble of the final rule, all of the facilities on the Oak Ridge Reservation, i.e., the Y–12 National Security Complex, Oak Ridge National Laboratory, East Tennessee Technology Park, and any other U.S. Department of Energy operations onmore » Oak Ridge Reservation, combined, must meet the annual dose limit of 0.1 mSv. At Oak Ridge National Laboratory, there are monitored sources and numerous unmonitored sources. To maintain radiological source and inventory information for these unmonitored sources, e.g., laboratory hoods, equipment exhausts, and room exhausts not currently venting to monitored stacks on the Oak Ridge National Laboratory campus, the Environmental Protection Rad NESHAPs Inventory Web Database was developed. This database is updated annually and is used to compile emissions data for the annual Radionuclide National Emission Standards for Hazardous Air Pollutants (Rad NESHAPs) report required by 40 CFR 61.94. It also provides supporting documentation for facility compliance audits. In addition, a Rad NESHAPs source and dose database was developed to import the source and dose summary data from Clean Air Act Assessment Package—1988 computer model files. As a result, this database provides Oak Ridge Reservation and facility-specific source inventory; doses associated with each source and facility; and total doses for the Oak Ridge Reservation dose.« less
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.
Scofield, Patricia A; Smith, Linda L; Johnson, David N
2017-07-01
The U.S. Environmental Protection Agency promulgated national emission standards for emissions of radionuclides other than radon from US Department of Energy facilities in Chapter 40 of the Code of Federal Regulations (CFR) 61, Subpart H. This regulatory standard limits the annual effective dose that any member of the public can receive from Department of Energy facilities to 0.1 mSv. As defined in the preamble of the final rule, all of the facilities on the Oak Ridge Reservation, i.e., the Y-12 National Security Complex, Oak Ridge National Laboratory, East Tennessee Technology Park, and any other U.S. Department of Energy operations on Oak Ridge Reservation, combined, must meet the annual dose limit of 0.1 mSv. At Oak Ridge National Laboratory, there are monitored sources and numerous unmonitored sources. To maintain radiological source and inventory information for these unmonitored sources, e.g., laboratory hoods, equipment exhausts, and room exhausts not currently venting to monitored stacks on the Oak Ridge National Laboratory campus, the Environmental Protection Rad NESHAPs Inventory Web Database was developed. This database is updated annually and is used to compile emissions data for the annual Radionuclide National Emission Standards for Hazardous Air Pollutants (Rad NESHAPs) report required by 40 CFR 61.94. It also provides supporting documentation for facility compliance audits. In addition, a Rad NESHAPs source and dose database was developed to import the source and dose summary data from Clean Air Act Assessment Package-1988 computer model files. This database provides Oak Ridge Reservation and facility-specific source inventory; doses associated with each source and facility; and total doses for the Oak Ridge Reservation dose.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Scofield, Patricia A.; Smith, Linda Lenell; Johnson, David N.
The U.S. Environmental Protection Agency promulgated national emission standards for emissions of radionuclides other than radon from US Department of Energy facilities in Chapter 40 of the Code of Federal Regulations (CFR) 61, Subpart H. This regulatory standard limits the annual effective dose that any member of the public can receive from Department of Energy facilities to 0.1 mSv. As defined in the preamble of the final rule, all of the facilities on the Oak Ridge Reservation, i.e., the Y–12 National Security Complex, Oak Ridge National Laboratory, East Tennessee Technology Park, and any other U.S. Department of Energy operations onmore » Oak Ridge Reservation, combined, must meet the annual dose limit of 0.1 mSv. At Oak Ridge National Laboratory, there are monitored sources and numerous unmonitored sources. To maintain radiological source and inventory information for these unmonitored sources, e.g., laboratory hoods, equipment exhausts, and room exhausts not currently venting to monitored stacks on the Oak Ridge National Laboratory campus, the Environmental Protection Rad NESHAPs Inventory Web Database was developed. This database is updated annually and is used to compile emissions data for the annual Radionuclide National Emission Standards for Hazardous Air Pollutants (Rad NESHAPs) report required by 40 CFR 61.94. It also provides supporting documentation for facility compliance audits. In addition, a Rad NESHAPs source and dose database was developed to import the source and dose summary data from Clean Air Act Assessment Package—1988 computer model files. As a result, this database provides Oak Ridge Reservation and facility-specific source inventory; doses associated with each source and facility; and total doses for the Oak Ridge Reservation dose.« less
Yap, Christina; Billingham, Lucinda J; Cheung, Ying Kuen; Craddock, Charlie; O'Quigley, John
2017-12-15
The ever-increasing pace of development of novel therapies mandates efficient methodologies for assessment of their tolerability and activity. Evidence increasingly support the merits of model-based dose-finding designs in identifying the recommended phase II dose compared with conventional rule-based designs such as the 3 + 3 but despite this, their use remains limited. Here, we propose a useful tool, dose transition pathways (DTP), which helps overcome several commonly faced practical and methodologic challenges in the implementation of model-based designs. DTP projects in advance the doses recommended by a model-based design for subsequent patients (stay, escalate, de-escalate, or stop early), using all the accumulated information. After specifying a model with favorable statistical properties, we utilize the DTP to fine-tune the model to tailor it to the trial's specific requirements that reflect important clinical judgments. In particular, it can help to determine how stringent the stopping rules should be if the investigated therapy is too toxic. Its use to design and implement a modified continual reassessment method is illustrated in an acute myeloid leukemia trial. DTP removes the fears of model-based designs as unknown, complex systems and can serve as a handbook, guiding decision-making for each dose update. In the illustrated trial, the seamless, clear transition for each dose recommendation aided the investigators' understanding of the design and facilitated decision-making to enable finer calibration of a tailored model. We advocate the use of the DTP as an integral procedure in the co-development and successful implementation of practical model-based designs by statisticians and investigators. Clin Cancer Res; 23(24); 7440-7. ©2017 AACR . ©2017 American Association for Cancer Research.
Use of artemether-lumefantrine to treat malaria during pregnancy: what do we know and need to know?
Mutabingwa, Theonest K; Adam, Ishag
2013-02-01
Artemether-lumefantrine is a fixed-dose combination containing 20 mg artemether/120 mg lumefantrine per tablet, used for treating uncomplicated malaria in patients weighing ≥5 kg. It is the first artemisinin-based combination registered in some European countries and in the USA. It is marketed in Europe as Riamet(®) (Novartis, Basel, Switzerland) and in malaria-endemic countries as Coartem(®) (Novartis). Safety concerns prevent early pregnancy usage, while limited postmarketing surveillance has delayed safety assessment and policy development. Large clinical studies, postmarketing surveillance and pharmacovigillance ongoing in some countries may soon bridge safety issues. Fatty diet requirements for optimal absorption, pregnancy-induced changes in pharmacokinetics, pregnancy-related anorexia and food taboos, and emerging reduced parasite sensitivity to artemisinin, challenges optimal artemether-lumefantrine dosing and efficacy during pregnancy. This evaluation addresses drug usage, safety concerns following early exposure, implications for changed pharmacokinetics and reduced parasite susceptibility. Clinical-use updates and strategies to address some knowledge gaps including key operational research are discussed.
EURADOS strategic research agenda: vision for dosimetry of ionising radiation.
Rühm, W; Fantuzzi, E; Harrison, R; Schuhmacher, H; Vanhavere, F; Alves, J; Bottollier Depois, J F; Fattibene, P; Knežević, Ž; Lopez, M A; Mayer, S; Miljanić, S; Neumaier, S; Olko, P; Stadtmann, H; Tanner, R; Woda, C
2016-02-01
Since autumn 2012, the European Radiation Dosimetry Group (EURADOS) has been developing its Strategic Research Agenda (SRA), which is intended to contribute to the identification of future research needs in radiation dosimetry in Europe. The present article summarises-based on input from EURADOS Working Groups (WGs) and Voting Members-five visions in dosimetry and defines key issues in dosimetry research that are considered important for the next decades. The five visions include scientific developments required towards (a) updated fundamental dose concepts and quantities, (b) improved radiation risk estimates deduced from epidemiological cohorts, (c) efficient dose assessment for radiological emergencies, (d) integrated personalised dosimetry in medical applications and (e) improved radiation protection of workers and the public. The SRA of EURADOS will be used as a guideline for future activities of the EURADOS WGs. A detailed version of the SRA can be downloaded as a EURADOS report from the EURADOS website (www.eurados.org). © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Bayesian analysis of physiologically based toxicokinetic and toxicodynamic models.
Hack, C Eric
2006-04-17
Physiologically based toxicokinetic (PBTK) and toxicodynamic (TD) models of bromate in animals and humans would improve our ability to accurately estimate the toxic doses in humans based on available animal studies. These mathematical models are often highly parameterized and must be calibrated in order for the model predictions of internal dose to adequately fit the experimentally measured doses. Highly parameterized models are difficult to calibrate and it is difficult to obtain accurate estimates of uncertainty or variability in model parameters with commonly used frequentist calibration methods, such as maximum likelihood estimation (MLE) or least squared error approaches. The Bayesian approach called Markov chain Monte Carlo (MCMC) analysis can be used to successfully calibrate these complex models. Prior knowledge about the biological system and associated model parameters is easily incorporated in this approach in the form of prior parameter distributions, and the distributions are refined or updated using experimental data to generate posterior distributions of parameter estimates. The goal of this paper is to give the non-mathematician a brief description of the Bayesian approach and Markov chain Monte Carlo analysis, how this technique is used in risk assessment, and the issues associated with this approach.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Desai, Neil B.; Stein, Nicholas F.; LaQuaglia, Michael P.
2013-01-01
Purpose: Desmoplastic small round cell tumor (DSRCT) is a rare malignancy typically involving the peritoneum in young men. Whole abdominopelvic radiation therapy (WAP-RT) using conventional 2-dimensional (2D) radiation therapy (RT) is used to address local recurrence but has been limited by toxicity. Our objectives were to assess the benefit of intensity modulated radiation therapy (IMRT) on toxicity and to update the largest series on radiation for DSRCT. Methods and Materials: The records of 31 patients with DSRCT treated with WAP-RT (22 with 2D-RT and 9 with IMRT) between 1992 and 2011 were retrospectively reviewed. All received multi-agent chemotherapy and maximalmore » surgical debulking followed by 30 Gy of WAP-RT. A further focal boost of 12 to 24 Gy was used in 12 cases. Boost RT and autologous stem cell transplantation were nearly exclusive to patients treated with 2D-RT. Toxicities were assessed with the Common Terminology Criteria for Adverse Events. Dosimetric analysis compared IMRT and simulated 2D-RT dose distributions. Results: Of 31 patients, 30 completed WAP-RT, with a median follow-up after RT of 19 months. Acute toxicity was reduced with IMRT versus 2D-RT: P=.04 for gastrointestinal toxicity of grade 2 or higher (33% vs 77%); P=.02 for grade 4 hematologic toxicity (33% vs 86%); P=.01 for rates of granulocyte colony-stimulating factor; and P=.04 for rates of platelet transfusion. Post treatment red blood cell and platelet transfusion rates were also reduced (P=.01). IMRT improved target homogeneity ([D05-D95]/D05 of 21% vs 46%) and resulted in a 21% mean bone dose reduction. Small bowel obstruction was the most common late toxicity (23% overall). Updated 3-year overall survival and progression-free survival rates were 50% and 24%, respectively. Overall survival was associated with distant metastasis at diagnosis on multivariate analysis. Most failures remained intraperitoneal (88%). Conclusions: IMRT for consolidative WAP-RT in DSRCT improves hematologic toxicity in particular. Although the long-term efficacy of current treatment options remains disappointing, the improved therapeutic index of IMRT may aid in generalizing its use and allowing the addition of novel approaches such as intraperitoneal immunotherapy.« less
Working Memory Updating as a Predictor of Academic Attainment
ERIC Educational Resources Information Center
Lechuga, M. Teresa; Pelegrina, Santiago; Pelaez, Jose L.; Martin-Puga, M. Eva; Justicia, M. Jose
2016-01-01
There is growing evidence supporting the importance of executive functions, and specifically working memory updating (WMU), for children's academic achievement. This study aimed to assess the specific contribution of updating to the prediction of academic performance. Two updating tasks, which included different updating components, were…
Toxicology of dimethyl and monomethyl derivatives of acetamide and formamide: a second update.
Kennedy, Gerald L
2012-11-01
Dimethylacetamide (DMAC) and dimethylformamide (DMF) continue to be important, widely used solvents involved in a wide variety of industrial applications. As liquids with relatively low vapor pressures, contact with both the integumentary and respiratory systems is the main source of human exposure. Although airborne control levels for the workplace have been established and industrial hygiene practices to limit dermal contact have been put in place, use of these chemicals has been associated with occupational illness, mainly in Asia where new and expanded uses have led to overexposures. Thus an update of the basic toxicology data including tables indicating the dose/exposure response characteristics of both DMAC and DMF is currently important. Both chemicals are similar from a toxicology perspective. Human experience has generally shown the materials to be without adverse effect except under conditions where airborne and dermal controls were not properly applied. The use of urinary metabolite monitoring has successfully been employed to measure integrated dermal and inhalation worker exposure. The chemicals are not particularly toxic following acute exposure but high doses can produce damage to the liver, the organ which is first affected by these two chemicals. Repeated dose/exposure studies have characterized both the targets of toxicity and the doses required to produce changes by various routes of exposure. Higher doses of these materials can produce changes in developing systems, infrequently in experiments at doses in which the maternal animal is unaffected, thus care needs to be taken when exposures are to women of child-bearing age. The chemicals appear to be low in genetic activity and inhalation exposures have not shown the materials to produce tumors in rodents except with DMF in a situation in which aerosol formation was encountered. This presentation extends the two previous reviews and, like those, includes updated information on acetamide and formamide and their monomethyl derivatives as well as the commercially important DMAC and DMF. Since a large portion of the newer information deals with effects in humans and biomonitoring, these sections are presented at the start of this review.
Pharmaceutical Approval Update.
Kaufman, Michele B
2017-12-01
Secnidazole (Solosec) for the one-dose treatment of bacterial vaginosis; triamcinolone acetonide extended-release injection (Zilretta) for osteoarthritis knee pain; and insulin aspart injection (Fiasp), a rapidacting human insulin analogue for glycemic control in diabetes mellitus.
Federal Register 2010, 2011, 2012, 2013, 2014
2010-05-21
... lobster. AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and Atmospheric Administration... and Workshop for South Atlantic and Gulf of Mexico spiny lobster. SUMMARY: This notice updates... lobster. This update will consist of a series of webinars and an Update Workshop. This assessment will...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Thomas, D; O’Connell, D; Lamb, J
Purpose: To demonstrate real-time dose calculation of free-breathing MRI guided Co−60 treatments, using a motion model and Monte-Carlo dose calculation to accurately account for the interplay between irregular breathing motion and an IMRT delivery. Methods: ViewRay Co-60 dose distributions were optimized on ITVs contoured from free-breathing CT images of lung cancer patients. Each treatment plan was separated into 0.25s segments, accounting for the MLC positions and beam angles at each time point. A voxel-specific motion model derived from multiple fast-helical free-breathing CTs and deformable registration was calculated for each patient. 3D images for every 0.25s of a simulated treatment weremore » generated in real time, here using a bellows signal as a surrogate to accurately account for breathing irregularities. Monte-Carlo dose calculation was performed every 0.25s of the treatment, with the number of histories in each calculation scaled to give an overall 1% statistical uncertainty. Each dose calculation was deformed back to the reference image using the motion model and accumulated. The static and real-time dose calculations were compared. Results: Image generation was performed in real time at 4 frames per second (GPU). Monte-Carlo dose calculation was performed at approximately 1frame per second (CPU), giving a total calculation time of approximately 30 minutes per treatment. Results show both cold- and hot-spots in and around the ITV, and increased dose to contralateral lung as the tumor moves in and out of the beam during treatment. Conclusion: An accurate motion model combined with a fast Monte-Carlo dose calculation allows almost real-time dose calculation of a free-breathing treatment. When combined with sagittal 2D-cine-mode MRI during treatment to update the motion model in real time, this will allow the true delivered dose of a treatment to be calculated, providing a useful tool for adaptive planning and assessing the effectiveness of gated treatments.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Herschtal, Alan, E-mail: Alan.Herschtal@petermac.org; Faculty of Health, Arts and Design, Swinburne University of Technology, Melbourne; Te Marvelde, Luc
Objective: To develop a mathematical tool that can update a patient's planning target volume (PTV) partway through a course of radiation therapy to more precisely target the tumor for the remainder of treatment and reduce dose to surrounding healthy tissue. Methods and Materials: Daily on-board imaging was used to collect large datasets of displacements for patients undergoing external beam radiation therapy for solid tumors. Bayesian statistical modeling of these geometric uncertainties was used to optimally trade off between displacement data collected from previously treated patients and the progressively accumulating data from a patient currently partway through treatment, to optimally predictmore » future displacements for that patient. These predictions were used to update the PTV position and margin width for the remainder of treatment, such that the clinical target volume (CTV) was more precisely targeted. Results: Software simulation of dose to CTV and normal tissue for 2 real prostate displacement datasets consisting of 146 and 290 patients treated with a minimum of 30 fractions each showed that re-evaluating the PTV position and margin width after 8 treatment fractions reduced healthy tissue dose by 19% and 17%, respectively, while maintaining CTV dose. Conclusion: Incorporating patient-specific displacement patterns from early in a course of treatment allows PTV adaptation for the remainder of treatment. This substantially reduces the dose to healthy tissues and thus can reduce radiation therapy–induced toxicities, improving patient outcomes.« less
Drugs for preventing red blood cell dehydration in people with sickle cell disease.
Nagalla, Srikanth; Ballas, Samir K
2016-03-04
Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs. This is an updated version of a previously published review. To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.Last search of the Group's Trials Register: 28 November 2015. Randomized or quasi-randomized controlled trials of drugs to rehydrate sickled red blood cells compared to placebo or an alternative treatment. Both authors independently selected studies for inclusion, assessed study quality and extracted data. Of the 51 studies identified, three met the inclusion criteria. The first study tested the effectiveness of zinc sulphate to prevent sickle cell-related crises in a total of 145 participants and showed a significant reduction in painful crises over one and a half years, mean difference -2.83 (95% confidence interval -3.51 to -2.15). However, analysis was restricted due to limited statistical data. Changes to red cell parameters and blood counts were inconsistent. No serious adverse events were noted in the study.The second study was a Phase II dose-finding study of senicapoc (a Gardos channel blocker) compared to placebo. Compared to the placebo group the high dose senicapoc showed significant improvement in change in hemoglobin level, number and proportion of dense red blood cells, red blood cell count and indices and hematocrit. The results with low-dose senicapoc were similar to the high-dose senicapoc group but of lesser magnitude. There was no difference in the frequency of painful crises between the three groups. A subsequent Phase III study of senicapoc was terminated early since there was no difference observed between the treatment and control groups in the primary end point of painful crises. While the results of zinc for reducing sickle-related crises are encouraging, larger and longer-term multicenter studies are needed to evaluate the effectiveness of this therapy for people with sickle cell disease.While the Phase II and the prematurely terminated phase III studies of senicapoc showed that the drug improved red cell survival (depending on dose), this did not lead to fewer painful crises.We will continue to run searches to identify any potentially relevant trials; however, we do not plan to update other sections of the review until new trials are published.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Manning, Karessa L.; Dolislager, Fredrick G.; Bellamy, Michael B.
The Preliminary Remediation Goal (PRG) and Dose Compliance Concentration (DCC) calculators are screening level tools that set forth Environmental Protection Agency's (EPA) recommended approaches, based upon currently available information with respect to risk assessment, for response actions at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) sites, commonly known as Superfund. The screening levels derived by the PRG and DCC calculators are used to identify isotopes contributing the highest risk and dose as well as establish preliminary remediation goals. Each calculator has a residential gardening scenario and subsistence farmer exposure scenarios that require modeling of the transfer of contaminants frommore » soil and water into various types of biota (crops and animal products). New publications of human intake rates of biota; farm animal intakes of water, soil, and fodder; and soil to plant interactions require updates be implemented into the PRG and DCC exposure scenarios. Recent improvements have been made in the biota modeling for these calculators, including newly derived biota intake rates, more comprehensive soil mass loading factors (MLFs), and more comprehensive soil to tissue transfer factors (TFs) for animals and soil to plant transfer factors (BV's). New biota have been added in both the produce and animal products categories that greatly improve the accuracy and utility of the PRG and DCC calculators and encompass greater geographic diversity on a national and international scale.« less
ERIC Educational Resources Information Center
Banta, Trudy W., Ed.
2014-01-01
This issue of "Assessment Update" presents the following articles: (1) Expanding Assessment Perspectives: The Importance of Student Leadership in Student Learning Outcomes Assessment (Abraham J. Lauer and Jamie R. Korin); (2) Empowering Faculty and Students with Assessment Data (Jane M. Souza); (3) Including Faculty in Accreditation…
Shulman, Stanford T; Bisno, Alan L; Clegg, Herbert W; Gerber, Michael A; Kaplan, Edward L; Lee, Grace; Martin, Judith M; Van Beneden, Chris
2012-11-15
The guideline is intended for use by healthcare providers who care for adult and pediatric patients with group A streptococcal pharyngitis. The guideline updates the 2002 Infectious Diseases Society of America guideline and discusses diagnosis and management, and recommendations are provided regarding antibiotic choices and dosing. Penicillin or amoxicillin remain the treatments of choice, and recommendations are made for the penicillin-allergic patient, which now include clindamycin.
Osadebe, Lynda U; MacNeil, Adam; Elmousaad, Hashim; Davis, Lora; Idris, Jibrin M; Haladu, Suleiman A; Adeoye, Olorunsogo B; Nguku, Patrick; Aliu-Mamudu, Uneratu; Hassan, Elizabeth; Vertefeuille, John; Bloland, Peter
2017-07-01
Kano State, Nigeria, introduced inactivated polio vaccine (IPV) into its routine immunization (RI) schedule in March 2015 and was the pilot site for an RI data module for the National Health Management Information System (NHMIS). We determined factors impacting IPV introduction and the value of the RI module on monitoring new vaccine introduction. Two assessment approaches were used: (1) analysis of IPV vaccinations reported in NHMIS, and (2) survey of 20 local government areas (LGAs) and 60 associated health facilities (HF). By April 2015, 66% of LGAs had at least 20% of HFs administering IPV, by June all LGAs had HFs administering IPV and by July, 91% of the HFs in Kano reported administering IPV. Among surveyed staff, most rated training and implementation as successful. Among HFs, 97% had updated RI reporting tools, although only 50% had updated microplans. Challenges among HFs included: IPV shortages (20%), hesitancy to administer 2 injectable vaccines (28%), lack of knowledge on multi-dose vial policy (30%) and age of IPV administration (8%). The introduction of IPV was largely successful in Kano and the RI module was effective in monitoring progress, although certain gaps were noted, which should be used to inform plans for future vaccine introductions. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
Bradley, Ann E; Shoenfelt, Joanna L; Durda, Judi L
2016-04-01
Alpha-hexachlorocyclohexane (alpha-HCH) is one of eight structural isomers that have been used worldwide as insecticides. Although no longer produced or used agriculturally in the United States, exposure to HCH isomers is of continuing concern due to legacy usage and persistence in the environment. The U.S. Environmental Protection Agency (EPA) classifies alpha-HCH as a probable human carcinogen and provides a slope factor of 6.3 (mg/kg-day)(-1) for the compound, based on hepatic nodules and hepatocellular carcinomas observed in male mice and derived using a default linear approach for modeling carcinogens. EPA's evaluation, last updated in 1993, does not consider more recently available guidance that allows for the incorporation of mode of action (MOA) for determining a compound's dose-response. Contrary to the linear approach assumed by EPA, the available data indicate that alpha-HCH exhibits carcinogenicity via an MOA that yields a nonlinear, threshold dose-response. In our analysis, we conducted an MOA evaluation and dose-response analysis for alpha-HCH-induced liver carcinogenesis. We concluded that alpha-HCH causes liver tumors in rats and mice through an MOA involving increased promotion of cell growth, or mitogenesis. Based on these findings, we developed a threshold, cancer-based, reference dose (RfD) for alpha-HCH. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Losigamone add-on therapy for focal epilepsy.
Xiao, Yousheng; Luo, Man; Wang, Jin; Luo, Hongye
2018-01-22
Epilepsy is a common neurologic disorder, affecting approximately 50 million people worldwide; nearly a third of these people have epilepsy that is not well controlled by a single antiepileptic drug (AED) and they usually require treatment with a combination of two or more AEDs. In recent years, many newer AEDs have been investigated as add-on therapy for focal epilepsy; losigamone is one of these drugs and is the focus of this systematic review. This is an update of a Cochrane review first published in 2012 (Cochrane Database of Systematic Reviews 2012, Issue 6) and updated in 2015. To investigate the efficacy and safety of losigamone when used as an add-on therapy for focal epilepsy. For the latest update on 9 February 2017, we searched the Cochrane Epilepsy Specialized Register, CENTRAL and MEDLINE . We searched trials registers and contacted the manufacturer of losigamone and authors of included studies for additional information. We did not impose any language restrictions. Randomized controlled, add-on trials comparing losigamone with placebo for focal epilepsy. Two review authors independently assessed trial quality and extracted data. The primary outcomes were 50% or greater reduction in seizure frequency and seizure freedom; the secondary outcomes were treatment withdrawal and adverse events. Results are presented as risk ratios (RRs) with 95% confidence intervals (CIs) or 99% CIs (for the individual listed adverse events to make an allowance for multiple testing). Two trials involving a total of 467 participants, aged over 18 years, were eligible for inclusion. Both trials assessed losigamone 1200 mg/day or 1500 mg/day as an add-on therapy for focal epilepsy. We assessed one trial as being of good methodological quality while the other was of uncertain quality. For the efficacy outcomes, results did show that participants taking losigamone were significantly more likely to achieve a 50% or greater reduction in seizure frequency (RR 1.76, 95% CI 1.14 to 2.72), but associated with a significant increase of treatment withdrawal when compared with those taking placebo (RR 2.16, 95% CI 1.28 to 3.67). For the safety outcomes, results indicated that the proportion of participants who experienced adverse events in the losigamone group was higher than in the placebo group (RR 1.34, 95% CI 1.00 to 1.80), dizziness was the only adverse event significantly reported in relation to losigamone (RR 3.82, 99% CI 1.69 to 8.64). The proportion of participants achieving seizure freedom was not reported in either trial report. A subgroup analysis according to different doses of losigamone showed that a higher dose of losigamone (1500 mg/day) was associated with a greater reduction in seizure frequency than lower doses, but was also associated with more dropouts due to adverse events. The results of this review showed that losigamone did reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with focal epilepsy. However, the included trials were of short-term duration and uncertain quality. Future well-designed randomized, double-blind, placebo-controlled trials with a longer-term duration are needed. No new studies have been found since the last version of this review. We judged the overall quality of the evidence for the outcomes assessed as moderate.
Amin, Jaimin; Huang, Brian; Yoon, Jessica; Shih, David Q
2015-02-01
The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine (AZA), remain as a mainstay therapy in inflammatory bowel disease (IBD). Differences in metabolism of these drugs lead to individual variation in thiopurine metabolite levels that can determine its therapeutic efficacy and development of adverse reactions. In this update, we will review thiopurine metabolic pathway along with the up-to-date approaches in administering thiopurine medications based on the current literature. A search of the PubMed database by 2 independent reviewers identifying 98 articles evaluating thiopurine metabolism and IBD management. Monitoring thiopurine metabolites can assist physicians in optimizing 6-MP and AZA therapy in treating patients with IBD. Of the dosing strategies reviewed, we found evidence for monitoring thiopurine metabolite level, use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of AZA or 6-MP to optimize thiopurine therapy and minimize adverse effects in IBD. Based on the currently available literature, various dosing strategies to improve therapeutic response and reduce adverse reactions can be considered, including use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of thiopurine.
Update and review of accuracy assessment techniques for remotely sensed data
NASA Technical Reports Server (NTRS)
Congalton, R. G.; Heinen, J. T.; Oderwald, R. G.
1983-01-01
Research performed in the accuracy assessment of remotely sensed data is updated and reviewed. The use of discrete multivariate analysis techniques for the assessment of error matrices, the use of computer simulation for assessing various sampling strategies, and an investigation of spatial autocorrelation techniques are examined.
Tracing Assessment Practice as Reflected in "Assessment Update." NILOA Occasional Paper #28
ERIC Educational Resources Information Center
Banta, Trudy W.; Ewell, Peter T.; Cogswell, Cynthia A.
2016-01-01
At some future point, when a definitive history of the assessment movement is written, one of the most frequently cited, influential publications will be "Assessment Update" ("AU"). Since 1989, this bimonthly newsletter has been published by Jossey-Bass in partnership with Indiana University-Purdue University Indianapolis…
IRIS Toxicological Review of Formaldehyde (Inhalation) ...
UPDATE EPA is currently revising its Integrated Risk Information System (IRIS) assessment of formaldehyde to address the 2011 NAS peer review recommendations. This assessment addresses both noncancer and cancer human health effects that are relevant to assessing the risks from chronic inhalation exposure to formaldehyde. To facilitate discussion of several scientific issues pertinent to the assessment, EPA convened a state-of-the-science workshop on April 30 and May 1, 2014. This workshop focused on the following three themes: Evidence pertaining to the influence of formaldehyde that is produced endogenously (by the body during normal biological processes) on the toxicity of inhaled formaldehyde, and implications for the health assessment; Mechanistic evidence relevant to formaldehyde inhalation exposure and lymphohematopoietic cancers (leukemia and lymphomas); and Epidemiological research examining the potential association between formaldehyde exposure and lymphohematopoietic cancers (leukemia and lymphomas). June 2010: EPA is conducting an independent expert peer review by the National Academy of Sciences and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Formaldehyde-Inhalation that when finalized will appear on the Integrated Risk Information System (IRIS) database. This draft IRIS health assessment addresses both noncancer and cancer human health effects that may result from chronic inhal
Yamanaka, Takashi; Nemoto, Manabu; Bannai, Hiroshi; Tsujimura, Koji; Matsumura, Tomio; Kokado, Hiroshi; Gildea, Sarah; Cullinane, Ann
2018-03-02
Equine influenza (EI) vaccine has been widely used. However, the causative EI virus (H3N8) undergoes continuous antigenic drift, and the vaccine strains must be periodically reviewed and if necessary, updated to maintain vaccine efficacy against circulating viruses. In 2016, the Japanese vaccine was updated by replacing the old viruses with the Florida sub-lineage Clade (Fc) 2 virus, A/equine/Yokohama/aq13/2010 (Y10). We investigated the virus neutralization (VN) antibody response to Fc2 viruses currently circulating in Europe, after booster or primary immunization with the new vaccine. These European viruses have the amino acid substitution A144V or I179V of the hemagglutinin. In horses that had previously received a primary course and bi-annual boosters with the old vaccine booster, immunization with the updated vaccine increased the VN antibody levels against the European Fc2 viruses as well as Y10. There were no significant differences in the VN titers against Y10 and the Fc2 viruses with A144V or I179V substitution in horses that had received a primary course of the updated vaccine. However, a mixed primary course where the first dose was the old vaccine and the second dose was the updated vaccine, reduced VN titers against the European viruses compared to that against Y10. In summary, the new vaccine affords horses protective level of VN titers against the Fc2 viruses carrying A144V or I179V substitution, but our results suggest that the combination of the old and new vaccines for primary immunization would not be optimum.
YAMANAKA, Takashi; NEMOTO, Manabu; BANNAI, Hiroshi; TSUJIMURA, Koji; MATSUMURA, Tomio; KOKADO, Hiroshi; GILDEA, Sarah; CULLINANE, Ann
2017-01-01
Equine influenza (EI) vaccine has been widely used. However, the causative EI virus (H3N8) undergoes continuous antigenic drift, and the vaccine strains must be periodically reviewed and if necessary, updated to maintain vaccine efficacy against circulating viruses. In 2016, the Japanese vaccine was updated by replacing the old viruses with the Florida sub-lineage Clade (Fc) 2 virus, A/equine/Yokohama/aq13/2010 (Y10). We investigated the virus neutralization (VN) antibody response to Fc2 viruses currently circulating in Europe, after booster or primary immunization with the new vaccine. These European viruses have the amino acid substitution A144V or I179V of the hemagglutinin. In horses that had previously received a primary course and bi-annual boosters with the old vaccine booster, immunization with the updated vaccine increased the VN antibody levels against the European Fc2 viruses as well as Y10. There were no significant differences in the VN titers against Y10 and the Fc2 viruses with A144V or I179V substitution in horses that had received a primary course of the updated vaccine. However, a mixed primary course where the first dose was the old vaccine and the second dose was the updated vaccine, reduced VN titers against the European viruses compared to that against Y10. In summary, the new vaccine affords horses protective level of VN titers against the Fc2 viruses carrying A144V or I179V substitution, but our results suggest that the combination of the old and new vaccines for primary immunization would not be optimum. PMID:29237998
Candy, Bridget; Jones, Louise; Vickerstaff, Victoria; Larkin, Philip J; Stone, Patrick
2018-06-05
Opioid-induced bowel dysfunction (OIBD) is characterised by constipation, incomplete evacuation, bloating, and gastric reflux. It is one of the major adverse events of treatment for pain in cancer and in palliative care, resulting in increased morbidity and reduced quality of life.This is an update of two Cochrane reviews. One was published in 2011, Issue 1 on laxatives and methylnaltrexone for the management of constipation in people receiving palliative care; this was updated in 2015 and excluded methylnaltrexone. The other was published in 2008, Issue 4 on mu-opioid antagonists (MOA) for OIBD. In this updated review, we only included trials on MOA (including methylnaltrexone) for OIBD in people with cancer and people receiving palliative care. To assess the effectiveness and safety of MOA for OIBD in people with cancer and people receiving palliative care. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, and Web of Science to August 2017. We also searched clinical trial registries and regulatory websites. We contacted manufacturers of MOA to identify further data. We included randomised controlled trials (RCTs) that assessed the effectiveness and safety of MOA for OIBD in people with cancer and people at a palliative stage irrespective of the type of terminal disease they experienced. Two review authors assessed risk of bias and extracted data. The appropriateness of combining data from the trials depended upon sufficient homogeneity across the trials. Our primary outcomes were laxation, impact on pain relief, and adverse events. Impact on pain relief was a primary outcome because a possible adverse effect of MOAs is a reduction in pain relief from opioids. We assessed the evidence on these outcomes using GRADE. We identified four new trials for this update, bringing the total number included in this review to eight. In total, 1022 men and women with cancer irrespective of stage or at a palliative care stage of any disease were randomised across the trials. The MOAs evaluated were oral naldemedine and naloxone (alone or in combination with oxycodone), and subcutaneous methylnaltrexone. The trials compared with MOA with a placebo or with the active intervention administered at different doses or in combination with other drugs. The trial of naldemedine and the two of naloxone in combination with oxycodone were in people with cancer irrespective of disease stage. The trial on naloxone alone was in people with advanced cancer. The four trials on methylnaltrexone were undertaken in palliative care where most participants had cancer. All trials were vulnerable to biases; four were at a high risk as they involved a sample of fewer than 50 participants per arm.In the trial of naldemedine compared to placebo in 225 participants, there were more spontaneous laxations over the two-week treatment for the intervention group (risk ratio (RR) 1.93, 95% confidence intervals (CI) 1.36 to 2.74; moderate-quality evidence). In comparison with higher doses, lower doses resulted in fewer spontaneous laxations (0.1 mg versus 0.2 mg: RR 0.73, 95% CI 0.55 to 0.95; 0.1 mg versus 0.4 mg: RR 0.69, 95% CI 0.53 to 0.89; moderate-quality evidence). There was moderate-quality evidence that naldemedine had no effect on opiate withdrawal. There were five serious adverse events. All were in people taking naldemedine (low-quality evidence). There was an increase in the occurrence of other (non-serious) adverse events in the naldemedine groups (RR 1.36, 95% CI 1.04 to 1.79, moderate-quality evidence). The most common adverse event was diarrhoea.The trials on naloxone taken either on its own, or in combination with oxycodone (an opioid) compared to oxycodone only did not evaluate laxation response over the first two weeks of administration. There was very low-quality evidence that naloxone alone, and moderate-quality evidence that oxycodone/naloxone, had no effect on analgesia. There was low-quality evidence that oxycodone/naloxone did not increase the risk of serious adverse events and moderate-quality evidence that it did not increase risk of adverse events.In combined analysis of two trials of 287 participants, we found methylnaltrexone compared to placebo induced more laxations within 24 hours (RR 2.77, 95% CI 1.91 to 4.04. I² = 0%; moderate-quality evidence). In combined analysis, we found methylnaltrexone induced more laxation responses over two weeks (RR 9.98, 95% CI 4.96 to 20.09. I² = 0%; moderate-quality evidence). The proportion of participants who had a rescue-free laxation response within 24 hours of the first dose was 59.1% in the methylnaltrexone arms and 19.1% in the placebo arm. There was moderate-quality evidence that the rate of opioid withdrawal was not affected. Methylnaltrexone did not increase the likelihood of a serious adverse event; there were fewer in the intervention arm (RR 0.59, 95% CI 0.38 to 0.93; I² = 0%; moderate-quality evidence). There was no difference in the proportion of participants experiencing an adverse event (RR 1.17, 95% CI 0.94 to 1.45; I² = 74%; low-quality evidence). Methylnaltrexone increased the likelihood of abdominal pain and flatulence.Two trials compared differing methylnaltrexone schedules of higher doses with lower doses. For early laxation, there was low-quality evidence of no clear difference between doses on analgesia and adverse events. Both trials measured laxation response within 24 hours of first dose (trial one: RR 0.82, 95% CI 0.41 to 1.66; trial two: RR 1.07, 95% CI 0.81 to 1.42). In this update, the conclusions for naldemedine are new. There is moderate-quality evidence to suggest that, taken orally, naldemedine improves bowel function over two weeks in people with cancer and OIBD but increases the risk of adverse events. The conclusions on naloxone and methylnaltrexone have not changed. The trials on naloxone did not assess laxation at 24 hours or over two weeks. There is moderate-quality evidence that methylnaltrexone improves bowel function in people receiving palliative care in the short term and over two weeks, and low-quality evidence that it does not increase adverse events. There is a need for more trials including more evaluation of adverse events. None of the current trials evaluated effects in children.
ERIC Educational Resources Information Center
Hundley, Stephen P., Ed.
2018-01-01
This issue of "Assessment Update" presents the following articles: (1) James Madison University: Reflections on Sustained Excellence in Assessment (Keston H. Fulcher and Elizabeth R. H. Sanchez); (2) Editor's Notes: Assessment Excellence Abounds! (Stephen P. Hundley); (3) The Promise of an All-in-One Assessment System for Student…
ERIC Educational Resources Information Center
Banta, Trudy W., Ed.
2013-01-01
This issue of "Assessment Update" presents the following articles: (1) Launching E-Portfolios: An Organic Process; (2) Editor's Notes: Envisioning Learning; (3) Promoting Student Affairs Buy-In for Assessment: Lessons Learned; (4) Working at Assessment; (5) Making the Case for Formative Assessment: How It Improves Student Engagement and…
ERIC Educational Resources Information Center
Hundley, Stephen P., Ed.
2017-01-01
This issue of "Assessment Update" presents the following articles: (1) Lessons Learned: Graduate Student Assessment (Michael Cherry and Lesley Page); (2) Assessing the Assessor: A Response to Fulcher and Bashkov's "Do We Practice What We Preach? The Accountability of an Assessment Office" (Christine Robinson, John G. M.…
IRIS Toxicological Review of Benzo[a]pyrene (Final Report) ...
EPA has finalized the Integrated Risk Information System (IRIS) assessment of benzo[a]pyrene. This assessment addresses the potential cancer and noncancer human health effects from long-term exposure to benzo[a]pyrene. Now final, this assessment will update the toxicological information on benzo[a]pyrene posted in 1987. EPA’s program and regional offices may use this assessment to inform decisions to protect human health. EPA is undertaking an update of the Integrated Risk Information System (IRIS) health assessment for benzo[a]pyrene (BaP). The outcome of this project is an updated Toxicological Review and IRIS Summary for BaP that will be entered into the IRIS database.
Does updating improve the methodological and reporting quality of systematic reviews?
Shea, Beverley; Boers, Maarten; Grimshaw, Jeremy M; Hamel, Candyce; Bouter, Lex M
2006-06-13
Systematic reviews (SRs) must be of high quality. The purpose of our research was to compare the methodological and reporting quality of original versus updated Cochrane SRs to determine whether updating had improved these two quality dimensions. We identified updated Cochrane SRs published in issue 4, 2002 of the Cochrane Library. We assessed the updated and original versions of the SRs using two instruments: the 10 item enhanced Overview Quality Assessment Questionnaire (OQAQ), and an 18-item reporting quality checklist and flow chart based upon the Quality of Reporting of Meta-analyses (QUOROM) statement. At least two reviewers extracted data and assessed quality. We calculated the percentage (with a 95% confidence interval) of 'yes' answers to each question. We calculated mean differences in percentage, 95% confidence intervals and p-values for each of the individual items and the overall methodological quality score of the updated and pre-updated versions using OQAQ. We assessed 53 SRs. There was no significant improvement in the global quality score of the OQAQ (mean difference 0.11 (-0.28; 0.70 p = 0.52)). Updated reviews showed a significant improvement of 18.9 (7.2; 30.6 p < .01) on the OQAQ item assessing whether the conclusions drawn by the author(s) were supported by the data and/or analysis presented in the SR. The QUOROM statement showed that the quality of reporting of Cochrane reviews improved in some areas with updating. Improvements were seen on the items relating to data sources reported in the abstract, with a significant difference of 17.0 (9.8; 28.7 p = 0.01), review methods, reported in the abstract 35 (24.1; 49.1 p = 0.00), searching methods 18.9 (9.7; 31.6 p = 0.01), and data abstraction 18.9 (11.7; 30.9 p = 0.00). The overall quality of Cochrane SRs is fair-to-good. Although reporting quality improved on certain individual items there was no overall improvement seen with updating and methodological quality remained unchanged. Further improvement of quality of reporting is possible. There is room for improvement of methodological quality as well. Authors updating reviews should address identified methodological or reporting weaknesses. We recommend to give full attention to both quality domains when updating SRs.
ERIC Educational Resources Information Center
Banta, Trudy W., Ed.
2012-01-01
This issue of "Assessment Update" presents the following articles: (1) Expectations for Assessment Reports: A Descriptive Analysis (Keston H. Fulcher, Matthew Swain, and Chris D. Orem); (2) Editor's Notes: A Surprising Reaction (Trudy W. Banta); (3) Getting SMART with Assessment: ACTION Steps to Institutional Effectiveness (Eric Daffron…
Federal Register 2010, 2011, 2012, 2013, 2014
2010-08-05
... product of the Data Workshop is a data report which compiles and evaluates potential datasets and recommends which datasets are appropriate for assessment analyses. The product of the Stock Assessment... conducted through the SEDAR program. Update assessments add additional data points to datasets incorporated...
Federal Register 2010, 2011, 2012, 2013, 2014
2010-06-22
... the Data Workshop is a data report which compiles and evaluates potential datasets and recommends which datasets are appropriate for assessment analyses. The product of the Stock Assessment Workshop is... conducted through the SEDAR program. Update assessments add additional data points to datasets incorporated...
ERIC Educational Resources Information Center
Banta, Trudy W., Ed.
2013-01-01
This issue of "Assessment Update" presents the following articles: (1) "Just Right" Outcomes Assessment: A Fable for Higher Education (Catherine M. Wehlburg); (2) Editor's Notes: Helping Faculty Members Learn (Linda Suskie); (3) Focus on the Bottom-Line: Assessing Business Writing (Michael Cherry and George Klemic); (4)…
Updates on clinical studies of selenium supplementation in radiotherapy
2014-01-01
To establish guidelines for the selenium supplementation in radiotherapy we assessed the benefits and risks of selenium supplementation in radiotherapy. Clinical studies on the use of selenium in radiotherapy were searched in the PubMed electronic database in January 2013. Sixteen clinical studies were identified among the 167 articles selected in the initial search. Ten articles were observational studies, and the other 6 articles reported studies on the effects of selenium supplementation in patients with cancer who underwent radiotherapy. The studies were conducted worldwide including European, American and Asian countries between 1987 and 2012. Plasma, serum or whole blood selenium levels were common parameters used to assess the effects of radiotherapy and the selenium supplementation status. Selenium supplementation improved the general conditions of the patients, improved their quality of life and reduced the side effects of radiotherapy. At the dose of selenium used in these studies (200–500 μg/day), selenium supplementation did not reduce the effectiveness of radiotherapy, and no toxicities were reported. Selenium supplementation may offer specific benefits for several types of cancer patients who undergo radiotherapy. Because high-dose selenium and long-term supplementation may be unsafe due to selenium toxicity, more evidence-based information and additional research are needed to ensure the therapeutic benefits of selenium supplementation. PMID:24885670
Ammari, Maha Al; Sultana, Khizra; Yunus, Faisal; Ghobain, Mohammed Al; Halwan, Shatha M. Al
2016-01-01
Objectives: To assess the proportion of critical errors committed while demonstrating the inhaler technique in hospitalized patients diagnosed with asthma and chronic obstructive pulmonary disease (COPD). Methods: This cross-sectional observational study was conducted in 47 asthmatic and COPD patients using inhaler devices. The study took place at King Abdulaziz Medical City, Riyadh, Saudi Arabia between September and December 2013. Two pharmacists independently assessed inhaler technique with a validated checklist. Results: Seventy percent of patients made at least one critical error while demonstrating their inhaler technique, and the mean number of critical errors per patient was 1.6. Most patients used metered dose inhaler (MDI), and 73% of MDI users and 92% of dry powder inhaler users committed at least one critical error. Conclusion: Inhaler technique in hospitalized Saudi patients was inadequate. Health care professionals should understand the importance of reassessing and educating patients on a regular basis for inhaler technique, recommend the use of a spacer when needed, and regularly assess and update their own inhaler technique skills. PMID:27146622
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dverstorp, B.; Andersson, J.
1995-12-01
Performance Assessment of a nuclear waste repository implies an analysis of a complex system with many interacting processes. Even if some of these processes may be known to large detail, problems arise when combining all information, and means of abstracting information from complex detailed models into models that couple different processes are needed. Clearly, one of the major objectives of performance assessment, to calculate doses or other performance indicators, implies an enormous abstraction of information compared to all information that is used as input. Other problems are that the knowledge of different parts or processes is strongly variable and adjustments,more » interpretations, are needed when combining models from different disciplines. In addition, people as well as computers, even today, always have a limited capacity to process information and choices have to be made. However, because abstraction of information clearly is unavoidable in performance assessment the validity of choices made, always need to be scrutinized and judgements made need to be updated in an iterative process.« less
IRIS TOXICOLOGICAL REVIEW AND SUMMARY DOCUMENTS FOR BERYLLIUM AND COMPOUNDS
EPA's assessment of the noncancer health effects and carcinogenic potential of Beryllium was added to the IRIS database in 1998. The IRIS program is updating the IRIS assessment for Beryllium. This update will incorporate health effects information published since the last assess...
Bartholomew, John R
2018-03-01
In the article, "Update on the management of venous thromboembolism" (Bartholomew JR, Cleve Clin J Med 2017; 84[suppl 3]:39-46), 2 sentences in the text regarding dose reduction for body weight have errors. The corrected sentences follow: On page 42, left column, the last 5 lines should read: "The recommended dose should be reduced to 2.5 mg twice daily in patients that meet 2 of the following criteria: age 80 or older; body weight of 60 kg or less; or with a serum creatinine 1.5 mg/dL or greater." And on page 42, right column, the sentence 10 lines from the top should read: "Edoxaban is given orally at 60 mg once daily but reduced to 30 mg once daily if the CrCL is 30 mL/min to 50 mL/min, if body weight is 60 kg or less, or with use of certain P-glycoprotein inhibitors."
A reassessment of Galileo radiation exposures in the Jupiter magnetosphere.
Atwell, William; Townsend, Lawrence; Miller, Thomas; Campbell, Christina
2005-01-01
Earlier particle experiments in the 1970s on Pioneer-10 and -11 and Voyager-1 and -2 provided Jupiter flyby particle data, which were used by Divine and Garrett to develop the first Jupiter trapped radiation environment model. This model was used to establish a baseline radiation effects design limit for the Galileo onboard electronics. Recently, Garrett et al. have developed an updated Galileo Interim Radiation Environment (GIRE) model based on Galileo electron data. In this paper, we have used the GIRE model to reassess the computed radiation exposures and dose effects for Galileo. The 34-orbit 'as flown' Galileo trajectory data and the updated GIRE model were used to compute the electron and proton spectra for each of the 34 orbits. The total ionisation doses of electrons and protons have been computed based on a parametric shielding configuration, and these results are compared with previously published results.
Updated recommendations: an assessment of NICE clinical guidelines
2014-01-01
Background Updating is important to ensure clinical guideline (CG) recommendations remain valid. However, little research has been undertaken in this field. We assessed CGs produced by the National Institute for Health and Care Excellence (NICE) to identify and describe updated recommendations and to investigate potential factors associated with updating. Also, we evaluated the reporting and presentation of recommendation changes. Methods We performed a descriptive analysis of original and updated CGs and recommendations, and an assessment of presentation formats and methods for recording information. We conducted a case-control study, defining cases as original recommendations that were updated (‘new-replaced’ recommendations), and controls as original recommendations that were considered to remain valid (‘not changed’ recommendations). We performed a comparison of main characteristics between cases and controls, and we planned a multiple regression analysis to identify potential predictive factors for updating. Results We included nine updated CGs (1,306 recommendations) and their corresponding original versions (1,106 recommendations). Updated CGs included 812 (62%) recommendations ‘not reviewed’, 368 (28.1%) ‘new’ recommendations, 104 (7.9%) ‘amended’ recommendations, and 25 (1.9%) recommendations reviewed but unchanged. The presentation formats used to indicate the changes in recommendations varied widely across CGs. Changes in ‘amended’, ‘deleted’, and ‘new-replaced’ recommendations (n = 296) were reported infrequently, mostly in appendices. These changes were recorded in 167 (56.4%) recommendations; and were explained in 81 (27.4%) recommendations. We retrieved a total of 7.1% (n = 78) case recommendations (‘new-replaced’) and 2.4% (n = 27) control recommendations (‘not changed’) in original CGs. The updates were mainly from ‘Fertility CG’, about ‘gynaecology, pregnancy and birth’ topic, and ‘treatment’ or ‘prevention’ purposes. We did not perform the multiple regression analysis as originally planned due to the small sample of recommendations retrieved. Conclusion Our study is the first to describe and assess updated CGs and recommendations from a national guideline program. Our results highlight the pressing need to standardise the reporting and presentation of updated recommendations and the research gap about the optimal way to present updates to guideline users. Furthermore, there is a need to investigate updating predictive factors. PMID:24919856
Updating of working memory in ecstasy polydrug users: Findings from fNIRS.
Montgomery, Catharine; Fisk, John E; Roberts, Carl A
2017-05-01
Cognitive deficits are now well documented in ecstasy (MDMA) users with type and relative demand of task emerging as important factors. The updating component of executive processes appears to be particularly affected. The study reported here used functional near infrared spectroscopy imaging to investigate changes in cortical haemodynamics during memory updating. Twenty ecstasy users and 20 non-users completed verbal and spatial memory updating tasks and brain blood oxygenation and deoxygenation change was measured using functional near infrared spectroscopy. There was no interaction between group and difficulty on the updating tasks, though there was a significant main effect of difficulty on both tasks. The effects of group approached significance on the verbal updating task. There were significant differences in blood oxygenation and deoxygenation change at optodes centred over the right and left dorsolateral prefrontal cortex, with ecstasy users showing greater blood oxygenation than the other groups. The lack of a behavioural difference on both tasks but presence of blood oxygenation and deoxygenation changes in letter updating provides support for the notion that ecstasy-polydrug users are investing more effort to achieve the same behavioural output. Total lifetime dose was high, and recency of use was significantly related to most changes, suggesting that heavy and recent use may be particularly detrimental. Copyright © 2017 John Wiley & Sons, Ltd.
