Problem formulation for risk assessment of combined exposures to chemicals and other stressors in humans.

Science.gov (United States)

Solomon, Keith R; Wilks, Martin F; Bachman, Ammie; Boobis, Alan; Moretto, Angelo; Pastoor, Timothy P; Phillips, Richard; Embry, Michelle R

2016-11-01

When the human health risk assessment/risk management paradigm was developed, it did not explicitly include a "problem formulation" phase. The concept of problem formulation was first introduced in the context of ecological risk assessment (ERA) for the pragmatic reason to constrain and focus ERAs on the key questions. However, this need also exists for human health risk assessment, particularly for cumulative risk assessment (CRA), because of its complexity. CRA encompasses the combined threats to health from exposure via all relevant routes to multiple stressors, including biological, chemical, physical and psychosocial stressors. As part of the HESI Risk Assessment in the 21st Century (RISK21) Project, a framework for CRA was developed in which problem formulation plays a critical role. The focus of this effort is primarily on a chemical CRA (i.e., two or more chemicals) with subsequent consideration of non-chemical stressors, defined as "modulating factors" (ModFs). Problem formulation is a systematic approach that identifies all factors critical to a specific risk assessment and considers the purpose of the assessment, scope and depth of the necessary analysis, analytical approach, available resources and outcomes, and overall risk management goal. There are numerous considerations that are specific to multiple stressors, and proper problem formulation can help to focus a CRA to the key factors in order to optimize resources. As part of the problem formulation, conceptual models for exposures and responses can be developed that address these factors, such as temporal relationships between stressors and consideration of the appropriate ModFs.

A new continuous-time formulation for scheduling crude oil operations

International Nuclear Information System (INIS)

Reddy, P. Chandra Prakash; Karimi, I.A.; Srinivasan, R.

2004-01-01

In today's competitive business climate characterized by uncertain oil markets, responding effectively and speedily to market forces, while maintaining reliable operations, is crucial to a refinery's bottom line. Optimal crude oil scheduling enables cost reduction by using cheaper crudes intelligently, minimizing crude changeovers, and avoiding ship demurrage. So far, only discrete-time formulations have stood up to the challenge of this important, nonlinear problem. A continuous-time formulation would portend numerous advantages, however, existing work in this area has just begun to scratch the surface. In this paper, we present the first complete continuous-time mixed integer linear programming (MILP) formulation for the short-term scheduling of operations in a refinery that receives crude from very large crude carriers via a high-volume single buoy mooring pipeline. This novel formulation accounts for real-world operational practices. We use an iterative algorithm to eliminate the crude composition discrepancy that has proven to be the Achilles heel for existing formulations. While it does not guarantee global optimality, the algorithm needs only MILP solutions and obtains excellent maximum-profit schedules for industrial problems with up to 7 days of scheduling horizon. We also report the first comparison of discrete- vs. continuous-time formulations for this complex problem. (Author)

Evaluation of Three Chitin Metal Silicate Co-Precipitates as a Potential Multifunctional Single Excipient in Tablet Formulations

Directory of Open Access Journals (Sweden)

Rana Al-Shaikh Hamid

2010-05-01

Full Text Available The performance of the novel chitin metal silicate (CMS co-precipitates as a single multifunctional excipient in tablet formulation using direct compression and wet granulation methods is evaluated. The neutral, acidic, and basic drugs Spironolactone (SPL, ibuprofen (IBU and metronidazole (MET, respectively, were used as model drugs. Commercial Aldactone®, Fleximex® and Dumazole® tablets containing SPL, IBU and MET, respectively, and tablets made using Avicel® 200, were used in the study for comparison purposes. Tablets of acceptable crushing strength (>40 N were obtained using CMS. The friability values for all tablets were well below the maximum 1% USP tolerance limit. CMS produced superdisintegrating tablets (disintegration time < 1 min with the three model drugs. Regarding the dissolution rate, the sequence was as follow: CMS > Fleximex® > Avicel® 200, CMS > Avicel® 200 > Dumazole® and Aldactone® > Avicel® 200 > CMS for IBU, MET and SPL, respectively. Compressional properties of formulations were analyzed using density measurements and the compression Kawakita equation as assessment parameters. On the basis of DSC results, CMS co precipitates were found to be compatible with the tested drugs. Conclusively, the CMS co-precipitates have the potential to be used as filler, binder, and superdisintegrant, all-in-one, in the design of tablets by the direct compression as well as wet granulation methods.

Autonomous learning by simple dynamical systems with a discrete-time formulation

Science.gov (United States)

Bilen, Agustín M.; Kaluza, Pablo

2017-05-01

We present a discrete-time formulation for the autonomous learning conjecture. The main feature of this formulation is the possibility to apply the autonomous learning scheme to systems in which the errors with respect to target functions are not well-defined for all times. This restriction for the evaluation of functionality is a typical feature in systems that need a finite time interval to process a unit piece of information. We illustrate its application on an artificial neural network with feed-forward architecture for classification and a phase oscillator system with synchronization properties. The main characteristics of the discrete-time formulation are shown by constructing these systems with predefined functions.

Lagged kernel machine regression for identifying time windows of susceptibility to exposures of complex mixtures.

Science.gov (United States)

Liu, Shelley H; Bobb, Jennifer F; Lee, Kyu Ha; Gennings, Chris; Claus Henn, Birgit; Bellinger, David; Austin, Christine; Schnaas, Lourdes; Tellez-Rojo, Martha M; Hu, Howard; Wright, Robert O; Arora, Manish; Coull, Brent A

2018-07-01

The impact of neurotoxic chemical mixtures on children's health is a critical public health concern. It is well known that during early life, toxic exposures may impact cognitive function during critical time intervals of increased vulnerability, known as windows of susceptibility. Knowledge on time windows of susceptibility can help inform treatment and prevention strategies, as chemical mixtures may affect a developmental process that is operating at a specific life phase. There are several statistical challenges in estimating the health effects of time-varying exposures to multi-pollutant mixtures, such as: multi-collinearity among the exposures both within time points and across time points, and complex exposure-response relationships. To address these concerns, we develop a flexible statistical method, called lagged kernel machine regression (LKMR). LKMR identifies critical exposure windows of chemical mixtures, and accounts for complex non-linear and non-additive effects of the mixture at any given exposure window. Specifically, LKMR estimates how the effects of a mixture of exposures change with the exposure time window using a Bayesian formulation of a grouped, fused lasso penalty within a kernel machine regression (KMR) framework. A simulation study demonstrates the performance of LKMR under realistic exposure-response scenarios, and demonstrates large gains over approaches that consider each time window separately, particularly when serial correlation among the time-varying exposures is high. Furthermore, LKMR demonstrates gains over another approach that inputs all time-specific chemical concentrations together into a single KMR. We apply LKMR to estimate associations between neurodevelopment and metal mixtures in Early Life Exposures in Mexico and Neurotoxicology, a prospective cohort study of child health in Mexico City.

Fast exposure time decision in multi-exposure HDR imaging

Science.gov (United States)

Piao, Yongjie; Jin, Guang

2012-10-01

Currently available imaging and display system exists the problem of insufficient dynamic range, and the system cannot restore all the information for an high dynamic range (HDR) scene. The number of low dynamic range(LDR) image samples and fastness of exposure time decision impacts the real-time performance of the system dramatically. In order to realize a real-time HDR video acquisition system, this paper proposed a fast and robust method for exposure time selection in under and over exposure area which is based on system response function. The method utilized the monotony of the imaging system. According to this characteristic the exposure time is adjusted to an initial value to make the median value of the image equals to the middle value of the system output range; then adjust the exposure time to make the pixel value on two sides of histogram be the middle value of the system output range. Thus three low dynamic range images are acquired. Experiments show that the proposed method for adjusting the initial exposure time can converge in two iterations which is more fast and stable than average gray control method. As to the exposure time adjusting in under and over exposed area, the proposed method can use the dynamic range of the system more efficiently than fixed exposure time method.

Co-grinding Effect on Crystalline Zaltoprofen with ?-cyclodextrin/Cucurbit[7]uril in Tablet Formulation

OpenAIRE

Li, Shanshan; Lin, Xiang; Xu, Kailin; He, Jiawei; Yang, Hongqin; Li, Hui

2017-01-01

This work aimed to investigate the co-grinding effects of ?-cyclodextrin (?-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline Z...

Untargeted LC-MS/MS Profiling of Cell Culture Media Formulations for Evaluation of High Temperature Short Time Treatment Effects.

Science.gov (United States)

Floris, Patrick; McGillicuddy, Nicola; Albrecht, Simone; Morrissey, Brian; Kaisermayer, Christian; Lindeberg, Anna; Bones, Jonathan

2017-09-19

An untargeted LC-MS/MS platform was implemented for monitoring variations in CHO cell culture media upon exposure to high temperature short time (HTST) treatment, a commonly used viral clearance upstream strategy. Chemically defined (CD) and hydrolysate-supplemented media formulations were not visibly altered by the treatment. The absence of solute precipitation effects during media treatment and very modest shifts in pH values observed indicated sufficient compatibility of the formulations evaluated with the HTST-processing conditions. Unsupervised chemometric analysis of LC-MS/MS data, however, revealed clear separation of HTST-treated samples from untreated counterparts as observed from analysis of principal components and hierarchical clustering sample grouping. An increased presence of Maillard products in HTST-treated formulations contributed to the observed differences which included organic acids, observed particularly in chemically defined formulations, and furans, pyridines, pyrazines, and pyrrolidines which were determined in hydrolysate-supplemented formulations. The presence of Maillard products in media did not affect cell culture performance with similar growth and viability profiles observed for CHO-K1 and CHO-DP12 cells when cultured using both HTST-treated and untreated media formulations.

Boundary-integral equation formulation for time-dependent inelastic deformation in metals

Energy Technology Data Exchange (ETDEWEB)

Kumar, V; Mukherjee, S

1977-01-01

The mathematical structure of various constitutive relations proposed in recent years for representing time-dependent inelastic deformation behavior of metals at elevated temperatues has certain features which permit a simple formulation of the three-dimensional inelasticity problem in terms of real time rates. A direct formulation of the boundary-integral equation method in terms of rates is discussed for the analysis of time-dependent inelastic deformation of arbitrarily shaped three-dimensional metallic bodies subjected to arbitrary mechanical and thermal loading histories and obeying constitutive relations of the kind mentioned above. The formulation is based on the assumption of infinitesimal deformations. Several illustrative examples involving creep of thick-walled spheres, long thick-walled cylinders, and rotating discs are discussed. The implementation of the method appears to be far easier than analogous BIE formulations that have been suggested for elastoplastic problems.

Development of a CO2 releasing co-formulation 1 based on starch, Saccharomyces cerevisiae and Beauveria bassiana attractive towards western corn rootworm larvae

Science.gov (United States)

CO2 is known as an attractant for many soil-dwelling pests. To implement an attract-and-kill strategy for soil pest control, CO2 emitting formulations need to be developed. This work aimed at the development of a slow release bead system in order to bridge the gap between application and hatching of...

Bioavailability of four oral Coenzyme Q formulations in healthy volunteers

DEFF Research Database (Denmark)

Weis, M.; Mortensen, S.A.; Rassing, M.R.

1994-01-01

The bioavailability of four different Coenzyme Q (CoQ) formulations was compared in ten healthy volunteers in a four-way randomised cross-over trial. The included formulations were: A hard gelatine capsule containing 100 mg of CoQ and 400 mg of Emcompress. Three soft gelatine capsules containing......Q (Bioquinon has the highest bioavailability. A difference in basic AUC and AUC after p.o.administration of CoQ was observed with respect to sex. A characteristic two peak-pattern was observed at the concentration-time profile....

In vitro inflammatory effects of hard metal (WC–Co nanoparticle exposure

Directory of Open Access Journals (Sweden)

Armstead AL

2016-11-01

Full Text Available Andrea L Armstead,1,2 Bingyun Li1–3 1Department of Orthopaedics, School of Medicine, 2School of Pharmacy, West Virginia University, 3Mary Babb Randolph Cancer Center, Morgantown, WV, USA Abstract: Identifying the toxicity of nanoparticles (NPs is an important area of research as the number of nanomaterial-based consumer and industrial products continually rises. In addition, the potential inflammatory effects resulting from pulmonary NP exposure are emerging as an important aspect of nanotoxicity. In this study, the toxicity and inflammatory state resulting from tungsten carbide–cobalt (WC–Co NP exposure in macrophages and a coculture (CC of lung epithelial cells (BEAS-2B and macrophages (THP-1 at a 3:1 ratio were examined. It was found that the toxicity of nano-WC–Co was cell dependent; significantly less toxicity was observed in THP-1 cells compared to BEAS-2B cells. It was demonstrated that nano-WC–Co caused reduced toxicity in the CC model compared to lung epithelial cell monoculture, which suggested that macrophages may play a protective role against nano-WC–Co-mediated toxicity in CCs. Nano-WC–Co exposure in macrophages resulted in increased levels of interleukin (IL-1β and IL-12 secretion and decreased levels of tumor necrosis factor alpha (TNFα. In addition, the polarizing effects of nano-WC–Co exposure toward the M1 (pro-inflammatory and M2 (anti-inflammatory macrophage phenotypes were investigated. The results of this study indicated that nano-WC–Co exposure stimulated the M1 phenotype, marked by high expression of CD40 M1 macrophage surface markers. Keywords: nanoparticle, nanotoxicity, inflammation, macrophage, lung disease 

Effect of formulation variables on preparation of celecoxib loaded polylactide-co-glycolide nanoparticles.

Directory of Open Access Journals (Sweden)

Dustin L Cooper

Full Text Available Polymer based nanoparticle formulations have been shown to increase drug bioavailability and/or reduce drug adverse effects. Nonsteroidal anti-inflammatory drugs (e.g. celecoxib reduce prostaglandin synthesis and cause side effects such as gastrointestinal and renal complications. The aim of this study was to formulate celecoxib entrapped poly lactide-co-glycolide based nanoparticles through a solvent evaporation process using didodecyldimethylammonium bromide or poly vinyl alcohol as stabilizer. Nanoparticles were characterized for zeta potential, particle size, entrapment efficiency, and morphology. Effects of stabilizer concentration (0.1, 0.25, 0.5, and 1% w/v, drug amount (5, 10, 15, and 20 mg, and emulsifier (lecithin on nanoparticle characterization were examined for formula optimization. The use of 0.1, 0.25, and 0.5% w/v didodecyldimethylammonium bromide resulted in a more than 5-fold increase in zeta potential and a more than 1.5-fold increase in entrapment efficiency with a reduction in particle size over 35%, when compared to stabilizer free formulation. Nanoparticle formulations were also highly influenced by emulsifier and drug amount. Using 0.25% w/v didodecyldimethylammonium bromide NP formulations, peak zeta potential was achieved using 15 mg celecoxib with emulsifier (17.15±0.36 mV and 20 mg celecoxib without emulsifier (25.00±0.18 mV. Peak NP size reduction and entrapment efficiency was achieved using 5 mg celecoxib formulations with (70.87±1.24 nm and 95.55±0.66%, respectively and without (92.97±0.51 nm and 95.93±0.27%, respectively emulsifier. In conclusion, formulations using 5 mg celecoxib with 0.25% w/v didodecyldimethylammonium bromide concentrations produced nanoparticles exhibiting enhanced size reduction and entrapment efficiency. Furthermore, emulsifier free formulations demonstrated improved zeta potential when compared to formulations containing emulsifier (p<0.01. Therefore, our results suggest the use of

Involvement of two uptake mechanisms of gold and iron oxide nanoparticles in a co-exposure scenario using mouse macrophages

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Dimitri Vanhecke

2017-11-01

Full Text Available Little is known about the simultaneous uptake of different engineered nanoparticle types, as it can be expected in our daily life. In order to test such co-exposure effects, murine macrophages (J774A.1 cell line were incubated with gold (AuNPs and iron oxide nanoparticles (FeOxNPs either alone or combined. Environmental scanning electron microscopy revealed that single NPs of both types bound within minutes on the cell surface but with a distinctive difference between FeOxNPs and AuNPs. Uptake analysis studies based on laser scanning microscopy, transmission electron microscopy, and inductively coupled plasma optical emission spectrometry revealed intracellular appearance of both NP types in all exposure scenarios and a time-dependent increase. This increase was higher for both AuNPs and FeOxNPs during co-exposure. Cells treated with endocytotic inhibitors recovered after co-exposure, which additionally hinted that two uptake mechanisms are involved. Cross-talk between uptake pathways is relevant for toxicological studies: Co-exposure acts as an uptake accelerant. If the goal is to maximize the cellular uptake, e.g., for the delivery of pharmaceutical agents, this can be beneficial. However, co-exposure should also be taken into account in the case of risk assessment of occupational settings. The demonstration of co-exposure-invoked pathway interactions reveals that synergetic nanoparticle effects, either positive or negative, must be considered for nanotechnology and nanomedicine in particular to develop to its full potential.

Hematological and biochemical effects of chronic CO exposure on the Japanese quail

Energy Technology Data Exchange (ETDEWEB)

Jaeger, J.J.; McGrath, J.J.

1975-01-01

Japanese Quail were exposed to a concentration of 300 to 350 ppm CO to maintain an equilibrium carboxyhemoglobin concentration of 30% for a period of 4 weeks. Compared to a control group of birds maintained in an identical chamber, the CO-exposed quail demonstrated increases in hematocrit ratio and hemoglobin concentration. At the end of the exposure period, the CO-exposed quail had significantly larger plasma glucose concentrations than the control birds. Cardiac and skeletal muscle carbohydrate stores were not affected by chronic CO exposure.

Co-Exposure with Fullerene May Strengthen Health Effects of Organic Industrial Chemicals

DEFF Research Database (Denmark)

Lehto, M.; Karilainen, T.; Rog, T.

2014-01-01

In vitro toxicological studies together with atomistic molecular dynamics simulations show that occupational co-exposure with C-60 fullerene may strengthen the health effects of organic industrial chemicals. The chemicals studied are acetophenone, benzaldehyde, benzyl alcohol, m-cresol, and toluene...... which can be used with fullerene as reagents or solvents in industrial processes. Potential co-exposure scenarios include a fullerene dust and organic chemical vapor, or a fullerene solution aerosolized in workplace air. Unfiltered and filtered mixtures of C-60 and organic chemicals represent different...... co-exposure scenarios in in vitro studies where acute cytotoxicity and immunotoxicity of C-60 and organic chemicals are tested together and alone by using human THP-1-derived macrophages. Statistically significant co-effects are observed for an unfiltered mixture of benzaldehyde and C-60 that is more...

Comparative Plasma Exposure and Lung Distribution of Two Human Use Commercial Azithromycin Formulations Assessed in Murine Model: A Preclinical Study

OpenAIRE

Rivulgo, Virginia Margarita; Sparo, Mónica; Ceci, Mónica; Fumuso, Elida; Confalonieri, Alejandra; Delpech, Gastón; Sanchez Bruni, Sergio Fabian

2016-01-01

Azithromycin(AZM)therapeutic failure and relapses of patients treated with generic -35 formulations have been observed in clinical practice.The main goal of this research was 36 to compare in a pre-clinical study the serum exposure and lung tissue concentrationof 37 two commercial formulations AZM-based in murine model. The current study involved 38 264 healthy Balb-C.Mice were divided in two groups (n=44): Animals of Group A 39 (Reference Formulation ?R-) were orally treated with AZM suspens...

Comparison of a soluble co-formulation of insulin degludec/insulin aspart vs biphasic insulin aspart 30 in type 2 diabetes

DEFF Research Database (Denmark)

Niskanen, Leo; Leiter, Lawrence A; Franek, Edward

2012-01-01

Insulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of insulin degludec (70%) and insulin aspart (IAsp: 30%). Here, we compare the efficacy and safety of IDegAsp, an alternative IDegAsp formulation (AF: containing 45% IAsp), and biphasic IAsp 30 (BIAsp 30)....

Exposure-related effects of formulated Pseudomonas fluorescens strain CL145A to glochidia from seven unionid mussel species

Science.gov (United States)

Luoma, James A.; Weber, Kerry L.; Severson, Todd J.; Schreier, Theresa M.; Mayer, Denise A.; Aloisi, Douglas B.; Eckert, Nathan L.

2015-01-01

The study was completed to evaluate the exposure-related effects of a biopesticide for dreissenid mussel (Dreissena polymorpha, zebra mussel and Dreissena rostriformis bugensis, quagga mussel) control on glochidia from unionid mussels endemic to the Great Lakes and Upper Mississippi River Basins. The commercially prepared biopesticide was either a spray-dried powder (SDP) or freeze-dried powder (FDP) formulation of Pseudomonas fluorescens, strain CL145A. Glochidia of the unionid mussel species Lampsilis cardium, Lampsilis siliquoidea,Lampsilis higginsii, Ligumia recta, Obovaria olivaria, and Actinonaias ligamentina were exposed to SDP-formulated P. fluorescens andLampsilis cardium and Megalonaias nervosa were exposed to FDP-formulated P. fluorescens.

Applications of an alternative formulation for one-layer real time optimization

Directory of Open Access Journals (Sweden)

Schiavon Júnior A.L.

2000-01-01

Full Text Available This paper presents two applications of an alternative formulation for one-layer real time structure for control and optimization. This new formulation have arisen from predictive controller QDMC (Quadratic Dynamic Matrix Control, a type of predictive control (Model Predictive Control - MPC. At each sampling time, the values of the outputs of process are fed into the optimization-control structure which supplies the new values of the manipulated variables already considering the best conditions of process. The variables of optimization are both set-point changes and control actions. The future stationary outputs and the future stationary control actions have both a different formulation of conventional one-layer structure and they are calculated from the inverse gain matrix of the process. This alternative formulation generates a convex problem, which can be solved by less sophisticated optimization algorithms. Linear and nonlinear economic objective functions were considered. The proposed approach was applied to two linear models, one SISO (single-input/single output and the other MIMO (multiple-input/multiple-output. The results showed an excellent performance.

An exact formulation of the time-ordered exponential using path-sums

International Nuclear Information System (INIS)

Giscard, P.-L.; Lui, K.; Thwaite, S. J.; Jaksch, D.

2015-01-01

We present the path-sum formulation for the time-ordered exponential of a time-dependent matrix. The path-sum formulation gives the time-ordered exponential as a branched continued fraction of finite depth and breadth. The terms of the path-sum have an elementary interpretation as self-avoiding walks and self-avoiding polygons on a graph. Our result is based on a representation of the time-ordered exponential as the inverse of an operator, the mapping of this inverse to sums of walks on a graphs, and the algebraic structure of sets of walks. We give examples demonstrating our approach. We establish a super-exponential decay bound for the magnitude of the entries of the time-ordered exponential of sparse matrices. We give explicit results for matrices with commonly encountered sparse structures

An exact formulation of the time-ordered exponential using path-sums

Science.gov (United States)

Giscard, P.-L.; Lui, K.; Thwaite, S. J.; Jaksch, D.

2015-05-01

We present the path-sum formulation for the time-ordered exponential of a time-dependent matrix. The path-sum formulation gives the time-ordered exponential as a branched continued fraction of finite depth and breadth. The terms of the path-sum have an elementary interpretation as self-avoiding walks and self-avoiding polygons on a graph. Our result is based on a representation of the time-ordered exponential as the inverse of an operator, the mapping of this inverse to sums of walks on a graphs, and the algebraic structure of sets of walks. We give examples demonstrating our approach. We establish a super-exponential decay bound for the magnitude of the entries of the time-ordered exponential of sparse matrices. We give explicit results for matrices with commonly encountered sparse structures.

Formulation, Pretreatment, and Densification Options to Improve Biomass Specifications for Co-Firing High Percentages with Coal

Energy Technology Data Exchange (ETDEWEB)

Jaya Shankar Tumuluru; J Richard Hess; Richard D. Boardman; Shahab Sokhansanj; Christopher T. Wright; Tyler L. Westover

2012-06-01

There is a growing interest internationally to use more biomass for power generation, given the potential for significant environmental benefits and long-term fuel sustainability. However, the use of biomass alone for power generation is subject to serious challenges, such as feedstock supply reliability, quality, and stability, as well as comparative cost, except in situations in which biomass is locally sourced. In most countries, only a limited biomass supply infrastructure exists. Alternatively, co-firing biomass alongwith coal offers several advantages; these include reducing challenges related to biomass quality, buffering the system against insufficient feedstock quantity, and mitigating the costs of adapting existing coal power plants to feed biomass exclusively. There are some technical constraints, such as low heating values, low bulk density, and grindability or size-reduction challenges, as well as higher moisture, volatiles, and ash content, which limit the co-firing ratios in direct and indirect co-firing. To achieve successful co-firing of biomass with coal, biomass feedstock specifications must be established to direct pretreatment options in order to modify biomass materials into a format that is more compatible with coal co-firing. The impacts on particle transport systems, flame stability, pollutant formation, and boiler-tube fouling/corrosion must also be minimized by setting feedstock specifications, which may include developing new feedstock composition by formulation or blending. Some of the issues, like feeding, co-milling, and fouling, can be overcome by pretreatment methods including washing/leaching, steam explosion, hydrothermal carbonization, and torrefaction, and densification methods such as pelletizing and briquetting. Integrating formulation, pretreatment, and densification will help to overcome issues related to physical and chemical composition, storage, and logistics to successfully co-fire higher percentages of biomass ( > 40

EFFECTS OF TRITIUM GAS EXPOSURE ON EPDM ELASTOMER

Energy Technology Data Exchange (ETDEWEB)

Clark, E.

2009-12-11

Samples of four formulations of ethylene-propylene diene monomer (EPDM) elastomer were exposed to initially pure tritium gas at one atmosphere and ambient temperature for various times up to about 420 days in closed containers. Two formulations were carbon-black-filled commercial formulations, and two were the equivalent formulations without filler synthesized for this work. Tritium effects on the samples were characterized by measuring the sample volume, mass, flexibility, and dynamic mechanical properties and by noting changes in appearance. The glass transition temperature was determined by analysis of the dynamic mechanical properties. The glass transition temperature increased significantly with tritium exposure, and the unfilled formulations ceased to behave as elastomers after the longest tritium exposure. The filled formulations were more resistant to tritium exposure. Tritium exposure made all samples significantly stiffer and therefore much less able to form a reliable seal when employed as O-rings. No consistent change of volume or density was observed; there was a systematic lowering of sample mass with tritium exposure. In addition, the significant radiolytic production of gas, mainly protium (H{sub 2}) and HT, by the samples when exposed to tritium was characterized by measuring total pressure in the container at the end of each exposure and by mass spectroscopy of a gas sample at the end of each exposure. The total pressure in the containers more than doubled after {approx}420 days tritium exposure.

A continuous time formulation of the Regge calculus

International Nuclear Information System (INIS)

Brewin, Leo

1988-01-01

A complete continuous time formulation of the Regge calculus is presented by developing the associated continuous time Regge action. It is shown that the time constraint is, by way of the Bianchi identities conserved by the evolution equations. This analysis leads to an explicit first integral for each of the evolution equations. The dynamical equations of the theory are therefore reduced to a set of first-order differential equations. In this formalism the time constraints reduce to a simple sum of the integration constants. This result is unique to the Regge calculus-there does not appear to be a complete set of first integrals available for the vacuum Einstein equations. (author)

Pharmacokinetics of IDX184, a liver-targeted oral prodrug of 2'-methylguanosine-5'-monophosphate, in the monkey and formulation optimization for human exposure.

Science.gov (United States)

Pan-Zhou, Xin-Ru; Mayes, Benjamin A; Rashidzadeh, Hassan; Gasparac, Rahela; Smith, Steven; Bhadresa, Sanjeev; Gupta, Kusum; Cohen, Marita Larsson; Bu, Charlie; Good, Steven S; Moussa, Adel; Rush, Roger

2016-10-01

IDX184 is a phosphoramidate prodrug of 2'-methylguanosine-5'-monophosphate, developed to treat patients infected with hepatitis C virus. A mass balance study of radiolabeled IDX184 and pharmacokinetic studies of IDX184 in portal vein-cannulated monkeys revealed relatively low IDX184 absorption but higher exposure of IDX184 in the portal vein than in the systemic circulation, indicating >90 % of the absorbed dose was subject to hepatic extraction. Systemic exposures to the main metabolite, 2'-methylguanosine (2'-MeG), were used as a surrogate for liver levels of the pharmacologically active entity 2'-MeG triphosphate, and accordingly, systemic levels of 2'-MeG in the monkey were used to optimize formulations for further clinical development of IDX184. Capsule formulations of IDX184 delivered acceptable levels of 2'-MeG in humans; however, the encapsulation process introduced low levels of the genotoxic impurity ethylene sulfide (ES), which necessitated formulation optimization. Animal pharmacokinetic data guided the development of a tablet with trace levels of ES and pharmacokinetic performance equal to that of the clinical capsule in the monkey. Under fed conditions in humans, the new tablet formulation showed similar exposure to the capsule used in prior clinical trials.

A general real-time formulation for multi-rate mass transfer problems

Directory of Open Access Journals (Sweden)

O. Silva

2009-08-01

Full Text Available Many flow and transport phenomena, ranging from delayed storage in pumping tests to tailing in river or aquifer tracer breakthrough curves or slow kinetics in reactive transport, display non-equilibrium (NE behavior. These phenomena are usually modeled by non-local in time formulations, such as multi-porosity, multiple processes non equilibrium, continuous time random walk, memory functions, integro-differential equations, fractional derivatives or multi-rate mass transfer (MRMT, among others. We present a MRMT formulation that can be used to represent all these models of non equilibrium. The formulation can be extended to non-linear phenomena. Here, we develop an algorithm for linear mass transfer, which is accurate, computationally inexpensive and easy to implement in existing groundwater or river flow and transport codes. We illustrate this approach by application to published data involving NE groundwater flow and solute transport in rivers and aquifers.

Influence of Solvent Composition on the Performance of Spray-Dried Co-Amorphous Formulations

Directory of Open Access Journals (Sweden)

Jaya Mishra

2018-04-01

Full Text Available Ball-milling is usually used to prepare co-amorphous drug–amino acid (AA mixtures. In this study, co-amorphous drug–AA mixtures were produced using spray-drying, a scalable industrially preferred preparation method. The influence of the solvent type and solvent composition was investigated. Mixtures of indomethacin (IND and each of the three AAs arginine, histidine, and lysine were ball-milled and spray-dried at a 1:1 molar ratio, respectively. Spray-drying was performed at different solvent ratios in (a ethanol and water mixtures and (b acetone and water mixtures. Different ratios of these solvents were chosen to study the effect of solvent mixtures on co-amorphous formulation. Residual crystallinity, thermal properties, salt/partial salt formation, and powder dissolution profiles of the IND–AA mixtures were investigated and compared to pure crystalline and amorphous IND. It was found that using spray-drying as a preparation method, all IND–AA mixtures could be successfully converted into the respective co-amorphous forms, irrespective of the type of solvent used, but depending on the solvent mixture ratios. Both ball-milled and spray-dried co-amorphous samples showed an enhanced dissolution rate and maintained supersaturation compared to the crystalline and amorphous IND itself. The spray-dried samples resulting in co-amorphous samples were stable for at least seven months of storage.

Simultaneously reducing CO2 and particulate exposures via fractional recirculation of vehicle cabin air.

Science.gov (United States)

Jung, Heejung S; Grady, Michael L; Victoroff, Tristan; Miller, Arthur L

2017-07-01

Prior studies demonstrate that air recirculation can reduce exposure to nanoparticles in vehicle cabins. However when people occupy confined spaces, air recirculation can lead to carbon dioxide (CO 2 ) accumulation which can potentially lead to deleterious effects on cognitive function. This study proposes a fractional air recirculation system for reducing nanoparticle concentration while simultaneously suppressing CO 2 levels in the cabin. Several recirculation scenarios were tested using a custom-programmed HVAC (heat, ventilation, air conditioning) unit that varied the recirculation door angle in the test vehicle. Operating the recirculation system with a standard cabin filter reduced particle concentrations to 1000 particles/cm 3 , although CO 2 levels rose to 3000 ppm. When as little as 25% fresh air was introduced (75% recirculation), CO 2 levels dropped to 1000 ppm, while particle concentrations remained below 5000 particles/cm 3 . We found that nanoparticles were removed selectively during recirculation and demonstrated the trade-off between cabin CO 2 concentration and cabin particle concentration using fractional air recirculation. Data showed significant increases in CO 2 levels during 100% recirculation. For various fan speeds, recirculation fractions of 50-75% maintained lower CO 2 levels in the cabin, while still reducing particulate levels. We recommend fractional recirculation as a simple method to reduce occupants' exposures to particulate matter and CO 2 in vehicles. A design with several fractional recirculation settings could allow air exchange adequate for reducing both particulate and CO 2 exposures. Developing this technology could lead to reductions in airborne nanoparticle exposure, while also mitigating safety risks from CO 2 accumulation.

Co-exposure with fullerene may strengthen health effects of organic industrial chemicals.

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Maili Lehto

Full Text Available In vitro toxicological studies together with atomistic molecular dynamics simulations show that occupational co-exposure with C60 fullerene may strengthen the health effects of organic industrial chemicals. The chemicals studied are acetophenone, benzaldehyde, benzyl alcohol, m-cresol, and toluene which can be used with fullerene as reagents or solvents in industrial processes. Potential co-exposure scenarios include a fullerene dust and organic chemical vapor, or a fullerene solution aerosolized in workplace air. Unfiltered and filtered mixtures of C60 and organic chemicals represent different co-exposure scenarios in in vitro studies where acute cytotoxicity and immunotoxicity of C60 and organic chemicals are tested together and alone by using human THP-1-derived macrophages. Statistically significant co-effects are observed for an unfiltered mixture of benzaldehyde and C60 that is more cytotoxic than benzaldehyde alone, and for a filtered mixture of m-cresol and C60 that is slightly less cytotoxic than m-cresol. Hydrophobicity of chemicals correlates with co-effects when secretion of pro-inflammatory cytokines IL-1β and TNF-α is considered. Complementary atomistic molecular dynamics simulations reveal that C60 co-aggregates with all chemicals in aqueous environment. Stable aggregates have a fullerene-rich core and a chemical-rich surface layer, and while essentially all C60 molecules aggregate together, a portion of organic molecules remains in water.

Optimizing the co-feeding strategy of Persian sturgeon (Acipenser persicus larvae using Artemia nauplii and formulated diet

Directory of Open Access Journals (Sweden)

Naser Agh

2013-07-01

Full Text Available High mortality and labor costs are associated with first-feeding sturgeon culture, particularly during the period of dietary transition from live to formulated feed. Therefore we investigated the effects of various feeding treatments on the survival and growth of the Persian sturgeon (Acipenser persicus larvae during a 20-day culture period. Three replicate groups (250 fish/replicate of first-feeding larvae were fed according to four main feeding regimes: (1 live food (live nauplii of brine shrimp Artemia urmiana; (2 indirect transition (5 days live food followed by gradual transition to formulated diet; (3 direct transition (using different combinations of live and formulated diet from the start feeding onwards; (4 formulated feed (FD from the start feeding. Results indicated that growth and survival were higher in the indirect transition feeding regime than in other regimes. Based on our study, co-feeding of A. persicus should start five days after prior feeding with live food.

Odd time formulation of the Batalin-Vilkovisky method of quantization

International Nuclear Information System (INIS)

Dayi, O.F.

1988-08-01

By using a Grassmann odd parameter which behaves like time, it is shown that the main features of the Batalin-Fradkin method of quantization of reducible gauge theories can be formulated systematically. (author). 6 refs

Co-exposure to nickel and cobalt chloride enhances cytotoxicity and oxidative stress in human lung epithelial cells

International Nuclear Information System (INIS)

Patel, Eshan; Lynch, Christine; Ruff, Victoria; Reynolds, Mindy

2012-01-01

Nickel and cobalt are heavy metals found in land, water, and air that can enter the body primarily through the respiratory tract and accumulate to toxic levels. Nickel compounds are known to be carcinogenic to humans and animals, while cobalt compounds produce tumors in animals and are probably carcinogenic to humans. People working in industrial and manufacturing settings have an increased risk of exposure to these metals. The cytotoxicity of nickel and cobalt has individually been demonstrated; however, the underlying mechanisms of co-exposure to these heavy metals have not been explored. In this study, we investigated the effect of exposure of H460 human lung epithelial cells to nickel and cobalt, both alone and in combination, on cell survival, apoptotic mechanisms, and the generation of reactive oxygen species and double strand breaks. For simultaneous exposure, cells were exposed to a constant dose of 150 μM cobalt or nickel, which was found to be relatively nontoxic in single exposure experiments. We demonstrated that cells exposed simultaneously to cobalt and nickel exhibit a dose-dependent decrease in survival compared to the cells exposed to a single metal. The decrease in survival was the result of enhanced caspase 3 and 7 activation and cleavage of poly (ADP-ribose) polymerase. Co-exposure increased the production of ROS and the formation of double strand breaks. Pretreatment with N-acetyl cysteine alleviated the toxic responses. Collectively, this study demonstrates that co-exposure to cobalt and nickel is significantly more toxic than single exposure and that toxicity is related to the formation of ROS and DSB. -- Highlights: ► Decreased survival following simultaneous exposure to NiCl 2 and CoCl 2 . ► Enhanced caspase and PARP cleavage following co-exposure. ► Increased formation of ROS in dual exposed cells. ► N-acetyl cysteine pretreatment decreases Co and Ni toxicity. ► Co-exposure to Ni and Co enhances the formation of double strand

Intra-uterine exposure to dual fetal programming sequences among surviving co-twins.

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Salihu, Hamisu M; Ibrahimou, Boubakari; Dagne, Getachew A

2011-01-01

The dynamics of fetal programming following in utero demise of a co-twin are poorly understood. The authors examined fetal programming using a unique application of the change-point analysis method, and identified two types of fetal programming that occurred when a viable twin sibling died in utero, while the co-twin survived. In one type, the initial twin fetal programming trajectory was maintained while in a subset of surviving co-twins a "switch" from a twin to a singleton fetal program (dual fetal programming exposure) was observed. The results suggest that the timing in utero of conversion from a twin to a singleton programming pattern occurred slightly earlier among opposite-sex than in same-sex surviving co-twins. For the conversion from a twin to a singleton program to happen, the surviving co-twin must have attained a "critical mass" when the twin sibling died. Whereas, for same-sex surviving co-twins the critical mass for conversion was the 80th percentile of gestational-age specific birth weight, opposite-sex surviving co-twins converted at a lower critical mass (70th percentile). These novel findings warrant further study to confirm the new hithertofore unknown phenomenon of dual fetal programming sequence, and to determine the implications in terms of subsequent morbidity or mortality during infancy, childhood and adult life.

Physical-chemical characterization of different hydrogels Formulations

International Nuclear Information System (INIS)

Rodriguez, Y.; Romero, M.; Soler, I.; Saldivar, D.

2001-01-01

They were carried out swelling studies at 37 0C of different hydrogels formulations whose composition was the following one: 3% PEG-1000, 1% Agar and concentrations of PVP and NVP 7, 10 and 14% and a maximum thickness of 2 mm, this formulations were irradiated to 25 kGy in a self-shield irradiator of 60Co and the same time studies of the mechanical properties. It was obtained that the hydrogels of PVP absorbs more water than those of NVP. It was described pseudo-Fickian s kinetic whose exponent diffusional is in the following range: 0.5 0.6

A new approach for the carbon monoxide (CO) exposure diagnosis: measurement of total CO in human blood versus carboxyhemoglobin (HbCO).

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Varlet, Vincent; De Croutte, Emma Lagroy; Augsburger, Marc; Mangin, Patrice

2013-07-01

The aim of the study is to present the application of a headspace-gas chromatography-mass spectrometry (HS-GC-MS) method for the determination of the carbon monoxide (CO) blood concentration and to compare it with carboxyhemoglobin (HbCO) saturation. In postmortem cases, the HbCO measured by spectrophotometry frequently leads to inaccurate results due to inadequate samples or analyses. The true role of CO intoxication in the death of a person could be misclassified. The estimation of HbCO from HS-GC-MS CO measurements provides helpful information by determining the total CO levels (CO linked to hemoglobin (HbCO) and CO dissociated from hemoglobin). The CO concentrations were converted in HbCO saturation levels to define cutoff blood CO values. CO limits were defined as less than 1 μmol/mL for living persons, less than 1.5 μmol/mL for dead persons without CO exposure, and greater than 3 μmol/mL for dead persons with clear CO poisoning. © 2013 American Academy of Forensic Sciences.

Real-time exposure fusion on a mobile computer

CSIR Research Space (South Africa)

Bachoo, AK

2009-12-01

Full Text Available information in these scenarios. An image captured using a short exposure time will not saturate bright image re- gions while an image captured with a long exposure time will show more detail in the dark regions. The pixel depth provided by most camera.... The auto exposure also creates strong blown-out highlights in the foreground (the grass patch). The short shutter time (Exposure 1) correctly exposes the grass while the long shutter time (Exposure 3) is able to correctly expose the camouflaged dummy...

Non-Perturbative Formulation of Time-Dependent String Solutions

CERN Document Server

Alexandre, J; Mavromatos, Nikolaos E; Alexandre, Jean; Ellis, John; Mavromatos, Nikolaos E.