Application of a computational decision model to examine acute drug effects on human risk taking.
Lane, Scott D; Yechiam, Eldad; Busemeyer, Jerome R
2006-05-01
In 3 previous experiments, high doses of alcohol, marijuana, and alprazolam acutely increased risky decision making by adult humans in a 2-choice (risky vs. nonrisky) laboratory task. In this study, a computational modeling analysis known as the expectancy valence model (J. R. Busemeyer & J. C. Stout, 2002) was applied to individual-participant data from these studies, for the highest administered dose of all 3 drugs and corresponding placebo doses, to determine changes in decision-making processes that may be uniquely engendered by each drug. The model includes 3 parameters: responsiveness to rewards and losses (valence or motivation); the rate of updating expectancies about the value of risky alternatives (learning/memory); and the consistency with which trial-by-trial choices match expected outcomes (sensitivity). Parameter estimates revealed 3 key outcomes: Alcohol increased responsiveness to risky rewards and decreased responsiveness to risky losses (motivation) but did not alter expectancy updating (learning/memory); both marijuana and alprazolam produced increases in risk taking that were related to learning/memory but not motivation; and alcohol and marijuana (but not alprazolam) produced more random response patterns that were less consistently related to expected outcomes on the 2 choices. No significant main effects of gender or dose by gender interactions were obtained, but 2 dose by gender interactions approached significance. These outcomes underscore the utility of using a computational modeling approach to deconstruct decision-making processes and thus better understand drug effects on risky decision making in humans.
Update on ibuprofen for rheumatoid arthritis.
Ward, J R
1984-07-13
In doses of 1,200 mg/day or more, ibuprofen is as effective as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis. The tolerability and safety of ibuprofen are superior to those of aspirin and compare favorably with those of other NSAIDs. Although additional controlled trials are indicated to determine optimal dose, ibuprofen's excellent therapeutic index establishes it as a useful drug in the treatment of rheumatoid arthritis.
General requirements to implement the personal dose equivalent Hp(10) in Brazil
NASA Astrophysics Data System (ADS)
Gomes Lopes, Amanda; Da Silva, Francisco Cesar Augusto
2018-03-01
To update the dosimetry quantity with the international community, Brazil is changing the Individual Dose (Hx) to the Personal Dose Equivalent Hp(10). A bibliographical survey on the technical and administrative requirements of nine countries that use Hp(10) was carried out to obtain the most relevant ones. All of them follow IEC and ISO guidelines for technical requirements, but administrative requirements change from country to country. Based on countries experiences, this paper presents a list of important general requirements to implement Hp(10) and to prepare the Brazilian requirements according to the international scientific community.
NASA Technical Reports Server (NTRS)
Yim, John T.; Soulas, George C.; Shastry, Rohit; Choi, Maria; Mackey, Jonathan A.; Sarver-Verhey, Timothy R.
2017-01-01
The service life assessment for NASA's Evolutionary Xenon Thruster is updated to incorporate the results from the successful and voluntarily early completion of the 51,184 hour long duration test which demonstrated 918 kg of total xenon throughput. The results of the numerous post-test investigations including destructive interrogations have been assessed against all of the critical known and suspected failure mechanisms to update the life and throughput expectations for each major component. Analysis results of two of the most acute failure mechanisms, namely pit-and-groove erosion and aperture enlargement of the accelerator grid, are not updated in this work but will be published at a future time after analysis completion.
TOPEX Radar Altimeter Engineering Assessment Report. Update: Launch to January 1, 1997
NASA Technical Reports Server (NTRS)
Hancock, D. W., III; Hayne, G. S.; Brooks, R. L.; Lee, J. E.; Lockwood, D. W.
1997-01-01
The initial TOPEX Mission Radar Altimeter Engineering Assessment Report, in February 1994, presented performance results for the NASA Radar Altimeter on the TOPEX/POSEIDON spacecraft, from its launch in August 1992 to February 1994. There have been supplemental Engineering Assessment Reports, issued in March 1995 and again in May 1996, which updated the performance results through the end of calendar years 1994 and 1995, respectively. This supplement updates the altimeter performance to the end of calendar year 1996, and describes significant events that occurred during 1996. As the performance data base has expanded, and as analysis tools and techniques continue to evolve, the longer-term trends of the altimeter data have become more apparent. The updated findings are presented here.
ERIC Educational Resources Information Center
Banta, Trudy W., Ed.
2012-01-01
This issue of "Assessment Update" presents the following articles: (1) Mission Accomplished! The Development of a Competence-based E-portfolio Assessment Model (Shelley Schuurman, Scott Berlin, Jamie Langlois, and Julie Guevara); (2) The Third Rail of Assessment--Dangerous but Powerful (Dale L. Mort); (3) Video Killed the Radio…
ERIC Educational Resources Information Center
Banta, Trudy W., Ed.
2012-01-01
This issue of "Assessment Update" presents the following articles: (1) Accreditation and Assessment: The Root of My Teaching Metamorphosis (Barbara June Rodriguez); (2) Editor's Notes: Addressing a Question of Credibility (Trudy W. Banta); (3) Do We Practice What We Preach? The Accountability of an Assessment Office (Keston H. Fulcher…
ERIC Educational Resources Information Center
Banta, Trudy W., Ed.
2012-01-01
This issue of "Assessment Update" presents the following articles: (1) A "Wisdom of Crowds" Approach to Outcomes Assessment (Gregory Burton); (2) Editor's Notes: Collective Assessment and DQP Follow-Up (Trudy W. Banta); (3) Satisfaction with Data Management Systems in Standards-Based Alignment (Brett Everhart and Jeanne M.…
Specific issues in small animal dosimetry and irradiator calibration
Yoshizumi, Terry; Brady, Samuel L.; Robbins, Mike E.; Bourland, J. Daniel
2013-01-01
Purpose In response to the increased risk of radiological terrorist attack, a network of Centers for Medical Countermeasures against Radiation (CMCR) has been established in the United States, focusing on evaluating animal model responses to uniform, relatively homogenous whole- or partial-body radiation exposures at relatively high dose rates. The success of such studies is dependent not only on robust animal models but on accurate and reproducible dosimetry within and across CMCR. To address this issue, the Education and Training Core of the Duke University School of Medicine CMCR organised a one-day workshop on small animal dosimetry. Topics included accuracy in animal dosimetry accuracy, characteristics and differences of cesium-137 and X-ray irradiators, methods for dose measurement, and design of experimental irradiation geometries for uniform dose distributions. This paper summarises the information presented and discussed. Conclusions Without ensuring accurate and reproducible dosimetry the development and assessment of the efficacy of putative countermeasures will not prove successful. Radiation physics support is needed, but is often the weakest link in the small animal dosimetry chain. We recommend: (i) A user training program for new irradiator users, (ii) subsequent training updates, and (iii) the establishment of a national small animal dosimetry center for all CMCR members. PMID:21961967
Bhandari, Sunil
2011-01-01
Background The clinical need to be able to administer high doses of intravenous iron conveniently as a rapid infusion has been addressed by the recent introduction of ferric carboxymaltose and subsequently iron isomaltoside 1000. Neither requires a test dose. The maximum dose of ferric carboxymaltose is 1000 mg. The maximum dose of iron isomaltoside 1000 is based on 20 mg/kg body weight without a specified ceiling dose, thereby increasing the scope of being able to achieve total iron repletion with a single infusion. This ability to give high doses of iron is important in the context of managing iron deficiency anemia, which is associated with a number of clinical conditions where demands for iron are high. It is also an important component of the strategy as an alternative to blood transfusion. Affordability is a key issue for health services. Recent price changes affecting iron sucrose and ferric carboxymaltose, plus modifications to the manufacturers’ prescribing information, have provoked this update. Methods This study is a comparative analysis of the costs of acquiring and administering the newly available intravenous iron formulations against standard treatments in the hospital setting. The costs include the medication, nursing costs, equipment, and patient transportation. Three dosage levels (600 mg, 1000 mg, and 1600 mg) are considered. Results and conclusion The traditional standard treatments, blood and iron sucrose, cost more than the alternative intravenous iron preparations across the dose spectrum and sensitivities. Low molecular weight iron dextran is the least expensive option at the 1600 mg dose level but has the caveat of a prolonged administration time and requirement for a test dose. At 600 mg and 1000 mg dose levels, both iron isomaltoside 1000 and ferric carboxymaltose are more economical than low molecular weight iron dextran. Iron isomaltoside 1000 is less expensive than ferric carboxymaltose at all dose levels. Newly available iron preparations appear to be clinically promising, cost effective, and practical alternatives to current standards of iron repletion. PMID:22241947
Lugo, Alessandra; Bosetti, Cristina; Peveri, Giulia; Rota, Matteo; Bagnardi, Vincenzo; Gallus, Silvano
2017-11-01
Only a limited number of meta-analyses providing risk curve functions of dose-response relationships between various smoking-related variables and cancer-specific risk are available. To identify all relevant original publications on the issue, we will conduct a series of comprehensive systematic reviews based on three subsequent literature searches: (1) an umbrella review, to identify meta-analyses, pooled analyses and systematic reviews published before 28 April 2017 on the association between cigarette smoking and the risk of 28 (namely all) malignant neoplasms; (2) for each cancer site, an updated review of original publications on the association between cigarette smoking and cancer risk, starting from the last available comprehensive review identified through the umbrella review; and (3) a review of all original articles on the association between cigarette smoking and site-specific cancer risk included in the publications identified through the umbrella review and the updated reviews. The primary outcomes of interest will be (1) the excess incidence/mortality of various cancers for smokers compared with never smokers; and (2) the dose-response curves describing the association between smoking intensity, duration and time since stopping and incidence/mortality for various cancers. For each cancer site, we will perform a meta-analysis by pooling study-specific estimates for smoking status. We will also estimate the dose-response curves for other smoking-related variables through random-effects meta-regression models based on a non-linear dose-response relationship framework. Ethics approval is not required for this study. Main results will be published in peer-reviewed journals and will also be included in a publicly available website. We will provide therefore the most complete and updated estimates on the association between various measures of cigarette smoking and site-specific cancer risk. This will allow us to obtain precise estimates on the cancer burden attributable to cigarette smoking. This protocol was registered in the International Prospective Register of Systematic Reviews (CRD42017063991). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
DOSE ASSESSMENT OF THE FINAL INVENTORIES IN CENTER SLIT TRENCHES ONE THROUGH FIVE
DOE Office of Scientific and Technical Information (OSTI.GOV)
Collard, L.; Hamm, L.; Smith, F.
2011-05-02
In response to a request from Solid Waste Management (SWM), this study evaluates the performance of waste disposed in Slit Trenches 1-5 by calculating exposure doses and concentrations. As of 8/19/2010, Slit Trenches 1-5 have been filled and are closed to future waste disposal in support of an ARRA-funded interim operational cover project. Slit Trenches 6 and 7 are currently in operation and are not addressed within this analysis. Their current inventory limits are based on the 2008 SA and are not being impacted by this study. This analysis considers the location and the timing of waste disposal in Slitmore » Trenches 1-5 throughout their operational life. In addition, the following improvements to the modeling approach have been incorporated into this analysis: (1) Final waste inventories from WITS are used for the base case analysis where variance in the reported final disposal inventories is addressed through a sensitivity analysis; (2) Updated K{sub d} values are used; (3) Area percentages of non-crushable containers are used in the analysis to determine expected infiltration flows for cases that consider collapse of these containers; (4) An updated representation of ETF carbon column vessels disposed in SLIT3-Unit F is used. Preliminary analyses indicated a problem meeting the groundwater beta-gamma dose limit because of high H-3 and I-129 release from the ETF vessels. The updated model uses results from a recent structural analysis of the ETF vessels indicating that water does not penetrate the vessels for about 130 years and that the vessels remain structurally intact throughout the 1130-year period of assessment; and (5) Operational covers are included with revised installation dates and sets of Slit Trenches that have a common cover. With the exception of the modeling enhancements noted above, the analysis follows the same methodology used in the 2008 PA (WSRC, 2008) and the 2008 SA (Collard and Hamm, 2008). Infiltration flows through the vadose zone are identical to the flows used in the 2008 PA, except for flows during the operational cover time period. The physical (i.e., non-geochemical) models of the vadose zone and aquifer are identical in most cases to the models used in the 2008 PA. However, the 2008 PA assumed a uniform distribution of waste within each Slit Trench (WITS Location) and assumed that the entire inventory of each trench was disposed of at the time the first Slit Trench was opened. The current analysis considers individual trench excavations (i.e., segments) and groups of segments (i.e., Inventory Groups also known as WITS Units) within Slit Trenches. Waste disposal is assumed to be spatially uniform in each Inventory Group and is distributed in time increments of six months or less between the time the Inventory Group was opened and closed.« less
Fractional poisson--a simple dose-response model for human norovirus.
Messner, Michael J; Berger, Philip; Nappier, Sharon P
2014-10-01
This study utilizes old and new Norovirus (NoV) human challenge data to model the dose-response relationship for human NoV infection. The combined data set is used to update estimates from a previously published beta-Poisson dose-response model that includes parameters for virus aggregation and for a beta-distribution that describes variable susceptibility among hosts. The quality of the beta-Poisson model is examined and a simpler model is proposed. The new model (fractional Poisson) characterizes hosts as either perfectly susceptible or perfectly immune, requiring a single parameter (the fraction of perfectly susceptible hosts) in place of the two-parameter beta-distribution. A second parameter is included to account for virus aggregation in the same fashion as it is added to the beta-Poisson model. Infection probability is simply the product of the probability of nonzero exposure (at least one virus or aggregate is ingested) and the fraction of susceptible hosts. The model is computationally simple and appears to be well suited to the data from the NoV human challenge studies. The model's deviance is similar to that of the beta-Poisson, but with one parameter, rather than two. As a result, the Akaike information criterion favors the fractional Poisson over the beta-Poisson model. At low, environmentally relevant exposure levels (<100), estimation error is small for the fractional Poisson model; however, caution is advised because no subjects were challenged at such a low dose. New low-dose data would be of great value to further clarify the NoV dose-response relationship and to support improved risk assessment for environmentally relevant exposures. © 2014 Society for Risk Analysis Published 2014. This article is a U.S. Government work and is in the public domain for the U.S.A.
NASA Astrophysics Data System (ADS)
Hwang, Junga; Yoon, Kyoung-Won; Jo, Gyeongbok; Noh, Sung-Jun
2016-12-01
The space radiation dose over air routes including polar routes should be carefully considered, especially when space weather shows sudden disturbances such as coronal mass ejections (CMEs), flares, and accompanying solar energetic particle events. We recently established a heliocentric potential (HCP) prediction model for real-time operation of the CARI-6 and CARI-6M programs. Specifically, the HCP value is used as a critical input value in the CARI-6/6M programs, which estimate the aviation route dose based on the effective dose rate. The CARI-6/6M approach is the most widely used technique, and the programs can be obtained from the U.S. Federal Aviation Administration (FAA). However, HCP values are given at a one month delay on the FAA official webpage, which makes it difficult to obtain real-time information on the aviation route dose. In order to overcome this critical limitation regarding the time delay for space weather customers, we developed a HCP prediction model based on sunspot number variations (Hwang et al. 2015). In this paper, we focus on improvements to our HCP prediction model and update it with neutron monitoring data. We found that the most accurate method to derive the HCP value involves (1) real-time daily sunspot assessments, (2) predictions of the daily HCP by our prediction algorithm, and (3) calculations of the resultant daily effective dose rate. Additionally, we also derived the HCP prediction algorithm in this paper by using ground neutron counts. With the compensation stemming from the use of ground neutron count data, the newly developed HCP prediction model was improved.
[Radiation-related heart toxicity: Update in women].
Marlière, S; Vautrin, E; Saunier, C; Chaikh, A; Gabelle-Flandin, I
2016-12-01
Breast cancer is a common diagnosis in women and thus women are at risk of radiation-induced heart disease, in particular during radiotherapy for left breast cancer and when the internal mammary chain is included. Rates of major cardiac events increase with younger age at the time of irradiation, diagnosis before 1990s, higher radiation doses, coexisting cardiovascular risk factors and adjuvant cardiotoxic chemotherapy. Radiation-induced heart disease comprises a spectrum of cardiac pathologies, including pericardial disease, cardiomyopathy, coronary artery disease and valvular disease. The cardiac injury can appear a long time after radiotherapy and can consist of complex lesions with poor prognosis. The disciplines of cardiology and oncology have increasingly recognized the benefits of collaborating in the care of cancer patients with cardiac disease, developing guidelines for the assessment and management of radiation-related cardiovascular disease. We could consider screening patients with previous chest radiation every 5 years with transthoracic echocardiography and functional imaging. However, prevention remains the primary goal, using cardiac sparing doses and avoidance techniques in radiotherapy to improve patient survival. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Towards a more transparent HTA process in Poland: new Polish HTA methodological guidelines
Lach, Krzysztof; Dziwisz, Michal; Rémuzat, Cécile; Toumi, Mondher
2017-01-01
ABSTRACT Introduction: Health technology assessment (HTA) in Poland supports reimbursement decisions via the Polish HTA Agency (AOTMiT), whose guidelines were updated in 2016. Methods: We identified key changes introduced by the update and, before guideline publication, analysed discrepancies between AOTMiT assessments and the submitting marketing authorisation holders (MAHs) to elucidate the context of the update. We compared the clarity and detail of the new guidelines versus those of the UK’s National Institute for Health and Care Excellence (NICE). Results: The update specified more precise requirements for items such as indirect comparison or input data for economic modelling. Agency–MAH discrepancies relating to the subjects of the HTA update were found in 14.6% of published documents. The new Polish HTA guidelines were as clear and detailed as NICE’s on topics such as assessing quality of evidence and economic modelling, but were less informative when describing (for example) pairwise meta-analysis. Conclusions: The Polish HTA guidelines update demonstrates lessons learned from internal and external experiences. The new guidelines adhere more closely to UK HTA standards, being clearer and more informative. While the update is expected to reduce Agency–MAH discrepancies, there remain areas for development, such as providing templates to aid HTA submissions. PMID:28804603
A novel method for routine quality assurance of volumetric-modulated arc therapy.
Wang, Qingxin; Dai, Jianrong; Zhang, Ke
2013-10-01
Volumetric-modulated arc therapy (VMAT) is delivered through synchronized variation of gantry angle, dose rate, and multileaf collimator (MLC) leaf positions. The delivery dynamic nature challenges the parameter setting accuracy of linac control system. The purpose of this study was to develop a novel method for routine quality assurance (QA) of VMAT linacs. ArcCheck is a detector array with diodes distributing in spiral pattern on cylindrical surface. Utilizing its features, a QA plan was designed to strictly test all varying parameters during VMAT delivery on an Elekta Synergy linac. In this plan, there are 24 control points. The gantry rotates clockwise from 181° to 179°. The dose rate, gantry speed, and MLC positions cover their ranges commonly used in clinic. The two borders of MLC-shaped field seat over two columns of diodes of ArcCheck when the gantry rotates to the angle specified by each control point. The ratio of dose rate between each of these diodes and the diode closest to the field center is a certain value and sensitive to the MLC positioning error of the leaf crossing the diode. Consequently, the positioning error can be determined by the ratio with the help of a relationship curve. The time when the gantry reaches the angle specified by each control point can be acquired from the virtual inclinometer that is a feature of ArcCheck. The gantry speed between two consecutive control points is then calculated. The aforementioned dose rate is calculated from an acm file that is generated during ArcCheck measurements. This file stores the data measured by each detector in 50 ms updates with each update in a separate row. A computer program was written in MATLAB language to process the data. The program output included MLC positioning errors and the dose rate at each control point as well as the gantry speed between control points. To evaluate this method, this plan was delivered for four consecutive weeks. The actual dose rate and gantry speed were compared with the QA plan specified. Additionally, leaf positioning errors were intentionally introduced to investigate the sensitivity of this method. The relationship curves were established for detecting MLC positioning errors during VMAT delivery. For four consecutive weeks measured, 98.4%, 94.9%, 89.2%, and 91.0% of the leaf positioning errors were within ± 0.5 mm, respectively. For the intentionally introduced leaf positioning systematic errors of -0.5 and +1 mm, the detected leaf positioning errors of 20 Y1 leaf were -0.48 ± 0.14 and 1.02 ± 0.26 mm, respectively. The actual gantry speed and dose rate closely followed the values specified in the VMAT QA plan. This method can assess the accuracy of MLC positions and the dose rate at each control point as well as the gantry speed between control points at the same time. It is efficient and suitable for routine quality assurance of VMAT.
Response functions for computing absorbed dose to skeletal tissues from photon irradiation—an update
NASA Astrophysics Data System (ADS)
Johnson, Perry B.; Bahadori, Amir A.; Eckerman, Keith F.; Lee, Choonsik; Bolch, Wesley E.
2011-04-01
A comprehensive set of photon fluence-to-dose response functions (DRFs) is presented for two radiosensitive skeletal tissues—active and total shallow marrow—within 15 and 32 bone sites, respectively, of the ICRP reference adult male. The functions were developed using fractional skeletal masses and associated electron-absorbed fractions as reported for the UF hybrid adult male phantom, which in turn is based upon micro-CT images of trabecular spongiosa taken from a 40 year male cadaver. The new DRFs expand upon both the original set of seven functions produced in 1985, and a 2007 update calculated under the assumption of secondary electron escape from spongiosa. In this study, it is assumed that photon irradiation of the skeleton will yield charged particle equilibrium across all spongiosa regions at energies exceeding 200 keV. Kerma coefficients for active marrow, inactive marrow, trabecular bone and spongiosa at higher energies are calculated using the DRF algorithm setting the electron-absorbed fraction for self-irradiation to unity. By comparing kerma coefficients and DRF functions, dose enhancement factors and mass energy-absorption coefficient (MEAC) ratios for active marrow to spongiosa were derived. These MEAC ratios compared well with those provided by the NIST Physical Reference Data Library (mean difference of 0.8%), and the dose enhancement factors for active marrow compared favorably with values calculated in the well-known study published by King and Spiers (1985 Br. J. Radiol. 58 345-56) (mean absolute difference of 1.9 percentage points). Additionally, dose enhancement factors for active marrow were shown to correlate well with the shallow marrow volume fraction (R2 = 0.91). Dose enhancement factors for the total shallow marrow were also calculated for 32 bone sites representing the first such derivation for this target tissue.
Johnson, Perry B; Bahadori, Amir A; Eckerman, Keith F; Lee, Choonsik; Bolch, Wesley E
2011-04-21
A comprehensive set of photon fluence-to-dose response functions (DRFs) is presented for two radiosensitive skeletal tissues-active and total shallow marrow-within 15 and 32 bone sites, respectively, of the ICRP reference adult male. The functions were developed using fractional skeletal masses and associated electron-absorbed fractions as reported for the UF hybrid adult male phantom, which in turn is based upon micro-CT images of trabecular spongiosa taken from a 40 year male cadaver. The new DRFs expand upon both the original set of seven functions produced in 1985, and a 2007 update calculated under the assumption of secondary electron escape from spongiosa. In this study, it is assumed that photon irradiation of the skeleton will yield charged particle equilibrium across all spongiosa regions at energies exceeding 200 keV. Kerma coefficients for active marrow, inactive marrow, trabecular bone and spongiosa at higher energies are calculated using the DRF algorithm setting the electron-absorbed fraction for self-irradiation to unity. By comparing kerma coefficients and DRF functions, dose enhancement factors and mass energy-absorption coefficient (MEAC) ratios for active marrow to spongiosa were derived. These MEAC ratios compared well with those provided by the NIST Physical Reference Data Library (mean difference of 0.8%), and the dose enhancement factors for active marrow compared favorably with values calculated in the well-known study published by King and Spiers (1985 Br. J. Radiol. 58 345-56) (mean absolute difference of 1.9 percentage points). Additionally, dose enhancement factors for active marrow were shown to correlate well with the shallow marrow volume fraction (R(2) = 0.91). Dose enhancement factors for the total shallow marrow were also calculated for 32 bone sites representing the first such derivation for this target tissue.
Johnson, Perry; Bahadori, Amir; Eckerman, Keith; Lee, Choonsik; Bolch, Wesley E.
2014-01-01
A comprehensive set of photon fluence-to-dose response functions (DRFs) are presented for two radiosensitive skeletal tissues – active and total shallow marrow – within 15 and 32 bones sites, respectively, of the ICRP reference adult male. The functions were developed using fractional skeletal masses and associated electron absorbed fractions as reported for the UF hybrid adult male phantom, which in turn is based upon microCT images of trabecular spongiosa taken from a 40-year male cadaver. The new DRFs expand upon both the original set of seven functions produced in 1985, as well as a 2007 update calculated under the assumption of secondary electron escape from spongiosa. In the present study, it is assumed that photon irradiation of the skeleton will yield charged particle equilibrium across all spongiosa regions at energies exceeding 200 keV. Kerma factors for active marrow, inactive marrow, trabecular bone, and spongiosa at higher energies are calculated using the DRF algorithm setting the electron absorbed fraction for self-irradiation to unity. By comparing kerma factors and DRF functions, dose enhancement factors and mass energy-absorption coefficient (MEAC) ratios for active marrow to spongiosa were derived. These MEAC ratios compared well with those provided by the NIST Physical Reference Data Library (mean difference of 0.8%), and the dose enhancement factors for active marrow compared favorably with values calculated in the well-known study published by King and Spiers (1985) (mean absolute difference of 1.9 percentage points). Additionally, dose enhancement factors for active marrow were shown to correlate well with the shallow marrow volume fraction (R2 = 0.91). Dose enhancement factors for the total shallow marrow were also calculated for 32 bone sites PMID:21427484
Tan, Sock Keow; Yeong, Chai Hong; Ng, Kwan Hoong; Abdul Aziz, Yang Faridah; Sun, Zhonghua
2016-01-01
This study aimed to measure the absorbed doses in selected organs for prospectively ECG-triggered coronary computed tomography angiography (CCTA) using five different generations CT scanners in a female adult anthropomorphic phantom and to estimate the effective dose (HE). Prospectively ECG-triggered CCTA was performed using five commercially available CT scanners: 64-detector-row single source CT (SSCT), 2 × 32-detector-row-dual source CT (DSCT), 2 × 64-detector-row DSCT and 320-detector-row SSCT scanners. Absorbed doses were measured in 34 organs using pre-calibrated optically stimulated luminescence dosimeters (OSLDs) placed inside a standard female adult anthropomorphic phantom. HE was calculated from the measured organ doses and compared to the HE derived from the air kerma-length product (PKL) using the conversion coefficient of 0.014 mSv∙mGy-1∙cm-1 for the chest region. Both breasts and lungs received the highest radiation dose during CCTA examination. The highest HE was received from 2 × 32-detector-row DSCT scanner (6.06 ± 0.72 mSv), followed by 64-detector-row SSCT (5.60 ± 0.68 and 5.02 ± 0.73 mSv), 2 × 64-detector-row DSCT (1.88 ± 0.25 mSv) and 320-detector-row SSCT (1.34 ± 0.48 mSv) scanners. HE calculated from the measured organ doses were about 38 to 53% higher than the HE derived from the PKL-to-HE conversion factor. The radiation doses received from a prospectively ECG-triggered CCTA are relatively small and are depending on the scanner technology and imaging protocols. HE as low as 1.34 and 1.88 mSv can be achieved in prospectively ECG-triggered CCTA using 320-detector-row SSCT and 2 × 64-detector-row DSCT scanners.
Tan, Sock Keow; Yeong, Chai Hong; Ng, Kwan Hoong; Abdul Aziz, Yang Faridah; Sun, Zhonghua
2016-01-01
Objectives This study aimed to measure the absorbed doses in selected organs for prospectively ECG-triggered coronary computed tomography angiography (CCTA) using five different generations CT scanners in a female adult anthropomorphic phantom and to estimate the effective dose (HE). Materials and Methods Prospectively ECG-triggered CCTA was performed using five commercially available CT scanners: 64-detector-row single source CT (SSCT), 2 × 32-detector-row-dual source CT (DSCT), 2 × 64-detector-row DSCT and 320-detector-row SSCT scanners. Absorbed doses were measured in 34 organs using pre-calibrated optically stimulated luminescence dosimeters (OSLDs) placed inside a standard female adult anthropomorphic phantom. HE was calculated from the measured organ doses and compared to the HE derived from the air kerma-length product (PKL) using the conversion coefficient of 0.014 mSv∙mGy-1∙cm-1 for the chest region. Results Both breasts and lungs received the highest radiation dose during CCTA examination. The highest HE was received from 2 × 32-detector-row DSCT scanner (6.06 ± 0.72 mSv), followed by 64-detector-row SSCT (5.60 ± 0.68 and 5.02 ± 0.73 mSv), 2 × 64-detector-row DSCT (1.88 ± 0.25 mSv) and 320-detector-row SSCT (1.34 ± 0.48 mSv) scanners. HE calculated from the measured organ doses were about 38 to 53% higher than the HE derived from the PKL-to-HE conversion factor. Conclusion The radiation doses received from a prospectively ECG-triggered CCTA are relatively small and are depending on the scanner technology and imaging protocols. HE as low as 1.34 and 1.88 mSv can be achieved in prospectively ECG-triggered CCTA using 320-detector-row SSCT and 2 × 64-detector-row DSCT scanners. PMID:27552224
NONCARCINOGENIC EFFECTS OF CHROMIUM: UPDATE TO HEALTH ASSESSMENT DOCUMENT
This 1990 document updates the 1984 Health Assessment Document for Chromium by addressing issues regarding noncarcinogenic health effects of chromium: oxidation states and persistence of these states in the environment, sampling and analytical methodology to differentiate these o...
Wilson, Nick; Selak, Vanessa; Blakely, Tony; Leung, William; Clarke, Philip; Jackson, Rod; Knight, Josh; Nghiem, Nhung
2016-03-11
Based on new systematic reviews of the evidence, the US Preventive Services Task Force has drafted updated guidelines on the use of low-dose aspirin for the primary prevention of both cardiovascular disease (CVD) and cancer. The Task Force generally recommends consideration of aspirin in adults aged 50-69 years with 10-year CVD risk of at least 10%, in who absolute health gain (reduction of CVD and cancer) is estimated to exceed absolute health loss (increase in bleeds). With the ongoing decline in CVD, current risk calculators for New Zealand are probably outdated, so it is difficult to be precise about what proportion of the population is in this risk category (roughly equivalent to 5-year CVD risk ≥5%). Nevertheless, we suspect that most smokers aged 50-69 years, and some non-smokers, would probably meet the new threshold for taking low-dose aspirin. The country therefore needs updated guidelines and risk calculators that are ideally informed by estimates of absolute net health gain (in quality-adjusted life-years (QALYs) per person) and cost-effectiveness. Other improvements to risk calculators include: epidemiological rigour (eg, by addressing competing mortality); providing enhanced graphical display of risk to enhance risk communication; and possibly capturing the issues of medication disutility and comparison with lifestyle changes.
Federal Register 2010, 2011, 2012, 2013, 2014
2010-09-02
... is a data report which compiles and evaluates potential datasets and recommends which datasets are... add additional data points to datasets incorporated in the original SEDAR benchmark assessment and run... Conference Call Using updated datasets adopted during the Data Webinar, participants will employ assessment...
Parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy.
Davies, Andrew N; Thompson, Jo
2015-10-05
This is an updated version of the original Cochrane review on parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy (published in Issue 3, 2007). Salivary gland dysfunction is a predictable side effect of radiotherapy to the head and neck region. Pilocarpine hydrochloride (a choline ester) is licensed in many countries for the treatment of radiation-induced salivary gland dysfunction. Other parasympathomimetics have also been used 'off licence' in the treatment of this condition. To determine the efficacy and tolerability of parasympathomimetic drugs in the treatment of radiation-induced salivary gland dysfunction (specifically radiation-induced xerostomia). For this update, we ran searches of the Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 6), MEDLINE, EMBASE, and CINAHL in July 2015. We checked the reference lists of retrieved articles for additional studies, contacted experts in the field for unpublished and ongoing trials, and contacted relevant pharmaceutical companies for unpublished and ongoing trials. The selection criteria for the review were: 1) randomised controlled trials; 2) people suffering from radiation-induced salivary gland dysfunction; 3) people treated with parasympathomimetic drugs; and 4) assessable data available on primary outcome measure. The two review authors independently collected data from the full-text version of relevant papers including: 1) citation details; 2) participants; 3) interventions; 4) assessments; 5) outcomes (that is efficacy, tolerability); and 6) quality issues.Due to a lack of appropriate data, we were unable to perform a meta-analysis. In the original review, three studies, including a total of 298 participants, fulfilled the inclusion criteria. All three studies involved the use of pilocarpine hydrochloride. We have included no additional studies in the update of the review; we have excluded eight additional studies.The data suggest that pilocarpine hydrochloride is more effective than placebo and at least as effective as artificial saliva. The response rate was 42% to 51%. The time to response was up to 12 weeks. The overall side effect rate was high, and side effects were the main reason for withdrawal (6% to 15% of participants taking 5 mg three times a day had to withdraw). The side effects were usually the result of generalised parasympathomimetic stimulation (for example sweating, headaches, urinary frequency, vasodilatation). Response rates were not dose dependent, but side effect rates were dose dependent. There is limited evidence to support the use of pilocarpine hydrochloride in the treatment of radiation-induced xerostomia. Currently, there is little evidence to support the use of other parasympathomimetic drugs in the treatment of radiation-induced xerostomia. Available studies suggest that approximately half of patients will respond, but side effects can be problematic. The conclusions of the update are the same as the conclusions of the original review, since no new relevant studies have been published in the interim.
Federal Register 2010, 2011, 2012, 2013, 2014
2011-07-26
... Uses of Bones, Horn, Antlers and Plants Environmental Assessment Update. 12. New Business. 13. Public... Board Update. 10. Alaska Board of Game Update. 11. Old Business: a. Subsistence Uses of Bones, Horn...
Guidance for updating clinical practice guidelines: a systematic review of methodological handbooks.
Vernooij, Robin W M; Sanabria, Andrea Juliana; Solà, Ivan; Alonso-Coello, Pablo; Martínez García, Laura
2014-01-02
Updating clinical practice guidelines (CPGs) is a crucial process for maintaining the validity of recommendations. Methodological handbooks should provide guidance on both developing and updating CPGs. However, little is known about the updating guidance provided by these handbooks. We conducted a systematic review to identify and describe the updating guidance provided by CPG methodological handbooks and included handbooks that provide updating guidance for CPGs. We searched in the Guidelines International Network library, US National Guidelines Clearinghouse and MEDLINE (PubMed) from 1966 to September 2013. Two authors independently selected the handbooks and extracted the data. We used descriptive statistics to analyze the extracted data and conducted a narrative synthesis. We included 35 handbooks. Most handbooks (97.1%) focus mainly on developing CPGs, including variable degrees of information about updating. Guidance on identifying new evidence and the methodology of assessing the need for an update is described in 11 (31.4%) and eight handbooks (22.8%), respectively. The period of time between two updates is described in 25 handbooks (71.4%), two to three years being the most frequent (40.0%). The majority of handbooks do not provide guidance for the literature search, evidence selection, assessment, synthesis, and external review of the updating process. Guidance for updating CPGs is poorly described in methodological handbooks. This guidance should be more rigorous and explicit. This could lead to a more optimal updating process, and, ultimately to valid trustworthy guidelines.
A Bayesian Dose-finding Design for Oncology Clinical Trials of Combinational Biological Agents
Cai, Chunyan; Yuan, Ying; Ji, Yuan
2013-01-01
Treating patients with novel biological agents is becoming a leading trend in oncology. Unlike cytotoxic agents, for which efficacy and toxicity monotonically increase with dose, biological agents may exhibit non-monotonic patterns in their dose-response relationships. Using a trial with two biological agents as an example, we propose a dose-finding design to identify the biologically optimal dose combination (BODC), which is defined as the dose combination of the two agents with the highest efficacy and tolerable toxicity. A change-point model is used to reflect the fact that the dose-toxicity surface of the combinational agents may plateau at higher dose levels, and a flexible logistic model is proposed to accommodate the possible non-monotonic pattern for the dose-efficacy relationship. During the trial, we continuously update the posterior estimates of toxicity and efficacy and assign patients to the most appropriate dose combination. We propose a novel dose-finding algorithm to encourage sufficient exploration of untried dose combinations in the two-dimensional space. Extensive simulation studies show that the proposed design has desirable operating characteristics in identifying the BODC under various patterns of dose-toxicity and dose-efficacy relationships. PMID:24511160
Federal Register 2010, 2011, 2012, 2013, 2014
2010-03-02
... Lobster AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and Atmospheric Administration... spiny lobster. SUMMARY: The SEDAR update of the assessment of the South Atlantic and Gulf of Mexico stock of spiny lobster will consist of a series of webinars and an Update Workshop. This assessment will...
ERIC Educational Resources Information Center
Hundley, Stephen P., Ed.
2017-01-01
This issue of "Assessment Update" presents the following articles: (1) Using National Benchmarking Data to Improve Student Learning in Chemistry at Lebanon Valley College (Marc A. Harris); (2) Mutually Dependent Outcomes: Using Assessment to Improve First-Year Retention and Student Learning (Alan Bearman and Elaine Lewis); (3) Emergent…
ERIC Educational Resources Information Center
Brown, Nicola
2017-01-01
While teaching methods tend to be updated frequently, the implementation of new innovative assessment tools is much slower. For example project based learning has become popular as a teaching technique, however, the assessment tends to be via traditional reports. This paper reports on the implementation and evaluation of using website development…
ERIC Educational Resources Information Center
Banta, Trudy W., Ed.
2014-01-01
This issue of "Assessment Update" presents the following articles: (1) Effective Leadership Assessment: A 360-Degree Process; (2) Editor's Notes: Accentuating the Positive in Our Work; (3) The Broadcast Education Association's Model Rubrics Project: Building Consensus One Rubric at a Time; (4) Building a Better…
Rizzo, J Douglas; Somerfield, Mark R; Hagerty, Karen L; Seidenfeld, Jerome; Bohlius, Julia; Bennett, Charles L; Cella, David F; Djulbegovic, Benjamin; Goode, Matthew J; Jakubowski, Ann A; Rarick, Mark U; Regan, David H; Lichtin, Alan E
2008-01-01
To update the American Society of Clinical Oncology/American Society of Hematology (ASCO/ASH) recommendations for the use of epoetin. The guideline was expanded to address use of darbepoetin and thromboembolic risk associated with these agents. An Update Committee ("Committee") reviewed and analyzed data published since 2002 through July 2007. MEDLINE and the Cochrane Collaboration Library databases were searched. For patients with chemotherapy-associated anemia, the Committee continues to recommend initiating an erythropoiesis-stimulating agent (ESA) as hemoglobin (Hb) approaches, or falls below, 10 g/dL, to increase Hb and decrease transfusions. ESA treatment continues to be recommended for patients with low-risk myelodysplasia for similar reasons. There is no evidence showing increased survival as a result of ESA treatment. Conclusive evidence is lacking that, absent clinical circumstances necessitating earlier treatment, initiating ESAs at Hb levels greater than 10 g/dL either spares more patients from transfusion or substantially improves their quality of life. Starting doses and dose modifications based on response or lack thereof should follow the package insert. Continuing ESAs beyond 6 to 8 weeks in the absence of response, assuming appropriate dose increase has been attempted in nonresponders as per US Food and Drug Administration-approved labeling, does not seem to be beneficial, and ESA therapy should be discontinued. The Committee recommends monitoring iron stores and supplementing iron intake for ESA-treated patients. ESAs should be used cautiously with chemotherapy, or in clinical states, associated with elevated risk for thromboembolic complications. The Committee also cautions against ESA use for patients with cancer who are not receiving chemotherapy, since recent trials report increased thromboembolic risks and decreased survival under these circumstances.
Rizzo, J Douglas; Somerfield, Mark R; Hagerty, Karen L; Seidenfeld, Jerome; Bohlius, Julia; Bennett, Charles L; Cella, David F; Djulbegovic, Benjamin; Goode, Matthew J; Jakubowski, Ann A; Rarick, Mark U; Regan, David H; Lichtin, Alan E
2008-01-01
To update the American Society of Clinical Oncology/American Society of Hematology (ASCO/ASH) recommendations for the use of epoetin. The guideline was expanded to address use of darbepoetin and thromboembolic risk associated with these agents. An Update Committee ("Committee") reviewed and analyzed data published since 2002 through July 2007. MEDLINE and the Cochrane Collaboration Library databases were searched. For patients with chemotherapy-associated anemia, the Committee continues to recommend initiating an erythropoiesis-stimulating agent (ESA) as hemoglobin (Hb) approaches, or falls below, 10 g/dL, to increase Hb and decrease transfusions. ESA treatment continues to be recommended for patients with low-risk myelodysplasia for similar reasons. There is no evidence showing increased survival as a result of ESA treatment. Conclusive evidence is lacking that, absent clinical circumstances necessitating earlier treatment, initiating ESAs at Hb levels greater than 10 g/dL either spares more patients from transfusion or substantially improves their quality of life. Starting doses and dose modifications based on response or lack thereof should follow the package insert. Continuing ESAs beyond 6 to 8 weeks in the absence of response, assuming appropriate dose increase has been attempted in nonresponders as per US Food and Drug Administration-approved label, does not seem to be beneficial, and ESA therapy should be discontinued. The Committee recommends monitoring iron stores and supplementing iron intake for ESA-treated patients. ESAs should be used cautiously with chemotherapy, or in clinical states, associated with elevated risk for thromo-embolic complications. The Committee also cautions against ESA use for patients with cancer who are not receiving chemotherapy, since recent trials report increased thromboembolic risks and decreased survival under these circumstances.
Single dose oral diclofenac for acute postoperative pain in adults
Derry, Philip; Derry, Sheena; Moore, R Andrew; McQuay, Henry J
2014-01-01
Background Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), available as a potassium salt (immediate-release) or sodium salt (delayed-release). This review updates an earlier review published in The Cochrane Database of Systematic Reviews (Issue 2, 2004) on ‘Single dose oral diclofenac for postoperative pain’. Objectives To assess single dose oral diclofenac for the treatment of acute postoperative pain. Search methods Cochrane CENTRAL, MEDLINE, EMBASE, Biological Abstracts, the Oxford Pain Relief Database, and reference lists of articles were searched; last search December 2008. Selection criteria Randomised, double-blind, placebo-controlled clinical trials of single dose, oral diclofenac (sodium or potassium) for acute postoperative pain in adults. Data collection and analysis Two review authors independently assessed studies for inclusion and quality, and extracted data. The area under the pain relief versus time curve was used to derive the proportion of participants with at least 50% pain relief over 4 to 6 hours, using validated equations. Relative benefit (risk) and number needed to treat to benefit (NNT) were calculated. Information on adverse events, time to remedication, and participants needing additional analgesia was also collected. Main results Fifteen studies (eight additional studies) with 1512 participants more than doubled the information available at each dose. Overall 50% to 60% of participants experienced at least 50% pain relief over 4 to 6 hours at any dose with diclofenac, compared to 10 to 20% with placebo, giving NNTs of about 2.5 for doses of 25 mg to 100 mg (similar to earlier review); no dose response was demonstrated. At 50 mg and 100 mg, NNTs for diclofenac potassium (2.1 (1.8 to 2.4) and 1.9 (1.7 to 2.2)) were significantly lower (better) than for diclofenac sodium (6.7 (4.2 to 17) and 4.5 (3.2 to 7.7)). The median time to use of rescue medication was 2 hours for placebo, 4.3 hours for diclofenac 50 mg and 4.9 hours for diclofenac 100 mg. Adverse events were reported at a similar rate to placebo, with no serious events. Authors’ conclusions Oral diclofenac is an effective single-dose treatment for moderate to severe postoperative pain. Significantly more participants experienced at least 50% pain relief over 4 to 6 hours with diclofenac potassium than with diclofenac sodium. There was no significant difference between diclofenac and placebo in the incidence of adverse events. PMID:19370609
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jannik, T.; Karapatakis, D.; Lee, P.
2010-08-06
Operations at the Savannah River Site (SRS) result in releases of small amounts of radioactive materials to the atmosphere and to the Savannah River. For regulatory compliance purposes, potential offsite radiological doses are estimated annually using computer models that follow U.S. Nuclear Regulatory Commission (NRC) Regulatory Guides. Within the regulatory guides, default values are provided for many of the dose model parameters but the use of site-specific values by the applicant is encouraged. A detailed survey of land and water use parameters was conducted in 1991 and is being updated here. These parameters include local characteristics of meat, milk andmore » vegetable production; river recreational activities; and meat, milk and vegetable consumption rates as well as other human usage parameters required in the SRS dosimetry models. In addition, the preferred elemental bioaccumulation factors and transfer factors to be used in human health exposure calculations at SRS are documented. Based on comparisons to the 2009 SRS environmental compliance doses, the following effects are expected in future SRS compliance dose calculations: (1) Aquatic all-pathway maximally exposed individual doses may go up about 10 percent due to changes in the aquatic bioaccumulation factors; (2) Aquatic all-pathway collective doses may go up about 5 percent due to changes in the aquatic bioaccumulation factors that offset the reduction in average individual water consumption rates; (3) Irrigation pathway doses to the maximally exposed individual may go up about 40 percent due to increases in the element-specific transfer factors; (4) Irrigation pathway collective doses may go down about 50 percent due to changes in food productivity and production within the 50-mile radius of SRS; (5) Air pathway doses to the maximally exposed individual may go down about 10 percent due to the changes in food productivity in the SRS area and to the changes in element-specific transfer factors; and (6) Air pathway collective doses may go down about 30 percent mainly due to the decrease in the inhalation rate assumed for the average individual.« less
IRIS Toxicological Review of Naphthalene (2004, External Review Draft, Update)
[Update Jun 2004] This document contains revision of the inhalation cancer assessment and other selected text from the 1998 draft as indicated: Sections of this document pertaining to the inhalation cancer assessment are presented as draft for external peer review purposes only ...
Ritalin Update: Implications for Reading Teachers.
ERIC Educational Resources Information Center
Cotter, Robert B., Jr.; Werner, Patrice Holden
1987-01-01
Investigates how Ritalin, a powerful stimulant drug frequently prescribed for children exhibiting hyperactive behavior, poor attention span, and/or distractibility, is prescribed for children in educational settings, what doses seem appropriate, and what effect Ritalin has on reading achievement. Discusses the implications of Ritalin research for…
DOSE RESPONSE MODELING FOR 2, 3, 7, 8-TETRACHLORODIBENZO-P-DIOXIN
As science continues to appreciate the prevalence and power of dioxins, so it learns more about the harmful effects and effective preventive measures regarding these chemicals. Updating the acclaimed First Edition, Dioxins and Health, Second Edition covers the latest major scient...
Federal Guidance Report No. 15: External Exposure to Radionuclides in Air, Water and Soil
FGR 15 updates the 1993 Federal Guidance Report No. 12 (FGR 12), External Exposure to Radionuclides in Air, Water, and Soil. FGR 15 incorporates advances in radiation protection science regarding how organ/tissue doses change with age and sex.
Makris, Susan L; Scott, Cheryl Siegel; Fox, John; Knudsen, Thomas B; Hotchkiss, Andrew K; Arzuaga, Xabier; Euling, Susan Y; Powers, Christina M; Jinot, Jennifer; Hogan, Karen A; Abbott, Barbara D; Hunter, E Sidney; Narotsky, Michael G
2016-10-01
The 2011 EPA trichloroethylene (TCE) IRIS assessment, used developmental cardiac defects from a controversial drinking water study in rats (Johnson et al. [51]), along with several other studies/endpoints to derive reference values. An updated literature search of TCE-related developmental cardiac defects was conducted. Study quality, strengths, and limitations were assessed. A putative adverse outcome pathway (AOP) construct was developed to explore key events for the most commonly observed cardiac dysmorphologies, particularly those involved with epithelial-mesenchymal transition (EMT) of endothelial origin (EndMT); several candidate pathways were identified. A hypothesis-driven weight-of-evidence analysis of epidemiological, toxicological, in vitro, in ovo, and mechanistic/AOP data concluded that TCE has the potential to cause cardiac defects in humans when exposure occurs at sufficient doses during a sensitive window of fetal development. The study by Johnson et al. [51] was reaffirmed as suitable for hazard characterization and reference value derivation, though acknowledging study limitations and uncertainties. Published by Elsevier Inc.
Dorman, David C.; Andersen, Melvin E.; Roper, Jerry M.; Taylor, Michael D.
2012-01-01
Concerns have been raised regarding environmental manganese exposure since high exposures have been associated with neurological disorders. The USA Environmental Protection Agency most recent human health risk assessment of inhaled manganese conducted in 1993 identified specific areas of uncertainty regarding manganese pharmacokinetics. This led to the development of a test rule under the USA Clean Air Act that required the generation of pharmacokinetic information on the inorganic manganese combustion products of the organometallic fuel additive methylcyclopentadienyl manganese tricarbonyl (MMT). The Alternative Tier 2 testing program for MMT, described in this paper, has yielded substantial pharmacokinetic data and has enabled the generation of physiologically based pharmacokinetic (PBPK) models for manganese. These models are capable of predicting tissue manganese concentrations across a variety of dose routes, levels, and durations while accounting for factors such as age, gender, and reproductive status, enabling the consideration of tissue dosimetry in future risk assessments. PMID:22545047
ADVISORY ON UPDATED METHODOLOGY FOR ...
The National Academy of Sciences (NAS) published the Biological Effects of Ionizing Radiation (BEIR) committee's report (BEIR VII) on risks from ionizing radiation exposures in 2006. The Committee analyzed the most recent epidemiology from the important exposed cohorts and factored in changes resulting from the updated analysis of dosimetry for the Japanese atomic bomb survivors. To the extent practical, the Committee also considered relevant radiobiological data, including that from the Department of Energy's low dose effects research program. Based on the review of this information, the Committee proposed a set of models for estimating risks from low-dose ionizing radiation. ORIA then prepared a white paper revising the Agency's methodology for estimating cancer risks from exposure to ionizing radiation in light of this report and other relevant information. This is the first product to be developed as a result of the BEIR VII report. We requested that the SAB conduct an advisory during the development of this methodology. The second product to be prepared will be a revised version of the document,
Seo, Songwon; Lim, Wan Young; Lee, Dal Nim; Kim, Jung Un; Cha, Eun Shil; Bang, Ye Jin; Lee, Won Jin; Park, Sunhoo; Jin, Young Woo
2018-03-30
The cancer risk of radiation exposure in the moderate-to-high dose range has been well established. However, the risk remains unclear at low-dose ranges with protracted low-dose rate exposure, which is typical of occupational exposure. Several epidemiological studies of Korean radiation workers have been conducted, but the data were analysed retrospectively in most cases. Moreover, groups with relatively high exposure, such as industrial radiographers, have been neglected. Therefore, we have launched a prospective cohort study of all Korean radiation workers to assess the health effects associated with occupational radiation exposure. Approximately 42 000 Korean radiation workers registered with the Nuclear Safety and Security Commission from 2016 to 2017 are the initial target population of this study. Cohort participants are to be enrolled through a nationwide self-administered questionnaire survey between 24 May 2016 and 30 June 2017. As of 31 March 2017, 22 982 workers are enrolled in the study corresponding to a response rate of 75%. This enrolment will be continued at 5-year intervals to update information on existing study participants and recruit newly hired workers. Survey data will be linked with the national dose registry, the national cancer registry, the national vital statistics registry and national health insurance data via personal identification numbers. Age-specific and sex-specific standardised incidence and mortality ratios will be calculated for overall comparisons of cancer risk. For dose-response assessment, excess relative risk (per Gy) and excess absolute risk (per Gy) will be estimated with adjustments for birth year and potential confounders, such as lifestyle factors and socioeconomic status. This study has received ethical approval from the institutional review board of the Korea Institute of Radiological and Medical Sciences (IRB No. K-1603-002-034). All participants provided written informed consent prior to enrolment. The findings of the study will be disseminated through scientific peer-reviewed journals and be provided to the public, including radiation workers, via the study website (http://www.rhs.kr/) and onsite radiation safety education. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Development of interim oak assessment guidelines for the silvah decision-support system
Patrick H. Brose
2007-01-01
Updates to the SILVAH decision-support system make it more applicable to the mixed oak forests of Pennsylvania and other mid-Atlantic states. This update required establishing interim inventory guidelines for assessing the competitive ability of advance oak regeneration. This assessment was complicated by oakâs growth strategy, emphasizing root development in lieu of...