2006-01-01

We formulate here a new world-sheet renormalization-group technique for the bosonic string, which is non-perturbative in the Regge slope alpha' and based on a functional method for controlling the quantum fluctuations, whose magnitudes are scaled by the value of alpha'. Using this technique we exhibit, in addition to the well-known linear-dilaton cosmology, a new, non-perturbative time-dependent background solution. Using the reparametrization invariance of the string S-matrix, we demonstrate that this solution is conformally invariant to alpha', and we give a heuristic inductive argument that conformal invariance can be maintained to all orders in alpha'. This new time-dependent string solution may be applicable to primordial cosmology or to the exit from linear-dilaton cosmology at large times.

Comparison of dermal absorption of zinc from different sunscreen formulations and differing UV exposure based on stable isotope tracing

International Nuclear Information System (INIS)

Gulson, Brian; Wong, Herbert; Korsch, Michael; Gomez, Laura; Casey, Philip; McCall, Maxine; McCulloch, Malcolm; Trotter, Julie; Stauber, Jenny; Greenoak, Gavin

2012-01-01

In a pilot study to determine if zinc (Zn) from zinc oxide nanoparticles in sunscreen can penetrate human skin in vivo, nanoparticles (∼ 30 nm) of a stable isotope (52% 68 Zn enrichment) were incorporated into an essentially phytochemical-based formulation and applied to the backs of 3 human subjects twice daily for 5 days during the Southern Hemisphere winter. Blood and urine were collected prior to application and at regular intervals and up to 50 days. As observed in a larger outdoor trial following this pilot study but with a different formulation and with UV exposure: values of 68 Zn in blood continued to increase beyond the 5 day application phase with the highest measurement at 14 days after the first application; variable amounts of the 68 Zn tracer were observed in urine; and the amounts of extra Zn added to blood were small and indicate very low levels of absorption (minimal estimate < 0.01% of the applied dose) through the skin. Reasons for differences in absorption detected in the stable isotope trials and previous investigations include: the sensitivity of the stable isotope method; the duration of the investigations; the number of applications of sunscreen formulation; in vitro methods with excised skin; lack of measurement of blood and urine; no skin flexing; and lack of UV exposure. - Highlights: ► A pilot study to test feasibility of using stable Zn isotopes in sunscreens. ► Three volunteers tested over 5 days with minimal UV exposure. ► Small amount of 68Zn from ZnO absorbed through skin. ► Results consistent with larger outdoor trial.

Space-time coupled spectral/hp least-squares finite element formulation for the incompressible Navier-Stokes equations

International Nuclear Information System (INIS)

Pontaza, J.P.; Reddy, J.N.

2004-01-01

We consider least-squares finite element models for the numerical solution of the non-stationary Navier-Stokes equations governing viscous incompressible fluid flows. The paper presents a formulation where the effects of space and time are coupled, resulting in a true space-time least-squares minimization procedure, as opposed to a space-time decoupled formulation where a least-squares minimization procedure is performed in space at each time step. The formulation is first presented for the linear advection-diffusion equation and then extended to the Navier-Stokes equations. The formulation has no time step stability restrictions and is spectrally accurate in both space and time. To allow the use of practical C 0 element expansions in the resulting finite element model, the Navier-Stokes equations are expressed as an equivalent set of first-order equations by introducing vorticity as an additional independent variable and the least-squares method is used to develop the finite element model of the governing equations. High-order element expansions are used to construct the discrete model. The discrete model thus obtained is linearized by Newton's method, resulting in a linear system of equations with a symmetric positive definite coefficient matrix that is solved in a fully coupled manner by a preconditioned conjugate gradient method in matrix-free form. Spectral convergence of the L 2 least-squares functional and L 2 error norms in space-time is verified using a smooth solution to the two-dimensional non-stationary incompressible Navier-Stokes equations. Numerical results are presented for impulsively started lid-driven cavity flow, oscillatory lid-driven cavity flow, transient flow over a backward-facing step, and flow around a circular cylinder; the results demonstrate the predictive capability and robustness of the proposed formulation. Even though the space-time coupled formulation is emphasized, we also present the formulation and numerical results for least

Nanotoxicity: emerging concerns regarding nanomaterial safety and occupational hard metal (WC-Co) nanoparticle exposure.

Science.gov (United States)

Armstead, Andrea L; Li, Bingyun

As the number of commercial and consumer products containing engineered nanomaterials (ENMs) continually rises, the increased use and production of these ENMs presents an important toxicological concern. Although ENMs offer a number of advantages over traditional materials, their extremely small size and associated characteristics may also greatly enhance their toxic potentials. ENM exposure can occur in various consumer and industrial settings through inhalation, ingestion, or dermal routes. Although the importance of accurate ENM characterization, effective dosage metrics, and selection of appropriate cell or animal-based models are universally agreed upon as important factors in ENM research, at present, there is no "standardized" approach used to assess ENM toxicity in the research community. Of particular interest is occupational exposure to tungsten carbide cobalt (WC-Co) "dusts," composed of nano- and micro-sized particles, in hard metal manufacturing facilities and mining and drilling industries. Inhalation of WC-Co dust is known to cause "hard metal lung disease" and an increased risk of lung cancer; however, the mechanisms underlying WC-Co toxicity, the inflammatory disease state and progression to cancer are poorly understood. Herein, a discussion of ENM toxicity is followed by a review of the known literature regarding the effects of WC-Co particle exposure. The risk of WC-Co exposure in occupational settings and the updates of in vitro and in vivo studies of both micro- and nano-WC-Co particles are discussed.

Pharmacological and toxicological effects of co-exposure of human gingival fibroblasts to silver nanoparticles and sodium fluoride

Directory of Open Access Journals (Sweden)

Inkielewicz-Stepniak I

2014-04-01

Full Text Available Iwona Inkielewicz-Stepniak,1,* Maria Jose Santos-Martinez,2–4,* Carlos Medina,2,4 Marek W Radomski2,41Department of Medicinal Chemistry, Medical University Gdansk, Debinki, Poland; 2The School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland; 3School of Medicine, Trinity College Dublin, Dublin, Ireland; 4Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland*These authors contributed equally to this workBackground: Silver nanoparticles (AgNPs and fluoride (F are pharmacological agents widely used in oral medicine and dental practice due to their anti-microbial/anti-cavity properties. However, risks associated with the co-exposure of local cells and tissues to these xenobiotics are not clear. Therefore, we have evaluated the effects of AgNPs and F co-exposure on human gingival fibroblast cells.Methods: Human gingival fibroblast cells (CRL-2014 were exposed to AgNPs and/or F at different concentrations for up to 24 hours. Cellular uptake of AgNPs was examined by transmission electron microscopy. Downstream inflammatory effects and oxidative stress were measured by real-time quantitative polymerase chain reaction (PCR and reactive oxygen species (ROS generation. Cytotoxicity and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and real-time quantitative PCR and flow cytometry, respectively. Finally, the involvement of mitogen-activated protein kinases (MAPK was studied using Western blot.Results: We found that AgNPs penetrated the cell membrane and localized inside the mitochondria. Co-incubation experiments resulted in increased oxidative stress, inflammation, and apoptosis. In addition, we found that co-exposure to both xenobiotics phosphorylated MAPK, particularly p42/44 MAPK.Conclusion: A combined exposure of human fibroblasts to AgNPs and F results in increased cellular damage. Further studies are needed in order to evaluate

Accounting for Unobservable Exposure Time Bias Wh...

Data.gov (United States)

U.S. Department of Health & Human Services — Accounting for Unobservable Exposure Time Bias When Using Medicare Prescription Drug Data Unobservable exposure time is common among Medicare Part D beneficiaries,...

Single Intravenous Dose of Novel Flurbiprofen-Loaded Proniosome Formulations Provides Prolonged Systemic Exposure and Anti-inflammatory Effect.

Science.gov (United States)

Verma, Preeti; Prajapati, Sunil K; Yadav, Rajbharan; Senyschyn, Danielle; Shea, Peter R; Trevaskis, Natalie L

2016-11-07

Vesicular and colloidal delivery systems can be designed to control drug release spatially and temporally to improve drug efficacy and side effect profiles. Niosomes (vesicles prepared from nonionic surfactants in aqueous media) are gaining interest as an alternative vesicular delivery system as they offer advantages such as biocompatibility, chemical stability, low cost, high purity, and versatility. However, the physical stability of niosomes, like other vesicular systems, is limited by vesicle fusion, aggregation, and leakage. Proniosomes (dehydrated powder or gel formulations that spontaneously form niosomes on hydration with aqueous media) can overcome these physical stability problems and are more convenient for sterilization, storage, transport, distribution, and dosing. Proniosomes have mostly been explored for their potential to enhance transdermal and oral absorption. In this study we assess, for the first time, the potential for hydrated proniosomes to sustain systemic exposure and therapeutic effect after intravenous delivery. Proniosomes carrying the anti-inflammatory drug, flurbiprofen, were prepared by spraying different nonionic surfactants (span 20, span 40, and span 60 in varying ratios with span 80) and cholesterol onto a sorbitol carrier. The proniosome powders were characterized for surface morphology and flow properties. Niosome formation was assessed at three different hydration temperatures (25, 37, and 45 °C), and the niosomes were assessed for vesicle size, entrapment efficiency, and sterility. OLP proniosomes prepared with a high ratio of span 80 to span 20 were found to spontaneously form vesicles of small size and high drug loading on hydration with aqueous media. The OLP derived niosomes successfully sustained in vitro drug release, in vivo pharmacokinetics, and the anti-inflammatory effect of flurbiprofen in an acute (rat paw edema) model of inflammation when compared to a control solution formulation. The study demonstrates that

Nanotoxicity: emerging concerns regarding nanomaterial safety and occupational hard metal (WC-Co nanoparticle exposure

Directory of Open Access Journals (Sweden)

Armstead AL

2016-12-01

Full Text Available Andrea L Armstead,1,2 Bingyun Li1–3 1Department of Orthopaedics, School of Medicine, 2School of Pharmacy, West Virginia University, 3Mary Babb Randolph Cancer Center, Morgantown, WV, USA Abstract: As the number of commercial and consumer products containing engineered nanomaterials (ENMs continually rises, the increased use and production of these ENMs presents an important toxicological concern. Although ENMs offer a number of advantages over traditional materials, their extremely small size and associated characteristics may also greatly enhance their toxic potentials. ENM exposure can occur in various consumer and industrial settings through inhalation, ingestion, or dermal routes. Although the importance of accurate ENM characterization, effective dosage metrics, and selection of appropriate cell or animal-based models are universally agreed upon as important factors in ENM research, at present, there is no “standardized” approach used to assess ENM toxicity in the research community. Of particular interest is occupational exposure to tungsten carbide cobalt (WC-Co “dusts,” composed of nano- and micro-sized particles, in hard metal manufacturing facilities and mining and drilling industries. Inhalation of WC-Co dust is known to cause “hard metal lung disease” and an increased risk of lung cancer; however, the mechanisms underlying WC-Co toxicity, the inflammatory disease state and progression to cancer are poorly understood. Herein, a discussion of ENM toxicity is followed by a review of the known literature regarding the effects of WC-Co particle exposure. The risk of WC-Co exposure in occupational settings and the updates of in vitro and in vivo studies of both micro- and nano-WC-Co particles are discussed. Keywords: engineered nanomaterial, occupational exposure, lung disease, cancer, toxicity, particle

Formulation and in vitro interaction of rhodamine-B loaded PLGA nanoparticles with cardiac myocytes.

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Antranik Jonderian

2016-12-01

Full Text Available This study aims to characterize rhodamine B (Rh B loaded poly(D,L-lactide-co-glycolide (PLGA nanoparticles (NPs and their interactions with cardiac myocytes. PLGA NPs were formulated using single emulsion solvent evaporation technique. The influence of varying parameters such as the stabilizer concentration, the sonication time, and the organic to aqueous ratio were investigated. The diameter, the dispersity, the encapsulation efficiency and the zeta potential of the optimized nanoparticles were about 184 nm, 0.19, 40% and -21.7 mV respectively. In vitro release showed that 29% of the Rh B was released within the first 8 hours. Scanning electron microscopy (SEM measurements performed on the optimized nanoparticles showed smooth surface and spherical shapes. No significant cytotoxic or apoptotic effects were observed on fetal cardiac myocytes after 24 and 48 hours of exposure with concentrations up to 200 µg/mL. The kinetic of the intracellular uptake was confirmed by confocal microscopy and cells took up PLGA NPs within the first hours. Interestingly, our data show an increase in the nanoparticles’ uptake with time of exposure. Taken together, we demonstrate for the first time that the designed NPs can be used as potential probes for drug delivery in cardiac myocytes.

Measurement of the Retention Time of Different Ophthalmic Formulations with Ultrahigh-Resolution Optical Coherence Tomography.

Science.gov (United States)

Gagliano, Caterina; Papa, Vincenzo; Amato, Roberta; Malaguarnera, Giulia; Avitabile, Teresio

2018-04-01

Purpose/aim of the study: The purpose of this study was to measure the pre-corneal retention time of two marketed formulations (eye drops and eye gel) of a steroid-antibiotic fixed combination (FC) containing 0.1% dexamethasone and 0.3% netilmicin. Pre-corneal retention time was evaluated in 16 healthy subjects using an ultrahigh-resolution anterior segment spectral domain optical coherence tomography (OCT). All subjects randomly received both formulations of the FC (Netildex, SIFI, Italy). Central tear film thickness (CTFT) was measured before instillation (time 0) and then after 1, 10, 20, 30, 40 50, 60 and 120 min. The pre-corneal retention time was calculated by plotting CTFT as a function of time. Differences between time points and groups were analyzed by Student's t-test. CTFT increased significantly after the instillation of the eye gel formulation (p < 0.001). CTFT reached its maximum value 1 min after instillation and returned to baseline after 60 min. No effect on CTFT was observed after the instillation of eye drops. The difference between the two formulations was statistically significant at time 1 min (p < 0.0001), 10 min (p < 0.001) and 20 min (p < 0.01). The FC formulated as eye gel was retained on the ocular surface longer than the corresponding eye drop solution. Consequently, the use of the eye gel might extend the interval between instillations and decrease the frequency of administration.

Time-activity relationships to VOC personal exposure factors

Science.gov (United States)

Edwards, Rufus D.; Schweizer, Christian; Llacqua, Vito; Lai, Hak Kan; Jantunen, Matti; Bayer-Oglesby, Lucy; Künzli, Nino

Social and demographic factors have been found to play a significant role in differences between time-activity patterns of population subgroups. Since time-activity patterns largely influence personal exposure to compounds as individuals move across microenvironments, exposure subgroups within the population may be defined by factors that influence daily activity patterns. Socio-demographic and environmental factors that define time-activity subgroups also define quantifiable differences in VOC personal exposures to different sources and individual compounds in the Expolis study. Significant differences in exposures to traffic-related compounds ethylbenzene, m- and p-xylene and o-xylene were observed in relation to gender, number of children and living alone. Categorization of exposures further indicated time exposed to traffic at work and time in a car as important determinants. Increased exposures to decane, nonane and undecane were observed for males, housewives and self-employed. Categorization of exposures indicated exposure subgroups related to workshop use and living downtown. Higher exposures to 3-carene and α-pinene commonly found in household cleaning products and fragrances were associated with more children, while exposures to traffic compounds ethylbenzene, m- and p-xylene and o-xylene were reduced with more children. Considerable unexplained variation remained in categorization of exposures associated with home product use and fragrances, due to individual behavior and product choice. More targeted data collection methods in VOC exposure studies for these sources should be used. Living alone was associated with decreased exposures to 2-methyl-1-propanol and 1-butanol, and traffic-related compounds. Identification of these subgroups may help to reduce the large amount of unexplained variation in VOC exposure studies. Further they may help in assessing impacts of urban planning that result in changes in behavior of individuals, resulting in shifts in

Predicting Cortisol Exposure from Paediatric Hydrocortisone Formulation Using a Semi-Mechanistic Pharmacokinetic Model Established in Healthy Adults.

Science.gov (United States)

Melin, Johanna; Parra-Guillen, Zinnia P; Hartung, Niklas; Huisinga, Wilhelm; Ross, Richard J; Whitaker, Martin J; Kloft, Charlotte

2018-04-01

Optimisation of hydrocortisone replacement therapy in children is challenging as there is currently no licensed formulation and dose in Europe for children under 6 years of age. In addition, hydrocortisone has non-linear pharmacokinetics caused by saturable plasma protein binding. A paediatric hydrocortisone formulation, Infacort ® oral hydrocortisone granules with taste masking, has therefore been developed. The objective of this study was to establish a population pharmacokinetic model based on studies in healthy adult volunteers to predict hydrocortisone exposure in paediatric patients with adrenal insufficiency. Cortisol and binding protein concentrations were evaluated in the absence and presence of dexamethasone in healthy volunteers (n = 30). Dexamethasone was used to suppress endogenous cortisol concentrations prior to and after single doses of 0.5, 2, 5 and 10 mg of Infacort ® or 20 mg of Infacort ® /hydrocortisone tablet/hydrocortisone intravenously. A plasma protein binding model was established using unbound and total cortisol concentrations, and sequentially integrated into the pharmacokinetic model. Both specific (non-linear) and non-specific (linear) protein binding were included in the cortisol binding model. A two-compartment disposition model with saturable absorption and constant endogenous cortisol baseline (Baseline cort ,15.5 nmol/L) described the data accurately. The predicted cortisol exposure for a given dose varied considerably within a small body weight range in individuals weighing cortisol exposure indicated the importance of defining an accurate hydrocortisone dose to mimic physiological concentrations for neonates and infants weighing <20 kg. EudraCT number: 2013-000260-28, 2013-000259-42.

Influence of exposure time on toxicity-An overview.

Science.gov (United States)

Connell, Des W; Yu, Qiming J; Verma, Vibha

2016-04-29

Data on toxicity of chemicals is usually reported as the LD50, or LC50, with the exposure time from experimental testing in the laboratory reported. But the exposure time is not considered to be a quantifiable variable which can be used to evaluate its importance in expressed toxicity, often described in general terms such as acute, chronic and so on. For the last hundred years Habers Rule has been successfully used to extrapolate from reported exposure times to other exposure times which may be needed for setting standards, health risk assessments and other applications. But it has limitations particularly in environmental applications where exposure levels are low and exposure times are relatively long. The Reduced Life Expectancy (RLE) model overcomes these problems and can be utilised under all exposure conditions. It can be expressed as ln(LT50)=-a (LC50)(ν)+b where the constants ν, a and b can be evaluated by fitting the model to experimental data on the LC50, and corresponding LT50, together with the Normal Life Expectancy (NLE) of the organism being considered as a data point when the LC50 is zero. The constant, ν, at a value of unity gives a linear relationship and where νmodel for fish, invertebrates and mammals involving 115 data sets and with a wide range of organic and inorganic toxicants the RLE model gave correlation coefficients of >0.8 with 107 sets of data. The RLE model can be used to extrapolate from a limited data set on exposure times and corresponding LT50 values to any exposure time and corresponding LT50 value. The discrepancy between Haber's Rule and RLE model increases as the exposure time increases. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Gauge-Invariant Formulation of Time-Dependent Configuration Interaction Singles Method

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Takeshi Sato

2018-03-01

Full Text Available We propose a gauge-invariant formulation of the channel orbital-based time-dependent configuration interaction singles (TDCIS method [Phys. Rev. A, 74, 043420 (2006], one of the powerful ab initio methods to investigate electron dynamics in atoms and molecules subject to an external laser field. In the present formulation, we derive the equations of motion (EOMs in the velocity gauge using gauge-transformed time-dependent, not fixed, orbitals that are equivalent to the conventional EOMs in the length gauge using fixed orbitals. The new velocity-gauge EOMs avoid the use of the length-gauge dipole operator, which diverges at large distance, and allows us to exploit computational advantages of the velocity-gauge treatment over the length-gauge one, e.g., a faster convergence in simulations with intense and long-wavelength lasers, and the feasibility of exterior complex scaling as an absorbing boundary. The reformulated TDCIS method is applied to an exactly solvable model of one-dimensional helium atom in an intense laser field to numerically demonstrate the gauge invariance. We also discuss the consistent method for evaluating the time derivative of an observable, which is relevant, e.g., in simulating high-harmonic generation.

Evaluation of exposure to carbon monoxide associated with passive smoking

International Nuclear Information System (INIS)

Jo, W.-K.; Oh, J.-W.; Dong, J.-I.

2004-01-01

The current study measured breath carbon monoxide (CO) concentrations prior to and at prescribed time intervals after exposure to passive smoking under controlled conditions, along with the air CO concentration in the exposure room during the exposure periods. The postexposure breath CO levels were 1.4-2.7 times higher than the background breath CO levels after 30 min of exposure, yet only slightly higher after 10 min of exposure, thereby confirming that exposure to CO from passive smoking causes a significant body burden of CO. The air CO concentration gradually increased during the burning of a cigarette(s), regardless of the exposure duration, whereas it slightly decreased after burning. However, the pattern of breath CO decay was similar for the two different types of exposure (during and after a cigarette(s)) in each subject. The decrease in the postexposure alveolar CO concentrations was slow even in the early phase of the decay curves, indicating a monocompartment uptake and elimination model for the human body. The half-lives (78-277 min) estimated in the present study were comparable to those reported in previous studies associated with CO exposure from active smoking or other activities. The current study also evaluated the CO exposure of visitors and workers at three different types of recreation facility (bars, Internet cafes, and billiard halls) typically associated with passive smoking. The results confirmed that passive smoking is the major contributor to the CO exposure of nonsmoking visitors in a recreation environment. In addition, workplace exposure to CO from passive smoking was found to be the most important contributor to the daily CO exposure of nonsmoking recreation workers

Formulation, optimization, and evaluation of self-emulsifying drug delivery systems of nevirapine.

Science.gov (United States)

Chintalapudi, Ramprasad; Murthy, T E G K; Lakshmi, K Rajya; Manohar, G Ganesh

2015-01-01

The aim of the present study was to formulate and optimize the self-emulsifying drug delivery systems (SEDDS) of nevirapine (NVP) by use of 2(2) factorial designs to enhance the oral absorption of NVP by improving its solubility, dissolution rate, and diffusion profile. SEDDS are the isotropic mixtures of oil, surfactant, co-surfactant and drug that form oil in water microemulsion when introduced into the aqueous phase under gentle agitation. Solubility of NVP in different oils, surfactants, and co-surfactants was determined for the screening of excipients. Pseudo-ternary phase diagrams were constructed by the aqueous titration method, and formulations were developed based on the optimum excipient combinations with the help of data obtained through the maximum micro emulsion region containing combinations of oil, surfactant, and co-surfactant. The formulations of SEDDS were optimized by 2(2) factorial designs. The optimum formulation of SEDDS contains 32.5% oleic acid, 44.16% tween 20, and 11.9% polyethylene glycol 600 as oil, surfactant, and co-surfactant respectively. The SEDDS was evaluated for the following drug content, self-emulsification time, rheological properties, zeta potential, in vitro diffusion studies, thermodynamic stability studies, and in vitro dissolution studies. An increase in dissolution was achieved by SEDDS compared to pure form of NVP. Overall, this study suggests that the dissolution and oral bioavailability of NVP could be improved by SEDDS technology.

Effects of long-term high CO2 exposure on two species of coccolithophores

Directory of Open Access Journals (Sweden)

K. G. Schulz

2010-03-01

Full Text Available The physiological performance of two coccolithophore species, Emiliania huxleyi and Coccolithus braarudii, was investigated during long-term exposure to elevated pCO2 levels. Mono-specific cultures were grown over 152 (E. huxleyi and 65 (C. braarudii generations while pCO2 was gradually increased to maximum levels of 1150 μatm (E. huxleyi and 930 μatm (C. braarudii and kept constant thereafter. Rates of cell growth and cell quotas of particulate organic carbon (POC, particulate inorganic carbon (PIC and total particulate nitrogen (TPN were determined repeatedly throughout the incubation period. Increasing pCO2 caused a decrease in cell growth rate of 9% and 29% in E. huxleyi and C. braarudii, respectively. In both species cellular PIC:TPN and PIC:POC ratios decreased in response to rising pCO2, whereas no change was observed in the POC:TPN ratios of E. huxleyi and C. braarudii. These results are consistent with those obtained in shorter-term high CO2 exposure experiments following abrupt pertubations of the seawater carbonate system and indicate that for the strains tested here a gradual CO2 increase does not alleviate CO2/pH sensitivity.

Treatment of phobophobia by exposure to CO2-induced anxiety symptoms.

Science.gov (United States)

Griez, E; van den Hout, M A

1983-08-01

It is argued that fear of fear, or phobophobia, can be an important maintaining factor in cases of seemingly free-floating anxiety with periodic panic attacks and that effective treatment consists of exposure to the feared neurovegetative sensations. The case history presented suggests that inhalation of CO2-O2 mixtures induces the phobic interoceptive sensations and that it can be used in the exposure treatment of phobophobia.

In vivo behavior of Co and evaluation of exposure to Co

International Nuclear Information System (INIS)

Inaba, Jiro

1983-01-01

Metabolism of Co was studied in vivo in mammalian animals. Approximately 3% of inorganic Co, 60 CoCl 2 , was absorbed in the digestive tract in rats. In humans, the absorption rate of 60 CoCl 2 approximated to that in rats, seemingly being influenced by the presence of carriers. Residue curves revealed that 60 CoCl 2 in the body was present in several forms. The distribution of 60 CoCl 2 was highest in the kidneys in rats and in the liver in humans. On the other hand, the absorption rate of organic Co, 58 Co-cyanocobalamin, into the digestive tract was 50% or more in rats, as well as in humans, greatly depending upon the presence of carriers. 58 Co-cyanocobalamin was present in a single form, and the distribution pattern of 58 Co-cyanocobalamin in organs was similar to that of 60 CoCl 2 . The residue value of Co 9 days after incorporation from foods into the body of rats was 20-30 times higher than that in the control group. This was marked especially in the kidneys. (Namekawa, K.)

Formulation and optimization of solid lipid nanoparticle formulation for pulmonary delivery of budesonide using Taguchi and Box-Behnken design.

Science.gov (United States)

Emami, J; Mohiti, H; Hamishehkar, H; Varshosaz, J

2015-01-01

Budesonide is a potent non-halogenated corticosteroid with high anti-inflammatory effects. The lungs are an attractive route for non-invasive drug delivery with advantages for both systemic and local applications. The aim of the present study was to develop, characterize and optimize a solid lipid nanoparticle system to deliver budesonide to the lungs. Budesonide-loaded solid lipid nanoparticles were prepared by the emulsification-solvent diffusion method. The impact of various processing variables including surfactant type and concentration, lipid content organic and aqueous volume, and sonication time were assessed on the particle size, zeta potential, entrapment efficiency, loading percent and mean dissolution time. Taguchi design with 12 formulations along with Box-Behnken design with 17 formulations was developed. The impact of each factor upon the eventual responses was evaluated, and the optimized formulation was finally selected. The size and morphology of the prepared nanoparticles were studied using scanning electron microscope. Based on the optimization made by Design Expert 7(®) software, a formulation made of glycerol monostearate, 1.2 % polyvinyl alcohol (PVA), weight ratio of lipid/drug of 10 and sonication time of 90 s was selected. Particle size, zeta potential, entrapment efficiency, loading percent, and mean dissolution time of adopted formulation were predicted and confirmed to be 218.2 ± 6.6 nm, -26.7 ± 1.9 mV, 92.5 ± 0.52 %, 5.8 ± 0.3 %, and 10.4 ± 0.29 h, respectively. Since the preparation and evaluation of the selected formulation within the laboratory yielded acceptable results with low error percent, the modeling and optimization was justified. The optimized formulation co-spray dried with lactose (hybrid microparticles) displayed desirable fine particle fraction, mass median aerodynamic diameter (MMAD), and geometric standard deviation of 49.5%, 2.06 μm, and 2.98 μm; respectively. Our results provide fundamental data for the

The primary exposure standard for Co-60 gamma radiation: characteristics and measurements procedures

International Nuclear Information System (INIS)

Laitano, R.F.; Toni, M.P.

1983-01-01

A description is given of a cavity ionization chamber used, as a primary exposure standard, at the Laboratorio di Metrologia delle Radiazioni Ionizzanti of the ENEA in Italy. The primary standard is designed to make absolute measurements of exposure due to the Co-60 gamma radiation. The procedures for the realizationof the exposure unit are also described. Finally results of some international comparisons are reported

Development of paracetamol-caffeine co-crystals to improve compressional, formulation and in vivo performance.

Science.gov (United States)

Latif, Sumera; Abbas, Nasir; Hussain, Amjad; Arshad, Muhammad Sohail; Bukhari, Nadeem Irfan; Afzal, Hafsa; Riffat, Sualeha; Ahmad, Zeeshan

2018-07-01

Paracetamol, a frequently used antipyretic and analgesic drug, has poor compression moldability owing to its low plasticity. In this study, new co-crystals of paracetamol (PCM) with caffeine (as a co-former) were prepared and delineated. Co-crystals exhibited improved compaction and mechanical behavior. A screening study was performed by utilizing a number of methods namely dry grinding, liquid assisted grinding (LAG), solvent evaporation (SE), and anti-solvent addition using various weight ratios of starting materials. LAG and SE were found successful in the screening study. Powders at 1:1 and 2:1 weight ratio of PCM/CAF by LAG and SE, respectively, resulted in the formation of co-crystals. Samples were characterized by PXRD, DSC, and ATR-FTIR techniques. Compressional properties of PCM and developed co-crystals were analyzed by in-die heckle model. Mean yield pressure (Py), an inverse measure of plasticity, obtained from the heckle plots decreased significantly (p < .05) for co-crystals than pure drug. Intrinsic dissolution profile of co-crystals showed up to 2.84-fold faster dissolution than PCM and physical mixtures in phosphate buffer pH 6.8 at 37 °C. In addition, co-crystals formulated into tablets by direct compression method showed better mechanical properties like hardness and tensile strength. In vitro dissolution studies on tablets also showed enhanced dissolution profiles (∼90-97%) in comparison to the tablets of PCM prepared by direct compression (∼55%) and wet granulation (∼85%) methods. In a single dose sheep model study, co-crystals showed up to twofold increase in AUC and C max . A significant (p < .05) decrease in clearance as compared to pure drug was also recorded. In conclusion, new co-crystals of PCM were successfully prepared with improved tabletability in vitro and in vivo profile. Enhancement in AUC and C max of PCM by co-crystallization might suggest the dose reduction and avoidance of side effects.

EXPOSURE TO ENVIRONMENTALLY RELEVANT CONCENTRATIONS OF DIFFERENT NONYLPHENOL FORMULATIONS IN JAPANESE MEDAKA

Science.gov (United States)

The time course of exposure to p-nonylphenol (NP) from two different sources was compared to equivalent exposures of 17-b-estradiol (E2) and a solvent control (ethanol: EtOH). Japanese medaka were exposed for 4 days to a nominal concentration of 20 ?g/l of either NP-I (Schenectad...

Chemical and anatomical changes in Liquidambar styraciflua L. xylem after long term exposure to elevated CO2

International Nuclear Information System (INIS)

Kim, Keonhee; Labbé, Nicole; Warren, Jeffrey M.; Elder, Thomas; Rials, Timothy G.

2015-01-01

The anatomical and chemical characteristics of sweetgum were studied after 11 years of elevated CO 2 (544 ppm, ambient at 391 ppm) exposure. Anatomically, branch xylem cells were larger for elevated CO 2 trees, and the cell wall thickness was thinner. Chemically, elevated CO 2 exposure did not impact the structural components of the stem wood, but non-structural components were significantly affected. Principal component analysis (PCA) was employed to detect differences between the CO 2 treatments by considering numerous structural and chemical variables, as well as tree size, and data from previously published sources (i.e., root biomass, production and turnover). The PCA results indicated a clear separation between trees exposed to ambient and elevated CO 2 conditions. Correlation loadings plots of the PCA revealed that stem structural components, ash, Ca, Mg, total phenolics, root biomass, production and turnover were the major responses that contribute to the separation between the elevated and ambient CO 2 treated trees. - Highlights: • First study of wood properties after 11 years of higher level of CO 2 treatment. • Elevated CO 2 exposure does not impact structural components of wood. • Total phenolics content and some inorganics were significantly affected. • Branch xylem cells were larger under elevated CO 2 . • Cell wall thickness was thinner under elevated CO 2 . - Elevated CO 2 in atmosphere did not impact the structural components yet altered some of non-structural components and anatomical properties after 11 years of exposure on sweetgum

Development of Protective Coatings for Co-Sequestration Processes and Pipelines

Energy Technology Data Exchange (ETDEWEB)

Bierwagen, Gordon; Huang, Yaping

2011-11-30

The program, entitled Development of Protective Coatings for Co-Sequestration Processes and Pipelines, examined the sensitivity of existing coating systems to supercritical carbon dioxide (SCCO2) exposure and developed new coating system to protect pipelines from their corrosion under SCCO2 exposure. A literature review was also conducted regarding pipeline corrosion sensors to monitor pipes used in handling co-sequestration fluids. Research was to ensure safety and reliability for a pipeline involving transport of SCCO2 from the power plant to the sequestration site to mitigate the greenhouse gas effect. Results showed that one commercial coating and one designed formulation can both be supplied as potential candidates for internal pipeline coating to transport SCCO2.

Heterogeneity of passenger exposure to air pollutants in public transport microenvironments

Science.gov (United States)

Yang, Fenhuan; Kaul, Daya; Wong, Ka Chun; Westerdahl, Dane; Sun, Li; Ho, Kin-fai; Tian, Linwei; Brimblecombe, Peter; Ning, Zhi

2015-05-01

Epidemiologic studies have linked human exposure to pollutants with adverse health effects. Passenger exposure in public transport systems contributes an important fraction of daily burden of air pollutants. While there is extensive literature reporting the concentrations of pollutants in public transport systems in different cities, there are few studies systematically addressing the heterogeneity of passenger exposure in different transit microenvironments, in cabins of different transit vehicles and in areas with different characteristics. The present study investigated PM2.5 (particulate matter with aerodynamic diameters smaller than 2.5 μm), black carbon (BC), ultrafine particles (UFP) and carbon monoxide (CO) pollutant concentrations in various public road transport systems in highly urbanized city of Hong Kong. Using a trolley case housing numerous portable air monitors, we conducted a total of 119 trips during the campaign. Transit microenvironments, classified as 1). busy and secondary roadside bus stops; 2). open and enclosed termini; 3). above- and under-ground Motor Rail Transport (MTR) platforms, were investigated and compared to identify the factors that may affect passenger exposures. The pollutants inside bus and MTR cabins were also investigated together with a comparison of time integrated exposure between the transit modes. Busy roadside and enclosed termini demonstrated the highest average particle concentrations while the lowest was found on the MTR platforms. Traffic-related pollutants BC, UFP and CO showed larger variations than PM2.5 across different microenvironments and areas confirming their heterogeneity in urban environments. In-cabin pollutant concentrations showed distinct patterns with BC and UFP high in diesel bus cabins and CO high in LPG bus cabins, suggesting possible self-pollution issues and/or penetration of on-road pollutants inside cabins during bus transit. The total passenger exposure along selected routes, showed bus

Stated product formulation preferences for HIV pre-exposure prophylaxis among women in the VOICE-D (MTN-003D) study.

Science.gov (United States)

Luecke, Ellen H; Cheng, Helen; Woeber, Kubashni; Nakyanzi, Teopista; Mudekunye-Mahaka, Imelda C; van der Straten, Ariane

2016-01-01

The effectiveness of HIV pre-exposure prophylaxis (PrEP) requires consistent and correct product use, thus a deeper understanding of women's stated product formulation preferences, and the correlates of those preferences, can help guide future research. VOICE-D (MTN-003D), a qualitative ancillary study conducted after the VOICE trial, retrospectively explored participants' tablet and gel use, as well as their preferences for other potential PrEP product formulations. We conducted an analysis of quantitative and qualitative data from VOICE-D participants. During in-depth interviews, women were presented with pictures and descriptions of eight potential PrEP product formulations, including the oral tablet and vaginal gel tested in VOICE, and asked to discuss which product formulations they would prefer to use and why. Seven of the original product formulations displayed were combined into preferred product formulation categories based on exploratory factor and latent class analyses. We examined demographic and behavioural correlates of these preferred product formulation categories. In-depth interviews with participants were conducted, coded, and analysed for themes related to product preference. Of the 68 female participants who completed in-depth interviews (22 South Africa, 24 Zimbabwe, 22 Uganda), median age was 28 (range 21-41), 81% were HIV negative, and 49% were married or living with a partner. Four preferred product formulation categories were identified via exploratory factor analysis: 1) oral tablets; 2) vaginal gel; 3) injectable, implant, or vaginal ring; and 4) vaginal film or suppository. A majority of women (81%) expressed a preference for product formulations included in category 3. Characteristics significantly associated with each preferred product category differed. Attributes described by participants as being important in a preferred product formulation included duration of activity, ease of use, route of administration, clinic- versus self

Time-Discrete Higher-Order ALE Formulations: Stability

KAUST Repository

Bonito, Andrea

2013-01-01

Arbitrary Lagrangian Eulerian (ALE) formulations deal with PDEs on deformable domains upon extending the domain velocity from the boundary into the bulk with the purpose of keeping mesh regularity. This arbitrary extension has no effect on the stability of the PDE but may influence that of a discrete scheme. We examine this critical issue for higher-order time stepping without space discretization. We propose time-discrete discontinuous Galerkin (dG) numerical schemes of any order for a time-dependent advection-diffusion-model problem in moving domains, and study their stability properties. The analysis hinges on the validity of the Reynold\\'s identity for dG. Exploiting the variational structure and assuming exact integration, we prove that our conservative and nonconservative dG schemes are equivalent and unconditionally stable. The same results remain true for piecewise polynomial ALE maps of any degree and suitable quadrature that guarantees the validity of the Reynold\\'s identity. This approach generalizes the so-called geometric conservation law to higher-order methods. We also prove that simpler Runge-Kutta-Radau methods of any order are conditionally stable, that is, subject to a mild ALE constraint on the time steps. Numerical experiments corroborate and complement our theoretical results. © 2013 Society for Industrial and Applied Mathematics.

Safety of spray-dried powder formulated Pseudomonas fluorescens strain CL145A exposure to subadult/adult unionid mussels during simulated open-water treatments

Science.gov (United States)

Luoma, James A.; Weber, Kerry L.; Waller, Diane L.; Wise, Jeremy K.; Mayer, Denise A.; Aloisi, Douglas B.

2015-01-01

The exposure effects of a commercially prepared spray dried powder (SDP) formulation ofPseudomonas fluorescens (strain CL145A) on the survival of seven species of unionid mussels endemic to the Great Lakes and Mississippi River basins was evaluated in this study. The study exposures were completed within replicated 350-liter test tanks contained within a mobile bioassay laboratory sited on the shores of the Black River near La Crosse, Wisconsin. The test tanks were supplied with flowing, filtered river water which was interrupted during the exposure period.

Sequential Measurement of Intermodal Variability in Public Transportation PM2.5 and CO Exposure Concentrations.

Science.gov (United States)

Che, W W; Frey, H Christopher; Lau, Alexis K H

2016-08-16

A sequential measurement method is demonstrated for quantifying the variability in exposure concentration during public transportation. This method was applied in Hong Kong by measuring PM2.5 and CO concentrations along a route connecting 13 transportation-related microenvironments within 3-4 h. The study design takes into account ventilation, proximity to local sources, area-wide air quality, and meteorological conditions. Portable instruments were compacted into a backpack to facilitate measurement under crowded transportation conditions and to quantify personal exposure by sampling at nose level. The route included stops next to three roadside monitors to enable comparison of fixed site and exposure concentrations. PM2.5 exposure concentrations were correlated with the roadside monitors, despite differences in averaging time, detection method, and sampling location. Although highly correlated in temporal trend, PM2.5 concentrations varied significantly among microenvironments, with mean concentration ratios versus roadside monitor ranging from 0.5 for MTR train to 1.3 for bus terminal. Measured inter-run variability provides insight regarding the sample size needed to discriminate between microenvironments with increased statistical significance. The study results illustrate the utility of sequential measurement of microenvironments and policy-relevant insights for exposure mitigation and management.

Evaluation of poly(lactic-co-glycolic acid) and poly(DL-lactide-co-ε-caprolactone) electrospun fibers for the treatment of HSV-2 infection

Energy Technology Data Exchange (ETDEWEB)

Aniagyei, Stella E.; Sims, Lee B. [Department of Bioengineering, University of Louisville, Louisville, KY 40202 (United States); Malik, Danial A. [Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202 (United States); Tyo, Kevin M. [Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202 (United States); Center for Predictive Medicine, University of Louisville, Louisville, KY 40202 (United States); Curry, Keegan C. [Department of Bioengineering, University of Louisville, Louisville, KY 40202 (United States); Kim, Woihwan [Department of Medicine, University of Louisville, Louisville, KY 40202 (United States); Hodge, Daniel A. [Department of Bioengineering, University of Louisville, Louisville, KY 40202 (United States); Duan, Jinghua [Department of Bioengineering, University of Louisville, Louisville, KY 40202 (United States); Center for Predictive Medicine, University of Louisville, Louisville, KY 40202 (United States); Steinbach-Rankins, Jill M., E-mail: jill.steinbach@louisville.edu [Department of Bioengineering, University of Louisville, Louisville, KY 40202 (United States); Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202 (United States); Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202 (United States); Center for Predictive Medicine, University of Louisville, Louisville, KY 40202 (United States)

2017-03-01

More diverse multipurpose prevention technologies are urgently needed to provide localized, topical pre-exposure prophylaxis against sexually transmitted infections (STIs). In this work, we established the foundation for a multipurpose platform, in the form of polymeric electrospun fibers (EFs), to physicochemically treat herpes simplex virus 2 (HSV-2) infection. To initiate this study, we fabricated different formulations of poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL) EFs that encapsulate Acyclovir (ACV), to treat HSV-2 infection in vitro. Our goals were to assess the release and efficacy differences provided by these two different biodegradable polymers, and to determine how differing concentrations of ACV affected fiber efficacy against HSV-2 infection and the safety of each platform in vitro. Each formulation of PLGA and PLCL EFs exhibited high encapsulation efficiency of ACV, sustained-delivery of ACV through one month, and in vitro biocompatibility at the highest doses of EFs tested. Additionally, all EF formulations provided complete and efficacious protection against HSV-2 infection in vitro, regardless of the timeframe of collected fiber eluates tested. This work demonstrates the potential for PLGA and PLCL EFs as delivery platforms against HSV-2, and indicates that these delivery vehicles may be expanded upon to provide protection against other sexually transmitted infections. - Highlights: • PLGA and PLCL EFs exhibit sustained-delivery of ACV through one month. • EFs exhibit high ACV encapsulation efficiency and in vitro biocompatibility. • EFs serve as both physical and chemical barriers to HSV-2 infection. • Potent in vitro efficacy is provided against HSV-2 infection for all formulations. • HSV-2 protection is independent of administration times within one month.