24 CFR 50.36 - Updating of environmental reviews.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Updating of environmental reviews... Urban Development PROTECTION AND ENHANCEMENT OF ENVIRONMENTAL QUALITY Environmental Assessments and Related Reviews § 50.36 Updating of environmental reviews. The environmental review must be re-evaluated...
24 CFR 50.36 - Updating of environmental reviews.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Updating of environmental reviews... Urban Development PROTECTION AND ENHANCEMENT OF ENVIRONMENTAL QUALITY Environmental Assessments and Related Reviews § 50.36 Updating of environmental reviews. The environmental review must be re-evaluated...
78 FR 21343 - Sunshine Act Meeting
Federal Register 2010, 2011, 2012, 2013, 2014
2013-04-10
... COMMISSION ON CIVIL RIGHTS Sunshine Act Meeting AGENCY: United States Commission on Civil Rights... Update on the Sex Trafficking: A Gender-Based Violation of Civil Rights briefing Update on the Federal Civil Rights Engagement with Arab & Muslim Communities Post 9/11 briefing Update on the Assessing the...
IRIS TOXICOLOGICAL REVIEW AND SUMMARY DOCUMENTS FOR 1,2,3-TRICHLOROPROPANE
EPA's assessment of the noncancer health effects and carcinogenic potential of 1,2,3-trichloropropane (TCP) was added to the IRIS database in 1990. The IRIS program is updating the IRIS assessment for TCP. This update will incorporate health effects information published since t...
Progress Toward Measles Elimination - African Region, 2013-2016.
Masresha, Balcha G; Dixon, Meredith G; Kriss, Jennifer L; Katsande, Reggis; Shibeshi, Messeret E; Luce, Richard; Fall, Amadou; Dosseh, Annick R G A; Byabamazima, Charles R; Dabbagh, Alya J; Goodson, James L; Mihigo, Richard
2017-05-05
In 2011, the 46 World Health Organization (WHO) African Region (AFR) member states established a goal of measles elimination* by 2020, by achieving 1) ≥95% coverage of their target populations with the first dose of measles-containing vaccine (MCV1) at national and district levels; 2) ≥95% coverage with measles-containing vaccine (MCV) per district during supplemental immunization activities (SIAs); and 3) confirmed measles incidence of <1 case per 1 million population in all countries (1). Two key surveillance performance indicator targets include 1) investigating ≥2 cases of nonmeasles febrile rash illness per 100,000 population annually, and 2) obtaining a blood specimen from ≥1 suspected measles case in ≥80% of districts annually (2). This report updates the previous report (3) and describes progress toward measles elimination in AFR during 2013-2016. Estimated regional MCV1 coverage † increased from 71% in 2013 to 74% in 2015. § Seven (15%) countries achieved ≥95% MCV1 coverage in 2015. ¶ The number of countries providing a routine second MCV dose (MCV2) increased from 11 (24%) in 2013 to 23 (49%) in 2015. Forty-one (79%) of 52 SIAs** during 2013-2016 reported ≥95% coverage. Both surveillance targets were met in 19 (40%) countries in 2016. Confirmed measles incidence in AFR decreased from 76.3 per 1 million population to 27.9 during 2013-2016. To eliminate measles by 2020, AFR countries and partners need to 1) achieve ≥95% 2-dose MCV coverage through improved immunization services, including second dose (MCV2) introduction; 2) improve SIA quality by preparing 12-15 months in advance, and using readiness, intra-SIA, and post-SIA assessment tools; 3) fully implement elimination-standard surveillance †† ; 4) conduct annual district-level risk assessments; and 5) establish national committees and a regional commission for the verification of measles elimination.
Wang, F; Yeung, K L; Chan, W C; Kwok, C C H; Leung, S L; Wu, C; Chan, E Y Y; Yu, I T S; Yang, X R; Tse, L A
2013-11-01
This study aimed to conduct a systematic review to sum up evidence of the associations between different aspects of night shift work and female breast cancer using a dose-response meta-analysis approach. We systematicly searched all cohort and case-control studies published in English on MEDLINE, Embase, PSYCInfo, APC Journal Club and Global Health, from January 1971 to May 2013. We extracted effect measures (relative risk, RR; odd ratio, OR; or hazard ratio, HR) from individual studies to generate pooled results using meta-analysis approaches. A log-linear dose-response regression model was used to evaluate the relationship between various indicators of exposure to night shift work and breast cancer risk. Downs and Black scale was applied to assess the methodological quality of included studies. Ten studies were included in the meta-analysis. A pooled adjusted relative risk for the association between 'ever exposed to night shift work' and breast cancer was 1.19 [95% confidence interval (CI) 1.05-1.35]. Further meta-analyses on dose-response relationship showed that every 5-year increase of exposure to night shift work would correspondingly enhance the risk of breast cancer of the female by 3% (pooled RR = 1.03, 95% CI 1.01-1.05; Pheterogeneity < 0.001). Our meta-analysis also suggested that an increase in 500-night shifts would result in a 13% (RR = 1.13, 95% CI 1.07-1.21; Pheterogeneity = 0.06) increase in breast cancer risk. This systematic review updated the evidence that a positive dose-response relationship is likely to present for breast cancer with increasing years of employment and cumulative shifts involved in the work.
2012 update in the treatment of prolactinomas.
Maiter, Dominique; Primeau, Vanessa
2012-04-01
New information has been provided over the last years regarding treatment of prolactinomas and will be reviewed in this update. Medical treatment with a dopamine agonist (DA) remains the cornerstone of therapy and cabergoline is the first choice, due to its high efficacy and good tolerability profile. Prolonged remission after discontinuation of DA may be observed if treatment has been given for at least two years, normal prolactin has been obtained with a low dose and tumoral diameter has been reduced by at least 50%. Although the risk of restrictive cardiac valve disease is low at the standard doses of cabergoline used for the treatment of hyperprolactinaemia, long-term echocardiographic surveillance is however indicated, in particular in resistant patients who need higher doses of cabergoline (2.0 mg/week or more). Neurosurgical treatment of prolactinomas is less effective than medical therapy and recurrence of hyperprolactinaemia is frequent. Besides classical indications such as drug intolerance, resistance or acute complications, new indications have emerged such as young patients with a high likelihood of complete tumour resection and who do not wish to take prolonged medical treatment, or patients who require high doses of cabergoline, in whom surgical debulking may significantly improve postoperative hormonal control. Finally, recent data indicate that cabergoline is safe for the developing foetus and for the mother, and therefore should not be preventively withdrawn in a young woman wishing to become pregnant. Copyright © 2012 Elsevier Masson SAS. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Borot de Battisti, M; Maenhout, M; Lagendijk, J J W
Purpose: To develop a new method which adaptively determines the optimal needle insertion sequence for HDR prostate brachytherapy involving divergent needle-by-needle dose delivery by e.g. a robotic device. A needle insertion sequence is calculated at the beginning of the intervention and updated after each needle insertion with feedback on needle positioning errors. Methods: Needle positioning errors and anatomy changes may occur during HDR brachytherapy which can lead to errors in the delivered dose. A novel strategy was developed to calculate and update the needle sequence and the dose plan after each needle insertion with feedback on needle positioning errors. Themore » dose plan optimization was performed by numerical simulations. The proposed needle sequence determination optimizes the final dose distribution based on the dose coverage impact of each needle. This impact is predicted stochastically by needle insertion simulations. HDR procedures were simulated with varying number of needle insertions (4 to 12) using 11 patient MR data-sets with PTV, prostate, urethra, bladder and rectum delineated. Needle positioning errors were modeled by random normally distributed angulation errors (standard deviation of 3 mm at the needle’s tip). The final dose parameters were compared in the situations where the needle with the largest vs. the smallest dose coverage impact was selected at each insertion. Results: Over all scenarios, the percentage of clinically acceptable final dose distribution improved when the needle selected had the largest dose coverage impact (91%) compared to the smallest (88%). The differences were larger for few (4 to 6) needle insertions (maximum difference scenario: 79% vs. 60%). The computation time of the needle sequence optimization was below 60s. Conclusion: A new adaptive needle sequence determination for HDR prostate brachytherapy was developed. Coupled to adaptive planning, the selection of the needle with the largest dose coverage impact increases chances of reaching the clinical constraints. M. Borot de Battisti is funded by Philips Medical Systems Nederland B.V.; M. Moerland is principal investigator on a contract funded by Philips Medical Systems Nederland B.V.; G. Hautvast and D. Binnekamp are fulltime employees of Philips Medical Systems Nederland B.V.« less
IRIS Toxicological Review and Summary Documents for N ...
EPA's assessment of the noncancer health effects and carcinogenic potential of n-hexane was last prepared and added to the IRIS data base in 1990. The IRIS program is updating the IRIS assessment for n-hexane; this update will incorporate health effects information published since the last assessment was prepared as well as new risk assessment methods. The IRIS assessment for n-hexane will consist of a Toxicological Review and IRIS Summary. The Toxicological Review is a critical review of the physicochemical and toxicokinetic properties of the chemical and its toxicity in humans and experimental systems. The assessment will present reference values for noncancer effects of n-hexane (RfD and RfC) and a cancer assessment, where supported by available data. The Toxicological Review and IRIS Summary will be subject to internal peer consultation, Agency review, and external scientific peer review. EPA is undertaking an update of the Integrated Risk Information System (IRIS) health assessment for n-hexane. The outcome of this project is an updated Toxicological Review and IRIS Summary for n-Hexane that will be entered into the IRIS database. IRIS is an EPA data base containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment
40 CFR 68.36 - Review and update.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 15 2011-07-01 2011-07-01 false Review and update. 68.36 Section 68.36 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Hazard Assessment § 68.36 Review and update. (a) The owner or operator shall...
40 CFR 68.36 - Review and update.
Code of Federal Regulations, 2012 CFR
2012-07-01
... 40 Protection of Environment 16 2012-07-01 2012-07-01 false Review and update. 68.36 Section 68.36 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Hazard Assessment § 68.36 Review and update. (a) The owner or operator shall...
40 CFR 68.36 - Review and update.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 40 Protection of Environment 16 2013-07-01 2013-07-01 false Review and update. 68.36 Section 68.36 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Hazard Assessment § 68.36 Review and update. (a) The owner or operator shall...
40 CFR 68.36 - Review and update.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 16 2014-07-01 2014-07-01 false Review and update. 68.36 Section 68.36 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Hazard Assessment § 68.36 Review and update. (a) The owner or operator shall...
Review of Natural Phenomena Hazard (NPH) Assessments for the DOE Hanford Site
DOE Office of Scientific and Technical Information (OSTI.GOV)
Snow, Robert L.; Ross, Steven B.
2011-09-15
The purpose of this review is to assess the need for updating Natural Phenomena Hazard (NPH) assessments for the DOE's Hanford Site, as required by DOE Order 420.1B Chapter IV, Natural Phenomena Hazards Mitigation, based on significant changes in state-of-the-art NPH assessment methodology or site-specific information. This review is an update and expansion to the September 2010 review of PNNL-19751, Review of Natural Phenomena Hazard (NPH) Assessments for the Hanford 200 Areas (Non-Seismic).
Reverse Toxicokinetics: From In Vitro Concentration to In Vivo Dose
This talk provided an update to an international audience about the state of the science to relate results from high-throughput bioactivity screening efforts out to an external exposure that would be required to achieve blood concentrations at which these bioactivities may be obs...
Development of PIMAL: Mathematical Phantom with Moving Arms and Legs
DOE Office of Scientific and Technical Information (OSTI.GOV)
Akkurt, Hatice; Eckerman, Keith F.
2007-05-01
The computational model of the human anatomy (phantom) has gone through many revisions since its initial development in the 1970s. The computational phantom model currently used by the Nuclear Regulatory Commission (NRC) is based on a model published in 1974. Hence, the phantom model used by the NRC staff was missing some organs (e.g., neck, esophagus) and tissues. Further, locations of some organs were inappropriate (e.g., thyroid).Moreover, all the computational phantoms were assumed to be in the vertical-upright position. However, many occupational radiation exposures occur with the worker in other positions. In the first phase of this work, updates onmore » the computational phantom models were reviewed and a revised phantom model, which includes the updates for the relevant organs and compositions, was identified. This revised model was adopted as the starting point for this development work, and hence a series of radiation transport computations, using the Monte Carlo code MCNP5, was performed. The computational results were compared against values reported by the International Commission on Radiation Protection (ICRP) in Publication 74. For some of the organs (e.g., thyroid), there were discrepancies between the computed values and the results reported in ICRP-74. The reasons behind these discrepancies have been investigated and are discussed in this report.Additionally, sensitivity computations were performed to determine the sensitivity of the organ doses for certain parameters, including composition and cross sections used in the simulations. To assess the dose for more realistic exposure configurations, the phantom model was revised to enable flexible positioning of the arms and legs. Furthermore, to reduce the user time for analyses, a graphical user interface (GUI) was developed. The GUI can be used to visualize the positioning of the arms and legs as desired posture is achieved to generate the input file, invoke the computations, and extract the organ dose values from the MCNP5 output file. In this report, the main features of the phantom model with moving arms and legs and user interface are described.« less
Macrolides for diffuse panbronchiolitis.
Lin, Xiufang; Lu, Jing; Yang, Ming; Dong, Bi Rong; Wu, Hong Mei
2015-01-25
Diffuse panbronchiolitis (DPB) is a chronic airways disease predominantly affecting East Asians. Macrolides, a class of antibiotics, have been used as the main treatment for DPB, based on evidence from retrospective and non-randomised studies. To assess the efficacy and safety of macrolides for DPB. We searched CENTRAL (2014, Issue 6), MEDLINE (1966 to July week 1, 2014), EMBASE (1974 to July 2014), Chinese Biomedical Literature Database (CBM) (1978 to July 2014), China National Knowledge Infrastructure (CNKI) (1974 to July 2014), KoreaMed (1997 to July 2014) and Database of Japana Centra Revuo Medicina (1983 to July 2014). Randomised controlled trials (RCTs) or quasi-RCTs assessing the effect of macrolides for DPB. Two review authors independently assessed study quality and subsequent risk of bias according to The Cochrane Collaboration's tool for assessing risk of bias. The primary outcomes were five-year survival rate, lung function and clinical response. We used risk ratios (RR) for individual trial results in the data analysis and measured all outcomes with 95% confidence intervals (CI). Only one RCT (19 participants) with significant methodological limitations was included in this review. It found that the computerised tomography images of all participants treated with a long-term, low-dose macrolide (erythromycin) improved from baseline, while the images of 71.4% of participants in the control group (with no treatment) worsened and 28.6% remained unchanged. Adverse effects were not reported. This review was previously published in 2010 and 2013. For this 2014 update, we identified no new trials for inclusion or exclusion. There is little evidence for macrolides in the treatment of DPB. We are therefore unable to make any new recommendations. It may be reasonable to use low-dose macrolides soon after diagnosis is made and to continue this treatment for at least six months, according to current guidelines.
Multiple Myeloma: Clinical Updates From the American Society of Hematology Annual Meeting, 2017.
Terpos, Evangelos
2018-05-01
The novel clinical data for myeloma that were presented in the 2017 Annual Meeting of the American Society of Hematology are summarized here. Studies with curative approach (CESAR) or prolonging progression-free survival (CENTAURUS) for patients with high-risk smoldering multiple myeloma (SMM) are described. Updated data from large phase III studies for patients with newly diagnosed MM (NDMM) who are eligible for autologous stem cell transplantation (ASCT) (EMN02, MRC XI) are described, along with the results of studies using novel anti-myeloma drug combinations for induction, consolidation, and maintenance as first-line therapy. The role of minimal residual disease for patients with MM is also discussed. We also present the results of novel phase III studies in patients with NDMM who are not eligible for ASCT (ALCYONE) and new data for their treatment. Recent updates of important studies in the field of relapsed/refractory MM (ASPIRE, POLLUX) along with novel immunotherapy approaches (anti-BCMA monoclonal antibodies, CART cells) are also reported. Finally, levofloxacin prophylaxis reduces febrile episodes and death events in NDMM, whereas 2 doses of high-dose influenza vaccine seem to maintain higher rates of seroprotection compared with those who received standard vaccination. All these data provide the basis for possible changes in the way we manage myeloma in the near future trying to "cure" the disease in many patients. Copyright © 2018 Elsevier Inc. All rights reserved.
Sonja N. Oswalt; W. Brad Smith; Patrick D. Miles; Scott A. Pugh
2014-01-01
Forest resource statistics from the 2010 Resources Planning Act (RPA) Assessment were updated to provide current information on the Nation's forests as a baseline for the 2015 national assessment. Resource tables present estimates of forest area, volume, mortality, growth, removals, and timber products output in various ways, such as by ownership, region, or State...
Statistical and perceptual updating: correlated impairments in right brain injury.
Stöttinger, Elisabeth; Filipowicz, Alex; Marandi, Elahe; Quehl, Nadine; Danckert, James; Anderson, Britt
2014-06-01
It has been hypothesized that many of the cognitive impairments commonly seen after right brain damage (RBD) can be characterized as a failure to build or update mental models. We (Danckert et al. in Neglect as a disorder of representational updating. NOVA Open Access, New York, 2012a; Cereb Cortex 22:2745-2760, 2012b) were the first to directly assess the association between RBD and updating and found that RBD patients were unable to exploit a strongly biased play strategy in their opponent in the children's game rock, paper, scissors. Given that this game required many other cognitive capacities (i.e., working memory, sustained attention, reward processing), RBD patients could have failed this task for various reasons other than a failure to update. To assess the generality of updating deficits after RBD, we had RBD, left brain-damaged (LBD) patients and healthy controls (HCs) describe line drawings that evolved gradually from one figure (e.g., rabbit) to another (e.g., duck) in addition to the RPS updating task. RBD patients took significantly longer to alter their perceptual report from the initial object to the final object than did LBD patients and HCs. Although both patient groups performed poorly on the RPS task, only the RBD patients showed a significant correlation between the two, very different, updating tasks. We suggest these data indicate a general deficiency in the ability to update mental representations following RBD.
In vivo dosimetry for total body irradiation: five‐year results and technique comparison
Warry, Alison J.; Eaton, David J.; Collis, Christopher H.; Rosenberg, Ivan
2014-01-01
The aim of this work is to establish if the new CT‐based total body irradiation (TBI) planning techniques used at University College London Hospital (UCLH) and Royal Free Hospital (RFH) are comparable to the previous technique at the Middlesex Hospital (MXH) by analyzing predicted and measured diode results. TBI aims to deliver a homogeneous dose to the entire body, typically using extended SSD fields with beam modulation to limit doses to organs at risk. In vivo dosimetry is used to verify the accuracy of delivered doses. In 2005, when the Middlesex Hospital was decommissioned and merged with UCLH, both UCLH and the RFH introduced updated CT‐planned TBI techniques, based on the old MXH technique. More CT slices and in vivo measurement points were used by both; UCLH introduced a beam modulation technique using MLC segments, while RFH updated to a combination of lead compensators and bolus. Semiconductor diodes were used to measure entrance and exit doses in several anatomical locations along the entire body. Diode results from both centers for over five years of treatments were analyzed and compared to the previous MXH technique for accuracy and precision of delivered doses. The most stable location was the field center with standard deviations of 4.1% (MXH), 3.7% (UCLH), and 1.7% (RFH). The least stable position was the ankles. Mean variation with fraction number was within 1.5% for all three techniques. In vivo dosimetry can be used to verify complex modulated CT‐planned TBI, and demonstrate improvements and limitations in techniques. The results show that the new UCLH technique is no worse than the previous MXH one and comparable to the current RFH technique. PACS numbers: 87.55.Qr, 87.56.N‐ PMID:25207423
Tuchscherer, Rhianna M; Nair, Kavita; Ghushchyan, Vahram; Saseen, Joseph J
2015-02-01
Muscle-related events, or myopathies, are a commonly reported adverse event associated with statin use. In June 2011, the US FDA released a Drug Safety Communication that provided updated product labeling with dosing restrictions for simvastatin to minimize the risk of myopathies. Our objective was to describe prescribing patterns of simvastatin in combination with medications known to increase the risk of myopathies following updated product labeling dosing restrictions in June 2011. A retrospective observational analysis was carried out, in which administrative claims data were utilized to identify prescribing patterns of simvastatin in combination with calcium channel blockers (CCBs) and other pre-specified drug therapies. Prescribing patterns were analyzed on a monthly basis 24 months prior to and 9 months following product label changes. Incidence of muscle-related events was also analyzed. In June 2011, a total of 60% of patients with overlapping simvastatin-CCB claims and 94% of patients with overlapping simvastatin-non-CCB claims were prescribed an against-label combination. As of March 2012, a total of 41% and 93% of patients continued to be prescribed against-label simvastatin-CCB and simvastatin-non-CCB combinations, respectively. The most commonly prescribed dose of simvastatin was 20 mg (39%). Against-label combinations were most commonly prescribed at a simvastatin dose of 40 mg (56%). Amlodipine was the most commonly prescribed CCB in combination with simvastatin (70%) and the most common CCB prescribed against-label (67%). Despite improvements in prescribing practices, many patients are still exposed to potentially harmful simvastatin combinations. Aggressive changes in simvastatin prescribing systems and processes are needed to improve compliance with FDA labeling to improve medication and patient safety.
In vivo dosimetry for total body irradiation: five-year results and technique comparison.
Patel, Reshma P; Warry, Alison J; Eaton, David J; Collis, Christopher H; Rosenberg, Ivan
2014-07-08
The aim of this work is to establish if the new CT-based total body irradiation (TBI) planning techniques used at University College London Hospital (UCLH) and Royal Free Hospital (RFH) are comparable to the previous technique at the Middlesex Hospital (MXH) by analyzing predicted and measured diode results. TBI aims to deliver a homogeneous dose to the entire body, typically using extended SSD fields with beam modulation to limit doses to organs at risk. In vivo dosimetry is used to verify the accuracy of delivered doses. In 2005, when the Middlesex Hospital was decommissioned and merged with UCLH, both UCLH and the RFH introduced updated CT-planned TBI techniques, based on the old MXH technique. More CT slices and in vivo measurement points were used by both; UCLH introduced a beam modulation technique using MLC segments, while RFH updated to a combination of lead compensators and bolus. Semiconductor diodes were used to measure entrance and exit doses in several anatomical locations along the entire body. Diode results from both centers for over five years of treatments were analyzed and compared to the previous MXH technique for accuracy and precision of delivered doses. The most stable location was the field center with standard deviations of 4.1% (MXH), 3.7% (UCLH), and 1.7% (RFH). The least stable position was the ankles. Mean variation with fraction number was within 1.5% for all three techniques. In vivo dosimetry can be used to verify complex modulated CT-planned TBI, and demonstrate improvements and limitations in techniques. The results show that the new UCLH technique is no worse than the previous MXH one and comparable to the current RFH technique.
Maraldo, Maja V; Giusti, Francesco; Vogelius, Ivan R; Lundemann, Michael; van der Kaaij, Marleen A E; Ramadan, Safaa; Meulemans, Bart; Henry-Amar, Michel; Aleman, Berthe M P; Raemaekers, John; Meijnders, Paul; Moser, Elisabeth C; Kluin-Nelemans, Hanneke C; Feugier, Pierre; Casasnovas, Olivier; Fortpied, Catherine; Specht, Lena
2015-11-01
Cardiovascular disease after treatment is an important concern in cancer survivors. However, knowledge of cardiotoxicity is limited by the retrospective nature of data, which often does not contain details of treatment exposure. To facilitate individual risk counselling of patients, we aimed to quantify the effect of anthracyclines, vinca-alkaloids, and radiotherapy on the risk of cardiovascular disease in patients treated for Hodgkin's lymphoma. In 2009-10, a Life Situation Questionnaire (LSQ) was distributed to patients by mail to assess late-onset effects of Hodgkin's lymphoma treatment in patients who were included in nine successive European Organisation for Research and Treatment of Cancer (EORTC) and the Groupe d'Etude des Lymphomes de l'Adulte (GELA, now renamed LYSA) randomised trials between 1964 and 2004. We reconstructed the mean radiation doses to the heart and carotid arteries and the cumulative doses of anthracyclines and vinca-alkaloids for all patients. Incidence of cardiovascular disease was reported during follow-up and updated through the LSQ. We applied Cox proportional hazards regression analyses to quantify the effect of chemotherapy and radiation on the risk of a first cardiovascular disease event. Information of primary treatment was complete for 6039 patients (median age at diagnosis 30 years [IQR 23-40]; median length of follow-up 9 years [6-14]). 1919 patients responded to the LSQ. 1238 first cardiovascular events were recorded in 703 patients, most were ischaemic heart disease (132 [19%]), congestive heart failure (85 [12%]), arrhythmia (110 [16%]), and valvular disease (77 [11%]). The mean heart radiation dose per 1 Gy increase (HR 1·015 [95% CI 1·006-1·024], p=0·0014) and the dose of anthracyclines per 50 mg/m(2) increase in cumulative dose (1·077 [1·021-1·137], p=0·0064) were significant predictors of cardiovascular disease. Cumulative dose of vinblastine (unadjusted model p=0·77), vincristine (p=0·36), and mean radiation dose to the left (p=0·41) or right (p=0·70) internal carotid artery did not predict for cardiovascular events. Quantification of the increased cardiovascular risk with specific doses of radiation and anthracycline exposure will enable a quantitative assessment of the optimum combination of systemic therapy and radiation, which will help clinicians to balance the risks and benefits of different regimens for individual patients. Rigshospitalet Research Committee, the EORTC Cancer Research Fund, and the Sally Snowman Survivorship Fellowship. Copyright © 2015 Elsevier Ltd. All rights reserved.
Armstrong, Gail E.; Dietrich, Mary; Norman, Linda; Barnsteiner, Jane; Mion, Lorraine
2016-01-01
Health care organizations have incorporated updated safety principles in the analysis of errors and in norms and standards. Yet no research exists that assesses bedside nurses’ perceived skills or attitudes toward updated safety concepts. The aims of this study were to develop a scale assessing nurses’ perceived skills and attitudes toward updated safety concepts, determine content validity, and examine internal consistency of the scale and subscales. Understanding nurses’ perceived skills and attitudes about safety concepts can be used in targeting strategies to enhance their safety practices. PMID:27479518
Armstrong, Gail E; Dietrich, Mary; Norman, Linda; Barnsteiner, Jane; Mion, Lorraine
Health care organizations have incorporated updated safety principles in the analysis of errors and in norms and standards. Yet no research exists that assesses bedside nurses' perceived skills or attitudes toward updated safety concepts. The aims of this study were to develop a scale assessing nurses' perceived skills and attitudes toward updated safety concepts, determine content validity, and examine internal consistency of the scale and subscales. Understanding nurses' perceived skills and attitudes about safety concepts can be used in targeting strategies to enhance their safety practices.
Amoush, Ahmad; Wilkinson, Douglas A.
2015-01-01
This work is a comparative study of the dosimetry calculated by Plaque Simulator, a treatment planning system for eye plaque brachytherapy, to the dosimetry calculated using Monte Carlo simulation for an Eye Physics model EP917 eye plaque. Monte Carlo (MC) simulation using MCNPX 2.7 was used to calculate the central axis dose in water for an EP917 eye plaque fully loaded with 17 IsoAid Advantage 125I seeds. In addition, the dosimetry parameters Λ, gL(r), and F(r,θ) were calculated for the IsoAid Advantage model IAI‐125 125I seed and benchmarked against published data. Bebig Plaque Simulator (PS) v5.74 was used to calculate the central axis dose based on the AAPM Updated Task Group 43 (TG‐43U1) dose formalism. The calculated central axis dose from MC and PS was then compared. When the MC dosimetry parameters for the IsoAid Advantage 125I seed were compared with the consensus values, Λ agreed with the consensus value to within 2.3%. However, much larger differences were found between MC calculated gL(r) and F(r,θ) and the consensus values. The differences between MC‐calculated dosimetry parameters are much smaller when compared with recently published data. The differences between the calculated central axis absolute dose from MC and PS ranged from 5% to 10% for distances between 1 and 12 mm from the outer scleral surface. When the dosimetry parameters for the 125I seed from this study were used in PS, the calculated absolute central axis dose differences were reduced by 2.3% from depths of 4 to 12 mm from the outer scleral surface. We conclude that PS adequately models the central dose profile of this plaque using its defaults for the IsoAid model IAI‐125 at distances of 1 to 7 mm from the outer scleral surface. However, improved dose accuracy can be obtained by using updated dosimetry parameters for the IsoAid model IAI‐125 125I seed. PACS number: 87.55.K‐ PMID:26699577
Federal Register 2010, 2011, 2012, 2013, 2014
2011-07-19
...--Association of Freestanding Radiation Oncology Centers AFS--Ambulance Fee Schedule AHA--American Heart...) Update Committee AMA-DE--American Medical Association Drug Evaluations AMI--Acute Myocardial Infarction.../Low-density lipoprotein HDRT--High dose radiation therapy HEMS--Helicopter Emergency Medical Services...
McCarty, L.S.; Landrum, P.F.; Luoma, S.N.; Meador, J.P.; Merten, A.A.; Shephard, B.K.; van Wezelzz, A.P.
2011-01-01
The tissue residue dose concept has been used, although in a limited manner, in environmental toxicology for more than 100 y. This review outlines the history of this approach and the technical background for organic chemicals and metals. Although the toxicity of both can be explained in tissue residue terms, the relationship between external exposure concentration, body and/or tissues dose surrogates, and the effective internal dose at the sites of toxic action tends to be more complex for metals. Various issues and current limitations related to research and regulatory applications are also examined. It is clear that the tissue residue approach (TRA) should be an integral component in future efforts to enhance the generation, understanding, and utility of toxicity testing data, both in the laboratory and in the field. To accomplish these goals, several key areas need to be addressed: 1) development of a risk-based interpretive framework linking toxicology and ecology at multiple levels of biological organization and incorporating organism-based dose metrics; 2) a broadly applicable, generally accepted classification scheme for modes/mechanisms of toxic action with explicit consideration of residue information to improve both single chemical and mixture toxicity data interpretation and regulatory risk assessment; 3) toxicity testing protocols updated to ensure collection of adequate residue information, along with toxicokinetics and toxicodynamics information, based on explicitly defined toxicological models accompanied by toxicological model validation; 4) continued development of residueeffect databases is needed ensure their ongoing utility; and 5) regulatory guidance incorporating residue-based testing and interpretation approaches, essential in various jurisdictions. ??:2010 SETAC.
Martin, MA; Klein, TE; Dong, BJ; Pirmohamed, M; Haas, DW; Kroetz, DL
2012-01-01
Human leukocyte antigen B (HLA-B) is responsible for presenting peptides to immune cells and plays a critical role in normal immune recognition of pathogens. A variant allele, HLA-B★57:01, is associated with increased risk of a hypersensitivity reaction to the anti-HIV drug abacavir. In the absence of genetic prescreening, hypersensitivity affects ∼6% of patients and can be life-threatening with repeated dosing. We provide recommendations (updated periodically at http://www.pharmkgb.org) for the use of abacavir based on HLA-B genotype. PMID:22378157
The 1993 RPA timber assessment update
Richard W. Haynes; Darius M. Adams; John R. Mills
1995-01-01
This update reports changes in the Nation's timber resource since the 1989 RPA timber assessment. The timber resource situation is analyzed to provide projections for future cost and availability of timber products to meet demands. Prospective trends in demands for and supplies of timber, and the factors that affect these trends are examined. These include changes...
Paracetamol (acetaminophen) poisoning.
Park, B Kevin; Dear, James W; Antoine, Daniel J
2015-10-19
Paracetamol directly causes around 150 deaths per year in UK. We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of treatments for acute paracetamol poisoning? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). At this update, searching of electronic databases retrieved 127 studies. After deduplication and removal of conference abstracts, 64 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 46 studies and the further review of 18 full publications. Of the 18 full articles evaluated, one systematic review was updated and one RCT was added at this update. In addition, two systematic reviews and three RCTs not meeting our inclusion criteria were added to the Comment sections. We performed a GRADE evaluation for three PICO combinations. In this systematic overview we categorised the efficacy for six interventions, based on information about the effectiveness and safety of activated charcoal (single or multiple dose), gastric lavage, haemodialysis, liver transplant, methionine, and acetylcysteine.
Gibbs, Ann E.; Richmond, Bruce M.
2017-09-25
Long-term rates of shoreline change for the north coast of Alaska, from the U.S.-Canadian border to the Icy Cape region of northern Alaska, have been updated as part of the U.S. Geological Survey’s National Assessment of Shoreline Change Project. Short-term shoreline change rates are reported for the first time. Additional shoreline position data were used to compute rates where the previous rate-of-change assessment only included two shoreline positions at a given location. The calculation of uncertainty associated with the long-term average rates has also been updated to match refined methods used in other study regions of the National Assessment of Shoreline Change Project. The average rates of this report have a reduced amount of uncertainty compared to those presented in the first assessment for this region.
Managing hypersensitivity to asparaginase in pediatrics, adolescents, and young adults.
Shinnick, Sara E; Browning, Mary L; Koontz, Susannah E
2013-01-01
Hypersensitivity reactions to chemotherapeutic drugs have been documented for numerous cancer therapies. Clinical hypersensitivity to Escherichia coli asparaginase has been reported to range from 0% to 75%. Throughout the United States, nurses assume frontline responsibility for the assessment of asparaginase-related hypersensitivity reactions. It is essential that nurses educate themselves on the signs and symptoms of asparaginase-related hypersensitivity reactions as well as current supportive care approaches. The purpose of this review is to summarize acute lymphoblastic leukemia and the role of asparaginase and the pathology of allergic reactions. We will also update nurses on the differences in asparaginase preparations including dosing, half-life, rates of hypersensitivity, and routes of administration. A summary of current management and supportive care strategies will be provided as will a discussion of the relationship between allergy, antibodies, and asparaginase activity.
IRIS Toxicological Review of Hexahydro-1,3,5-Trinitro-1,3,5 ...
EPA is developing an Integrated Risk Information System (IRIS) assessment of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and has released the draft assessment for public comment. When final, the assessment will appear on the IRIS database. EPA is undertaking an update of the Integrated Risk Information System (IRIS) health assessment for RDX. The outcome of this project is an updated Toxicological Review and IRIS Summary for RDX that will be entered into the IRIS database.
IRIS Toxicological Review of Benzo[a]pyrene (Public ...
EPA is developing an Integrated Risk Information System (IRIS) assessment of benzo[a]pyrene and has released the draft assessment for public comment and external peer review. When final, the assessment will appear on the IRIS database. EPA is undertaking an update of the Integrated Risk Information System (IRIS) health assessment for benzo[a]pyrene (BaP). The outcome of this project is an updated Toxicological Review and IRIS Summary for BaP that will be entered into the IRIS database.
Minneci, P. C.; Deans, K. J.; Eichacker, P. Q.; Natanson, C.
2012-01-01
A previous meta-analysis determined that the effects of steroids during sepsis were dose-dependent; since then, additional trials have been published. The current analysis updates our previous analysis examining the effects of steroids during sepsis. A literature search from 2004 to 2008 identified seven randomized controlled trials in adult patients; these were added to 14 previously identified trials. The effects of steroids on mortality were highly variable among the 21 trials (p <0.001, I2 = 60%). In trials published before 1989, which involved short courses of high-dose steroids, steroids increased mortality (n = 8, I2 = 14%, OR of death 1.39 (95% CI 1.04–1.86), p 0.03). In trials published after 1997, which involved longer courses of lower-dose steroids, steroids consistently improved shock reversal (n = 7, I2 = 0%, OR of shock reversal 1.66 [95% CI 1.25–2.20), p <0.001), but demonstrated a more heterogeneous beneficial effect on mortality (n = 12, I2 = 25%, OR of death 0.64 (95% CI 0.45–0.93), p 0.02). An inverse linear relationship between severity of illness and the effects of steroids on mortality was identified across all trials (p 0.03) and within the subgroup of trials published after 1997 (p 0.03); steroids were harmful in less severely ill patient populations and beneficial in more severely ill patient populations. There was no effect of response to adrenocorticotrophic hormone (ACTH) stimulation testing concerning the effects of steroids and no increase in steroid-associated adverse events. Low-dose steroids appear to improve mortality rates in patients with septic shock who are at high risk of death; however, additional trials in this subpopulation are necessary to definitively determine the role of low-dose steroids during sepsis. PMID:19416302
Guideline on terminology and definitions of updating clinical guidelines: The Updating Glossary.
Martínez García, Laura; Pardo-Hernández, Hector; Sanabria, Andrea Juliana; Alonso-Coello, Pablo; Penman, Katrina; McFarlane, Emma
2018-03-01
The Guidelines International Network (G-I-N) Updating Guidelines Working Group launched an initiative to develop a glossary (the Updating Glossary) with domains, terms, definitions, and synonyms related to updating of clinical guidelines (CGs). The steering committee developed an initial list of domains, terms, definitions, and synonyms through brainstorming and discussion. The panel members participated in three rounds of feedback to discuss, refine, and clarify the proposed terms, definitions, and synonyms. Finally, the panel members were surveyed to assess their level of agreement regarding the glossary. Eighteen terms were identified and defined: (1) continuous updating, (2) decision to update, (3) fixed updating, (4) full updating, (5) impact of the new evidence, (6) partial updating, (7) prioritization process, (8) reporting process, (9) signal for an update, (10) surveillance process, (11) time of validity, (12) timeframe, (13) tools and resources, (14) up to date, (15) update cycle, (16) update unit, (17) updated version, and (18) updating strategy. Consensus was reached for all terms, definitions, and synonyms (median agreement scores ≥ 6); except for one term. The G-I-N Updating Guidelines Working Group assembled the Updating Glossary to facilitate and improve the knowledge exchange among CGs developers, researchers, and users. Copyright © 2017 Elsevier Inc. All rights reserved.
World Health Organization
2017-10-13
This article presents the World Health Organization's (WHO) recommendations on the use of fractional doses of yellow fever vaccines excerpted from the "Yellow fever vaccine: WHO position on the use of fractional doses - June 2017, Addendum to Vaccines and vaccination against yellow fever WHO: Position Paper - June 2013″, published in the Weekly Epidemiological Record [1,2]. This addendum to the 2013 position paper pertains specifically to use of fractional dose YF (fYF) vaccination (fractional dose yellow fever vaccination refers to administration of a reduced volume of vaccine dose, which has been reconstituted as usual per manufacturer recommendations) in the context of YF vaccine supply shortages beyond the capacity of the global stockpile. The current WHO position on the use of yellow fever (YF) vaccine is set out in the 2013 WHO position paper on vaccines and vaccination against YF and those recommendations are unchanged. Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of Yellow Fever vaccines were discussed by SAGE in October 2016; evidence presented at these meetings can be accessed at: www.who.int/immunization/sage/meetings/2016/October/presentations_background_docs/en/. Copyright © 2017. Published by Elsevier Ltd.
Uses of megavoltage digital tomosynthesis in radiotherapy
NASA Astrophysics Data System (ADS)
Sarkar, Vikren
With the advent of intensity modulated radiotherapy, radiation treatment plans are becoming more conformal to the tumor with the decreasing margins. It is therefore of prime importance that the patient be positioned correctly prior to treatment. Therefore, image guided treatment is necessary for intensity modulated radiotherapy plans to be implemented successfully. Current advanced imaging devices require costly hardware and software upgrade, and radiation imaging solutions, such as cone beam computed tomography, may introduce extra radiation dose to the patient in order to acquire better quality images. Thus, there is a need to extend current existing imaging device ability and functions while reducing cost and radiation dose. Existing electronic portal imaging devices can be used to generate computed tomography-like tomograms through projection images acquired over a small angle using the technique of cone-beam digital tomosynthesis. Since it uses a fraction of the images required for computed tomography reconstruction, use of this technique correspondingly delivers only a fraction of the imaging dose to the patient. Furthermore, cone-beam digital tomosynthesis can be offered as a software-only solution as long as a portal imaging device is available. In this study, the feasibility of performing digital tomosynthesis using individually-acquired megavoltage images from a charge coupled device-based electronic portal imaging device was investigated. Three digital tomosynthesis reconstruction algorithms, the shift-and-add, filtered back-projection, and simultaneous algebraic reconstruction technique, were compared considering the final image quality and radiation dose during imaging. A software platform, DART, was created using a combination of the Matlab and C++ languages. The platform allows for the registration of a reference Cone Beam Digital Tomosynthesis (CBDT) image against a daily acquired set to determine how to shift the patient prior to treatment. Finally, the software was extended to investigate if the digital tomosynthesis dataset could be used in an adaptive radiotherapy regimen through the use of the Pinnacle treatment planning software to recalculate dose delivered. The feasibility study showed that the megavoltage CBDT visually agreed with corresponding megavoltage computed tomography images. The comparative study showed that the best compromise between imaging quality and imaging dose is obtained when 11 projection images, acquired over an imaging angle of 40°, are used with the filtered back-projection algorithm. DART was successfully used to register reference and daily image sets to within 1 mm in-plane and 2.5 mm out of plane. The DART platform was also effectively used to generate updated files that the Pinnacle treatment planning system used to calculate updated dose in a rigidly shifted patient. These doses were then used to calculate a cumulative dose distribution that could be used by a physician as reference to decide when the treatment plan should be updated. In conclusion, this study showed that a software solution is possible to extend existing electronic portal imaging devices to function as cone-beam digital tomosynthesis devices and achieve daily requirement for image guided intensity modulated radiotherapy treatments. The DART platform also has the potential to be used as a part of adaptive radiotherapy solution.
Radiological environment within an NPP after a severe nuclear accident
NASA Astrophysics Data System (ADS)
Andgren, Karin; Fritioff, Karin; Buhr, Anna Maria Blixt; Huutoniemi, Tommi
2017-09-01
The radiological environment following a severe nuclear accident can be visualised on building layouts. The direct radiation in an area (or room) can be visualized on the layout by a colouring scheme depending on the dose rate level (for example orange for high gamma dose rate level and purple for an intermediate gamma dose rate level). Following the Fukushima accident, a need for update of these layouts has been identified at the Swedish nuclear power plant of Forsmark. Shielding calculations for areas where access is desired for severe accident management have been performed. Many different sources of radiation together with different types of shielding material contribute to the dose that would be received by a person entering the area. External radiation from radioactivity within e.g. pipes and components is considered and also external radiation from radioactivity in the air (originating from diffuse leakage of the containment atmosphere). Results are presented as dose rates for relevant dose points together with a method for estimating the dose rate levels for each of the rooms of the reactor building.
Future of America's Forests and Rangelands: Update to the 2010 Resources Planning Act Assessment
Forest Service U.S. Department of Agriculture
2016-01-01
The Update to the 2010 Resources Planning Act (RPA) Assessment summarizes findings about the status, trends, and projected future of forests, rangelands, wildlife, biodiversity, water, outdoor recreation, and urban forests, as well as the effects of climate change upon these resources. Varying assumptions about population and economic growth, land use change, and...
Threshold-driven optimization for reference-based auto-planning
NASA Astrophysics Data System (ADS)
Long, Troy; Chen, Mingli; Jiang, Steve; Lu, Weiguo
2018-02-01
We study threshold-driven optimization methodology for automatically generating a treatment plan that is motivated by a reference DVH for IMRT treatment planning. We present a framework for threshold-driven optimization for reference-based auto-planning (TORA). Commonly used voxel-based quadratic penalties have two components for penalizing under- and over-dosing of voxels: a reference dose threshold and associated penalty weight. Conventional manual- and auto-planning using such a function involves iteratively updating the preference weights while keeping the thresholds constant, an unintuitive and often inconsistent method for planning toward some reference DVH. However, driving a dose distribution by threshold values instead of preference weights can achieve similar plans with less computational effort. The proposed methodology spatially assigns reference DVH information to threshold values, and iteratively improves the quality of that assignment. The methodology effectively handles both sub-optimal and infeasible DVHs. TORA was applied to a prostate case and a liver case as a proof-of-concept. Reference DVHs were generated using a conventional voxel-based objective, then altered to be either infeasible or easy-to-achieve. TORA was able to closely recreate reference DVHs in 5-15 iterations of solving a simple convex sub-problem. TORA has the potential to be effective for auto-planning based on reference DVHs. As dose prediction and knowledge-based planning becomes more prevalent in the clinical setting, incorporating such data into the treatment planning model in a clear, efficient way will be crucial for automated planning. A threshold-focused objective tuning should be explored over conventional methods of updating preference weights for DVH-guided treatment planning.
Wright, Jennifer Gordon; Quinn, Conrad P; Shadomy, Sean; Messonnier, Nancy
2010-07-23
These recommendations from the Advisory Committee on Immunization Practices (ACIP) update the previous recommendations for anthrax vaccine adsorbed (AVA) (CDC. Use of anthrax vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2000;49:1-20; CDC. Use of anthrax vaccine in response to terrorism: supplemental recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2002;51:1024-6) and reflect the status of anthrax vaccine supplies in the United States. This statement 1) provides updated information on anthrax epidemiology; 2) summarizes the evidence regarding the effectiveness and efficacy, immunogenicity, and safety of AVA; 3) provides recommendations for pre-event and preexposure use of AVA; and 4) provides recommendations for postexposure use of AVA. In certain instances, recommendations that did not change were clarified. No new licensed anthrax vaccines are presented. Substantial changes to these recommendations include the following: 1) reducing the number of doses required to complete the pre-event and preexposure primary series from 6 doses to 5 doses, 2) recommending intramuscular rather than subcutaneous AVA administration for preexposure use, 3) recommending AVA as a component of postexposure prophylaxis in pregnant women exposed to aerosolized Bacillus anthracis spores, 4) providing guidance regarding preexposure vaccination of emergency and other responder organizations under the direction of an occupational health program, and 5) recommending 60 days of antimicrobial prophylaxis in conjunction with 3 doses of AVA for optimal protection of previously unvaccinated persons after exposure to aerosolized B. anthracis spores.
An Online Risk Monitor System (ORMS) to Increase Safety and Security Levels in Industry
NASA Astrophysics Data System (ADS)
Zubair, M.; Rahman, Khalil Ur; Hassan, Mehmood Ul
2013-12-01
The main idea of this research is to develop an Online Risk Monitor System (ORMS) based on Living Probabilistic Safety Assessment (LPSA). The article highlights the essential features and functions of ORMS. The basic models and modules such as, Reliability Data Update Model (RDUM), running time update, redundant system unavailability update, Engineered Safety Features (ESF) unavailability update and general system update have been described in this study. ORMS not only provides quantitative analysis but also highlights qualitative aspects of risk measures. ORMS is capable of automatically updating the online risk models and reliability parameters of equipment. ORMS can support in the decision making process of operators and managers in Nuclear Power Plants.
Federal Register 2010, 2011, 2012, 2013, 2014
2012-05-25
... dishwashers with a separate soil- sensing cycle, and the normal cycle definition, power supply and detergent... Soiling Requirements 5. Detergent Dosing Specifications E. Incorporation by Reference of an Updated AHAM...: (1) The addition of a method to rate the efficiency of soil-sensing products; (2) the addition of a...
Disposition of Depleted Uranium Oxide
DOE Office of Scientific and Technical Information (OSTI.GOV)
Crandall, J.L.
2001-08-13
This document summarizes environmental information which has been collected up to June 1983 at Savannah River Plant. Of particular interest is an updating of dose estimates from changes in methodology of calculation, lower cesium transport estimates from Steel Creek, and new sports fish consumption data for the Savannah River. The status of various permitting requirements are also discussed.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Carter, L.M.
2008-07-01
As a student intern with the United States Environmental Protection Agency (EPA) Headquarters, the author was trained in the National Response Plan (NRP) and assisted in the editing of the new (unpublished) EPA Protective Action Guides (PAGs) [1] which has been revised in light of the perceived post 9/11 potential for 'Dirty Bomb' and 'Improvised Nuclear Device' attacks on civilian areas. Technical aspects and the public policy aspects of developing the new guides are discussed. Early Phase initial responses discussed include: Notification of state and/or local authorities, immediate evacuation/sheltering prior to release information or measurements, monitoring of releases and exposuremore » rate measurements, estimation of dose consequences, implementation of protective actions in other areas. The new PAG clarifies the use of 1992 PAGs [2] for incidents other than nuclear power plant accidents, lowers projected thyroid dose for potassium iodine (KI), provides drinking water guidance, includes guidance for long-term site restoration, and updates dosimetry from ICRP 26 to ICRP 60. (authors)« less
Gambito, Ephraim D V; Gonzalez-Suarez, Consuelo B; Grimmer, Karen A; Valdecañas, Carolina M; Dizon, Janine Margarita R; Beredo, Ma Eulalia J; Zamora, Marcelle Theresa G
2015-11-04
Clinical practice guidelines need to be regularly updated with current literature in order to remain relevant. This paper reports on the approach taken by the Philippine Academy of Rehabilitation Medicine (PARM). This dovetails with its writing guide, which underpinned its foundational work in contextualizing guidelines for stroke and low back pain (LBP) in 2011. Working groups of Filipino rehabilitation physicians and allied health practitioners met to reconsider and modify, where indicated, the 'typical' Filipino patient care pathways established in the foundation guidelines. New clinical guidelines on stroke and low back pain which had been published internationally in the last 3 years were identified using a search of electronic databases. The methodological quality of each guideline was assessed using the iCAHE Guideline Quality Checklist, and only those guidelines which provided full text references, evidence hierarchy and quality appraisal of the included literature, were included in the PARM update. Each of the PARM-endorsed recommendations was then reviewed, in light of new literature presented in the included clinical guidelines. A novel standard updating approach was developed based on the criteria reported by Johnston et al. (Int J Technol Assess Health Care 19(4):646-655, 2003) and then modified to incorporate wording from the foundational PARM writing guide. The new updating tool was debated, pilot-tested and agreed upon by the PARM working groups, before being applied to the guideline updating process. Ten new guidelines on stroke and eleven for low back pain were identified. Guideline quality scores were moderate to good, however not all guidelines comprehensively linked the evidence body underpinning recommendations with the literature. Consequently only five stroke and four low back pain guidelines were included. The modified PARM updating guide was applied by all working groups to ensure standardization of the wording of updated recommendations and the underpinning evidence bases. The updating tool provides a simple, standard and novel approach that incorporates evidence hierarchy and quality, and wordings of recommendations. It could be used efficiently by other guideline updaters particularly in developing countries, where resources for guideline development and updates are limited. When many people are involved in guideline writing, there is always the possibility of 'slippage' in use of wording and interpretation of evidence. The PARM updating tool provides a mechanism for maintaining a standard process for guideline updating processes that can be followed by clinicians with basic training in evidence-based practice principles.
Cooney, Lewis; Loke, Yoon K; Golder, Su; Kirkham, Jamie; Jorgensen, Andrea; Sinha, Ian; Hawcutt, Daniel
2017-06-02
Many medicines are dosed to achieve a particular therapeutic range, and monitored using therapeutic drug monitoring (TDM). The evidence base for a therapeutic range can be evaluated using systematic reviews, to ensure it continues to reflect current indications, doses, routes and formulations, as well as updated adverse effect data. There is no consensus on the optimal methodology for systematic reviews of therapeutic ranges. An overview of systematic reviews of therapeutic ranges was undertaken. The following databases were used: Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts and Reviews of Effects (DARE) and MEDLINE. The published methodologies used when systematically reviewing the therapeutic range of a drug were analyzed. Step by step recommendations to optimize such systematic reviews are proposed. Ten systematic reviews that investigated the correlation between serum concentrations and clinical outcomes encompassing a variety of medicines and indications were assessed. There were significant variations in the methodologies used (including the search terms used, data extraction methods, assessment of bias, and statistical analyses undertaken). Therapeutic ranges should be population and indication specific and based on clinically relevant outcomes. Recommendations for future systematic reviews based on these findings have been developed. Evidence based therapeutic ranges have the potential to improve TDM practice. Current systematic reviews investigating therapeutic ranges have highly variable methodologies and there is no consensus of best practice when undertaking systematic reviews in this field. These recommendations meet a need not addressed by standard protocols.
Off-site Emergency Planning at UK Nuclear Licensed Sites.
Leonard, Paul; Thomas, Gareth
2017-04-01
Nuclear emergency planning arrangements in the UK are continually kept under review. This work proposes to outline how experience from nuclear exercises and undertaking emergency response duties can be based on radiological knowledge of specific sites and utilised in the future. In 2014, the UK regulator, the Office for Nuclear Regulation (ONR) revised their principles for the determination of off-site emergency planning areas around nuclear sites where predetermined countermeasures and other protection measures are applied to protect those people who may be affected by a radiation emergency. The revised principles also enhanced communication from the nuclear site operators and local authorities to the public. This updated ONR's application of the UK Radiation (Emergency Preparedness and Public Information) Regulations 2001 (REPPIR) http://www.hse.gov.uk/radiation/ionising/reppir.htm, which includes details of minimising potential doses to the public, as well as assessment and reassurance, linked to other concurrent risks such as flooding. ONR undertakes site-specific assessments of each operators' hazard identification and risk evaluation, which include consideration of whether the public might receive a significant radiation dose in the year following the emergency (excluding countermeasures in the first 24 hours). In defining the areas for off-site emergency planning, practical and strategic factors are then considered, which include other local non-nuclear emergency planning arrangements and experience, and whether local geographic and demographic aspects could aid public credibility and confidence. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Efficacy and safety of immunomodulatory drugs in patients with anterior uveitis
Gómez-Gómez, Alejandro; Loza, Estíbaliz; Rosario, Maria Piedad; Espinosa, Gerard; de Morales, José M. García Ruiz; Herreras, Jose M.; Muñoz-Fernández, Santiago; Cordero-Coma, Miguel
2017-01-01
Abstract Background: To assess the efficacy and safety of immunomodulatory drugs in patients with noninfectious anterior uveitis (AU). Methods: Systematic review of studies were retrieved from Medline (1961 to March 2016), Embase (1961 to March 2016), and Cochrane Library (up to March 2016), and a complementary hand search was also performed. The selection criteria were as follows: (population) noninfectious AU patients, adults; (intervention) immunomodulatory drugs (any dose, regimen, route of administration, duration of treatment); (outcome) control of inflammation, steroid-sparing effect, AU flares, adverse events, and so on; (study design) systematic literature reviews, randomized controlled trials, and observational studies. The study quality was assessed using the Jadad scale and according to The Oxford Centre for Evidence-based Medicine (update 2009). Results: We included 13 studies of moderate-poor quality, with a mean duration from 5 months to 20 years, and number of AU patients ranging from 9 to 274. Patient's demographic and clinical characteristics were very heterogeneous. In most cases, uveitis anatomic classification criteria and outcomes definitions were unclear. Some of the studies only included AU patients with a systemic disease associated, mostly spondyloarthritis, others, mixed populations (idiopathic and systemic disease associated patients), and in some articles this data is not described. We found that methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might prevent AU flares, improve ocular inflammation and visual acuity, and decrease systemic steroids doses. Conclusions: Although there is a lack of robust evidence, methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might be effective in AU patients. PMID:29049193
Marsee, Kevin; Woodruff, Tracey J.; Axelrad, Daniel A.; Calafat, Antonia M.; Swan, Shanna H.
2006-01-01
Phthalate diesters have been shown to be developmental and reproductive toxicants in animal studies. A recent epidemiologic study showed certain phthalates to be significantly associated with reduced anogenital distance in human male infants, the first evidence of subtle developmental effects in human male infants exposed prenatally to phthalates. We used two previously published methods to estimate the daily phthalate exposures for the four phthalates whose urinary metabolites were statistically significantly associated with developmental effects in the 214 mother–infant pairs [di-n-butyl phthalate (DnBP), diethyl phthalate (DEP), butylbenzyl phthalate (BBzP), diisobutyl phthalate (DiBP)] and for another important phthalate [di-2-ethylhexyl phthalate (DEHP)]. We estimated the median and 95th percentile of daily exposures to DBP to be 0.99 and 2.68 μg/kg/day, respectively; for DEP, 6.64 and 112.3 μg/kg/day; for BBzP, 0.50 and 2.47 μg/kg/day; and for DEHP, 1.32 and 9.32 μg/kg/day. The U.S. Environmental Protection Agency (EPA) reference doses for these chemicals are 100 (DBP), 800 (DEP), 200 (BBzP), and 20 (DEHP) μg/kg/day. The median and 95th percentile exposure estimates for the phthalates associated with reduced anogenital distance in the study population are substantially lower than current U.S. EPA reference doses for these chemicals and could be informative to any updates of the hazard assessments and risk assessments for these chemicals. PMID:16759976
Gómez-Gómez, Alejandro; Loza, Estíbaliz; Rosario, Maria Piedad; Espinosa, Gerard; Morales, José M García Ruiz de; Herreras, Jose M; Muñoz-Fernández, Santiago; Cordero-Coma, Miguel
2017-10-01
To assess the efficacy and safety of immunomodulatory drugs in patients with noninfectious anterior uveitis (AU). Systematic review of studies were retrieved from Medline (1961 to March 2016), Embase (1961 to March 2016), and Cochrane Library (up to March 2016), and a complementary hand search was also performed. The selection criteria were as follows: (population) noninfectious AU patients, adults; (intervention) immunomodulatory drugs (any dose, regimen, route of administration, duration of treatment); (outcome) control of inflammation, steroid-sparing effect, AU flares, adverse events, and so on; (study design) systematic literature reviews, randomized controlled trials, and observational studies. The study quality was assessed using the Jadad scale and according to The Oxford Centre for Evidence-based Medicine (update 2009). We included 13 studies of moderate-poor quality, with a mean duration from 5 months to 20 years, and number of AU patients ranging from 9 to 274. Patient's demographic and clinical characteristics were very heterogeneous. In most cases, uveitis anatomic classification criteria and outcomes definitions were unclear. Some of the studies only included AU patients with a systemic disease associated, mostly spondyloarthritis, others, mixed populations (idiopathic and systemic disease associated patients), and in some articles this data is not described. We found that methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might prevent AU flares, improve ocular inflammation and visual acuity, and decrease systemic steroids doses. Although there is a lack of robust evidence, methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might be effective in AU patients.
Wu, Lei; Sun, Dali
2017-01-01
Recent articles have presented inconsistent findings on the impact of Mediterranean diet in the occurrence of cognitive disorders; therefore, we performed an updated systematic review and meta-analysis to evaluate the potential association and dose-response pattern with accumulating evidence. We searched the PubMed and the Embase for the records relevant to this topic. A generic inverse-variance method was used to pool the outcome data for continuous variable, and categories of high vs. low, median vs. low of Mediterranean diet score with a random-effects model. Generalized least-squares trend estimation model was used to estimate the potential dose-response patterns of Mediterranean diet score on incident cognitive disorders. We identified 9 cohort studies involving 34,168 participants. Compared with the lowest category, the pooled analysis showed that the highest Mediterranean diet score was inversely associated with the developing of cognitive disorders, and the pooled RR (95% CI) was 0.79 (0.70, 0.90). Mediterranean diet score of the median category was not significantly associated with cognitive disorders. Dose-response analysis indicated a trend of an approximately linear relationship of the Mediterranean diet score with the incident risk of cognitive disorders. Further studies of randomized controlled trials are warranted to confirm the observed association in different populations. PMID:28112268
SU-E-T-446: Group-Sparsity Based Angle Generation Method for Beam Angle Optimization
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gao, H
2015-06-15
Purpose: This work is to develop the effective algorithm for beam angle optimization (BAO), with the emphasis on enabling further improvement from existing treatment-dependent templates based on clinical knowledge and experience. Methods: The proposed BAO algorithm utilizes a priori beam angle templates as the initial guess, and iteratively generates angular updates for this initial set, namely angle generation method, with improved dose conformality that is quantitatively measured by the objective function. That is, during each iteration, we select “the test angle” in the initial set, and use group-sparsity based fluence map optimization to identify “the candidate angle” for updating “themore » test angle”, for which all the angles in the initial set except “the test angle”, namely “the fixed set”, are set free, i.e., with no group-sparsity penalty, and the rest of angles including “the test angle” during this iteration are in “the working set”. And then “the candidate angle” is selected with the smallest objective function value from the angles in “the working set” with locally maximal group sparsity, and replaces “the test angle” if “the fixed set” with “the candidate angle” has a smaller objective function value by solving the standard fluence map optimization (with no group-sparsity regularization). Similarly other angles in the initial set are in turn selected as “the test angle” for angular updates and this chain of updates is iterated until no further new angular update is identified for a full loop. Results: The tests using the MGH public prostate dataset demonstrated the effectiveness of the proposed BAO algorithm. For example, the optimized angular set from the proposed BAO algorithm was better the MGH template. Conclusion: A new BAO algorithm is proposed based on the angle generation method via group sparsity, with improved dose conformality from the given template. Hao Gao was partially supported by the NSFC (#11405105), the 973 Program (#2015CB856000) and the Shanghai Pujiang Talent Program (#14PJ1404500)« less
Gonçalves, M A D; Bello, N M; Dritz, S S; Tokach, M D; DeRouchey, J M; Woodworth, J C; Goodband, R D
2016-05-01
Advanced methods for dose-response assessments are used to estimate the minimum concentrations of a nutrient that maximizes a given outcome of interest, thereby determining nutritional requirements for optimal performance. Contrary to standard modeling assumptions, experimental data often present a design structure that includes correlations between observations (i.e., blocking, nesting, etc.) as well as heterogeneity of error variances; either can mislead inference if disregarded. Our objective is to demonstrate practical implementation of linear and nonlinear mixed models for dose-response relationships accounting for correlated data structure and heterogeneous error variances. To illustrate, we modeled data from a randomized complete block design study to evaluate the standardized ileal digestible (SID) Trp:Lys ratio dose-response on G:F of nursery pigs. A base linear mixed model was fitted to explore the functional form of G:F relative to Trp:Lys ratios and assess model assumptions. Next, we fitted 3 competing dose-response mixed models to G:F, namely a quadratic polynomial (QP) model, a broken-line linear (BLL) ascending model, and a broken-line quadratic (BLQ) ascending model, all of which included heteroskedastic specifications, as dictated by the base model. The GLIMMIX procedure of SAS (version 9.4) was used to fit the base and QP models and the NLMIXED procedure was used to fit the BLL and BLQ models. We further illustrated the use of a grid search of initial parameter values to facilitate convergence and parameter estimation in nonlinear mixed models. Fit between competing dose-response models was compared using a maximum likelihood-based Bayesian information criterion (BIC). The QP, BLL, and BLQ models fitted on G:F of nursery pigs yielded BIC values of 353.7, 343.4, and 345.2, respectively, thus indicating a better fit of the BLL model. The BLL breakpoint estimate of the SID Trp:Lys ratio was 16.5% (95% confidence interval [16.1, 17.0]). Problems with the estimation process rendered results from the BLQ model questionable. Importantly, accounting for heterogeneous variance enhanced inferential precision as the breadth of the confidence interval for the mean breakpoint decreased by approximately 44%. In summary, the article illustrates the use of linear and nonlinear mixed models for dose-response relationships accounting for heterogeneous residual variances, discusses important diagnostics and their implications for inference, and provides practical recommendations for computational troubleshooting.
Walsh, L; Zhang, W; Shore, R E; Auvinen, A; Laurier, D; Wakeford, R; Jacob, P; Gent, N; Anspaugh, L R; Schüz, J; Kesminiene, A; van Deventer, E; Tritscher, A; del Rosarion Pérez, M
2014-11-01
We present here a methodology for health risk assessment adopted by the World Health Organization that provides a framework for estimating risks from the Fukushima nuclear accident after the March 11, 2011 Japanese major earthquake and tsunami. Substantial attention has been given to the possible health risks associated with human exposure to radiation from damaged reactors at the Fukushima Daiichi nuclear power station. Cumulative doses were estimated and applied for each post-accident year of life, based on a reference level of exposure during the first year after the earthquake. A lifetime cumulative dose of twice the first year dose was estimated for the primary radionuclide contaminants ((134)Cs and (137)Cs) and are based on Chernobyl data, relative abundances of cesium isotopes, and cleanup efforts. Risks for particularly radiosensitive cancer sites (leukemia, thyroid and breast cancer), as well as the combined risk for all solid cancers were considered. The male and female cumulative risks of cancer incidence attributed to radiation doses from the accident, for those exposed at various ages, were estimated in terms of the lifetime attributable risk (LAR). Calculations of LAR were based on recent Japanese population statistics for cancer incidence and current radiation risk models from the Life Span Study of Japanese A-bomb survivors. Cancer risks over an initial period of 15 years after first exposure were also considered. LAR results were also given as a percentage of the lifetime baseline risk (i.e., the cancer risk in the absence of radiation exposure from the accident). The LAR results were based on either a reference first year dose (10 mGy) or a reference lifetime dose (20 mGy) so that risk assessment may be applied for relocated and non-relocated members of the public, as well as for adult male emergency workers. The results show that the major contribution to LAR from the reference lifetime dose comes from the first year dose. For a dose of 10 mGy in the first year and continuing exposure, the lifetime radiation-related cancer risks based on lifetime dose (which are highest for children under 5 years of age at initial exposure), are small, and much smaller than the lifetime baseline cancer risks. For example, after initial exposure at age 1 year, the lifetime excess radiation risk and baseline risk of all solid cancers in females were estimated to be 0.7 · 10(-2) and 29.0 · 10(-2), respectively. The 15 year risks based on the lifetime reference dose are very small. However, for initial exposure in childhood, the 15 year risks based on the lifetime reference dose are up to 33 and 88% as large as the 15 year baseline risks for leukemia and thyroid cancer, respectively. The results may be scaled to particular dose estimates after consideration of caveats. One caveat is related to the lack of epidemiological evidence defining risks at low doses, because the predicted risks come from cancer risk models fitted to a wide dose range (0-4 Gy), which assume that the solid cancer and leukemia lifetime risks for doses less than about 0.5 Gy and 0.2 Gy, respectively, are proportional to organ/tissue doses: this is unlikely to seriously underestimate risks, but may overestimate risks. This WHO-HRA framework may be used to update the risk estimates, when new population health statistics data, dosimetry information and radiation risk models become available.
IRIS TOXICOLOGICAL REVIEW AND SUMMARY ...
EPA's assessment of the noncancer health effects and carcinogenic potential of Beryllium was added to the IRIS database in 1998. The IRIS program is updating the IRIS assessment for Beryllium. This update will incorporate health effects information published since the last assessment was prepared as well as new risk assessment methods. The IRIS assessment for Beryllium will consist of an updated Toxicological Review and IRIS Summary. The Toxicological Review is a critical review of the physicochemical and toxicokinetic properties of the chemical and its toxicity in humans and experimental systems. The assessment will present reference values for noncancer effects of Beryllium (RfD and RfC) and a cancer assessment. The Toxicological Review and IRIS Summary will be subject to internal peer consultation, Agency and Interagency review, and external scientific peer review. The final products will constitute the Agency's opinion on the toxicity of Beryllium. Beryllium is a light alkaline earth metal used in metal alloys and in high-performance products in the metallurgical, aerospace, and nuclear industries. According to the Superfund database, beryllium is found in over 300 NPL sites
Implementation and application of an interactive user-friendly validation software for RADIANCE
NASA Astrophysics Data System (ADS)
Sundaram, Anand; Boonn, William W.; Kim, Woojin; Cook, Tessa S.
2012-02-01
RADIANCE extracts CT dose parameters from dose sheets using optical character recognition and stores the data in a relational database. To facilitate validation of RADIANCE's performance, a simple user interface was initially implemented and about 300 records were evaluated. Here, we extend this interface to achieve a wider variety of functions and perform a larger-scale validation. The validator uses some data from the RADIANCE database to prepopulate quality-testing fields, such as correspondence between calculated and reported total dose-length product. The interface also displays relevant parameters from the DICOM headers. A total of 5,098 dose sheets were used to test the performance accuracy of RADIANCE in dose data extraction. Several search criteria were implemented. All records were searchable by accession number, study date, or dose parameters beyond chosen thresholds. Validated records were searchable according to additional criteria from validation inputs. An error rate of 0.303% was demonstrated in the validation. Dose monitoring is increasingly important and RADIANCE provides an open-source solution with a high level of accuracy. The RADIANCE validator has been updated to enable users to test the integrity of their installation and verify that their dose monitoring is accurate and effective.
Re-evaluation of the reward comparison hypothesis for alcohol abuse.
He, Alan Bo-Han; Chang, Yu-Chieh; Meng, Anna Wan Yun; Huang, Andrew Chih Wei
2017-08-14
This study examined whether various doses of ethanol induced reward or aversion and then evaluated Grigson's reward comparison hypothesis (1997). Rats were given a 0.1% saccharin solution (conditioned stimulus 1 [CS1]) 15min prior to administration of a 0, 0.05, 0.125, 0.20, 0.35, or 0.50g/kg dose of ethanol (unconditioned stimulus [US]). The rats were then exposed to a paired compartment (CS2) for 30min. The low dose of 0.05g/kg ethanol did not induce conditioned suppression (i.e., conditioned taste aversion [CTA]) or conditioned place preference (CPP). The dose of 0.125g/kg ethanol induced CPP but not CTA. High doses of ethanol, including 0.35g/kg and 0.50g/kg, produced CTA but not CPP. The middle dose of 0.20g/kg ethanol simultaneously induced CTA and CPP. As a result, the reward comparison hypothesis cannot explain the present finding that the middle dose of ethanol induced CTA and CPP. Meanwhile, the high doses of ethanol induced motivationally aversive CTA but not rewarding CPP. The reward comparison hypothesis should be updated further. Copyright © 2017 Elsevier B.V. All rights reserved.
Update on Ramazzini Institute Data in IRIS Assessments
This page provides an update to EPA's response to the differences of opinion between NTP scientists and the Ramazzini Institute (RI) in the diagnosis of certain cancers reported in a study on methanol.
Correlation-study about the ambient dose rate and the weather conditions
NASA Astrophysics Data System (ADS)
Furuya, Masato; Hatano, Yuko; Aoyama, Tomoo; Igarashi, Yasuhito; Kita, Kazuyuki; Ishizuka, Masahide
2016-04-01
The long-term radiation risks are believed to be heavily affected by the resuspension process. We therefore focus on the surface-atmosphere exchange process of released radioactive materials in this study. Radioactive materials were deposited on the soil and float in the air, and such complicated process are influenced by the weather conditions deeply. We need to reveal the correlation between the weather conditions and the ambient dose rate. In this study, we study the correlation between the weather conditions and the ambient dose rate with the correction of the decrease due to the radioactive decay. We found that there is a negative correlation between the ambient dose rate and the soil water content by the correlation coefficient. Using this result, we reconstruct the ambient dose rate from the weather conditions by the multiple regression analysis and found that the reconstructed data agree with the observation very well. Using Kalman filter, which can be sequentially updates the state estimate, we obtained such a good agreement.
NASA Technical Reports Server (NTRS)
Turflinger, T.; Schmeichel, W.; Krieg, J.; Titus, J.; Campbell, A.; Reeves, M.; Marshall (P.); Hardage, Donna (Technical Monitor)
2004-01-01
This effort is a detailed analysis of existing microelectronics and photonics test bed satellite data from one experiment, the bipolar test board, looking to improve our understanding of the enhanced low dose rate sensitivity (ELDRS) phenomenon. Over the past several years, extensive total dose irradiations of bipolar devices have demonstrated that many of these devices exhibited ELDRS. In sensitive bipolar transistors, ELDRS produced enhanced degradation of base current, resulting in enhanced gain degradation at dose rates <0.1 rd(Si)/s compared to similar transistors irradiated at dose rates >1 rd(Si)/s. This Technical Publication provides updated information about the test devices, the in-flight experiment, and both flight-and ground-based observations. Flight data are presented for the past 5 yr of the mission. These data are compared to ground-based data taken on devices from the same date code lots. Information about temperature fluctuations, power shutdowns, and other variables encountered during the space flight are documented.
Updated Mortality Analysis of Radiation Workers at Rocketdyne (Atomics International), 1948-2008
DOE Office of Scientific and Technical Information (OSTI.GOV)
Boice Jr JD, Colen SS, Mumma MT, Ellis ED, Eckerman DF, Leggett RW, Boecker BB, Brill B, Henderson BE
Updated analyses of mortality data are presented on 46,970 workers employed 1948-1999 at Rocketdyne (Atomics International). Overall, 5,801 workers were involved in radiation activities, including 2,232 who were monitored for intakes of radionuclides, and 41,169 workers were engaged in rocket testing or other non-radiation activities. The worker population is unique in that lifetime occupational doses from all places of employment were sought, updated and incorporated into the analyses. Further, radiation doses from intakes of 14 different radionuclides were calculated for 16 organs or tissues using biokinetic models of the International Commission on Radiation Protection (ICRP). Because only negligible exposures weremore » received by the 247 workers monitored for radiation activities after 1999, the mean dose from external radiation remained essentially the same at 13.5 mSv (maximum 1 Sv) as reported previously, as did the mean lung dose from external and internal radiation combined at 19.0 mSv (maximum 3.6 Sv). An additional 9 years of follow-up, from December 31,1999 through 2008, increased the person-years of observation for the radiation workers by 21.7% to 196,674 (mean 33.9 years) and the number of cancer deaths by 50% to 684. Analyses included external comparisons with the general population and the computation of standardized mortality ratios (SMRs) and internal comparisons using proportional hazards models and the computation of relative risks (RRs). A low SMR for all causes of death (SMR 0.82; 95% CI 0.78-0.85) continued to indicate that the Rocketdyne radiation workers were healthier than the general population and were less likely to die. The SMRs for all cancers taken together (SMR 0.88; 95% CI 0.81-0.95), lung cancer (SMR 0.87; 95% CI 0.76-1.00) and leukemia other than chronic lymphocytic leukemia (CLL) (SMR 1.04; 95% 0.67-1.53) were not significantly elevated. Cox regression analyses revealed no significant dose-response trends for any cancer. For all cancers excluding leukemia, the RR at 100 mSv was estimated as 0.98 (95% CI 0.82-1.17), and for all leukemia other than CLL it was 1.06 (95% CI 0.50-2.23). Uranium was the primary radionuclide contributing to internal exposures, but no significant increases in lung and kidney disease were seen. The extended follow-up reinforces the findings in the previous study in failing to observe a detectable increase in cancer deaths associated with radiation, but strong conclusions still cannot be drawn because of small numbers and relatively low career doses. Larger combined studies of early workers in the United States using similar methodologies are warranted to refine and clarify radiation risks after protracted exposures.« less
Intraoperative irradiation: precision medicine for quality cancer control promotion.
Calvo, Felipe A
2017-02-02
Intraoperative irradiation was implemented 4 decades ago, pioneering the efforts to improve precision in local cancer therapy by combining real-time surgical exploration/resection with high single dose radiotherapy (Gunderson et al., Intraoperative irradiation: techniques and results, 2011). Clinical and technical developments have led to very precise radiation dose deposit. The ability to deliver a very precise dose of radiation is an essential element of contemporary multidisciplinary individualized oncology.This issue of Radiation Oncology contains a collection of expert review articles and updates with relevant data regarding intraoperative radiotherapy. Technology, physics, biology of single dose and clinical results in a variety of cancer sites and histologies are described and analyzed. The state of the art for advanced cancer care through medical innovation opens a significant opportunity for individualize cancer management across a broad spectrum of clinical practice. The advantage for tailoring diagnostic and treatment decisions in an individualized fashion will translate into precise medical treatment.
Rare problems with RhD immunoglobulin for postnatal prophylaxis after large fetomaternal haemorrhage
Kidson-Gerber, Giselle
2015-01-01
We report a case of unusually large fetomaternal haemorrhage in a RhD- patient; of symptomatic non-sustained haemolysis of fetal red cells in the maternal circulation with infusion of intravenous high-dose RhD immunoglobulin; and of a failure to prevent RhD alloimmunisation. The haemolytic reaction is not previously reported in this patient group and we suggest would be limited to patients where the number of fetal red cells in the circulation is high. We advocate caution in treatment and spaced dosing of RhD immunoglobulin where the required dose is high, and refer readers to the WinRhoSDF™ RhD immunoglobulin product information for their updated dosing recommendations. There is a need for better understanding of pathophysiology and RhD immunoglobulin effects, to further reduce alloimmunisation rates, and we support the reporting of prophylaxis failures to haemovigilance programmes as is in place in the United Kingdom. PMID:27512480
Johnson, JA; Gong, L; Whirl-Carrillo, M; Gage, BF; Scott, SA; Stein, CM; Anderson, JL; Kimmel, SE; Lee, MTM; Pirmohamed, M; Wadelius, M; Klein, TE; Altman, RB
2011-01-01
Warfarin is a widely used anticoagulant with a narrow therapeutic index and large interpatient variability in the dose required to achieve target anticoagulation. Common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K–epoxide reductase complex (VKORC1) enzymes, in addition to known nongenetic factors, account for ~50% of warfarin dose variability. The purpose of this article is to assist in the interpretation and use of CYP2C9 and VKORC1 geno-type data for estimating therapeutic warfarin dose to achieve an INR of 2–3, should genotype results be available to the clinician. The Clinical Pharmacogenetics Implementation Consortium (CPIC) of the National Institutes of Health Pharmacogenomics Research Network develops peer-reviewed gene–drug guidelines that are published and updated periodically on http://www.pharmgkb.org based on new developments in the field.1 PMID:21900891
Himmelstoss, Emily A.; Kratzmann, Meredith G.; Thieler, E. Robert
2017-07-18
Long-term rates of shoreline change for the Gulf of Mexico and Southeast Atlantic regions of the United States have been updated as part of the U.S. Geological Survey’s National Assessment of Shoreline Change project. Additional shoreline position data were used to compute rates where the previous rate-of-change assessment only included four shoreline positions at a given location. The long-term shoreline change rates also incorporate the proxy-datum bias correction to account for the unidirectional onshore bias of the proxy-based high water line shorelines relative to the datum-based mean high water shorelines. The calculation of uncertainty associated with the long-term average rates has also been updated to match refined methods used in other study regions of the National Assessment project. The average rates reported here have a reduced amount of uncertainty relative to those presented in the previous assessments for these two regions.
Zschäbitz, Stefanie; Lasitschka, Felix; Hadaschik, Boris; Hofheinz, Ralf-Dieter; Jentsch-Ullrich, Kathleen; Grüner, Marcus; Jäger, Dirk; Grüllich, Carsten
2017-05-01
Treatment options for patients with platinum refractory metastatic germ cell tumours (GCT) relapsing after high-dose chemotherapy and autologous stem cell transplantation are limited and survival is poor. Antibodies directed against programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) are currently assessed within clinical trials. We present updated data on our experience with checkpoint inhibitors as a compassionate use off-label treatment attempt for highly-pretreated patients with GCT and provide an overview of the current literature on PD-L1 expression in this rare tumour entity. We analysed all patients with platinum refractory GCT treated with checkpoint inhibitors at our institutions between 2015 and 2017. Data were retrieved retrospectively from the patient charts. Seven patients were treated with nivolumab or pembrolizumab. Four patients received single-dose treatment and died shortly afterwards due to tumour progression; the remaining three patients received treatment for at least 6 months. No significant treatment toxicity was observed. Long-term tumour response was achieved in two of the three patients, both of them highly positive for PD-L1 staining. We consider checkpoint inhibition to be efficient in carefully selected patients with platinum refractory GCT. However, predictive markers associated with tumour response are not yet known and larger prospective clinical trials are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.
Rocuronium versus succinylcholine for rapid sequence induction intubation.
Tran, Diem T T; Newton, Ethan K; Mount, Victoria A H; Lee, Jacques S; Wells, George A; Perry, Jeffrey J
2015-10-29
Patients often require a rapid sequence induction (RSI) endotracheal intubation technique during emergencies or electively to protect against aspiration, increased intracranial pressure, or to facilitate intubation. Traditionally succinylcholine has been the most commonly used muscle relaxant for this purpose because of its fast onset and short duration; unfortunately, it can have serious side effects. Rocuronium has been suggested as an alternative to succinylcholine for intubation. This is an update of our Cochrane review published first in 2003 and then updated in 2008 and now in 2015. To determine whether rocuronium creates intubating conditions comparable to those of succinylcholine during RSI intubation. In our initial review we searched all databases until March 2000, followed by an update to June 2007. This latest update included searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 2), MEDLINE (1966 to February Week 2 2015), and EMBASE (1988 to February 14 2015 ) for randomized controlled trials (RCTs) or controlled clinical trials (CCTs) relating to the use of rocuronium and succinylcholine. We included foreign language journals and handsearched the references of identified studies for additional citations. We included any RCT or CCT that reported intubating conditions in comparing the use of rocuronium and succinylcholine for RSI or modified RSI in any age group or clinical setting. The dose of rocuronium was at least 0.6 mg/kg and succinylcholine was at least 1 mg/kg. Two authors (EN and DT) independently extracted data and assessed methodological quality for the 'Risk of bias' tables. We combined the outcomes in Review Manager 5 using a risk ratio (RR) with a random-effects model. The previous update (2008) had identified 53 potential studies and included 37 combined for meta-analysis. In this latest update we identified a further 13 studies and included 11, summarizing the results of 50 trials including 4151 participants. Overall, succinylcholine was superior to rocuronium for achieving excellent intubating conditions: RR 0.86 (95% confidence interval (CI) 0.81 to 0.92; n = 4151) and clinically acceptable intubation conditions (RR 0.97, 95% CI 0.95 to 0.99; n = 3992, 48 trials). A high incidence of detection bias amongst the trials coupled with significant heterogeneity provides moderate-quality evidence for these conclusions, which are unchanged from the previous update. Succinylcholine was more likely to produce excellent intubating conditions when using thiopental as the induction agent: RR 0.81 (95% CI: 0.73 to 0.88; n = 2302, 28 trials). In the previous update, we had concluded that propofol was the superior induction agent with succinylcholine. There were no reported incidences of severe adverse outcomes. We found no statistical difference in intubation conditions when succinylcholine was compared to 1.2 mg/kg rocuronium; however, succinylcholine was clinically superior as it has a shorter duration of action. Succinylcholine created superior intubation conditions to rocuronium in achieving excellent and clinically acceptable intubating conditions.
Montgomery, Catharine; Fisk, John E; Newcombe, Russell; Murphy, Phillip N
2005-10-01
Recent theoretical models suggest that the central executive may not be a unified structure. The present study explored the nature of central executive deficits in ecstasy users. In study 1, 27 ecstasy users and 34 non-users were assessed using tasks to tap memory updating (computation span; letter updating) and access to long-term memory (a semantic fluency test and the Chicago Word Fluency Test). In study 2, 51 ecstasy users and 42 non-users completed tasks that assess mental set switching (number/letter and plus/minus) and inhibition (random letter generation). MANOVA revealed that ecstasy users performed worse on both tasks used to assess memory updating and on tasks to assess access to long-term memory (C- and S-letter fluency). However, notwithstanding the significant ecstasy group-related effects, indices of cocaine and cannabis use were also significantly correlated with most of the executive measures. Unexpectedly, in study 2, ecstasy users performed significantly better on the inhibition task, producing more letters than non-users. No group differences were observed on the switching tasks. Correlations between indices of ecstasy use and number of letters produced were significant. The present study provides further support for ecstasy/polydrug-related deficits in memory updating and in access to long-term memory. The surplus evident on the inhibition task should be treated with some caution, as this was limited to a single measure and has not been supported by our previous work.
Kim, Dong-Wan; Mehra, Ranee; Tan, Daniel S W; Felip, Enriqueta; Chow, Laura Q M; Camidge, D Ross; Vansteenkiste, Johan; Sharma, Sunil; De Pas, Tommaso; Riely, Gregory J; Solomon, Benjamin J; Wolf, Jürgen; Thomas, Michael; Schuler, Martin; Liu, Geoffrey; Santoro, Armando; Sutradhar, Santosh; Li, Siyu; Szczudlo, Tomasz; Yovine, Alejandro; Shaw, Alice T
2016-04-01
ALK-rearranged non-small-cell lung cancer (NSCLC) is sensitive to ALK tyrosine kinase inhibitors (ALK inhibitors) such as crizotinib, but resistance invariably develops, often with progression in the brain. Ceritinib is a more potent ALK inhibitor than crizotinib in vitro, crosses the blood-brain barrier in vivo, and shows clinical responses in patients with crizotinib-resistant disease. We aimed to assess whole-body activity of ceritinib in both ALK inhibitor-pretreated and ALK inhibitor-naive patients with ALK-rearranged NSCLC. ASCEND-1 was an open-label, phase 1 trial that recruited patients from 20 academic hospitals or cancer centres in 11 countries in Europe, North America, and Asia-Pacific. Eligible patients were aged 18 years or older with ALK-rearranged locally advanced or metastatic cancer that had progressed despite standard therapy (or for which no effective standard therapy existed), who had at least one measurable lesion at baseline. The primary objective (to determine the maximum tolerated dose) has been reported previously. This updated analysis includes all patients with ALK-rearranged NSCLC given oral ceritinib at the recommended dose of 750 mg/day in the dose-escalation and expansion phases. Here we report the secondary outcomes of overall response, duration of response, and progression-free survival, analysed in all patients who received at least one 750 mg dose of ceritinib. Exploratory analyses included retrospective analysis of intracranial activity by independent neuroradiologists, in patients with untreated or locally treated neurologically stable brain metastases at baseline. Safety was assessed in all patients who received at least one dose of ceritinib. This study is no longer recruiting patients; however, treatment and follow-up are ongoing. This study is registered with ClinicalTrials.gov, number NCT01283516. Between Jan 24, 2011, and July 31, 2013, 255 patients were enrolled and received at least one dose of ceritinib 750 mg/day, of whom 246 had ALK-rearranged NSCLC. At data cutoff (April 14, 2014), median follow-up was 11·1 months (IQR 6·7-15·2) and 147 (60%) patients had discontinued treatment, 98 (40%) as a result of disease progression. An overall response was reported in 60 (72% [95% CI 61-82]) of 83 ALK inhibitor-naive patients and 92 (56% [49-64]) of 163 ALK inhibitor-pretreated patients. Median duration of response was 17·0 months (95% CI 11·3-non-estimable [NE]) in ALK inhibitor-naive patients and 8·3 months (6·8-9·7) in ALK inhibitor-pretreated patients. Median progression-free survival was 18·4 months (95% CI 11·1-NE) in ALK inhibitor-naive patients and 6·9 months (5·6-8·7) in ALK inhibitor-pretreated patients. Of 94 patients with retrospectively confirmed brain metastases and at least one post-baseline MRI or CT tumour assessment, intracranial disease control was reported in 15 (79% [95% CI 54-94]) of 19 ALK inhibitor-naive patients and in 49 (65% [54-76]) of 75 ALK inhibitor-pretreated patients. Of these 94 patients, 11 had measurable brain lesions and no previous radiotherapy to the brain, six of whom achieved a partial intracranial response. Serious adverse events were recorded in 117 (48%) of 246 patients. The most common grade 3-4 laboratory abnormalities were increased alanine aminotransferase (73 [30%] patients) and increased aspartate aminotransferase (25 [10%]). The most common grade 3-4 non-laboratory adverse events were diarrhoea and nausea, both of which occurred in 15 (6%) patients. Two on-treatment deaths during the study were deemed to be related to study drug by the investigators, one due to interstitial lung disease and one as a result of multiorgan failure that occurred in the context of infection and ischaemic hepatitis. The durable whole-body responses reported, together with the intracranial activity, support a clinical benefit for treatment with ceritinib in patients with ALK-rearranged NSCLC who have received crizotinib, or as an alternative to crizotinib. A confirmatory phase 2 clinical trial is ongoing to assess ceritinib activity in patients with ALK-rearranged NSCLC and brain or leptomeningeal metastases. Novartis Pharmaceuticals Corporation. Copyright © 2016 Elsevier Ltd. All rights reserved.
Meissner, Axel; Limmroth, Volker
2016-07-01
Fingolimod (FTY720) has been approved as the first oral representative of the class of sphingosine-1-phosphate (S1P) receptor modulators for the treatment of relapsing-remitting multiple sclerosis (MS). Besides inducing vaso-relaxation, fingolimod can also influence electrical conduction in the myocardium and vascular endothelium by having a transient negative chronotropic effect on the sinus node. Cardiac safety and tolerability of fingolimod in the cardiac sense were reviewed by analysing the data collected from the FREEDOMS and TRANSFORMS studies -both relevant studies for marketing authorisation, from their extension studies, as well as the clinical data collected from a practice-related MS patient cohort with cardiovascular risk factors and corresponding co-medication (FIRST study). The safety analyses on file gave no indication of any increased cardiovascular risk. The 2-3mmHg increase in blood pressure observed after the first dose of fingolimod has no therapeutic consequences. The first dose of 0.5mg fingolimod resulted in an average decrease in heart rate of 7-8beats/min. The onset of effect occurred approximately 1-2h after the first dose and the nadir was reached after approximately 4-5h. This negative chronotropic effect returned to normal after internalisation of the S1P1 receptors on maintenance therapy. There were no indications that patients with cardiac risk factors required closer observation beyond the monitoring recommended by the EMA following the first dose of fingolimod. Case study observations from the routine clinical setting show that patients accept this method of monitoring, which they assess as being a positive aspect of attentive medical care and concern. Copyright © 2016 Elsevier B.V. All rights reserved.
Dose-response relationships in multifunctional food design: assembling the evidence.
Aggett, Peter J
2012-03-01
Demonstrating single and multiple functions attributable to foods or specific food components is a challenge. The International Life Sciences Institute Europe co-ordinated EU concerted actions, Functional Food Science in Europe (FUFOSE) and the Process for the Assessment of Scientific Support for Claims on Food (PASSCLAIM), respectively, addressed the soundness of the evidence and its coherence with a mechanistic schema comprising valid markers of exposure, intermediate and final outcomes and the quality and integrity of the evidence overall. Demonstrating causality often relies on randomized controlled trials (RCTs). However, in public health and biomedical science there is concern about the suitability of RCTs as sole standards of evidence-based approaches. Alternative and complementary approaches using updated Hill's viewpoints for appraising the evidence can be used in conjunction with evidence-based mechanistic reasoning and the quality criteria proposed in FUFOSE and PASSCLAIM to design studies and to assemble evidence exploring single or multiple benefits from food components and foods.
Vitamin K supplementation for cystic fibrosis.
Jagannath, Vanitha A; Thaker, Vidhu; Chang, Anne B; Price, Amy I
2017-08-22
Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. This is an updated version of the review. To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 30 January 2017. Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing). Two authors independently screened papers, extracted trial details and assessed their risk of bias. Two trials (total of 32 participants) each lasting one month were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial in children (aged 8 to 18 years); and the other (with an older cohort) had a cross-over design comparing supplements to no treatment, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin levels to the normal range after one month of daily supplementation with 1 mg of vitamin K. Evidence from randomised controlled trials on the benefits of routine vitamin K supplementation for people with CF is currently weak and limited to two small trials of short duration. However, no harm was found and until further evidence is available, the present recommendations should be adhered to.
Recommendations for kidney disease guideline updating: a report by the KDIGO Methods Committee
Uhlig, Katrin; Berns, Jeffrey S.; Carville, Serena; Chan, Wiley; Cheung, Michael; Guyatt, Gordon H.; Hart, Allyson; Lewis, Sandra Zelman; Tonelli, Marcello; Webster, Angela C.; Wilt, Timothy J.; Kasiske, Bertram L.
2017-01-01
Updating rather than de novo guideline development now accounts for the majority of guideline activities for many guideline development organizations, including Kidney Disease: Improving Global Outcomes (KDIGO), an international kidney disease guideline development entity that has produced guidelines on kidney diseases since 2008. Increasingly, guideline developers are moving away from updating at fixed intervals in favor of more flexible approaches that use periodic expert assessment of guideline currency (with or without an updated systematic review) to determine the need for updating. Determining the need for guideline updating in an efficient, transparent, and timely manner is challenging, and updating of systematic reviews and guidelines is labor intensive. Ideally, guidelines should be updated dynamically when new evidence indicates a need for a substantive change in the guideline based on a priori criteria. This dynamic updating (sometimes referred to as a living guideline model) can be facilitated with the use of integrated electronic platforms that allow updating of specific recommendations. This report summarizes consensus-based recommendations from a panel of guideline methodology professionals on how to keep KDIGO guidelines up to date. PMID:26994574
ERIC Educational Resources Information Center
Christensen, Laurene L.; Lazarus, Sheryl S.; Crone, Melissa; Thurlow, Martha L.
2008-01-01
This document presents an update of a 2006 report from NCEO tracking and analyzing state policies on assessment participation and accommodations since 1992. The purpose of the current analysis is to update information on these policies that was last reported by NCEO in 2006 (based on 2005 data). In this analysis, policies from all 50 states, plus…
[Interpretation of the updates of NCCN 2017 version 1.0 guideline for colorectal cancer].
Chen, Gong
2017-01-25
The NCCN has recently released its 2017 version 1.0 guideline for colorectal cancer. There are several updates from this new version guideline which are believed to change the current clinical practice. Update one, low-dose aspirin is recommended for patients with colorectal cancer after colectomy for secondary chemoprevention. Update two, biological agents are removed from the neoadjuvant treatment regimen for resectable metastatic colorectal cancer (mCRC). This update is based on lack of evidence to support benefits of biological agents including bevacizumab and cetuximab in the neoadjuvant setting. Both technical criteria and prognostic information should be considered for decision-making. Currently biological agents may not be excluded from the neoadjuvant setting for patients with resectable but poor prognostic disease. Update three, panitumumab and cetuximab combination therapy is only recommended for left-sided tumors in the first line therapy. The location of the primary tumor can be both prognostic and predictive in response to EGFR inhibitors in metastatic colorectal cancer. Cetuximab and panitumumab confer little benefit to patients with metastatic colorectal cancer in the primary tumor originated on the right side. On the other hand, EGFR inhibitors provide significant benefit compared with bevacizumab-containing therapy or chemotherapy alone for patients with left primary tumor. Update four, PD-1 immune checkpoint inhibitors including pembrolizumab or nivolumab are recommended as treatment options in patients with metastatic deficient mismatch repair (dMMR) colorectal cancer in second- or third-line therapy. dMMR tumors contain thousands of mutations, which can encode mutant proteins with the potential to be recognized and targeted by the immune system. It has therefore been hypothesized that dMMR tumors may be sensitive to PD-1 inhibitors.
Ansell, Stephen M
2011-10-01
Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 8,500 new patients annually and representing approximately 11% of all lymphomas in the United States. HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups under the designation of classical HL. An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence are used to optimize therapy for patients with limited or advanced stage disease. Initial therapy for HL patients is based on the histology of the disease, the anatomical stage, and the presence of poor prognostic features. Patients with early stage disease are treated with combined modality strategies using abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. High-dose chemotherapy (HDCT) followed by an autologous stem-cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, palliative chemotherapy, nonmyeloablative allogeneic transplant, or participation in a clinical trial should be considered. 2011 Wiley-Liss, Inc.
NASA Astrophysics Data System (ADS)
Vignion-Dewalle, Anne-Sophie; Betrouni, Nacim; Tylcz, Jean-Baptiste; Vermandel, Maximilien; Mortier, Laurent; Mordon, Serge
2015-05-01
Photodynamic therapy (PDT) is an emerging treatment modality for various diseases, especially for cancer therapy. Although high efficacy is demonstrated for PDT using standardized protocols in nonhyperkeratotic actinic keratoses, alternative light doses expected to increase efficiency, to reduce adverse effects or to expand the use of PDT, are still being evaluated and refined. We propose a comparison of the three most common light doses in the treatment of actinic keratosis with 5-aminolevulinic acid PDT through mathematical modeling. The proposed model is based on an iterative procedure that involves determination of the local fluence rate, updating of the local optical properties, and estimation of the local damage induced by the therapy. This model was applied on a simplified skin sample model including an actinic keratosis lesion, with three different light doses (red light dose, 37 J/cm2, 75 mW/cm2, 500 s blue light dose, 10 J/cm2, 10 mW/cm2, 1000 s and daylight dose, 9000 s). Results analysis shows that the three studied light doses, although all efficient, lead to variable local damage. Defining reference damage enables the nonoptimal parameters for the current light doses to be refined and the treatment to be more suitable.
Acute myeloid leukemia: 2013 update on risk-stratification and management.
Estey, Elihu H
2013-04-01
Acute myeloid leukemia (AML) results from accumulation of abnormal blasts in the marrow. These cells interfere with normal hematopoiesis, can escape into the peripheral blood, and infiltrate CSF and lung. It is likely that many different mutations, epigenetic aberrations, or abnormalities in micro RNA expression can produce the same morphologic disease with these differences responsible for the very variable response to therapy, which is AMLs principal feature. This rests on demonstration that the marrow or blood has > 20% blasts of myeloid lineage. Blast lineage is assessed by multiparameter flow cytometry, with CD33 and CD13 being surface markers typically expressed by myeloid blasts. It should be realized that clinical/prognostic considerations, not the blast % per se, should be the main factor determining how a patient is treated. Two features determine risk: the probability of treatment-related mortality (TRM) and, more important, even in patients aged >75 with Zubrod performance status 1, the probability of resistance to standard therapy despite not incurring TRM. The chief predictor of resistance is cytogenetics, with a monosomal karyotype (MK) denoting the disease is essentially incurable with standard therapy even if followed by a standard allogeneic transplant (HCT). The most common cytogentic finding is a normal karyotype(NK) and those of such patients with an NPM1 mutation but no FLT3 internal tandem duplication (ITD), or with a CEBPA mutation, have a prognosis similar to that of patients with the most favorable cytogenetics (inv 16 or t[8;21]) (60-70% cure rate). In contrast, NK patients with a FLT3 ITD have only a 30-40% chance of cure even after HCT. Accordingly analyses of NPM1, FLT3, and CEBPA should be part of routine evaluation, much as is cytogenetics. Risk is best assessed considering several variables simultaneously rather than, for example, only age. Increasing evidence indicates that other mutations and abnormalities in microRNA (miRNA) expression also affect resistance as do post treatment factors, in particular the presence of minimal residual disease. These newer mutations and MRD are discussed in this update. Patients with inv (16) or t(8;21) or who are NPM1+/FLT3ITD-can receive standard therapy (daunorubicin + cytarabine) and should not receive HCT in first CR. It seems likely that use of a daily daunorubicin dose of 90 mg/m(2) will further improve outcome in these patients. There appears no reason to use doses of cytarabine > 1 g/m(2) (for example bid X 6 days), as opposed to the more commonly used 3 g/m(2) . Patients with an unfavorable karyotype (particularly MK) are unlikely to benefit from standard therapy (even with dose escalation) and are thus prime candidates for clinical trials of new drugs or new approaches to HCT; the latter should be done in first CR. Patients with intermediate prognoses (for example NK and NPM and FLT3ITD negative) should also receive HCT in first CR and can plausibly receive either investigational or standard induction therapy, with the same prognostic information about standard therapy leading one patient to choose the standard and another an investigational option. This update discusses results with newer agents: quizartinib and crenolanib, gemtuzumab ozogamicin, clofarabine and cladribine, azacitidine and decitabine, volasertib, and means to prevent relapse after allogeneic transplant. The diagnosis of AML essentially is made as it was in 2012. Thus this review will emphasize new developments in risk stratification and treatment using as references many papers published in 2012. Copyright © 2013 Wiley Periodicals, Inc.
NASA Astrophysics Data System (ADS)
Syrakov, Dimiter; Veleva, Blagorodka; Georgievs, Emilia; Prodanova, Maria; Slavov, Kiril; Kolarova, Maria
2014-05-01
The development of the Bulgarian Emergency Response System (BERS) for short term forecast in case of accidental radioactive releases to the atmosphere has been started in the mid 1990's [1]. BERS comprises of two main parts - operational and accidental, for two regions 'Europe' and 'Northern Hemisphere'. The operational part runs automatically since 2001 using the 72 hours meteorological forecast from DWD Global model, resolution in space of 1.5o and in time - 12 hours. For specified Nuclear power plants (NPPs), 3 days trajectories are calculated and presented on NIMH's specialized Web-site (http://info.meteo.bg/ews/). The accidental part is applied when radioactive releases are reported or in case of emergency exercises. BERS is based on numerical weather forecast information and long-range dispersion model accounting for the transport, dispersion, and radioactive transformations of pollutants. The core of the accidental part of the system is the Eulerian 3D dispersion model EMAP calculating concentration and deposition fields [2]. The system is upgraded with a 'dose calculation module' for estimation of the prognostic dose fields of 31 important radioactive gaseous and aerosol pollutants. The prognostic doses significant for the early stage of a nuclear accident are calculated as follows: the effective doses from external irradiation (air submersion + ground shinning); effective dose from inhalation; summarized effective dose and absorbed thyroid dose [3]. The output is given as 12, 24, 36, 48, 60 and 72 hours prognostic dose fields according the updated meteorology. The BERS was upgraded to simulate the dispersion of nuclear materials from Fukushima NPP [4], and results were presented in NIMH web-site. In addition BERS took part in the respective ENSEMBLE exercises to model 131I and 137Cs in Fukushima source term. In case of governmental request for expertise BERS was applied for environmental impact assessment of hypothetical accidental transboundary radioactive pollution. The consequences were estimated based on the worst emission scenario for the existing basic reactor type, selection of real meteorological forecast conditions, favoring the direct transport of the contaminated air masses to the territory of the country in consideration. In the present work BERS is used to estimate the worst case accidental scenario impact from a possible new unit of Paks Nuclear Power Plant, Hungary over the territory of Bulgaria. 1. D.Syrakov, M.Prodanova, 1998, Atmospheric Environment, 32 (24), 4367-4375. 2. D. Syrakov, M. Prodanova, K. Slavov, Inernationsal J. Environment and Pollution, 20, 1-6 (2003) 286-296. 3. D. Syrakov, B. Veleva, M. Prodanova, T. Popova, M. Kolarova, Journal of Environmental Radioactivity 100 (2009) 151-156. 4. D.Syrakov, M Prodanova, J. Intern. Sci. Publ.: Ecology & Safety Vol. 6 Part 1 (2011) 94-102. www.scientific-publications.net.
Energy Savings Potential and RD&D Opportunities for Commercial Building Appliances (2015 Update)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Goetzler, William; Guernsey, Matt; Foley, Kevin
The Department of Energy commissioned a technology characterization and assessment of appliances used in commercial buildings for cooking, cleaning, water heating, and other end-uses. The primary objectives of this study were to document the energy consumed by commercial appliances and identify research, development, and demonstration opportunities to improve energy efficiency in each end-use. This report serves as an update to a 2009 report of the same name by incorporating updated data and sources where possible and updating the available technology options that provide opportunities for efficiency improvements.