Evaluation of poly(lactic-co-glycolic acid) and poly(DL-lactide-co-ε-caprolactone) electrospun fibers for the treatment of HSV-2 infection

International Nuclear Information System (INIS)

Aniagyei, Stella E.; Sims, Lee B.; Malik, Danial A.; Tyo, Kevin M.; Curry, Keegan C.; Kim, Woihwan; Hodge, Daniel A.; Duan, Jinghua; Steinbach-Rankins, Jill M.

2017-01-01

More diverse multipurpose prevention technologies are urgently needed to provide localized, topical pre-exposure prophylaxis against sexually transmitted infections (STIs). In this work, we established the foundation for a multipurpose platform, in the form of polymeric electrospun fibers (EFs), to physicochemically treat herpes simplex virus 2 (HSV-2) infection. To initiate this study, we fabricated different formulations of poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL) EFs that encapsulate Acyclovir (ACV), to treat HSV-2 infection in vitro. Our goals were to assess the release and efficacy differences provided by these two different biodegradable polymers, and to determine how differing concentrations of ACV affected fiber efficacy against HSV-2 infection and the safety of each platform in vitro. Each formulation of PLGA and PLCL EFs exhibited high encapsulation efficiency of ACV, sustained-delivery of ACV through one month, and in vitro biocompatibility at the highest doses of EFs tested. Additionally, all EF formulations provided complete and efficacious protection against HSV-2 infection in vitro, regardless of the timeframe of collected fiber eluates tested. This work demonstrates the potential for PLGA and PLCL EFs as delivery platforms against HSV-2, and indicates that these delivery vehicles may be expanded upon to provide protection against other sexually transmitted infections. - Highlights: • PLGA and PLCL EFs exhibit sustained-delivery of ACV through one month. • EFs exhibit high ACV encapsulation efficiency and in vitro biocompatibility. • EFs serve as both physical and chemical barriers to HSV-2 infection. • Potent in vitro efficacy is provided against HSV-2 infection for all formulations. • HSV-2 protection is independent of administration times within one month.

Personal carbon monoxide exposures of preschool children in Helsinki, Finland - comparison to ambient air concentrations

Energy Technology Data Exchange (ETDEWEB)

Alm, S.; Mukala, K.; Tittanen, P.; Jantunen, M.J. [KTL National Public Health Institute, Kuopio (Finland). Dept. of Environmental Health

2001-07-01

The associations of personal carbon monoxide (CO) exposures with ambient air CO concentrations measured at fixed monitoring sites, were studied among 194 children aged 3-6yr in four downtown and four suburban day-care centers in Helsinki, Finland. Each child carried a personal CO exposure monitor between 1 and 4 times for a time period of between 20 and 24h. CO concentrations at two fixed monitoring sites were measured simultaneously. The CO concentrations measured at the fixed monitoring sites were usually lower (mean maximum 8-h concentration: 0.9 and 2.6mgm{sup -3}) than the personal CO exposure concentrations (mean maximum 8-h concentration: 3.3mgm{sup -3}).The fixed site CO concentrations were poor predictors of the personal CO exposure concentrations. However, the correlations between the personal CO exposure and the fixed monitoring site CO concentrations increased (-0.03 -- -0.12 to 0.13-0.16) with increasing averaging times from 1 to 8h. Also, the fixed monitoring site CO concentrations explained the mean daily or weekly personal CO exposures of a group of simultaneously measured children better than individual exposure CO concentrations. This study suggests that the short-term CO personal exposure of children cannot be meaningfully assessed using fixed monitoring sites. (author)

Time-discrete higher order ALE formulations: a priori error analysis

KAUST Repository

Bonito, Andrea

2013-03-16

We derive optimal a priori error estimates for discontinuous Galerkin (dG) time discrete schemes of any order applied to an advection-diffusion model defined on moving domains and written in the Arbitrary Lagrangian Eulerian (ALE) framework. Our estimates hold without any restrictions on the time steps for dG with exact integration or Reynolds\\' quadrature. They involve a mild restriction on the time steps for the practical Runge-Kutta-Radau methods of any order. The key ingredients are the stability results shown earlier in Bonito et al. (Time-discrete higher order ALE formulations: stability, 2013) along with a novel ALE projection. Numerical experiments illustrate and complement our theoretical results. © 2013 Springer-Verlag Berlin Heidelberg.

Modelling the effects of PSII inhibitor pulse exposure on two algae in co-culture.

Science.gov (United States)

Copin, Pierre-Jean; Chèvre, Nathalie

2018-03-01

A weakness of standard testing procedures is that they do not consider interactions between organisms, and they focus only on single species. Furthermore, these procedures do not take into account pulse exposure. However, pulse exposure is of particular importance because in streams, after crop application and during and after precipitation, herbicide concentrations fluctuate widely and can exceed the Annual Average Environmental Quality Standards (AA-EQS), which aim to protect the aquatic environment. The sensitivity of the algae Scenedesmus vacuolatus and Pseudokirchneriella subcapitata in a co-culture exposed to pulses is thus analysed in this study. As a first step, the growths of the algae in co-culture are investigated. For initial cell densities fixed, respectively, to 100,000 and 50,000 cells/mL, the growth of each alga is exponential over at least 48 h. S. vacuolatus seems to influence the growth of P. subcapitata negatively. Allelopathy is a possible explanation for this growth inhibition. The toxicity of the herbicide isoproturon is later tested on the algae S. vacuolatus and P. subcapitata cultured alone and in the co-culture. Despite the supplementary stress on the algae in the co-culture competing for nutrients, the toxicity of the herbicide is lower for the two algae when they are in the co-culture than when they are in separated culture. A model is adapted and used to predict the cell-density inhibition on the alga S. vacuolatus in the co-culture with the alga P. subcapitata exposed to a pulse concentration of isoproturon. Four laboratory experiments are performed to validate the model. The comparison between the laboratory and the modelled effects shows good agreement. The differences can be considered minor most of time. For future studies, it is important to ensure that the cell count is precise, as it is used to determine the parameters of the model. The differences can be also induced by the fact that the cell number of the alga P

Biological monitoring of occupational exposure to N,N-dimethylformamide--the effects of co-exposure to toluene or dermal exposure.

Science.gov (United States)

Yang, J S; Kim, E A; Lee, M Y; Park, I J; Kang, S K

2000-09-01

The objective of this study is to assess the exposure and intake dose of N,N-dimethylformamide (DMF) and the correlation between them, according to the type of exposure for the workers in the DMF industry. We monitored 345 workers occupationally exposed to DMF, from 15 workshops in the synthetic fiber, fiber coating, synthetic leather and paint manufacturing industries. Ambient monitoring was carried out with personal samplers to monitor the external exposure. Biological monitoring was done to determine the internal dose by analyzing N-methylformamide (NMF) in end-shift urine. Work procedure and exposure type of each DMF workshop was carefully surveyed, to classify workers by exposure type according to work details. Workers were classified into three groups (Group A: continuous and direct exposure through inhalation and skin; Group B: intermittent and short-term exposure through inhalation and skin; Group C: continuous and indirect exposure mostly through inhalation). Geometric mean of DMF concentration in air was 2.62 (GSD 5.30) ppm and that of NMF in urine was 14.50 (GSD 3.89) mg/l. In the case of continuous absorption through inhalation and dermal exposure (Group A), the value of NMF in urine corresponding to 10 ppm of DMF was 45.3 mg/l (r = 0.524, n = 178), 39.1 mg/g creatinine (r = 0.424), while it was 37.7 mg/l (r = 0.788, n = 37), 24.2 mg/g creatinine (r = 0.743) in the case of absorption mostly through inhalation (Group C). Creatinine correction reduced the correlation between two parameters. The NMF in urine corresponding to 10 ppm DMF, of the dermal and inhalation exposure group was 39.1 mg/g creatinine (r = 0.424, n = 178), while that of the inhalation exposure-only group was 24.2 mg/g creatinine (r = 0.743, n = 37). Co-exposure with toluene reduced the NMF excretion in urine.

Formaldehyde and co-exposure with benzene induce compensation of bone marrow and hematopoietic stem/progenitor cells in BALB/c mice during post-exposure period

Energy Technology Data Exchange (ETDEWEB)

Wei, Chenxi [Key Laboratory of Ecological Safety Monitoring and Evaluation, School of Life Sciences, Hunan Normal University, Changsha 410081, Hunan (China); Section of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, Hubei (China); Chen, Mouying [Key Laboratory of Ecological Safety Monitoring and Evaluation, School of Life Sciences, Hunan Normal University, Changsha 410081, Hunan (China); You, Huihui [Section of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, Hubei (China); Qiu, Feng [Key Laboratory of Ecological Safety Monitoring and Evaluation, School of Life Sciences, Hunan Normal University, Changsha 410081, Hunan (China); Wen, Huaxiao; Yuan, Junlin [Section of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, Hubei (China); Xiang, Shuanglin, E-mail: xshlin@hunnu.edu.cn [Key Laboratory of Ecological Safety Monitoring and Evaluation, School of Life Sciences, Hunan Normal University, Changsha 410081, Hunan (China); Yang, Xu, E-mail: yangxu@mail.ccnu.edu.cn [Section of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, Hubei (China)

2017-06-01

Formaldehyde (FA) is a human leukemogen. Since there is a latency period between initial FA exposure and the development of leukemia, the subsequent impact of FA on hematopoietic stem or progenitor cells (HSCs/HPCs) in post-exposure stage is crucial for a deep understanding of FA-induced hematotoxicity. BALB/c mice were exposed to 3 mg/m{sup 3} FA for 2 weeks, mimicking occupational exposure, and were monitored for another 7 days post-exposure. Meanwhile, we included benzene (BZ) as a positive control, separately and together with FA because co-exposure occurs frequently. After 7-day recovery, colonies of progenitors for CFU-GM and BFU-E, and nucleated bone marrow cells in FA-exposed mice were comparable to controls, although they were significantly reduced during exposure. Levels of reactive oxygen species (ROS) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in CFU-GM and BFU-E from FA-exposed mice were higher than controls, although the increase in 8-OHdG was not significant. Granulocyte-macrophage colony stimulating factor (GM-CSF) level in the FA group was lower than controls, but the expression level for the receptor was not upregulated. It suggests that HSCs/HPCs in FA-exposed mice respond to a small amount of GM-CSF and proliferate rapidly, which may cause a possible risk of expansion of abnormal stem/progenitor cell clones. FA co-exposure with BZ was more potent for promoting CFU-GM formation and inducing ROS in BFU-E and 8-OHdG in CFU-GM during the post-exposure period. The compensation of myeloid progenitors with elevated ROS and 8-OHdG may lead to a risk of transforming normal HSCs/HPCs to leukemic stem/progenitor cells. Thus, co-exposure may pose a greater leukemia risk. - Highlights: • Nucleated bone marrow cell count recovered after 7 days post-FA and/or BZ exposure. • CFU-GM showed an increase in colonies and 8-OHdG after 7 days post-FA + BZ exposure. • Levels of ROS in CFU-GM and BFU-E were increased by FA or FA + BZ during recovery. • Levels of

Formaldehyde and co-exposure with benzene induce compensation of bone marrow and hematopoietic stem/progenitor cells in BALB/c mice during post-exposure period

International Nuclear Information System (INIS)

Wei, Chenxi; Chen, Mouying; You, Huihui; Qiu, Feng; Wen, Huaxiao; Yuan, Junlin; Xiang, Shuanglin; Yang, Xu

2017-01-01

Formaldehyde (FA) is a human leukemogen. Since there is a latency period between initial FA exposure and the development of leukemia, the subsequent impact of FA on hematopoietic stem or progenitor cells (HSCs/HPCs) in post-exposure stage is crucial for a deep understanding of FA-induced hematotoxicity. BALB/c mice were exposed to 3 mg/m 3 FA for 2 weeks, mimicking occupational exposure, and were monitored for another 7 days post-exposure. Meanwhile, we included benzene (BZ) as a positive control, separately and together with FA because co-exposure occurs frequently. After 7-day recovery, colonies of progenitors for CFU-GM and BFU-E, and nucleated bone marrow cells in FA-exposed mice were comparable to controls, although they were significantly reduced during exposure. Levels of reactive oxygen species (ROS) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in CFU-GM and BFU-E from FA-exposed mice were higher than controls, although the increase in 8-OHdG was not significant. Granulocyte-macrophage colony stimulating factor (GM-CSF) level in the FA group was lower than controls, but the expression level for the receptor was not upregulated. It suggests that HSCs/HPCs in FA-exposed mice respond to a small amount of GM-CSF and proliferate rapidly, which may cause a possible risk of expansion of abnormal stem/progenitor cell clones. FA co-exposure with BZ was more potent for promoting CFU-GM formation and inducing ROS in BFU-E and 8-OHdG in CFU-GM during the post-exposure period. The compensation of myeloid progenitors with elevated ROS and 8-OHdG may lead to a risk of transforming normal HSCs/HPCs to leukemic stem/progenitor cells. Thus, co-exposure may pose a greater leukemia risk. - Highlights: • Nucleated bone marrow cell count recovered after 7 days post-FA and/or BZ exposure. • CFU-GM showed an increase in colonies and 8-OHdG after 7 days post-FA + BZ exposure. • Levels of ROS in CFU-GM and BFU-E were increased by FA or FA + BZ during recovery. • Levels of GM

Effects of UV irradiation and UV/chlorine co-exposure on natural organic matter in water

International Nuclear Information System (INIS)

Liu, Wei; Zhang, Zaili; Yang, Xin; Xu, Yiyue; Liang, Yongmei

2012-01-01

The effects of co-exposure to ultraviolet (UV) irradiation (with either low- or medium-pressure UV lamps) and free chlorine (chloramine) at practical relevant conditions on changes in natural organic matter (NOM) properties were investigated using four waters. The changes were characterized using the specific disinfection by-product formation potential (SDBPFP), specific total organic halogen formation potential (STOXFP), differential UV absorbance (∆UVA), and size-exclusion chromatography (SEC). The results for exposure to UV irradiation alone and for samples with no exposure were also obtained. The SDBPFPs in all UV-irradiated NOM waters observed were higher than those of non-irradiated samples. UV irradiation led to increases in STOXFPs as a result of chlorination, but no changes, or only small decreases, from chloramination. UV irradiation alone led to positive ∆UVA spectra of the four NOM waters; co-exposure to UV and chlorine gave larger negative ∆UVA spectra than those obtained by chlorine exposure alone. No obvious changes in SEC results were observed for samples only irradiated with UV light; co-exposure gave no detectable changes in the abundances of small fractions for exposure to chlorine only. Both UV photooxidation and photocatalytic oxidation appear to affect the reactivity of the NOM toward subsequent chlorination, and the magnitude of the changes is generally greater for medium-pressure lamps than for low-pressure lamps. These results suggest that applying UV disinfection technology to a particular source may not always be disinfection by-product-problem-free, and the interactions between UV light, chlorine, and NOM may need to be considered. - Highlights: ► We discussed the effects of co-exposure to UV light and chlorine on properties of natural organic matters in waters. ► UV irradiation led to increases in SDBPFP and STOXFP of NOM waters from chlorination. ► We suggest that applying an UV disinfection technology to a particular

Element uptake and physiological responses of Lactuca sativa upon co-exposures to tourmaline and dissolved humic acids.

Science.gov (United States)

Jia, Weili; Wang, Cuiping; Ma, Chuanxin; Wang, Jicheng; Sun, Hongwen

2018-03-27

Element migration and physiological response in Lactuca sativa upon co-exposure to tourmaline (T) and dissolved humic acids (DHAs) were investigated. Different fractions of DHA 1 and DHA 4 and three different doses of T were introduced into Hoagland's solution. The results indicated that T enhanced the contents of elements such as N and C, Si and Al in the roots and shoots. The correlation between TF values of Si and Al (R 2  = 0.7387) was higher than that of Si and Mn (R 2  = 0.4961) without the presence of DHAs. However, both DHA 1 and DHA 4 increased the correlation between Si and Mn, but decreased the one between Si and Al. CAT activities in T treatments were positively correlated to the contents of N and Al in the shoots, whose R 2 was 0.9994 and 0.9897, respectively. In the co-exposure of DHAs and tourmaline, DHA 4 exhibited more impacts on element uptake, CAT activities, as well as ABA contents in comparison with the presence of DHA 1 , regardless of the T exposure doses. These results suggested that DHAs have effects on mineral element behaviors and physiological response in Lactuca sativa upon exposure to tourmaline for the first time, which had great use in guiding soil remediation.

Noise-induced hearing loss in Korean workers: co-exposure to organic solvents and heavy metals in nationwide industries.

Science.gov (United States)

Choi, Yoon-Hyeong; Kim, KyooSang

2014-01-01

Noise exposure is a well-known contributor to work-related hearing loss. Recent biological evidence suggests that exposure to ototoxic chemicals such as organic solvents and heavy metals may be additional contributors to hearing loss. However, in industrial settings, it is difficult to determine the risks of hearing loss due to these chemicals in workplaces accompanied by excessive noise exposure. A few studies suggest that the effect of noise may be enhanced by ototoxic chemicals. Therefore, this study investigated whether co-exposure to organic solvents and/or heavy metals in the workplace modifies the risk of noise exposure on hearing loss in a background of excessive noise. We examined 30,072 workers nationwide in a wide range of industries from the Korea National Occupational Health Surveillance 2009. Data on industry-based exposure (e.g., occupational noise, heavy metals, and organic solvents) and subject-specific health outcomes (e.g., audiometric examination) were collected. Noise was measured as the daily 8-h time-weighted average level. Air conduction hearing thresholds were measured from 0.5 to 6 kHz, and pure-tone averages (PTA) (i.e., means of 2, 3, and 4 kHz) were computed. In the multivariate linear model, PTA increment with occupational noise were 1.64-fold and 2.15-fold higher in individuals exposed to heavy metals and organic solvents than in unexposed individuals, respectively. This study provides nationwide evidence that co-exposure to heavy metals and/or organic solvents may exacerbate the effect of noise exposure on hearing loss in workplaces. These findings suggest that workers in industries dealing with heavy metals or organic solvents are susceptible to such risks.

Noise-Induced Hearing Loss in Korean Workers: Co-Exposure to Organic Solvents and Heavy Metals in Nationwide Industries

Science.gov (United States)

Choi, Yoon-Hyeong; Kim, KyooSang

2014-01-01

Background Noise exposure is a well-known contributor to work-related hearing loss. Recent biological evidence suggests that exposure to ototoxic chemicals such as organic solvents and heavy metals may be additional contributors to hearing loss. However, in industrial settings, it is difficult to determine the risks of hearing loss due to these chemicals in workplaces accompanied by excessive noise exposure. A few studies suggest that the effect of noise may be enhanced by ototoxic chemicals. Therefore, this study investigated whether co-exposure to organic solvents and/or heavy metals in the workplace modifies the risk of noise exposure on hearing loss in a background of excessive noise. Methods We examined 30,072 workers nationwide in a wide range of industries from the Korea National Occupational Health Surveillance 2009. Data on industry-based exposure (e.g., occupational noise, heavy metals, and organic solvents) and subject-specific health outcomes (e.g., audiometric examination) were collected. Noise was measured as the daily 8-h time-weighted average level. Air conduction hearing thresholds were measured from 0.5 to 6 kHz, and pure-tone averages (PTA) (i.e., means of 2, 3, and 4 kHz) were computed. Results In the multivariate linear model, PTA increment with occupational noise were 1.64-fold and 2.15-fold higher in individuals exposed to heavy metals and organic solvents than in unexposed individuals, respectively. Conclusion This study provides nationwide evidence that co-exposure to heavy metals and/or organic solvents may exacerbate the effect of noise exposure on hearing loss in workplaces. These findings suggest that workers in industries dealing with heavy metals or organic solvents are susceptible to such risks. PMID:24870407

A time-dependent neutron transport method of characteristics formulation with time derivative propagation

Energy Technology Data Exchange (ETDEWEB)

Hoffman, Adam J., E-mail: adamhoff@umich.edu; Lee, John C., E-mail: jcl@umich.edu

2016-02-15

A new time-dependent Method of Characteristics (MOC) formulation for nuclear reactor kinetics was developed utilizing angular flux time-derivative propagation. This method avoids the requirement of storing the angular flux at previous points in time to represent a discretized time derivative; instead, an equation for the angular flux time derivative along 1D spatial characteristics is derived and solved concurrently with the 1D transport characteristic equation. This approach allows the angular flux time derivative to be recast principally in terms of the neutron source time derivatives, which are approximated to high-order accuracy using the backward differentiation formula (BDF). This approach, called Source Derivative Propagation (SDP), drastically reduces the memory requirements of time-dependent MOC relative to methods that require storing the angular flux. An SDP method was developed for 2D and 3D applications and implemented in the computer code DeCART in 2D. DeCART was used to model two reactor transient benchmarks: a modified TWIGL problem and a C5G7 transient. The SDP method accurately and efficiently replicated the solution of the conventional time-dependent MOC method using two orders of magnitude less memory.

A time-dependent neutron transport method of characteristics formulation with time derivative propagation

International Nuclear Information System (INIS)

Hoffman, Adam J.; Lee, John C.

2016-01-01

A new time-dependent Method of Characteristics (MOC) formulation for nuclear reactor kinetics was developed utilizing angular flux time-derivative propagation. This method avoids the requirement of storing the angular flux at previous points in time to represent a discretized time derivative; instead, an equation for the angular flux time derivative along 1D spatial characteristics is derived and solved concurrently with the 1D transport characteristic equation. This approach allows the angular flux time derivative to be recast principally in terms of the neutron source time derivatives, which are approximated to high-order accuracy using the backward differentiation formula (BDF). This approach, called Source Derivative Propagation (SDP), drastically reduces the memory requirements of time-dependent MOC relative to methods that require storing the angular flux. An SDP method was developed for 2D and 3D applications and implemented in the computer code DeCART in 2D. DeCART was used to model two reactor transient benchmarks: a modified TWIGL problem and a C5G7 transient. The SDP method accurately and efficiently replicated the solution of the conventional time-dependent MOC method using two orders of magnitude less memory.

Small airway epithelial cells exposure to printer-emitted engineered nanoparticles induces cellular effects on human microvascular endothelial cells in an alveolar-capillary co-culture model.

Science.gov (United States)

Sisler, Jennifer D; Pirela, Sandra V; Friend, Sherri; Farcas, Mariana; Schwegler-Berry, Diane; Shvedova, Anna; Castranova, Vincent; Demokritou, Philip; Qian, Yong

2015-01-01

The printer is one of the most common office equipment. Recently, it was reported that toner formulations for printing equipment constitute nano-enabled products (NEPs) and contain engineered nanomaterials (ENMs) that become airborne during printing. To date, insufficient research has been performed to understand the potential toxicological properties of printer-emitted particles (PEPs) with several studies using bulk toner particles as test particles. These studies demonstrated the ability of toner particles to cause chronic inflammation and fibrosis in animal models. However, the toxicological implications of inhalation exposures to ENMs emitted from laser printing equipment remain largely unknown. The present study investigates the toxicological effects of PEPs using an in vitro alveolar-capillary co-culture model with Human Small Airway Epithelial Cells (SAEC) and Human Microvascular Endothelial Cells (HMVEC). Our data demonstrate that direct exposure of SAEC to low concentrations of PEPs (0.5 and 1.0 µg/mL) caused morphological changes of actin remodeling and gap formations within the endothelial monolayer. Furthermore, increased production of reactive oxygen species (ROS) and angiogenesis were observed in the HMVEC. Analysis of cytokine and chemokine levels demonstrates that interleukin (IL)-6 and MCP-1 may play a major role in the cellular communication observed between SAEC and HMVEC and the resultant responses in HMVEC. These data indicate that PEPs at low, non-cytotoxic exposure levels are bioactive and affect cellular responses in an alveolar-capillary co-culture model, which raises concerns for potential adverse health effects.

Plant Growth Biostimulants, Dietary Feed Supplements and Cosmetics Formulated with Supercritical CO2 Algal Extracts

Directory of Open Access Journals (Sweden)

Izabela Michalak

2017-01-01

Full Text Available The review paper presents the use of algal extracts as safe and solvent-free components of plant growth biostimulants, dietary feed additives and cosmetics. Innovative technology that uses extracts obtained by supercritical CO2 extraction, as a method of isolation of biologically active compounds from algal biomass, is presented. An important part of the complete technology is the final formulation of the product. This enabled realization of the further step which was assessment of the utilitarian properties of the extract-based products. The extracts were analysed for the presence of biologically active molecules (e.g., plant hormones, polyphenols which provide useful properties such as antioxidant, antiviral, anti-inflammatory and antibacterial. The bio-products were tested in germination tests and underwent field trials to search for plant growth biostimulatory properties. Tests on animals (laying hens experiments were conducted to assess pro-health properties of new dietary feed supplement. Another application were cosmetic formulations (dermatological tests. The results of the application tests were very promising, however further studies are required for the registration of the products and successful implementation to the market.

Investigation of Lipid Oxidation in High- and Low-Lipid-Containing Topical Skin Formulations

DEFF Research Database (Denmark)

Raagaard Thomsen, Birgitte; Frisenfeldt Horn, Anna; Hyldig, G.

2017-01-01

in the skin care formulations (especially during exposure to light), whereas in the lip care formulations the best candidates were pentanal (especially during exposure to light and iron), 2-methyl furan and 3-methyl-3-buten-2-one (especially during exposure to light, iron and high temperatures). Graphical...... Abstract: [Figure not available: see fulltext.]...

Worldwide Mycotoxins Exposure in Pig and Poultry Feed Formulations

Directory of Open Access Journals (Sweden)

Philippe Guerre

2016-11-01

Full Text Available The purpose of this review is to present information about raw materials that can be used in pig and poultry diets and the factors responsible for variations in their mycotoxin contents. The levels of mycotoxins in pig and poultry feeds are calculated based on mycotoxin contamination levels of the raw materials with different diet formulations, to highlight the important role the stage of production and the raw materials used can have on mycotoxins levels in diets. Our analysis focuses on mycotoxins for which maximum tolerated levels or regulatory guidelines exist, and for which sufficient contamination data are available. Raw materials used in feed formulation vary considerably depending on the species of animal, and the stage of production. Mycotoxins are secondary fungal metabolites whose frequency and levels also vary considerably depending on the raw materials used and on the geographic location where they were produced. Although several reviews of existing data and of the literature on worldwide mycotoxin contamination of food and feed are available, the impact of the different raw materials used on feed formulation has not been widely studied.

Worldwide Mycotoxins Exposure in Pig and Poultry Feed Formulations.

Science.gov (United States)

Guerre, Philippe

2016-11-24

The purpose of this review is to present information about raw materials that can be used in pig and poultry diets and the factors responsible for variations in their mycotoxin contents. The levels of mycotoxins in pig and poultry feeds are calculated based on mycotoxin contamination levels of the raw materials with different diet formulations, to highlight the important role the stage of production and the raw materials used can have on mycotoxins levels in diets. Our analysis focuses on mycotoxins for which maximum tolerated levels or regulatory guidelines exist, and for which sufficient contamination data are available. Raw materials used in feed formulation vary considerably depending on the species of animal, and the stage of production. Mycotoxins are secondary fungal metabolites whose frequency and levels also vary considerably depending on the raw materials used and on the geographic location where they were produced. Although several reviews of existing data and of the literature on worldwide mycotoxin contamination of food and feed are available, the impact of the different raw materials used on feed formulation has not been widely studied.

A formulation to encapsulate nootkatone for tick control.

Science.gov (United States)

Behle, Robert W; Flor-Weiler, Lina B; Bharadwaj, Anuja; Stafford, Kirby C

2011-11-01

Nootkatone is a component of grapefruit oil that is toxic to the disease-vectoring tick, Ixodes scapularis Say, but unfortunately causes phytotoxicity to treated plants and has a short residual activity due to volatility. We prepared a lignin-encapsulated nootkatone formulation to compare with a previously used emulsifiable formulation for volatility, plant phytotoxicity, and toxicity to unfed nymphs of I. scapularis. Volatility of nootkatone was measured directly by trapping nootkatone vapor in a closed system and indirectly by measuring nootkatone residue on treated filter paper after exposure to simulated sunlight (Xenon). After 24 h in the closed system, traps collected only 15% of the nootkatone applied as the encapsulated formulation compared with 40% applied as the emulsifiable formulation. After a 1-h light exposure, the encapsulated formulation retained 92% of the nootkatone concentration compared with only 26% retained by the emulsifiable formulation. For plant phytotoxicity, cabbage, Brassica oleracea L., leaves treated with the encapsulated formulation expressed less necrosis, retaining greater leaf weight compared with leaves treated with the emusifiable formulation. The nootkatone in the emulsifiable formulation was absorbed by cabbage and oat, Avena sativa L., plants (41 and 60% recovered 2 h after application, respectively), as opposed to 100% recovery from the plants treated with encapsulated nootkatone. Using a treated vial technique, encapsulated nootkatone was significantly more toxic to I. scapularis nymphs (LC50 = 20 ng/cm2) compared with toxicity of the emulsifiable formulation (LC50 = 35 ng/cm2). Thus, the encapsulation of nootkatone improved toxicity for tick control, reduced nootkatone volatility, and reduced plant phytotoxicity.

Noise-induced hearing loss in Korean workers: co-exposure to organic solvents and heavy metals in nationwide industries.

Directory of Open Access Journals (Sweden)

Yoon-Hyeong Choi

Full Text Available BACKGROUND: Noise exposure is a well-known contributor to work-related hearing loss. Recent biological evidence suggests that exposure to ototoxic chemicals such as organic solvents and heavy metals may be additional contributors to hearing loss. However, in industrial settings, it is difficult to determine the risks of hearing loss due to these chemicals in workplaces accompanied by excessive noise exposure. A few studies suggest that the effect of noise may be enhanced by ototoxic chemicals. Therefore, this study investigated whether co-exposure to organic solvents and/or heavy metals in the workplace modifies the risk of noise exposure on hearing loss in a background of excessive noise. METHODS: We examined 30,072 workers nationwide in a wide range of industries from the Korea National Occupational Health Surveillance 2009. Data on industry-based exposure (e.g., occupational noise, heavy metals, and organic solvents and subject-specific health outcomes (e.g., audiometric examination were collected. Noise was measured as the daily 8-h time-weighted average level. Air conduction hearing thresholds were measured from 0.5 to 6 kHz, and pure-tone averages (PTA (i.e., means of 2, 3, and 4 kHz were computed. RESULTS: In the multivariate linear model, PTA increment with occupational noise were 1.64-fold and 2.15-fold higher in individuals exposed to heavy metals and organic solvents than in unexposed individuals, respectively. CONCLUSION: This study provides nationwide evidence that co-exposure to heavy metals and/or organic solvents may exacerbate the effect of noise exposure on hearing loss in workplaces. These findings suggest that workers in industries dealing with heavy metals or organic solvents are susceptible to such risks.

Quaternionic formulation of tachyons, superluminal transformations and a complex space-time

Energy Technology Data Exchange (ETDEWEB)

Imaeda, K [Dublin Inst. for Advanced Studies (Ireland)

1979-04-11

A theory of tachyons and superluminal transformations is developed on the basis of the quaternionic formulation. A complex space-time adn a complex transformation group which contains both Lorentz transformations and superluminal transformations are introduced. The complex space-time '' the biquaternion space'' which is closed under the superluminal transformations is introduced. The principle of special relativity, such as the conservation of the quadratic form of the metric of the space-time, and the principle of duality are extended to the complex space-time and to bradyons, luxons and tachyons under the complex transformations. SeVeral characteristic features of the superluminal transformations and of tachyons are derived.

Effect of exposure time and image resolution on fractal dimension

International Nuclear Information System (INIS)

An, Byung Mo; Heo, Min Suk; Lee, Seung Pyo; Lee, Sam Sun; Choi, Soon Chul; Park, Tae Won; Kim, Jong Dae

2002-01-01

To evaluate the effect of exposure time and image resolution on fractal dimension calculations for determining the optimal range of these two variances. Thirty-one radiographs of the mandibular angle area of sixteen human dry mandibles were taken at different exposure times (0.01, 0.08, 0.16, 0.25, 0.40, 0.64, and 0.80 s). Each radiograph was digitized at 1200 dpi, 8 bit, 256 gray level using a film scanner. We selected an Region of Interest (ROI) that corresponded to the same region as in each radiograph, but the resolution of ROI was degraded to 1000, 800, 600, 500, 400, 300, 200, and 100 dpi. The fractal dimension was calculated by using the tile-counting method for each image, and the calculated values were then compared statistically. As the exposure time and the image resolution increased, the mean value of the fractal dimension decreased, except the case where exposure time was set at 0.01 seconds (alpha = 0.05). The exposure time and image resolution affected the fractal dimension by interaction (p<0.001). When the exposure time was set to either 0.64 seconds or 0.80 seconds, the resulting fractal dimensions were lower, irrespective of image resolution, than at shorter exposure times (alpha = 0.05). The optimal range for exposure time and resolution was determined to be 0.08-0.40 seconds and from 400-1000 dpi, respectively. Adequate exposure time and image resolution is essential for acquiring the fractal dimension using tile-counting method for evaluation of the mandible.

Application of UV Imaging in Formulation Development.

Science.gov (United States)

Sun, Yu; Østergaard, Jesper

2017-05-01

Efficient drug delivery is dependent on the drug substance dissolving in the body fluids, being released from dosage forms and transported to the site of action. A fundamental understanding of the interplay between the physicochemical properties of the active compound and pharmaceutical excipients defining formulation behavior after exposure to the aqueous environments and pharmaceutical performance is critical in pharmaceutical development, manufacturing and quality control of drugs. UV imaging has been explored as a tool for qualitative and quantitative characterization of drug dissolution and release with the characteristic feature of providing real-time visualization of the solution phase drug transport in the vicinity of the formulation. Events occurring during drug dissolution and release, such as polymer swelling, drug precipitation/recrystallization, or solvent-mediated phase transitions related to the structural properties of the drug substance or formulation can be monitored. UV imaging is a non-intrusive and simple-to-operate analytical technique which holds potential for providing a mechanistic foundation for formulation development. This review aims to cover applications of UV imaging in the early and late phase pharmaceutical development with a special focus on the relation between structural properties and performance. Potential areas of future advancement and application are also discussed.

Neonates need tailored drug formulations.

Science.gov (United States)

Allegaert, Karel

2013-02-08

Drugs are very strong tools used to improve outcome in neonates. Despite this fact and in contrast to tailored perfusion equipment, incubators or ventilators for neonates, we still commonly use drug formulations initially developed for adults. We would like to make the point that drug formulations given to neonates need to be tailored for this age group. Besides the obvious need to search for active compounds that take the pathophysiology of the newborn into account, this includes the dosage and formulation. The dosage or concentration should facilitate the administration of low amounts and be flexible since clearance is lower in neonates with additional extensive between-individual variability. Formulations need to be tailored for dosage variability in the low ranges and also to the clinical characteristics of neonates. A specific focus of interest during neonatal drug development therefore is a need to quantify and limit excipient exposure based on the available knowledge of their safety or toxicity. Until such tailored vials and formulations become available, compounding practices for drug formulations in neonates should be evaluated to guarantee the correct dosing, product stability and safety.

Understanding Pesticide Risks: Toxicity and Formulation

OpenAIRE

Muntz, Helen; Miller, Rhonda; Alston, Diane

2016-01-01

This fact sheet provides information about pesticide risks to human health, primary means of pesticide exposure, standardized measures of pesticide toxicity, pesticide signal words and type of pesticide formulations.

EXPOSURE TO ENVIRONMENTALLY RELEVANT CONCENTRATIONS OF DIFFERENT NONYLPHENOL FORMULATIONS IN JAPANESE MEDAKA. (R827098)

Science.gov (United States)

The time course of exposure to p-nonylphenol (NP) from two different sources was compared to equalivent exposures of 17--estradiol (E2) and a solvent control (ethanol; EtOH). Japanese medaka were exposed for 4 days to a nomina...

New tablet formulation of tacrolimus with smaller interindividual variability may become a better treatment option than the conventional capsule formulation in organ transplant patients

Directory of Open Access Journals (Sweden)

Kim YK

2017-09-01

Full Text Available Yu Kyong Kim,1 Anhye Kim,1,2 Shin Jung Park,3 Howard Lee1,4 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 2Clinical Trial Center, Ajou University Medical Center, Suwon, 3Research Institute, Chong Kun Dang Pharmaceutical Corp, Yongin, 4Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Suwon, Republic of Korea Abstract: To evaluate the pharmacokinetic (PK and tolerability profiles of a new tablet formulation of tacrolimus and its interindividual variability (IIV in the systemic exposure, and to compare them with those of the conventional capsule formulation, a randomized, open-label, two-treatment, two-period, two-sequence, crossover study was performed in 47 healthy males. The capsule or tablet formulation of tacrolimus was orally administered, and serial blood samples were collected up to 96 hours after dosing. Whole-blood tacrolimus concentration was determined using liquid chromatography–tandem mass spectrometry. The maximum whole-blood tacrolimus concentration (Cmax and the area under the whole-blood tacrolimus concentration–time curve from 0 hour to the last quantifiable concentration (AUClast were compared between the two formulations. The similarity factor (f2 of the in vitro dissolution profiles was calculated. The geometric mean ratio (90% confidence interval of tablet to capsule was 0.9680 (0.8873–1.0560 and 1.0322 (0.9359–1.1385 for Cmax and AUClast, respectively. The IIV of Cmax and AUClast of the tablet was smaller than the capsule. The f2 values were >50 in all media. Both formulations were well tolerated. Thus, the tablet formulation of tacrolimus has smaller IIV in the systemic exposure than capsule, while having comparable PK and tolerability profiles, which may render it as a better treatment option for organ transplant patients. Keywords: new formulation, incrementally

Application of UV Imaging in Formulation Development

DEFF Research Database (Denmark)

Sun, Yu; Østergaard, Jesper

2017-01-01

defining formulation behavior after exposure to the aqueous environments and pharmaceutical performance is critical in pharmaceutical development, manufacturing and quality control of drugs. UV imaging has been explored as a tool for qualitative and quantitative characterization of drug dissolution...... related to the structural properties of the drug substance or formulation can be monitored. UV imaging is a non-intrusive and simple-to-operate analytical technique which holds potential for providing a mechanistic foundation for formulation development. This review aims to cover applications of UV...

Effects of stunning with different carbon dioxide concentrations and exposure times on suckling lamb meat quality.

Science.gov (United States)

Bórnez, R; Linares, M B; Vergara, H

2009-03-01

Forty-nine Manchega breed male suckling lambs were used to determine the effect of different stunning methods (using two different CO2 concentrations and exposure times) on lamb meat quality. The lambs were allocated to five stunning treatments including four CO2 treatments [80% CO2 for 90s (G1); 90% CO2 for 90s (G2); 90% CO2 for 60s (G3); 80% CO2 for 60s (G4)] and an electrically stunned control group (G5). The gas-stunning treatments did not cause neither haematomas nor blood splash in the carcasses. Meat quality was evaluated by testing pH, colour (L(∗), a(∗), b(∗), chroma, hue values), water holding capacity (WHC), cooking loss (CL), shear force (SF), drip loss (DL) and total aerobic bacteria. Statistical differences in pH at 24h post-mortem, colour, WHC and CL were not found among groups. After 7 days post-mortem, there were statistical differences among groups in pH (highest in G4 and G5) and in DL (highest in G1). There were differences in SF due to stunning method evident after 72h and 7 days ageing. The statistical differences (Plambs since a highest stability with ageing time on meat quality was found using 90% CO2.

Mediation analysis with time varying exposures and mediators.

Science.gov (United States)

VanderWeele, Tyler J; Tchetgen Tchetgen, Eric J

2017-06-01

In this paper we consider causal mediation analysis when exposures and mediators vary over time. We give non-parametric identification results, discuss parametric implementation, and also provide a weighting approach to direct and indirect effects based on combining the results of two marginal structural models. We also discuss how our results give rise to a causal interpretation of the effect estimates produced from longitudinal structural equation models. When there are time-varying confounders affected by prior exposure and mediator, natural direct and indirect effects are not identified. However, we define a randomized interventional analogue of natural direct and indirect effects that are identified in this setting. The formula that identifies these effects we refer to as the "mediational g-formula." When there is no mediation, the mediational g-formula reduces to Robins' regular g-formula for longitudinal data. When there are no time-varying confounders affected by prior exposure and mediator values, then the mediational g-formula reduces to a longitudinal version of Pearl's mediation formula. However, the mediational g-formula itself can accommodate both mediation and time-varying confounders and constitutes a general approach to mediation analysis with time-varying exposures and mediators.

Impacts of ocean acidification on sperm develop with exposure time for a polychaete with long lived sperm.

Science.gov (United States)

Campbell, Anna L; Ellis, Robert P; Urbina, Mauricio A; Mourabit, Sulayman; Galloway, Tamara S; Lewis, Ceri

2017-08-01

The majority of marine invertebrate species release eggs and sperm into seawater for external fertilisation. Seawater conditions are currently changing at an unprecedented rate as a consequence of ocean acidification (OA). Sperm are thought to be particularly vulnerable to these changes and may be exposed to external environmental conditions for variable periods of time between spawning and fertilisation. Here, we undertook a mechanistic investigation of sperm swimming performance in the coastal polychaete Arenicola marina during an extended exposure to OA conditions (pH NBS 7.77, 1000 μatm pCO 2 ). We found that key fitness-related aspects of sperm functioning declined faster under OA conditions i.e. impacts became apparent with exposure time. Sperm swimming speed (VCL), the number of motile sperm and sperm path linearity all dropped significantly after 4 h under OA conditions whilst remaining constant under ambient conditions at this time point. Our results highlight the importance of sperm exposure duration in ocean acidification experiments and may help towards explaining species specific differences in response. Copyright © 2017 Elsevier Ltd. All rights reserved.

Long-acting poly(DL:lactic acid-castor oil) 3:7-bupivacaine formulation: effect of hydrophobic additives.

Science.gov (United States)

Sokolsky-Papkov, Marina; Golovanevski, Ludmila; Domb, Abraham J; Weiniger, Carolyn F

2011-12-01

To reduce formulation viscosity of bupivacaine/poly(DL lactic acid co castor oil) 3:7 without increasing bupivacaine release rates. Poly(DL lactic acid) 3:7 was synthesized and bupivacaine formulation prepared by mixing with additives ricinoleic acid or castor oil. In vitro release measurements identified optimum formulation. Anesthetized ICR mice were injected around left sciatic nerve using nerve stimulator with 0.1 mL of formulation. Animals received 10% bupivacaine-polymer formulation with 10% castor oil (p(DLLA:CO)3:7-10% bupi-10% CO) or 15% bupivacaine-polymer with 10% castor oil (p(DLLA:CO)3:7-15% bupi-10% CO). Sensory and motor block were measured. Viscosity of 10% and 15% bupivacaine-p(DLLA:CO)3:7 formulations was reduced using hydrophobic additives; however, castor oil reduced bupivacaine release rates and eliminated burst effect. Less than 10% of the incorporated bupivacaine was released during 6 h, and less than 25% released in 24 h in vitro. In vivo formulation injection resulted in a 24 h motor block and a sensory block lasting at least 72 h. Incorporation of hydrophobic low-viscosity additive reduced viscosity in addition to burst release effects. Bupivacaine-polymer formulation with castor oil additive demonstrated prolonged sensory analgesia in vivo, with reduced duration of motor block.

Formulation of an inhibitor radiopharmaceutical of prostatic antigen of 177Lu-Glu-Nh-CO-Nh-Lys membrane

International Nuclear Information System (INIS)

Ortega S, D.

2015-01-01

The prostate specific membrane antigen (PSMA) is a zinc metalloenzyme that is expressed on the cell membrane and highly expressed in prostate cancer. Recently, it has been demonstrated that the peptide sequence Glu-Nh-CO-Nh-Lys inhibit PSMA activity through an electrostatic interaction with the Zn. Several theragnostic radiopharmaceuticals with base in 177 Lu have been developed for radiotherapy of specific molecular targets because gamma and beta emissions of the radionuclide (β = 0.498 MeV and γ= 0.133 MeV). However, there is currently no label a formulation for preparing a radiopharmaceutical of 177 Lu-Glu-Nh-CO-Nh-Lys useful treatment of prostate cancer. The aim of this research was to optimize and document the process of production of the radiopharmaceutical 177 Lu-Glu-Nh-CO-Nh-Lys for sanitary registration application before the Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS). The optimization of the production process was assessed a factorial design of three variables with mixed levels (3 x 3 x 2) where the dependent variable is the radiochemical purity, the analytical method was validated by UV-Vis spectrophotometry. Next, process validation was carried out by labeling 3 lots of the optimized formulation of the radiopharmaceutical (5.55 GBq (2.16 μg) of 177 LuCl 3 , 90 mg peptide PSMA, 50 mg ascorbic acid and 150 μL of acetate buffer 1 M ph 5), long-term stability was performed by high resolution liquid chromatography) to determine its useful shelf life. 3 validation batches were prepared under protocols of Good Manufacturing Practice (GMP) in the Production Plant of Radiopharmaceuticals of the Instituto Nacional de Investigaciones Nucleares (ININ), meet specifications preset by obtaining a sterile and free development of bacterial endotoxin yields of labeled 100% and which retains its quality characteristics radiochemical purity greater than 90% for at least 15 days. (Author)

Content of carbon monoxide in the tissues of rats intoxicated with carbon monoxide in various conditions of acute exposure

Energy Technology Data Exchange (ETDEWEB)

Sokal, J.A.; Majka, J.; Palus, J.

1984-12-01

Tissue carbon monoxide (CO) content was investigated in rats severely intoxicated with CO under various exposure conditions: 1% CO for 4 min, 0.4% CO for 40 min and 0.12% CO for 12 h. Extravascular CO was determined in the heart and skeletal muscles immediately after termination of exposure, and carboxymyoglobin (MbCO) percent saturation was calculated. Total brain CO was estimated immediately after termination of exposure and after the time periods of restitution. After the same exposure conditions, MbCO percent saturation was higher in the heart than in skeletal muscle. In both types of muscle, saturation on myoglobin (Mb) with CO depended on blood carboxyhemoglobin (HbCO) level and not on the duration of exposure. The time course of CO elimination was the same for blood and brain, irrespective of CO exposure conditions. The results obtained showed that acute CO intoxication induced by long duration exposures did not involve CO accumulation in the tissues.

An approach for assessing human exposures to chemical mixtures in the environment

International Nuclear Information System (INIS)

Rice, Glenn; MacDonell, Margaret; Hertzberg, Richard C.; Teuschler, Linda; Picel, Kurt; Butler, Jim; Chang, Young-Soo; Hartmann, Heidi

2008-01-01

Humans are exposed daily to multiple chemicals, including incidental exposures to complex chemical mixtures released into the environment and to combinations of chemicals that already co-exist in the environment because of previous releases from various sources. Exposures to chemical mixtures can occur through multiple pathways and across multiple routes. In this paper, we propose an iterative approach for assessing exposures to environmental chemical mixtures; it is similar to single-chemical approaches. Our approach encompasses two elements of the Risk Assessment Paradigm: Problem Formulation and Exposure Assessment. Multiple phases of the assessment occur in each element of the paradigm. During Problem Formulation, analysts identify and characterize the source(s) of the chemical mixture, ensure that dose-response and exposure assessment measures are concordant, and develop a preliminary evaluation of the mixture's fate. During Exposure Assessment, analysts evaluate the fate of the chemicals comprising the mixture using appropriate models and measurement data, characterize the exposure scenario, and estimate human exposure to the mixture. We also describe the utility of grouping the chemicals to be analyzed based on both physical-chemical properties and an understanding of environmental fate. In the article, we also highlight the need for understanding of changes in the mixture composition in the environment due to differential transport, differential degradation, and differential partitioning to other media. The section describes the application of the method to various chemical mixtures, highlighting issues associated with assessing exposures to chemical mixtures in the environment

Time and Place as Modifiers of Personal UV Exposure

Directory of Open Access Journals (Sweden)

Brian L. Diffey

2018-05-01

Full Text Available It is a common belief that, if we want to limit our sun exposure during outdoor recreational activities and holidays in order to avoid sunburn or reduce our risk of skin cancer, we need to reach for the bottle of sunscreen or cover up with clothing. As important as these measures are, there is another way to enjoy our time outdoors and still benefit from the experience. In this article, we consider the impact of time, place, and behaviour outdoors on our exposure to solar ultraviolet (UV radiation. Some of the simple actions we can take in controlling our UV exposure include being aware of the position of the sun in the sky, understanding how we can use the UV index to guide our outdoor exposure, and the importance of reducing our sun exposure around the middle of the day. Finally we review our preferred holiday activities and destinations, and the influence of outdoor leisure pursuits. By planning where and when we spend our leisure time in the sun, we can maximise our enjoyment whilst limiting our UV exposure.

Time and Place as Modifiers of Personal UV Exposure.

Science.gov (United States)

Diffey, Brian L

2018-05-30

It is a common belief that, if we want to limit our sun exposure during outdoor recreational activities and holidays in order to avoid sunburn or reduce our risk of skin cancer, we need to reach for the bottle of sunscreen or cover up with clothing. As important as these measures are, there is another way to enjoy our time outdoors and still benefit from the experience. In this article, we consider the impact of time, place, and behaviour outdoors on our exposure to solar ultraviolet (UV) radiation. Some of the simple actions we can take in controlling our UV exposure include being aware of the position of the sun in the sky, understanding how we can use the UV index to guide our outdoor exposure, and the importance of reducing our sun exposure around the middle of the day. Finally we review our preferred holiday activities and destinations, and the influence of outdoor leisure pursuits. By planning where and when we spend our leisure time in the sun, we can maximise our enjoyment whilst limiting our UV exposure.

General time-dependent formulation of quantum scattering theory

International Nuclear Information System (INIS)

Althorpe, Stuart C.

2004-01-01

We derive and explain the key ideas behind a time-dependent formulation of quantum scattering theory, applicable generally to systems with a finite-range scattering potential. The scattering is initiated and probed by plane wave packets, which are localized just outside the range of the potential. The asymptotic limits of conventional scattering theory (initiation in the remote past; detection in the remote future) are not taken. Instead, the differential cross section (DCS) is obtained by projecting the scattered wave packet onto the probe plane wave packets. The projection also yields a time-dependent version of the DCS. Cuts through the wave packet, just as it exits the scattering potential, yield time-dependent and time-independent angular distributions that give a close-up picture of the scattering which complements the DCS. We have previously applied the theory to interpret experimental cross sections of chemical reactions [e.g., S. C. Althorpe, F. Fernandez-Alonso, B. D. Bean, J. D. Ayers, A. E. Pomerantz, R. N. Zare, and E. Wrede, Nature (London) 416, 67 (2002)]. This paper gives the derivation of the theory, and explains its relation to conventional scattering theory. For clarity, the derivation is restricted to spherical-particle scattering, though it may readily be extended to general multichannel systems. We illustrate the theory using a simple application to hard-sphere scattering

A simulation study to quantify the impacts of exposure measurement error on air pollution health risk estimates in copollutant time-series models.

Science.gov (United States)

Dionisio, Kathie L; Chang, Howard H; Baxter, Lisa K

2016-11-25

Exposure measurement error in copollutant epidemiologic models has the potential to introduce bias in relative risk (RR) estimates. A simulation study was conducted using empirical data to quantify the impact of correlated measurement errors in time-series analyses of air pollution and health. ZIP-code level estimates of exposure for six pollutants (CO, NO x , EC, PM 2.5 , SO 4 , O 3 ) from 1999 to 2002 in the Atlanta metropolitan area were used to calculate spatial, population (i.e. ambient versus personal), and total exposure measurement error. Empirically determined covariance of pollutant concentration pairs and the associated measurement errors were used to simulate true exposure (exposure without error) from observed exposure. Daily emergency department visits for respiratory diseases were simulated using a Poisson time-series model with a main pollutant RR = 1.05 per interquartile range, and a null association for the copollutant (RR = 1). Monte Carlo experiments were used to evaluate the impacts of correlated exposure errors of different copollutant pairs. Substantial attenuation of RRs due to exposure error was evident in nearly all copollutant pairs studied, ranging from 10 to 40% attenuation for spatial error, 3-85% for population error, and 31-85% for total error. When CO, NO x or EC is the main pollutant, we demonstrated the possibility of false positives, specifically identifying significant, positive associations for copollutants based on the estimated type I error rate. The impact of exposure error must be considered when interpreting results of copollutant epidemiologic models, due to the possibility of attenuation of main pollutant RRs and the increased probability of false positives when measurement error is present.

Cumulative exposure to carbon monoxide during the day

Energy Technology Data Exchange (ETDEWEB)

Joumard, R. (INRETS, 69 - Bron (FR))

The carbon monoxide, CO, has the advantage of being very easily and accurately measured under various conditions. In addition, it allows the translation of CO concentrations into their biological effects. The cumulative CO exposure should be considered according to current environment conditions during a given period of life, e.g. the day. In addition, the translation of concentrations and exposure times of CO fixed on blood haemoglobine (carboxyhaemoglobine) depends on physiological factors such as age, size, sex, or physical activity. This paper gives some examples of CO exposure translated into curves of carboxyhaemoglobine: case of 92 persons whose schedule was studied in details, of customs officers whose exposure was measured during one week, or other theoretical cases. In all the cases studied, smoking is by far the first factor of pollution by carbon monoxide. If not considering this case, the CO contents observed are preoccupying for sensitive subjects (in particular children) only in very rare cases. Furthermore, this approach allows the assessment of maximal allowable concentrations during specific exposures (work, e.g. in a tunnel) by integrating them into normal life conditions and population current exposure.

Real-time personal exposure and health condition monitoring system

Energy Technology Data Exchange (ETDEWEB)

Saitou, Isamu; Kanda, Hiroaki; Asai, Akio; Takeishi, Naoki; Ota, Yoshito [Hitachi Aloka Medical, Ltd., Measuring Systems Engineering Dept., Tokyo (Japan); Hanawa, Nobuhiro; Ueda, Hisao; Kusunoki, Tsuyoshi; Ishitsuka, Etsuo; Kawamura, Hiroshi [Japan Atomic Energy Agency, Oarai Research and Development Center, Oarai, Ibaraki (Japan)

2012-03-15

JAEA (Japan Atomic Energy Agency) and HAM (Hitachi Aloka Medical, Ltd) have proposed novel monitoring system for workers of nuclear facility. In these facilities, exposure management for workers is mainly used access control and personal exposure recordings. This system is currently only for reports management but is not confirmative for surveillance when work in progress. Therefore, JAEA and HAM integrate access control and personal exposure recordings and two real-time monitoring systems which are position sensing and vital sign monitor. Furthermore change personal exposure management to real-time management, this system integration prevents workers from risk of accidents, and makes possible take appropriate action quickly. This novel system is going to start for tentative operation, using position sensing and real-time personal dosimeter with database in Apr. 2012. (author)

Co-exposure to nickel and cobalt chloride enhances cytotoxicity and oxidative stress in human lung epithelial cells.

Science.gov (United States)

Patel, Eshan; Lynch, Christine; Ruff, Victoria; Reynolds, Mindy

2012-02-01

Nickel and cobalt are heavy metals found in land, water, and air that can enter the body primarily through the respiratory tract and accumulate to toxic levels. Nickel compounds are known to be carcinogenic to humans and animals, while cobalt compounds produce tumors in animals and are probably carcinogenic to humans. People working in industrial and manufacturing settings have an increased risk of exposure to these metals. The cytotoxicity of nickel and cobalt has individually been demonstrated; however, the underlying mechanisms of co-exposure to these heavy metals have not been explored. In this study, we investigated the effect of exposure of H460 human lung epithelial cells to nickel and cobalt, both alone and in combination, on cell survival, apoptotic mechanisms, and the generation of reactive oxygen species and double strand breaks. For simultaneous exposure, cells were exposed to a constant dose of 150 μM cobalt or nickel, which was found to be relatively nontoxic in single exposure experiments. We demonstrated that cells exposed simultaneously to cobalt and nickel exhibit a dose-dependent decrease in survival compared to the cells exposed to a single metal. The decrease in survival was the result of enhanced caspase 3 and 7 activation and cleavage of poly (ADP-ribose) polymerase. Co-exposure increased the production of ROS and the formation of double strand breaks. Pretreatment with N-acetyl cysteine alleviated the toxic responses. Collectively, this study demonstrates that co-exposure to cobalt and nickel is significantly more toxic than single exposure and that toxicity is related to the formation of ROS and DSB. Copyright © 2011 Elsevier Inc. All rights reserved.

CoCoNuT: General relativistic hydrodynamics code with dynamical space-time evolution

Science.gov (United States)

Dimmelmeier, Harald; Novak, Jérôme; Cerdá-Durán, Pablo

2012-02-01

CoCoNuT is a general relativistic hydrodynamics code with dynamical space-time evolution. The main aim of this numerical code is the study of several astrophysical scenarios in which general relativity can play an important role, namely the collapse of rapidly rotating stellar cores and the evolution of isolated neutron stars. The code has two flavors: CoCoA, the axisymmetric (2D) magnetized version, and CoCoNuT, the 3D non-magnetized version.

Skin decontamination cream for radiological contaminants: Formulation development and evaluation.

Science.gov (United States)

Khan, Abdul Wadood; Kotta, Sabna; Rana, Sudha; Ansari, Shahid Husain; Sharma, Rakesh Kumar; Ali, Javed

2013-01-01

Increased use of the radioactive materials in the field of research, medical, nuclear power plant, and industry has increased the risk of accidental exposure. Intentional use of the radioisotopes by terrorist organizations could cause exposure/contamination of a number of the population. In view of the accidental contamination, there is a need to develop self-usable decontamination formulations that could be used immediately after contamination is suspected. Present work was planned to optimize and develop self-usable radiation decontamination cream formulation. Various pharmaceutical parameters were characterized. (99m)Tc-sodium pertechnetate was used as radiocontaminant. Static counts were recorded before and after decontamination using single photon emission computed tomography. Decontamination efficacy of the cream was found to be 42% ± 3% at 0-0.5 h after the exposure. Primary skin irritancy test was satisfactory as no erythema or edema was observed visually after 2 weeks of the formulation application. The decontamination studies proved the potential of EDTA to remove the radiological contaminants effectively.

Radiographic apparatus and method for monitoring film exposure time

International Nuclear Information System (INIS)

Vatne, R.S.; Woodmansee, W.E.

1981-01-01

In connection with radiographic inspection of structural and industrial materials, method and apparatus are disclosed for automatically determining and displaying the time required to expose a radiographic film positioned to receive radiation passed by a test specimen, so that the finished film is exposed to an optimum blackening (density) for maximum film contrast. A plot is made of the variations in a total exposure parameter (representing the product of detected radiation rate and time needed to cause optimum film blackening) as a function of the voltage level applied to an X-ray tube. An electronic function generator storing the shape of this plot is incorporated into an exposure monitoring apparatus, such that for a selected tube voltage setting, the function generator produces an electrical analog signal of the corresponding exposure parameter. During the exposure, another signal is produced representing the rate of radiation as monitored by a diode detector positioned so as to receive the same radiation that is incident on the film. The signal representing the detected radiation rate is divided, by an electrical divider circuit into the signal representing total exposure, and the resulting quotient is an electrical signal representing the required exposure time. (author)

Ultrafine PEG-coated poly(lactic-co-glycolic acid) nanoparticles formulated by hydrophobic surfactant-assisted one-pot synthesis for biomedical applications.

Science.gov (United States)

Chu, Chih-Hang; Wang, Yu-Chao; Huang, Hsin-Ying; Wu, Li-Chen; Yang, Chung-Shi

2011-05-06

A novel method was developed for the one-pot synthesis of ultrafine poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs), using an emulsion solvent evaporation formulation method. Using either cetyltrimethylammonium bromide (CTAB) or poly(ethylene glycol)-distearyl phosphoethanolamine (PEGPE) as an oily emulsifier during the emulsion process, produced PLGA particle sizes of less than 50 nm, constituting a breakthrough in emulsion formulation methods. The yield of ultrafine PLGA NPs increased with PEGPE/PLGA ratio, reaching a plateau at around 85%, when the PEGPE/PLGA ratio reached 3:1. The PEGPE-PLGA NPs exhibited high drug loading content, reduced burst release, good serum stability, and enhanced cell uptake rate compared with traditional PLGA NPs. Sub-50 nm diameter PEG-coated ultrafine PLGA NPs show great potential for in vivo drug delivery systems.

An in vitro analysis of disintegration times of different formulations of olanzapine orodispersible tablet: a preliminary report.

Science.gov (United States)

Hobbs, David; Karagianis, Jamie; Treuer, Tamas; Raskin, Joel

2013-12-01

Orodispersible tablets (ODTs) are tablet or wafer forms of medication that disintegrate in the mouth, aided only by saliva. ODTs rely on different fast dissolve/disintegration manufacturing technologies. Disintegration time differences for several olanzapine ODT forms were investigated. Risperdal M-Tab(®) was included as a non-olanzapine ODT comparator. Eleven olanzapine ODT examples and orodispersible risperidone strengths were evaluated in vitro for formulation composition, manufacturing method, disintegration and dissolution characteristics, and formulation differences in comparison with freeze dried Zydis(®) ODT. Automated dissolution test equipment captured ODT dissolution rates by measuring real-time release of active ingredient. A high-speed video camera was used to capture tablet disintegration times in warm simulated saliva. The main outcome measure was the disintegration and dissolution characteristics of the ODT formulations. The ODT manufacturing method was associated with time to disintegrate; the fastest were freeze dried tablets, followed by soft compressed tablets and then hard/dense tablets. Olanzapine Zydis(®) was the only ODT that completely disintegrated in less than 4 s for all strengths (5, 10, 15, and 20 mg), followed by 5-mg Prolanz FAST(®) (12 s) and then risperidone ODT 4 mg (40 s). Reasons for slow dissolution of the olanzapine generics may include low product potency, excipient binding, excipient solubility, active ingredient particle size and incomplete disintegration. Differences in the formulation and manufacturing process of olanzapine ODTs appear to have a strong influence on the disintegration time of the active compound; differences that may potentially impact their use in clinical practice.

Carbon monoxide exposure and information processing during perceptual-motor performance

Energy Technology Data Exchange (ETDEWEB)

Mihevic, P.M.; Gliner, J.A.; Horvath, S.M.

1983-01-01

This study examined the influence of exposure to ambient carbon monoxide resulting in final carboxyhemoglobin (COHb) levels of approximately 5.0% on the ability to process information during motor performance. Subjects (n . 16) performed a primary reciprocal tapping task and a secondary digit manipulation task singly and/or concurrently during 2.5 h exposure to room air (0 ppm CO) or 100 ppm CO. Five levels of tapping difficulty and two levels of digit manipulation were employed. Tapping performance was unaffected when COHb levels were as high as 5%. However, at this level of COHb it was noted that CO exposure interacted with task difficulty of both tasks to influence reaction time on the digit manipulation task. It was concluded that motor performance was not influenced by exposure to CO leading to COHb concentrations of 5%. Task difficulty was a significant factor mediating behavioral effects of CO exposure.

Carbon monoxide exposure and information processing during perceptual-motor performance

Energy Technology Data Exchange (ETDEWEB)

Mihevic, P.M.; Gliner, J.A.; Horvath, S.M.

1983-04-01

This study examined the influence of exposure to ambient carbon monoxide resulting in final carboxyhemoglobin (COHb) levels of approximately 5.0% on the ability to process information during motor performance. Subjects (n = 16) performed a primary reciprocal tapping task and a secondary digit manipulation task singly and/or concurrently during 2.5 h exposure to room air (0 ppm CO) or 100 ppm CO. Five levels of tapping difficulty and two levels of digit manipulation were employed. Tapping performance was unaffected when COHb levels were as high as 5%. However, at this level of COHb it was noted that CO exposure interacted with task difficulty of both tasks to influence reaction time on the digit manipulation task. It was concluded that motor performance was not influenced by exposure to CO leading to COHb concentrations of 5%. Task difficulty was a significant factor mediating behavioral effects of CO exposure.

Formulation of Biocides Increases Antimicrobial Potency and Mitigates the Enrichment of Nonsusceptible Bacteria in Multispecies Biofilms

Science.gov (United States)

Forbes, Sarah; Cowley, Nicola; Mistry, Hitesh; Amézquita, Alejandro

2017-01-01

ABSTRACT The current investigation aimed to generate data to inform the development of risk assessments of biocide usage. Stabilized domestic drain biofilm microcosms were exposed daily over 6 months to increasing concentrations (0.01% to 1%) of the biocide benzalkonium chloride (BAC) in a simple aqueous solution (BAC-s) or in a complex formulation (BAC-f) representative of a domestic cleaning agent. Biofilms were analyzed by culture, differentiating by bacterial functional group and by BAC or antibiotic susceptibility. Bacterial isolates were identified by 16S rRNA sequencing, and changes in biofilm composition were assessed by high-throughput sequencing. Exposure to BAC-f resulted in significantly larger reductions in levels of viable bacteria than exposure to BAC-s, while bacterial diversity greatly decreased during exposure to both BAC-s and BAC-f, as evidenced by sequencing and viable counts. Increases in the abundance of bacteria exhibiting reduced antibiotic or BAC susceptibility following exposure to BAC at 0.1% were significantly greater for BAC-s than BAC-f. Bacteria with reduced BAC and antibiotic susceptibility were generally suppressed by higher BAC concentrations, and formulation significantly enhanced this effect. Significant decreases in the antimicrobial susceptibility of bacteria isolated from the systems before and after long-term BAC exposure were not detected. In summary, dose-dependent suppression of bacterial viability by BAC was enhanced by formulation. Biocide exposure decreased bacterial diversity and transiently enriched populations of organisms with lower antimicrobial susceptibility, and the effects were subsequently suppressed by exposure to 1% BAC-f, the concentration most closely reflecting deployment in formulated products. IMPORTANCE Assessment of the risks of biocide use has been based mainly on the exposure of axenic cultures of bacteria to biocides in simple aqueous solutions. The current investigation aimed to assess the

Variability of intra-urban exposure to particulate matter and CO from Asian-type community pollution sources

Science.gov (United States)

Lung, Shih-Chun Candice; Hsiao, Pao-Kuei; Wen, Tzu-Yao; Liu, Chun-Hu; Fu, Chi Betsy; Cheng, Yu-Ting

2014-02-01

Asian residential communities are usually dotted with various spot pollution sources (SPS), such as restaurants, temples, and home factories, with traffic arteries passing through, resulting in higher intra-urban pollution variability compared with their western counterparts. Thus, it is important to characterize spatial variability of pollutant levels in order to assess accurately residents' exposures in their communities. The objectives of this study are to assess the actual pollutant levels and variability within an Asian urban area and to evaluate the influence of vehicle emission and various SPS on the exposure levels within communities. Real-time monitoring was conducted for a total of 123 locations for particulate matter (PM) and CO in Taipei metropolitan, Taiwan. The mean concentrations for PM1, PM2.5, PM10, and CO are 29.8 ± 22.7, 36.0 ± 25.5, 61.9 ± 35.0 μg m-3 and 4.0 ± 2.5 ppm, respectively. The mean values of PM1/PM2.5 and PM2.5/PM10 are 0.80 ± 0.10 and 0.57 ± 0.15, respectively. PM and CO levels at locations near SPS could be increased by 3.5-4.9 times compared with those at background locations. Regression results show that restaurants contribute significantly 6.18, 6.33, 7.27 μg m-3, and 1.64 ppm to community PM1, PM2.5, PM10, and CO levels, respectively; while the contribution from temples are 13.2, 15.1, and 17.2 μg m-3 for PM1, PM2.5 and PM10, respectively. Additionally, construction sites elevate nearby PM10 levels by 14.2 μg m-3. At bus stops and intersections, vehicle emissions increased PM1 and PM2.5 levels by 5 μg m-3. These results demonstrate significant contribution of community sources to air pollution, and thus the importance of assessing intra-community variability in Asian cities for air pollution and health studies. The methodology used is applicable to other Asian countries with similar features.

The effects of acute and long-term exposure to CO 2 on the respiratory physiology and production performance of Atlantic salmon ( Salmo salar ) in freshwater

DEFF Research Database (Denmark)

Khan, Javed Rafiq; Johansen, D.; Skov, Peter Vilhelm

2018-01-01

of recovery from stress. They also show that these effects are driven primarily by CO2 exposure, and to a much lesser extent by the associated reduction in pH. Growth and feed conversion experiments during chronic exposure suggest that there is no CO2 concentration where production performance is unaffected.......A high-level of free CO2 is a prevalent feature of intensive RAS and chronic exposure is common for most species during the production process. Currently, standard operating procedures, regulations and “safe” levels of CO2 are based on values that do not necessarily represent a point at, up...... the effects of both; acute increases in dissolved CO2 on the physiological capacity of Atlantic salmon, as well the effects of chronic exposure to different CO2 concentrations on production in freshwater. Results show that acute exposure (up to 40 mg L−1) significantly reduces aerobic capacity and the rate...

Arsenic and nicotine co-exposure lead to some synergistic effects on oxidative stress and apoptotic markers in young rat blood, liver, kidneys and brain

Directory of Open Access Journals (Sweden)

Anshu Jain

2015-01-01

Full Text Available Arsenic and nicotine exposure has been a major health concern globally. Individually both these toxicants increase the risk to various diseases including cancers. However, limited information exists on the co-exposure. In this study, we evaluate the effects of their individual and combined exposure and if co-exposure to these toxicants might have a synergism or antagonism. Male rats were exposed to a very low dose of arsenic (25 ppm in drinking water or nicotine (0.25 mg/kg, sub-cutaneously for a period of 5 months and post exposure various biochemical variables indicative of oxidative stress and apoptosis evaluated. Almost all glutathione linked enzymes showed marked alteration in individual as well as co-exposure treated groups. While serum creatinine and apoptosis indicator, lactate dehydrogenase (LDH were significantly increased in both treatments, an additive effect was noted in co-exposure group. A similar trend was also seen in brain and liver but not in kidneys. Gene expression studies showed marked reduction in catalase, Cu-Zn SOD, GST, there was a significant up regulation in Bax, caspase 3 in various tissues along with urinary 8-OHdG levels, indicative of DNA damage and apoptosis. Interestingly, a decrease in liver arsenic concentration was noted in co-exposed group compared to arsenic alone exposed group. In conclusion, the present study suggests that arsenic and nicotine exhibited significant toxicity during individual exposure whereas co-exposure to these toxins showed variable conditions (indicative of both synergism and antagonism in male rats.

Development of a CO2 -releasing coformulation based on starch, Saccharomyces cerevisiae and Beauveria bassiana attractive towards western corn rootworm larvae.

Science.gov (United States)

Vemmer, Marina; Schumann, Mario; Beitzen-Heineke, Wilhelm; French, Bryan W; Vidal, Stefan; Patel, Anant V

2016-11-01

CO 2 is known as an attractant for many soil-dwelling pests. To implement an attract-and-kill strategy for soil pest control, CO 2 -emitting formulations need to be developed. The aim of the present work was to develop a slow-release bead system in order to bridge the gap between application and hatching of western corn rootworm larvae. We compared different Ca-alginate beads containing Saccharomyces cerevisiae for their potential to release CO 2 over a period of several weeks. The addition of starch improved CO 2 release, resulting in significantly higher CO 2 concentrations in soil for at least 4 weeks. The missing amylase activity was compensated for either by microorganisms present in the soil or by coencapsulation of Beauveria bassiana. Formulations containing S. cerevisiae, starch and B. bassiana were attractive for western corn rootworm larvae within the first 4 h following exposure; however, when considering the whole testing period, the maize root systems remained more attractive for the larvae. Coencapsulation of S. cerevisiae, starch and B. bassiana is a promising approach for the development of attractive formulations for soil applications. For biological control strategies, the attractiveness needs to be increased by phagostimuli to extend contact between larvae and the entomopathogenic fungus growing out of these formulations. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

An exploratory, randomized, parallel-group, open-label, relative bioavailability study with an additional two-period crossover food-effect study exploring the pharmacokinetics of two novel formulations of pexmetinib (ARRY-614

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Wollenberg LA

2015-09-01

Full Text Available Lance A Wollenberg,1 Donald T Corson,2,3 Courtney A Nugent,1 Farran L Peterson,1 Ann M Ptaszynski,1 Alisha Arrigo,2,3 Coralee G Mannila,2,3 Kevin S Litwiler,1 Stacie J Bell1,4 1Array BioPharma, Boulder, 2Array BioPharma, Longmont, CO, 3Avista Pharma Solutions, Longmont, CO, 4Mallinckrodt Pharmaceuticals, Ellicott City, MD, USA Background: Pexmetinib (ARRY-614 is a dual inhibitor of p38 mitogen-activated protein kinase and Tie2 signaling pathways implicated in the pathogenesis of myelodysplastic syndromes. Previous clinical experience in a Phase I dose-escalation study of myelodysplastic syndrome patients using pexmetinib administered as neat powder-in-capsule (PIC exhibited high variability in pharmacokinetics and excessive pill burden, prompting an effort to improve the formulation of pexmetinib. Methods: A relative bioavailability assessment encompassed three parallel treatment cohorts of unique subjects comparing the two new formulations (12 subjects per cohort, a liquid oral suspension (LOS and liquid-filled capsule (LFC and the current clinical PIC formulation (six subjects in a fasted state. The food-effect assessment was conducted as a crossover of the LOS and LFC formulations administered under fed and fasted conditions. Subjects were divided into two groups of equal size to evaluate potential period effects on the food-effect assessment. Results: The geometric mean values of the total plasma exposures based upon area-under-the-curve to the last quantifiable sample (AUClast of pexmetinib were approximately four- and twofold higher after administration of the LFC and LOS formulations, respectively, than after the PIC formulation, when the formulations were administered in the fasted state. When the LFC formulation was administered in the fed state, pexmetinib AUClast decreased by <5% compared with the fasted state. After administration of the LOS formulation in the fed state, pexmetinib AUClast was 34% greater than observed in the fasted

Long-Term CO2 Exposure Experiments - Geochemical Effects on Brine-Saturated Reservoir Sandstone

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Fischer, Sebastian; Zemke, Kornelia; Liebscher, Axel; Wandrey, Maren

2010-05-01

The injection of CO2 into deep saline aquifers is the most promising strategy for the reduction of CO2 emissions to the atmosphere via long-term geological storage. The study is part of the CO2SINK project conducted at Ketzin, situated 40 km west of Berlin. There, food grade CO2 has been pumped into the Upper Triassic Stuttgart Formation since June 2008. The main objective of the experimental program is to investigate the effects of long-term CO2 exposure on the physico-chemical properties of the reservoir rock. To achieve this goal, core samples from observation well Ktzi 202 have been saturated with synthetic brine and exposed to CO2 in high quality steel autoclaves at simulated reservoir P-T-conditions of 5.5 MPa and 40 ° C. The synthetic brine had a composition representative of the formation fluid (Förster et al., 2006) of 172.8 g/l NaCl, 8.0 g/l MgCl2×2H2O, 4.8 g/l CaCl2×2H2O and 0.6 g/l KCl. After 15 months, the first set of CO2-exposed samples was removed from the pressure vessels. Thin sections, XRD, SEM as well as EMP data were used to determine the mineralogical features of the reservoir rocks before and after the experiments. Additionally, NMR relaxation and MP was performed to measure poroperm and pore size distribution values of the twin samples. The analyzed samples are fine- to medium grained, moderately well- to well sorted and weakly consolidated sandstones. Quartz and plagioclase are the major components, while K-feldspar, hematite, white & dark mica, chlorite and illite are present in minor and varying amounts. Cements are composed of analcime, dolomite and anhydrite. Some samples show mm- to cm-scale cross-beddings. The laminae comprise lighter, quartz- and feldspar-dominated layers and dark-brownish layers with notably less quartz and feldspars. The results are consistent with those of Blaschke et al. (2008). The plagioclase composition indicates preferred dissolution of the Ca-component and a trend toward albite-rich phases or even pure

Co-exposure to ultrafine particulate matter and ozone causes electrocardiogram changes indicative of increased arrhythmia risk in mice

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Numerous studies have shown a relationship between acute air pollution exposure and increased risk for cardiovascular morbidity and mortality. Due to the inherent complexity of air pollution, recent studies have focused on co-exposures to better understand potential interactions....

Conference report: formulating better medicines for children: 4th European Paediatric Formulation Initiative conference.

Science.gov (United States)

Walsh, Jennifer; Mills, Simon

2013-01-01

The fourth annual European Paediatric Formulation Initiative (EuPFI) conference on Formulating Better Medicines for Children was held on 19-20 September 2012 at the Institute of Molecular Genetics Congress Centre, Prague, Czech Republic. The 2-day conference concentrated on the latest advances, challenges and opportunities for developing medicinal products and administration devices for pediatric use, both from European and US perspectives. It was aimed specifically at providing exposure to emerging practical applications, and for illustrating remedies utilized by pediatric drug-development teams to overcome hurdles faced in developing medicines for pediatric patients. The conference format included plenary talks, focus sessions on each of the EuPFI work streams (extemporaneous preparations, excipients, pediatric administration devices, taste masking and taste assessment, age-appropriate formulations), case studies, soapbox sessions and a parallel poster display. This conference report summarizes the keynote lectures and also gives a flavor of other presentations and posters from the conference.

CoSix contact resistance after etching and ashing plasma exposure

International Nuclear Information System (INIS)

Katahira, Ken; Fukasawa, Masanaga; Kobayashi, Shoji; Takizawa, Toshifumi; Isobe, Michio; Hamaguchi, Satoshi; Nagahata, Kazunori; Tatsumi, Tetsuya

2009-01-01

The authors investigated the contact resistance fluctuation caused by CoSi x damage in plasma etching and ashing processes. They found that CoSi x layers damaged by plasma process exposure are readily oxidized when exposed to air resulting in increased resistance. They also found that the contact resistance increases more when CH 3 F is used instead of CF 4 during etching process. The lower the mass number of dominant ions becomes, the deeper the ions penetrate. Molecular dynamics simulation revealed that dissociated species from lighter ions penetrate deeper and that this stimulates deeper oxidation. They also found that contact resistance further increased by using postetch ashing plasma even in an H 2 /N 2 ashing process in which O 2 was not used. Here, too, the reason for this is that the ion penetration causes deep oxidation. They observed that the contact resistance has a linear relationship with the oxide concentration in CoSi x . This leads to the conclusion that it is essential to precisely control the ion energy as well as to properly select the ion species in the plasma process in the fabrication of next-generation semiconductor devices.

γ-ray induced chromosome aberration in rabbit peripheral blood lymphocytes irradiated in partial and whole body and decline of aberration rate with time post-exposure

International Nuclear Information System (INIS)

Zhang Lianzhen; Deng Zhicheng; Wang Haiyan

1997-01-01

Te author presents the results of study on 60 Co γ-ray induced chromosome aberration in rabbits peripheral blood lymphocytes irradiated in partial and whole body and the aberration rate decrease with the time of post-exposure. The experiments included 5 groups, it was whole-body exposure group, partial-body exposure (abdomen and pelvic cavity) group, blood irradiation group in vitro and control group respectively. Radiation dose was 3.0 Gy delivered at rate of 0.5 Gy/min. The results show that it was no significant differences between whole body and in blood irradiation group. The chromosome aberration yield in whole body exposure group was higher than that in partial-body group and in the abdomen exposure group was higher than in that in the pelvic cavity irradiation; The chromosome aberration rate decreased with the time of post-exposure in partial and whole body by γ-ray irradiation

Female exposure to phthalates and time to pregnancy

DEFF Research Database (Denmark)

Thomsen, Anne Marie L.; Riis, Anders H.; Olsen, Jørn

2017-01-01

STUDY QUESTION: Is female exposure to phthalate metabolites associated with reduced fecundity, as estimated by prolonged time to pregnancy (TTP)? SUMMARY ANSWER: Female exposure to monoethyl phthalate (MEP) but not monobutyl phthalate (MBP), monobenzyl phthalate (MBzP) and monoethylhexyl phthalate...... with prospective data based on 229 women from a Danish cohort of 430 first pregnancy planning couples enrolled in 1992-1994. In 2009, urinary analyses of phthalate metabolites were performed on stored urine samples from this cohort. PARTICIPANTS/MATERIALS, SETTING AND METHODS: We analyzed MEP, MBP, MBzP and MEHP...... to estimate fecundability ratios (FRs) and 95% CI in relation to the average urine metabolite concentration exposure level, controlled for age and BMI, and the time-varying variables smoking and alcohol. MAIN RESULT AND ROLE OF CHANCE: Urinary concentration of MEP was associated with a decreased fecundity...

Terbinafine: novel formulations that potentiate antifungal activities.