Acellular vaccines for preventing whooping cough in children.
Zhang, Linjie; Prietsch, Sílvio O M; Axelsson, Inge; Halperin, Scott A
2014-09-17
Routine use of whole-cell pertussis (wP) vaccines was suspended in some countries in the 1970s and 1980s because of concerns about adverse effects. Following this action, there was a resurgence of whooping cough. Acellular pertussis (aP) vaccines, containing purified or recombinant Bordetella pertussis (B. pertussis) antigens, were developed in the hope that they would be as effective, but less reactogenic than the whole-cell vaccines. This is an update of a Cochrane review first published in 1999, and previously updated in 2012. In this update, we included no new studies. To assess the efficacy and safety of acellular pertussis vaccines in children and to compare them with the whole-cell vaccines. We searched CENTRAL (2013, Issue 12), MEDLINE (1950 to January week 2, 2014), EMBASE (1974 to January 2014), Biosis Previews (2009 to January 2014) and CINAHL (2009 to January 2014). We selected double-blind randomised efficacy and safety trials of aP vaccines in children up to six years old, with active follow-up of participants and laboratory verification of pertussis cases. Two review authors independently extracted data and assessed the risk of bias in the studies. Differences in trial design precluded a meta-analysis of the efficacy data. We pooled the safety data from individual trials using a random-effects meta-analysis model. We included six efficacy trials with a total of 46,283 participants and 52 safety trials with a total of 136,541 participants. Most of the safety trials did not report the methods for random sequence generation, allocation concealment and blinding, which made it difficult to assess the risk of bias in the studies. The efficacy of multi-component (≥ three) vaccines varied from 84% to 85% in preventing typical whooping cough (characterised by 21 or more consecutive days of paroxysmal cough with confirmation of B. pertussis infection by culture, appropriate serology or contact with a household member who has culture-confirmed pertussis), and from 71% to 78% in preventing mild pertussis disease (characterised by seven or more consecutive days of cough with confirmation of B. pertussis infection by culture or appropriate serology). In contrast, the efficacy of one- and two-component vaccines varied from 59% to 78% against typical whooping cough and from 41% to 58% against mild pertussis disease. Multi-component acellular vaccines are more effective than low-efficacy whole-cell vaccines, but may be less effective than the highest-efficacy whole-cell vaccines. Most systemic and local adverse events were significantly less common with aP vaccines than with wP vaccines for the primary series as well as for the booster dose. Multi-component (≥ three) aP vaccines are effective in preventing whooping cough in children. Multi-component aP vaccines have higher efficacy than low-efficacy wP vaccines, but they may be less efficacious than the highest-efficacy wP vaccines. Acellular vaccines have fewer adverse effects than whole-cell vaccines for the primary series as well as for booster doses.
A review of immunogenicity and tolerability of live attenuated Hepatitis A vaccine in children.
Rao, Sameer; Mao, J S; Motlekar, Salman; Fangcheng, Zhuang; Kadhe, Ganesh
2016-12-01
Changing epidemiology of Hepatitis A virus (HAV) has led to an increased susceptibility of adolescents and adults to the infection. Vaccination can remarkably reduce the incidence and associated morbidity of HAV infection. This review is focused on the safety and efficacy of H2 strain derived live attenuated Hepatitis A vaccine. We found the vaccine to be highly immunogenic with minimal or negligible safety issues. Moreover, a single dose of live attenuated vaccine persists a long term immune response and can be a preferred option for developing countries. In 2014, Indian Academy of Paediatrics (IAP) also updated their recommendations for H2 vaccine as a single dose as against the previous 2 dose schedule. A focused approach to include the vaccine in national immunization program should be explored.
Meek, M E; Boobis, A; Cote, I; Dellarco, V; Fotakis, G; Munn, S; Seed, J; Vickers, C
2014-01-01
The World Health Organization/International Programme on Chemical Safety mode of action/human relevance framework has been updated to reflect the experience acquired in its application and extend its utility to emerging areas in toxicity testing and non-testing methods. The underlying principles have not changed, but the framework's scope has been extended to enable integration of information at different levels of biological organization and reflect evolving experience in a much broader range of potential applications. Mode of action/species concordance analysis can also inform hypothesis-based data generation and research priorities in support of risk assessment. The modified framework is incorporated within a roadmap, with feedback loops encouraging continuous refinement of fit-for-purpose testing strategies and risk assessment. Important in this construct is consideration of dose-response relationships and species concordance analysis in weight of evidence. The modified Bradford Hill considerations have been updated and additionally articulated to reflect increasing experience in application for cases where the toxicological outcome of chemical exposure is known. The modified framework can be used as originally intended, where the toxicological effects of chemical exposure are known, or in hypothesizing effects resulting from chemical exposure, using information on putative key events in established modes of action from appropriate in vitro or in silico systems and other lines of evidence. This modified mode of action framework and accompanying roadmap and case examples are expected to contribute to improving transparency in explicitly addressing weight of evidence considerations in mode of action/species concordance analysis based on both conventional data sources and evolving methods. Copyright © 2013 John Wiley & Sons, Ltd. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.
Walking through doorways causes forgetting: environmental integration.
Radvansky, Gabriel A; Tamplin, Andrea K; Krawietz, Sabine A
2010-12-01
Memory for objects declines when people move from one location to another (the location updating effect). However, it is unclear whether this is attributable to event model updating or to task demands. The focus here was on the degree of integration for probed-for information with the experienced environment. In prior research, the probes were verbal labels of visual objects. Experiment 1 assessed whether this was a consequence of an item-probe mismatch, as with transfer-appropriate processing. Visual probes were used to better coordinate what was seen with the nature of the memory probe. In Experiment 2, people received additional word pairs to remember, which were less well integrated with the environment, to assess whether the probed-for information needed to be well integrated. The results showed location updating effects in both cases. These data are consistent with an event cognition view that mental updating of a dynamic event disrupts memory.
Brown, J E; Alfonso, B; Avila, R; Beresford, N A; Copplestone, D; Hosseini, A
2016-03-01
A new version of the ERICA Tool (version 1.2) was released in November 2014; this constitutes the first major update of the Tool since release in 2007. The key features of the update are presented in this article. Of particular note are new transfer databases extracted from an international compilation of concentration ratios (CRwo-media) and the modification of 'extrapolation' approaches used to select transfer data in cases where information is not available. Bayesian updating approaches have been used in some cases to draw on relevant information that would otherwise have been excluded in the process of deriving CRwo-media statistics. All of these efforts have in turn led to the requirement to update Environmental Media Concentration Limits (EMCLs) used in Tier 1 assessments. Some of the significant changes with regard to EMCLs are highlighted. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
An Update of the Nation's Long-Term Strategic Needs for NASA's Aeronautics Test Facilities
NASA Technical Reports Server (NTRS)
Anton, Philip S.; Raman, Raj; Osburg, Jan; Kallimani, James G.
2009-01-01
The National Aeronautics and Space Administration's (NASA's) major wind tunnel (WT), propulsion test (PT), and simulation facilities exist to serve NASA's and the nation's aeronautics needs. RAND Corporation researchers conducted a prior study of these facilities from 2002 to 2003, identifying (1) NASA's continuing ability to serve national needs, (2) which facilities appear strategically important from an engineering perspective given the vehicle classes the nation investigates and produces, and (3) management challenges and issues. This documented briefing (DB) is the final report from a new, one-year study (conducted from September 2006 through January 2008), partially updating the prior assessment. The study focuses on updating the list of facilities in the prior study that were deemed to be strategically important (again, from an engineering perspective) in serving those needs. This update also adds a new assessment of national needs for six major aeronautics simulators at NASA and lists those deemed strategically important.
McKenzie, Y A; Thompson, J; Gulia, P; Lomer, M C E
2016-10-01
Probiotics are often taken by individuals with irritable bowel syndrome (IBS). Which products are effective is unclear, despite an increasing research base. This project will systematically review which strain- and dose- specific probiotics can be recommended to adults with IBS to improve symptoms and quality of life (QoL). It is part of a broader systematic review to update British Dietetic Association guidelines for the dietary management of IBS in adults. CINAHL, Cochrane, Embase, Medline, Scopus and Web of Science were searched for systematic reviews (SRs) of randomised controlled trial (RCT)s recruiting adults with IBS comparing probiotic intervention with placebo. AMSTAR, risk of bias and diet bias tools were used to appraise methodological quality. Symptom and QoL data were appraised to develop probiotic-specific evidence statements on clinically meaningful and marginal outcomes in various settings, graded clinical practice recommendations and practical considerations. Nine systematic reviews and 35 RCTs were included (3406 participants) using 29 dose-specific probiotic formulations. None of the RCTs were at low risk of bias. Twelve out of 29 probiotics (41%) showed no symptom or QoL benefits. Evidence indicated that no strain or dose specific probiotic was consistently effective to improve any IBS symptoms or QoL. Two general clinical practice recommendations were made. Symptom outcomes for dose-specific probiotics were heterogeneous. Specific probiotic recommendations for IBS management in adults were not possible at this time. More data from high-quality RCTs treating specific symptom profiles are needed to support probiotic therapy in the management of IBS. © 2016 The British Dietetic Association Ltd.
Pantelis, Evaggelos; Papagiannis, Panagiotis; Anagnostopoulos, Giorgos; Baltas, Dimos
2013-12-01
To determine the relative dose rate distribution around the new (125)I brachytherapy source IsoSeed I25.S17plus and report results in a form suitable for clinical use. Results for the new source are also compared to corresponding results for other commercially available (125)I sources of similar design. Monte Carlo simulations were performed using the MCNP5 v.1.6 general purpose code. The model of the new source was prepared from information provided by the manufacturer and verified by imaging a sample of ten non-radioactive sources. Corresponding simulations were also performed for the 6711 (125)I brachytherapy source, using updated geometric information presented recently in the literature. The uncertainty of the dose distribution around the new source, as well as the dosimetric quantities derived from it according to the Task Group 43 formalism, were determined from the standard error of the mean of simulations for a sample of fifty source models. These source models were prepared by randomly selecting values of geometric parameters from uniform distributions defined by manufacturer stated tolerances. Results are presented in the form of the quantities defined in the update of the Task Group 43 report, as well as a relative dose rate table in Cartesian coordinates. The dose rate distribution of the new source is comparable to that of sources of similar design (IsoSeed I25.S17, Oncoseed 6711, SelectSeed 130.002, Advantage IAI-125A, I-Seed AgX100, Thinseed 9011). Noticeable differences were observed only for the IsoSeed I25.S06 and Best 2301 sources.
Memory-updating abrogates extinction of learned immunosuppression.
Hadamitzky, Martin; Bösche, Katharina; Wirth, Timo; Buck, Benjamin; Beetz, Oliver; Christians, Uwe; Schniedewind, Björn; Lückemann, Laura; Güntürkün, Onur; Engler, Harald; Schedlowski, Manfred
2016-02-01
When memories are recalled, they enter a transient labile phase in which they can be impaired or enhanced followed by a new stabilization process termed reconsolidation. It is unknown, however, whether reconsolidation is restricted to neurocognitive processes such as fear memories or can be extended to peripheral physiological functions as well. Here, we show in a paradigm of behaviorally conditioned taste aversion in rats memory-updating in learned immunosuppression. The administration of sub-therapeutic doses of the immunosuppressant cyclosporin A together with the conditioned stimulus (CS/saccharin) during retrieval blocked extinction of conditioned taste aversion and learned suppression of T cell cytokine (interleukin-2; interferon-γ) production. This conditioned immunosuppression is of clinical relevance since it significantly prolonged the survival time of heterotopically transplanted heart allografts in rats. Collectively, these findings demonstrate that memories can be updated on both neural and behavioral levels as well as on the level of peripheral physiological systems such as immune functioning. Copyright © 2015 Elsevier Inc. All rights reserved.
The reference individual of radiation protection
DOE Office of Scientific and Technical Information (OSTI.GOV)
Eckerman, K.F.; Cristy, M.
1995-12-31
The 70-kg {open_quotes}standard man{close_quotes} representing a typical Western adult male has been used in physiological models since at least the 1920s. In 1949 at the Chalk River conference, health physicists from the U.S., UK, and Canada agreed on the concept of a standard man to facilitate comparison of internal dose estimates. The 70-kg standard man included specifications of the masses of 25 organs and tissues, total body content of 15 elements, total water intake and output, water content of the body, and some anatomical and physiological data for the respiratory and gastrointestinal tracts. In 1959, in its Publication 2{sup 2}more » on permissible doses for internal radiation the International Commission on Radiological Protection (ICRP) modified standard man. In 1963 the ICRP established a task group to revise and extend the standard man concept. The name was changed later to Reference Man and the task group`s work was published in 1975 as ICRP Publication 23{sup 3}. Publication 23 similar to Publication 2, updates and documents the sources of the data. Data on women, children, and fetuses were also collected, where available, but these data were limited primarily to anatomical data and only a few reference values were established for these groups. Information assembled during the course of the effort on the Reference Man report was used at Oak Ridge National Laboratory (ORNL) to construct a mathematical representation of the body (a phantom) that was suitable for use with Monte Carlo methods in the calculation of organ doses. That effort was undertaken to improve estimates of dose from photon-emitting radionuclides residing within organs, so-called internal emitters. The phantom, although updated throughout the years, remains today as the basis for organ dose estimates in nuclear medicine and radiation protection and underlies the radiation risk data derived from the epidemiologic studies of the atomic bomb survivors of Hiroshima and Nagasaki.« less
Calvo-Lerma, Joaquim; Hulst, Jessie M; Asseiceira, Inês; Claes, Ine; Garriga, Maria; Colombo, Carla; Fornés, Victoria; Woodcock, Sandra; Martins, Tiago; Boon, Mieke; Ruperto, Mar; Walet, Sylvia; Speziali, Chiara; Witters, Peter; Masip, Etna; Barreto, Celeste; de Boeck, Kris; Ribes-Koninckx, Carmen
2017-07-01
The New European guidelines have established the most updated recommendations on nutrition and pancreatic enzyme replacement therapy (PERT) in CF. In the context of MyCyFAPP project - a European study in children with CF aimed at developing specific tools for improvement of self-management - the objective of the current study was to assess nutritional status, daily energy and macronutrient intake, and PERT dosing with reference to these new guidelines. Cross sectional study in paediatric patients with CF from 6 European centres. SD-scores for weight-for-age (WFA), height-for-age (HFA) and body mass index-for-age (BMI) were obtained. Through a specific 4-day food and enzyme-dose record, energy and macronutrients intake and PERT-use (LU/g lipids) were automatically calculated by the MyCyFAPP system. Comparisons were made using linear regression models. The lowest quartiles for BMI and HFA were between 0 and -1SD in all the centres with no significant differences, and 33.5% of the patients had a SD-score <0 for all three parameters. The minimum energy intake recommendation was not reached by 40% of the children and mean nutrients intake values were 14%, 51% and 34% of the total energy for protein, carbohydrates and lipids respectively. When assessed per centre, reported PERT doses were in the recommended range in only 13.8% to 46.6% of the patients; from 5.6% up to 82.7% of children were above the recommended doses and 3.3% to 75% were below. Among the 6 centres, a large variability and inconsistency with new guidelines on nutrition and PERT-use was found. Our findings document the lack of a general criterion to adjust PERT and suggest the potential benefit of educational and self-managerial tools to ensure adherence to therapies, both for clinical staff and families. They will be taken into account when developing these new tools during the next stages of MyCyFAPP Project. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
Alpha emitter radium-223 and survival in metastatic prostate cancer.
Parker, C; Nilsson, S; Heinrich, D; Helle, S I; O'Sullivan, J M; Fosså, S D; Chodacki, A; Wiechno, P; Logue, J; Seke, M; Widmark, A; Johannessen, D C; Hoskin, P; Bottomley, D; James, N D; Solberg, A; Syndikus, I; Kliment, J; Wedel, S; Boehmer, S; Dall'Oglio, M; Franzén, L; Coleman, R; Vogelzang, N J; O'Bryan-Tear, C G; Staudacher, K; Garcia-Vargas, J; Shan, M; Bruland, Ø S; Sartor, O
2013-07-18
Radium-223 dichloride (radium-223), an alpha emitter, selectively targets bone metastases with alpha particles. We assessed the efficacy and safety of radium-223 as compared with placebo, in addition to the best standard of care, in men with castration-resistant prostate cancer and bone metastases. In our phase 3, randomized, double-blind, placebo-controlled study, we randomly assigned 921 patients who had received, were not eligible to receive, or declined docetaxel, in a 2:1 ratio, to receive six injections of radium-223 (at a dose of 50 kBq per kilogram of body weight intravenously) or matching placebo; one injection was administered every 4 weeks. In addition, all patients received the best standard of care. The primary end point was overall survival. The main secondary efficacy end points included time to the first symptomatic skeletal event and various biochemical end points. A prespecified interim analysis, conducted when 314 deaths had occurred, assessed the effect of radium-223 versus placebo on survival. An updated analysis, when 528 deaths had occurred, was performed before crossover from placebo to radium-223. At the interim analysis, which involved 809 patients, radium-223, as compared with placebo, significantly improved overall survival (median, 14.0 months vs. 11.2 months; hazard ratio, 0.70; 95% confidence interval [CI], 0.55 to 0.88; two-sided P=0.002). The updated analysis involving 921 patients confirmed the radium-223 survival benefit (median, 14.9 months vs. 11.3 months; hazard ratio, 0.70; 95% CI, 0.58 to 0.83; P<0.001). Assessments of all main secondary efficacy end points also showed a benefit of radium-233 as compared with placebo. Radium-223 was associated with low myelosuppression rates and fewer adverse events. In this study, which was terminated for efficacy at the prespecified interim analysis, radium-223 improved overall survival. (Funded by Algeta and Bayer HealthCare Pharmaceuticals; ALSYMPCA ClinicalTrials.gov number, NCT00699751.).
Tsuji, Joyce S; Alexander, Dominik D; Perez, Vanessa; Mink, Pamela J
2014-03-20
While exposures to high levels of arsenic in drinking water are associated with excess cancer risk (e.g., skin, bladder, and lung), exposures at lower levels (e.g., <100-200 µg/L) generally are not. Lack of significant associations may result from methodological issues (e.g., inadequate statistical power, exposure misclassification), or a different dose-response relationship at low exposures, possibly associated with a toxicological mode of action that requires a sufficient dose for increased tumor formation. The extent to which bladder cancer risk for low-level arsenic exposure can be statistically measured by epidemiological studies was examined using an updated meta-analysis of bladder cancer risk with data from two new publications. The summary relative risk estimate (SRRE) for all nine studies was elevated slightly, but not significantly (1.07; 95% confidence interval [CI]: 0.95-1.21, p-Heterogeneity [p-H]=0.543). The SRRE among never smokers was 0.85 (95% CI: 0.66-1.08, p-H=0.915), whereas the SRRE was positive and more heterogeneous among ever smokers (1.18; 95% CI: 0.97-1.44, p-H=0.034). The SRRE was statistically significantly lower than relative risks predicted for never smokers in the United States based on linear extrapolation of risks from higher doses in southwest Taiwan to arsenic water exposures >10 µg/L for more than one-third of a lifetime. By contrast, for all study subjects, relative risks predicted for one-half of lifetime exposure to 50 µg/L were just above the upper 95% CI on the SRRE. Thus, results from low-exposure studies, particularly for never smokers, were statistically inconsistent with predicted risk based on high-dose extrapolation. Additional studies that better characterize tobacco use and stratify analyses of arsenic and bladder cancer by smoking status are necessary to further examine risks of arsenic exposure for smokers. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
Curtis H. Flather; Michael S. Knowles; Jason McNees
2008-01-01
This technical document supports the Forest Service's requirement to assess the status of renewable natural resources as mandated by the Forest and Rangeland Renewable Resources Planning Act of 1974. It updates past reports on the trends and geographic patterns of species formally listed as threatened or endangered under the Endangered Species Act of 1973. We...
Forest area and conditions: a 2010 update of Chapter 16 of the Southern Forest Resource Assessment
Andrew J. Hartsell; Roger C. Conner
2013-01-01
This report updates the findings of Chapter 16 of the Southern Forest Resource Assessment (Wear and Greis 2002), based on 2010 report year data. Analysis focuses on changes in the Southâs forest resources since 1999 using annual inventory, mapped-plot design data available for the first time for all 13 Southern States (excluding west Oklahoma and west Texas). The...
Casetta, Brunilda; Videla, Alejandro J; Bardach, Ariel; Morello, Paola; Soto, Natalie; Lee, Kelly; Camacho, Paul Anthony; Hermoza Moquillaza, Rocío Victoria; Ciapponi, Agustín
2017-11-07
Previous evidence linked low socioeconomic status with higher smoking prevalence. Our objective was to assess the strength of this association in the world population, updating a previous work. Systematic review and meta-analysis of observational studies. Subgroup analyses included continents, WHO regions, country mortality levels, gender, age, risk of bias, and study publication date. Independent reviewers selected studies, assessed potential bias and extracted data. We searched MEDLINE, EMBASE, CENTRAL, SOCINDEX, AFRICAN INDEX MEDICUS, and LILACS, and other sources from 1989 to 2013 reporting direct measurements of income and current cigarette smoking. We retrieved 13,583 articles and included 93 for meta-analysis. Median smoking prevalence was 17.8% (range 3-70%). Lower income was consistently associated with higher smoking prevalence (odds ratio [OR]: 1.45; 95% confidence interval [CI]: 1.35-1.56). This association was statistically significant in the subgroup analysis by WHO regions for the Americas (OR: 1.54; 95% CI: 1.42-1.68), South East Asia (OR: 1.53; 95% CI: 1.10-2.00), Europe (OR: 1.45; 95% CI: 1.29-1.63), and Western Pacific (OR: 1.32; 95% CI: 1.02-1.72), and in studies conducted during 1990s (OR: 1.42; 95% CI: 1.24-1.62) and 2000s (OR: 1.48; 95%CI: 1.30-1.64). Likewise, it was noted in low-mortality countries (OR: 1.48; 95% CI: 1.37-1.60) and for both genders. Prevalence was highest in the lowest income levels compared to the middle (OR: 1.69; 95% CI: 1.49-1.92), followed by the middle level compared to the highest (OR: 1.31; 95% CI: 1.20-1.43). Our results show that current cigarette smoking was significantly associated with lower income worldwide and across subgroups, suggesting a dose-response relationship. This unique updated systematic review shows a consistent inverse dose-response relationship between cigarette smoking and income level, present among most geographical areas and country characteristics. Public health measures should take into account this potential inequity and consider special efforts directed to disadvantaged populations. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
77 FR 52316 - U.S. Air Force Academy Board of Visitors; Notice of Meeting
Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-29
...; Superintendent's Update; Character Update; USAFA Sexual Assault Prevention and Response Program; Critical Thinking Assessment Tool; and the Diversity in the Dean's Faculty brief. In accordance with 5 U.S.C. 552b...
Antibiotics for acute pyelonephritis in children.
Strohmeier, Yvonne; Hodson, Elisabeth M; Willis, Narelle S; Webster, Angela C; Craig, Jonathan C
2014-07-28
Urinary tract infection (UTI) is one of the most common bacterial infections in infants. The most severe form of UTI is acute pyelonephritis, which results in significant acute morbidity and may cause permanent kidney damage. There remains uncertainty regarding the optimum antibiotic regimen, route of administration and duration of treatment. This is an update of a review that was first published in 2003 and updated in 2005 and 2007. To evaluate the benefits and harms of antibiotics used to treat children with acute pyelonephritis. The aspects of therapy considered were 1) different antibiotics, 2) different dosing regimens of the same antibiotic, 3) different duration of treatment, and 4) different routes of administration. We searched the Cochrane Renal Group's Specialised Register, CENTRAL, MEDLINE, EMBASE, reference lists of articles and conference proceedings without language restriction to 10 April 2014. Randomised and quasi-randomised controlled trials comparing different antibiotic agents, routes, frequencies or durations of therapy in children aged 0 to 18 years with proven UTI and acute pyelonephritis were selected. Four authors independently assessed study quality and extracted data. Statistical analyses were performed using the random-effects model and the results expressed as risk ratio (RR) for dichotomous outcomes or mean difference (MD) for continuous data with 95% confidence intervals (CI). This updated review included 27 studies (4452 children). This update included evidence from three new studies, and following re-evaluation, a previously excluded study was included because it now met our inclusion criteria.Risk of bias was assessed as low for sequence generation (12 studies), allocation concealment (six studies), blinding of outcome assessors (17 studies), incomplete outcome reporting (19 studies) and selective outcome reporting (13 studies). No study was blinded for participants or investigators. The 27 included studies evaluated 12 different comparisons. No significant differences were found in duration of fever (2 studies, 808 children: MD 2.05 hours, 95% CI -0.84 to 4.94), persistent UTI at 72 hours after commencing therapy (2 studies, 542 children: RR 1.10, 95% CI 0.07 to 17.41) or persistent kidney damage at six to 12 months (4 studies, 943 children: RR 0.82, 95% CI 0.59 to 1.12) between oral antibiotic therapy (10 to 14 days) and intravenous (IV) therapy (3 days) followed by oral therapy (10 days). Similarly, no significant differences in persistent bacteriuria at the end of treatment (4 studies, 305 children: RR 0.78, 95% CI 0.24 to 2.55) or persistent kidney damage (4 studies, 726 children: RR 1.01, 95% CI 0.80 to 1.29) were found between IV therapy (three to four days) followed by oral therapy and IV therapy (seven to 14 days). No significant differences in efficacy were found between daily and thrice daily administration of aminoglycosides (1 study, 179 children, persistent clinical symptoms at three days: RR 1.98, 95% CI 0.37 to 10.53). Adverse events were mild and uncommon and rarely resulted in discontinuation of treatment. This updated review increases the body of evidence that oral antibiotics alone are as effective as a short course (three to four days) of IV antibiotics followed by oral therapy for a total treatment duration of 10 to 14 days for the treatment of acute pyelonephritis in children. When IV antibiotics are given, a short course (two to four days) of IV therapy followed by oral therapy is as effective as a longer course (seven to 10 days) of IV therapy. If IV therapy with aminoglycosides is chosen, single daily dosing is safe and effective. Insufficient data are available to extrapolate these findings to children aged less than one month of age or to children with dilating vesicoureteric reflux (grades III-V). Further studies are required to determine the optimal total duration of antibiotic therapy required for acute pyelonephritis.
Dependence of the Martian radiation environment on atmospheric depth: Modeling and measurement
NASA Astrophysics Data System (ADS)
Guo, Jingnan; Slaba, Tony C.; Zeitlin, Cary; Wimmer-Schweingruber, Robert F.; Badavi, Francis F.; Böhm, Eckart; Böttcher, Stephan; Brinza, David E.; Ehresmann, Bent; Hassler, Donald M.; Matthiä, Daniel; Rafkin, Scot
2017-02-01
The energetic particle environment on the Martian surface is influenced by solar and heliospheric modulation and changes in the local atmospheric pressure (or column depth). The Radiation Assessment Detector (RAD) on board the Mars Science Laboratory rover Curiosity on the surface of Mars has been measuring this effect for over four Earth years (about two Martian years). The anticorrelation between the recorded surface Galactic Cosmic Ray-induced dose rates and pressure changes has been investigated by Rafkin et al. (2014) and the long-term solar modulation has also been empirically analyzed and modeled by Guo et al. (2015). This paper employs the newly updated HZETRN2015 code to model the Martian atmospheric shielding effect on the accumulated dose rates and the change of this effect under different solar modulation and atmospheric conditions. The modeled results are compared with the most up-to-date (from 14 August 2012 to 29 June 2016) observations of the RAD instrument on the surface of Mars. Both model and measurements agree reasonably well and show the atmospheric shielding effect under weak solar modulation conditions and the decline of this effect as solar modulation becomes stronger. This result is important for better risk estimations of future human explorations to Mars under different heliospheric and Martian atmospheric conditions.
Updated mortality analysis of radiation workers at Rocketdyne (Atomics International), 1948-2008
DOE Office of Scientific and Technical Information (OSTI.GOV)
Boice, John; Cohen, Sarah; Mumma, Michael
Updated analyses of mortality data are presented on 5,801 radiation workers, including 2,232 monitored for radionuclide intakes, and 41,169 non-radiation workers employed 1948-1999 at Rocketdyne (Atomics International). The worker population is unique in that lifetime occupational doses from all places of employment were sought and incorporated into the analyses. Further, radiation doses from intakes of 14 different radionuclides were calculated for 16 organs or tissues using biokinetic models of the International Commission on Radiation Protection (ICRP). The mean dose from external radiation was 13.5 mSv (maximum 1 Sv), and the mean lung dose from external and internal radiation combined wasmore » 19.0 mSv (maximum 3.6 Sv). An additional nine years of follow-up, from December 31,1999 through 2008, increased the person-years of observation by 21.7% to 196,674 (mean 33.9 years) and the number of cancer deaths by 50% to 684. Analyses included comparisons with the general population and the computation of standardized mortality ratios (SMRs), and internal comparisons using proportional hazards models. All cancers taken together (SMR 0.88; 95% CI 0.81-0.95), lung cancer (SMR 0.87; 95% CI 0.76-1.00) and leukemia other than chronic lymphocytic leukemia (CLL) (SMR 1.04; 95% 0.67-1.53) were not significantly elevated. Cox regression analyses revealed no significant dose-response trends for any cancer. For all cancers excluding leukemia, the relative risk (RR) at 100 mSv was estimated as 0.98 (95% CI 0.82-1.17) and for all leukemia other than CLL it was 1.06 (95% CI 0.50-2.23). Uranium was the primary radionuclide contributing to internal exposures, but significant increases in lung and kidney disease were not seen. The extended follow-up re-enforces the findings in the previous study in failing to observe a detectable increase in cancer deaths associated with radiation, but strong conclusions still cannot be drawn because of small numbers and relatively low career doses. Larger combined studies of early workers in the United States following similar methodologies are warranted to refine and clarify radiation risks following protracted exposures.« less
Recommended vaccinations for asplenic and hyposplenic adult patients.
Bonanni, Paolo; Grazzini, Maddalena; Niccolai, Giuditta; Paolini, Diana; Varone, Ornella; Bartoloni, Alessandro; Bartalesi, Filippo; Santini, Maria Grazia; Baretti, Simonetta; Bonito, Carlo; Zini, Paola; Mechi, Maria Teresa; Niccolini, Fabrizio; Magistri, Lea; Pulci, Maria Beatrice; Boccalini, Sara; Bechini, Angela
2017-02-01
Asplenic or hyposplenic (AH) individuals are particularly vulnerable to invasive infections caused by encapsulated bacteria. Such infections have often a sudden onset and a fulminant course. Infectious diseases (IDs) incidence in AH subjects can be reduced by preventive measures such as vaccination. The aim of our work is to provide updated recommendations on prevention of infectious diseases in AH adult patients, and to supply a useful and practical tool to healthcare workers for the management of these subjects, in hospital setting and in outpatients consultation. A systematic literature review on evidence based measures for the prevention of IDs in adult AH patients was performed in 2015. Updated recommendations on available vaccines were consequently provided. Vaccinations against S. pneumoniae, N. meningitidis, H. influenzae type b and influenza virus are strongly recommended and should be administered at least 2 weeks before surgery in elective cases or at least 2 weeks after the surgical intervention in emergency cases. In subjects without evidence of immunity, 2 doses of live attenuated vaccines against measles-mumps-rubella and varicella should be administered 4-8 weeks apart from each other; a booster dose of tetanus, diphtheria and pertussis vaccine should be administered also to subjects fully vaccinated, and a 3-dose primary vaccination series is recommended in AH subjects with unknown or incomplete vaccination series (as in healthy people). Evidence based prevention data support the above recommendations to reduce the risk of infection in AH individuals.
Recommended vaccinations for asplenic and hyposplenic adult patients
Grazzini, Maddalena; Niccolai, Giuditta; Paolini, Diana; Varone, Ornella; Bartoloni, Alessandro; Bartalesi, Filippo; Santini, Maria Grazia; Baretti, Simonetta; Bonito, Carlo; Zini, Paola; Mechi, Maria Teresa; Niccolini, Fabrizio; Magistri, Lea; Pulci, Maria Beatrice; Bechini, Angela
2017-01-01
ABSTRACT Asplenic or hyposplenic (AH) individuals are particularly vulnerable to invasive infections caused by encapsulated bacteria. Such infections have often a sudden onset and a fulminant course. Infectious diseases (IDs) incidence in AH subjects can be reduced by preventive measures such as vaccination. The aim of our work is to provide updated recommendations on prevention of infectious diseases in AH adult patients, and to supply a useful and practical tool to healthcare workers for the management of these subjects, in hospital setting and in outpatients consultation. A systematic literature review on evidence based measures for the prevention of IDs in adult AH patients was performed in 2015. Updated recommendations on available vaccines were consequently provided. Vaccinations against S. pneumoniae, N. meningitidis, H. influenzae type b and influenza virus are strongly recommended and should be administered at least 2 weeks before surgery in elective cases or at least 2 weeks after the surgical intervention in emergency cases. In subjects without evidence of immunity, 2 doses of live attenuated vaccines against measles-mumps-rubella and varicella should be administered 4–8 weeks apart from each other; a booster dose of tetanus, diphtheria and pertussis vaccine should be administered also to subjects fully vaccinated, and a 3-dose primary vaccination series is recommended in AH subjects with unknown or incomplete vaccination series (as in healthy people). Evidence based prevention data support the above recommendations to reduce the risk of infection in AH individuals. PMID:27929751
Potential Oil Production from Coastal Plain of Arctic National Wildlife Refuge: Updated Assessment
2000-01-01
The Energy Information Administration (EIA) received a letter (dated March 10, 2000) from Senator Frank H. Murkowski as Chairman of the Senate Committee on Energy and Natural Resources requesting an EIA Service Report with plausible scenarios for the Arctic National Wildlife Refuge (ANWR) supply development consistent with the most recent U.S. Geological Survey resource assessments. This service report is prepared in response to the request of Senator Murkowski. It focuses on the ANWR coastal plain, a region currently restricted from exploration and development, and updates EIA's 1987 ANWR assessment.
A biokinetic model for systemic nickel
Melo, Dunstana; Leggett, Richard Wayne
2017-01-01
The International Commission on Radiological Protection (ICRP) is updating its suite of reference biokinetic models for internally deposited radionuclides. This paper reviews data for nickel and proposes an updated biokinetic model for systemic (absorbed) nickel in adult humans for use in radiation protection. Compared with the ICRP s current model for nickel, the proposed model is based on a larger set of observations of the behavior of nickel in human subjects and laboratory animals and provides a more realistic description of the paths of movement of nickel in the body. For the two most important radioisotopes of nickel, 59Ni andmore » 63Ni, the proposed model yields substantially lower dose estimates per unit of activity reaching blood than the current ICRP model.« less
A biokinetic model for systemic nickel
DOE Office of Scientific and Technical Information (OSTI.GOV)
Melo, Dunstana; Leggett, Richard Wayne
The International Commission on Radiological Protection (ICRP) is updating its suite of reference biokinetic models for internally deposited radionuclides. This paper reviews data for nickel and proposes an updated biokinetic model for systemic (absorbed) nickel in adult humans for use in radiation protection. Compared with the ICRP s current model for nickel, the proposed model is based on a larger set of observations of the behavior of nickel in human subjects and laboratory animals and provides a more realistic description of the paths of movement of nickel in the body. For the two most important radioisotopes of nickel, 59Ni andmore » 63Ni, the proposed model yields substantially lower dose estimates per unit of activity reaching blood than the current ICRP model.« less
An industry update: the latest developments in Therapeutic delivery.
Steinbach, Oliver C
2018-05-01
The present industry update covers the period of 1 January-31 January 2018, with information sourced from company press releases, regulatory and patent agencies as well as scientific literature. Several public offerings (Gecko, Insmed), licensing (Foresee) and commercialization agreements (Alnylam, Collegium Pharmaceutical) as well as patent filings (Elute) continue to prove the sustained investments in the drug delivery market. In increasing numbers, more effective ways to deliver the active ingredient to the right location and the right dose through devices (Boehringer Ingelheim's Respimat, Medtronics' SynchroMedII) or improved compound properties through formulation (Aquestive Therapeutics' PharmFilm, Noven Pharmaceuticals' transdermal patch) are reaching the market. Furthering biologics and gene delivery (Avacta, Bracco) proves that novel drug delivery technologies are successfully addressing more challenging drug formats.
Automatically updating predictive modeling workflows support decision-making in drug design.
Muegge, Ingo; Bentzien, Jörg; Mukherjee, Prasenjit; Hughes, Robert O
2016-09-01
Using predictive models for early decision-making in drug discovery has become standard practice. We suggest that model building needs to be automated with minimum input and low technical maintenance requirements. Models perform best when tailored to answering specific compound optimization related questions. If qualitative answers are required, 2-bin classification models are preferred. Integrating predictive modeling results with structural information stimulates better decision making. For in silico models supporting rapid structure-activity relationship cycles the performance deteriorates within weeks. Frequent automated updates of predictive models ensure best predictions. Consensus between multiple modeling approaches increases the prediction confidence. Combining qualified and nonqualified data optimally uses all available information. Dose predictions provide a holistic alternative to multiple individual property predictions for reaching complex decisions.
Lung Cancer Screening with Low-Dose Computed Tomography for Primary Care Providers
Richards, Thomas B.; White, Mary C.; Caraballo, Ralph S.
2015-01-01
This review provides an update on lung cancer screening with low-dose computed tomography (LDCT) and its implications for primary care providers. One of the unique features of lung cancer screening is the potential complexity in patient management if an LDCT scan reveals a small pulmonary nodule. Additional tests, consultation with multiple specialists, and follow-up evaluations may be needed to evaluate whether lung cancer is present. Primary care providers should know the resources available in their communities for lung cancer screening with LDCT and smoking cessation, and the key points to be addressed in informed and shared decision-making discussions with patients. PMID:24830610
Curtis H. Flather; Michael S. Knowles; Stephen J. Brady
2009-01-01
This technical document supports the Forest Service's requirement to assess the status of renewable natural resources as mandated by the Forest and Rangeland Renewable Resources Planning Act of 1974 (RPA). It updates past reports on national and regional trends in population and harvest estimates for species classified as big game and small game. The trends...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yoo, Jun Soo; Choi, Yong Joon; Smith, Curtis Lee
2016-09-01
This document addresses two subjects involved with the RELAP-7 Software Verification and Validation Plan (SVVP): (i) the principles and plan to assure the independence of RELAP-7 assessment through the code development process, and (ii) the work performed to establish the RELAP-7 assessment plan, i.e., the assessment strategy, literature review, and identification of RELAP-7 requirements. Then, the Requirements Traceability Matrices (RTMs) proposed in previous document (INL-EXT-15-36684) are updated. These RTMs provide an efficient way to evaluate the RELAP-7 development status as well as the maturity of RELAP-7 assessment through the development process.
ERIC Educational Resources Information Center
Florida State Univ., Tallahassee. Learning Systems Inst.
This publication contains the first two of three training workshop manuals designed to be used in conducting an update of the Indonesian Education and Human Resources Sector Assessment. Workshop I covers the basic concepts, skills, and methods needed to design subsector updates and develop a draft plan for update activities. Workshops II and III…
Assessing the motor carrier industry and its segments : current and prospective issues, 2006.
DOT National Transportation Integrated Search
2006-04-01
This report updates the Motor Carrier Industry Profile: An Update 2004-2005 to reflect recent changes in the motor carrier industry. This document relies heavily on industry trade journals, company annual reports and other industry surveys as sources...
Highly efficient model updating for structural condition assessment of large-scale bridges.
DOT National Transportation Integrated Search
2015-02-01
For eciently updating models of large-scale structures, the response surface (RS) method based on radial basis : functions (RBFs) is proposed to model the input-output relationship of structures. The key issues for applying : the proposed method a...
40 CFR 68.36 - Review and update.
Code of Federal Regulations, 2010 CFR
2010-07-01
... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Hazard Assessment § 68.36 Review and update. (a) The owner or operator shall... processes, quantities stored or handled, or any other aspect of the stationary source might reasonably be...
Update on the use of trilostane in dogs.
Lemetayer, Julie; Blois, Shauna
2018-04-01
Many articles published in the past few years have contributed to a better understanding of the use of trilostane in dogs. Trilostane is a competitive inhibitor of 3β-hydroxysteroid dehydrogenase, the enzyme essential for synthesis of cortisol and all other steroids. Trilostane is reported to be safe and effective in the treatment of pituitary-dependent hyperadrenocorticism (HAC), adrenal-dependent HAC, and alopecia X. While trilostane controls most of the clinical signs associated with HAC, abnormalities such as hypertension, hypercoagulability, and proteinuria may persist despite therapy. Because the duration of cortisol suppression after a dose of trilostane is often less than 12 hours, many dogs with HAC could benefit from low dose trilostane treatment every 12 hours. Many controversies regarding trilostane still exist. This review provides a comprehensive commentary on trilostane's indications, mode of action, dose, monitoring, efficacy, and adverse effects.
A review of immunogenicity and tolerability of live attenuated Hepatitis A vaccine in children
Rao, Sameer; Mao, J. S.; Motlekar, Salman; Fangcheng, Zhuang; Kadhe, Ganesh
2016-01-01
ABSTRACT Changing epidemiology of Hepatitis A virus (HAV) has led to an increased susceptibility of adolescents and adults to the infection. Vaccination can remarkably reduce the incidence and associated morbidity of HAV infection. This review is focused on the safety and efficacy of H2 strain derived live attenuated Hepatitis A vaccine. We found the vaccine to be highly immunogenic with minimal or negligible safety issues. Moreover, a single dose of live attenuated vaccine persists a long term immune response and can be a preferred option for developing countries. In 2014, Indian Academy of Paediatrics (IAP) also updated their recommendations for H2 vaccine as a single dose as against the previous 2 dose schedule. A focused approach to include the vaccine in national immunization program should be explored. PMID:27532370
Advances in In Vitro and In Silico Tools for Toxicokinetic Dose ...
Recent advances in vitro assays, in silico tools, and systems biology approaches provide opportunities for refined mechanistic understanding for chemical safety assessment that will ultimately lead to reduced reliance on animal-based methods. With the U.S. commercial chemical landscape encompassing thousands of chemicals with limited data, safety assessment strategies that reliably predict in vivo systemic exposures and subsequent in vivo effects efficiently are a priority. Quantitative in vitro-in vivo extrapolation (QIVIVE) is a methodology that facilitates the explicit and quantitative application of in vitro experimental data and in silico modeling to predict in vivo system behaviors and can be applied to predict chemical toxicokinetics, toxicodynamics and also population variability. Tiered strategies that incorporate sufficient information to reliably inform the relevant decision context will facilitate acceptance of these alternative data streams for safety assessments. This abstract does not necessarily reflect U.S. EPA policy. This talk will provide an update to an international audience on the state of science being conducted within the EPA’s Office of Research and Development to develop and refine approaches that estimate internal chemical concentrations following a given exposure, known as toxicokinetics. Toxicokinetic approaches hold great potential in their ability to link in vitro activities or toxicities identified during high-throughput screen
Liew, Danny; Park, Hye-Jin; Ko, Su-Kyoung
2009-10-01
In Korea, the treatment of hypertension and dyslipidemia constitutes an important strategy for the prevention of cardiovascular disease (CVD). This study sought to investigate the cost-effectiveness (from the Korean health care system perspective) of prescribing a proprietary formulation single-tablet fixed-dose combination of amlodipine and atorvastatin (at weighted mean doses of 5 mg and 10.25 mg, respectively) to all eligible patients aged > or = 45 years for the primary prevention of CVD (ie, coronary heart disease and ischemic stroke) in Korea, compared with currently observed patterns of blood-pressure and lipid-lowering medication prescription and use. A Markov model was developed with 4 health states: alive without CVD, alive with CVD, dead from CVD, and dead from non-CVD causes. The model population comprised 244 Koreans aged >/=45 years from the 2005 Korean National Health and Nutrition Examination Survey (KNHNES) without a history of myocardial infarction (MI) or stroke who met current criteria for both blood-pressure and lipid-lowering treatment. From a 2008 baseline, follow-up was simulated for 40 years. Cardiovascular risk was estimated for each subject individually using a multivariate, Asian population-specific equation, and updated with ongoing cycles. Decision analysis compared the effects of prescribing the fixed-dose combination to all subjects versus currently observed patterns of treatment. Data regarding the blood-pressure and lipid-lowering efficacies of combination therapy were drawn from the Respond trial. Costs of the fixed-dose combination tablet and CVD were sourced from pharmaceutical pricing lists and Korean Health Insurance Review and Assessment Services estimates, respectively. Utility values for CVD were obtained from a large Korean utility study. In the model, of the 244 treatment-eligible subjects, 126 (51.6%) and 13 (5.3%) were taking blood-pressure and lipid-lowering therapy, respectively. Use of single-tablet fixed-dose combination amlodipine and atorvastatin by all subjects was associated with estimated incremental cost-effectiveness ratios of 7,773,063 Korean won (KRW) per quality-adjusted life-year gained and 10,378,230 KRW per overall life-year gained (1300 KRW approximately US $1). Sensitivity and uncertainty analyses indicated these results to be robust. In this model, based on data from the 2005 KNHNES, hypertension and dyslipidemia were undertreated among Koreans aged > or = 45 years without a history of MI or stroke. The administration of single-tablet fixed-dose combination amlodipine and atorvastatin to all such individuals was likely to represent a cost-effective means of preventing first-onset CVD (ie, coronary heart disease and ischemic stroke) in this subgroup, compared with current patterns of treatment.
Update on the biological effects of ionizing radiation, relative dose factors and radiation hygiene.
White, Stuart C; Mallya, S M
2012-03-01
Diagnostic imaging is an indispensable part of contemporary medical and dental practice. Over the last few decades there has been a dramatic increase in the use of ionizing radiation for diagnostic imaging. The carcinogenic effects of high-dose exposure are well known. Does diagnostic radiation rarely cause cancer? We don't know but we should act as if it does. Accordingly, dentists should select patients wisely - only make radiographs when there is patient-specific reason to believe there is a reasonable expectation the radiograph will offer unique information influencing diagnosis or treatment. Low-dose examinations should be made: intraoral imaging - use fast film or digital sensors, thyroid collars, rectangular collimation; panoramic and lateral cephalometric imaging - use digital systems or rare-earth film screen combinations; and cone beam computed tomography - use low-dose machines, restrict field size to region of interest, reduce mA and length of exposure arc as appropriate. © 2012 Australian Dental Association.
Risk Assessment in the 21st Century - Conference Abstract ...
For the past ~50 years, risk assessment depended almost exclusively on animal testing for hazard identification and dose-response assessment. Originally sound and effective, with increasing dependence on chemical tools and the number of chemicals in commerce, this traditional approach is no longer sufficient. This presentation provides an update on current progress in achieving the goals outlined in the NAS reports: “Toxicology Testing in the 21st Century”, “Exposure Science in the 21st Century”, and most recently, “Using 21st Century Science to Improve Risk-Related Evaluations.” The presentation highlights many of the advances lead by the EPA. Topics covered include the evolution of the mode of action concept into the chemically agnostic, adverse outcome pathway (AOP), a systems-based data framework that facilitates integration of modifiable factors (e.g., genetic variation, life stages), and an understanding of networks, and mixtures. Further, the EDSP pivot is used to illustrate how AOPs drive development of predictive models for risk assessment based on assembly of high throughput assays representing AOP key elements. The birth of computational exposure science, capable of large-scale predictive exposure models, is reviewed. Although still in its infancy, development of non-targeted analysis to begin addressing the exposome is presented, as is the systems-based AEP that integrates exposure, toxicokinetics and AOPs into a comprehensive framework
DOT National Transportation Integrated Search
2011-09-30
The Intelligent Transportation Systems in Federal Public Lands report details the state of ITS deployment across all federal land management agencies (FLMAs) in 2011, updating a Volpe Center report completed in 2005. An assessment of the types ...
Update of correlations between cone penetration and boring log data : technical summary report.
DOT National Transportation Integrated Search
2009-12-01
The main objective of this project is to update the correlations that are currently used to interpret : Cone Penetration Test (CPT) data for engineering design purposes and to assess the reliability of : using CPT data to predict soil shear strength....
Research Productivity in Counseling Psychology: An Update. Conference
ERIC Educational Resources Information Center
Buboltz, Walter C., Jr.; Jenkins, Steve M.; Thomas, Adrian; Lindley, Lori D.; Schwartz, Jonathan P.; Loveland, James M.
2005-01-01
This article is an update and review of institutional research productivity in counseling psychology. Institutional research productivity is assessed by totaling credits for articles published from 1993 to 2002 in the following journals: "Journal of Counseling Psychology," "The Counseling Psychologist," "Journal of Consulting and Clinical…
GRAPPA 2015 Research and Education Project Reports.
Mease, Philip J; Helliwell, Philip S; Boehncke, Wolf-Henning; Coates, Laura C; FitzGerald, Oliver; Gladman, Dafna D; Deodhar, Atul A; Callis Duffin, Kristina
2016-05-01
At the 2015 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), attendees were presented with brief updates on several ongoing initiatives, including educational projects. Updates were presented on the treatment recommendations project, the development of simple criteria to identify inflammatory musculoskeletal disease, new patient/physician Delphi exercises, and BIODAM (identifying biomarkers that predict progressive structural joint damage). The publication committee also gave a report. Herein we summarize those project updates.
NASA Astrophysics Data System (ADS)
Makarevich, K. O.; Minenko, V. F.; Verenich, K. A.; Kuten, S. A.
2016-05-01
This work is dedicated to modeling dental radiographic examinations to assess the absorbed doses of patients and effective doses. For simulating X-ray spectra, the TASMIP empirical model is used. Doses are assessed on the basis of the Monte Carlo method by using MCNP code for voxel phantoms of ICRP. The results of the assessment of doses to individual organs and effective doses for different types of dental examinations and features of X-ray tube are presented.
Gating based on internal/external signals with dynamic correlation updates.
Wu, Huanmei; Zhao, Qingya; Berbeco, Ross I; Nishioka, Seiko; Shirato, Hiroki; Jiang, Steve B
2008-12-21
Precise localization of mobile tumor positions in real time is critical to the success of gated radiotherapy. Tumor positions are usually derived from either internal or external surrogates. Fluoroscopic gating based on internal surrogates, such as implanted fiducial markers, is accurate however requiring a large amount of imaging dose. Gating based on external surrogates, such as patient abdominal surface motion, is non-invasive however less accurate due to the uncertainty in the correlation between tumor location and external surrogates. To address these complications, we propose to investigate an approach based on hybrid gating with dynamic internal/external correlation updates. In this approach, the external signal is acquired at high frequency (such as 30 Hz) while the internal signal is sparsely acquired (such as 0.5 Hz or less). The internal signal is used to validate and update the internal/external correlation during treatment. Tumor positions are derived from the external signal based on the newly updated correlation. Two dynamic correlation updating algorithms are introduced. One is based on the motion amplitude and the other is based on the motion phase. Nine patients with synchronized internal/external motion signals are simulated retrospectively to evaluate the effectiveness of hybrid gating. The influences of different clinical conditions on hybrid gating, such as the size of gating windows, the optimal timing for internal signal acquisition and the acquisition frequency are investigated. The results demonstrate that dynamically updating the internal/external correlation in or around the gating window will reduce false positive with relatively diminished treatment efficiency. This improvement will benefit patients with mobile tumors, especially greater for early stage lung cancers, for which the tumors are less attached or freely floating in the lung.
Individual Radiation Protection Monitoring in the Marshall Islands: Rongelap Atoll (2002-2004)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hamilton, T F; Kehl, S; Hickman, D
2006-01-17
The United States Department of Energy (U.S. DOE) has recently implemented a series of strategic initiatives to address long-term radiological surveillance needs at former U.S. nuclear test sites in the Marshall Islands. The plan is to engage local atoll communities in developing shared responsibilities for implementing radiation protection monitoring programs for resettled and resettling populations in the northern Marshall Islands. Using the pooled resources of the U.S. DOE and local atoll governments, individual radiological surveillance programs have been developed in whole body counting and plutonium urinalysis in order to accurately assess radiation doses resulting from the ingestion and uptake ofmore » fallout radionuclides contained in locally grown foods. Permanent whole body counting facilities have been established at three separate locations in the Marshall Islands including Rongelap Atoll (Figure 1). These facilities are operated and maintained by Marshallese technicians with scientists from the Lawrence Livermore National Laboratory (LLNL) providing on-going technical support services. Bioassay samples are collected under controlled conditions and analyzed for plutonium isotopes at the Center for Accelerator Mass Spectrometry at LLNL using state-of-the art measurement technologies. We also conduct an on-going environmental monitoring and characterization program at selected sites in the northern Marshall Islands. The aim of the environmental program is to determine the level and distribution of important fallout radionuclides in soil, water and local foods with a view towards providing more accurate and updated dose assessments, incorporating knowledge of the unique behaviors and exposure pathways of fallout radionuclides in coral atoll ecosystems. These scientific studies have also been essential in helping guide the development of remedial options used in support of island resettlement. Together, the individual and environmental radiological surveillance programs are helping meet the informational needs of the U.S. DOE and the Republic of the Marshall Islands. Our updated environmental assessments provide a strong scientific basis for predicting future change in exposure conditions especially in relation to changes in lifestyle, diet and/or land-use patterns. This information has important implications in addressing questions about existing (and future) radiological conditions on the islands, in determining as well as the implementation, cost and effectiveness of potential intervention options, and in general policy support considerations. Perhaps most importantly, the recently established individual radiological surveillance programs provide affected atoll communities with an unprecedented level of radiation protection monitoring where, for the first time, local resources are being made available to monitor resettled and resettling populations on a continuous basis. As a hard copy supplement to Marshall Islands Program website (http://eed.llnl.gov/mi/), this document provides an overview of the individual radiation protection monitoring program established for resettlement workers living on Rongelap Island along with a full disclosure of all verified measurement data (2002-2004). Readers are advised that an additional feature of the associated web site is a provision where users are able calculate and track doses delivered to volunteers (de-identified information only) participating the Marshall Islands Radiological Surveillance Program.« less
Individual Radiation Protection Monitoring in the Marshall Islands: Enewetak Atoll (2002-2004)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hamilton, T F; Kehl, S; Hickman, D
2006-01-17
The United States Department of Energy (U.S. DOE) has recently implemented a series of strategic initiatives to address long-term radiological surveillance needs at former U.S. nuclear test sites in the Marshall Islands. The plan is to engage local atoll communities in developing shared responsibilities for implementing radiation protection monitoring programs for resettled and resettling populations in the northern Marshall Islands. Using the pooled resources of the U.S. DOE and local atoll governments, individual radiological surveillance programs have been developed in whole body counting and plutonium urinalysis in order to accurately assess radiation doses resulting from the ingestion and uptake ofmore » fallout radionuclides contained in locally grown foods. Permanent whole body counting facilities have been established at three separate locations in the Marshall Islands including Enewetak Island (Figure 1) (Bell et al., 2002). These facilities are operated and maintained by Marshallese technicians with scientists from the Lawrence Livermore National Laboratory (LLNL) providing on-going technical support services. Bioassay samples are collected under controlled conditions and analyzed for plutonium isotopes at the Center for Accelerator Mass Spectrometry at LLNL using state-of-the art measurement technologies. We also conduct an on-going environmental monitoring and characterization program at selected sites in the northern Marshall Islands. The aim of the environmental program is to determine the level and distribution of important fallout radionuclides in soil, water and local foods with a view towards providing more accurate and updated dose assessments, incorporating knowledge of the unique behaviors and exposure pathways of fallout radionuclides in coral atoll ecosystems. These scientific studies have also been essential in helping guide the development of remedial options used in support of island resettlement. Together, the individual and environmental radiological surveillance programs are helping meet the informational needs of the U.S. DOE and the Republic of the Marshall Islands. Our updated environmental assessments provide a strong scientific basis for predicting future change in exposure conditions especially in relation to changes in lifestyle, diet and/or land-use patterns. This information has important implications in addressing questions about existing (and future) radiological conditions on the islands, in determining the cost and estimating the effectiveness of potential remedial measures, and in general policy support considerations. Perhaps most importantly, the recently established individual radiological surveillance programs provide affected atoll communities with an unprecedented level of radiation protection monitoring where, for the first time, local resources are being made available to monitor resettled and resettling populations on a continuous basis. As a hard copy supplement to Marshall Islands Program website (http://eed.llnl.gov/mi/), this document provides an overview of the individual radiation protection monitoring program established for the Enewetak Atoll population group along with a full disclosure of all verified measurement data (2002-2004). Readers are advised that an additional feature of the associated web site is a provision where users are able calculate and track doses delivered to volunteers (de-identified information only) participating in the Marshall Islands Radiological Surveillance Program.« less
Update On the Status of the FLUKA Monte Carlo Transport Code*
NASA Technical Reports Server (NTRS)
Ferrari, A.; Lorenzo-Sentis, M.; Roesler, S.; Smirnov, G.; Sommerer, F.; Theis, C.; Vlachoudis, V.; Carboni, M.; Mostacci, A.; Pelliccioni, M.
2006-01-01
The FLUKA Monte Carlo transport code is a well-known simulation tool in High Energy Physics. FLUKA is a dynamic tool in the sense that it is being continually updated and improved by the authors. We review the progress achieved since the last CHEP Conference on the physics models, some technical improvements to the code and some recent applications. From the point of view of the physics, improvements have been made with the extension of PEANUT to higher energies for p, n, pi, pbar/nbar and for nbars down to the lowest energies, the addition of the online capability to evolve radioactive products and get subsequent dose rates, upgrading of the treatment of EM interactions with the elimination of the need to separately prepare preprocessed files. A new coherent photon scattering model, an updated treatment of the photo-electric effect, an improved pair production model, new photon cross sections from the LLNL Cullen database have been implemented. In the field of nucleus-- nucleus interactions the electromagnetic dissociation of heavy ions has been added along with the extension of the interaction models for some nuclide pairs to energies below 100 MeV/A using the BME approach, as well as the development of an improved QMD model for intermediate energies. Both DPMJET 2.53 and 3 remain available along with rQMD 2.4 for heavy ion interactions above 100 MeV/A. Technical improvements include the ability to use parentheses in setting up the combinatorial geometry, the introduction of pre-processor directives in the input stream. a new random number generator with full 64 bit randomness, new routines for mathematical special functions (adapted from SLATEC). Finally, work is progressing on the deployment of a user-friendly GUI input interface as well as a CAD-like geometry creation and visualization tool. On the application front, FLUKA has been used to extensively evaluate the potential space radiation effects on astronauts for future deep space missions, the activation dose for beam target areas, dose calculations for radiation therapy as well as being adapted for use in the simulation of events in the ALICE detector at the LHC.
Exposure Factors Handbook Chapter 11 (Update): Intake of Meats, Dairy Products, and Fats
This update includes new information and factors needed to assess exposure to environmental agents that occur from ingestion of meats, dairy products, and fats that has become available since the Exposure Factors Handbook: 2011 Edition was released. The recommended value...
Update on BioVapor Analysis (Draft Deliberative Document)
An update is given on EPA ORD's evaluation of the BioVapor model for petroleum vapor intrusion assessment. Results from two scenarios are presented: a strong petroleum source and a weaker source. Model results for the strong source are shown to depend on biodegradation rate, oxyg...
Federal Register 2010, 2011, 2012, 2013, 2014
2011-04-27
... DEPARTMENT OF AGRICULTURE Agricultural Marketing Service [Document Number AMS-FV-10-0063] Hass... AGENCY: Agricultural Marketing Service, USDA. ACTION: Notice. This notice announces an updated... Agricultural Marketing Service at http://www.ams.usda.gov/FVPromotion . The updated computation will become...
Marin, Mona; Broder, Karen R; Temte, Jonathan L; Snider, Dixie E; Seward, Jane F
2010-05-07
This report presents new recommendations adopted in June 2009 by CDC's Advisory Committee on Immunization Practices (ACIP) regarding use of the combination measles, mumps, rubella, and varicella vaccine (MMRV, ProQuad, Merck & Co., Inc.). MMRV vaccine was licensed in the United States in September 2005 and may be used instead of measles, mumps, rubella vaccine (MMR, M-M-RII, Merck & Co., Inc.) and varicella vaccine (VARIVAX, Merck & Co., Inc.) to implement the recommended 2-dose vaccine schedule for prevention of measles, mumps, rubella, and varicella among children aged 12 months-12 years. At the time of its licensure, use of MMRV vaccine was preferred for both the first and second doses over separate injections of equivalent component vaccines (MMR vaccine and varicella vaccine), which was consistent with ACIP's 2006 general recommendations on use of combination vaccines (CDC. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2006;55;[No. RR-15]). Since July 2007, supplies of MMRV vaccine have been temporarily unavailable as a result of manufacturing constraints unrelated to efficacy or safety. MMRV vaccine is expected to be available again in the United States in May 2010. In February 2008, on the basis of preliminary data from two studies conducted postlicensure that suggested an increased risk for febrile seizures 5-12 days after vaccination among children aged 12-23 months who had received the first dose of MMRV vaccine compared with children the same age who had received the first dose of MMR vaccine and varicella vaccine administered as separate injections at the same visit, ACIP issued updated recommendations regarding MMRV vaccine use (CDC. Update: recommendations from the Advisory Committee on Immunization Practices [ACIP] regarding administration of combination MMRV vaccine. MMWR 2008;57:258-60). These updated recommendations expressed no preference for use of MMRV vaccine over separate injections of equivalent component vaccines for both the first and second doses. The final results of the two postlicensure studies indicated that among children aged 12--23 months, one additional febrile seizure occurred 5-12 days after vaccination per 2,300-2,600 children who had received the first dose of MMRV vaccine compared with children who had received the first dose of MMR vaccine and varicella vaccine administered as separate injections at the same visit. Data from postlicensure studies do not suggest that children aged 4--6 years who received the second dose of MMRV vaccine had an increased risk for febrile seizures after vaccination compared with children the same age who received MMR vaccine and varicella vaccine administered as separate injections at the same visit. In June 2009, after consideration of the postlicensure data and other evidence, ACIP adopted new recommendations regarding use of MMRV vaccine for the first and second doses and identified a personal or family (i.e., sibling or parent) history of seizure as a precaution for use of MMRV vaccine. For the first dose of measles, mumps, rubella, and varicella vaccines at age 12--47 months, either MMR vaccine and varicella vaccine or MMRV vaccine may be used. Providers who are considering administering MMRV vaccine should discuss the benefits and risks of both vaccination options with the parents or caregivers. Unless the parent or caregiver expresses a preference for MMRV vaccine, CDC recommends that MMR vaccine and varicella vaccine should be administered for the first dose in this age group. For the second dose of measles, mumps, rubella, and varicella vaccines at any age (15 months-12 years) and for the first dose at age >or=48 months, use of MMRV vaccine generally is preferred over separate injections of its equivalent component vaccines (i.e., MMR vaccine and varicella vaccine). This recommendation is consistent with ACIP's 2009 provisional general recommendations regarding use of combination vaccines (available at http://www.cdc.gov/vaccines/recs/provisional/downloads/combo-vax-Aug2009-508.pdf), which state that use of a combination vaccine generally is preferred over its equivalent component vaccines.
Mechanisms of Action of Isothiocyanates in Cancer Chemoprevention: An Update
Navarro, Sandi L.; Li, Fei; Lampe, Johanna W.
2011-01-01
Isothiocyanates, derived from glucosinolates, are thought to be responsible for the chemoprotective actions conferred by higher cruciferous vegetable intake. Evidence suggests that isothiocyanates exert their effects through a variety of distinct but interconnected signaling pathways important for inhibiting carcinogenesis, including those involved in detoxification, inflammation, apoptosis, and cell cycle and epigenetic regulation, among others. This article provides an update on the latest research on isothiocyanates and these mechanisms, and points out remaining gaps in our understanding of these events. Given the variety of ITC produced from glucosinolates, and the diverse pathways on which these compounds act, a systems biology approach, in vivo, may help to better characterize their integrated role in cancer prevention. In addition, the effects of dose, duration of exposure, and specificity of different ITC should be considered. PMID:21935537
Mechanism of action of recombinant activated factor VII: an update.
Hedner, Ulla
2006-01-01
Bleeding episodes in patients with hemophilia and inhibitors must be managed using agents that are hemostatically active in the absence of factor VIII or IX. Activated prothrombin complex concentrates have long been used in this context. However, the search for safer and more effective agents has led to the development of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark). This paper presents an update on the mechanism of action of rFVIIa, and describes how pharmacologic doses of this agent enhance thrombin production and thus contribute to the development of a stable, lysis-resistant fibrin plug at the site of vessel damage. This mechanism explains the reported efficacy of rFVIIa in a range of clinical situations characterized by impaired thrombin generation.
On the effect of updated MCNP photon cross section data on the simulated response of the HPA TLD.
Eakins, Jonathan
2009-02-01
The relative response of the new Health Protection Agency thermoluminescence dosimeter (TLD) has been calculated for Narrow Series X-ray distribution and (137)Cs photon sources using the Monte Carlo code MCNP5, and the results compared with those obtained during its design stage using the predecessor code, MCNP4c2. The results agreed at intermediate energies (approximately 0.1 MeV to (137)Cs), but differed at low energies (<0.1 MeV) by up to approximately 10%. This disparity has been ascribed to differences in the default photon interaction data used by the two codes, and derives ultimately from the effect on absorbed dose of the recent updates to the photoelectric cross sections. The sources of these data have been reviewed.
Rapid Acute Dose Assessment Using MCNP6
NASA Astrophysics Data System (ADS)
Owens, Andrew Steven
Acute radiation doses due to physical contact with a high-activity radioactive source have proven to be an occupational hazard. Multiple radiation injuries have been reported due to manipulating a radioactive source with bare hands or by placing a radioactive source inside a shirt or pants pocket. An effort to reconstruct the radiation dose must be performed to properly assess and medically manage the potential biological effects from such doses. Using the reference computational phantoms defined by the International Commission on Radiological Protection (ICRP) and the Monte Carlo N-Particle transport code (MCNP6), dose rate coefficients are calculated to assess doses for common acute doses due to beta and photon radiation sources. The research investigates doses due to having a radioactive source in either a breast pocket or pants back pocket. The dose rate coefficients are calculated for discrete energies and can be used to interpolate for any given energy of photon or beta emission. The dose rate coefficients allow for quick calculation of whole-body dose, organ dose, and/or skin dose if the source, activity, and time of exposure are known. Doses are calculated with the dose rate coefficients and compared to results from the International Atomic Energy Agency (IAEA) reports from accidents that occurred in Gilan, Iran and Yanango, Peru. Skin and organ doses calculated with the dose rate coefficients appear to agree, but there is a large discrepancy when comparing whole-body doses assessed using biodosimetry and whole-body doses assessed using the dose rate coefficients.
Auchter, Allison M.; Shumake, Jason; Gonzalez-Lima, Francisco; Monfils, Marie H.
2017-01-01
Many factors account for how well individuals extinguish conditioned fears, such as genetic variability, learning capacity and conditions under which extinction training is administered. We predicted that memory-based interventions would be more effective to reduce the reinstatement of fear in subjects genetically predisposed to display more extinction learning. We tested this hypothesis in rats genetically selected for differences in fear extinction using two strategies: (1) attenuation of fear memory using post-retrieval extinction training, and (2) pharmacological enhancement of the extinction memory after extinction training by low-dose USP methylene blue (MB). Subjects selectively bred for divergent extinction phenotypes were fear conditioned to a tone stimulus and administered either standard extinction training or retrieval + extinction. Following extinction, subjects received injections of saline or MB. Both reconsolidation updating and MB administration showed beneficial effects in preventing fear reinstatement, but differed in the groups they targeted. Reconsolidation updating showed an overall effect in reducing fear reinstatement, whereas pharmacological memory enhancement using MB was an effective strategy, but only for individuals who were responsive to extinction. PMID:28397861
Motzer, Robert J.; Hutson, Thomas E.; Tomczak, Piotr; Michaelson, M. Dror; Bukowski, Ronald M.; Oudard, Stéphane; Negrier, Sylvie; Szczylik, Cezary; Pili, Roberto; Bjarnason, Georg A.; Garcia-del-Muro, Xavier; Sosman, Jeffrey A.; Solska, Ewa; Wilding, George; Thompson, John A.; Kim, Sindy T.; Chen, Isan; Huang, Xin; Figlin, Robert A.
2009-01-01
Purpose A randomized, phase III trial demonstrated superiority of sunitinib over interferon alfa (IFN-α) in progression-free survival (primary end point) as first-line treatment for metastatic renal cell carcinoma (RCC). Final survival analyses and updated results are reported. Patients and Methods Seven hundred fifty treatment-naïve patients with metastatic clear cell RCC were randomly assigned to sunitinib 50 mg orally once daily on a 4 weeks on, 2 weeks off dosing schedule or to IFN-α 9 MU subcutaneously thrice weekly. Overall survival was compared by two-sided log-rank and Wilcoxon tests. Progression-free survival, response, and safety end points were assessed with updated follow-up. Results Median overall survival was greater in the sunitinib group than in the IFN-α group (26.4 v 21.8 months, respectively; hazard ratio [HR] = 0.821; 95% CI, 0.673 to 1.001; P = .051) per the primary analysis of unstratified log-rank test (P = .013 per unstratified Wilcoxon test). By stratified log-rank test, the HR was 0.818 (95% CI, 0.669 to 0.999; P = .049). Within the IFN-α group, 33% of patients received sunitinib, and 32% received other vascular endothelial growth factor–signaling inhibitors after discontinuation from the trial. Median progression-free survival was 11 months for sunitinib compared with 5 months for IFN-α (P < .001). Objective response rate was 47% for sunitinib compared with 12% for IFN-α (P < .001). The most commonly reported sunitinib-related grade 3 adverse events included hypertension (12%), fatigue (11%), diarrhea (9%), and hand-foot syndrome (9%). Conclusion Sunitinib demonstrates longer overall survival compared with IFN-α plus improvement in response and progression-free survival in the first-line treatment of patients with metastatic RCC. The overall survival highlights an improved prognosis in patients with RCC in the era of targeted therapy. PMID:19487381
Arnold, J Malcolm O; Howlett, Jonathan G; Dorian, Paul; Ducharme, Anique; Giannetti, Nadia; Haddad, Haissam; Heckman, George A; Ignaszewski, Andrew; Isaac, Debra; Jong, Philip; Liu, Peter; Mann, Elizabeth; McKelvie, Robert S; Moe, Gordon W; Parker, John D; Svendsen, Anna M; Tsuyuki, Ross T; O’Halloran, Kelly; Ross, Heather J; Rao, Vivek; Sequeira, Errol J; White, Michel
2007-01-01
Heart failure is common, yet it is difficult to treat. It presents in many different guises and circumstances in which therapy needs to be individualized. The Canadian Cardiovascular Society published a comprehensive set of recommendations in January 2006 on the diagnosis and management of heart failure, and the present update builds on those core recommendations. Based on feedback obtained through a national program of heart failure workshops during 2006, several topics were identified as priorities because of the challenges they pose to health care professionals. New evidence-based recommendations were developed using the structured approach for the review and assessment of evidence adopted and previously described by the Society. Specific recommendations and practical tips were written for the prevention of heart failure, the management of heart failure during intercurrent illness, the treatment of acute heart failure, and the current and future roles of biomarkers in heart failure care. Specific clinical questions that are addressed include: which patients should be identified as being at high risk of developing heart failure and which interventions should be used? What complications can occur in heart failure patients during an intercurrent illness, how should these patients be monitored and which medications may require a dose adjustment or discontinuation? What are the best therapeutic, both drug and nondrug, strategies for patients with acute heart failure? How can new biomarkers help in the treatment of heart failure, and when and how should BNP be measured in heart failure patients? The goals of the present update are to translate best evidence into practice, to apply clinical wisdom where evidence for specific strategies is weaker, and to aid physicians and other health care providers to optimally treat heart failure patients to result in a measurable impact on patient health and clinical outcomes in Canada. PMID:17245481
Arnold, J Malcom O; Howlett, Jonathan G; Dorian, Paul; Ducharme, Anique; Giannetti, Nadia; Haddad, Haissam; Heckman, George A; Ignaszewski, Andrew; Isaac, Debra; Jong, Philip; Liu, Peter; Mann, Elizabeth; McKelvie, Robert S; Moe, Gordon W; Parker, John D; Svendsen, Anna M; Tsuyuki, Ross T; O'Halloran, Kelly; Ross, Heather J; Rao, Vivek; Sequeira, Errol J; White, Michel
2007-01-01
Heart failure is common, yet it is difficult to treat. It presents in many different guises and circumstances in which therapy needs to be individualized. The Canadian Cardiovascular Society published a comprehensive set of recommendations in January 2006 on the diagnosis and management of heart failure, and the present update builds on those core recommendations. Based on feedback obtained through a national program of heart failure workshops during 2006, several topics were identified as priorities because of the challenges they pose to health care professionals. New evidence-based recommendations were developed using the structured approach for the review and assessment of evidence adopted and previously described by the Society. Specific recommendations and practical tips were written for the prevention of heart failure, the management of heart failure during intercurrent illness, the treatment of acute heart failure, and the current and future roles of biomarkers in heart failure care. Specific clinical questions that are addressed include: which patients should be identified as being at high risk of developing heart failure and which interventions should be used? What complications can occur in heart failure patients during an intercurrent illness, how should these patients be monitored and which medications may require a dose adjustment or discontinuation? What are the best therapeutic, both drug and nondrug, strategies for patients with acute heart failure? How can new biomarkers help in the treatment of heart failure, and when and how should BNP be measured in heart failure patients? The goals of the present update are to translate best evidence into practice, to apply clinical wisdom where evidence for specific strategies is weaker, and to aid physicians and other health care providers to optimally treat heart failure patients to result in a measurable impact on patient health and clinical outcomes in Canada.
FRAMEWORK FOR DEVELOPING AMBIENT WATER ...
Currently, Ambient Water Quality Criteria (AWQC) for aquatic life protection are derived according to the Guidelines for Derivation of Ambient Water Quality Criteria for the Protection of Aquatic Life and Their Uses, published in 1985. To ensure that AWQC are derived from the best available science, Office of Water assessed the need to update the Guidelines and identified issues that should be addressed in the revisions. In December 2002, EPA's Science Advisory Board concurred with EPA's assessment of the need to update the Guidelines as well as with the issues EPA identified to address. Updating the Guidelines is a Priority Strategic Action included in OST's Strategy for Water Quality Standards and Criteria (Next Priority Strategic Action #1). To revise existing methodology for deriving ambient water quality criteria for the protection of aquatic life.
Radiation protection in dental radiology - Recent advances and future directions.
Tsapaki, V
2017-12-01
Dental radiology uses X-ray technology to diagnose and design treatment of various clinical problems related to the oral cavity and surrounding tissues. As technology quickly evolves, there are numerous X-ray modalities using different tools in the attempt to best image and treat efficiently these diseases, disorders or other related clinical conditions. The reported numbers of dental X-rays, the fact that these may be under-reported in many countries and because dental X-rays are performed more on younger individuals, whose teeth and dentition are still developing, calls for increased need on radiation protection. The objectives of this paper are to report on the latest technology updates and related radiation protection issues, to present future directions and define gaps. Most of existing radiation protection national and international guidelines are more than a decade old. Update is needed to account for newer technologies such as cone beam computed tomography (CBCT) and digital imaging. Diagnostic Reference Levels (DRLs), a well established method for dose optimization, are not yet defined for CBCT and have to be set for various clinical indications. As far as shielding is concerned, recent data confirm that use of lead apron, even in pregnant patients, or gonadal shielding are not recommended, due to negligible radiation dose reduction. Thyroid lead shielding should be used in case the organ is in or close to the primary beam. Specifically for CBCT, leaded glasses, thyroid collars and collimation (smaller field of view (FOV) especially for paediatric patients) minimize the dose to organs outside the FOV. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016.
Bikson, Marom; Grossman, Pnina; Thomas, Chris; Zannou, Adantchede Louis; Jiang, Jimmy; Adnan, Tatheer; Mourdoukoutas, Antonios P; Kronberg, Greg; Truong, Dennis; Boggio, Paulo; Brunoni, André R; Charvet, Leigh; Fregni, Felipe; Fritsch, Brita; Gillick, Bernadette; Hamilton, Roy H; Hampstead, Benjamin M; Jankord, Ryan; Kirton, Adam; Knotkova, Helena; Liebetanz, David; Liu, Anli; Loo, Colleen; Nitsche, Michael A; Reis, Janine; Richardson, Jessica D; Rotenberg, Alexander; Turkeltaub, Peter E; Woods, Adam J
2016-01-01
This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose-response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3-13 A/m(2)) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (≤40 min, ≤4 milliamperes, ≤7.2 Coulombs) has not produced any reports of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1000 subjects with repeated sessions. This includes a wide variety of subjects, including persons from potentially vulnerable populations. Copyright © 2016 Elsevier Inc. All rights reserved.
Safety of transcranial Direct Current Stimulation: Evidence Based Update 2016
Bikson, Marom; Grossman, Pnina; Thomas, Chris; Zannou, Adantchede Louis; Jiang, Jimmy; Adnan, Tatheer; Mourdoukoutas, Antonios P; Kronberg, Greg; Truong, Dennis; Boggio, Paulo; Brunoni, André R.; Charvet, Leigh; Fregni, Felipe; Fritsch, Brita; Gillick, Bernadette; Hamilton, Roy H.; Hampstead, Benjamin M.; Jankord, Ryan; Kirton, Adam; Knotkova, Helena; Liebetanz, David; Liu, Anli; Loo, Colleen; Nitsche, Michael A.; Reis, Janine; Richardson, Jessica D.; Rotenberg, Alexander; Turkeltaub, Peter E.; Woods, Adam J.
2016-01-01
This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose-response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3–13 A/m2) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (≤40 min, ≤4 mA, ≤7.2 Coulombs) has not produced any reports of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1,000 subjects with repeated sessions. This includes a wide variety of subjects, including persons from potentially vulnerable populations. PMID:27372845
UPDATE ON THE ECOLOGICAL CONDITION OF THE DELMARVA COASTAL BAYS
The results of the 1993 assessment of the ecological condition of the Delaware and Maryland coastal bays were discussed at the Delmarva Coastal Bays Conference in 1996. The objective of this paper is to update our knowledge on the condition of the coastal bays with information fr...
An updated and expanded Carbon Bond mechanism (CB05) has been incorporated into the Community Multiscale Air Quality modeling system to more accurately simulate wintertime, pristine, and high altitude situations. The CB05 mechanism has nearly twice the number of reactions compare...
An Updated Measure for Assessing Subtle Rape Myths
ERIC Educational Resources Information Center
McMahon, Sarah; Farmer, G. Lawrence
2011-01-01
Social workers responsible for developing rape prevention programs on college campuses must have valid evaluation instruments. This article presents the challenges encountered by the authors when they attempted to keep rape myth measures relevant to student populations by updating the language to reflect the subtleties involved with rape myths.…
Tourette's Disorder: Genetic Update, Neurological Correlates, and Evidence-Based Interventions
ERIC Educational Resources Information Center
Phelps, LeAdelle
2008-01-01
This article provides an update of the search for genetic markers related to Tourette's Disorder. The probable neurophysiology of the disorder is reviewed. Frequently prescribed medications are related to the probable biological bases of the disorder. Behavioral interventions and assessment tools are examined. It is concluded that evidence based…
NASA Astrophysics Data System (ADS)
Thurston, Jim
2010-10-01
This report by Committee 6 of the Council is an extensive update of a previous report on the exposure of the US population to ionizing radiation sources from data gathered in the 1980s (published as Report 93 in 1987). It is combined with an update on the more in-depth assessment of data on medical exposures previously reported in 1989 (Report 100). Individual chapters in this new report are dedicated to specific sources of exposure to the US population—both from natural and artificial radiation—and the level of detail in each chapter is intended to reflect the significance of the contribution of each source to the total collective dose of the population. The first chapter is on the most significant contributor: background radiation. It expands on the concept of natural background radiation in Report 93, renaming it 'ubiquitous background', and describing in detail the contributions from both extra-terrestrial and terrestrial sources. The data demonstrates that the average dose from such exposure has varied little since the previous report (a slight increase from 3.0 mSv to 3.1 mSv). The next chapter is on medical radiation, i.e. the exposure to the population when attending as patients, not including occupational exposure to hospital workers. The most striking data published in the entire report is the increase in the contribution to the total US population dose attributed to such medical exposures. It is now as significant as that from background radiation: medical exposures now account for an average effective dose to the US citizen of 3.00 mSv, up from 0.53 mSv in 1992 (Report 100). The most important contribution to this increase is the 1.46 mSv from CT scanning alone. The nuclear medicine (including PET) contribution is up from 0.14 mSv to 0.77mSv. This evidently must be due to significant changes in medical radiological practice in the US tied to the increase in the availability of CT and PET imaging facilities. These increasing contributions have driven the overall average effective dose to a US citizen from approximately 3.6 mSv reported in 1987 to 6.2 mSv per annum, with medical exposures now responsible for 48% of the total (up from 15% in 1992). It is interesting to note that over roughly the same period of time, the total dose to the UK population has been revised upwards from 2.6 mSv to 2.7mSv to reflect (amongst other factors) the increase in CT scanning in the UK—obviously a much smaller change. However, one has to consider whether medical radiological practices in the UK might similarly change in the coming years, and UK population doses subsequently follow the US trend reported here. There is now a more detailed chapter on exposure to the population from consumer products and activities. Of the contributing factors in this category, the radiation dose received from radioactivity in tobacco smoke is the most significant, followed by building materials and air travel. There has been no significant change in the total dose received from these sources when compared to the earlier Report 93, at 0.13 mSv. The report also gives significant detail on exposure to the public from industrial sources (not just nuclear power), and discusses occupational exposure. Both these categories of exposure, averaged out of the whole population, give very small contributions to the total dose (0.003 mSv and 0.005 mSv, respectively). There are two final points to make about this report. Firstly, it continues the NCRP policy introduced for Report 93 of using SI units rather than the radiation units more commonly used within the US, hence making this report more readily accessible to an international audience. Secondly, in all the descriptions of the exposures and radiation doses received, no attempt is made to convert the doses into risk. The view of the Council, as stated in the forward to the report, is that attempting to quantify the risks associated with such levels of radiation exposure falls outside the remit of the Committee that prepared the report.
Real-World Conundrums and Biases in the Use of White Cell Growth Factors.
Smith, Thomas J; Hillner, Bruce E
2016-01-01
We present the 2015 American Society of Clinical Oncology (ASCO) white cell growth factors, or colony-stimulating factor (CSF), guidelines, updated from 2006. One new indication has been added-dose-intense chemotherapy for bladder cancer-to accompany the existing use for dose-dense breast cancer chemotherapy. Colony-stimulating factors remain appropriate for any regimen where the risk of febrile neutropenia is about 20% per cycle and dose reduction is not appropriate. Based on new evidence from multiple trials, CSF use is no longer indicated in treatment of lymphoma unless there are special risk factors. The United States accounts for 78% of the sales of CSF. The panel approved the use of all biosimilars, but the cost savings will be small as the price is about 80% of the branded CSFs. More biosimilars at lower cost are awaited. Methods to reduce use without harm to patients, by requiring justification according to accepted guidelines, are ongoing.
Clarke, Christina A; Canchola, Alison J; Moy, Lisa M; Neuhausen, Susan L; Chung, Nadia T; Lacey, James V; Bernstein, Leslie
2017-05-01
Regular users of aspirin may have reduced risk of breast cancer. Few studies have addressed whether risk reduction pertains to specific breast cancer subtypes defined jointly by hormone receptor (estrogen and progesterone receptor) and human epidermal growth factor receptor 2 (HER2) expression. This study assessed the prospective risk of breast cancer (overall and by subtype) according to use of aspirin and other non-steroidal anti-inflammatory medications (NSAIDs) in a cohort of female public school professionals in California. In 1995 - 1996, participants in the California Teachers Study completed a baseline questionnaire on family history of cancer and other conditions, use of NSAIDs, menstrual and reproductive history, self-reported weight and height, living environment, diet, alcohol use, and physical activity. In 2005-2006, 57,164 participants provided some updated information, including use of NSAIDs and 1457 of these participants developed invasive breast cancer before January 2013. Multivariable Cox proportional hazards regression models provided hazard rate ratios (HRR) for the association between NSAID use and risk of invasive breast cancer as well as hormone receptor- and HER2-defined subtypes. Developing breast cancer was associated inversely with taking three or more tablets of low-dose aspirin per week (23% of participants). Among women reporting this exposure, the HRR was 0.84 (95% confidence interval (CI) 0.72-0.98) compared to those not taking NSAIDs and this was particularly evident in women with the hormone receptor-positive/HER2-negative subtype (HRR = 0.80, 95% CI 0.66-0.96). Use of three or more tablets of "other" NSAIDs was marginally associated with lower risk of breast cancer (HRR = 0.79, 95% CI 0.62-1.00). Other associations with NSAIDs were generally null. Our observation of reduced risk of breast cancer, among participants who took three or more tablets of low-dose aspirin weekly, is consistent with other reports looking at aspirin without differentiation by dose. This is the first report to suggest that the reduction in risk occurs for low-dose aspirin and not for regular-dose aspirin and only among women with the hormone receptor-positive/HER2-negative subtype. This preliminary study builds on previous knowledge and further supports the need for formal cancer chemoprevention studies of low-dose aspirin.
Time to Update and Quantitative Changes in the Results of Cochrane Pregnancy and Childbirth Reviews
Jaidee, Wanlop; Moher, David; Laopaiboon, Malinee
2010-01-01
Background The recommended interval between updates for systematic reviews included in The Cochrane Library is 2 years. However, it is unclear whether this interval is always appropriate. Whereas excessive updating wastes time and resources, insufficient updating allows out-of-date or incomplete evidence to guide clinical decision-making. We set out to determine, for Cochrane pregnancy and childbirth reviews, the frequency of updates, factors associated with updating, and whether updating frequency was appropriate. Methodology/Principal Findings Cochrane pregnancy and childbirth reviews published in Issue 3, 2007 of the Cochrane Database of Systematic Reviews were retrieved, and data were collected from their original and updated versions. Quantitative changes were determined for one of the primary outcomes (mortality, or the outcome of greatest clinical significance). Potential factors associated with time to update were assessed using the Cox proportional hazard model. Among the 101 reviews in our final sample, the median time before the first update was 3.3 years (95% CI 2.7–3.8). Only 32.7% had been updated within the recommended interval of 2 years. In 75.3% (76/101), a median of 3 new trials with a median of 576 additional participants were included in the updated versions. There were quantitative changes in 71% of the reviews that included new trials (54/76): the median change in effect size was 18.2%, and the median change in 95% CI width was 30.8%. Statistical significance changed in 18.5% (10/54) of these reviews, but conclusions were revised in only 3.7% (2/54). A shorter time to update was associated with the same original review team at updating. Conclusions/Significance Most reviews were updated less frequently than recommended by Cochrane policy, but few updates had revised conclusions. Prescribed time to update should be reconsidered to support improved decision-making while making efficient use of limited resources. PMID:20644625
Auditing the management of vaccine-preventable disease outbreaks: the need for a tool.
Torner, Nuria; Carnicer-Pont, Dolors; Castilla, Jesus; Cayla, Joan; Godoy, Pere; Dominguez, Angela
2011-01-13
Public health activities, especially infectious disease control, depend on effective teamwork. We present the results of a pilot audit questionnaire aimed at assessing the quality of public health services in the management of VPD outbreaks. Audit questionnaire with three main areas indicators (structure, process and results) was developed. Guidelines were set and each indicator was assessed by three auditors. Differences in indicator scores according to median size of outbreaks were determined by ANOVA (significance at p≤0.05). Of 154 outbreaks; eighteen indicators had a satisfactory mean score, indicator "updated guidelines" and "timely reporting" had a poor mean score (2.84±106 and 2.44±1.67, respectively). Statistically significant differences were found according to outbreak size, in the indicators "availability of guidelines/protocol updated less than 3 years ago" (p = 0.03) and "days needed for outbreak control" (p = 0.04). Improving availability of updated guidelines, enhancing timely reporting and adequate recording of control procedures taken is needed to allow for management assessment and improvement.
Konold, Timm; Arnold, Mark E; Austin, Anthony R; Cawthraw, Saira; Hawkins, Steve A C; Stack, Michael J; Simmons, Marion M; Sayers, A Robin; Dawson, Michael; Wilesmith, John W; Wells, Gerald A H
2012-12-05
To provide information on dose-response and aid in modelling the exposure dynamics of the BSE epidemic in the United Kingdom groups of cattle were exposed orally to a range of different doses of brainstem homogenate of known infectious titre from clinical cases of classical bovine spongiform encephalopathy (BSE). Interim data from this study was published in 2007. This communication documents additional BSE cases, which occurred subsequently, examines possible influence of the bovine prion protein gene on disease incidence and revises estimates of effective oral exposure. Following interim published results, two further cattle, one dosed with 100 mg and culled at 127 months post exposure and the other dosed with 10 mg and culled at 110 months post exposure, developed BSE. Both had a similar pathological phenotype to previous cases. Based on attack rate and incubation period distribution according to dose, the dose estimate at which 50% of confirmed cases would be clinically affected was revised to 0.15 g of the brain homogenate used in the experiment, with a 95% confidence interval of 0.03-0.79 g. Neither the full open reading frame nor the promoter region of the prion protein gene of dosed cattle appeared to influence susceptibility to BSE, but this may be due to the sample size. Oral exposure of cattle to a large range of doses of a BSE brainstem homogenate produced disease in all dose groups. The pathological presentation resembled natural disease. The attack rate and incubation period were dependent on the dose.
Pelegrina, Santiago; Capodieci, Agnese; Carretti, Barbara; Cornoldi, Cesare
2015-01-01
It has been argued that children with learning disabilities (LD) encounter severe problems in working memory (WM) tasks, especially when they need to update information stored in their WM. It is not clear, however, to what extent this is due to a generally poor updating ability or to a difficulty specific to the domain to be processed. To examine this issue, two groups of children with arithmetic or reading comprehension LD and a group of typically developing children (9 to 10 years old) were assessed using two updating tasks requiring to select the smallest numbers or objects presented. The results showed that children with an arithmetic disability failed in a number updating task, but not in the object updating task. The opposite was true for the group with poor reading comprehension, whose performance was worse in the object than in the number updating task. It may be concluded that the problem of WM updating in children with LD is also due to a poor representation of the material to be updated. In addition, our findings suggest that the mental representation of the size of objects relates to the semantic representation of the objects' properties and differs from the quantitative representation of numbers. © Hammill Institute on Disabilities 2014.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Borot de Battisti, Maxence, E-mail: M.E.P.Borot@um
Purpose: The development of MR-guided high dose rate (HDR) brachytherapy is under investigation due to the excellent tumor and organs at risk visualization of MRI. However, MR-based localization of needles (including catheters or tubes) has inherently a low update rate and the required image interpretation can be hampered by signal voids arising from blood vessels or calcifications limiting the precision of the needle guidance and reconstruction. In this paper, a new needle tracking prototype is investigated using fiber Bragg gratings (FBG)-based sensing: this prototype involves a MR-compatible stylet composed of three optic fibers with nine sets of embedded FBG sensorsmore » each. This stylet can be inserted into brachytherapy needles and allows a fast measurement of the needle deflection. This study aims to assess the potential of FBG-based sensing for real-time needle (including catheter or tube) tracking during MR-guided intervention. Methods: First, the MR compatibility of FBG-based sensing and its accuracy was evaluated. Different known needle deflections were measured using FBG-based sensing during simultaneous MR-imaging. Then, a needle tracking procedure using FBG-based sensing was proposed. This procedure involved a MR-based calibration of the FBG-based system performed prior to the interventional procedure. The needle tracking system was assessed in an experiment with a moving phantom during MR imaging. The FBG-based system was quantified by comparing the gold-standard shapes, the shape manually segmented on MRI and the FBG-based measurements. Results: The evaluation of the MR compatibility of FBG-based sensing and its accuracy shows that the needle deflection could be measured with an accuracy of 0.27 mm on average. Besides, the FBG-based measurements were comparable to the uncertainty of MR-based measurements estimated at half the voxel size in the MR image. Finally, the mean(standard deviation) Euclidean distance between MR- and FBG-based needle position measurements was equal to 0.79 mm(0.37 mm). The update rate and latency of the FBG-based needle position measurement were 100 and 300 ms, respectively. Conclusions: The FBG-based needle tracking procedure proposed in this paper is able to determine the position of the complete needle, under MR-imaging, with better accuracy and precision, higher update rate, and lower latency compared to current MR-based needle localization methods. This system would be eligible for MR-guided brachytherapy, in particular, for an improved needle guidance and reconstruction.« less
Respirators, internal dose, and Oyster Creek
DOE Office of Scientific and Technical Information (OSTI.GOV)
Michal, R.
1996-06-01
This article looks at the experience of Oyster Creek in relaxing the requirements for the use of respirators in all facets of plant maintenance, on the overall dose received by plant maintenance personnel. For Roger Shaw, director of radiological controls for three years at GPU Nuclear Corporation`s Oyster Creek nuclear plant the correct dose balance is determined on a job-by-job basis: Does the job require a respirator, which is an effective means of decreasing worker inhalation of airborne radioactive particles? Will wearing a respirator slow down a worker, consequently increasing whole body radiation exposure by prolonging the time spent inmore » fields of high external radiation? How does respiratory protection affect worker safety and to what degree? While changes to the Nuclear Regulatory Commission`s 10CFR20 have updated the radiation protection requirements for the nuclear industry, certain of the revisions have been directed specifically at reducing worker dose, Shaw said. {open_quotes}It basically delineates that dose is dose,{close_quotes} Shaw said, {open_quotes}regardless of whether it is acquired externally or internally.{close_quotes} The revision of Part 20 changed the industry`s attitude toward internal dose, which had always been viewed negatively. {open_quotes}Internal dose was always seen as preventable by wearing respirators and by using engineering techniques such as ventilation control and decontamination,{close_quotes} Shaw said, {open_quotes}whereas external dose, although reduced where practical, was seen as a fact of the job.{close_quotes}« less
On effective dose for radiotherapy based on doses to nontarget organs and tissues
DOE Office of Scientific and Technical Information (OSTI.GOV)
Uselmann, Adam J., E-mail: ajuselmann@wisc.edu; Thomadsen, Bruce R.
2015-02-15
Purpose: The National Council for Radiation Protection and Measurement (NCRP) published estimates for the collective population dose and the mean effective dose to the population of the United States from medical imaging procedures for 1980/1982 and for 2006. The earlier report ignored the effective dose from radiotherapy and the latter gave a cursory discussion of the topic but again did not include it in the population exposure for various reasons. This paper explains the methodology used to calculate the effective dose in due to radiotherapy procedures in the latter NCRP report and revises the values based on more detailed modeling.more » Methods: This study calculated the dose to nontarget organs from radiotherapy for reference populations using CT images and published peripheral dose data. Results: Using International Commission on Radiological Protection (ICRP) 60 weighting factors, the total effective dose to nontarget organs in radiotherapy patients is estimated as 298 ± 194 mSv per patient, while the U.S. population effective dose is 0.939 ± 0.610 mSv per person, with a collective dose of 283 000 ± 184 000 person Sv per year. Using ICRP 103 weighting factors, the effective dose is 281 ± 183 mSv per patient, 0.887 ± 0.577 mSv per person in the U.S., and 268 000 ± 174 000 person Sv per year. The uncertainty in the calculations is largely governed by variations in patient size, which was accounted for by considering a range of patient sizes and taking the average treatment site to nontarget organ distance. Conclusions: The methods used to estimate the effective doses from radiotherapy used in NCRP Report No. 160 have been explained and the values updated.« less
Palumbo, Antonio; Rajkumar, S. Vincent; San Miguel, Jesus F.; Larocca, Alessandra; Niesvizky, Ruben; Morgan, Gareth; Landgren, Ola; Hajek, Roman; Einsele, Hermann; Anderson, Kenneth C.; Dimopoulos, Meletios A.; Richardson, Paul G.; Cavo, Michele; Spencer, Andrew; Stewart, A. Keith; Shimizu, Kazuyuki; Lonial, Sagar; Sonneveld, Pieter; Durie, Brian G.M.; Moreau, Philippe; Orlowski, Robert Z.
2014-01-01
Purpose To provide an update on recent advances in the management of patients with multiple myeloma who are not eligible for autologous stem-cell transplantation. Methods A comprehensive review of the literature on diagnostic criteria is provided, and treatment options and management of adverse events are summarized. Results Patients with symptomatic disease and organ damage (ie, hypercalcemia, renal failure, anemia, or bone lesions) require immediate treatment. The International Staging System and chromosomal abnormalities identify high- and standard-risk patients. Proteasome inhibitors, immunomodulatory drugs, corticosteroids, and alkylating agents are the most active agents. The presence of concomitant diseases, frailty, or disability should be assessed and, if present, treated with reduced-dose approaches. Bone disease, renal damage, hematologic toxicities, infections, thromboembolism, and peripheral neuropathy are the most frequent disabling events requiring prompt and active supportive care. Conclusion These recommendations will help clinicians ensure the most appropriate care for patients with myeloma in everyday clinical practice. PMID:24419113
Modeling Of In-Vehicle Human Exposure to Ambient Fine Particulate Matter
Liu, Xiaozhen; Frey, H. Christopher
2012-01-01
A method for estimating in-vehicle PM2.5 exposure as part of a scenario-based population simulation model is developed and assessed. In existing models, such as the Stochastic Exposure and Dose Simulation model for Particulate Matter (SHEDS-PM), in-vehicle exposure is estimated using linear regression based on area-wide ambient PM2.5 concentration. An alternative modeling approach is explored based on estimation of near-road PM2.5 concentration and an in-vehicle mass balance. Near-road PM2.5 concentration is estimated using a dispersion model and fixed site monitor (FSM) data. In-vehicle concentration is estimated based on air exchange rate and filter efficiency. In-vehicle concentration varies with road type, traffic flow, windspeed, stability class, and ventilation. Average in-vehicle exposure is estimated to contribute 10 to 20 percent of average daily exposure. The contribution of in-vehicle exposure to total daily exposure can be higher for some individuals. Recommendations are made for updating exposure models and implementation of the alternative approach. PMID:23101000
Levetiracetam induced acute reversible psychosis in a patient with uncontrolled seizures
Kumar, Nithin; Swaroop, H. S.; Chakraborty, Ananya; Chandran, Suhas
2014-01-01
Levetiracetam (LEV) is a relatively newer antiepileptic drug with novel mechanism of action. It was introduced to the market in the year 2000. Pre-marketing clinical trials of the drug reported good tolerability with a wide safety margin. On post-marketing updates, there are few reports of psychosis after treatment with the drug. Here, we report a case of 52-year-old epileptic man who developed acute, reversible psychosis within 3 days of initiation of treatment. The drug was prescribed at a dose of 500 mg per day. After 3 days of treatment, the patient developed visual hallucinations, mood swings, withdrawal and suspicious behavior. Delirium was ruled out as there was no fluctuation in his sensorium or focal neurological deficits. His lab investigations for electrolytes, renal function test, thyroid, liver function and other related tests levels were within normal limits. A diagnosis of LEV induced psychosis was reached based on clinical judgment and causality assessment. PMID:25298593
Low-Level Analytical Methodology Updates to Support Decontaminant Performance Evaluations
2011-06-01
from EPDM and tire rubber coupon materials that were spiked with a known amount of the chemical agent VX, treated with bleach decontaminant, and...to evaluate the performance of bleach decontaminant on EPDM and tire rubber coupons. Dose-confirmation or Tool samples were collected by delivering...components • An aging or damaged analytical column • Dirty detector • Other factors related to general instrument and/or sample analysis performance
Development of probabilistic internal dosimetry computer code
NASA Astrophysics Data System (ADS)
Noh, Siwan; Kwon, Tae-Eun; Lee, Jai-Ki
2017-02-01
Internal radiation dose assessment involves biokinetic models, the corresponding parameters, measured data, and many assumptions. Every component considered in the internal dose assessment has its own uncertainty, which is propagated in the intake activity and internal dose estimates. For research or scientific purposes, and for retrospective dose reconstruction for accident scenarios occurring in workplaces having a large quantity of unsealed radionuclides, such as nuclear power plants, nuclear fuel cycle facilities, and facilities in which nuclear medicine is practiced, a quantitative uncertainty assessment of the internal dose is often required. However, no calculation tools or computer codes that incorporate all the relevant processes and their corresponding uncertainties, i.e., from the measured data to the committed dose, are available. Thus, the objective of the present study is to develop an integrated probabilistic internal-dose-assessment computer code. First, the uncertainty components in internal dosimetry are identified, and quantitative uncertainty data are collected. Then, an uncertainty database is established for each component. In order to propagate these uncertainties in an internal dose assessment, a probabilistic internal-dose-assessment system that employs the Bayesian and Monte Carlo methods. Based on the developed system, we developed a probabilistic internal-dose-assessment code by using MATLAB so as to estimate the dose distributions from the measured data with uncertainty. Using the developed code, we calculated the internal dose distribution and statistical values ( e.g. the 2.5th, 5th, median, 95th, and 97.5th percentiles) for three sample scenarios. On the basis of the distributions, we performed a sensitivity analysis to determine the influence of each component on the resulting dose in order to identify the major component of the uncertainty in a bioassay. The results of this study can be applied to various situations. In cases of severe internal exposure, the causation probability of a deterministic health effect can be derived from the dose distribution, and a high statistical value ( e.g., the 95th percentile of the distribution) can be used to determine the appropriate intervention. The distribution-based sensitivity analysis can also be used to quantify the contribution of each factor to the dose uncertainty, which is essential information for reducing and optimizing the uncertainty in the internal dose assessment. Therefore, the present study can contribute to retrospective dose assessment for accidental internal exposure scenarios, as well as to internal dose monitoring optimization and uncertainty reduction.
Citrome, Leslie
2017-10-01
Long-acting injectable (LAI) antipsychotics are a useful but underutilized option in the management of schizophrenia. Areas covered: This is a narrative review of newer LAI antipsychotics approved by the US Food and Drug Administration and is an update to a previously published review from 2013. Emphasized are new indications and new dosing intervals. Expert commentary: Ensuring that persons receiving oral antipsychotics are aware that LAI antipsychotics are available is important. The use of LAI antipsychotics can decrease the risk of relapse in both first-episode and chronic schizophrenia. Available treatments differ in terms of specific indications, approved injection sites, needle gauge, injection volume, injection interval, requirements for oral supplementation, availability of pre-filled syringes, storage needs, and post-injection observation period, as well as potential drug-drug interactions and commonly encountered adverse reactions. Approved indications have expanded beyond schizophrenia to also include bipolar maintenance (risperidone microspheres and aripiprazole monohydrate) and schizoaffective disorder (paliperidone palmitate monthly). Intervals between injections can be longer than one month (six-week or two-month aripiprazole lauroxil, and three-month paliperidone palmitate). After a review of the evidence-base, guidance is offered on the appropriate selection among the LAI formulations of both first and second-generation antipsychotics.