Science.gov (United States)

Ma, Y; Chen, X; Guan, S

2015-03-01

Terbinafine, an orally and topically active antifungal agent, has been available for the treatment of dermatophytic infections and onychomycosis for more than a decade. In addition, oral administration has been shown to be associated with drug-drug interactions, hepatotoxicity, low concentration at the infected sites, gastrointestinal and systemic side effects and other adverse effects. Since topical drug delivery can provide higher patient compliance, allow immediate access to the infected site and reduce unwanted systemic drug exposure, an improved topical drug delivery approach with high permeability, sustained release and prolonged retainment could overcome the limitations and side effects caused by oral administration. Conventional topical formulations cannot keep the drug in the targeted sites for a long duration of time and hence a novel drug delivery that can avoid the side effects while still providing sustained efficacy in treatment should be developed. This brief review of novel formulations based on polymers and nanostructure carriers provides insight into the efficacy and topical delivery of terbinafine. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

Channel-Island Connectivity Affects Water Exposure Time Distributions in a Coastal River Delta

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Hiatt, Matthew; Castañeda-Moya, Edward; Twilley, Robert; Hodges, Ben R.; Passalacqua, Paola

2018-03-01

The exposure time is a water transport time scale defined as the cumulative amount of time a water parcel spends in the domain of interest regardless of the number of excursions from the domain. Transport time scales are often used to characterize the nutrient removal potential of aquatic systems, but exposure time distribution estimates are scarce for deltaic systems. Here we analyze the controls on exposure time distributions using a hydrodynamic model in two domains: the Wax Lake delta in Louisiana, USA, and an idealized channel-island complex. In particular, we study the effects of river discharge, vegetation, network geometry, and tides and use a simple model for the fractional removal of nitrate. In both domains, we find that channel-island hydrological connectivity significantly affects exposure time distributions and nitrate removal. The relative contributions of the island and channel portions of the delta to the overall exposure time distribution are controlled by island vegetation roughness and network geometry. Tides have a limited effect on the system's exposure time distribution but can introduce significant spatial variability in local exposure times. The median exposure time for the WLD model is 10 h under the conditions tested and water transport within the islands contributes to 37-50% of the network-scale exposure time distribution and 52-73% of the modeled nitrate removal, indicating that islands may account for the majority of nitrate removal in river deltas.

Traffic Related Aerosol Exposure And Their Risk Assessment Of Associated Metals In Delhi, India

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Rajesh Kushwaha

2013-12-01

Full Text Available A pilot study was carried out in New Delhi, India, to assess the level of traffic related aerosol exposure, individually and associated metals. These investigations also try to formulate their risk assessment using different modes of transport on a typical journey to work route and compared Bus, Auto-rickshaws and Bike (Two Wheelers during the journey. The inhalable particulate matter monitored in winter period and also evaluated the potential health risk due to inhalation in the study. The exposure of Particulate matter was observed maximum in the Bike (502 ± 176.38 μgm-3 and minimum in the Auto-rickshaw (208.15 ± 61.38 μgm-3. In case of human exposure to metals (viz. Cu, Cd, Mn, Pb, Ni, Co, Cr, Fe, Zn, it was mostly exposed by Fe, Zn and Co and least exposed by Cd, Cr and Pb. Human health risk was estimated based on exposure and dosage response. The assessment of particulate-bound elements was calculated by assuming exposure of 6 h. The findings indicated that the exposure to particulate bound elements have relatively more adverse health effects. International Journal of Environment, Volume-2, Issue-1, Sep-Nov 2013, Pages 26-36 DOI: http://dx.doi.org/10.3126/ije.v2i1.9205

The exposure of honey bees (Apis mellifera; Hymenoptera: Apidae) to pesticides: Room for improvement in research.

Science.gov (United States)

Benuszak, Johanna; Laurent, Marion; Chauzat, Marie-Pierre

2017-06-01

Losses of honey bees have been repeatedly reported from many places worldwide. The widespread use of synthetic pesticides has led to concerns regarding their environmental fate and their effects on pollinators. Based on a standardised review, we report the use of a wide variety of honey bee matrices and sampling methods in the scientific papers studying pesticide exposure. Matrices such as beeswax and beebread were very little analysed despite their capacities for long-term pesticide storage. Moreover, bioavailability and transfer between in-hive matrices were poorly understood and explored. Many pesticides were studied but interactions between molecules or with other stressors were lacking. Sampling methods, targeted matrices and units of measure should have been, to some extent, standardised between publications to ease comparison and cross checking. Data on honey bee exposure to pesticides would have also benefit from the use of commercial formulations in experiments instead of active ingredients, with a special assessment of co-formulants (quantitative exposure and effects). Finally, the air matrix within the colony must be explored in order to complete current knowledge on honey bee pesticide exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

Formulation and Evaluation of Thermosensitive Biogels for Nose to Brain Delivery of Doxepin

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Anuja Naik

2014-01-01

Full Text Available Thermoreversible biogels can serve as effective systems for delivery of drugs through nose with increased nasal residence time. The objective of this study was to use chitosan and glycerophosphate based thermoreversible systems for delivery of doxepin to brain through intranasal administration. Formulations were prepared by admixture of suitable dilutions of chitosan and glycerophosphate with or without polyethylene glycol, followed by addition of the antidepressant doxepin hydrochloride. Both systems were evaluated for gelling characteristics, rheology, mucoadhesion, in vitro release, and ex vivo permeation through sheep nasal mucosa. In vivo efficacy was evaluated in Swiss albino mice through the forced swim test. Nasal tissues of mice subjected to repeated exposure to formulation were evaluated histopathologically. Both formulations gelled rapidly at 37°C, returned to sol state on cooling, and exhibited thixotropy. Addition of polyethylene glycol decreased the glycerophosphate content required for gelation and rendered the formulation isotonic. Both gels showed good mucoadhesion, enhanced drug permeation, and provided prolonged in vitro release at 37°C. Efficacy of the formulation in treated groups was inferred from the measured pharmacodynamic parameter and histopathological reports of formulation treated groups showed no significant local toxicity. The biogels could be potential systems for effective drug delivery to brain via nose.

Cumulative response of ecosystem carbon and nitrogen stocks to chronic CO2 exposure in a subtropical oak woodland

Science.gov (United States)

Hungate, Bruce A; Dijkstra, Paul; Wu, Zhuoting; Duval, Benjamin D; Day, Frank P; Johnson, Dale W; Megonigal, J Patrick; Brown, Alisha L P; Garland, Jay L

2013-01-01

Summary Rising atmospheric carbon dioxide (CO2) could alter the carbon (C) and nitrogen (N) content of ecosystems, yet the magnitude of these effects are not well known. We examined C and N budgets of a subtropical woodland after 11 yr of exposure to elevated CO2. We used open-top chambers to manipulate CO2 during regrowth after fire, and measured C, N and tracer 15N in ecosystem components throughout the experiment. Elevated CO2 increased plant C and tended to increase plant N but did not significantly increase whole-system C or N. Elevated CO2 increased soil microbial activity and labile soil C, but more slowly cycling soil C pools tended to decline. Recovery of a long-term 15N tracer indicated that CO2 exposure increased N losses and altered N distribution, with no effect on N inputs. Increased plant C accrual was accompanied by higher soil microbial activity and increased C losses from soil, yielding no statistically detectable effect of elevated CO2 on net ecosystem C uptake. These findings challenge the treatment of terrestrial ecosystems responses to elevated CO2 in current biogeochemical models, where the effect of elevated CO2 on ecosystem C balance is described as enhanced photosynthesis and plant growth with decomposition as a first-order response. PMID:23718224

Novel microwell-based spectrophotometric assay for determination of atorvastatin calcium in its pharmaceutical formulations

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Abdel-Rahman Hamdy M

2011-10-01

Full Text Available Abstract The formation of a colored charge-transfer (CT complex between atorvastatin calcium (ATR-Ca as a n-electron donor and 2, 3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ as a π-electron acceptor was investigated, for the first time. The spectral characteristics of the CT complex have been described, and the reaction mechanism has been proved by computational molecular modeling. The reaction was employed in the development of a novel microwell-based spectrophotometric assay for determination of ATR-Ca in its pharmaceutical formulations. The proposed assay was carried out in 96-microwell plates. The absorbance of the colored-CT complex was measured at 460 nm by microwell-plate absorbance reader. The optimum conditions of the reaction and the analytical procedures of the assay were established. Under the optimum conditions, linear relationship with good correlation coefficient (0.9995 was found between the absorbance and the concentration of ATR-Ca in the range of 10-150 μg/well. The limits of detection and quantitation were 5.3 and 15.8 μg/well, respectively. No interference was observed from the additives that are present in the pharmaceutical formulation or from the drugs that are co-formulated with ATR-Ca in its combined formulations. The assay was successfully applied to the analysis of ATR-Ca in its pharmaceutical dosage forms with good accuracy and precision. The assay described herein has great practical value in the routine analysis of ATR-Ca in quality control laboratories, as it has high throughput property, consumes minimum volume of organic solvent thus it offers the reduction in the exposures of the analysts to the toxic effects of organic solvents, and reduction in the analysis cost by 50-fold. Although the proposed assay was validated for ATR-Ca, however, the same methodology could be used for any electron-donating analyte for which a CT reaction can be performed.

BaP-metals co-exposure induced tissue-specific antioxidant defense in marine mussels Mytilus coruscus.

Science.gov (United States)

Chen, Siyu; Qu, Mengjie; Ding, Jiawei; Zhang, Yifei; Wang, Yi; Di, Yanan

2018-04-18

Both benzo(α)pyrene (BaP) and metals are frequently found in marine ecosystem and can cause detrimental effects in marine organism, especially the filter feeder-marine mussels. Although the biological responses in mussels have been well-studied upon the single metal or BaP exposure, the information about antioxidant defense, especially in different tissues of mussels, are still limited. Considering the variety of contaminants existing in the actual marine environment, single BaP (56 μg/L) and the co-exposure with Cu, Cd and Pb (50 μg/L, 50 μg/L and 3 mg/L respectively) were applied in a 6 days exposure followed by 6 days depuration experiment. The alterations of superoxide dismutase (SOD), catalase (CAT) activities and total antioxidant capacity (TAC) level were assessed in haemolymph, gills and digestive glands of marine mussels, Mytilus coruscus. An unparalleled change in antioxidant biomarkers was observed in all cells/tissues, with the SOD activity showing higher sensitivity to exposure. A tissue-specific response showing unique alteration in gill was investigated, indicating the different function of tissues during stress responses. Depressed antioxidant effects were induced by BaP-metals co-exposure, indicating the interaction may alter the intact properties of BaP. To our knowledge, this is the first research to explore the antioxidant defense induced by combined exposure of BaP-metals regarding to tissue-specific responses in marine mussels. The results and experimental model will provide valuable information and can be utilized in the investigation of stress response mechanisms, especially in relation to tissue functions in marine organism in the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

Radiation exposure during ESWL

International Nuclear Information System (INIS)

McCullough, D.L.; Van Swearingen, F.L.; Dyer, R.B.; Appel, B.

1987-01-01

This paper discusses exposure to ionizing radiation by the ESWL patient and for health professionals. Although the patient is exposed acutely to the highest level of radiation, the lithotripter team is chronically exposed to ionizing radiation at varying levels. Attention to detail is important in reducing that exposure. The operator should follow the guidelines set forth in this chapter in order to minimize exposure to the patient, himself or herself, and to all co-workers. At the present time, investigation of an alternative modality for stone localization, ultrasound, is being investigated

Temperature changes across CO2-lased dentin during multiple exposures

Science.gov (United States)

Zakariasen, Kenneth L.; Barron, Joseph R.; Boran, Thomas L.

1990-06-01

2000 m section utilizing two exposures. Analysis of Variance (p < .0001) and Duncan's Multiple Range Test (p =.05) indicated significant differences existed among the mean temperature elevations observed. While significant differences in temperature elevation can be observed both by numbers of exposures and by dentin thickness, it would appear that, under the conditions of this study, the temperature changes across CO2 lased dentin are all relatively low. It should be reiterated that the lasing parameters used in this study are far in excess of those necessary for preventive applications and are, in fact, in the range of exposures which will fuse enamel and dental porcelain, or remove dental caries. The modest temperature elevations observed, combined with the relatively severe exposure parameters utilized on thin sections of dentin, demonstrate the effective protective barrier which dentin provides for the dental pulp relative to heat damage from C02 lasing.

Caries like lesion initiation in sound enamel following CW CO2 laser irradiation: an in vitro study

International Nuclear Information System (INIS)

Nafie, A.; Issam, A.; Ali, M. S. R.

2005-01-01

This Study aimed to asses the caries - preventive potential of various CW CO 2 laser parameters, and to explore the effect of the laser power density, and the exposure time on the varies inhibition activity. Materials and Methods: Extracted human premolar teeth were irradiated with three different power densities (7.95, 15.9 and 31.8) W/Cm 2 for three different exposure times (0.2, 0.4 and 0.8) sec of 10.6 μm CW CO 2 laser. All teeth were subjected to caries like lesion formation by 3.5 pH lactic acid for 21 days. The teeth after that were sectioned into ground cross section and the lesion depths were measured using a graticule polarizing microscope. CW CO 2 laser preventive treatments inhibit caries like lesion progression up to 44%. This effect was improved with: (1) Increased power density for each of the three exposure times. (2) Decreased exposure time for each of the three power densities within the limits of the previously listed laser parameters. Conclusion: (1) short exposure time of CW CO 2 laser results in a significant inhibition of the enamel caries like lesion formation. (2) The inhibitory effect depends upon the power density and the exposure time of the laser beam. (3) The optimal CW CO 2 laser parameters used for caries inhibition purpose is achieved with approximately 30 W/Cm 2 power density and 0.2 sec exposure time. (author)

Immediate changes in estimated cardiac output and vascular resistance after 60Co exposure in monkeys: implication for performance decrement

International Nuclear Information System (INIS)

Bruner, A.

1977-01-01

Aortic blood flow velocity, blood pressure, and heart rate were recorded in 12 unanesthetized, nonperforming monkeys during exposure to 1000 rad 60 Co at 129--164 rad/min. The first postradiation changes were seen within 3--4 min of the exposure's start and included tachycardia, a transient hypotension secondary to a loss in peripheral resistance, and a brief increase followed by a decrease to subnormal levels in cardiac output. The lowest cardiac output occurred between 10 and 20 min postexposure while blood pressure and peripheral resistance were recovering. It was proposed that the concurrent combination of low cardiac output, low blood pressure, and supranormal peripheral resistance might sufficiently attenuate cerebral perfusion temporarily to account for the transient behavioral decrements often seen during this time. Histamine release was postulated as responsible for this vascular shock syndrome

Assessment of Nicotine Exposure From Active Human Cigarette Smoking Time

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Cahours Xavier

2017-09-01

Full Text Available The burning of a cigarette is a series of consecutive sequences of both passive and active burnings when a smoking cycle is applied to the cigarette. A previous study, using a smoking machine, showed that cigarette nicotine yields are dependent linearly on the difference between the time of smouldering (passive burning and the time of smoking (active burning. It is predicted that the smoker’s nicotine yield increases when the intensity of smoking increases, i.e., when the time to smoke a cigarette (smoking time decreases. Note that observations made on machines might not be comparable to human behaviours. The aim of this study was to determine whether nicotine mouth-level exposure could be predicted through measurement of human smoking time. A smoking behaviour study was conducted to compare human smoking nicotine yields obtained from both filter tip analysis and the cigarette burning time model. Results showed that smokers’ exposure to the smoke depends essentially on the speed at which the cigarette is smoked. An increase in human smoking intensity, resulting in a decrease in smoking time, generates an increase in smoke exposure, whatever the puff number, puff duration, puff volume and filter ventilation (open or blocked. The association of a machine smoking yield with a corresponding smoking time, and the time taken by a consumer to smoke the cigarette would provide information on the exposure to smoke constituents in a simple and effective manner.

Improved oral bioavailability of cyclosporin A in male Wistar rats. Comparison of a Solutol HS 15 containing self-dispersing formulation and a microsuspension.

Science.gov (United States)

Bravo González, Roberto Carlos; Huwyler, Jörg; Walter, Isabelle; Mountfield, Richard; Bittner, Beate

2002-10-01

Oral bioavailability of the highly lipophilic and poorly water-soluble immunosuppressive agent cyclosporin A (CyA) in two different formulations was investigated in male Wistar rats. An aqueous microsuspension and a self-dispersing formulation composed of the surface-active ingredients Solutol HS 15:Labrafil M2125CS:oleic acid=7:2:1 (v/v/v) were administered to the animals at a dose level of 20 mg/kg. In order to calculate the absolute oral bioavailability, CyA was additionally administered intravenously at 10 mg/kg as microsuspension. It was found that the oral bioavailability of CyA in the Solutol HS 15-based formulation was twofold higher as compared to the microsuspension (69.9+/-2.8 vs. 35.7+/-3.3%, P=0.001). By contrast, the time to reach maximum plasma concentration (t(max)) and the terminal half-life (t(1/2)) did not differ significantly with the different formulations (t(max): 7.0+/-1.0 vs. 6.3+/-1.7 h; t(1/2): 20.5+/-2.9 vs. 16.7+/-4.7 h). In vitro solubility experiments demonstrated a marked increase in the aqueous solubility of CyA in the presence of the self-dispersing formulation as compared to the micronized powder alone (solubility after 120 min at 37 degrees C: 136 vs. 23.2 microg/ml in human gastric juice; 133 vs. 10.8 microg/ml in simulated intestinal juice). Most likely, the enhanced systemic exposure of CyA in the self-dispersing formulation was caused by improved solubility of CyA in the gastrointestinal fluids in the presence of the surface-active ingredients. Additional factors that may have contributed to increased oral bioavailability are inhibition of metabolism and/or transport processes as well as permeability enhancement by the co-administered excipients.

Dynamics of soil CO 2 efflux under varying atmospheric CO 2 concentrations reveal dominance of slow processes

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Dohyoung Kim; Ram Oren; James S. Clark; Sari Palmroth; A. Christopher Oishi; Heather R. McCarthy; Chris A. Maier; Kurt Johnsen

2017-01-01

We evaluated the effect on soil CO2 efflux (FCO2) of sudden changes in photosynthetic rates by altering CO2 concentration in plots subjected to +200 ppmv for 15 years. Five-day intervals of exposure to elevated CO2 (eCO2) ranging 1.0–1.8 times ambient did not affect FCO2. FCO2 did not decrease until 4 months after termination of the long-term eCO2 treatment, longer...

Antioxidant status in oral subchronic toxicity of fipronil and fluoride co-exposure in buffalo calves.

Science.gov (United States)

Gill, Kamalpreet Kaur; Dumka, Vinod Kumar

2016-02-01

The effects of fipronil and fluoride co-exposure were investigated on antioxidant status of buffalo calves. A total of 24 healthy male buffalo calves divided into 4 groups were treated for 98 consecutive days. Group I, receiving no treatment, served as the control. Animals of groups II and III were orally administered with fipronil at the dosage of 0.5 mg/kg/day and sodium fluoride (NaF) at the dosage of 6.67 mg/kg/day, respectively, for 98 days. Group IV was coadministered with fipronil and NaF at the same dosages as groups II and III. Administration of fipronil alone produced significant elevation in lipid peroxidation (LPO) and decrease in the levels of nonenzymatic antioxidant glutathione (GSH). However, it did not produce any significant effect on the activities of enzymatic antioxidants including glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). NaF exposure led to enhanced oxidative stress as shown by significant increase in the LPO and SOD activities while GPx and CAT activities and GSH levels were significantly decreased. Co-exposure to fipronil and NaF showed additive effects on LPO, GPx activity, and GSH levels. © The Author(s) 2013.

Effect of the transgenerational exposure to elevated CO2 on the drought response of winter wheat

DEFF Research Database (Denmark)

Li, Yafei; Li, Xiangnan; Yu, Jingjie

2017-01-01

Abstract Climate change predicts more frequent drought spells along with an elevation in atmospheric CO2 concentration (e[CO2]). Although the responses of winter wheat (Triticum aestivum L.) plants to drought or a single generation exposure to e[CO2] have been well documented, the transgenerational...... effect of e[CO2] in combination of drought on stomatal behavior, plant water consumption and water use efficiency (WUE) have not been investigated. Seeds harvested from plants after two generations (2014–2015) continuously grown in ambient CO2 (a[CO2], 400 μmol L−1) and e[CO2] (800 μmol L−1) were sown...... in 4 L pots, and the plants were grown separately in greenhouse cells with either a[CO2] or e[CO2]. At stem elongation stage, in each of the cells half of the plants were subjected to progressive drought stress until all the plant available soil water was depleted, and the other half were well-watered...

Understanding the exposure-time effect on speckle contrast measurements for laser displays

Science.gov (United States)

Suzuki, Koji; Kubota, Shigeo

2018-02-01

To evaluate the influence of exposure time on speckle noise for laser displays, speckle contrast measurement method was developed observable at a human eye response time using a high-sensitivity camera which has a signal multiplying function. The nonlinearity of camera light sensitivity was calibrated to measure accurate speckle contrasts, and the measuring lower limit noise of speckle contrast was improved by applying spatial-frequency low pass filter to the captured images. Three commercially available laser displays were measured over a wide range of exposure times from tens of milliseconds to several seconds without adjusting the brightness of laser displays. The speckle contrast of raster-scanned mobile projector without any speckle-reduction device was nearly constant over various exposure times. On the contrary to this, in full-frame projection type laser displays equipped with a temporally-averaging speckle-reduction device, some of their speckle contrasts close to the lower limits noise were slightly increased at the shorter exposure time due to the noise. As a result, the exposure-time effect of speckle contrast could not be observed in our measurements, although it is more reasonable to think that the speckle contrasts of laser displays, which are equipped with the temporally-averaging speckle-reduction device, are dependent on the exposure time. This discrepancy may be attributed to the underestimation of temporal averaging factor. We expected that this method is useful for evaluating various laser displays and clarify the relationship between the speckle noise and the exposure time for a further verification of speckle reduction.

Bulky PAH-DNA induced by exposure of a co-culture model of human alveolar macrophages and embryonic epithelial cells to atmospheric particulate pollution

International Nuclear Information System (INIS)

Abbas, Imane; Garcon, Guillaume; Billet, Sylvain; Shirali, Pirouz; Andre, Veronique; Le Goff, Jeremie; Sichel, Francois; Roy Saint-Georges, Francoise; Mulliez, Philippe

2012-01-01

Because of their deep penetration in human lungs, fine airborne particulate matter were described as mainly responsible for the deleterious effects of exposure to air pollution on health. Organic constituents are adsorbed on particles surface and, after inhalation, some (polycyclic aromatic hydrocarbons, PAHs) can be activated into reactive metabolites and can bind to DNA. The formation of bulky DNA adducts has been researched after exposure of mono-and co-cultures of alveolar macrophages (AM) and human embryonic human lung epithelial (L132), to fine air pollution particulate matter Air samples have been collected with cascade impactor and characterized: size distribution (92.15% 2 /g), inorganic (Fe, AI, Ca, Na, K, Mg, Pb, etc.) and organic compounds (PAHs, etc.). 32 P post-labeling method was applied to detect bulky DNA adducts in AM and L132, in mono-and co-cultures, 72 h after their exposure to atmospheric particles at their Lethals and Effects concentrations or (LC or CE) to 50% (i.e. MA: EC 50 = 74.63 μg/mL and L132: LC-5-0 = 75.36 μg/mL). Exposure to desorbed particles (MA: C1= 61.11 μg/mL and L132 : C2 = 61.71 μg/mL) and B[a]P (1 μM) were included. Bulky PAH-DNA adducts were detected in AM in mono-culture after exposure to total particles (Pt), to B[a]P and desorbed particles (Pd). Whatever the exposure, no DNA adduct was detected in L132 in mono-culture. These results are coherent with the enzymatic activities of cytochrome P450 l Al in AM and L132. Exposure of co-culture to Pt, or Pd induced bulky adducts to DNA in AM but not in L132. Exposure to B[a]P alone has altered the DNA of AM and L132, in co-culture. Exposure to Pt is closer to the environmental conditions, but conferred an exposure to amounts of genotoxic agents compared to studies using organic extracts. The formation of bulky DNA adducts was nevertheless observed in AM exposed to Pt, in mono- or co-culture, indicating that they were competent in terms of metabolic activation of PAHs. The

Improving stability of stabilized and multiscale formulations in flow simulations at small time steps

KAUST Repository

Hsu, Ming-Chen

2010-02-01

The objective of this paper is to show that use of the element-vector-based definition of stabilization parameters, introduced in [T.E. Tezduyar, Computation of moving boundaries and interfaces and stabilization parameters, Int. J. Numer. Methods Fluids 43 (2003) 555-575; T.E. Tezduyar, Y. Osawa, Finite element stabilization parameters computed from element matrices and vectors, Comput. Methods Appl. Mech. Engrg. 190 (2000) 411-430], circumvents the well-known instability associated with conventional stabilized formulations at small time steps. We describe formulations for linear advection-diffusion and incompressible Navier-Stokes equations and test them on three benchmark problems: advection of an L-shaped discontinuity, laminar flow in a square domain at low Reynolds number, and turbulent channel flow at friction-velocity Reynolds number of 395. © 2009 Elsevier B.V. All rights reserved.

Wide-field time-correlated single photon counting (TCSPC) microscopy with time resolution below the frame exposure time

Energy Technology Data Exchange (ETDEWEB)

Hirvonen, Liisa M. [Department of Physics, King' s College London, Strand, London WC2R 2LS (United Kingdom); Petrášek, Zdeněk [Max Planck Institute of Biochemistry, Department of Cellular and Molecular Biophysics, Am Klopferspitz 18, D-82152 Martinsried (Germany); Suhling, Klaus, E-mail: klaus.suhling@kcl.ac.uk [Department of Physics, King' s College London, Strand, London WC2R 2LS (United Kingdom)

2015-07-01

Fast frame rate CMOS cameras in combination with photon counting intensifiers can be used for fluorescence imaging with single photon sensitivity at kHz frame rates. We show here how the phosphor decay of the image intensifier can be exploited for accurate timing of photon arrival well below the camera exposure time. This is achieved by taking ratios of the intensity of the photon events in two subsequent frames, and effectively allows wide-field TCSPC. This technique was used for measuring decays of ruthenium compound Ru(dpp) with lifetimes as low as 1 μs with 18.5 μs frame exposure time, including in living HeLa cells, using around 0.1 μW excitation power. We speculate that by using an image intensifier with a faster phosphor decay to match a higher camera frame rate, photon arrival time measurements on the nanosecond time scale could well be possible.

Proteomic profiling of halloysite clay nanotube exposure in intestinal cell co-culture.

Science.gov (United States)

Lai, Xianyin; Agarwal, Mangilal; Lvov, Yuri M; Pachpande, Chetan; Varahramyan, Kody; Witzmann, Frank A

2013-11-01

Halloysite is aluminosilicate clay with a hollow tubular structure with nanoscale internal and external diameters. Assessment of halloysite biocompatibility has gained importance in view of its potential application in oral drug delivery. To investigate the effect of halloysite nanotubes on an in vitro model of the large intestine, Caco-2/HT29-MTX cells in monolayer co-culture were exposed to nanotubes for toxicity tests and proteomic analysis. Results indicate that halloysite exhibits a high degree of biocompatibility characterized by an absence of cytotoxicity, in spite of elevated pro-inflammatory cytokine release. Exposure-specific changes in expression were observed among 4081 proteins analyzed. Bioinformatic analysis of differentially expressed protein profiles suggest that halloysite stimulates processes related to cell growth and proliferation, subtle responses to cell infection, irritation and injury, enhanced antioxidant capability, and an overall adaptive response to exposure. These potentially relevant functional effects warrant further investigation in in vivo models and suggest that chronic or bolus occupational exposure to halloysite nanotubes may have unintended outcomes. Copyright © 2013 John Wiley & Sons, Ltd.

The impact of trauma exposure characteristics on post-traumatic stress disorder and psychiatric co-morbidity among Syrian refugees.

Science.gov (United States)

Cheung Chung, Man; AlQarni, Nowf; AlMazrouei, Mariam; Al Muhairi, Shamsa; Shakra, Mudar; Mitchell, Britt; Al Mazrouei, Sara; Al Hashimi, Shurooq

2018-01-01

This study investigated the impact of trauma exposure characteristics on post-traumatic stress disorder (PTSD) and psychiatric co-morbidity among Syrian refugees. One thousand one hundred and ninety-seven refugees residing in Turkey and Sweden participated in the research. They completed the Harvard Trauma Questionnaire and the General Health Questionnaire-28. Forty-three percent of refugees met the cutoff for PTSD. After adjusting for location of residence, witnessing horror and exposure to life threat and assault were significantly correlated with PTSD and psychiatric co-morbidity respectively. Death of, or life threat to family members or friends were significantly correlated with both distress outcomes. Refugees residing in Turkey had significantly higher levels of PTSD, psychiatric co-morbidity and trauma characteristics than those living in Sweden. To conclude, Syrian refugees who witnessed horror, life threat or had family or friends die, tended to have elevated psychological distress. Levels of distress among resettled refugees can vary depending on country of resettlement. We recommend systematic mental health screening and implementation of psychotherapeutic interventions to address issues pertaining to subjective experience of resettlement and trauma exposure for Syrian refugees. Copyright © 2017 Elsevier B.V. All rights reserved.

The difficulties for a photolabile drug in topical formulations: the case of diclofenac.

Science.gov (United States)

Ioele, Giuseppina; De Luca, Michele; Tavano, Lorena; Ragno, Gaetano

2014-04-25

Topical commercial formulations containing diclofenac (DC) were submitted to photostability tests, according to the international rules, showing a clear degradation of the drug. The degradation process was monitored by applying the multivariate curve resolution technique to the UV spectral data from samples exposed to stressing irradiation. This method was able to estimate the number of components evolved as well as to draw their spectra and concentration profiles. Three photoproducts (PhPs) were resolved by the analysis of photodegradation kinetics, according to two consecutive reactions with a mechanism postulated as DC>PhP₁>PhP₂ and PhP₃. Photodegradation rate of DC in gel was found to be very fast, with a residual content of 90% only after 3.90 min under a radiant exposure of 450 Wm(-2). Because of a very slow skin uptake of DC, a prolonged time of exposure to light could lead to a significant decrease of drug available or the uptake of undesired photoproducts. New gel formulations were designed to increase the photostability of DC by incorporating chemical light-absorbers or entrapping the drug into cyclodextrin. Drug photostability resulted increased significantly in comparison with that of the commercial formulations. The gel containing the light-absorbers such as octisilate, octyl methoxycinnamate and a combination thereof showed a residual DC of 90% up to 12.22 min, 13.75 min and 15.71 min, respectively, under the same irradiation power. The best results were obtained by incorporating the drug in β-cyclodextrin with a degradation of 10% after 25.01 min of light exposure. Copyright © 2014 Elsevier B.V. All rights reserved.

Formulation and stability testing of photolabile drugs.

Science.gov (United States)

Tønnesen, H H

2001-08-28

Exposure of a drug to irradiation can influence the stability of the formulation, leading to changes in the physicochemical properties of the product. The influence of excipients of frequently used stabilizers is often difficult to predict and, therefore, stability testing of the final preparation is important. The selection of a protective packaging must be based on knowledge about the wavelength causing the instability. Details on drug photoreactivity will also be helpful in order to minimize side-effects and/or optimize drug targeting by developing photoresponsive drug delivery systems. This review focuses on practical problems related to formulation and stability testing of photolabile drugs.

Efficacy of an oral and tropically stable lipid-based formulation of Amphotericin B (iCo-010) in an experimental mouse model of systemic candidiasis.

Science.gov (United States)

Ibrahim, Fady; Sivak, Olena; Wasan, Ellen K; Bartlett, Karen; Wasan, Kishor M

2013-10-29

An oral lipid based formulation that exhibits tropical stability (iCo-010) was developed to enhance the absorption of orally administered amphotericin B (AmB). iCo-010 has previously shown high efficacy in an acute model of systemic candidiasis in rats, directing the focus of this study to be its efficacy in a chronic model of systemic candidiasis in mice. Mice were infected with 0.6 to 1×108 CFUs of Candida albicans ATCC 18804 strain by tail vein injection and were left for three days to develop the infection after which time treatment was initiated. The infected animals were assigned to the following treatment groups: no treatment (control) or iCo-010 at 5, 10 and 20 mg/kg administered by oral gavage once daily (QD) for 5 consecutive days. The animals were sacrificed 7 days after the last dose and the concentration of AmB and the fungal burden were assessed within the liver, kidneys, heart, lungs, spleen and brain. Although the infection was relatively low (~ 60-100 CFUs/ 1 ml tissue homogenate) in the liver, lungs and heart, the infection level was very high (70 000 CFUs / 1 ml tissue homogenate) in the kidney tissues for the control group. The highest concentrations of AmB were recovered in the kidneys and the spleen. The fungal burden in the tissues was lowered by 69-96% in the treatment groups when compared to the control group. Oral iCo-010 is an effective treatment of systemic candidiasis in the mouse model.

Impact of co-exposure with butachlor and triadimefon on thyroid endocrine system in larval zebrafish.

Science.gov (United States)

Cao, Chuyan; Wang, Qiangwei; Jiao, Fang; Zhu, Guonian

2016-09-01

Butachlor (BTL) and triadimefon (TDF), the widely used herbicide and fungicide, are unavoidable enter into the aquatic environment. However, there were limited study regarding to the joint toxicity of these two pesticides on fish at present. To evaluate the potential thyroid-disrupting toxicity and exposed to different concentrations of BTL mixed with TDF. Zebrafish embryo (n=3) were exposed to 0.01 and 0.05 fold of LC50 from the acute joint toxicity test, of which 0.32mg/L (BTL) and 9.41mg/L (TDF) for single or mixture agents (BTL: 0.0064mg/L, 0.032mg/L; TDF: 0.1882mg/L, 0.9410mg/L; co-exposure: 0.0032mg/L BTL+0.0941mg/L TDF, 0.016mg/l BTL+0.4705mg/L TDF) after 10-day post-fertilization. Hatching, malformation, survival rates and thyroid hormones (THs), genes expression involved in HPT-axis of embryos were measured and detected in control and separately/co-exposure treatments. THs contents were evaluated by ELISA kit and the expression levels of genes were determined by RT-PCR. Hatching, malformation and survival rates of embryos exposed to single BTL exhibited no statistically significant difference from the control besides decreased of high concentration in survival rates. Exposure to TDF reduced hatching, survival rate and increased malformation. The combined exposure to BTL and TDF resulted in greater adverse effects on embryonic development. BTL exposure significantly increased free T3 and T4 contents. Elevated free T3 content was also observed in the larvae exposed with single BTL. Co-exposure of the two pesticides caused greater enhanced of T3 and T4 levels. Furthermore, gene data showed BTL up-regulated the mRNA expression of tpo, tshβ, tg, ttr, dio2, TDF up-regulated the mRNA expression of tpo, trα, ttr, dio2 and down-regulated trβ gene. The mixture of the two pesticides caused up-regulation mRNA expression of trα, trβ, tg, ttr, dio2. BTL and TDF resulted in adverse effects on zebrafish embryonic development and caused thyroid endocrine disruption

Human skin in vitro permeation of bentazon and isoproturon formulations with or without protective clothing suit.

Science.gov (United States)

Berthet, Aurélie; Hopf, Nancy B; Miles, Alexandra; Spring, Philipp; Charrière, Nicole; Garrigou, Alain; Baldi, Isabelle; Vernez, David

2014-01-01

Skin exposures to chemicals may lead, through percutaneous permeation, to a significant increase in systemic circulation. Skin is the primary route of entry during some occupational activities, especially in agriculture. To reduce skin exposures, the use of personal protective equipment (PPE) is recommended. PPE efficiency is characterized as the time until products permeate through material (lag time, Tlag). Both skin and PPE permeations are assessed using similar in vitro methods; the diffusion cell system. Flow-through diffusion cells were used in this study to assess the permeation of two herbicides, bentazon and isoproturon, as well as four related commercial formulations (Basagran(®), Basamais(®), Arelon(®) and Matara(®)). Permeation was measured through fresh excised human skin, protective clothing suits (suits) (Microchem(®) 3000, AgriSafe Pro(®), Proshield(®) and Microgard(®) 2000 Plus Green), and a combination of skin and suits. Both herbicides, tested by itself or as an active ingredient in formulations, permeated readily through human skin and tested suits (Tlag < 2 h). High permeation coefficients were obtained regardless of formulations or tested membranes, except for Microchem(®) 3000. Short Tlag, were observed even when skin was covered with suits, except for Microchem(®) 3000. Kp values tended to decrease when suits covered the skin (except when Arelon(®) was applied to skin covered with AgriSafe Pro and Microgard(®) 2000), suggesting that Tlag alone is insufficient in characterizing suits. To better estimate human skin permeations, in vitro experiments should not only use human skin but also consider the intended use of the suit, i.e., the active ingredient concentrations and type of formulations, which significantly affect skin permeation.

Journey-time exposure to particulate air pollution

Science.gov (United States)

Gulliver, John; Briggs, David J.

Journey-time exposures to particulate air pollution were investigated in Leicester, UK, between January and March 2005. Samples of TSP, PM 10, PM 2.5, and PM 1 were simultaneously collected using light scattering devices whilst journeys were made by walking an in-car. Over a period of two months, 33 pairs of walking and in-car measurements were collected along two circular routes. Average exposures while walking were seen to be higher than those found in-car for each of the particle fractions: average walking to in-car ratios were 1.2 (± 0.6), 1.5 (± 0.6), 1.3 (± 0.6), and 1.4 (± 0.6) μg m -3 for coarse (TSP-PM 10), intermediate (PM 10-PM 2.5), fine (PM 2.5-PM 1), and very fine particles (PM 1), respectively. Correlations between walking and in-car exposures were seen to be weak for coarse particles ( r=0.10, p=0.58), moderate for the intermediate particles ( r=0.49, pcar exposures were 25% higher than the same fixed-site monitor. Particles with an aerodynamic diameter of less than 2.5 μm were seen to be highly correlated between walking and in-car particle exposures and a rural fixed-site monitor about 30 km south of Leicester.

Bioremediation of trace cobalt from simulated spent decontamination solutions of nuclear power reactors using E. coli expressing NiCoT genes

International Nuclear Information System (INIS)

Raghu, G.; Maruthi Mohan, P.; Balaji, V.; Venkateswaran, G.; Rodrigue, A.; Lyon 1 Univ., 69

2008-01-01

Removal of radioactive cobalt at trace levels (∼nM) in the presence of large excess (10 6 -fold) of corrosion product ions of complexed Fe, Cr, and Ni in spent chemical decontamination formulations (simulated effluent) of nuclear reactors is currently done by using synthetic organic ion exchangers. A large volume of solid waste is generated due to the nonspecific nature of ion sorption. Our earlier work using various fungi and bacteria, with the aim of nuclear waste volume reduction, realized up to 30% of Co removal with specific capacities calculated up to 1 μg/g in 6-24 h. In the present study using engineered Escherichia coli expressing NiCoT genes from Rhodopseudomonas palustris CGA009 (RP) and Novosphingobium aromaticivorans F-199 (NA), we report a significant increase in the specific capacity for Co removal (12 μg/g) in 1-h exposure to simulated effluent. About 85% of Co removal was achieved in a two-cycle treatment with the cloned bacteria. Expression of NiCoT genes in the E. coli knockout mutant of NiCoT efflux gene (rcnA) was more efficient as compared to expression in wild-type E. coli MC4100, JM109 and BL21 (DE3) hosts. The viability of the E. coli strains in the formulation as well as at different doses of gamma rays exposure and the effect of gamma dose on their cobalt removal capacity are determined. The potential application scheme of the above process of bioremediation of cobalt from nuclear power reactor chemical decontamination effluents is discussed. (orig.)

A stabilized second-order time accurate finite element formulation for incompressible viscous flow with heat transfer

International Nuclear Information System (INIS)

Curi, Marcos Filardy

2011-01-01

In view of the problem of global warming and the search for clean energy sources, a worldwide expansion on the use of nuclear energy is foreseen. Thus, the development of science and technology regarding nuclear power plants is essential, in particular in the field of reactor engineering. Fluid mechanics and heat transfer play an important role in the development of nuclear reactors. Computational Fluid Mechanics (CFD) is becoming ever more important in the optimization of cost and safety of the designs. This work presents a stabilized second-order time accurate finite element formulation for incompressible flows with heat transfer. A second order time discretization precedes a spatial discretization using finite elements. The terms that stabilize the finite element method arise naturally from the discretization process, rather than being introduced a priori in the variational formulation. The method was implemented in the program 'ns n ew s olvec2d av 2 M PI' written in FORTRAN90, developed in the Parallel Computing Laboratory at the Institute of Nuclear Engineering (LCP/IEN). Numerical solutions of some representative examples, including free, mixed and forced convection, demonstrate that the proposed stabilized formulation attains very good agreement with experimental and computational results available in the literature. (author)

Maintenance of C sinks sustains enhanced C assimilation during long-term exposure to elevated [CO2] in Mojave Desert shrubs.

Science.gov (United States)

Aranjuelo, Iker; Ebbets, Allison L; Evans, R Dave; Tissue, David T; Nogués, Salvador; van Gestel, Natasja; Payton, Paxton; Ebbert, Volker; Adams, Williams W; Nowak, Robert S; Smith, Stanley D

2011-10-01

During the first few years of elevated atmospheric [CO(2)] treatment at the Nevada Desert FACE Facility, photosynthetic downregulation was observed in desert shrubs grown under elevated [CO(2)], especially under relatively wet environmental conditions. Nonetheless, those plants maintained increased A (sat) (photosynthetic performance at saturating light and treatment [CO(2)]) under wet conditions, but to a much lesser extent under dry conditions. To determine if plants continued to downregulate during long-term exposure to elevated [CO(2)], responses of photosynthesis to elevated [CO(2)] were examined in two dominant Mojave Desert shrubs, the evergreen Larrea tridentata and the drought-deciduous Ambrosia dumosa, during the eighth full growing season of elevated [CO(2)] treatment at the NDFF. A comprehensive suite of physiological processes were collected. Furthermore, we used C labeling of air to assess carbon allocation and partitioning as measures of C sink activity. Results show that elevated [CO(2)] enhanced photosynthetic performance and plant water status in Larrea, especially during periods of environmental stress, but not in Ambrosia. δ(13)C analyses indicate that Larrea under elevated [CO(2)] allocated a greater proportion of newly assimilated C to C sinks than Ambrosia. Maintenance by Larrea of C sinks during the dry season partially explained the reduced [CO(2)] effect on leaf carbohydrate content during summer, which in turn lessened carbohydrate build-up and feedback inhibition of photosynthesis. δ(13)C results also showed that in a year when plant growth reached the highest rates in 5 years, 4% (Larrea) and 7% (Ambrosia) of C in newly emerging organs were remobilized from C that was assimilated and stored for at least 2 years prior to the current study. Thus, after 8 years of continuous exposure to elevated [CO(2)], both desert perennials maintained their photosynthetic capacities under elevated [CO(2)]. We conclude that C storage, remobilization

Interactive effects of hypoxia and PCB co-exposure on expression of CYP1A and its potential regulators in Atlantic croaker liver.

Science.gov (United States)

Rahman, Md Saydur; Thomas, Peter

2018-04-01

Although marine and coastal environments which are contaminated with xenobiotic organic compounds often become hypoxic during the summer, the interactive effects of hypoxia and xenobiotic exposure on marine species such as teleost fishes remain poorly understood. The expression and activity of monooxygenase enzyme cytochrome P450-1A (CYP1A) in fishes are upregulated by exposure to polychlorinated biphenyls (PCBs), whereas they are down-regulated during hypoxia exposure. We investigated the interactive effects of hypoxia and PCB co-exposure on hepatic CYP1A expression in Atlantic croaker and on potential regulators of CYP1A. Croaker were exposed to hypoxia (1.7 mg/L dissolved oxygen), 3,3',4,4'-tetrachlorobiphenyl (PCB 77, dose: 2 and 8 µg/g body weight), and Aroclor 1254 (a common PCB mixture, dose: 0.5 and 1 µg/g body weight), alone and in combination for 4 weeks. PCB 77 exposure markedly increased hepatic CYP1A mRNA and protein expression, and ethoxyresorufin-O-deethylase (EROD, an indicator of CYP1A enzyme) activity and increased endothelial nitric oxide synthase (eNOS) protein expression. PCB 77 treatment also increased interleukin-1β (IL-1β, a cytokine) mRNA levels and protein carbonyl (PC, an indicator of reactive oxygen species, ROS) contents. These marked PCB 77- and Aroclor 1254-induced increases in CYP1A mRNA levels and EROD activity were significantly attenuated by co-exposure to hypoxia, whereas the increases in hepatic eNOS protein and IL-1β mRNA expression, and PC contents were augmented by hypoxia co-exposure. The results suggest that biotransformation of organic xenobiotics by CYP1A is reduced in fish during co-exposure to hypoxia and is accompanied by alterations in eNOS, ROS, and IL-1β levels. © 2018 Wiley Periodicals, Inc.

Assessing the importance of different exposure metrics and time-activity data to predict 24-H personal PM2.5 exposures.

Science.gov (United States)

Chang, Li-Te; Koutrakis, Petros; Catalano, Paul J; Suh, Helen H

Personal PM(2.5) data from two recent exposure studies, the Scripted Activity Study and the Older Adults Study, were used to develop models predicting 24-h personal PM(2.5) exposures. Both studies were conducted concurrently in the summer of 1998 and the winter of 1999 in Baltimore, MD. In the Scripted Activity Study, 1-h personal PM(2.5) exposures were measured. Data were used to identify significant factors affecting personal exposures and to develop 1-h personal exposure models for five different micro-environments. By incorporating the time-activity diary data, these models were then combined to develop a time-weighted microenvironmental personal model (model M1AD) to predict the 24-h PM(2.5) exposures measured for individuals in the Older Adults Study. Twenty-four-hour time-weighted models were also developed using 1-h ambient PM(2.5) levels and time-activity data (model A1AD) or using 24-h ambient PM(2.5) levels and time-activity data (model A24AD). The performance of these three models was compared to that using 24-h ambient concentrations alone (model A24). Results showed that factors affecting 1-h personal PM(2.5) exposures included air conditioning status and the presence of environmental tobacco smoke (ETS) for indoor micro-environments, consistent with previous studies. ETS was identified as a significant contributor to measured 24-h personal PM(2.5) exposures. Staying in an ETS-exposed microenvironment for 1 h elevated 24-h personal PM(2.5) exposures by approximately 4 microg/m 3 on average. Cooking and washing activities were identified in the winter as significant contributors to 24-h personal exposures as well, increasing 24-h personal PM(2.5) exposures by about 4 and 5 microg/m 3 per hour of activity, respectively. The ability of 3 microenvironmental personal exposure models to estimate 24-h personal PM(2.5) exposures was generally comparable to and consistently greater than that of model A24. Results indicated that using time-activity data with 1

Thermal stress ratcheting analysis of a time-hardening structure

International Nuclear Information System (INIS)

Hada, Kazuhiko

1999-01-01

Thermal stress ratcheting and shakedown is analyzed for a time-hardening structure: the yield stress increases as time goes on under exposure to neutron irradiation or thermal aging. New three modes of ratcheting and shakedown are identified as transition to other deformation modes. Stress regimes and thermal ratchet strains are formulated as a function of time-increasing yield stress. Moreover, a new model of trouble occurrence frequency as a modification to a bath-tube curve is proposed for calculating a time period of a thermal cycle. Application of the proposed formulation tells us a benefit of taking into account the time hardening due to neutron irradiation. (author)

Radiation exposure and examination time during enteroclysis and small bowel follow-through

International Nuclear Information System (INIS)

Thoeni, R.F.; Gould, R.G.

1989-01-01

The authors have investigated radiation exposures and total examination and fluoroscopy times in enterolysis and small-bowel-follow-through (SBFT). Enteroclysis was performed in 25 patients and SBFT in another 25 (17 with UGI/SBFT and 8 with SBFT alone), with 5 TLD dosimeters placed in areas of the back exposed to primary x-rays during fluoroscopy, spot, and overhead radiography. Skin entry exposures, fluoroscopy, and total examination times in enteroclysis were compared to those in SBFTs. Biphasic enteroclyis was performed, with an average of 18 radiographs per study, SBFT with 16, and UGI/SBFT with 23. Indications and pathology for enteroclysis and SBFT were similar. Detailed findings are presented. The authors conclude that total examination time for enteroclysis is two to three times shorter and skin entry exposure is less than two to three times higher than for SBFT. Higher radiation exposure of enteroclysis should be weighted against very short examination times and reported high accuracy in deciding between enteroclysis and SBFT

Complex effects of Ayurvedic formulation – Guduchi and ...

Indian Academy of Sciences (India)

Surabhi

adult exposure) on standard food supplemented with 0.5% Guduchi or 0.5% Madhuyashti ... formulations on a range of life-history traits in a holistic way in order to ... with Withania somnifera tends to increase their life span (Kumar et al., 2013).

Co-crystallization as a separation technology: controlling product concentrations by co-crystals

NARCIS (Netherlands)

Urbanus, J.; Roelands, C.P.M.; Verdoes, D.; Jansens, P.J.; Horst, J.H. ter

2010-01-01

Co-crystallization is known as a product formulation technology, but it can also be used as a tool to solve crystallization problems. Product removal by co-crystallization in fermentations is used as a showcase to demonstrate the potential of co-crystallization as a separation technique. In

Study of the examination times using radiation equipments and the radiation exposure control

Energy Technology Data Exchange (ETDEWEB)

Koshida, Kichiro; Orito, Takeo; Maekawa, Ryuichi; Hiraki, Tatsunosuke [Kanazawa Univ. (Japan). School of Paramedicine; Koga, Sukehiko

1985-01-01

The relation between the examination time and the exposure to the personnel was investigated. In order to minimize radiation injury, special exposure dose-rate distribution curves were performed at the maximum exposure condition setting the phantom, and the examination times could be limited from the exprosure dose for the place where the personnel presented. The examination times are possible to be ten times by those with the Medical X-ray Protective Aprons.

Scalable organic solvent free supercritical fluid spray drying process for producing dry protein formulations.

Science.gov (United States)

Nuchuchua, O; Every, H A; Hofland, G W; Jiskoot, W

2014-11-01

In this study, we evaluated the influence of supercritical carbon dioxide (scCO2) spray drying conditions, in the absence of organic solvent, on the ability to produce dry protein/trehalose formulations at 1:10 and 1:4 (w/w) ratios. When using a 4L drying vessel, we found that decreasing the solution flow rate and solution volume, or increasing the scCO2 flow rate resulted in a significant reduction in the residual water content in dried products (Karl Fischer titration). The best conditions were then used to evaluate the ability to scale the scCO2 spray drying process from 4L to 10L chamber. The ratio of scCO2 and solution flow rate was kept constant. The products on both scales exhibited similar residual moisture contents, particle morphologies (SEM), and glass transition temperatures (DSC). After reconstitution, the lysozyme activity (enzymatic assay) and structure (circular dichroism, HP-SEC) were fully preserved, but the sub-visible particle content was slightly increased (flow imaging microscopy, nanoparticle tracking analysis). Furthermore, the drying condition was applicable to other proteins resulting in products of similar quality as the lysozyme formulations. In conclusion, we established scCO2 spray drying processing conditions for protein formulations without an organic solvent that holds promise for the industrial production of dry protein formulations. Copyright © 2014 Elsevier B.V. All rights reserved.

Worldwide Mycotoxins Exposure in Pig and Poultry Feed Formulations

OpenAIRE

Guerre, Philippe

2016-01-01

The purpose of this review is to present information about raw materials that can be used in pig and poultry diets and the factors responsible for variations in their mycotoxin contents. The levels of mycotoxins in pig and poultry feeds are calculated based on mycotoxin contamination levels of the raw materials with different diet formulations, to highlight the important role the stage of production and the raw materials used can have on mycotoxins levels in diets. Our analysis focuses on myc...

Nonphotosynthetic CO2 fixation by alfalfa (Medicago sativa L.) roots and nodules

International Nuclear Information System (INIS)

Anderson, M.P.; Heichel, G.H.; Vance, C.P.

1987-01-01

The dependence of alfalfa (Medicago sativa L.) root and nodule nonphotosynthetic CO 2 fixation on the supply of currently produced photosynthate and nodule nitrogenase activity was examined a various times after phloem-girdling and exposure of nodules to Ar:O 2 . Phloem-girdling was effected 20 hours and exposure to Ar:O 2 was effected 2 to 3 hours before initiation of experiments. Nodule and root CO 2 fixation rates of phloem-girdled plants were reduced to 38 and 50%, respectively, of those of control plants. Exposure to Ar:O 2 decreased nodule CO 2 fixation rates to 45%, respiration rates to 55%, and nitrogenase activities to 51% of those of the controls. The products of nodule CO 2 fixation were exported through the xylem to the shoot mainly as amino acids within 30 to 60 minutes after exposure to 14 CO 2 . In contrast to nodules, roots exported very little radioactivity, and most of the 14 C was exported as organic acids. The nonphotosynthetic CO 2 fixation rate of roots and nodules averaged 26% of the gross respiration rate, i.e. the sum of net respiration and nonphotosynthetic CO 2 assimilation. Nodules fixed CO 2 at a rate 5.6 times that of roots, but since nodules comprised a small portion of root system mass, roots accounted for 76% of the nodulated roots system CO 2 fixation. The results indicate that nodule CO 2 fixation in alfalfa is associated with N assimilation

Exposure influences expressive timing judgments in music

NARCIS (Netherlands)

Honing, H.; Ladinig, O.

2009-01-01

This study is concerned with the question whether, and to what extent, listeners' previous exposure to music in everyday life, and expertise as a result of formal musical training, play a role in making expressive timing judgments in music. This was investigated by using a Web-based listening

Surgery for subacromial impingement syndrome in relation to intensities of occupational mechanical exposures across 10-year exposure time windows.

Science.gov (United States)

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

2018-03-01

We aimed to identify intensities of occupational mechanical exposures (force, arm elevation and repetition) that do not entail an increased risk of surgery for subacromial impingement syndrome (SIS) even after prolonged durations of exposure. Additionally, we wanted to evaluate if exposure to hand-arm vibration (HAV) is an independent risk factor. We used data from a register-based cohort study of the entire Danish working population (n=2 374 403). During follow-up (2003-2008), 14 118 first-time events of surgery for SIS occurred. For each person, we linked register-based occupational codes (1993-2007) to a general population job exposure matrix to obtain year-by-year exposure intensities on measurement scales for force, upper arm elevation >90° and repetition and expert rated intensities of exposure to HAV. For 10-year exposure time windows, we calculated the duration of exposure at specific intensities above minimal (low, medium and high). We used a logistic regression technique equivalent to discrete survival analysis adjusting for cumulative effects of other mechanical exposures. We found indications of safe exposure intensities for repetition (median angular velocity 90° >2 min/day implied an increased risk reaching ORs of 1.7 and 1.5 after 10 years at low intensities. No associations were found for HAV. We found indications of safe exposure intensities for repetition. Any intensities of force and upper arm elevation >90° above minimal implied an increased risk across 10-year exposure time windows. No independent associations were found for HAV. © 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.

Association of Light Exposure on Physical Activity and Sedentary Time in Young People

Directory of Open Access Journals (Sweden)

Daniel Aggio

2015-03-01

Full Text Available Background: To investigate whether light exposure was associated with objectively measured physical activity (PA and sedentary behaviour in young people. Methods: Participants (n = 229, 46.7% female were young people (mean 8.8 years [SD ± 2.2] from the borough of Camden, UK. Daily sedentary time, moderate and vigorous PA (MVPA and light exposure were measured using a tri-axial accelerometer with an ambient light sensor during the summer. Multiple linear regression models examined associations between average daily light exposure, sedentary time and time in MVPA. Models were repeated investigating weekdays and weekend days separately. Analyses were adjusted for pre-specified covariables, including age, sex, device wear time, ethnic group, school and body fat. Results: There were significant associations between average daily light exposure and time sedentary (β coefficient = −11.2, 95% CI, −19.0 to −3.4 and in MVPA (β coefficient = 3.5, 95% CI, 1.2 to 5.9. Light exposure was significantly associated with weekend sedentary time (β coefficient = −10.0, 95% CI, −17.6, −2.4, weekend MVPA (β coefficient = 3.7, 95% CI, 1.7, 5.7, weekday sedentary time (β coefficient = −15.0, 95% CI, −22.7 to −7.2, but not weekday MVPA (β coefficient = 2.0, 95% CI, −0.5 to 4.5. Conclusion: Average daily light exposure is positively associated with time in MVPA and negatively associated with sedentary time. Increasing daylight exposure may be a useful intervention strategy for promoting physical activity.

Study of the examination times using radiation equipments and the radiation exposure control

International Nuclear Information System (INIS)

Koshida, Kichiro; Orito, Takeo; Maekawa, Ryuichi; Hiraki, Tatsunosuke; Koga, Sukehiko.

1985-01-01

It was investigated for the relation between the examination times and the exposure to the personnel. At the purpose to minimize the radiation injury, the special exposure dose-rate distribution curves were performed at the maximum exposure condition setting the phantom, and the examination times could be limited from the exprosure dose for the place where the personnel presented. The examination times are possible to be ten times by those with the Medical X-ray Protective Aprons. (author)

Occupational radiation protection: Protecting workers against exposure to ionizing radiation. Contributed papers

International Nuclear Information System (INIS)

2003-07-01

Occupational exposure to ionizing radiation can occur in a range of industries, mining and milling; medical institutions, educational and research establishments and nuclear fuel cycle facilities. The term 'occupational exposure' refers to the radiation exposure incurred by a worker, which is attributable to the worker's occupation and committed during a period of work. According to the latest (2000) Report of the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), an estimated 11 million workers are monitored for exposure to ionizing radiation. They incur radiation doses attributable to their occupation, which range from a small fraction of the global average background exposure to natural radiation up to several times that value. It should be noted that the UNSCEAR 2000 Report describes a downward trend in the exposure of several groups of workers, but it also indicates that occupational exposure is affecting an increasingly large group of people worldwide. The International Basic Safety Standards for Protection against Ionizing Radiation and for the Safety of Radiation Sources (BSS), which are co-sponsored by, inter alia, the International Atomic Energy Agency (IAEA), the International Labour Organization (ILO), the OECD Nuclear Energy Agency (NEA) and the World Health Organization (WHO), establish a system of radiation protection which includes radiation dose limits for occupational exposure. Guidance supporting the requirements of the BSS for occupational protection is provided in three interrelated Safety Guides, jointly sponsored by the IAEA and the ILO. These Guides describe, for example, the implications for employers in discharging their main responsibilities (such as setting up appropriate radiation protection programmes) and similarly for workers (such as properly using the radiation monitoring devices provided to them). The IAEA i organized its first International Conference on Occupational Radiation Protection. The

Inter-generational co-residence and women's work and leisure time in Egypt

Directory of Open Access Journals (Sweden)

Nadia Diamond-Smith

2015-10-01

Full Text Available Background: Labor force participation among women in Egypt remains low, and due to falling fertility and increases life expectancy, women in Egypt in the future may spend more time co-residing with aging in-laws. Past literature has suggested that co-residence in some settings allows women to enter the labor force more, as mother-in-laws help care for their grandchildren, or inhibits labor force participation when mother-in-laws reinforce traditional values. There is little research on co-residence and labor supply, or leisure time, in Egypt. Objective: This paper examines the role of intergenerational co-residence in women's work, work time, and leisure time using data on time allocation in Egypt. Methods: Data were collected from 548 women with a living mother-in-law: 291 co-residing their mother-in-law and 257 not. Survey data included work status, a 24-hour time diary, and a health assessment of the mother-in-law. Multivariate regression models predicted work, work time, and leisure time use using standard models. Results: Co-residing with a disabled mother-in-law was associated with decreased odds of women working and fewer minutes spent working a day. Leisure time was not associated with the co-residence and disability status of a mother-in-law. Factors related to couples' relationships and the woman's views on gender norms were also associated with women working. Conclusions: Co-residence appears to be associated with women's work, depending on the disability status of the co-residing mother-in-law. If increased life expectancy is associated with more time spent in a disabled state for mothers-in-law, this could put downward pressure on women's work in this setting.

Co-exposure to an ortho-substituted PCB (PCB 153) and methylmercury enhances developmental neurotoxic effects

Energy Technology Data Exchange (ETDEWEB)

Fischer, C.; Fredriksson, A.; Eriksson, P. [Dept. Environment. Toxicol., Uppsala Univ. (Sweden)

2004-09-15

In our environment there are innumerable hazardous contaminants. Many of these compounds are the well-known persistent organic pollutants (POPs) like PCB and DDT. Another persistent agent in our environment is methylmercury (MeHg). These agents are known to be neurotoxic in laboratory animals and humans. Fetuses and neonates are known to be high-risk groups for exposure to these agents. A naturally occurring circumstance is the exposure to a combination of different persistent compounds. The knowledge of interaction between different toxic agents during development is sparse. In several studies we have shown that low-dose exposure of environmental toxic agents such as PCBs, DDT, BFRs (brominated flame retardants) as well as well-known neurotoxic agents such as nicotine, organophosphorous compounds and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), during the ''BGS'', in neonatal mice can lead to disruption of the adult brain function, and to an increased susceptibility to toxic agents as adults. Our studies concerning developmental neurotoxic effects after neonatal exposure to single PCB congeners have shown that some orthosubstituted PCBs (such as PCB 28, PCB 52, PCB 153) and some co-planar PCBs (such as PCB 77, PCB 126, PCB 169) cause derangement of adult behaviour that can worsen with age. Furthermore, the cholinergic receptors in the brain were also found to be affected8. Just recently we have seen that neonatal co-exposure to an ortho-substituted PCB, 2,2',5,5'-tetrachlorobiphenyl (PCB 52), together with a brominated flame retardant, 2,2',4,4',5-pentabromodiphenylether (PBDE 99), can enhance developmental neurotoxic effects when the exposure occurs during a critical stage of neonatal brain development. The present study was carried out in order to see whether PCB and MeHg could interact to cause enhanced developmental neurotoxic effects on spontaneous behaviour and habituation capability when given to neonatal mice.

Exposure to CO during home-to-work trips depending on mode of transport

Energy Technology Data Exchange (ETDEWEB)

Joumard, R.; Humbert, D.; Racamier, C.

1983-01-01

Personal exposure to carbon monoxide during journeys to work is compared for two methods of transport (private car and public transport). Eighty-five different journeys were accomplished (sixteen journeys concurrently in a car and in public transport). The CO concentrations were clearly lower with public transport, but they last longer. Quantities and carboxyhaemoglobin levels were not clearly different. In the course of twenty-eight car journeys, internal concentration was 14% lower than external concentration.

A pharmacokinetic-pharmacodynamic model of morphine exposure and subsequent morphine consumption in postoperative pain

DEFF Research Database (Denmark)

Juul, Rasmus Vestergaard; Nyberg, Joakim; Lund, Trine Meldgaard

2016-01-01

Purpose To characterize the pharmacokinetic-pharmacodynamic (PK-PD) relationship between exposure of morphine and subsequent morphine consumption and to develop simulation tools for model validation. Methods Dose, formulation and time of morphine administration was available from a published study...

Formulation and In vitro Evaluation of Carvedilol Transdermal ...

African Journals Online (AJOL)

... effect was observed in F1 to F8 formulations, highlighting the interplay of ... Index Medicus, JournalSeek, Journal Citation Reports/Science Edition, ..... Raymond, C.R.; Paul, J.S.; Sian, C.O. Hand book of. Pharmaceutical Excipients. 5th ed.

Unknown risk: co-exposure to lead and other heavy metals among children living in small-scale mining communities in Zamfara State, Nigeria.

Science.gov (United States)

Bartrem, Casey; Tirima, Simba; von Lindern, Ian; von Braun, Margrit; Worrell, Mary Claire; Mohammad Anka, Shehu; Abdullahi, Aishat; Moller, Gregory

2014-08-01

The lead poisoning crisis in Zamfara State, Northern Nigeria has been called the worst such case in modern history and it presents unique challenges for risk assessment and management of co-exposure to multiple heavy metals. More than 400 children have died in Zamfara as a result of ongoing lead intoxication since early in 2010. A review of the common toxic endpoints of the major heavy metals advances analysis of co-exposures and their common pathologies. Environmental contamination in Bagega village, examined by X-ray fluorescence of soils, includes lead, mercury, cadmium, arsenic and manganese. Co-exposure risk is explored by scoring common toxic endpoints and hazard indices to calculate a common pathology hazard risk ranking of Pb > As > Hg > Cd > Mn. Zamfara presents an extreme picture of both lead and multiple heavy metal mortality and morbidity, but similar situations have become increasingly prevalent worldwide.

Root causes, clinical effects, and outcomes of unintentional exposures to buprenorphine by young children.

Science.gov (United States)

Lavonas, Eric J; Banner, William; Bradt, Pamela; Bucher-Bartelson, Becki; Brown, Kimberly R; Rajan, Pradeep; Murrelle, Lenn; Dart, Richard C; Green, Jody L

2013-11-01

To characterize the rates, root causes, and clinical effects of unintentional exposures to buprenorphine sublingual formulations among young children and to determine whether exposure characteristics differ between formulations. Unintentional exposures to buprenorphine-containing products among children 28 days to less than 6 years old were collected from the Researched Abuse, Diversion, and Addiction-Related Surveillance System Poison Center Program and Reckitt Benckiser Pharmaceuticals' pharmacovigilance system from October 2009-March 2012. After adjustment for drug availability, negative binomial regression was used to estimate average exposure rates. Root cause assessment was conducted, and an expert clinician panel adjudicated causality and severity of moderate to severe adverse events (AEs). A total of 2380 cases were reviewed, including 4 deaths. Exposures to buprenorphine-naloxone combination film were significantly less frequent than exposures to buprenorphine tablets (rate ratio 3.5 [95% CI, 2.7-4.5]) and buprenorphine-naloxone combination tablets (rate ratio 8.8 [7.2-10.6]). The most commonly identified root causes were medication stored in sight, accessed from a bag or purse, and not stored in the original packaging. Among 536 panel review cases, the most common AEs reported for all formulations were lethargy, respiratory depression, miosis, and vomiting. The highest level AE severity did not differ significantly by formulation. Unintentional exposure to buprenorphine can cause central nervous system depression, respiratory depression, and death in young children. Exposure rates to film formulations are significantly less than to tablet formulations. Package and storage deficiencies contribute to unintentional exposures in young children. Copyright © 2013 Mosby, Inc. All rights reserved.

Exposure Influences Expressive Timing Judgments in Music

Science.gov (United States)

Honing, Henkjan; Ladinig, Olivia

2009-01-01

This study is concerned with the question whether, and to what extent, listeners' previous exposure to music in everyday life, and expertise as a result of formal musical training, play a role in making expressive timing judgments in music. This was investigated by using a Web-based listening experiment in which listeners with a wide range of…

Solvent free amorphisation for pediatric formulations (minitablets) using mesoporous silica

DEFF Research Database (Denmark)

Monsuur, Fred; Choudhari, Yogesh; Reddy, Upendra

2016-01-01

Introduction: Most silica based amorphisation strategies are using organic solvent loading methods. Towards pediatric formulations this is creating concerns. With this in mind the development of a dry amorphisation strategy was the focus of this study. The high internal surface area of mesoporous...... silica gel is densely crowded with silanol groups, which can provide hydrogen-bonding possibilities with a drug, potentially resulting in amorphisation. Purpose: Amorphous drugs provide an advantage in solubility; however, their low physical stability always remained concern. Additional there was a need...... to understand the mechanism and variables of dry amorphisation. Method: Ibuprofen (IBU) and Syloid® silica at different ratios were co-milled at variable milling times between 1 and 90 min. The interaction with; and amorphisation of IBU; on Syloid® silica was analyzed using SEM, FTIR, DSC and XRD. The co...

Long-Term Stability of New Co-Amorphous Drug Binary Systems: Study of Glass Transitions as a Function of Composition and Shelf Time

Directory of Open Access Journals (Sweden)

Luz María Martínez

2016-12-01

Full Text Available The amorphous state is of particular interest in the pharmaceutical industry due to the higher solubility that amorphous active pharmaceutical ingredients show compared to their respective crystalline forms. Due to their thermodynamic instability, drugs in the amorphous state tend to recrystallize; in order to avoid crystallization, it has been a common strategy to add a second component to hinder the crystalline state and form a thermally stable co-amorphous system, that is to say, an amorphous binary system which retains its amorphous structure. The second component can be a small molecule excipient (such as a sugar or an aminoacid or a second drug, with the advantage that a second active pharmaceutical ingredient could be used for complementary or combined therapeutic purposes. In most cases, the compositions studied are limited to 1:1, 2:1 and 1:2 molar ratios, leaving a gap of information about phase transitions and stability on the amorphous state in a wider range of compositions. In the present work, a study of novel co–amorphous formulations in which the selection of the active pharmaceutical ingredients was made according to the therapeutic effect is presented. Resistance against crystallization and behavior of glass transition temperature ( T g were studied through calorimetric measurements as a function of composition and shelf time. It was found that binary formulations with T g temperatures higher than those of pure components presented long-term thermal stability. In addition, significant increments of T g values, of as much as 15 ∘ C, were detected as a result of glass relaxation at room temperature during storage time; this behavior of glass transition has not been previously reported for co-amorphous drugs. Based on these results, it can be concluded that monitoring behavior of T g and relaxation processes during the first weeks of storage leads to a more objective evaluation of the thermomechanical stability of an amorphous

Pharmacokinetic and technical comparison of Sandostatin® LAR® and other formulations of long-acting octreotide

Directory of Open Access Journals (Sweden)

Bizec Jean-Claude

2011-09-01

Full Text Available Abstract Background Sandostatin® LAR® (Novartis Pharma AG is a long-acting repeatable formulation of the somatostatin analogue octreotide, the safety and efficacy of which has been established through 15 years of clinical experience. Recently, other formulations of octreotide using polymer poly(lactic-co-glycolic acid technology have been developed. This study compares the composition and pharmacokinetic (PK profile of Sandostatin LAR with three other versions of the depot delivery system (formulations A, B and C, available in selected countries. Findings Sandostatin LAR exhibited a characteristic concentration-time profile with a limited initial release of octreotide ('burst', an erosion phase from weeks 3-5, and a slowly declining concentration to day 52. The PK profiles of formulations A and B were characterized by a large initial burst during days 0-2, with up to 41% of the overall area under the plasma-concentration time curve achieved. Low and variable octreotide concentrations were observed during the microparticle erosion phase (days 2-62 [day 82 formulation C] for formulations A, B and C. Sandostatin LAR microparticles are spherical in shape with an average diameter of approximately 50 μm, determined by scanning electron microscopy evaluation. Formulation A had smaller, irregular microparticles, and formulations B and C exhibited a large range of particle diameters ( 100 μm. Inductively coupled plasma-optical emission spectroscopy detected a high tin content of 104 mg/kg in formulation B, the presence of which may suggest inadequate purification following polymer synthesis using tin(II-octoate as catalyst. PK profiles for formulations A, B and C after a single intramuscular injection of 4 mg/kg in male New Zealand rabbits differed markedly from the PK profile of Sandostatin LAR. Conclusions Clear differences were seen between Sandostatin LAR and formulations A, B and C, including variations in microparticle size, shape and impurity

In vitro human epidermal permeation of nicotine from electronic cigarette refill liquids and implications for dermal exposure assessment.

Science.gov (United States)

Frasch, H Frederick; Barbero, Ana M

2017-11-01

Nicotine plus flavorings in a propylene glycol (PG) vehicle are the components of electronic cigarette liquids (e-liquids), which are vaporized and inhaled by the user. Dermal exposure to nicotine and e-liquids may occur among workers in mixing and filling of e-cigarettes in the manufacturing process. Inadvertent skin contact among consumers is also a concern. In vitro nicotine permeation studies using heat-separated human epidermis were performed with surrogate and two commercial e-liquids, neat and aqueous nicotine donor formulations. Steady-state fluxes (J ss ), and lag times (t lag ) were measured for each formulation. In addition, transient (4 h) exposure and finite dose (1-10 μl/cm 2 ) experiments were undertaken using one commercial e-liquid. Average J ss (μg/cm 2 /h) from formulations were: nicotine in PG (24 mg/ml): 3.97; commercial e-liquid containing menthol (25 mg/ml nicotine): 10.2; commercial e-liquid containing limonene (25 mg/ml nicotine): 23.7; neat nicotine: 175. E-liquid lag times ranged from 5 to 10 h. Absorbed fraction of nicotine from finite doses was ≈0.3 at 48 h. The data were applied to transient exposure and finite dose dermal exposure assessment models and to a simple pharmacokinetic model. Three illustrative exposure scenarios demonstrate use of the data to predict systemic uptake and plasma concentrations from dermal exposure. The data demonstrate the potential for significant nicotine absorption through skin contact with e-cigarette refill solutions and the neat nicotine used to mix them.

A comparison of personal exposure to air pollutants in different travel modes on national highways in India.

Science.gov (United States)

Kolluru, Soma Sekhara Rao; Patra, Aditya Kumar; Sahu, Satya Prakash

2018-04-01

People often travel a long distance on highways to the nearest city for professional/business activities. However, relatively few publications on passenger exposure to pollutants on highways in India or elsewhere are available. The aim of this study was to examine the contribution of different travel modes to passengers' pollutant exposure for a long distance travel on a national highway in India. We measured PM 2.5 and CO exposure levels of the passengers over 200km on a national highway using two portable air monitors, EVM-7 and EPAM-5000. Personal concentration exposures and per min-, per hour-, per trip- and round trip mass exposures for three travel modes were calculated for 9 trips. Association between pollutants and weather variables were evaluated using levels Spearman correlation. ANOVA was carried out to evaluate the influence of travel mode, the timing of trips, temperature and RH on personal exposures. On an average, PM 2.5 personal concentration exposure levels were highest in the car (85.41±61.85μgm -3 ), followed by the bus (75.08±55.39μgm -3 ) and lowest in the car (ac) (54.43±34.09μgm -3 ). In contrast, CO personal exposure was highest in the car (ac) (1.81±1.3ppm). Travel mode explained the highest variability for CO (18.1%), CO 2 (9.9%), PM 2.5 (1.2%) exposures. In-city mass exposures were higher than trip averages; PM 2.5 :1.21-1.22, 1.13-1.19 and 1.03-1.28 times; CO: 1.20-1.57, 1.37-2.10 and 1.76-2.22 times for bus, car and car (ac) respectively. Traveling by car (ac) results in the lowest PM 2.5 exposures, although it exposes the passenger to high CO level. Avoiding national highways passing through cities can reduce up to 25% PM 2.5 and 50% CO mass exposures. This information can be useful for increasing environmental awareness among the passengers and for framing better pollution control strategies on highways. Copyright © 2017 Elsevier B.V. All rights reserved.

[Experimental study of brain lesions after combined coaxial exposure to high-peaked pulse wave form CO2 and Nd: YAG lasers on the brain].

Science.gov (United States)

Tsuyumu, M; Verasques, G; Yamazaki, S; Kuroiwa, T; Suzuki, R; Takei, H; Suzuki, K; Inaba, Y

1985-04-01

The CO2 laser is useful for cutting and vaporization but not for coagulation and hemostasis. On the contrary, YAG laser is effective for coagulation and hemostasis but not for cutting. The purpose of this study is to examine the effect of the exposure of combined, coaxial CO2 and YAG laser on the animal brain to supplement the advantages and draw-backs of each other. To compare these results, each of non-combined pulse wave form CO2 and YAG lasers was employed separately. The lasers in this study were pulse wave form CO2 and YAG lasers, employed separately or simultaneously using 130 YZ of Nihon Infrared Industries Company. Japanese white rabbits were anesthetized with pentobarbital. Fronto-parietal burr holes were made, the dura was removed and then Evans blue solution was injected intravenously. The lasers were employed to the cerebral cortex without great vessels using a micromanipulator attached to the operative microscope with a distance of 30 cm. The spot size was 700 mu for CO2 laser and 1200 mu for YAG laser. The first experiment was to see the effect of nine combinations of simultaneous coaxial CO2 of 2, 4 and 8 watts and YAG lasers of 10, 20 and 40 watts, 1 sec on the brain. In the second experiment, also combining two lasers, the exposure time of YAG laser was elongated from 1 or 2 seconds into 2 or 4 seconds and the arrangement of powers was the same as that of the first experiment. The lesions were thus made in 18 different conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Constant exposure technique in industrial radiography

International Nuclear Information System (INIS)

Domanus, J.C.

1983-08-01

The principles and advantages of the constant exposure technique are explained. Choice of exposure factors is analyzed. Film, paper and intensifying screens used throughout the investigation and film and paper processing are described. Exposure technique and the use of image quality indicators are given. Methods of determining of radiographic image quality are presented. Conclusions about the use of constant exposure vs. constant kilovoltage technique are formulated. (author)

Proteomic and metabolomic responses of Pacific oyster Crassostrea gigas to elevated pCO2 exposure.

Science.gov (United States)

Wei, Lei; Wang, Qing; Wu, Huifeng; Ji, Chenglong; Zhao, Jianmin

2015-01-01

The gradually increased atmospheric CO2 partial pressure (pCO2) has thrown the carbonate chemistry off balance and resulted in decreased seawater pH in marine ecosystem, termed ocean acidification (OA). Anthropogenic OA is postulated to affect the physiology of many marine calcifying organisms. However, the susceptibility and metabolic pathways of change in most calcifying animals are still far from being well understood. In this work, the effects of exposure to elevated pCO2 were characterized in gills and hepatopancreas of Crassostrea gigas using integrated proteomic and metabolomic approaches. Metabolic responses indicated that high CO2 exposure mainly caused disturbances in energy metabolism and osmotic regulation marked by differentially altered ATP, glucose, glycogen, amino acids and organic osmolytes in oysters, and the depletions of ATP in gills and the accumulations of ATP, glucose and glycogen in hepatopancreas accounted for the difference in energy distribution between these two tissues. Proteomic responses suggested that OA could not only affect energy and primary metabolisms, stress responses and calcium homeostasis in both tissues, but also influence the nucleotide metabolism in gills and cytoskeleton structure in hepatopancreas. This study demonstrated that the combination of proteomics and metabolomics could provide an insightful view into the effects of OA on oyster C. gigas. The gradually increased atmospheric CO2 partial pressure (pCO2) has thrown the carbonate chemistry off balance and resulted in decreased seawater pH in marine ecosystem, termed ocean acidification (OA). Anthropogenic OA is postulated to affect the physiology of many marine calcifying organisms. However, the susceptibility and metabolic pathways of change in most calcifying animals are still far from being understood. To our knowledge, few studies have focused on the responses induced by pCO2 at both protein and metabolite levels. The pacific oyster C. gigas, widely distributed

Modeling of CO2 storage in aquifers

International Nuclear Information System (INIS)

Savioli, Gabriela B; Santos, Juan E

2011-01-01

Storage of CO 2 in geological formations is a means of mitigating the greenhouse effect. Saline aquifers are a good alternative as storage sites due to their large volume and their common occurrence in nature. The first commercial CO 2 injection project is that of the Sleipner field in the Utsira Sand aquifer (North Sea). Nevertheless, very little was known about the effectiveness of CO 2 sequestration over very long periods of time. In this way, numerical modeling of CO 2 injection and seismic monitoring is an important tool to understand the behavior of CO 2 after injection and to make long term predictions in order to prevent CO 2 leaks from the storage into the atmosphere. The description of CO 2 injection into subsurface formations requires an accurate fluid-flow model. To simulate the simultaneous flow of brine and CO 2 we apply the Black-Oil formulation for two phase flow in porous media, which uses the PVT data as a simplified thermodynamic model. Seismic monitoring is modeled using Biot's equations of motion describing wave propagation in fluid-saturated poroviscoelastic solids. Numerical examples of CO 2 injection and time-lapse seismics using data of the Utsira formation show the capability of this methodology to monitor the migration and dispersal of CO 2 after injection.

Comparison of four different fuller's earth formulations in skin decontamination.

Science.gov (United States)

Roul, Annick; Le, Cong-Anh-Khanh; Gustin, Marie-Paule; Clavaud, Emmanuel; Verrier, Bernard; Pirot, Fabrice; Falson, Françoise

2017-12-01

Industrial accidents, wars and terrorist threats are potential sources of skin contamination by highly toxic chemical warfare agents and manufacturing compounds. We have compared the time-dependent adsorption capacity and decontamination efficiency of fuller's earth (FE) for four different formulations for the molecular tracer, 4-cyanophenol (4-CP), in vitro and ex vivo using water decontamination as standard. The adsorption capacity of FE was assessed in vitro for 4-CP aqueous solutions whereas decontamination efficiency was investigated ex vivo by tracking porcine skin 4-CP content using attenuated total reflectance Fourier transform infrared spectroscopy. Decontamination was performed on short time, exposed porcine skin to 4-CP by application of FE: (1) as free powder; (2) loaded on adhesive tape; (3) on powdered glove; or (4) in suspension. Removal rate of 4-CP from aqueous solutions correlates with the amount of FE and its contact time. Decontamination efficiency estimated by the percentage of 4-CP recovery from contaminated porcine skin, achieved 54% with water, ranged between ~60 and 70% with dry FE and reached ~90% with FE suspension. Successful decontamination of the FE suspension, enabling a dramatic reduction of skin contamination after a brief exposure scenario, appears to be rapid, reliable and should be formulated in a new device ready to use for self-application. Copyright © 2017 John Wiley & Sons, Ltd.

Workplace exposure to nanoparticles and the application of provisional nanoreference values in times of uncertain risks

Science.gov (United States)

van Broekhuizen, Pieter; van Broekhuizen, Fleur; Cornelissen, Ralf; Reijnders, Lucas

2012-03-01

Nano reference values (NRVs) for occupational use of nanomaterials were tested as provisional substitute for Occupational Exposure Limits (OELs). NRVs can be used as provisional limit values until Health-Based OELs or derived no-effect levels (DNEL) become available. NRVs were defined for 8 h periods (time weighted average) and for short-term exposure periods (15 min-time weighted average). To assess the usefulness of these NRVs, airborne number concentrations of nanoparticles (NPs) in the workplace environment were measured during paint manufacturing, electroplating, light equipment manufacturing, non-reflective glass production, production of pigment concentrates and car refinishing. Activities monitored were handling of solid engineered NPs (ENP), abrasion, spraying and heating during occupational use of nanomaterials (containing ENPs) and machining nanosurfaces. The measured concentrations are often presumed to contain ENPs as well as process-generated NPs (PGNP). The PGNP are found to be a significant source for potential exposure and cannot be ignored in risk assessment. Levels of NPs identified in workplace air were up to several millions of nanoparticles/cm3. Conventional components in paint manufacturing like CaCO3 and talc may contain a substantial amount of nanosized particulates giving rise to airborne nanoparticle concentrations. It is argued that risk assessments carried out for e.g. paint manufacturing processes using conventional non-nano components should take into account potential nanoparticle emissions as well. The concentrations measured were compared with particle-based NRVs and with mass-based values that have also been proposed for workers protection. It is concluded that NRVs can be used for risk management for handling or processing of nanomaterials at workplaces provided that the scope of NRVs is not limited to ENPs only, but extended to the exposure to process-generated NPs as well.