Operational CryoSat Product Quality Assessment
NASA Astrophysics Data System (ADS)
Mannan, Rubinder; Webb, Erica; Hall, Amanda; Bouzinac, Catherine
2013-12-01
The performance and quality of the CryoSat data products are routinely assessed by the Instrument Data quality Evaluation and Analysis Service (IDEAS). This information is then conveyed to the scientific and user community in order to allow them to utilise CryoSat data with confidence. This paper presents details of the Quality Control (QC) activities performed for CryoSat products under the IDEAS contract. Details of the different QC procedures and tools deployed by IDEAS to assess the quality of operational data are presented. The latest updates to the Instrument Processing Facility (IPF) for the Fast Delivery Marine (FDM) products and the future update to Baseline-C are discussed.
Tomographic Imaging on a Cobalt Radiotherapy Machine
NASA Astrophysics Data System (ADS)
Marsh, Matthew Brendon
Cancer is a global problem, and many people in low-income countries do not have access to the treatment options, such as radiation therapy, that are available in wealthy countries. Where radiation therapy is available, it is often delivered using older Co-60 equipment that has not been updated to modern standards. Previous research has indicated that an updated Co-60 radiation therapy machine could deliver treatments that are equivalent to those performed with modern linear accelerators. Among the key features of these modern treatments is a tightly conformal dose distribution-- the radiation dose is shaped in three dimensions to closely match the tumour, with minimal irradiation of surrounding normal tissues. Very accurate alignment of the patient in the beam is therefore necessary to avoid missing the tumour, so all modern radiotherapy machines include imaging systems to verify the patient's position before treatment. Imaging with the treatment beam is relatively cost-effective, as it avoids the need for a second radiation source and the associated control systems. The dose rate from a Co-60 therapy source, though, is more than an order of magnitude too high to use for computed tomography (CT) imaging of a patient. Digital tomosynthesis (DT), a limited-arc imaging method that can be thought of as a hybrid of CT and conventional radiography, allows some of the three-dimensional selectivity of CT but with shorter imaging times and a five- to fifteen-fold reduction in dose. In the present work, a prototype Co-60 DT imaging system was developed and characterized. A class of clinically useful Co-60 DT protocols has been identified, based on the filtered backprojection algorithm originally designed for CT, with images acquired over a relatively small arc. Parts of the reconstruction algorithm must be modified for the DT case, and a way to reduce the beam intensity will be necessary to reduce the imaging dose to acceptable levels. Some additional study is required to determine whether improvements made to the DT imaging protocol translate to improvements in the accuracy of the image guidance process, but it is clear that Co-60 DT is feasible and will probably be practical for clinical use.
Sargent, Edward V; Flueckiger, Andreas; Barle, Ester Lovsin; Luo, Wendy; Molnar, Lance R; Sandhu, Reena; Weideman, Patricia A
2016-08-01
Cross-contamination in multi-product pharmaceutical manufacturing facilities can impact both product safety and quality. This issue has been recognized by regulators and industry for some time, leading to publication of a number of continually evolving guidelines. This manuscript provides a historical overview of the regulatory framework for managing cross-contamination in multi-product facilities to provide context for current approaches. Early guidelines focused on the types of pharmaceuticals for which dedicated facilities and control systems were needed, and stated the requirements for cleaning validation. More recent guidelines have promoted the idea of using Acceptable Daily Exposures (ADEs) to establish cleaning limits for actives and other potentially hazardous substances. The ADE approach is considered superior to previous methods for setting cleaning limits such as using a predetermined general limit (e.g., 10 ppm or a fraction of the median lethal dose (LD50) or therapeutic dose). The ADEs can be used to drive the cleaning process and as part of the overall assessment of whether dedicated production facilities are required. While great strides have been made in using the ADE approach, work remains to update good manufacturing practices (GMPs) to ensure that the approaches are clear, consistent with the state-of-the-science, and broadly applicable yet flexible enough for adaptation to unique products and situations. Copyright © 2016 Elsevier Inc. All rights reserved.
Retrospective review of Contura HDR breast cases to improve our standardized procedure
DOE Office of Scientific and Technical Information (OSTI.GOV)
Iftimia, Ileana, E-mail: Ileana.n.iftimia@lahey.org; Cirino, Eileen T.; Ladd, Ron
2013-07-01
To retrospectively review our first 20 Contura high dose rate breast cases to improve and refine our standardized procedure and checklists. We prepared in advance checklists for all steps, developed an in-house Excel spreadsheet for second checking the plan, and generated a procedure for efficient contouring and a set of optimization constraints to meet the dose volume histogram criteria. Templates were created in our treatment planning system for structures, isodose levels, optimization constraints, and plan report. This study reviews our first 20 high dose rate Contura breast treatment plans. We followed our standardized procedure for contouring, planning, and second checking.more » The established dose volume histogram criteria were successfully met for all plans. For the cases studied here, the balloon-skin and balloon-ribs distances ranged between 5 and 43 mm and 1 and 33 mm, respectively; air{sub s}eroma volume/PTV{sub E}val volume≤5.5% (allowed≤10%); asymmetry<1.2 mm (goal≤2 mm); PTV{sub E}val V90%≥97.6%; PTV{sub E}val V95%≥94.9%; skin max dose≤98%Rx; ribs max dose≤137%Rx; V150%≤29.8 cc; V200%≤7.8 cc; the total dwell time range was 225.4 to 401.9 seconds; and the second check agreement was within 3%. Based on this analysis, more appropriate ranges for the total dwell time and balloon diameter tolerance were found. Three major problems were encountered: balloon migration toward the skin for small balloon-to-skin distances, lumen obstruction, and length change for the flexible balloon. Solutions were found for these issues and our standardized procedure and checklists were updated accordingly. Based on our review of these cases, the use of checklists resulted in consistent results, indicating good coverage for the target without sacrificing the critical structures. This review helped us to refine our standardized procedure and update our checklists.« less
NASA Astrophysics Data System (ADS)
Fu, Y.; Yang, W.; Xu, O.; Zhou, L.; Wang, J.
2017-04-01
To investigate time-variant and nonlinear characteristics in industrial processes, a soft sensor modelling method based on time difference, moving-window recursive partial least square (PLS) and adaptive model updating is proposed. In this method, time difference values of input and output variables are used as training samples to construct the model, which can reduce the effects of the nonlinear characteristic on modelling accuracy and retain the advantages of recursive PLS algorithm. To solve the high updating frequency of the model, a confidence value is introduced, which can be updated adaptively according to the results of the model performance assessment. Once the confidence value is updated, the model can be updated. The proposed method has been used to predict the 4-carboxy-benz-aldehyde (CBA) content in the purified terephthalic acid (PTA) oxidation reaction process. The results show that the proposed soft sensor modelling method can reduce computation effectively, improve prediction accuracy by making use of process information and reflect the process characteristics accurately.
Skeletal dosimetry based on µCT images of trabecular bone: update and comparisons
NASA Astrophysics Data System (ADS)
Kramer, R.; Cassola, V. F.; Vieira, J. W.; Khoury, H. J.; de Oliveira Lira, C. A. B.; Robson Brown, K.
2012-06-01
Two skeletal dosimetry methods using µCT images of human bone have recently been developed: the paired-image radiation transport (PIRT) model introduced by researchers at the University of Florida (UF) in the US and the systematic-periodic cluster (SPC) method developed by researchers at the Federal University of Pernambuco in Brazil. Both methods use µCT images of trabecular bone (TB) to model spongiosa regions of human bones containing marrow cavities segmented into soft tissue volumes of active marrow (AM), trabecular inactive marrow and the bone endosteum (BE), which is a 50 µm thick layer of marrow on all TB surfaces and on cortical bone surfaces next to TB as well as inside the medullary cavities. With respect to the radiation absorbed dose, the AM and the BE are sensitive soft tissues for the induction of leukaemia and bone cancer, respectively. The two methods differ mainly with respect to the number of bone sites and the size of the µCT images used in Monte Carlo calculations and they apply different methods to simulate exposure from radiation sources located outside the skeleton. The PIRT method calculates dosimetric quantities in isolated human bones while the SPC method uses human bones embedded in the body of a phantom which contains all relevant organs and soft tissues. Consequently, the SPC method calculates absorbed dose to the AM and to the BE from particles emitted by radionuclides concentrated in organs or from radiation sources located outside the human body in one calculation step. In order to allow for similar calculations of AM and BE absorbed doses using the PIRT method, the so-called dose response functions (DRFs) have been developed based on absorbed fractions (AFs) of energy for electrons isotropically emitted in skeletal tissues. The DRFs can be used to transform the photon fluence in homogeneous spongiosa regions into absorbed dose to AM and BE. This paper will compare AM and BE AFs of energy from electrons emitted in skeletal tissues calculated with the SPC and the PIRT method and AM and BE absorbed doses and AFs calculated with PIRT-based DRFs and with the SPC method. The results calculated with the two skeletal dosimetry methods agree well if one takes the differences between the two models properly into account. Additionally, the SPC method will be updated with larger µCT images of TB.
This ECO Update builds on the standard approach to ERA (U.S. EPA 1997), by providing a framework for incorporating groundwater/surface-water (GW/SW) interactions into existing ERAs (see U.S. EPA 1997 and 2001a for an introduction to ecological risk....
Update on Research and Leadership, Fall 2001-Spring 2002.
ERIC Educational Resources Information Center
Barnett, Elisabeth, Ed.
2001-01-01
This issue of On Research and Leadership Update (v13 n1) focuses on the concerns surrounding dual enrollment and dual credit. "Dual Enrollment Programs: Assessing the American Dream," by Katherine Boswell, addresses the problems inherent in development of these programs when institutions fail to collaborate with one another in an effective way.…
Business and Office Curriculum Update. Final Report.
ERIC Educational Resources Information Center
Kjosnes, Iva S.
A project was conducted to update an existing high school business and office occupations education curriculum to include instruction in the use of computers and word processing equipment. The existing curriculum was assessed and revised in order to provide students with training in the following areas: the impact of computers on employment; the…
Electronic Continuing Education in the Health Professions: An Update on Evidence from RCTs
ERIC Educational Resources Information Center
Lam-Antoniades, Margarita; Ratnapalan, Savithiri; Tait, Gordon
2009-01-01
Introduction: Demonstrating the effectiveness of the rapidly expanding field of electronic continuing education (e-CE) has important implications for CE in the health professions. This study provides an update on evidence from randomized controlled trials (RCTs) assessing the effectiveness of e-CE in the health professions. Methods: A literature…
The paper is an update on U.S. research to develop tools and information for evaluating integrated solid waste management strategies. In the past, waste management systems consisted primarily of waste collection and disposal at a local landfill. Today's municipal solid waste ma...
Dauer, Lawrence T; Ainsbury, Elizabeth A; Dynlacht, Joseph; Hoel, David; Klein, Barbara E K; Mayer, Don; Prescott, Christina R; Thornton, Raymond H; Vano, Eliseo; Woloschak, Gayle E; Flannery, Cynthia M; Goldstein, Lee E; Hamada, Nobuyuki; Tran, Phung K; Grissom, Michael P; Blakely, Eleanor A
2016-02-01
Previous National Council on Radiation Protection and Measurements (NCRP) publications have addressed the issues of risk and dose limitation in radiation protection and included guidance on specific organs and the lens of the eye. NCRP decided to prepare an updated commentary intended to enhance the previous recommendations provided in earlier reports. The NCRP Scientific Committee 1-23 (SC 1-23) is charged with preparing a commentary that will evaluate recent studies on the radiation dose response for the development of cataracts and also consider the type and severity of the cataracts as well as the dose rate; provide guidance on whether existing dose limits to the lens of the eye should be changed in the United States; and suggest research needs regarding radiation effects on and dose limits to the lens of the eye. A status of the ongoing work of SC 1-23 was presented at the Annual Meeting, "Changing Regulations and Radiation Guidance: What Does the Future Hold?" The following represents a synopsis of a few main points in the current draft commentary. It is likely that several changes will be forthcoming as SC 1-23 responds to subject matter expert review and develops a final document, expected by mid 2016.
A product of independent beta probabilities dose escalation design for dual-agent phase I trials.
Mander, Adrian P; Sweeting, Michael J
2015-04-15
Dual-agent trials are now increasingly common in oncology research, and many proposed dose-escalation designs are available in the statistical literature. Despite this, the translation from statistical design to practical application is slow, as has been highlighted in single-agent phase I trials, where a 3 + 3 rule-based design is often still used. To expedite this process, new dose-escalation designs need to be not only scientifically beneficial but also easy to understand and implement by clinicians. In this paper, we propose a curve-free (nonparametric) design for a dual-agent trial in which the model parameters are the probabilities of toxicity at each of the dose combinations. We show that it is relatively trivial for a clinician's prior beliefs or historical information to be incorporated in the model and updating is fast and computationally simple through the use of conjugate Bayesian inference. Monotonicity is ensured by considering only a set of monotonic contours for the distribution of the maximum tolerated contour, which defines the dose-escalation decision process. Varied experimentation around the contour is achievable, and multiple dose combinations can be recommended to take forward to phase II. Code for R, Stata and Excel are available for implementation. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
Evidence supporting radiation hormesis in atomic bomb survivor cancer mortality data.
Doss, Mohan
2012-12-01
A recent update on the atomic bomb survivor cancer mortality data has concluded that excess relative risk (ERR) for solid cancers increases linearly with dose and that zero dose is the best estimate for the threshold, apparently validating the present use of the linear no threshold (LNT) model for estimating the cancer risk from low dose radiation. A major flaw in the standard ERR formalism for estimating cancer risk from radiation (and other carcinogens) is that it ignores the potential for a large systematic bias in the measured baseline cancer mortality rate, which can have a major effect on the ERR values. Cancer rates are highly variable from year to year and between adjacent regions and so the likelihood of such a bias is high. Calculations show that a correction for such a bias can lower the ERRs in the atomic bomb survivor data to negative values for intermediate doses. This is consistent with the phenomenon of radiation hormesis, providing a rational explanation for the decreased risk of cancer observed at intermediate doses for which there is no explanation based on the LNT model. The recent atomic bomb survivor data provides additional evidence for radiation hormesis in humans.
Low-Dose Carcinogenicity Studies
One of the major deficiencies of cancer risk assessments is the lack of low-dose carcinogenicity data. Most assessments require extrapolation from high to low doses, which is subject to various uncertainties. Only 4 low-dose carcinogenicity studies and 5 low-dose biomarker/pre-n...
Fiorina, E; Ferrero, V; Pennazio, F; Baroni, G; Battistoni, G; Belcari, N; Cerello, P; Camarlinghi, N; Ciocca, M; Del Guerra, A; Donetti, M; Ferrari, A; Giordanengo, S; Giraudo, G; Mairani, A; Morrocchi, M; Peroni, C; Rivetti, A; Da Rocha Rolo, M D; Rossi, S; Rosso, V; Sala, P; Sportelli, G; Tampellini, S; Valvo, F; Wheadon, R; Bisogni, M G
2018-05-07
Hadrontherapy is a method for treating cancer with very targeted dose distributions and enhanced radiobiological effects. To fully exploit these advantages, in vivo range monitoring systems are required. These devices measure, preferably during the treatment, the secondary radiation generated by the beam-tissue interactions. However, since correlation of the secondary radiation distribution with the dose is not straightforward, Monte Carlo (MC) simulations are very important for treatment quality assessment. The INSIDE project constructed an in-beam PET scanner to detect signals generated by the positron-emitting isotopes resulting from projectile-target fragmentation. In addition, a FLUKA-based simulation tool was developed to predict the corresponding reference PET images using a detailed scanner model. The INSIDE in-beam PET was used to monitor two consecutive proton treatment sessions on a patient at the Italian Center for Oncological Hadrontherapy (CNAO). The reconstructed PET images were updated every 10 s providing a near real-time quality assessment. By half-way through the treatment, the statistics of the measured PET images were already significant enough to be compared with the simulations with average differences in the activity range less than 2.5 mm along the beam direction. Without taking into account any preferential direction, differences within 1 mm were found. In this paper, the INSIDE MC simulation tool is described and the results of the first in vivo agreement evaluation are reported. These results have justified a clinical trial, in which the MC simulation tool will be used on a daily basis to study the compliance tolerances between the measured and simulated PET images. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
The linear nonthreshold (LNT) model as used in radiation protection: an NCRP update.
Boice, John D
2017-10-01
The linear nonthreshold (LNT) model has been used in radiation protection for over 40 years and has been hotly debated. It relies heavily on human epidemiology, with support from radiobiology. The scientific underpinnings include NCRP Report No. 136 ('Evaluation of the Linear-Nonthreshold Dose-Response Model for Ionizing Radiation'), UNSCEAR 2000, ICRP Publication 99 (2004) and the National Academies BEIR VII Report (2006). NCRP Scientific Committee 1-25 is reviewing recent epidemiologic studies focusing on dose-response models, including threshold, and the relevance to radiation protection. Recent studies after the BEIR VII Report are being critically reviewed and include atomic-bomb survivors, Mayak workers, atomic veterans, populations on the Techa River, U.S. radiological technologists, the U.S. Million Person Study, international workers (INWORKS), Chernobyl cleanup workers, children given computerized tomography scans, and tuberculosis-fluoroscopy patients. Methodologic limitations, dose uncertainties and statistical approaches (and modeling assumptions) are being systematically evaluated. The review of studies continues and will be published as an NCRP commentary in 2017. Most studies reviewed to date are consistent with a straight-line dose response but there are a few exceptions. In the past, the scientific consensus process has worked in providing practical and prudent guidance. So pragmatic judgment is anticipated. The evaluations are ongoing and the extensive NCRP review process has just begun, so no decisions or recommendations are in stone. The march of science requires a constant assessment of emerging evidence to provide an optimum, though not necessarily perfect, approach to radiation protection. Alternatives to the LNT model may be forthcoming, e.g. an approach that couples the best epidemiology with biologically-based models of carcinogenesis, focusing on chronic (not acute) exposure circumstances. Currently for the practical purposes of radiation protection, the LNT hypothesis reigns supreme as the best of the rest, but new epidemiology and radiobiology might change these conclusions. Stay tuned!
MacGrogan, Gaëtan; Mathieu, Marie-Christine; Poulet, Bruno; Penault-Llorca, Frédérique; Vincent-Salomon, Anne; Roger, Pascal; Treilleux, Isabelle; Valent, Alexander; Antoine, Martine; Becette, Véronique; Bor, Catherine; Brabencova, Eva; Charafe-Jauffret, Emmanuelle; Chenard, Marie-Pierre; Dauplat, Marie-Mélanie; Delrée, Paul; Devouassoux, Mojgan; Fiche, Maryse; Fondrevelle, Marie-Eve; Fridman, Viviana; Garbar, Christian; Genin, Pascal; Ghnassia, Jean-Pierre; Haudebourg, Juliette; Laberge-Le Couteulx, Sophie; Loussouarn, Delphine; Maran-Gonzalez, Aurélie; Marcy, Myriam; Michenet, Patrick; Sagan, Christine; Trassard, Martine; Verriele, Véronique; Arnould, Laurent; Lacroix-Triki, Magali
2014-10-01
Biomarker assessment of breast cancer tumor samples is part of the routine workflow of pathology laboratories. International guidelines have recently been updated, with special regards to the pre-analytical steps that are critical for the quality of immunohistochemical and in situ hybridization procedures, whatever the biomarker analyzed. Fixation and specimen handling protocols must be standardized, validated and carefully tracked. Cooperation and training of the personnel involved in the specimen workflow (e.g. radiologists, surgeons, nurses, technicians and pathologists) are of paramount importance. The GEFPICS' update of the recommendations herein details and comments the different steps of the pre-analytical process. Application of these guidelines and participation to quality insurance programs are mandatory to ensure the correct evaluation of oncotheranostic biomarkers. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kuhne, W.
The purpose of this report is to 1) update previous Savannah River National Laboratory (SRNL) assessment reports (Kvartek et al. 1994 and Halverson et al. 2008) on the fate of mercury in the Savannah River Site (SRS) environment and 2) address comments and recommendations from the review of SRS by the Agency for Toxic Substances and Disease Registry (ATSDR) concerning the evaluation of exposures to contaminants in biota originating from the SRS. The ATSDR reviewed and evaluated data from SRS, South Carolina Department of Health & Environmental Control (SCDHEC) and the Georgia Department of Natural Resources (GDNR) concerning the non-radioactivemore » contaminant mercury. This report will provide a response and update to conclusions and recommendations made by the ATSDR.« less
High School Equivalency Assessment and Recognition in the United States: An Eyewitness Account
ERIC Educational Resources Information Center
McLendon, Lennox
2017-01-01
This chapter on high school equivalency describes recent events involved in updating the adult education high school equivalency assessment services and the entrance of additional assessments into the field.
Dougherty, T B; Porche, V H; Thall, P F
2000-04-01
This study investigated the ability of the modified continual reassessment method (MCRM) to determine the maximum tolerated dose of the opioid antagonist nalmefene, which does not reverse analgesia in an acceptable number of postoperative patients receiving epidural fentanyl in 0.075% bupivacaine. In the postanesthetic care unit, patients received a single intravenous dose of 0.25, 0.50, 0.75, or 1.00 microg/kg nalmefene. Reversal of analgesia was defined as an increase in pain score of two or more integers above baseline on a visual analog scale from 0 through 10 after nalmefene administration. Patients were treated in cohorts of one, starting with the lowest dose. The maximum tolerated dose of nalmefene was defined as that dose, among the four studied, with a final mean probability of reversal of anesthesia (PROA) closest to 0.20 (ie., a 20% chance of causing reversal). The modified continual reassessment method is an iterative Bayesian statistical procedure that, in this study, selected the dose for each successive cohort as that having a mean PROA closest to the preselected target PROA of 0.20. The modified continual reassessment method repeatedly updated the PROA of each dose level as successive patients were observed for presence or absence of ROA. After 25 patients, the maximum tolerated dose of nalmefene was selected as 0.50 microg/kg (final mean PROA = 0.18). The 1.00-microg/kg dose was never tried because its projected PROA was far above 0.20. The modified continual reassessment method facilitated determination of the maximum tolerated dose ofnalmefene . Operating characteristics of the modified continual reassessment method suggest it may be an effective statistical tool for dose-finding in trials of selected analgesic or anesthetic agents.
Dose-Response Modelling of Paralytic Shellfish Poisoning (PSP) in Humans
Arnich, Nathalie; Thébault, Anne
2018-01-01
Paralytic shellfish poisoning (PSP) is caused by a group of marine toxins with saxitoxin (STX) as the reference compound. Symptoms in humans after consumption of contaminated shellfish vary from slight neurological and gastrointestinal effects to fatal respiratory paralysis. A systematic review was conducted to identify reported cases of human poisoning associated with the ingestion of shellfish contaminated with paralytic shellfish toxins (PSTs). Raw data were collected from 143 exposed individuals (113 with symptoms, 30 without symptoms) from 13 studies. Exposure estimates were based on mouse bioassays except in one study. A significant relationship between exposure to PSTs and severity of symptoms was established by ordinal modelling. The critical minimal dose with a probability higher than 10% of showing symptoms is 0.37 µg STX eq./kg b.w. This means that 10% of the individuals exposed to this dose would have symptoms (without considering the severity of the symptoms). This dose is four-fold lower than the lowest-observed-adverse-effect-level (LOAEL) established by the European Food Safety Authority (EFSA, 2009) in the region of 1.5 μg STX eq./kg b.w. This work provides critical doses that could be used as point of departure to update the acute reference dose for STX. This is the first time a dose-symptoms model could be built for marine toxins using epidemiological data. PMID:29597338
NCRP Vision for the Future and Program Area Committee Activities.
Boice, John D
2017-02-01
The National Council on Radiation Protection and Measurements (NCRP) believes that the most critical need for the nation in radiation protection is to train, engage, and retain radiation professionals for the future. Not only is the pipeline shrinking, but for some areas there is no longer a pipe! When the call comes to respond, there may be no one to answer the phone! The NCRP "Where are the Radiation Professionals?" initiative, Council Committee (CC) 2, and this year's annual meeting are to focus our efforts to find solutions and not just reiterate the problems. Our next major initiative is CC 1, where the NCRP is making recommendations for the United States on all things dealing with radiation protection. Our last publication was NCRP Report No. 116, Limitation of Exposure to Ionizing Radiation, in 1993-time for an update. NCRP has seven active Program Area Committees on biology and epidemiology, operational concerns, emergency response and preparedness, medicine, environmental issues and waste management, dosimetry, and communications. A major scientific research initiative is the Million Person Study of Low Dose Radiation Health Effects. It includes workers from the Manhattan Project, nuclear weapons test participants (atomic veterans), industrial radiographers, and early medical workers such as radiologists and technologists. This research will answer the one major gap in radiation risk evaluation: what are the health effects when the exposure occurs gradually over time? Other cutting edge initiatives include a re-evaluation of science behind recommendations for lens of the eye dose limits, recommendations for emergency responders on dosimetry after a major radiological incident, guidance to the National Aeronautics and Space Administration with regard to possible central nervous system effects from galactic cosmic rays (the high energy, high mass particles bounding through space), re-evaluating the population exposure to medical radiation (NCRP Report No. 160, Ionizing Radiation Exposure of the Population of the United States, is over 10 y old, and computed tomography exams have increased substantially since then), and concerning whether the linear no-, threshold model is still the best available for purposes of radiation protection (not for risk assessment). We believe evaluation of heart disease and cerebral vascular disease following low-dose and dose-rate exposure is important for assessments of possible detriment from such exposures. We continue to seek the necessary resources to follow our quest to improve radiation protection for the public!
NRC Monitoring of Salt Waste Disposal at the Savannah River Site - 13147
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pinkston, Karen E.; Ridge, A. Christianne; Alexander, George W.
2013-07-01
As part of monitoring required under Section 3116 of the Ronald W. Reagan National Defense Authorization Act for Fiscal Year 2005 (NDAA), the NRC staff reviewed an updated DOE performance assessment (PA) for salt waste disposal at the Saltstone Disposal Facility (SDF). The NRC staff concluded that it has reasonable assurance that waste disposal at the SDF meets the 10 CFR 61 performance objectives for protection of individuals against intrusion (chap.61.42), protection of individuals during operations (chap.61.43), and site stability (chap.61.44). However, based on its evaluation of DOE's results and independent sensitivity analyses conducted with DOE's models, the NRC staffmore » concluded that it did not have reasonable assurance that DOE's disposal activities at the SDF meet the performance objective for protection of the general population from releases of radioactivity (chap.61.41) evaluated at a dose limit of 0.25 mSv/yr (25 mrem/yr) total effective dose equivalent (TEDE). NRC staff also concluded that the potential dose to a member of the public is expected to be limited (i.e., is expected to be similar to or less than the public dose limit in chap.20.1301 of 1 mSv/yr [100 mrem/yr] TEDE) and is expected to occur many years after site closure. The NRC staff used risk insights gained from review of the SDF PA, its experience monitoring DOE disposal actions at the SDF over the last 5 years, as well as independent analysis and modeling to identify factors that are important to assessing whether DOE's disposal actions meet the performance objectives. Many of these factors are similar to factors identified in the NRC staff's 2005 review of salt waste disposal at the SDF. Key areas of interest continue to be waste form and disposal unit degradation, the effectiveness of infiltration and erosion controls, and estimation of the radiological inventory. Based on these factors, NRC is revising its plan for monitoring salt waste disposal at the SDF in coordination with South Carolina Department of Health and Environmental Control (SCDHEC). DOE has completed or begun additional work related to salt waste disposal to address these factors. NRC staff continues to evaluate information related to the performance of the SDF and has been working with DOE and SCDHEC to resolve NRC staff's technical concerns. (authors)« less
NASA ESTO Lidar Technologies Investment Strategy: 2016 Decadal Update
NASA Technical Reports Server (NTRS)
Valinia, Azita; Komar, George J.; Tratt, David M.; Lotshaw, William T.; Gaab, Kevin M.
2016-01-01
The NASA Earth Science Technology Office (ESTO) recently updated its investment strategy in the area of lidar technologies as it pertains to NASA's Earth Science measurement goals in the next decade. The last ESTO lidar strategy was documented in 2006. The current (2016) report assesses the state-of-the-art in lidar technologies a decade later. Lidar technology maturation in the past decade has been evaluated, and the ESTO investment strategy is updated and laid out in this report according to current NASA Earth science measurement needs and new emerging technologies.
NASA ESTO Lidar Technologies Investment Strategy: 2016 Decadal Update
NASA Technical Reports Server (NTRS)
Valinia, Azita; Komar, George J.; Tratt, David M.; Lotshaw, William; Gaab, Kevin; Mayo, David
2016-01-01
The NASA Earth Science Technology Office (ESTO) recently updated its investment strategy in the area of lidar technologies as it pertains to NASAs Earth Science measurement goals in the next decade. The last ESTO lidar strategy was documented in 2006. The current (2016) report assesses the state-of-the-art in lidar technologies a decade later. Lidar technology maturation in the past decade has been evaluated, and the ESTO investment strategy is updated and laid out in this report according to current NASA Earth science measurement needs and new emerging technologies.
NASA ESTO Lidar Technologies Investment Strategy: 2016 Decadal Update
NASA Technical Reports Server (NTRS)
Valinia, Azita; Komar, George J.; Tratt, David M.; Lotshaw, William T.; Gaab, Kevin M.
2017-01-01
The NASA Earth Science Technology Office (ESTO) recently updated its investment strategy in the area of lidar technologies as it pertains to NASA's Earth Science measurement goals in the next decade. The last ESTO lidar strategy was documented in 2006. The current (2016) report assesses the state-of-the-art in lidar technologies a decade later. Lidar technology maturation in the past decade has been evaluated, and the ESTO investment strategy is updated and laid out in this report according to current NASA Earth science measurement needs and new emerging technologies.
Update on the Medical Management of Crohn's Disease.
Deepak, Parakkal; Bruining, David H
2015-11-01
The medical management of Crohn's disease is a rapidly evolving field with expanding therapeutic drug options and treatment strategies. In addition to corticosteroids, immunomodulators, and anti-tumor necrosis (anti-TNF) agents, a new anti-adhesion medication (vedolizumab) has been approved. Individualized patient-based dosing of immunomodulators and biologic agents is now possible with therapeutic drug monitoring (TDM). There is a changing paradigm in treatment goals to achieve deeper remission identified by composite clinical and endoscopic endpoints. More aggressive treatment strategies in the postoperative setting have been proposed due to emerging data on medication efficacy in this setting. Management algorithms that stratify CD patients into risk groups to balance treatment benefit against adverse events and costs are being developed to translate research into clinical practice. This review provides an update on these new developments for practicing gastroenterologists.
An Update on Drugs Used for Lumbosacral Epidural Anesthesia and Analgesia in Dogs
Steagall, Paulo V. M.; Simon, Bradley T.; Teixeira Neto, Francisco J.; Luna, Stelio P. L.
2017-01-01
This review aims to report an update on drugs administered into the epidural space for anesthesia and analgesia in dogs, describing their potential advantages and disadvantages in the clinical setting. Databases searched include Pubmed, Google scholar, and CAB abstracts. Benefits of administering local anesthetics, opioids, and alpha2 agonists into the epidural space include the use of lower doses of general anesthetics (anesthetic “sparing” effect), perioperative analgesia, and reduced side effects associated with systemic administration of drugs. However, the potential for cardiorespiratory compromise, neurotoxicity, and other adverse effects should be considered when using the epidural route of administration. When these variables are considered, the epidural technique is useful as a complementary method of anesthesia for preventive and postoperative analgesia and/or as part of a balanced anesthesia technique. PMID:28553642
Stranden, E; Widmark, A; Sekse, T
2008-05-01
Interventional radiologists receive significant radiation doses, and it is important to have simple methods for routine monitoring of their exposure. To evaluate the usefulness of a dosimeter worn outside the protective apron for assessments of dose to interventional radiologists. Assessments of effective dose versus dose to dosimeters worn outside the protective apron were achieved by phantom measurements. Doses outside and under the apron were assessed by phantom measurements and measurements on eight radiologists wearing two routine dosimeters for a 2-month period during ordinary working conditions. Finger doses for the same radiologists were recorded using thermoluminescent dosimeters (TLD; DXT-RAD Extremity dosimeters). Typical values for the ratio between effective dose and dosimeter dose were found to be about 0.02 when the radiologist used a thyroid shield and about 0.03 without. The ratio between the dose to the dosimeter under and outside a protective apron was found to be less than 0.04. There was very good correlation between finger dose and dosimeter dose. A personal dosimeter worn outside a protective apron is a good screening device for dose to the eyes and fingers as well as for effective dose, even though the effective dose is grossly overestimated. Relatively high dose to the fingers and eyes remains undetected by a dosimeter worn under the apron.
Updating Dosimetry for Emergency Response Dose Projections.
DeCair, Sara
2016-02-01
In 2013, the U.S. Environmental Protection Agency (EPA) proposed an update to the 1992 Protective Action Guides (PAG) Manual. The PAG Manual provides guidance to state and local officials planning for radiological emergencies. EPA requested public comment on the proposed revisions, while making them available for interim use by officials faced with an emergency situation. Developed with interagency partners, EPA's proposal incorporates newer dosimetric methods, identifies tools and guidelines developed since the current document was issued, and extends the scope of the PAGs to all significant radiological incidents, including radiological dispersal devices or improvised nuclear devices. In order to best serve the emergency management community, scientific policy direction had to be set on how to use International Commission on Radiological Protection Publication 60 age groups in dose assessment when implementing emergency guidelines. Certain guidelines that lend themselves to different PAGs for different subpopulations are the PAGs for potassium iodide (KI), food, and water. These guidelines provide age-specific recommendations because of the radiosensitivity of the thyroid and young children with respect to ingestion and inhalation doses in particular. Taking protective actions like using KI, avoiding certain foods or using alternative sources of drinking water can be relatively simple to implement by the parents of young children. Clear public messages can convey which age groups should take which action, unlike how an evacuation or relocation order should apply to entire households or neighborhoods. New in the PAG Manual is planning guidance for the late phase of an incident, after the situation is stabilized and efforts turn toward recovery. Because the late phase can take years to complete, decision makers are faced with managing public exposures in areas not fully remediated. The proposal includes quick-reference operational guidelines to inform re-entry to the contaminated zone. Broad guidance on approaches to wide-area cleanup and cleanup goals is also provided. EPA adapted the cleanup process from the 2008 U.S. Department of Homeland Security (DHS) Planning Guidance for Protection and Recovery Following Radiological Dispersal Device (RDD) and Improvised Nuclear Device (IND) Incidents, and the final PAG Manual will supersede that DHS guidance. Waste management guidance is also provided. Recognizing that an incident could result in radioactive waste volumes that severely strain or exceed available resources and capacity, officials may consider alternatives for disposal of waste that is relatively lightly contaminated. Waste management, including treatment, staging, and interim and long-term storage, must be an integral part of recovery.
Steen, Dylan L; Khan, Irfan; Ansell, David; Sanchez, Robert J; Ray, Kausik K
2017-02-17
In 2014, guidelines from the National Institute for Health and Care Excellence (NICE) provided updated recommendations on lipid-modifying therapy (LMT). We assessed clinical practice contemporaneous to release of these guidelines in a UK general practice setting for secondary and high-risk primary-prevention populations, and extrapolated the findings to UK nation level. Patients from The Health Improvement Network database with the following criteria were included: lipid profile in 2014 (index date); ≥20 years of age; ≥2 years representation in database prior to index; ≥1 statin indication either for atherosclerotic cardiovascular disease (ASCVD) or the non-ASCVD conditions high-risk diabetes mellitus and/or chronic kidney disease. Overall, 183 565 patients met the inclusion criteria (n=91 479 for ASCVD, 92 086 for non-ASCVD). In those with ASCVD, 79% received statin treatment and 31% received high-intensity statin. In the non-ASCVD group, 62% were on a statin and 57% received medium-intensity or high-intensity statin. In the ASCVD and non-ASCVD cohorts, 6% and 15%, respectively, were already treated according to dosing recommendations as per updated NICE guidelines. Extrapolation to the 2014 UK population indicated that, of the 3.3 million individuals with ASCVD, 2.4 million would require statin uptitration and 680 000 would require statin initiation (31% de novo initiation, 60% reinitiation, 9% addition to non-statin LMT) to achieve full concordance with updated guidelines. Of the 3.5 million high-risk non-ASCVD individuals, 1.6 million would require statin uptitration and 1.4 million would require statin initiation (59% de novo initiation, 36% reinitiation, 5% addition to non-statin LMT). A large proportion of UK individuals with ASCVD and high-risk non-ASCVD received statin treatment (79% and 62%, respectively) during the year of NICE 2014 guidelines release. Up to 94% of patients with ASCVD and 85% of high-risk non-ASCVD individuals, representing ∼3 million individuals in each group, would require statin uptitration or initiation to achieve full concordance with updated guidelines. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Gernant, Stephanie A; Bastien, Rachel; Lai, Andrea
2015-01-01
To present the development of a multidisciplinary controlled substances committee and describe its effectiveness in relation to prescribers' acceptance of committee recommendations, the number of premature deaths associated with controlled substances, and prescribers' need for education on controlled substances. A patient-centered medical home and accountable care organization in Maine that serves more than 60,000 patients across a large rural area, 70% of whom are classified as lower income. A multidisciplinary group of prescribers and PharmD residents created a committee to influence organizational culture regarding controlled substances. The Controlled Substances Initiative Committee (CSIC) updated institutional policies, developed provider education, and made personalized patient recommendations to prescribers. The primary outcome was average change in daily morphine equivalent dose (MED) in patients for whom CSIC recommended a dose reduction to the patient's prescriber. Secondary outcomes included the proportion of patients who died of a known overdose or suspected drug-related death during 2012-2013 or 2013-2014. In addition, prescriber beliefs about controlled substances were measured via a needs assessment. The average daily MED for patients whom CSIC recommended dose reduction was lower after 3 months compared with at baseline (175.5 ± 344.3 mg vs. 292.7 ± 466.5 mg; P <0.05). The proportion of patients who died of a known overdose did not differ between 2012-2013 and 2013-2014 (11.8% vs. 11.1%; P = 1.00). However, a greater number of patients had a suspected drug-related death during 2013-2014 compared with during 2012-2013 (0% vs. 27.3%; P = 0.05). A multidisciplinary controlled substances committee may improve patient safety and outcomes by offering prescriber support and helping alter prescribing culture.
Case study thoracic radiotherapy in an elderly patient with pacemaker: The issue of pacing leads
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kirova, Youlia M., E-mail: youlia.kirova@curie.net; Menard, Jean; Chargari, Cyrus
2012-07-01
To assess clinical outcome of patients with pacemaker treated with thoracic radiation therapy for T8-T9 paravertebral chloroma. A 92-year-old male patient with chloroma presenting as paravertebral painful and compressive (T8-T9) mass was referred for radiotherapy in the Department of Radiation Oncology, Institut Curie. The patient presented with cardiac dysfunction and a permanent pacemaker that had been implanted prior. The decision of Multidisciplinary Meeting was to deliver 30 Gy in 10 fractions for reducing the symptoms and controlling the tumor growth. The patient received a total dose of 30 Gy in 10 fractions using 4-field conformal radiotherapy with 20-MV photons. Themore » dose to pacemaker was 0.1 Gy but a part of the pacing leads was in the irradiation fields. The patient was treated the first time in the presence of his radiation oncologist and an intensive care unit doctor. Moreover, the function of his pacemaker was monitored during the entire radiotherapy course. No change in pacemaker function was observed during any of the radiotherapy fractions. The radiotherapy was very well tolerated without any side effects. The function of the pacemaker was checked before and after the radiotherapy treatment by the cardiologist and no pacemaker dysfunction was observed. Although updated guidelines are needed with acceptable dose criteria for implantable cardiac devices, it is possible to treat patients with these devices and parts encroaching on the radiation field. This case report shows we were able to safely treat our patient through a multidisciplinary approach, monitoring the patient during each step of the treatment.« less
Update: Mode of action (MOA) for liver tumors induced by oral exposure to 1,4-dioxane.
Dourson, Michael L; Higginbotham, Jeri; Crum, Jeff; Burleigh-Flayer, Heather; Nance, Patricia; Forsberg, Norman D; Lafranconi, Mark; Reichard, John
2017-08-01
Previous work has shown that the weight of evidence supports the hypothesis that 1,4-dioxane causes liver tumors in rodents through cytotoxicity and subsequent regenerative hyperplasia. Questions regarding a lack of concordant findings for this mode of action (MOA) in mice have not been resolved, however. In the current work, a reanalysis of data from two chronic mouse cancer bioassays on 1,4-dioxane, one 13-week mouse study, seven rat cancer bioassays, coupled with other data such as 1,4-dioxane's negative mutagenicity, its lack of up-regulated DNA repair, and the appearance of liver tumors with a high background incidence, support the conclusion that rodent liver tumors, including those in mice, are evoked by a regenerative hyperplasia MOA. The initiating event for this MOA is metabolic saturation of 1,4-dioxane. Above metabolic saturation, higher doses of the parent compound cause an ever increasing toxicity in the rodent liver as evidenced by higher blood levels of enzymes indicative of liver cell damage and associated histopathology that occurs in a dose and time related manner. Importantly, alternative modes of action can be excluded. The observed liver toxicity has a threshold in the dose scale at or below levels that saturate metabolism, and generally in the range of 9.6-42 mg/kg-day for rats and 57 to 66 mg/kg-day for mice. It follows that threshold approaches to the assessment of this chemical's toxicity are supported by the non-mutagenic, metabolic saturation kinetics, and cytotoxicity-generated regenerative repair information available for 1,4-dioxane promoted rodent liver tumors. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
EVALUATING QUANTITATIVE FORMULAS FOR DOSE-RESPONSE ASSESSMENT OF CHEMICAL MIXTURES
Risk assessment formulas are often distinguished from dose-response models by being rough but necessary. The evaluation of these rough formulas is described here, using the example of mixture risk assessment. Two conditions make the dose-response part of mixture risk assessment d...
Methods for Probabilistic Radiological Dose Assessment at a High-Level Radioactive Waste Repository.
NASA Astrophysics Data System (ADS)
Maheras, Steven James
Methods were developed to assess and evaluate the uncertainty in offsite and onsite radiological dose at a high-level radioactive waste repository to show reasonable assurance that compliance with applicable regulatory requirements will be achieved. Uncertainty in offsite dose was assessed by employing a stochastic precode in conjunction with Monte Carlo simulation using an offsite radiological dose assessment code. Uncertainty in onsite dose was assessed by employing a discrete-event simulation model of repository operations in conjunction with an occupational radiological dose assessment model. Complementary cumulative distribution functions of offsite and onsite dose were used to illustrate reasonable assurance. Offsite dose analyses were performed for iodine -129, cesium-137, strontium-90, and plutonium-239. Complementary cumulative distribution functions of offsite dose were constructed; offsite dose was lognormally distributed with a two order of magnitude range. However, plutonium-239 results were not lognormally distributed and exhibited less than one order of magnitude range. Onsite dose analyses were performed for the preliminary inspection, receiving and handling, and the underground areas of the repository. Complementary cumulative distribution functions of onsite dose were constructed and exhibited less than one order of magnitude range. A preliminary sensitivity analysis of the receiving and handling areas was conducted using a regression metamodel. Sensitivity coefficients and partial correlation coefficients were used as measures of sensitivity. Model output was most sensitive to parameters related to cask handling operations. Model output showed little sensitivity to parameters related to cask inspections.
NASA Technical Reports Server (NTRS)
Burns, Lee; Merry, Carl; Decker, Ryan; Harrington, Brian
2008-01-01
The 2006 Cape Canaveral Air Force Station (CCAFS) Range Reference Atmosphere (RRA) is a statistical model summarizing the wind and thermodynamic atmospheric variability from surface to 70 kin. Launches of the National Aeronautics and Space Administration's (NASA) Space Shuttle from Kennedy Space Center utilize CCAFS RRA data to evaluate environmental constraints on various aspects of the vehicle during ascent. An update to the CCAFS RRA was recently completed. As part of the update, a validation study on the 2006 version was conducted as well as a comparison analysis of the 2006 version to the existing CCAFS RRA database version 1983. Assessments to the Space Shuttle vehicle ascent profile characteristics were performed to determine impacts of the updated model to the vehicle performance. Details on the model updates and the vehicle sensitivity analyses with the update model are presented.
An update on childhood bone health: mineral accrual, assessment and treatment.
Sopher, Aviva B; Fennoy, Ilene; Oberfield, Sharon E
2015-02-01
To update the reader's knowledge about the factors that influence bone mineral accrual and to review the advances in the assessment of bone health and treatment of bone disorders. Maternal vitamin D status influences neonatal calcium levels, bone mineral density (BMD) and bone size. In turn, BMD z-score tends to track in childhood. These factors highlight the importance of bone health as early as fetal life. Dual-energy x-ray absorptiometry is the mainstay of clinical bone health assessment in this population because of the availability of appropriate reference data. Recently, more information has become available about the assessment and treatment of bone disease in chronically ill pediatric patients. Bone health must become a health focus starting prenatally in order to maximize peak bone mass and to prevent osteoporosis-related bone disease in adulthood. Vitamin D, calcium and weight-bearing activity are the factors of key importance throughout childhood in achieving optimal bone health as BMD z-score tracks through childhood and into adulthood. Recent updates of the International Society for Clinical Densitometry focus on the appropriate use of dual-energy x-ray absorptiometry in children of all ages, including children with chronic disease, and on the treatment of pediatric bone disease.
EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016.
Babjuk, Marko; Böhle, Andreas; Burger, Maximilian; Capoun, Otakar; Cohen, Daniel; Compérat, Eva M; Hernández, Virginia; Kaasinen, Eero; Palou, Joan; Rouprêt, Morgan; van Rhijn, Bas W G; Shariat, Shahrokh F; Soukup, Viktor; Sylvester, Richard J; Zigeuner, Richard
2017-03-01
The European Association of Urology (EAU) panel on Non-muscle-invasive Bladder Cancer (NMIBC) released an updated version of the guidelines on Non-muscle-invasive Bladder Cancer. To present the 2016 EAU guidelines on NMIBC. A broad and comprehensive scoping exercise covering all areas of the NMIBC guidelines published between April 1, 2014, and May 31, 2015, was performed. Databases covered by the search included Medline, Embase, and the Cochrane Libraries. Previous guidelines were updated, and levels of evidence and grades of recommendation were assigned. Tumours staged as TaT1 or carcinoma in situ (CIS) are grouped as NMIBC. Diagnosis depends on cystoscopy and histologic evaluation of the tissue obtained by transurethral resection of the bladder (TURB) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TURB is essential for the patient's prognosis. If the initial resection is incomplete, there is no muscle in the specimen, or a high-grade or T1 tumour is detected, a second TURB should be performed within 2-6 wk. The risks of both recurrence and progression may be estimated for individual patients using the European Organisation for Research and Treatment of Cancer (EORTC) scoring system and risk tables. The stratification of patients into low-, intermediate-, and high-risk groups is pivotal to recommending adjuvant treatment. For patients with a low-risk tumour and intermediate-risk patients at a lower risk of recurrence, one immediate instillation of chemotherapy is recommended. Patients with an intermediate-risk tumour should receive 1 yr of full-dose bacillus Calmette-Guérin (BCG) intravesical immunotherapy or instillations of chemotherapy for a maximum of 1 yr. In patients with high-risk tumours, full-dose intravesical BCG for 1-3 yr is indicated. In patients at highest risk of tumour progression, immediate radical cystectomy (RC) should be considered. RC is recommended in BCG-refractory tumours. The long version of the guidelines is available at the EAU Web site (www.uroweb.org/guidelines). These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice. The European Association of Urology has released updated guidelines on Non-muscle-invasive Bladder Cancer (NMIBC). Stratification of patients into low-, intermediate-, and high-risk groups is essential for decisions about adjuvant intravesical instillations. Risk tables can be used to estimate risks of recurrence and progression. Radical cystectomy should be considered only in case of failure of instillations or in NMIBC with the highest risk of progression. Copyright © 2016. Published by Elsevier B.V.
Bumper 3 Update for IADC Protection Manual
NASA Technical Reports Server (NTRS)
Christiansen, Eric L.; Nagy, Kornel; Hyde, Jim
2016-01-01
The Bumper code has been the standard in use by NASA and contractors to perform meteoroid/debris risk assessments since 1990. It has undergone extensive revisions and updates [NASA JSC HITF website; Christiansen et al., 1992, 1997]. NASA Johnson Space Center (JSC) has applied BUMPER to risk assessments for Space Station, Shuttle, Mir, Extravehicular Mobility Units (EMU) space suits, and other spacecraft (e.g., LDEF, Iridium, TDRS, and Hubble Space Telescope). Bumper continues to be updated with changes in the ballistic limit equations describing failure threshold of various spacecraft components, as well as changes in the meteoroid and debris environment models. Significant efforts are expended to validate Bumper and benchmark it to other meteoroid/debris risk assessment codes. Bumper 3 is a refactored version of Bumper II. The structure of the code was extensively modified to improve maintenance, performance and flexibility. The architecture was changed to separate the frequently updated ballistic limit equations from the relatively stable common core functions of the program. These updates allow NASA to produce specific editions of the Bumper 3 that are tailored for specific customer requirements. The core consists of common code necessary to process the Micrometeoroid and Orbital Debris (MMOD) environment models, assess shadowing and calculate MMOD risk. The library of target response subroutines includes a board range of different types of MMOD shield ballistic limit equations as well as equations describing damage to various spacecraft subsystems or hardware (thermal protection materials, windows, radiators, solar arrays, cables, etc.). The core and library of ballistic response subroutines are maintained under configuration control. A change in the core will affect all editions of the code, whereas a change in one or more of the response subroutines will affect all editions of the code that contain the particular response subroutines which are modified. Note that the Bumper II program is no longer maintained or distributed by NASA.
Application of spectroscopic techniques in the radiation dosimetry of glasses: An update
NASA Astrophysics Data System (ADS)
Natarajan, V.
2009-07-01
The colorimetry and thermoluminescence properties of gamma irradiated glass were reported in as early as 1920. The utility of radio-photoluminescence (RPL) of silver activated metaphosphate glass for monitoring high doses of accidental and routine gamma radiation was reported in the 1960s. Since then considerable amount of research work has been carried out to study the thermoluminescence (TL), optical absorption (OA), electron paramagnetic resonance (EPR) and optically stimulated luminescence (OSL) of different commercially available glasses for high as well as low dose applications. A brief review of the progress made in the spectroscopic studies of glasses during the past few decades and the application of glasses for radiation dosimetry has been given in this paper.
Update on invasive meningococcal vaccination for Canadian children and youth.
Robinson, Joan L
2018-02-01
Invasive meningococcal disease (IMD) is serious, often resulting in fulminant sepsis or meningitis. IMD in Canada is primarily attributable to serogroups B and C. There are routine programs for serogroup C vaccine at 12 months of age, with some jurisdictions routinely providing additional earlier doses. Adolescents routinely receive a booster dose of serogroup C vaccine or of a quadrivalent (serogroups A, C, W and Y) vaccine. Serogroup B vaccines are not recommended for routine use pending further data on the efficacy and duration of protection from the available vaccine. However, children at increased risk for IMD should start immunization for serogroups B and C as soon as possible, assuming that they are at least 2 months of age.
An update on 'dose calibrator' settings for nuclides used in nuclear medicine.
Bergeron, Denis E; Cessna, Jeffrey T
2018-06-01
Most clinical measurements of radioactivity, whether for therapeutic or imaging nuclides, rely on commercial re-entrant ionization chambers ('dose calibrators'). The National Institute of Standards and Technology (NIST) maintains a battery of representative calibrators and works to link calibration settings ('dial settings') to primary radioactivity standards. Here, we provide a summary of NIST-determined dial settings for 22 radionuclides. We collected previously published dial settings and determined some new ones using either the calibration curve method or the dialing-in approach. The dial settings with their uncertainties are collected in a comprehensive table. In general, current manufacturer-provided calibration settings give activities that agree with National Institute of Standards and Technology standards to within a few percent.