Workplace exposure to nanoparticles and the application of provisional nanoreference values in times of uncertain risks

International Nuclear Information System (INIS)

Broekhuizen, Pieter van; Broekhuizen, Fleur van; Cornelissen, Ralf; Reijnders, Lucas

2012-01-01

Nano reference values (NRVs) for occupational use of nanomaterials were tested as provisional substitute for Occupational Exposure Limits (OELs). NRVs can be used as provisional limit values until Health-Based OELs or derived no-effect levels (DNEL) become available. NRVs were defined for 8 h periods (time weighted average) and for short-term exposure periods (15 min-time weighted average). To assess the usefulness of these NRVs, airborne number concentrations of nanoparticles (NPs) in the workplace environment were measured during paint manufacturing, electroplating, light equipment manufacturing, non-reflective glass production, production of pigment concentrates and car refinishing. Activities monitored were handling of solid engineered NPs (ENP), abrasion, spraying and heating during occupational use of nanomaterials (containing ENPs) and machining nanosurfaces. The measured concentrations are often presumed to contain ENPs as well as process-generated NPs (PGNP). The PGNP are found to be a significant source for potential exposure and cannot be ignored in risk assessment. Levels of NPs identified in workplace air were up to several millions of nanoparticles/cm 3 . Conventional components in paint manufacturing like CaCO 3 and talc may contain a substantial amount of nanosized particulates giving rise to airborne nanoparticle concentrations. It is argued that risk assessments carried out for e.g. paint manufacturing processes using conventional non-nano components should take into account potential nanoparticle emissions as well. The concentrations measured were compared with particle-based NRVs and with mass-based values that have also been proposed for workers protection. It is concluded that NRVs can be used for risk management for handling or processing of nanomaterials at workplaces provided that the scope of NRVs is not limited to ENPs only, but extended to the exposure to process-generated NPs as well.

Estimating Time-Varying PCB Exposures Using Person-Specific Predictions to Supplement Measured Values: A Comparison of Observed and Predicted Values in Two Cohorts of Norwegian Women

Science.gov (United States)

Nøst, Therese Haugdahl; Breivik, Knut; Wania, Frank; Rylander, Charlotta; Odland, Jon Øyvind; Sandanger, Torkjel Manning

2015-01-01

Background Studies on the health effects of polychlorinated biphenyls (PCBs) call for an understanding of past and present human exposure. Time-resolved mechanistic models may supplement information on concentrations in individuals obtained from measurements and/or statistical approaches if they can be shown to reproduce empirical data. Objectives Here, we evaluated the capability of one such mechanistic model to reproduce measured PCB concentrations in individual Norwegian women. We also assessed individual life-course concentrations. Methods Concentrations of four PCB congeners in pregnant (n = 310, sampled in 2007–2009) and postmenopausal (n = 244, 2005) women were compared with person-specific predictions obtained using CoZMoMAN, an emission-based environmental fate and human food-chain bioaccumulation model. Person-specific predictions were also made using statistical regression models including dietary and lifestyle variables and concentrations. Results CoZMoMAN accurately reproduced medians and ranges of measured concentrations in the two study groups. Furthermore, rank correlations between measurements and predictions from both CoZMoMAN and regression analyses were strong (Spearman’s r > 0.67). Precision in quartile assignments from predictions was strong overall as evaluated by weighted Cohen’s kappa (> 0.6). Simulations indicated large inter-individual differences in concentrations experienced in the past. Conclusions The mechanistic model reproduced all measurements of PCB concentrations within a factor of 10, and subject ranking and quartile assignments were overall largely consistent, although they were weak within each study group. Contamination histories for individuals predicted by CoZMoMAN revealed variation between study subjects, particularly in the timing of peak concentrations. Mechanistic models can provide individual PCB exposure metrics that could serve as valuable supplements to measurements. Citation Nøst TH, Breivik K, Wania F

Carbon monoxide exposures inside an automobile traveling on an urban arterial highway.

Science.gov (United States)

Ott, W; Switzer, P; Willits, N

1994-08-01

Carbon monoxide (CO) exposures were measured inside a motor vehicle during 88 standardized drives on a major urban arterial highway, El Camino Real (traffic volume of 30,500-45,000 vehicles per day), over a 13-1/2 month period. On each trip (lasting between 31 and 61 minutes), the test vehicle drove the same 5.9-mile segment of roadway in both directions, for a total of 11.8 miles, passing through 20 intersections with traffic lights (10 in each direction) in three California cities (Menlo Park, Palo Alto, and Los Altos). Earlier tests showed that the test vehicle was free of CO intrusion. For the 88 trips, the mean CO concentration was 9.8 ppm, with a standard deviation of 5.8 ppm. Of nine covariates that were examined to explain the variability in the mean CO exposures observed on the 88 trips (ambient CO at two fixed stations, atmospheric stability, seasonal trend function, time of day, average surrounding vehicle count, trip duration, proportion of time stopped at lights, and instrument type), a fairly strong seasonal trend was found. A model consisting of only a single measure of traffic volume and a seasonal trend component had substantial predictive power (R2 = 0.68); by contrast, the ambient CO levels, although partially correlated with average exposures, contributed comparatively little predictive power to the model. The CO exposures experienced while drivers waited at the red lights at an intersection ranged from 6.8 to 14.9 ppm and differed considerably from intersection to intersection.(ABSTRACT TRUNCATED AT 250 WORDS)

Odors: appetizing or satiating? Development of appetite during odor exposure over time.

Science.gov (United States)

Ramaekers, M G; Boesveldt, S; Lakemond, C M M; van Boekel, M A J S; Luning, P A

2014-05-01

Exposure to palatable food odors influences appetite responses, either promoting or inhibiting food intake. Possibly, food odors are appetizing after a short exposure (of circa 1-3 min), but become satiating over time (circa 10-20 min). To investigate the effect of odor exposure on general appetite and sensory-specific appetite (SSA) over time. In a cross-over study, 21 unrestrained women (age: 18-45 years; BMI: 18.5-25 kg m(-2)) were exposed for 20 min to eight different odor types: five food odors, two nonfood odors and no-odor. All odors were distributed in a test room at suprathreshold levels. General appetite, SSA and salivation were measured over time. All food odors significantly increased general appetite and SSA, compared with the no-odor condition. The nonfood odors decreased general appetite. All effects did not change over time during odor exposure. Savory odors increased the appetite for savory foods, but decreased appetite for sweet foods, and vice versa after exposure to sweet odors. Neither food odors nor nonfood odors affected salivation. Palatable food odors were appetizing during and after odor exposure and did not become satiating over a 20-min period. Food odors had a large impact on SSA and a small impact on general appetite. Moreover, exposure to food odors increased the appetite for congruent foods, but decreased the appetite for incongruent foods. It may be hypothesized that, once the body is prepared for intake of a certain food with a particular macronutrient composition, it is unfavorable to consume foods that are very different from the cued food.

Excision technique in constrained formulations of Einstein equations: collapse scenario

International Nuclear Information System (INIS)

Cordero-Carrión, I; Vasset, N; Novak, J; Jaramillo, J L

2015-01-01

We present a new excision technique used in constrained formulations of Einstein equations to deal with black hole in numerical simulations. We show the applicability of this scheme in several scenarios. In particular, we present the dynamical evolution of the collapse of a neutron star to a black hole, using the CoCoNuT code and this excision technique. (paper)

Timing-Constrained FPGA Placement: A Force-Directed Formulation and Its Performance Evaluation

Directory of Open Access Journals (Sweden)

Srilata Raman

1996-01-01

Full Text Available In this paper we present a simple but efficient timing-driven placement algorithm for FPGAs. The algorithm computes forces acting on a logic block in the FPGA to determine its relative location with respect to other blocks. The forces depend on the criticality of nets shared between the two blocks. Unlike other net-based approaches, timing constraints are incorporated directly into the force equations to guide the placement. Slot assignment is then used to move the blocks into valid slot locations on the FPGA chip. The assignment algorithm also makes use of the delay information of nets so that the final placement is able to meet the timing criteria specified for the circuit. The novelty of the approach lies in the formulation of the force equations and the manner in which weights of the nets are dynamically altered to influence the placement. Experiments conducted on industrial test circuits and MCNC circuits give very promising results and indicate that the algorithm succeeds in significantly reducing the maximum delay in the circuit. In addition, routability is not adversely affected and running time is low.

Assessing the risks from exposure to radon in dwellings

International Nuclear Information System (INIS)

Walsh, P.J.; Lowder, W.M.

1983-07-01

The factors used to assess the radiation dose and health risks from human exposure to radon in dwellings are critically reviewed in this summary. Sources of indoor radon and determinants of air concentrations and exposure levels are given as well as the uncertainties that exist in their formulation. Methods of assessing health effects from inhalation of radon and its progeny are discussed with emphasis on dosimetry of radon daughters and formulation of risk per dose values. Finally, methods of assessing risks for general population exposures to indoor radon concentrations are treated

Use of solid dispersions to increase stability of dithranol in topical formulations

Directory of Open Access Journals (Sweden)

Marilene Estanqueiro

2014-09-01

Full Text Available The present study was planned to improve the stability of dithranol using solid dispersions (SD. Two different SD at a 1:9 ratio of dithranol/excipient were prepared: one of them using glyceryl behenate as excipient and the other using a mixture of argan oil with stearic acid (1:8 ratio as excipient. Pure dithranol and SD of dithranol were incorporated in an oil-in-water cream and in a hydrophobic ointment in a drug/dermatological base ratio of 1:10. The physical and mechanical properties of semisolid formulations incorporating the pure drug and the developed SD were evaluated through rheological and textural analysis. To evaluate the stability, L*a*b* color space parameters of SD and semisolid formulations, and pH of hydrophilic formulations were determined at defined times, during one month. Each sample was stored at different conditions namely, light exposure (room temperature, high temperature exposition (37 °C (protected from light and protected from light (room temperature. Despite higher values of firmness and adhesiveness, hydrophobic ointment exhibited the best rheological features compared to the oil-in-water cream, namely a shear-thinning behavior and high thixotropy. These formulations have also presented more stability, with minor changes in L*a*b* color space parameters. The results of this study indicate that is possible to conclude that the developed SD contributed to the increased stability of dithranol.

Exposure assessment of acrylates/methacrylates in radiation-cured applications

International Nuclear Information System (INIS)

1987-01-01

Occupational exposures to radiation-cured acrylates/methacrylates during their processing and use in coatings, inks, and adhesives were evaluated in 12 walk-through surveys at formulator and applicator sites. Inhalation and dermal-exposure routes were studied. According to the authors, the basic process used to formulate coatings, inks, and adhesives consists of blending raw materials in closed mixing vessels using local exhaust ventilation in the form of elephant trunks at vessel charging and packaging locations. Application methods surveyed included reverse-roll coaters, direct roll coaters, curtain/rain coaters, laminators, pneumatic injection, spray guns, and manual application. At the sites surveyed, the number of workers potentially exposed at each site ranged from two to 142. Process operators at applicator sites had the greatest potential for dermal exposure. Generally, the potential for inhalation exposure was low due to low volatility of the multifunctional acrylates/methacrylates used in the formulations. No reliable air-monitoring data were available at any site. Respirator use was limited and sporadic

The consistent differential expression of genetic pathways following exposure of an industrial Pseudomonas aeruginosa strain to preservatives and a laundry detergent formulation

Science.gov (United States)

Amézquita, Alejandro; Le Marc, Yvan; Bull, Matthew J; Connor, Thomas R; Mahenthiralingam, Eshwar

2018-01-01

Abstract Pseudomonas aeruginosa is a common contaminant associated with product recalls in the home and personal care industry. Preservation systems are used to prevent spoilage and protect consumers, but greater knowledge is needed of preservative resistance mechanisms used by P. aeruginosa contaminants. We aimed to identify genetic pathways associated with preservative exposure by using an industrial P. aeruginosa strain and implementing RNA-Seq to understand gene expression changes in response to industry relevant conditions. The consistent differential expression of five genetic pathways during exposure to multiple industrial growth conditions associated with benzisothiazolone (BIT) and phenoxyethanol (POE) preservatives, and a laundry detergent (LD) formulation, was observed. A MexPQ-OpmE Resistance Nodulation Division efflux pump system was commonly upregulated in response to POE, a combination of BIT and POE, and LD together with BIT. In response to all industry conditions, a putative sialic acid transporter and isoprenoid biosynthesis gnyRDBHAL operon demonstrated consistent upregulation. Two operons phnBA and pqsEDCBA involved in Pseudomonas quinolone signaling production and quorum-sensing were also consistently downregulated during exposure to all the industry conditions. The ability to identify consistently differentially expressed genetic pathways in P. aeruginosa can inform the development of future targeted preservation systems that maintain product safety and minimise resistance development. PMID:29548026

Co-Phenylcaine Spray: can we improve the taste? A randomised, double-blind, crossover study.

Science.gov (United States)

Bailey, S; Panizza, B; Cabot, P; Wallwork, B

2018-02-01

Co-Phenylcaine Forte is a nasal spray routinely prescribed by otolaryngologists in Australia. The taste of Co-Phenylcaine Forte is typically described as unpleasant. This study sought to improve the overall patient experience associated with Co-Phenylcaine Forte by generating a Co-Phenylcaine Forte formulation, referred to as Co-Phenylcaine Zest, which contains an added vanilla flavour and masking agent. Participants were randomised to receive two actuations of Co-Phenylcaine Forte in each nostril followed by two actuations of Co-Phenylcaine Zest, or vice versa. There was a 6-36-hour washout period between each treatment. After the administration of each spray, participants completed a questionnaire to rate various sensory attributes of each formulation on seven-point ordinal scales. Patients reported their overall formulation preference after receiving both treatments. A total of 86 participants completed the trial. Seventy-four per cent of patients preferred Co-Phenylcaine Zest, 21 per cent preferred Co-Phenylcaine Forte and 5 per cent had no preference (p < 0.001). The satisfaction score associated with Co-Phenylcaine Zest was 1.22 points greater than with Co-Phenylcaine Forte (p < 0.001). A novel formulation of Co-Phenylcaine Forte was created by adding a flavour and a masking agent; this formulation was preferred by most patients.

[Solar exposure time for sunburn in Mexican population].

Science.gov (United States)

Castanedo Cázares, Juan Pablo; Torres Álvarez, Bertha; Sobrevilla Ondarza, Salvador; Ehnis Pérez, Adriana; Gordillo Moscoso, Antonio

2012-01-01

THe minimal erythemal dose (MED) quantifies an individual's sensitivity to UV radiation (UVR). To estimate it in our population and establish the time of exposure inducing it during daily activities would allow us to calculate risk intervals. From 2005-2012, the UV solar radiation was measured with terrestrial radiometry and compared to public UV index (UVI). We determined the MED in 90 individuals with the prevalent phototypes in Mexico (III, IV, V), and estimated the time needed for the development of sunburn. The average MED for phototype III was 39 (IC 95%: 35-42) mJ/cm2, for IV 48 (IC 95%:42-53) mJ/cm2, and for V was 84 (IC 95%:75-92) mJ/cm2 (ANOVA, p ≤ 0.001). Approximately, 80% of the daily UVR was accumulated between 10:00-16:00 h, and 77% of the annual UV dose is received between March-October. The public UVI had a high correlation with the one quantified at terrestrial level (r = 0.89; p ≤ 0.001). Mexico receives continuously high levels of UVR. Phototype III will present sunburn after 22-33 min in a summer day, while phototype V will require over one hour of exposure. This last group is at risk of chronic exposure without considering consequences.

Effects of post exposure bake temperature and exposure time on SU-8 nanopattern obtained by electron beam lithography

Science.gov (United States)

Yasui, Manabu; Kazawa, Elito; Kaneko, Satoru; Takahashi, Ryo; Kurouchi, Masahito; Ozawa, Takeshi; Arai, Masahiro

2014-11-01

SU-8 is a photoresist imaged using UV rays. However, we investigated the characteristics of an SU-8 nanopattern obtained by electron beam lithography (EBL). In particular, we studied the relationship between post-exposure bake (PEB) temperature and exposure time on an SU-8 nanopattern with a focus on phase transition temperature. SU-8 residue was formed by increasing both PEB temperature and exposure time. To prevent the formation of this, Monte Carlo simulation was performed; the results of such simulation showed that decreasing the thickness of SU-8 can reduce the amount of residue from the SU-8 nanopattern. We confirmed that decreasing the thickness of SU-8 can also prevent the formation of residue from the SU-8 nanopattern with EBL.

Assessment of the vaginal residence time of biomarkers of semen exposure.

Science.gov (United States)

Thurman, Andrea; Jacot, Terry; Melendez, Johan; Kimble, Thomas; Snead, Margaret; Jamshidi, Roxanne; Wheeless, Angie; Archer, David F; Doncel, Gustavo F; Mauck, Christine

2016-11-01

The primary objective of this pilot study is to determine and compare the residence time in the vagina of biomarkers of semen exposure for up to 15 days post exposure. The biomarkers are prostate-specific antigen (PSA), Y chromosome DNA, the sex determining region of the Y chromosome (SRY) and testis-specific protein Y-encoded 4 (TSPY4). The secondary objectives are to determine if biomarker concentrations differed between intercourse and inoculation groups, to establish whether the sampling frequency post exposure affected biomarker concentrations and decay profile and to determine if biomarker concentrations in vaginal swabs obtained by the participant at home were similar to swabs obtained by the nurse in the clinic. We randomized healthy women to unprotected intercourse (n=17) versus vaginal inoculation with the male partner's semen in the clinic (n=16). Women were then further randomized to have vaginal swabs obtained at either 7 or 4 time points after semen exposure, up to 15 days post exposure, either obtained at home by the participant or in the clinic by the research nurse. PSA and SRY were markers of recent semen exposure. TSPY4 was detectable in approximately 50% of participants at 15 days post exposure. Unprotected intercourse resulted in significantly higher concentrations of select biomarkers. Sampling frequency and home versus clinic sampling had no significant effect on biomarker concentrations. Objective biomarkers of recent or distant semen exposure may have great utility for verifying protocol compliance in a variety of clinical trials. Copyright © 2016 Elsevier Inc. All rights reserved.

CoSi{sub x} contact resistance after etching and ashing plasma exposure

Energy Technology Data Exchange (ETDEWEB)

Katahira, Ken; Fukasawa, Masanaga; Kobayashi, Shoji; Takizawa, Toshifumi; Isobe, Michio; Hamaguchi, Satoshi; Nagahata, Kazunori; Tatsumi, Tetsuya [Nagasaki Production Division 1, Sony Semiconductor Kyushu Corporation, 1883-43 Tsukuba-machi, Isahaya-shi, Nagasaki 854-0065 (Japan); Semiconductor Technology Development Division, Semiconductor Business Group, Sony Corporation, 4-14-1 Asahi-cho, Atsugi-shi, Kanagawa 243-0014 (Japan); Center for Atomic and Molecular Technologies, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan); Semiconductor Technology Development Division, Semiconductor Business Group, Sony Corporation, 4-14-1 Asahi-cho, Atsugi-shi, Kanagawa 243-0014 (Japan)

2009-07-15

The authors investigated the contact resistance fluctuation caused by CoSi{sub x} damage in plasma etching and ashing processes. They found that CoSi{sub x} layers damaged by plasma process exposure are readily oxidized when exposed to air resulting in increased resistance. They also found that the contact resistance increases more when CH{sub 3}F is used instead of CF{sub 4} during etching process. The lower the mass number of dominant ions becomes, the deeper the ions penetrate. Molecular dynamics simulation revealed that dissociated species from lighter ions penetrate deeper and that this stimulates deeper oxidation. They also found that contact resistance further increased by using postetch ashing plasma even in an H{sub 2}/N{sub 2} ashing process in which O{sub 2} was not used. Here, too, the reason for this is that the ion penetration causes deep oxidation. They observed that the contact resistance has a linear relationship with the oxide concentration in CoSi{sub x}. This leads to the conclusion that it is essential to precisely control the ion energy as well as to properly select the ion species in the plasma process in the fabrication of next-generation semiconductor devices.

Evaluating the Properties of Poly(lactic-co-glycolic acid) Nanoparticle Formulations Encapsulating a Hydrophobic Drug by Using the Quality by Design Approach.

Science.gov (United States)

Kozaki, Masato; Kobayashi, Shin-Ichiro; Goda, Yukihiro; Okuda, Haruhiro; Sakai-Kato, Kumiko

2017-01-01

We applied the Quality by Design (QbD) approach to the development of poly(lactic-co-glycolic acid) (PLGA) nanoparticle formulations encapsulating triamcinolone acetonide, and the critical process parameters (CPPs) were identified to clarify the correlations between critical quality attributes and CPPs. Quality risk management was performed by using an Ishikawa diagram and experiments with a fractional factorial design (ANOVA). The CPPs for particle size were PLGA concentration and rotation speed, and the CPP for relative drug loading efficiency was the poor solvent to good solvent volume ratio. By assessing the mutually related factors in the form of ratios, many factors could be efficiently considered in the risk assessment. We found a two-factor interaction between rotation speed and rate of addition of good solvent by using a fractional factorial design with resolution V. The system was then extended by using a central composite design, and the results obtained were visualized by using the response surface method to construct a design space. Our research represents a case study of the application of the QbD approach to pharmaceutical development, including formulation screening, by taking actual production factors into consideration. Our findings support the feasibility of using a similar approach to nanoparticle formulations under development. We could establish an efficient method of analyzing the CPPs of PLGA nanoparticles by using a QbD approach.

Physiological responses to exposure to carbon dioxide and human bioeffluents

DEFF Research Database (Denmark)

Zhang, Xiaojing; Wargocki, Pawel; Lian, Zhiwei

2015-01-01

Present paper describes physiological responses as a result of exposures to CO2 (between 500 ppm to 3,000 ppm) with and without bioeffluents. Twenty-five subjects participated. They were exposed in the climate chamber for 255 minutes in groups of five at a time. During exposure, they performed di...

Paraquat and maneb co-exposure induces noradrenergic locus coeruleus neurodegeneration through NADPH oxidase-mediated microglial activation

International Nuclear Information System (INIS)

Hou, Liyan; Zhang, Cong; Wang, Ke; Liu, Xiaofang; Wang, Hongwei; Che, Yuning; Sun, Fuqiang; Zhou, Xueying; Zhao, Xiulan; Wang, Qingshan

2017-01-01

Highlights: • Microglial activation induced by paraquat and maneb precedes noradrenergic neurodegeneration in locus coeruleus. • NADPH oxidase activation contributes to microglia-mediated neuroinflammation and related noradrenergic neurodegeneration. • Inhibition of NADPH oxidase by apocynin protects noradrenergic neurons against paraquat and maneb-induced toxicity. - Abstract: Co-exposure to paraquat (PQ) and maneb (Mb) has been shown to increase the risk of Parkinson’s disease (PD) and dopaminergic (DA) neurodegeneration in the substantia nigra pars compacta (SNpc) is observed in PQ and Mb-treated experimental animals. The loss of noradrenergic locus coeruleus (LC/NE) neurons in brainstem is a common feature shared by multiple neurodegenerative diseases, including PD. However, whether PQ and Mb is able to damage LC/NE neurons remains undefined. In this study, mice treated with combined PQ and Mb displayed progressive LC/NE neurodegeneration. Time course studies revealed that the activation of microglia preceded LC/NE neurodegeneration. Mechanistically, the activation of NADPH oxidase contributed to microglial activation and subsequent LC/NE neurodegeneration. We found that PQ and Mb co-exposure induced activation of NADPH oxidase as shown by increased superoxide production and membrane translocation of p47 phox , a cytosolic subunit of NADPH oxidase. Inhibition of NADPH oxidase by apocynin, a widely used NADPH oxidase inhibitor, suppressed microglial activation and gene expressions of proinflammatory factors. Furthermore, reduced activation of nuclear factor-κB (NF-κB) pathway was observed in apocynin-treated mice. More importantly, inhibition of NADPH oxidase by apocynin afforded LC/NE neuroprotection against PQ and Mb-induced neurotoxicity. Thus, our findings revealed the critical role NADPH oxidase-mediated microglial activation in driving LC/NE neurodegeneration induced by PQ and Mb, providing new insights into the pathogenesis of environmental

The Diesel Exhaust in Miners Study: I. Overview of the Exposure Assessment Process

Science.gov (United States)

Stewart, Patricia A.; Coble, Joseph B.; Vermeulen, Roel; Schleiff, Patricia; Blair, Aaron; Lubin, Jay; Attfield, Michael; Silverman, Debra T.

2010-01-01

This report provides an overview of the exposure assessment process for an epidemiologic study that investigated mortality, with a special focus on lung cancer, associated with diesel exhaust (DE) exposure among miners. Details of several components are provided in four other reports. A major challenge for this study was the development of quantitative estimates of historical exposures to DE. There is no single standard method for assessing the totality of DE, so respirable elemental carbon (REC), a component of DE, was selected as the primary surrogate in this study. Air monitoring surveys at seven of the eight study mining facilities were conducted between 1998 and 2001 and provided reference personal REC exposure levels and measurements for other agents and DE components in the mining environment. (The eighth facility had closed permanently prior to the surveys.) Exposure estimates were developed for mining facility/department/job/year combinations. A hierarchical grouping strategy was developed for assigning exposure levels to underground jobs [based on job titles, on the amount of time spent in various areas of the underground mine, and on similar carbon monoxide (CO, another DE component) concentrations] and to surface jobs (based on the use of, or proximity to, diesel-powered equipment). Time trends in air concentrations for underground jobs were estimated from mining facility-specific prediction models using diesel equipment horsepower, total air flow rates exhausted from the underground mines, and, because there were no historical REC measurements, historical measurements of CO. Exposures to potentially confounding agents, i.e. respirable dust, silica, radon, asbestos, and non-diesel sources of polycyclic aromatic hydrocarbons, also were assessed. Accuracy and reliability of the estimated REC exposures levels were evaluated by comparison with several smaller datasets and by development of alternative time trend models. During 1998–2001, the average

A new perspective on human health risk assessment: Development of a time dependent methodology and the effect of varying exposure durations

International Nuclear Information System (INIS)

Siirila, Erica R.; Maxwell, Reed M.

2012-01-01

We present a new Time Dependent Risk Assessment (TDRA) that stochastically considers how joint uncertainty and inter-individual variability (JUV) associated with human health risk change as a function of time. In contrast to traditional, time independent assessments of risk, this new formulation relays information on when the risk occurs, how long the duration of risk is, and how risk changes with time. Because the true exposure duration (ED) is often uncertain in a risk assessment, we also investigate how varying the magnitude of fixed size durations (ranging between 5 and 70 years) of this parameter affects the distribution of risk in both the time independent and dependent methodologies. To illustrate this new formulation and to investigate these mechanisms for sensitivity, an example of arsenic contaminated groundwater is used in conjunction with two scenarios of different environmental concentration signals resulting from rate dependencies in geochemical reactions. Cancer risk is computed and compared using environmental concentration ensembles modeled with sorption as 1) a linear equilibrium assumption (LEA) and 2) first order kinetics (Kin). Results show that the information attained in the new time dependent methodology reveals how the uncertainty in other time-dependent processes in the risk assessment may influence the uncertainty in risk. We also show that individual susceptibility also affects how risk changes in time, information that would otherwise be lost in the traditional, time independent methodology. These results are especially pertinent for forecasting risk in time, and for risk managers who are assessing the uncertainty of risk. - Highlights: ► A human health, Time Dependent Risk Assessment (TDRA) methodology is presented. ► TDRA relays information on the magnitude, duration, and fluxes of risk in time. ► Kinetic and equilibrium concentration signals show sensitivity in TDRA results. ► In the TDRA results, individual susceptibility

A new perspective on human health risk assessment: Development of a time dependent methodology and the effect of varying exposure durations

Energy Technology Data Exchange (ETDEWEB)

Siirila, Erica R., E-mail: esiirila@mymail.mines.edu [Hydrologic Science and Engineering Program, Colorado School of Mines, 1500 Illinois St., Golden, CO 80401 (United States); Department of Geology and Geological Engineering, Colorado School of Mines, 1500 Illinois St., Golden, CO 80401 (United States); Maxwell, Reed M., E-mail: rmaxwell@mines.edu [Hydrologic Science and Engineering Program, Colorado School of Mines, 1500 Illinois St., Golden, CO 80401 (United States); Integrated Groundwater Modeling Center (IGWMC), Colorado School of Mines, 1500 Illinois St., Golden, CO 80401 (United States); Department of Geology and Geological Engineering, Colorado School of Mines, 1500 Illinois St., Golden, CO 80401 (United States)

2012-08-01

We present a new Time Dependent Risk Assessment (TDRA) that stochastically considers how joint uncertainty and inter-individual variability (JUV) associated with human health risk change as a function of time. In contrast to traditional, time independent assessments of risk, this new formulation relays information on when the risk occurs, how long the duration of risk is, and how risk changes with time. Because the true exposure duration (ED) is often uncertain in a risk assessment, we also investigate how varying the magnitude of fixed size durations (ranging between 5 and 70 years) of this parameter affects the distribution of risk in both the time independent and dependent methodologies. To illustrate this new formulation and to investigate these mechanisms for sensitivity, an example of arsenic contaminated groundwater is used in conjunction with two scenarios of different environmental concentration signals resulting from rate dependencies in geochemical reactions. Cancer risk is computed and compared using environmental concentration ensembles modeled with sorption as 1) a linear equilibrium assumption (LEA) and 2) first order kinetics (Kin). Results show that the information attained in the new time dependent methodology reveals how the uncertainty in other time-dependent processes in the risk assessment may influence the uncertainty in risk. We also show that individual susceptibility also affects how risk changes in time, information that would otherwise be lost in the traditional, time independent methodology. These results are especially pertinent for forecasting risk in time, and for risk managers who are assessing the uncertainty of risk. - Highlights: Black-Right-Pointing-Pointer A human health, Time Dependent Risk Assessment (TDRA) methodology is presented. Black-Right-Pointing-Pointer TDRA relays information on the magnitude, duration, and fluxes of risk in time. Black-Right-Pointing-Pointer Kinetic and equilibrium concentration signals show

How to statistically analyze nano exposure measurement results: using an ARIMA time series approach

International Nuclear Information System (INIS)

Klein Entink, Rinke H.; Fransman, Wouter; Brouwer, Derk H.

2011-01-01

Measurement strategies for exposure to nano-sized particles differ from traditional integrated sampling methods for exposure assessment by the use of real-time instruments. The resulting measurement series is a time series, where typically the sequential measurements are not independent from each other but show a pattern of autocorrelation. This article addresses the statistical difficulties when analyzing real-time measurements for exposure assessment to manufactured nano objects. To account for autocorrelation patterns, Autoregressive Integrated Moving Average (ARIMA) models are proposed. A simulation study shows the pitfalls of using a standard t-test and the application of ARIMA models is illustrated with three real-data examples. Some practical suggestions for the data analysis of real-time exposure measurements conclude this article.

Apoptosis induction in human lymphocytes after in vitro exposure to cobalt/hard metal compounds

International Nuclear Information System (INIS)

Boeck, M. de; Decordier, I.; Lombaert, N.; Cundari, E.; Kirsch-Volders, M.; Lison, D.

2001-01-01

Full text: An increased risk of lung cancer is associated with occupational exposure to mixtures of cobalt metal (Co) and tungsten carbide (WC) particles, but apparently not when exposure is to cobalt alone. The mechanism for this increased cancer risk is not fully understood. The evaluation of the in vitro genotoxic effects in lymphocytes exposed to varying cobalt species demonstrated that the WC-Co hard metal mixture is more genotoxic (DNA damage, chromosome/genome mutations) than metallic Co alone. WC alone was not genotoxic. Thus, WC-Co represents a specific (geno)toxic entity. In order to assess the survival of human lymphocytes after in vitro exposure to metallic Co, CoCl 2 , WC and the WC-Co mixture, two apoptosis/necrosis detection methods were applied (annexin V staining and flow cytometry). Annexin-V staining of early apoptotic cells demonstrated a dose- and time dependent induction of apoptosis by metallic Co, CoCl 2 , WC and the WC-Co mixture. The time course of the process varied according to the metal species tested. Metallic Co and CoCl 2 caused a gradually increasing frequency of apoptotic cells with time (up to 24 h). WC-induced apoptosis displayed a typical 6 hour peak, which was not the case for the WC-Co mixture or for Co. Apoptosis induction by the WC-Co mixture was intermediate between that induced by Co and WC separately. Analysis of propidium iodide stained cells by flow cytometry was performed as a later marker for apoptosis induction. Preliminary data indicate similar tendencies of apoptosis induction as those detected by annexin-V. Identification of the apoptotic pathway triggered by the metal compounds was studied by inhibition of the ceramide-apoptosis pathway by fumonisin causing reduction of apoptosis induction for all compounds, but strongest after 6 hour exposure to WC. The use of specific caspase inhibitors will allow to further elucidate the different pathways involved. The current data demonstrating in vitro the apoptosis

Apoptosis induction in human lymphocytes after in vitro exposure to cobalt/hard metal compounds

Energy Technology Data Exchange (ETDEWEB)

Boeck, M de; Decordier, I; Lombaert, N; Cundari, E; Kirsch-Volders, M [Vrije Universiteit Brussel, Laboratorium voor Cellulaire Genetica, Brussel (Belgium); Lison, D [Universite catholique de Louvain, Unite de Toxicologie industrielle et Medecine du Travail, Bruxelles (Belgium)

2001-07-01

Full text: An increased risk of lung cancer is associated with occupational exposure to mixtures of cobalt metal (Co) and tungsten carbide (WC) particles, but apparently not when exposure is to cobalt alone. The mechanism for this increased cancer risk is not fully understood. The evaluation of the in vitro genotoxic effects in lymphocytes exposed to varying cobalt species demonstrated that the WC-Co hard metal mixture is more genotoxic (DNA damage, chromosome/genome mutations) than metallic Co alone. WC alone was not genotoxic. Thus, WC-Co represents a specific (geno)toxic entity. In order to assess the survival of human lymphocytes after in vitro exposure to metallic Co, CoCl{sub 2}, WC and the WC-Co mixture, two apoptosis/necrosis detection methods were applied (annexin V staining and flow cytometry). Annexin-V staining of early apoptotic cells demonstrated a dose- and time dependent induction of apoptosis by metallic Co, CoCl{sub 2}, WC and the WC-Co mixture. The time course of the process varied according to the metal species tested. Metallic Co and CoCl{sub 2} caused a gradually increasing frequency of apoptotic cells with time (up to 24 h). WC-induced apoptosis displayed a typical 6 hour peak, which was not the case for the WC-Co mixture or for Co. Apoptosis induction by the WC-Co mixture was intermediate between that induced by Co and WC separately. Analysis of propidium iodide stained cells by flow cytometry was performed as a later marker for apoptosis induction. Preliminary data indicate similar tendencies of apoptosis induction as those detected by annexin-V. Identification of the apoptotic pathway triggered by the metal compounds was studied by inhibition of the ceramide-apoptosis pathway by fumonisin causing reduction of apoptosis induction for all compounds, but strongest after 6 hour exposure to WC. The use of specific caspase inhibitors will allow to further elucidate the different pathways involved. The current data demonstrating in vitro the

Green chemistry volumetric titration kit for pharmaceutical formulations: Econoburette

Directory of Open Access Journals (Sweden)

Man Singh

2009-08-01

Full Text Available Stopcock SC and Spring Sp models of Econoburette (Calibrated, RTC (NR, Ministry of Small Scale Industries, Government of India, developed for semimicro volumetric titration of pharmaceutical formulations are reported. These are economized and risk free titration where pipette is replaced by an inbuilt pipette and conical flask by inbuilt bulb. A step of pipetting of stock solution by mouth is deleted. It is used to allow solution exposure to user’s body. This risk is removed and even volatile and toxic solutions are titrated with full proof safety. Econoburette minimizes use of materials and time by 90 % and prevent discharge of polluting effluent to environment. Few acid and base samples are titrated and an analysis of experimental expenditure is described in the papers.

Sunlight persistence and rainfastness of spray-dried formulations of baculovirus isolated from Anagrapha falcifera (Lepidoptera: Noctuidae).

Science.gov (United States)

Tamez-Guerra, P; McGuire, M R; Behle, R W; Hamm, J J; Sumner, H R; Shasha, B S

2000-04-01

Nuclear polyhedrosis viruses such as the one isolated from the celery looper, Anagrapha falcifera (Kirby) (AfMNPV), have the potential to be successful bioinsecticides if improved formulations can prevent rapid loss of insecticidal activity from environmental conditions such as sunlight and rainfall. We tested 16 spray-dried formulations of AfMNPV to determine the effect of different ingredients (e.g., lignin, corn flour, and so on) on insecticidal activity after simulated rain and simulated sunlight (at Peoria, IL) and natural sunlight exposures (at Tifton, GA). The most effective formulation contained pregelatinized corn flour and potassium lignate, which retained more than half of its original activity after 5 cm of simulated rain, and almost full activity after 8 h of simulated sunlight. In Georgia, formulations made with and without lignin were compared for persistence of insecticidal activity when exposed to natural sunlight. In addition, the effect of fluorescent brighteners as formulation components and spray tank additives was tested. Results showed that the formulations with lignin had more insecticidal activity remaining after sunlight exposure than formulations without lignin. The inclusion of brighteners in the formulation did not improve initial activity or virus persistence. However, a 1% tank mix significantly enhanced activity and improved persistence. Scanning electron micrographs revealed discreet particles, and transmission electron micrographs showed virus embedded within microgranules. Results demonstrated that formulations made with natural ingredients could improve persistence of virus-based biopesticides.

Preparation of radiopharmaceutical formulations

International Nuclear Information System (INIS)

Simon, J.; Garlich, J.R.; Frank, R.K.; McMillan, K.

1998-01-01

Radiopharmaceutical formulations for complexes comprising at least one radionuclide complexed with a ligand, or its physiologically-acceptable salts thereof, especially 153 samarium-ethylenediaminetetramethylenephosphonic acid, which optionally contains a divalent metal ion, e.g. calcium, and is frozen, thawed, and then administered by injection. Alternatively, the radiopharmaceutical formulations must contain the divalent metal and are frozen only if the time before administration is sufficiently long to cause concern for radiolysis of the ligand. 2 figs., 9 tabs

Relative bioavailability of diclofenac potassium from softgel capsule versus powder for oral solution and immediate-release tablet formulation.

Science.gov (United States)

Bende, Girish; Biswal, Shibadas; Bhad, Prafulla; Chen, Yuming; Salunke, Atish; Winter, Serge; Wagner, Robert; Sunkara, Gangadhar

2016-01-01

The oral bioavailability of diclofenac potassium 50 mg administered as a soft gelatin capsule (softgel capsule), powder for oral solution (oral solution), and tablet was evaluated in a randomized, open-label, 3-period, 6-sequence crossover study in healthy adults. Plasma diclofenac concentrations were measured using a validated liquid chromatography-mass spectrometry/mass spectrometry method, and pharmacokinetic analysis was performed by noncompartmental methods. The median time to achieve peak plasma concentrations of diclofenac was 0.5, 0.25, and 0.75 hours with the softgel capsule, oral solution, and tablet formulations, respectively. The geometric mean ratio and associated 90%CI for AUCinf, and Cmax of the softgel capsule formulation relative to the oral solution formulation were 0.97 (0.95-1.00) and 0.85 (0.76-0.95), respectively. The geometric mean ratio and associated 90%CI for AUCinf and Cmax of the softgel capsule formulation relative to the tablet formulation were 1.04 (1.00-1.08) and 1.67 (1.43-1.96), respectively. In conclusion, the exposure (AUC) of diclofenac with the new diclofenac potassium softgel capsule formulation was comparable to that of the existing oral solution and tablet formulations. The peak plasma concentration of diclofenac from the new softgel capsule was 67% higher than the existing tablet formulation, whereas it was 15% lower in comparison with the oral solution formulation. © 2015, The American College of Clinical Pharmacology.

DNA/RNA-based formulations for treatment of breast cancer

DEFF Research Database (Denmark)

Xie, Zhaolu; Zeng, Xianghui

2017-01-01

utilized targets are not effective enough as monotherapy for breast cancer. Secondly, the requirements for co-delivery system make the preparation of formulation more complicated. Thirdly, nanoparticles with the modification of tumor-targeting ligands could be more unstable in circulation and normal...

Extended‐Release Once‐Daily Formulation of Tofacitinib: Evaluation of Pharmacokinetics Compared With Immediate‐Release Tofacitinib and Impact of Food

Science.gov (United States)

Wang, Rong; Fletcher, Tracey; Alvey, Christine; Kushner, Joseph; Stock, Thomas C.

2016-01-01

Abstract Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. An extended‐release (XR) formulation has been designed to provide a once‐daily (QD) dosing option to patients to achieve comparable pharmacokinetic (PK) parameters to the twice‐daily immediate‐release (IR) formulation. We conducted 2 randomized, open‐label, phase 1 studies in healthy volunteers. Study A characterized single‐dose and steady‐state PK of tofacitinib XR 11 mg QD and intended to demonstrate equivalence of exposure under single‐dose and steady‐state conditions to tofacitinib IR 5 mg twice daily. Study B assessed the effect of a high‐fat meal on the bioavailability of tofacitinib from the XR formulation. Safety and tolerability were monitored in both studies. In study A (N = 24), the XR and IR formulations achieved time to maximum plasma concentration at 4 hours and 0.5 hours postdose, respectively; terminal half‐life was 5.9 hours and 3.2 hours, respectively. Area under plasma concentration‐time curve (AUC) and maximum plasma concentration (Cmax) after single‐ and multiple‐dose administration were equivalent between the XR and IR formulations. In study B (N = 24), no difference in AUC was observed for fed vs fasted conditions. Cmax increased by 27% under the fed state. On repeat administration, negligible accumulation (Tofacitinib administration as an XR or IR formulation was generally well tolerated in these studies. PMID:26970526

Development of a versatile high-temperature short-time (HTST) pasteurization device for small-scale processing of cell culture medium formulations.