How to Manual: How to Update and Enhance Your Local Source Water Protection Assessments
Describes opportunities for improving source water assessments performed under the Safe Drinking Water Act 1453. It includes: local delineations, potential contaminant source inventories, and susceptibility determinations of source water assessment.
An update on local anesthesia for pediatric dental patients
Peedikayil, Faizal C.; Vijayan, Ajoy
2013-01-01
Pain control is an important part of dentistry, particularly in the management of children. Behavior guidance, and dose and technique of administration of the local anesthetic are important considerations in the successful treatment of a pediatric patient. The purpose of the present review is to discuss the relevant data on topics involved, and on the current methods available in the administration of local anesthesia used for pediatric dental patients. PMID:25885712
Maier, A; Vincent, M; Hack, E; Nance, P; Ball, W
2014-04-01
Inorganic borates are encountered in many settings worldwide, spurring international efforts to develop exposure guidance (US EPA, 2004; WHO, 2009; ATSDR, 2010) and occupational exposure limits (OEL) (ACGIH, 2005; MAK, 2011). We derived an updated OEL to reflect new data and current international risk assessment frameworks. We assessed toxicity and epidemiology data on inorganic borates to identify relevant adverse effects. International risk assessment frameworks (IPCS, 2005, 2007) were used to evaluate endpoint candidates: reproductive toxicity, developmental toxicity, and sensory irritation. For each endpoint, a preliminary OEL was derived and adjusted based on consideration of toxicokinetics, toxicodynamics, and other uncertainties. Selection of the endpoint point of departures (PODs) is supported by dose-response modeling. Developmental toxicity was the most sensitive systemic effect. An OEL of 1.6mgB/m(3) was estimated for this effect based on a POD of 63mgB/m(3) with an uncertainty factor (UF) of 40. Sensory irritation was considered to be the most sensitive effect for the portal of entry. An OEL of 1.4mgB/m(3) was estimated for this effect based on the identified POD and an UF of 1. An OEL of 1.4mgB/m(3) as an 8-h time-weighted average (TWA) is recommended. Copyright © 2014 Elsevier Inc. All rights reserved.
Nerenberg, Kara A; Zarnke, Kelly B; Leung, Alexander A; Dasgupta, Kaberi; Butalia, Sonia; McBrien, Kerry; Harris, Kevin C; Nakhla, Meranda; Cloutier, Lyne; Gelfer, Mark; Lamarre-Cliche, Maxime; Milot, Alain; Bolli, Peter; Tremblay, Guy; McLean, Donna; Padwal, Raj S; Tran, Karen C; Grover, Steven; Rabkin, Simon W; Moe, Gordon W; Howlett, Jonathan G; Lindsay, Patrice; Hill, Michael D; Sharma, Mike; Field, Thalia; Wein, Theodore H; Shoamanesh, Ashkan; Dresser, George K; Hamet, Pavel; Herman, Robert J; Burgess, Ellen; Gryn, Steven E; Grégoire, Jean C; Lewanczuk, Richard; Poirier, Luc; Campbell, Tavis S; Feldman, Ross D; Lavoie, Kim L; Tsuyuki, Ross T; Honos, George; Prebtani, Ally P H; Kline, Gregory; Schiffrin, Ernesto L; Don-Wauchope, Andrew; Tobe, Sheldon W; Gilbert, Richard E; Leiter, Lawrence A; Jones, Charlotte; Woo, Vincent; Hegele, Robert A; Selby, Peter; Pipe, Andrew; McFarlane, Philip A; Oh, Paul; Gupta, Milan; Bacon, Simon L; Kaczorowski, Janusz; Trudeau, Luc; Campbell, Norman R C; Hiremath, Swapnil; Roerecke, Michael; Arcand, Joanne; Ruzicka, Marcel; Prasad, G V Ramesh; Vallée, Michel; Edwards, Cedric; Sivapalan, Praveena; Penner, S Brian; Fournier, Anne; Benoit, Geneviève; Feber, Janusz; Dionne, Janis; Magee, Laura A; Logan, Alexander G; Côté, Anne-Marie; Rey, Evelyne; Firoz, Tabassum; Kuyper, Laura M; Gabor, Jonathan Y; Townsend, Raymond R; Rabi, Doreen M; Daskalopoulou, Stella S
2018-05-01
Hypertension Canada provides annually updated, evidence-based guidelines for the diagnosis, assessment, prevention, and treatment of hypertension in adults and children. This year, the adult and pediatric guidelines are combined in one document. The new 2018 pregnancy-specific hypertension guidelines are published separately. For 2018, 5 new guidelines are introduced, and 1 existing guideline on the blood pressure thresholds and targets in the setting of thrombolysis for acute ischemic stroke is revised. The use of validated wrist devices for the estimation of blood pressure in individuals with large arm circumference is now included. Guidance is provided for the follow-up measurements of blood pressure, with the use of standardized methods and electronic (oscillometric) upper arm devices in individuals with hypertension, and either ambulatory blood pressure monitoring or home blood pressure monitoring in individuals with white coat effect. We specify that all individuals with hypertension should have an assessment of global cardiovascular risk to promote health behaviours that lower blood pressure. Finally, an angiotensin receptor-neprilysin inhibitor combination should be used in place of either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in individuals with heart failure (with ejection fraction < 40%) who are symptomatic despite appropriate doses of guideline-directed heart failure therapies. The specific evidence and rationale underlying each of these guidelines are discussed. Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
Poet, Torka S; Timchalk, Charles; Bartels, Michael J; Smith, Jordan N; McDougal, Robin; Juberg, Daland R; Price, Paul S
2017-06-01
A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model combined with Monte Carlo analysis of inter-individual variation was used to assess the effects of the insecticide, chlorpyrifos and its active metabolite, chlorpyrifos oxon in humans. The PBPK/PD model has previously been validated and used to describe physiological changes in typical individuals as they grow from birth to adulthood. This model was updated to include physiological and metabolic changes that occur with pregnancy. The model was then used to assess the impact of inter-individual variability in physiology and biochemistry on predictions of internal dose metrics and quantitatively assess the impact of major sources of parameter uncertainty and biological diversity on the pharmacodynamics of red blood cell acetylcholinesterase inhibition. These metrics were determined in potentially sensitive populations of infants, adult women, pregnant women, and a combined population of adult men and women. The parameters primarily responsible for inter-individual variation in RBC acetylcholinesterase inhibition were related to metabolic clearance of CPF and CPF-oxon. Data Derived Extrapolation Factors that address intra-species physiology and biochemistry to replace uncertainty factors with quantitative differences in metrics were developed in these same populations. The DDEFs were less than 4 for all populations. These data and modeling approach will be useful in ongoing and future human health risk assessments for CPF and could be used for other chemicals with potential human exposure. Copyright © 2017 Elsevier Inc. All rights reserved.
Vernooij, Robin W. M.; Alonso-Coello, Pablo; Brouwers, Melissa
2017-01-01
Background Scientific knowledge is in constant development. Consequently, regular review to assure the trustworthiness of clinical guidelines is required. However, there is still a lack of preferred reporting items of the updating process in updated clinical guidelines. The present article describes the development process of the Checklist for the Reporting of Updated Guidelines (CheckUp). Methods and Findings We developed an initial list of items based on an overview of research evidence on clinical guideline updating, the Appraisal of Guidelines for Research and Evaluation (AGREE) II Instrument, and the advice of the CheckUp panel (n = 33 professionals). A multistep process was used to refine this list, including an assessment of ten existing updated clinical guidelines, interviews with key informants (response rate: 54.2%; 13/24), a three-round Delphi consensus survey with the CheckUp panel (33 participants), and an external review with clinical guideline methodologists (response rate: 90%; 53/59) and users (response rate: 55.6%; 10/18). CheckUp includes 16 items that address (1) the presentation of an updated guideline, (2) editorial independence, and (3) the methodology of the updating process. In this article, we present the methodology to develop CheckUp and include as a supplementary file an explanation and elaboration document. Conclusions CheckUp can be used to evaluate the completeness of reporting in updated guidelines and as a tool to inform guideline developers about reporting requirements. Editors may request its completion from guideline authors when submitting updated guidelines for publication. Adherence to CheckUp will likely enhance the comprehensiveness and transparency of clinical guideline updating for the benefit of patients and the public, health care professionals, and other relevant stakeholders. PMID:28072838
Defense.gov - Special Report: Travels with Mullen
updated and may no longer be applicable as a result of changes in law, regulation and/or administration 2009 Top Stories Mullen Updates, Changes Joint Guidance WASHINGTON, Dec. 21, 2009 Â The Afghanistan trip to Afghanistan, Pakistan and Iraq has given him an opportunity to assess changes in strategy and
Federal Register 2010, 2011, 2012, 2013, 2014
2013-08-05
... provides an updated cost/benefit analysis providing an assessment of the benefits attained by HUD through... the scope of the existing computer matching program to now include the updated cost/ benefit analysis... change, and find a continued favorable examination of benefit/cost results; and (2) All parties certify...
Complex Burn Region Module (CBRM) update
NASA Technical Reports Server (NTRS)
Adams, Carl L.; Jenkins, Billy
1991-01-01
Presented here is a Complex Burn Region Module (CBRM) update for the Solid Rocket Internal Ballistics Module (SRIBM) Program for the Advanced Solid Rocket Motor (ASRM) design/performance assessments. The goal was to develop an improved version of the solid rocket internal ballistics module program that contains a diversified complex region model for motor grain design, performance prediction, and evaluation.
The 2005 RPA timber assessment update.
Richard W. Haynes; Darius M. Adams; Ralph J. Alig; Peter J. Ince; John R. Mills; Xiaoping. Zhou
2007-01-01
This update reports changes in the Nation's timber resource since the Analysis of the Timber Situation in the United States was completed in 2003. Prospective trends in demands for and supplies of timber, and the factors that affect these trends are examined. These trends include changes in the U.S. economy, increased salvage of British Columbia beetle-killed...
Federal Register 2010, 2011, 2012, 2013, 2014
2013-08-07
... Environmental Assessment (NCEA) within EPA's Office of Research and Development. In November 2006, EPA released... classified as preliminary and not included in the quantitative inventory. The updated inventory lists the top... 2000. The quantitative results are expressed in terms of the toxicity equivalent (TEQ) of the mixture...
IRIS Toxicological Review of Hexahydro-1,3,5-Trinitro-1,3,5 ...
The IRIS Toxicological Review of Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) was released for external peer review in September 2016. The EPA’s Science Advisory Board’s (SAB) Chemical Assessment Advisory Committee (CAAC) will conduct a peer review of the scientific basis supporting the RDX assessment and release a final report of their review. Information regarding the peer review can be found on the SAB website. EPA is undertaking an update of the Integrated Risk Information System (IRIS) health assessment for RDX. The outcome of this project is an updated Toxicological Review and IRIS Summary for RDX that will be entered into the IRIS database.
Transatlantic Comparison of CT Radiation Doses in the Era of Radiation Dose-Tracking Software.
Parakh, Anushri; Euler, Andre; Szucs-Farkas, Zsolt; Schindera, Sebastian T
2017-12-01
The purpose of this study is to compare diagnostic reference levels from a local European CT dose registry, using radiation-tracking software from a large patient sample, with preexisting European and North American diagnostic reference levels. Data (n = 43,761 CT scans obtained over the course of 2 years) for the European local CT dose registry were obtained from eight CT scanners at six institutions. Means, medians, and interquartile ranges of volumetric CT dose index (CTDI vol ), dose-length product (DLP), size-specific dose estimate, and effective dose values for CT examinations of the head, paranasal sinuses, thorax, pulmonary angiogram, abdomen-pelvis, renal-colic, thorax-abdomen-pelvis, and thoracoabdominal angiogram were obtained using radiation-tracking software. Metrics from this registry were compared with diagnostic reference levels from Canada and California (published in 2015), the American College of Radiology (ACR) dose index registry (2015), and national diagnostic reference levels from local CT dose registries in Switzerland (2010), the United Kingdom (2011), and Portugal (2015). Our local registry had a lower 75th percentile CTDI vol for all protocols than did the individual internationally sourced data. Compared with our study, the ACR dose index registry had higher 75th percentile CTDI vol values by 55% for head, 240% for thorax, 28% for abdomen-pelvis, 42% for thorax-abdomen-pelvis, 128% for pulmonary angiogram, 138% for renal-colic, and 58% for paranasal sinus studies. Our local registry had lower diagnostic reference level values than did existing European and North American diagnostic reference levels. Automated radiation-tracking software could be used to establish and update existing diagnostic reference levels because they are capable of analyzing large datasets meaningfully.
Systematic review: reliability of compendia methods for off-label oncology indications.
Abernethy, Amy P; Raman, Gowri; Balk, Ethan M; Hammond, Julia M; Orlando, Lori A; Wheeler, Jane L; Lau, Joseph; McCrory, Douglas C
2009-03-03
The Centers for Medicare & Medicaid Services limit coverage of cancer drugs for off-label indications to indications listed in specified compendia. To assess whether compendia provide comprehensive, research-based, and timely information for off-label prescribing in oncology. 6 drug compendia, English-language literature searches of MEDLINE and the Cochrane Central Register of Controlled Trials from 2006 and 2008, and American Society of Clinical Oncology annual meeting abstracts from 2004 to 2007. Data Assessment: The compendia's stated methods, literature related to off-label indications of 14 cancer drugs in 2006, updated literature related to 1 off-label indication between 2006 and 2008, and completeness of compendia content and citations were assessed. The compendia's stated methods varied greatly from their actual practices. Compendia cited little of the available evidence, often neither the most recent nor that of highest methodological quality. Compendia differed in evidence cited, terminology, detail, presentation, and referencing. For the 14 off-label indications studied, the compendia differed in the indications included and whether and how they recommended particular agents for particular types of cancer. Update schedules varied, and documentation practices made it difficult to determine whether and when compendia content was updated. For 1 indication, compendia citations did not increase between 2006 and 2008 despite newly published articles. The 2006 analysis was limited to 14 off-label indications; the 2008 update examined 1 indication. Only off-label indications for cancer drugs were included, and results cannot be generalized to noncancer drugs or indications. Oncologists rely on compendia for up-to-date access to evidence and reimbursement information for off-label indications. Current compendia lack transparency, cite little current evidence, and lack systematic methods to review or update evidence.
NASA Astrophysics Data System (ADS)
Li, Ning; McLaughlin, Dennis; Kinzelbach, Wolfgang; Li, WenPeng; Dong, XinGuang
2015-10-01
Model uncertainty needs to be quantified to provide objective assessments of the reliability of model predictions and of the risk associated with management decisions that rely on these predictions. This is particularly true in water resource studies that depend on model-based assessments of alternative management strategies. In recent decades, Bayesian data assimilation methods have been widely used in hydrology to assess uncertain model parameters and predictions. In this case study, a particular data assimilation algorithm, the Ensemble Smoother with Multiple Data Assimilation (ESMDA) (Emerick and Reynolds, 2012), is used to derive posterior samples of uncertain model parameters and forecasts for a distributed hydrological model of Yanqi basin, China. This model is constructed using MIKESHE/MIKE11software, which provides for coupling between surface and subsurface processes (DHI, 2011a-d). The random samples in the posterior parameter ensemble are obtained by using measurements to update 50 prior parameter samples generated with a Latin Hypercube Sampling (LHS) procedure. The posterior forecast samples are obtained from model runs that use the corresponding posterior parameter samples. Two iterative sample update methods are considered: one based on an a perturbed observation Kalman filter update and one based on a square root Kalman filter update. These alternatives give nearly the same results and converge in only two iterations. The uncertain parameters considered include hydraulic conductivities, drainage and river leakage factors, van Genuchten soil property parameters, and dispersion coefficients. The results show that the uncertainty in many of the parameters is reduced during the smoother updating process, reflecting information obtained from the observations. Some of the parameters are insensitive and do not benefit from measurement information. The correlation coefficients among certain parameters increase in each iteration, although they generally stay below 0.50.
Major clinical research advances in gynecologic cancer in 2017.
Suh, Dong Hoon; Kim, Miseon; Lee, Kyung Hun; Eom, Keun Yong; Kjeldsen, Maj Kamille; Mirza, Mansoor Raza; Kim, Jae Weon
2018-03-01
In 2017, 10 topics were selected as major clinical research advances in gynecologic oncology. For cervical cancer, efficacy and safety analysis results of a 9-valent human papillomavirus (HPV) vaccine and long-term impact of reduced dose of quadrivalent vaccine were updated. Brief introduction of KEYNOTE trials of pembrolizumab, a monoclonal antibody that blocks the interaction between programmed death (PD)-1 and its ligands, PD-L1 and PD-L2, followed. Tailored surveillance programs for gynecologic cancer related with Lynch syndrome and update on sentinel lymph node mapping were reviewed for uterine corpus cancer. For ovarian cancer, 5 topics were selected including poly(ADP-ribose) polymerases inhibitors and immunotherapy. The other potential practice changers covered in this review were lymphadenectomy in advanced disease, secondary cytoreductive surgery in recurrent disease, weekly dose-dense regimen for first-line chemotherapy, incorporation of bevacizumab maintenance in platinum-sensitive recurrent disease, and effect of platinum-free interval prolongation. Conflicting opinions of academic societies on periodic pelvic examination were introduced in conjunction with relevant literature review. For the field of radiation oncology, results of 2 big trials, The Postoperative Radiation Therapy in Endometrial Carcinoma-3 and Gynecologic Oncology Group-258, for endometrial cancer and recent advance in high-dose-rate brachytherapy for cervical cancer were reported. Topics for breast cancer covered adjuvant capecitabine after preoperative chemotherapy, adjuvant pertuzumab and trastuzumab in early human epidermal growth factor receptor 2-positive disease, olaparib for metastatic cancer in patients with a germline BRCA mutation, 20-year risks of recurrence after stopping endocrine therapy at 5 years, and contemporary hormonal contraception and the risk of breast cancer. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.
Updated Human Health Risk Analyses for Chlorpyrifos
EPA has revised the human health hazard assessment and drinking water exposure assessment for chlorpyrifos that supported our October 2015 proposal to revoke all food residue tolerances for chlorpyrifos.
IRIS Toxicological Review of Benzo[a]pyrene (Interagency ...
In January 2017, EPA finalized the IRIS assessment of Benzo[a]pyrene. The Toxicological Review was reviewed internally by EPA and by other federal agencies and White House Offices before public release. Consistent with the May 2009 IRIS assessment development process, all written comments on IRIS assessments submitted by other federal agencies and White House Offices are made publicly available. Accordingly, interagency comments and the interagency science discussion materials provided to other agencies, including interagency review drafts of the IRIS Toxicological Review of Benzo[a]pyrene are posted on this site. EPA is undertaking an update of the Integrated Risk Information System (IRIS) health assessment for benzo[a]pyrene (BaP). The outcome of this project is an updated Toxicological Review and IRIS Summary for BaP that will be entered into the IRIS database.
Bello, Segun; Meremikwu, Martin M; Ejemot-Nwadiaro, Regina I; Oduwole, Olabisi
2016-08-31
Reduced vitamin A concentration increases the risk of blindness in children infected with the measles virus. Promoting vitamin A supplementation in children with measles contributes to the control of blindness in children, which is a high priority within the World Health Organization (WHO) VISION 2020 The Right to Sight Program. To assess the efficacy of vitamin A in preventing blindness in children with measles without prior clinical features of vitamin A deficiency. We searched CENTRAL 2015, Issue 11, MEDLINE (1950 to December week 3, 2015), Embase (1974 to December 2015) and LILACS (1985 to December 2015). Randomised controlled trials (RCTs) assessing the efficacy of vitamin A in preventing blindness in well-nourished children diagnosed with measles but with no prior clinical features of vitamin A deficiency. For the original review, two review authors independently assessed studies for eligibility and extracted data on reported outcomes. We contacted trial authors of the included studies for additional information on unpublished data. We included two RCTs which were clinically heterogenous. We presented the continuous outcomes reported as the mean difference (MD) with 95% confidence interval (CI) and dichotomous outcomes as risk ratio (RR) with 95% CI. Due to marked clinical heterogeneity we considered it inappropriate to perform a meta-analysis. For the first publication of this review, two RCTs involving 260 children with measles which compared vitamin A with placebo met the inclusion criteria. Neither study reported blindness or other ocular morbidities as end points. One trial of moderate quality suggested evidence of a significant increase in serum retinol levels in the vitamin A group one week after two doses of vitamin A (MD 9.45 µg/dL, 95% CI 2.19 to 16.71; 17 participants, moderate-quality evidence), but not six weeks after three doses of vitamin A (MD 2.56 µg/dL, 95% CI -5.28 to 10.40; 39 participants, moderate-quality evidence). There was no significant difference in weight gain six weeks (MD 0.39 kg, -0.04 to 0.82; 48 participants, moderate-quality evidence) and six months (MD 0.52 kg, 95% CI -0.08 to 1.12; 36 participants, moderate-quality evidence) after three doses of vitamin A.The second trial found no significant difference in serum retinol levels two weeks after a single dose of vitamin A (MD 2.67 µg/dL, 95% CI -0.29 to 5.63; 155 participants, moderate-quality evidence). Percentage of undernutrition between the two groups did not differ significantly at one week (RR 0.93, 95% CI 0.56 to 1.54, 145 participants) and two weeks (RR 0.82, 95% CI 0.52 to 1.29, 147 participants) after a single dose of vitamin A. No adverse event was reported in either study. We did not find any new RCTS for this second update. We did not find any trials assessing whether or not vitamin A supplementation in children with measles prevents blindness, as neither study reported blindness or other ocular morbidities as end points.
Roe, Matthew T; Green, Cynthia L; Giugliano, Robert P; Gibson, C Michael; Baran, Kenneth; Greenberg, Mark; Palmeri, Sebastian T; Crater, Suzanne; Trollinger, Kathleen; Hannan, Karen; Harrington, Robert A; Krucoff, Mitchell W
2004-02-18
This sub-study of the Integrilin and Tenecteplase in Acute Myocardial Infarction (INTEGRITI) trial evaluated of the impact of combination reperfusion therapy with reduced-dose tenecteplase plus eptifibatide on continuous ST-segment recovery and angiographic results. Combination therapy with reduced-dose fibrinolytics and glycoprotein IIb/IIIa inhibitors for ST-segment elevation myocardial infarction improves biomarkers of reperfusion success but has not reduced mortality when compared with full-dose fibrinolytics. We evaluated 140 patients enrolled in the INTEGRITI trial with 24-h continuous 12-lead ST-segment monitoring and angiography at 60 min. The dose-combination regimen of 50% of standard-dose tenecteplase (0.27 microg/kg) plus high-dose eptifibatide (2 boluses of 180 microg/kg separated by 10 min, 2.0 microg/kg/min infusion) was compared with full-dose tenecteplase (0.53 microg/kg). The dose-confirmation regimen of reduced-dose tenecteplase plus high-dose eptifibatide was associated with a faster median time to stable ST-segment recovery (55 vs. 98 min, p = 0.06), improved stable ST-segment recovery by 2 h (89.6% vs. 67.7%, p = 0.02), and less recurrent ischemia (34.0% vs. 57.1%, p = 0.05) when compared with full-dose tenecteplase. Continuously updated ST-segment recovery analyses demonstrated a modest trend toward greater ST-segment recovery at 30 min (57.7% vs. 40.6%, p = 0.13) and 60 min (82.7% vs. 65.6%, p = 0.08) with this regimen. These findings correlated with improved angiographic results at 60 min. Combination therapy with reduced-dose tenecteplase and eptifibatide leads to faster, more stable ST-segment recovery and improved angiographic flow patterns, compared with full-dose tenecteplase. These findings question the relationship between biomarkers of reperfusion success and clinical outcomes.
ERIC Educational Resources Information Center
Pennsylvania Department of Education, 2010
2010-01-01
This handbook describes the responsibilities of district and school assessment coordinators in the administration of the Pennsylvania System of School Assessment (PSSA). This updated guidebook contains the following sections: (1) General Assessment Guidelines for All Assessments; (2) Writing Specific Guidelines; (3) Reading and Mathematics…
Prevention of recurrent urinary tract infection in children.
Williams, Gabrielle; Craig, Jonathan C
2009-02-01
Urinary tract infection (UTI) in children is common (5-10%) and recurs in 10-30%. UTI causes an unpleasant, usually febrile illness in children. This review focuses on studies evaluating interventions to prevent UTI in children and published between January 2007 and June 2008. Three relevant updated Cochrane reviews, six randomized trials and an evidence-based guideline were published in the study period. Five of the six trials and one of the three Cochrane updates included data on the effects of relevant interventions in children. Three of the six trials investigated the efficacy of long-term, low-dose antibiotics as prophylaxis, and the other trials and both Cochrane updates evaluated complementary therapies such as vitamin A, probiotics and herbal supplements. The benefit of prophylactic antibiotics for the prevention of recurrent UTI in children remains unclear because of underpowered and suboptimally designed trials, but these studies suggest that any benefit is likely to be small, and clinical significance may be limited. The trials of complementary interventions (vitamin A, probiotics, cranberry, nasturtium and horseradish) generally gave favourable results but were not conclusive. Children and families who use these products should be aware that further infections are possible despite their use.
Treatment 2.0: catalyzing the next phase of treatment, care and support.
Duncombe, Chris; Ball, Andrew; Passarelli, Carlos; Hirnschall, Gottfried
2013-01-01
This review provides an update on the WHO/UNAIDS Treatment 2.0 strategy by reviewing the documents and technical updates issued under the initiative. Launched in 2010, this global initiative provides a framework for the continued scale-up of access to HIV care and treatment. WHO has prioritized once daily fixed-dose combination as the preferred antiretroviral (ARV) regimen to initiate HIV treatment, paving the way for programmatic simplification, with reduced toxicity and improved adherence. WHO also recommends the use of point-of-care diagnostics, with CD4 cell count technologies being implemented in the field and progress towards improving access to simplified viral load testing. The strategy also seeks mechanisms that can contribute to reducing treatment costs, such as pooled commodity procurement and public health-oriented licensing approaches. Improved service delivery, specifically through decentralization, task shifting, integration and community mobilization also has the potential to reduce costs and improve access. Support to countries has been provided through the timely release of a series of programmatic and technical updates on specific treatment-related topics. The Treatment 2.0 strategy articulates how innovation and greater efficiency can make HIV care and treatment more accessible and affordable, and guide treatment and prevention scale-up.
Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017.
Hiemke, C; Bergemann, N; Clement, H W; Conca, A; Deckert, J; Domschke, K; Eckermann, G; Egberts, K; Gerlach, M; Greiner, C; Gründer, G; Haen, E; Havemann-Reinecke, U; Hefner, G; Helmer, R; Janssen, G; Jaquenoud, E; Laux, G; Messer, T; Mössner, R; Müller, M J; Paulzen, M; Pfuhlmann, B; Riederer, P; Saria, A; Schoppek, B; Schoretsanitis, G; Schwarz, M; Gracia, M Silva; Stegmann, B; Steimer, W; Stingl, J C; Uhr, M; Ulrich, S; Unterecker, S; Waschgler, R; Zernig, G; Zurek, G; Baumann, P
2018-01-01
Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs. © Georg Thieme Verlag KG Stuttgart · New York.
Individual Radiation Protection Monitoring in the Marshall Islands: Utrok Atoll (2003-2004)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hamilton, T F; Kehl, S; Hickman, D
2006-01-17
The United States Department of Energy (U.S. DOE) has recently implemented a series of strategic initiatives to address long-term radiological surveillance needs at former U.S. nuclear test sites in the Marshall Islands. The plan is to engage local atoll communities in developing shared responsibilities for implementing radiation protection monitoring programs for resettled and resettling populations in the northern Marshall Islands. Using the pooled resources of the U.S. DOE and local atoll governments, individual radiological surveillance programs have been developed in whole body counting and plutonium urinalysis in order to accurately assess radiation doses resulting from the ingestion and uptake ofmore » fallout radionuclides contained in locally grown foods. Permanent whole body counting facilities have been established at three separate locations in the Marshall Islands (Figure 1). These facilities are operated and maintained by Marshallese technicians with scientists from the Lawrence Livermore National Laboratory (LLNL) providing on-going technical support services. Bioassay samples are collected under controlled conditions and analyzed for plutonium isotopes at the Center for Accelerator Mass Spectrometry at LLNL using state-of-the art measurement technologies. We also conduct an on-going environmental monitoring and characterization program at selected sites in the northern Marshall Islands. The aim of the environmental program is to determine the level and distribution of important fallout radionuclides in soil, water and local foods with a view towards providing more accurate and updated dose assessments, incorporating knowledge of the unique behaviors and exposure pathways of fallout radionuclides in coral atoll ecosystems. These scientific studies have also been essential in helping guide the development of remedial options used in support of island resettlement. Together, the individual and environmental radiological surveillance programs are helping meet the informational needs of the U.S. DOE and the Republic of the Marshall Islands. Our updated environmental assessments provide a strong scientific basis for predicting future change in exposure conditions especially in relation to changes in life-style, diet and/or land-use patterns. This information has important implications in addressing questions about existing (and future) radiological conditions on the islands, in determining the cost and the effectiveness of potential remedial measures, and in general policy support considerations. Perhaps most importantly, the recently established individual radiological surveillance programs provide affected atoll communities with an unprecedented level of radiation protection monitoring where, for the first time, local resources are being made available to monitor resettled and resettling populations on a continuous basis. As a hard copy supplement to Marshall Islands Program website (http://eed.llnl.gov/mi/), this document provides an overview of the individual radiation surveillance monitoring program established for the Utrok Atoll population group along with a full disclosure of all verified measurement data (2003-2004). The Utrok whole body counting facility has been temporarily stationed on Majuro Atoll and, in cooperation with the Utrok Atoll Local Government, serves as a national facility open to the general public. Readers are advised that an additional feature of the associated website is a provision whereby users are able to calculate and track radiation doses delivered to volunteers (de-identified information only) participating in the Marshall Islands Radiological Surveillance Program.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kabolizadeh, Peyman, E-mail: peyman.kabolizadeh@beaumont.org; Chen, Yen-Lin; Liebsch, Norbert
Purpose: Treatment of spine and sacral chordoma generally involves surgical resection, usually in conjunction with radiation therapy. In certain circumstances where resection may result in significant neurologic or organ dysfunction, patients can be treated definitively with radiation therapy alone. Herein, we report the outcome and the assessment of tumor response to definitive radiation therapy. Methods and Materials: A retrospective analysis was performed on 40 patients with unresected chordoma treated with photon/proton radiation therapy. Nineteen patients had complete sets of imaging scans. The soft tissue and bone compartments of the tumor were defined separately. Tumor response was evaluated by the modifiedmore » Response Evaluation Criteria in Solid Tumors (RECIST) and volumetric analysis. Results: With a median follow-up time of 50.3 months, the rates of 5-year local control, overall survival, disease-specific survival, and distant failure were 85.4%, 81.9%, 89.4%, and 20.2%, respectively. Eighty-four computed tomographic and magnetic resonance imaging scans were reviewed. Among the 19 patients, only 4 local failures occurred, and the median tumor dose was 77.4 GyRBE. Analysis at a median follow-up time of 18 months showed significant volumetric reduction of the total target volume (TTV) and the soft tissue target volume (STTV) within the first 24 months after treatment initiation, followed by further gradual reduction throughout the rest of the follow-up period. The median maximum percentage volumetric regressions of TTV and STTV were 43.2% and 70.4%, respectively. There was only a small reduction in bone target volume over time. In comparison with the modified RECIST, volumetric analysis was more reliable, more reproducible, and could help in measuring minimal changes in the tumor volume. Conclusion: These results continue to support the use of high-dose definitive radiation therapy for selected patients with unresected spine and sacral chordomas. Assessment of tumor response to radiation therapy by volumetric analysis is superior to modified RECIST in chordoma patients. Evaluating the soft tissue target volume is an excellent indicator of tumor response.« less
Thrombosis and antiphospholipid antibody syndrome during acute Q fever: A cross-sectional study.
Million, Matthieu; Bardin, Nathalie; Bessis, Simon; Nouiakh, Nadia; Douliery, Charlaine; Edouard, Sophie; Angelakis, Emmanouil; Bosseray, Annick; Epaulard, Olivier; Branger, Stéphanie; Chaudier, Bernard; Blanc-Laserre, Karine; Ferreira-Maldent, Nicole; Demonchy, Elisa; Roblot, France; Reynes, Jacques; Djossou, Felix; Protopopescu, Camelia; Carrieri, Patrizia; Camoin-Jau, Laurence; Mege, Jean-Louis; Raoult, Didier
2017-07-01
Q fever is a neglected and potentially fatal disease. During acute Q fever, antiphospholipid antibodies are very prevalent and have been associated with fever, thrombocytopenia, acquired heart valve disease, and progression to chronic endocarditis. However, thrombosis, the main clinical criterion of the 2006 updated classification of the antiphospholipid syndrome, has not been assessed in this context. To test whether thrombosis is associated with antiphospholipid antibodies and whether the criteria for antiphospholipid syndrome can be met in patients with acute Q fever, we conducted a cross-sectional study at the French National Referral Center for Q fever.Patients included were diagnosed with acute Q fever in our Center between January 2007 and December 2015. Each patient's history and clinical characteristics were recorded with a standardized questionnaire. Predictive factors associated with thrombosis were assessed using a rare events logistic regression model. IgG anticardiolipin antibodies (IgG aCL) assessed by an enzyme-linked immunosorbent assay were tested on the Q fever diagnostic serum. A dose-dependent relationship between IgG aCL levels and thrombosis was tested using a receiver operating characteristic (ROC) analysis.Of the 664 patients identified for inclusion in the study, 313 (47.1%) had positive IgG aCL and 13 (1.9%) were diagnosed with thrombosis. Three patients fulfilled the antiphospholipid syndrome criteria. After multiple adjustments, only positive IgG aCL (relative risk, 14.46 [1.85-113.14], P = .011) were independently associated with thrombosis. ROC analysis identified a dose-dependent relationship between IgG aCL levels and occurrence of thrombosis (area under curve, 0.83, 95%CI [0.73-0.93], P < .001).During acute Q fever, antiphospholipid antibodies are associated with thrombosis, thrombocytopenia, and acquired valvular heart disease. Antiphospholipid antibodies should be systematically assessed in acute Q fever patients. Hydroxychloroquine, which has been previously shown to antagonize IgG aCL pathogenic properties, should be tested in acute Q fever patients with anticardiolipin antibodies to prevent antiphospholipid-associated complications.Key Point: In addition to fever, thrombocytopenia and acquired valvular heart disease, antiphospholipid antibodies are associated with thrombosis during acute Q fever.
FOCUSING ON CHILDREN’S INHALATION DOSIMETRY AND HEALTH EFFECTS FOR RISK ASSESSMENT: AN INTRODUCTION
Substantial effort has been invested in improving children’s health risk assessment in recent years. However, the body of scientific evidence in support of children’s health assessment is constantly advancing requiring continual updating of risk assessment methods. Children’s i...
IRIS Toxicological Review of Ammonia Noncancer Inhalation (Final Report)
EPA has finalized the Integrated Risk Information System (IRIS) Assessment of Ammonia (Noncancer Inhalation). This assessment addresses the potential noncancer human health effects from long-term inhalation exposure to ammonia. Now final, this assessment will update the ...
LIFE CYCLE ASSESSMENT: PRINCIPLES AND PRACTICE
The following document provides an introductory overview of Life Cycle Assessment (LCA) and describes the general uses and major components of LCA. This document is an update and merger of two previous EPA documents on LCA ("Life Cycle Assessment: Inventory Guidelines and Princip...
IRIS Toxicological Review of Formaldehyde (Inhalation) (External Review Draft 2010)
UPDATE EPA is currently revising its Integrated Risk Information System (IRIS) assessment of formaldehyde to address the 2011 NAS peer review recommendations. This assessment addresses both noncancer and cancer human health effects that are relevant to assessing ...
ERIC Educational Resources Information Center
Brandt, Steffen
2010-01-01
This article presents the author's commentary on "Updating the Duplex Design for Test-Based Accountability in the Twenty-First Century," in which Isaac I. Bejar and E. Aurora Graf propose the application of a test design--the duplex design (which was proposed in 1988 by Bock and Mislevy) for application in current accountability assessments.…
ERIC Educational Resources Information Center
Bellizio, Dan
2012-01-01
This December 2012 Brief updates NSCC's 2011 report "State Policies on School Climate and Bully Prevention Efforts: Challenges and Opportunities for Deepening State Policy Support for Safe and Civil School"s (www.schoolclimate.org/climate/papers-briefs.php). This Brief provides a summary of State level: (1) anti-bullying legislation; (2)…
2007-01-25
the joint staff (J-6) and the intelligence directorate of a joint staff (J-2). The joint restricted frequency list (JRFL) is prepared and promulgated...J-3, and J-6, prepares a joint restricted frequency list (JRFL) for approval by the J-3 (through the information operations [IO] cell or equivalent...SPECTRUM MANAGEMENT PLAN DEGRADATION REPORTS ASSESS FREQUENCY PLAN EFFECTIVENESS UPDATE ASSIGNMENTS UPDATE JOINT RESTRICTED FREQUENCY LIST (JRFL
A medical image-based graphical platform -- features, applications and relevance for brachytherapy.
Fonseca, Gabriel P; Reniers, Brigitte; Landry, Guillaume; White, Shane; Bellezzo, Murillo; Antunes, Paula C G; de Sales, Camila P; Welteman, Eduardo; Yoriyaz, Hélio; Verhaegen, Frank
2014-01-01
Brachytherapy dose calculation is commonly performed using the Task Group-No 43 Report-Updated protocol (TG-43U1) formalism. Recently, a more accurate approach has been proposed that can handle tissue composition, tissue density, body shape, applicator geometry, and dose reporting either in media or water. Some model-based dose calculation algorithms are based on Monte Carlo (MC) simulations. This work presents a software platform capable of processing medical images and treatment plans, and preparing the required input data for MC simulations. The A Medical Image-based Graphical platfOrm-Brachytherapy module (AMIGOBrachy) is a user interface, coupled to the MCNP6 MC code, for absorbed dose calculations. The AMIGOBrachy was first validated in water for a high-dose-rate (192)Ir source. Next, dose distributions were validated in uniform phantoms consisting of different materials. Finally, dose distributions were obtained in patient geometries. Results were compared against a treatment planning system including a linear Boltzmann transport equation (LBTE) solver capable of handling nonwater heterogeneities. The TG-43U1 source parameters are in good agreement with literature with more than 90% of anisotropy values within 1%. No significant dependence on the tissue composition was observed comparing MC results against an LBTE solver. Clinical cases showed differences up to 25%, when comparing MC results against TG-43U1. About 92% of the voxels exhibited dose differences lower than 2% when comparing MC results against an LBTE solver. The AMIGOBrachy can improve the accuracy of the TG-43U1 dose calculation by using a more accurate MC dose calculation algorithm. The AMIGOBrachy can be incorporated in clinical practice via a user-friendly graphical interface. Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
Exposure Factors Handbook - 2009 Update (External Review ...
The mission of National Center for Environmental Assessment (NCEA) of EPA's Office of Research and Development is to provide guidance and risk assessments aimed at protecting human health and the environment. To accomplish this mission, NCEA works to develop and improve the models, databases, tools, assumptions, and extrapolations used in risk assessments. This handbook is a tool developed by NCEA aimed at refining the assumptions used in exposure assessments and reducing uncertainty. This handbook was first published in 1989 and updated in 1997 to provide statistical data on the various human factors used in assessing exposure. This revised version of the handbook provides the up-to-date data on these exposure factors. The recommended values are based solely on our interpretations of the available data. In many situations different values may be appropriate to use in consideration of policy, precedent or other factors. External Review Draft
Dunbar, Paula K.; Weaver, Craig S.
2015-01-01
The first U.S. Tsunami Hazard Assessment (Dunbar and Weaver, 2008) was prepared at the request of the National Tsunami Hazard Mitigation Program (NTHMP). The NTHMP is a partnership formed between federal and state agencies to reduce the impact of tsunamis through hazard assessment, warning guidance, and mitigation. The assessment was conducted in response to a 2005 joint report by the Sub-Committee on Disaster Reduction and the U.S. Group on Earth Observations entitled Tsunami Risk Reduction for the United States: A Framework for Action. The first specific action called for in the Framework was to “develop standardized and coordinated tsunami hazard and risk assessments for all coastal regions of the United States and its territories.” Since the first assessment, there have been a number of very significant tsunamis, including the 2009 Samoa, 2010 Chile, and 2011 Japan tsunamis. As a result, the NTHMP requested an update of the U.S. tsunami hazard assessment.
NASA Astrophysics Data System (ADS)
Joyce, C. J.; Schwadron, N. A.; Townsend, L. W.; deWet, W. C.; Wilson, J. K.; Spence, H. E.; Tobiska, W. K.; Shelton-Mur, K.; Yarborough, A.; Harvey, J.; Herbst, A.; Koske-Phillips, A.; Molina, F.; Omondi, S.; Reid, C.; Reid, D.; Shultz, J.; Stephenson, B.; McDevitt, M.; Phillips, T.
2016-09-01
We provide an analysis of the galactic cosmic ray radiation environment of Earth's atmosphere using measurements from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) aboard the Lunar Reconnaissance Orbiter (LRO) together with the Badhwar-O'Neil model and dose lookup tables generated by the Earth-Moon-Mars Radiation Environment Module (EMMREM). This study demonstrates an updated atmospheric radiation model that uses new dose tables to improve the accuracy of the modeled dose rates. Additionally, a method for computing geomagnetic cutoffs is incorporated into the model in order to account for location-dependent effects of the magnetosphere. Newly available measurements of atmospheric dose rates from instruments aboard commercial aircraft and high-altitude balloons enable us to evaluate the accuracy of the model in computing atmospheric dose rates. When compared to the available observations, the model seems to be reasonably accurate in modeling atmospheric radiation levels, overestimating airline dose rates by an average of 20%, which falls within the uncertainty limit recommended by the International Commission on Radiation Units and Measurements (ICRU). Additionally, measurements made aboard high-altitude balloons during simultaneous launches from New Hampshire and California provide an additional comparison to the model. We also find that the newly incorporated geomagnetic cutoff method enables the model to represent radiation variability as a function of location with sufficient accuracy.
Chromosome aberrations in workers occupationally exposed to tritium.
Tawn, E Janet; Curwen, Gillian B; Riddell, Anthony E
2018-06-01
This paper reports the findings of an historical chromosome analysis for unstable aberrations, undertaken on 34 nuclear workers with monitored exposure to tritium. The mean recorded β-particle dose from tritium was 9.33 mGy (range 0.25-79.71 mGy) and the mean occupational dose from external, mainly γ-ray, irradiation was 1.94 mGy (range 0.00-7.71 mGy). The dicentric frequency of 1.91 ± 0.53 × 10 -3 per cell was significantly raised, in comparison with that of 0.61 ± 0.30 × 10 -3 per cell for a group of 66 comparable worker controls unexposed to occupational radiation. The frequency of total aberrations was also significantly higher in the tritium workers. Comparisons with in vitro studies indicate that at these dose levels an increase in aberration frequency is not expected. However, the available historical tritium dose records were produced for the purposes of radiological protection and based on a methodology that has since been updated, so tritium doses are subject to considerable uncertainty. It is therefore recommended that, if possible, tritium doses are reassessed using information on historical recording practices in combination with current dosimetry methodology, and that further chromosome studies are undertaken using modern FISH techniques to establish stable aberration frequencies, as these will provide information on a cumulative biological effect.
An update on the use of antibodies against the filoviruses
Saphire, Erica Ollmann
2015-01-01
Multiple recent, independent studies have confirmed that passively administered antibodies can provide effective postexposure therapy in nonhuman primates after exposure to an otherwise lethal dose of Ebola virus or Marburg virus. In this article, we review composition and performance of the antibody cocktails tested thus far, what is known about antibody epitopes on the viral glycoprotein target and ongoing research questions in further development of such cocktails for pre-exposure or emergency postexposure use. PMID:24188676
International ITS Program Assessment
DOT National Transportation Integrated Search
1995-08-01
THIS PAPER ATTEMPTS TO MAKE AN UPDATED COMPARISON OF WORLDWIDE ACTIVITIES IN INTELLIGENT TRANSPORTATION SYSTEMS (ITS) AND TO RECOMMEND A STRATEGY FOR CONTINUING INTERNATIONAL PROGRAM ASSESSMENT FOR DISCUSSION AT THE BENEFITS, EVALUATION AND COSTS (BE...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jannik, G. T.; Dixon, K. L.
This report presents the environmental dose assessment methods and the estimated potential doses to the offsite public from 2015 Savannah River Site (SRS) atmospheric and liquid radioactive releases. Also documented are potential doses from special-case exposure scenarios - such as the consumption of deer meat, fish, and goat milk.
An update on the pharmacotherapy of attention-deficit/hyperactivity disorder in adults
Wilens, Timothy E; Morrison, Nicholas R; Prince, Jefferson
2011-01-01
Adults with attention-deficit/hyperactivity disorder (ADHD) are more frequently presenting for diagnosis and treatment. Medication is considered to be appropriate among available treatments for ADHD; however, the evidence supporting the use of pharmacotherapeutics for adults with ADHD remains less established. In this article, the effectiveness and dosing parameters of the various agents investigated for adult ADHD are reviewed. In adults with ADHD, short-term improvements in symptomatology have been documented through the use of stimulants and antidepressants. Studies suggest that methylphenidate and amphetamine maintained an immediate onset of action, whereas the ADHD response to the nonstimulants appeared to be delayed. At a group level, there appears to be some, albeit not entirely consistent, dose-dependent responses to amphetamine and methylphenidate. Generally speaking, variability in diagnostic criteria, dosing parameters and response rates between the various studies was considerable, and most studies were of a relatively short duration. The aggregate literature shows that the stimulants and catecholaminergic nonstimulants investigated had a clinically significant beneficial effect on treating ADHD in adults. PMID:21955201
Fast online Monte Carlo-based IMRT planning for the MRI linear accelerator
NASA Astrophysics Data System (ADS)
Bol, G. H.; Hissoiny, S.; Lagendijk, J. J. W.; Raaymakers, B. W.
2012-03-01
The MRI accelerator, a combination of a 6 MV linear accelerator with a 1.5 T MRI, facilitates continuous patient anatomy updates regarding translations, rotations and deformations of targets and organs at risk. Accounting for these demands high speed, online intensity-modulated radiotherapy (IMRT) re-optimization. In this paper, a fast IMRT optimization system is described which combines a GPU-based Monte Carlo dose calculation engine for online beamlet generation and a fast inverse dose optimization algorithm. Tightly conformal IMRT plans are generated for four phantom cases and two clinical cases (cervix and kidney) in the presence of the magnetic fields of 0 and 1.5 T. We show that for the presented cases the beamlet generation and optimization routines are fast enough for online IMRT planning. Furthermore, there is no influence of the magnetic field on plan quality and complexity, and equal optimization constraints at 0 and 1.5 T lead to almost identical dose distributions.
Updated preparedness and response framework for influenza pandemics.
Holloway, Rachel; Rasmussen, Sonja A; Zaza, Stephanie; Cox, Nancy J; Jernigan, Daniel B
2014-09-26
The complexities of planning for and responding to the emergence of novel influenza viruses emphasize the need for systematic frameworks to describe the progression of the event; weigh the risk of emergence and potential public health impact; evaluate transmissibility, antiviral resistance, and severity; and make decisions about interventions. On the basis of experience from recent influenza responses, CDC has updated its framework to describe influenza pandemic progression using six intervals (two prepandemic and four pandemic intervals) and eight domains. This updated framework can be used for influenza pandemic planning and serves as recommendations for risk assessment, decision-making, and action in the United States. The updated framework replaces the U.S. federal government stages from the 2006 implementation plan for the National Strategy for Pandemic Influenza (US Homeland Security Council. National strategy for pandemic influenza: implementation plan. Washington, DC: US Homeland Security Council; 2006. Available at http://www.flu.gov/planning-preparedness/federal/pandemic-influenza-implementation.pdf). The six intervals of the updated framework are as follows: 1) investigation of cases of novel influenza, 2) recognition of increased potential for ongoing transmission, 3) initiation of a pandemic wave, 4) acceleration of a pandemic wave, 5) deceleration of a pandemic wave, and 6) preparation for future pandemic waves. The following eight domains are used to organize response efforts within each interval: incident management, surveillance and epidemiology, laboratory, community mitigation, medical care and countermeasures, vaccine, risk communications, and state/local coordination. Compared with the previous U.S. government stages, this updated framework provides greater detail and clarity regarding the potential timing of key decisions and actions aimed at slowing the spread and mitigating the impact of an emerging pandemic. Use of this updated framework is anticipated to improve pandemic preparedness and response in the United States. Activities and decisions during a response are event-specific. These intervals serve as a reference for public health decision-making by federal, state, and local health authorities in the United States during an influenza pandemic and are not meant to be prescriptive or comprehensive. This framework incorporates information from newly developed tools for pandemic planning and response, including the Influenza Risk Assessment Tool and the Pandemic Severity Assessment Framework, and has been aligned with the pandemic phases restructured in 2013 by the World Health Organization.
Update on pediatric resuscitation drugs: high dose, low dose, or no dose at all.
Sorrentino, Annalise
2005-04-01
Pediatric resuscitation has been a topic of discussion for years. It is difficult to keep abreast of changing recommendations, especially for busy pediatricians who do not regularly use these skills. This review will focus on the most recent guidelines for resuscitation drugs. Three specific questions will be discussed: standard dose versus high-dose epinephrine, amiodarone use, and the future of vasopressin in pediatric resuscitation. The issue of using high-dose epinephrine for cardiopulmonary resuscitation refractory to standard dose epinephrine has been a topic of debate for many years. Recently, a prospective, double-blinded study was performed to help settle the debate. These results will be reviewed and compared with previous studies. Amiodarone is a medication that was added to the pediatric resuscitation algorithms with the most recent recommendations from the American Heart Association in 2000. Its use and safety will also be discussed. Another topic that is resurfacing in resuscitation is the use of vasopressin. Its mechanism and comparisons to other agents will be highlighted, although its use in the pediatric patient has not been thoroughly studied. Pediatric resuscitation is a constantly evolving subject that is on the mind of anyone taking care of sick children. Clinicians are continually searching for the most effective methods to resuscitate children in terms of short- and long-term outcomes. It is important to be familiar with not only the agents being used but also the optimal way to use them.
Harwell, Mark A.; Gentile, John H.
2014-01-01
The Exxon Valdez oil spill occurred more than two decades ago, and the Prince William Sound ecosystem has essentially recovered. Nevertheless, discussion continues on whether or not localized effects persist on sea otters (Enhydra lutris) at northern Knight Island (NKI) and, if so, what are the associated attributable risks. A recent study estimated new rates of sea otter encounters with subsurface oil residues (SSOR) from the oil spill. We previously demonstrated that a potential pathway existed for exposures to polycyclic aromatic hydrocarbons (PAHs) and conducted a quantitative ecological risk assessment using an individual-based model that simulated this and other plausible exposure pathways. Here we quantitatively update the potential for this exposure pathway to constitute an ongoing risk to sea otters using the new estimates of SSOR encounters. Our conservative model predicted that the assimilated doses of PAHs to the 1-in-1000th most-exposed sea otters would remain 1–2 orders of magnitude below the chronic effects thresholds. We re-examine the baseline estimates, post-spill surveys, recovery status, and attributable risks for this subpopulation. We conclude that the new estimated frequencies of encountering SSOR do not constitute a plausible risk for sea otters at NKI and these sea otters have fully recovered from the oil spill. PMID:24587690
Health Assessment Document for Diesel Emissions (SAB Review Draft February 1998)
The US. EPA has prepared a draft assessment of the possible health hazards from human exposure to diesel engine exhaust emissions. This 1998 draft assessment is an update of a December 1994 draft assessment that was reviewed in 1995 by the Agency's Clean Air Scientific Advisory C...