Science.gov (United States)

Floris, Patrick; Curtin, Sean; Kaisermayer, Christian; Lindeberg, Anna; Bones, Jonathan

2018-07-01

The compatibility of CHO cell culture medium formulations with all stages of the bioprocess must be evaluated through small-scale studies prior to scale-up for commercial manufacturing operations. Here, we describe the development of a bespoke small-scale device for assessing the compatibility of culture media with a widely implemented upstream viral clearance strategy, high-temperature short-time (HTST) treatment. The thermal stability of undefined medium formulations supplemented with soy hydrolysates was evaluated upon variations in critical HTST processing parameters, namely, holding times and temperatures. Prolonged holding times of 43 s at temperatures of 110 °C did not adversely impact medium quality while significant degradation was observed upon treatment at elevated temperatures (200 °C) for shorter time periods (11 s). The performance of the device was benchmarked against a commercially available mini-pilot HTST system upon treatment of identical formulations on both platforms. Processed medium samples were analyzed by untargeted LC-MS/MS for compositional profiling followed by chemometric evaluation, which confirmed the observed degradation effects caused by elevated holding temperatures but revealed comparable performance of our developed device with the commercial mini-pilot setup. The developed device can assist medium optimization activities by reducing volume requirements relative to commercially available mini-pilot instrumentation and by facilitating fast throughput evaluation of heat-induced effects on multiple medium lots.

Structural Changes of Silica Mesocellular Foam Supported Amine-Functionalized CO 2 Adsorbents Upon Exposure to Steam

KAUST Repository

Li, Wen

2010-11-24

Three classes of amine-functionalized mesocellular foam (MCF) materials are prepared and evaluated as CO2 adsorbents. The stability of the adsorbents under steam/air and steam/nitrogen conditions is investigated using a Parr autoclave reactor to simulate, in an accelerated manner, the exposure that such adsorbents will see under steam stripping regeneration conditions at various temperatures. The CO2 capacity and organic content of all adsorbents decrease after steam treatment under both steam/air and steam/nitrogen conditions, primarily due to structural collapse of the MCF framework, but with additional contributions likely associated with amine degradation during treatment under harsh conditions. Treatment with steam/air is found to have stronger effect on the CO2 capacity of the adsorbents compared to steam/nitrogen. © 2010 American Chemical Society.

Structural Changes of Silica Mesocellular Foam Supported Amine-Functionalized CO 2 Adsorbents Upon Exposure to Steam

KAUST Repository

Li, Wen; Bollini, Praveen; Didas, Stephanie A.; Choi, Sunho; Drese, Jeffrey H.; Jones, Christopher W.

2010-01-01

Three classes of amine-functionalized mesocellular foam (MCF) materials are prepared and evaluated as CO2 adsorbents. The stability of the adsorbents under steam/air and steam/nitrogen conditions is investigated using a Parr autoclave reactor to simulate, in an accelerated manner, the exposure that such adsorbents will see under steam stripping regeneration conditions at various temperatures. The CO2 capacity and organic content of all adsorbents decrease after steam treatment under both steam/air and steam/nitrogen conditions, primarily due to structural collapse of the MCF framework, but with additional contributions likely associated with amine degradation during treatment under harsh conditions. Treatment with steam/air is found to have stronger effect on the CO2 capacity of the adsorbents compared to steam/nitrogen. © 2010 American Chemical Society.

Making Time for Nature: Visual Exposure to Natural Environments Lengthens Subjective Time Perception and Reduces Impulsivity.

Directory of Open Access Journals (Sweden)

Meredith S Berry

Full Text Available Impulsivity in delay discounting is associated with maladaptive behaviors such as overeating and drug and alcohol abuse. Researchers have recently noted that delay discounting, even when measured by a brief laboratory task, may be the best predictor of human health related behaviors (e.g., exercise currently available. Identifying techniques to decrease impulsivity in delay discounting, therefore, could help improve decision-making on a global scale. Visual exposure to natural environments is one recent approach shown to decrease impulsive decision-making in a delay discounting task, although the mechanism driving this result is currently unknown. The present experiment was thus designed to evaluate not only whether visual exposure to natural (mountains, lakes relative to built (buildings, cities environments resulted in less impulsivity, but also whether this exposure influenced time perception. Participants were randomly assigned to either a natural environment condition or a built environment condition. Participants viewed photographs of either natural scenes or built scenes before and during a delay discounting task in which they made choices about receiving immediate or delayed hypothetical monetary outcomes. Participants also completed an interval bisection task in which natural or built stimuli were judged as relatively longer or shorter presentation durations. Following the delay discounting and interval bisection tasks, additional measures of time perception were administered, including how many minutes participants thought had passed during the session and a scale measurement of whether time "flew" or "dragged" during the session. Participants exposed to natural as opposed to built scenes were less impulsive and also reported longer subjective session times, although no differences across groups were revealed with the interval bisection task. These results are the first to suggest that decreased impulsivity from exposure to natural as

Temperature changes across porcelain during multiple exposure CO2 lasing

Science.gov (United States)

Barron, Joseph R.; Zakariasen, Kenneth L.; Peacocke, Larry

1990-06-01

Research indicates that laser energy may provide a useful method for glazing and fusing porcelain for intraoral prosthetic purposes. However, it is not known whether such lasing will result in the production of heat levels that may be damaging to adjacent vital tissues such as the dental pulp and periodontal tissues. This research is designed to measure the magnitude of temperature rise across porcelain observed during multiple exposure C02 lasing. Fifteen porcelain examples of 1000 jim (5), 1500 pm (5) and 2000 tm (5) x each received five C02 laser exposures on the same exposure site at 1.0 sec. intervals at 8.0 watts (0.2 sec. per exposure with a 1 mm focal spot). A YSI 144201 thermilinear precision thermistor was placed on the porcelain surface opposite each laser exposure site. Temperature rise above ambient was recorded by an HP3421A data acquisition unit and HP9816 technical microcomputer. Recording continued for sufficient time to allow temperatures to return to ambient. The mean temperature elevations ranged from a low of 2.97 0C (2000 pm) to a high of 7.77 °C (1000 μm). ANOVA and Duncan's Multiple Range Test indicated significant differences in temperature rise by porcelain thickness. It would appear from the results of this research that temperature elevations adjacent to lased porcelain may be sufficiently controllable that safe intraoral porcelain lasing will be possible.

A new topical formulation enhances relative diclofenac bioavailability in healthy male subjects.

Science.gov (United States)

Brunner, Martin; Davies, David; Martin, Wolfgang; Leuratti, Chiara; Lackner, Edith; Müller, Markus

2011-06-01

• Therapy with topical non-steroidal anti-inflammatory drugs (NSAIDs) relies on the ability of the active drug to penetrate the skin in sufficiently high amounts to exert a clinical effect, which is linked to the specific galenic properties of the formulation. • This phase 1 study characterizes the transdermal penetration and plasma exposure of different dose levels with galenic differences of a novel topical diclofenac formulation under development and indicates greater diclofenac penetration through the skin when compared with a commercially available formulation. To evaluate the relative plasma and tissue availability of diclofenac after repeated topical administration of a novel diclofenac acid-based delivery system under development (DCF100C). This was a single-centre, open-label, three-period, crossover clinical trial of five discrete diclofenac formulations. Test preparations comprised two concentrations (1.0% and 2.5%) of DCF100C, with and without menthol and eucalyptus oil (total daily doses of 5 mg and 12.5 mg). Voltaren Emulgel gel (1.0%) was the commercially available comparator (total daily dose of 40 mg). Topical application was performed onto the thigh of 20 male healthy subjects for 3 days. Applying a Youden square design, each drug was evaluated in 12 subjects, with each subject receiving three test preparations. Blood sampling and in vivo microdialysis in subcutaneous adipose and skeletal muscle tissues were performed for 10 h after additional final doses on the morning of day 4. All four DCF100C formulations demonstrated a three- to fivefold, dose-dependent increase in systemic diclofenac availability compared with Voltaren Emulgel and were approximately 30-40 times more effective at facilitating diclofenac penetration through the skin, taking different dose levels into account. Tissue concentrations were low and highly variable. The 2.5% DCF100C formulation without sensory excipients reached the highest tissue concentrations. AUC(0,10 h) was

Effect of exposure time reduction towards sensitivity and SNR for computed radiography (CR) application in NDT

International Nuclear Information System (INIS)

Sapizah Rahim; Khairul Anuar Mohd Salleh; Noorhazleena Azaman; Shaharudin Sayuti; Siti Madiha Muhammad Amir; Arshad Yassin; Abdul Razak Hamzah

2010-01-01

Signal-to-noise ratio (SNR) and sensitivity study of Computed Radiography (CR) system with reduction of exposure time is presented. The purposes of this research are to determine the behavior of SNR toward three different thicknesses (step wedge; 5, 10 and 15 mm) and the ability of CR system to recognize hole type penetrameter when the exposure time decreased up to 80 % according to the exposure chart (D7; ISOVOLT Titan E). It is shown that the SNR is decreased with decreasing of exposure time percentage but the high quality image is achieved until 80 % reduction of exposure time. (author)

Pharmacokinetics and bioequivalence of a liquid formulation of hydroxyurea in children with sickle cell anemia.

Science.gov (United States)

Estepp, Jeremie H; Melloni, Chiara; Thornburg, Courtney D; Wiczling, Paweł; Rogers, Zora; Rothman, Jennifer A; Green, Nancy S; Liem, Robert; Brandow, Amanda M; Crary, Shelley E; Howard, Thomas H; Morris, Maurine H; Lewandowski, Andrew; Garg, Uttam; Jusko, William J; Neville, Kathleen A

2016-03-01

Hydroxyurea (HU) is a crucial therapy for children with sickle cell anemia, but its off-label use is a barrier to widespread acceptance. We found HU exposure is not significantly altered by liquid vs capsule formulation, and weight-based dosing schemes provide consistent exposure. HU is recommended for all children starting as young as 9 months of age with sickle cell anemia (SCA; HbSS and HbSβspan(0) thalassemia); however; a paucity of pediatric data exists regarding the pharmacokinetics (PK) or the exposure-response relationship of HU. This trial aimed to characterize the PK of HU in children and to evaluate and compare the bioavailability of a liquid vs capsule formulation. This multicenter; prospective; open-label trial enrolled 39 children with SCA who provided 682 plasma samples for PK analysis following administration of HU. Noncompartmental and population PK models are described. We report that liquid and capsule formulations of HU are bioequivalent; weight-based dosing schemes provide consistent drug exposure; and age-based dosing schemes are unnecessary. These data support the use of liquid HU in children unable to swallow capsules and in those whose weight precludes the use of fixed capsule formulations. Taken with existing safety and efficacy literature; these findings should encourage the use of HU across the spectrum of age and weight in children with SCA; and they should facilitate the expanded use of HU as recommended in the National Heart; Lung; and Blood Institute guidelines for individuals with SCA. © 2015, The American College of Clinical Pharmacology.

TURVA-2012: Formulation of radionuclide release scenarios

International Nuclear Information System (INIS)

Marcos, Nuria; Hjerpe, Thomas; Snellman, Margit; Ikonen, Ari; Smith, Paul

2014-01-01

TURVA-2012 is Posiva's safety case in support of the Preliminary Safety Analysis Report (PSAR) and application for a construction licence for a repository for disposal of spent nuclear fuel at the Olkiluoto site in south-western Finland. This paper gives a summary of the scenarios and the methodology followed in formulating them as described in TURVA-2012: Formulation of Radionuclide Release Scenarios (Posiva, 2013). The scenarios are further analysed in TURVA-2012: Assessment of Radionuclide Release Scenarios for the Repository System and TURVA-2012: Biosphere Assessment (Posiva, 2012a, 2012b). The formulation of scenarios takes into account the safety functions of the main barriers of the repository system and the uncertainties in the features, events, and processes (FEP) that may affect the entire disposal system (i.e. repository system plus the surface environment) from the emplacement of the first canister until the far future. In the report TURVA-2012: Performance Assessment (2012d), the performance of the engineered and natural barriers has been assessed against the loads expected during the evolution of the repository system and the site. Uncertainties have been identified and these are taken into account in the formulation of radionuclide release scenarios. The uncertainties in the FEP and evolution of the surface environment are taken into account in formulating the surface environment scenarios used ultimately in estimating radiation exposure. Formulating radionuclide release scenarios for the repository system links the reports Performance Assessment and Assessment of Radionuclide Release Scenarios for the Repository System. The formulation of radionuclide release scenarios for the surface environment brings together biosphere description and the surface environment FEP and is the link to the assessment of the surface environment scenarios summarised in TURVA-2012: Biosphere Assessment. (authors)

Formulation studies for mirtazapine orally disintegrating tablets.

Science.gov (United States)

Yıldız, Simay; Aytekin, Eren; Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Ünlü, Nurşen

2016-01-01

Orally disintegrating tablets (ODTs) recently have gained much attention to fulfill the needs for pediatric, geriatric, and psychiatric patients with dysphagia. Aim of this study was to develop new ODT formulations containing mirtazapine, an antidepressant drug molecule having bitter taste, by using simple and inexpensive preparation methods such as coacervation, direct compression and to compare their characteristics with those of reference product (Remereon SolTab). Coacervation method was chosen for taste masking of mirtazapine. In vitro characterization studies such as diameter and thickness, weight variation, tablet hardness, tablet friability and disintegration time were performed on tablet formulations. Wetting time and in vitro dissolution tests of developed ODTs also studied using 900 mL 0.1 N HCl medium, 900 mL pH 6.8 phosphate buffer or 900 mL pH 4.5 acetate buffer at 37 ± 0.2 °C as dissolution medium. Ratio of Eudragit® E-100 was chosen as 6% (w/w) since the dissolution profile of A1 (6% Eudragit® E-100) was found closer to the reference product than A2 (4% Eudragit® E-100) and A3 (8% Eudragit® E-100). Group D, E and F formulations were presented better results in terms of disintegration time. Dissolution results indicated that Group E and F formulations showed optimum properties in all three dissolution media. Formulations D1, D4, D5, E3, E4, F1 and F5 found suitable as ODT formulations due to their favorable disintegration times and dissolution profiles. Developed mirtazapine ODTs were found promising in terms of showing the similar characteristics to the original formulation.

A direct comparison of physical block occupancy versus timed block occupancy in train timetabling formulations

DEFF Research Database (Denmark)

Harrod, Steven; Schlechte, Thomas

2013-01-01

Two fundamental mathematical formulations for railway timetabling are compared on a common set of sample problems, representing both multiple track high density services in Europe and single track bidirectional operations in North America. One formulation, ACP, enforces against conflicts by const......Two fundamental mathematical formulations for railway timetabling are compared on a common set of sample problems, representing both multiple track high density services in Europe and single track bidirectional operations in North America. One formulation, ACP, enforces against conflicts...

The decline in kidney function with chromium exposure is exacerbated with co-exposure to lead and cadmium.

Science.gov (United States)

Tsai, Tsung-Lin; Kuo, Chin-Chi; Pan, Wen-Harn; Chung, Yu-Teh; Chen, Chiu-Ying; Wu, Trong-Neng; Wang, Shu-Li

2017-09-01

Environmental factors contribute significantly to the pathogenesis of chronic kidney disease. However, these factors, and particularly the toxic effects of heavy metals, have not been completely evaluated. Chromium is a widespread industrial contaminant that has been linked to nephrotoxicity in animal and occupational population studies. Nevertheless, its role in population renal health and its potential interactions with other nephrotoxic metals, such as lead and cadmium, remain unknown. We assessed the association between exposure to chromium, lead, and cadmium with renal function using estimated glomerular filtration rate (eGFR) in an analysis of 360 Taiwanese adults aged 19-84 years from the National Nutrition and Health Survey in Taiwan (2005-2008). Doubling of urinary chromium or lead decreased the eGFR by -5.99 mL/min/1.73 m 2 (95% confidence interval -9.70, -2.27) and -6.61 (-9.71, -3.51), respectively, after adjusting for age, sex, body mass index, hypertension, diabetes, cigarette smoking, sodium intake, education, urinary volume, and other metals. For those in the highest tertile of cadmium exposure, the eGFR decreased by -12.68 mL/min/1.73 m 2 (95% confidence interval -20.44, -4.93) and -11.22 mL/min/1.73 m 2 (-17.01, -5.44), as urinary chromium or lead levels doubled, respectively. Thus, there is a significant and independent association between chromium exposure and decreased renal function. Furthermore, co-exposure to chromium with lead and cadmium is potentially associated with additional decline in the glomerular filtration rate in Taiwanese adults. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Combined CO/CH4 oxidation tests over Pd/Co3O4 monolithic catalyst. Effects of high reaction temperature and SO2 exposure on the deactivation process

International Nuclear Information System (INIS)

Liotta, L.F.; Venezia, A.M.; Di Carlo, G.; Pantaleo, G.; Deganello, G.; Merlone Borla, E.; Pidria, M.

2007-01-01

CO and CH 4 combined oxidation tests were performed over a Pd (70 g/ft 3 )/Co 3 O 4 monolithic catalyst in conditions of GHSV = 100,000 h -1 and feed composition close to that of emission from bi-fuel vehicles. The effect of SO 2 (5 ppm) on CO and CH 4 oxidation activity under lean condition (λ 2) was investigated. The presence of sulphur strongly deactivated the catalyst towards methane oxidation, while the poisoning effect was less drastic in the oxidation of CO. Saturation of the Pd/Co 3 O 4 catalytic sites via chemisorbed SO 3 and/or sulphates occurred upon exposure to SO 2 . A treatment of regeneration to remove sulphate species was attempted by performing a heating/cooling cycle up to 900 C in oxidizing atmosphere. Decomposition of PdO and Co 3 O 4 phases at high temperature, above 750 C, was observed. Moreover, sintering of Pd 0 and PdO particles along with of CoO crystallites takes place. (author)

Formulation and in vitro evaluation of ibuprofen-loaded poly(D,L ...

African Journals Online (AJOL)

co-glycolide) (PLGA) microparticles. Methods: Ibuprofen-loaded microparticles containing PLGA were formulated using a emulsification/solvent evaporation method. Various concentrations of ibuprofen (200, 300, 400 and 0 mg) were loaded ...

Time series analysis and mortality model of dog bite victims presented for treatment at a referral clinic for rabies exposure in Monrovia, Liberia, 2010-2013.

Science.gov (United States)

Olarinmoye, Ayodeji O; Ojo, Johnson F; Fasunla, Ayotunde J; Ishola, Olayinka O; Dakinah, Fahnboah G; Mulbah, Charles K; Al-Hezaimi, Khalid; Olugasa, Babasola O

2017-08-01

We developed time trend model, determined treatment outcome and estimated annual human deaths among dog bite victims (DBVs) from 2010 to 2013 in Monrovia, Liberia. Data obtained from clinic records included victim's age, gender and site of bite marks, site name of residence of rabies-exposed patients, promptness of care sought, initial treatment and post-exposure-prophylaxis (PEP) compliance. We computed DBV time-trend plot, seasonal index and year 2014 case forecast. Associated annual human death (AHD) was estimated using a standardized decision tree model. Of the 775 DBVs enlisted, care seeking time was within 24h of injury in 328 (42.32%) DBVs. Victim's residential location, site of bite mark, and time dependent variables were significantly associated with treatment outcome (prabies implied urgent need for policy formulation on national programme for rabies prevention in Liberia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Simultaneous Determination of Acetaminophen and Synthetic Color(s) by Derivative Spectroscopy in Syrup Formulations and Validation by HPLC: Exposure Risk of Colors to Children.

Science.gov (United States)

Rastogi, Shanya Das; Dixit, Sumita; Tripathi, Anurag; Das, Mukul

2015-06-01

Color additives are used in pediatric syrup formulations as an excipient; though not pre-requisite, but pediatric syrup formulations are normally colored. An attempt has been made to measure simultaneously the single drug, acetaminophen (AT), along with the colors, carmoisine (CA), erythrosine (ET), and sunset yellow FCF (SSY) added in it by three derivative spectroscopy methods namely, 1st order, ratio, and differential derivative methods. Moreover, evaluation has been made for the exposure assessment of the colors added as excipient because some colors have been reported to cause allergic reactions and hypersensitivity in children. The present methods provide simple, accurate, and reproducible quantitative determination of the drug, AT, along with the color in synthetic mixtures and commercial drug formulations without any interference. The limit of detection varied from 0.0001-0.31 μg/ml while limit of quantification ranged from 0.002-1.04 μg/ml in all the three methods. The calibration curve of all the three derivative methods exhibited good linear relationship with excellent regression coefficients (0.9986-1.000). Both intra-day and inter-day precisions showed %RSD value less than 2% while the percentage recovery was found between 96.8-103.8%. The sensitivity of the proposed methods is almost comparable to HPLC and thus, can be used for determination of drug AT, and color simultaneously in pharmaceutical formulation on routine basis. The present methods also showed that colors like SSY and ET are saturating more than 50% of acceptable daily intake (ADI) value which is alarming and needs to be considered for modification by regulatory authorities to safeguard the health of children.

Joint analysis of French and Czech uranium miners: lung cancer risk at low radon exposure rates and modifying effects of time since exposure and age at exposure

International Nuclear Information System (INIS)

Ladislav Tomasek; Agnes Rogel; Margot Tirmarche; Dominique Laurier

2006-01-01

The present analysis was conducted in the frame of European project 'Quantification of lung cancer risk after low radon exposure and low exposure rate: synthesis from epidemiologic and experimental data'. The overall goal of the project related to uranium miners was the evaluation of lung cancer dose-response relationship and of dose rate effects among European uranium miners exposed to low doses and low dose rates of radon decay products. In addition, modifying factors like attained age, age at exposure and time since exposure were investigated. The joint analysis of French and Czech uranium miners was conducted mainly in order to increase the statistical power and to allow a more detailed description of the variation of dose-response relationship in time. (N.C.)

Joint analysis of French and Czech uranium miners: lung cancer risk at low radon exposure rates and modifying effects of time since exposure and age at exposure

Energy Technology Data Exchange (ETDEWEB)

Ladislav Tomasek [National Radiation Protection Institute, Prague (Czech Republic); Agnes Rogel; Margot Tirmarche; Dominique Laurier [Institut de Radioprotection et de Surete Nucleaire, Fontenay-aux-Roses (France)

2006-07-01

The present analysis was conducted in the frame of European project 'Quantification of lung cancer risk after low radon exposure and low exposure rate: synthesis from epidemiologic and experimental data'. The overall goal of the project related to uranium miners was the evaluation of lung cancer dose-response relationship and of dose rate effects among European uranium miners exposed to low doses and low dose rates of radon decay products. In addition, modifying factors like attained age, age at exposure and time since exposure were investigated. The joint analysis of French and Czech uranium miners was conducted mainly in order to increase the statistical power and to allow a more detailed description of the variation of dose-response relationship in time. (N.C.)

Surgery for subacromial impingement syndrome in relation to intensities of occupational mechanical exposures across 10-year exposure time windows

DEFF Research Database (Denmark)

Dalbøge, Annett; Frost, Poul; Andersen, Johan Hviid

2018-01-01

OBJECTIVES: We aimed to identify intensities of occupational mechanical exposures (force, arm elevation and repetition) that do not entail an increased risk of surgery for subacromial impingement syndrome (SIS) even after prolonged durations of exposure. Additionally, we wanted to evaluate...... if exposure to hand-arm vibration (HAV) is an independent risk factor. METHODS: We used data from a register-based cohort study of the entire Danish working population (n=2 374 403). During follow-up (2003-2008), 14 118 first-time events of surgery for SIS occurred. For each person, we linked register...... of exposure at specific intensities above minimal (low, medium and high). We used a logistic regression technique equivalent to discrete survival analysis adjusting for cumulative effects of other mechanical exposures. RESULTS: We found indications of safe exposure intensities for repetition (median angular...

Left truncation results in substantial bias of the relation between time-dependent exposures and adverse events

NARCIS (Netherlands)

Hazelbag, Christijan M; Klungel, Olaf H; van Staa, Tjeerd P; de Boer, Anthonius; Groenwold, Rolf H H

PURPOSE: To assess the impact of random left truncation of data on the estimation of time-dependent exposure effects. METHODS: A simulation study was conducted in which the relation between exposure and outcome was based on an immediate exposure effect, a first-time exposure effect, or a cumulative

Left truncation results in substantial bias of the relation between time-dependent exposures and adverse events

NARCIS (Netherlands)

Hazelbag, Christijan M.; Klungel, Olaf H.; van Staa, Tjeerd P.; de Boer, Anthonius; Groenwold, Rolf H H

2015-01-01

PURPOSE: To assess the impact of random left truncation of data on the estimation of time-dependent exposure effects. METHODS: A simulation study was conducted in which the relation between exposure and outcome was based on an immediate exposure effect, a first-time exposure effect, or a cumulative

Night shift work characteristics and occupational co-exposures in industrial plants in Łódź, Poland

Directory of Open Access Journals (Sweden)

Beata Pepłońska

2013-08-01

Full Text Available Objectives: Night shift work involving circadian rhythm disruption has been classified by IARC as a probably carcinogenic to humans (Group 2A. Little is known about co-exposures of the night shift work in occupational settings. The aim of our study was to characterize night shift work systems and industrial exposures occurring in the manufacturing plants in Łódź, Poland, where night shift work system operates, with particular focus on potential carcinogens. Material and Methods: Data on the night shift work systems and hazardous agents were collected through survey performed in 44 enterprises. The identified hazardous agents were checked using the IARC carcinogen list, and the harmonized EU classification of chemical substances. We also examined databases of the Central Register of Data on exposure to substances, preparations, agents and technological processes showing carcinogenic or mutagenic properties in Poland. Results: The most common system of work among studied enterprises employed 3 (8-hour shifts within a 5-day cycle. We identified as many as 153 hazards occurring in the environment of the plants, with noise, carbon monoxide and formaldehyde recorded as the most common ones. Out of these hazards, 11 agents have been classified by IARC to group 1 - carcinogenic to humans, whereas 10 agents have been classified as carcino - gens by the regulation of European Classification of carcinogens. Analysis of the data from the Central Register revealed that 6 plants reported presence of carcinogens in the environment of work. Conclusions: In our study we observed that in none of the workplaces the night shift work was a single exposure. Further epidemiological studies focusing on investigation of health effects of the night shift work should identify occupational co -exposures and examine them as potential confounders.

Reduction of radiation exposure in Japanese BWR Nuclear Power Plants

International Nuclear Information System (INIS)

Morikawa, Yoshitake

1995-01-01

The reduction of occupational exposure to radiation during the annual inspection and maintenance outages of Japanese boiling water reactors (BWR) is one of the most important objectives for stable and reliable operation. It was shown that this radiation exposure is caused by radionuclides, such as Co-60, Co-58 and Mn-54 which are produced from the metal elements Co, Ni, and Fe present in the corrosion products of structural materials that had been irradiated by neutrons. Therefore, to reduce radiation sources and exposures in Japanese BWRs, attempts have been reinforced to remove corrosion products and activated corrosion products from the primary coolant system. This paper describes the progress of the application of these measures to Japanese BWRs. Most Japanese BWR-4 and BWR-5 type nuclear power plants started their commercial operations during the 1970s. With the elapse of time during operations, a problem came to the forefront, namely that occupational radiation exposure during plant outages gradually increased, which obstructed the smooth running of inspections and maintenance work. To overcome this problem, extensive studies to derive effective countermeasures for radiation exposure reduction were undertaken, based on the evaluation of the plants operation data

Reduction of radiation exposure in Japanese BWR Nuclear Power Plants

Energy Technology Data Exchange (ETDEWEB)

Morikawa, Yoshitake [ISOGO Nuclear Engineering Center, Yokohama (Japan)

1995-03-01

The reduction of occupational exposure to radiation during the annual inspection and maintenance outages of Japanese boiling water reactors (BWR) is one of the most important objectives for stable and reliable operation. It was shown that this radiation exposure is caused by radionuclides, such as Co-60, Co-58 and Mn-54 which are produced from the metal elements Co, Ni, and Fe present in the corrosion products of structural materials that had been irradiated by neutrons. Therefore, to reduce radiation sources and exposures in Japanese BWRs, attempts have been reinforced to remove corrosion products and activated corrosion products from the primary coolant system. This paper describes the progress of the application of these measures to Japanese BWRs. Most Japanese BWR-4 and BWR-5 type nuclear power plants started their commercial operations during the 1970s. With the elapse of time during operations, a problem came to the forefront, namely that occupational radiation exposure during plant outages gradually increased, which obstructed the smooth running of inspections and maintenance work. To overcome this problem, extensive studies to derive effective countermeasures for radiation exposure reduction were undertaken, based on the evaluation of the plants operation data.

Allowable exposure limits for carbon dioxide during extravehicular activity

Science.gov (United States)

Seter, Andrew J.

1993-01-01

The intent was to review the research pertaining to human exposure to carbon dioxide (CO2) and to recommend allowable exposure limits for extravehicular activity (EVA). Respiratory, renal, and gastrointestinal systems may be adversely affected by chronic low dose CO2 exposure. Ventilation was increased 15 percent with 1 percent CO2 and 50 percent with 2 percent CO2. Chronic exposure to less than 2 percent CO2 led to 20 day cycles of uncompensated and compensated respiratory acidosis. Acid-base changes were small. Histopathologic changes in guinea pig lungs have been noted with long term exposure to 1 percent CO2. No changes were seen with exposure to 0.5 percent CO2. Cycling of bone calcium stores with associated changes in blood and urinary calcium levels occurs with long term CO2 exposure. Histologic changes in bone have been noted in guinea pigs exposed to 1 percent CO2. Renal calcification has been noted in guinea pigs with exposure to as low as 0.5 percent CO2. An increase in gastric acidity was noted in subjects with long term exposure to 1 percent CO2. Cardiovascular and neurologic function were largely unaffected. A decrease in the incidence of respiratory, renal, and gastrointestinal disease was noted in submariners coincident with a decrease in ambient CO2 from 1.2 percent to 0.8-0.9 percent. Oxygen (O2) and CO2 stimulate respiration independently and cumulatively. The addition of CO2 to high dose O2 led to the faster onset of seizure activity in mice. Experiments evaluating the physiologic responses to intermittent, repetitive exposures to low dose CO2 and 100 percent O2 mixtures should be performed. A reduction in the current NASA standard for CO2 exposure during EVA of 1 percent (7.6 mmHg) for nominal and 2 percent (15.2 mmHg) for heavy exertion to 0.5 percent (3.8 mmHg) for nominal and 1 percent (7.6 mmHg) for heavy exertion may be prudent. At a minimum, the current NASA standard should not be liberalized.

Economic efficiency of CO2 reduction programs

International Nuclear Information System (INIS)

Tahvonen, O.; Storch, H. von; Storch, J. von

1993-01-01

A highly simplified time-dependent low-dimensional system has been designed to describe conceptually the interaction of climate and economy. Enhanced emission of carbon dioxide (CO 2 ) is understood as the agent that not only favors instantaneous consumption but also causes unfavorable climate changes at a later time. The problem of balancing these two counterproductive effects of CO 2 emissions on a finite time horizon is considered. The climate system is represented by just two parameters, namely a globally averaged near-surface air-temperature and a globally averaged troposheric CO 2 concentration. The costs of abating CO 2 emissions are monitored by a function which depends quadratically on the percentage reduction of emission compared to an 'uncontrolled emission' scenario. Parameters are fitted to historical climate data and to estimates from studies of CO 2 abatement costs. Two optimization approaches, which differ from earlier attempts to describe the interaction of economy and climate, are discussed. In the 'cost oriented' strategy an optimal emission path is identified which balances the abatement costs and explicitly formulated damage costs. These damage costs, whose estimates are very uncertain, are hypothesized to be a linear function of the time-derivative of temperature. In the 'target oriented' strategy an emission path is chosen so that the abatement costs are minimal while certain restrictions on the terminal temperature and concentration change are met. (orig.)

Exposure to organophosphate flame retardants in spray polyurethane foam applicators: Role of dermal exposure.

Science.gov (United States)

Bello, Anila; Carignan, Courtney C; Xue, Yalong; Stapleton, Heather M; Bello, Dhimiter

2018-04-01

Spray polyurethane foam (SPF) is a highly effective thermal insulation material that has seen considerable market growth in the past decade. Organophosphate flame retardants (PFRs) are added to SPF formulations to meet fire code requirements. A common flame retardant used in SPF formulations is tris 1-chloro 2-propyl phosphate (TCIPP), a suspected endocrine disruptor. Exposure monitoring efforts during SPF applications have focused primarily on the isocyanate component, a potent respiratory and dermal sensitizer. However, to our knowledge, there is no monitoring data for TCIPP. To characterize occupational exposures to TCIPP and other flame retardants during SPF insulation. Workers at four SPF insulation sites and one foam removal site (total n = 14) were recruited as part of this pilot study. Personal inhalation exposure to TCIPP was monitored with a CIP-10MI inhalable sampler and potential dermal exposure was assessed through the use of a glove dosimeter. Biomarkers of TCIPP and three other PFRs were measured in urine collected from workers pre-and post-shift. Linear mixed effect models were used to analyze associations of urinary biomarkers with inhalation and dermal exposures and paired t-tests were used to examine the difference on the means of urinary biomarkers pre-and post-shift. Chemical analysis of all species was performed with liquid chromatography-electrospray ionization tandem mass spectrometry. Geometric mean (GM) concentrations of TCIPP in personal air monitors and glove dosimeters collected from SPF applicators, 294.7 μg/m 3 and 18.8 mg/pair respectively. Overall, GM concentrations of the two TCIPP urinary biomarkers BCIPP and BCIPHIPP and (6.2 and 88.8 μg/mL) were 26-35 times higher than reported in the general population. Post-shift levels of TCIPP biomarkers were higher than pre-shift even though workers at insulation sites wore supplied air respirators, gloves and coveralls. The urinary biomarkers for the other PFRs were not

Formulation of cilostazol spherical agglomerates by crystallo-co-agglomeration technique and optimization using design of experimentation.

Science.gov (United States)

Deshkar, Sanjeevani Shekhar; Borde, Govind R; Kale, Rupali N; Waghmare, Balasaheb A; Thomas, Asha Biju

2017-01-01

Spherical agglomeration is one of the novel techniques for improvement of flow and dissolution properties of drugs. Cilostazol is a biopharmaceutics classification system Class II drug with poor solubility resulting in limited bioavailability. The present study aims at improving the solubility and dissolution of cilostazol by crystallo-co-agglomeration technique. Cilostazol agglomerates were prepared using various polymers with varying concentration of hydroxypropyl methylcellulose E 50 (HPMC E50), polyvinyl pyrrolidone K30 (PVP K30), and polyethylene glycol 6000. The influence of polymer concentration on spherical agglomerate formation was studied by 3 2 factorial design. Cilostazol agglomerates were evaluated for percent yield, mean particle size, drug content, aqueous solubility, and in vitro dissolution and further characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The agglomeration process resulted in optimized formulation, F3 with mean agglomerate size of 210.0 ± 0.56 μm, excellent flow properties, approximately 15-fold increase in solubility than pure cilostazol and complete drug release in 60 min. Process yield, agglomerate size, and drug release were affected by amount of PVP K 30 and HPMC E50. The presence of drug microcrystal was confirmed by SEM, whereas FTIR study indicated no chemical change. Increase in drug solubility was attributed to change of crystalline drug to amorphous form that is evident in DSC and XRD. Crystallo-co-agglomeration can be adopted as an important approach for increasing the solubility and dissolution of poorly soluble drug.

Topical formulations with superoxide dismutase: influence of formulation composition on physical stability and enzymatic activity.

Science.gov (United States)

Di Mambro, Valéria M; Borin, Maria F; Fonseca, Maria J V

2003-04-24

Three different topical formulations were supplemented with superoxide dismutase (SOD) and evaluated concerning physical and chemical stabilities in order to determine the most stable formulation that would maintain SOD activity. Physical stability was evaluated by storing the formulation at room temperature, and at 37 and 45 degrees C for 28 days. Samples were collected at 7-day intervals for assessment of rheological behavior. Chemical stability was evaluated by the measurement of enzymatic activity in formulations stored at room temperature and at 45 degrees C for 75 days. The formulations showed a pseudoplastic behavior, with a flow index of less than 1. There was no significant difference in the initial values of flow index, hysteresis loop or minimum apparent viscosity. The simple emulsion and the one stabilized with hydroxyethylcellulose showed decreased viscosity by the 21st day and with higher temperature, but no significant changes concerning the presence of SOD. Although there were no significant changes concerning storage time or temperature, the formulation stabilized with hydroxyethylcellulose showed a marked loss of SOD activity. The addition of SOD to the formulations studied did not affect their physical stability. Simple emulsions or emulsions stabilized with carboxypolymethylene seem to be better bases for enzyme addition than emulsion stabilized with hydroxyethylcellulose.

DNA/RNA-based formulations for treatment of breast cancer.

Science.gov (United States)

Xie, Zhaolu; Zeng, Xianghui

2017-12-01

To develop a successful formulation for the gene therapy of breast cancer, an effective therapeutic nucleic acid and a proper delivery system are essential. Increased understanding of breast cancer, and developments in biotechnology, material science and nanotechnology have provided a major impetus in the development of effective formulations for the gene therapy of breast cancer. Areas covered: We discuss DNA/RNA-based formulations that can inhibit the growth of breast cancer cells and control the progress of breast cancer. Targets for the gene therapy of breast cancer, DNA/RNA-based therapeutics and delivery systems are summarized. And examples of successful DNA/RNA-based formulations for breast cancer gene therapy are reviewed. Expert opinion: Several challenges remain in developing effective DNA/RNA-based formulations for treatment of breast cancer. Firstly, most of the currently utilized targets are not effective enough as monotherapy for breast cancer. Secondly, the requirements for co-delivery system make the preparation of formulation more complicated. Thirdly, nanoparticles with the modification of tumor-targeting ligands could be more unstable in circulation and normal tissues. Lastly, immune responses against the viral vectors are unfavorable for the gene therapy of breast cancer because of the damage to the host and the impaired therapeutic ability.

Exposure to hazardous volatile organic compounds, PM 10 and CO while walking along streets in urban Guangzhou, China

Science.gov (United States)

Zhao, Lirong; Wang, Xinming; He, Qiusheng; Wang, Hao; Sheng, Guoying; Chan, L. Y.; Fu, Jiamo; Blake, D. R.

Toxic air pollutants in street canyons are important issues concerning public health especially in some large Asian cities like Guangzhou. In 1998 Guangzhou citizens used public transportation modes, with a majority commuting on foot (42%) or by bicycle (22%). Of the pedestrians, 57% were either senior citizens or students. In the present study, we measured toxic air pollutants while walking along urban streets in Guangzhou to evaluate pedestrian exposure. Volatile organic compounds (VOCs) were collected with sorbent tubes, and PM 10 and CO were measured simultaneously with portable analyzers. Our results showed that pedestrian exposure to PM 10 (with an average of 303 μg m -3 for all samples) and some toxic VOCs (for example, benzene) was relatively high. Monocyclic aromatic hydrocarbons were found to be the most abundant VOCs, and 71% of the samples had benzene levels higher than 30 μg m -3. Benzene, PM 10 and CO in walk-only streets were significantly lower ( ptransportation modes (bus and subway). The good correlations between BTEX, PM 10 and CO in the streets indicated that automotive emission might be their major source. Our study also showed that the risk to pedestrians due to air pollution was misinterpreted by the reported air quality index based on measurement of SO 2, NO x and PM 10 in the government monitoring stations. An urban roadside monitoring station might be needed by air quality monitoring networks in large Asian cities like Guangzhou, in order to survey exposure to air toxics in urban roadside microenvironments.

Co-exposure to lead increases the renal response to low levels of cadmium in metallurgy workers.

Science.gov (United States)

Hambach, R; Lison, D; D'Haese, P C; Weyler, J; De Graef, E; De Schryver, A; Lamberts, L V; van Sprundel, M

2013-10-24

Research on the effect of co-exposure to Cd and Pb on the kidney is scarce. The objective of the present study was to assess the effect of co-exposure to these metals on biomarkers of early renal effect. Cd in blood (Cd-B), Cd in urine (Cd-U), Pb in blood (Pb-B) and urinary renal biomarkers, i.e., microalbumin (μ-Alb), beta-2-microglobulin (β₂-MG), retinol binding protein (RBP), N-acetyl-β-d-glucosaminidase (NAG), intestinal alkaline phosphatase (IAP) were measured in 122 metallurgic refinery workers examined in a cross-sectional survey. The median Cd-B, Cd-U, Pb-B were: 0.8 μg/l (IQR = 0.5, 1.2), 0.5 μg/g creatinine (IQR = 0.3, 0.8) and 158.5 μg/l (IQR = 111.0, 219.3), respectively. The impact of Cd-B on the urinary excretion of NAG and IAP was only evident among workers with Pb-B concentrations ≥ 75th percentile. The association between Cd-U and the renal markers NAG and RBP was also evidenced when Pb-B ≥ 75th percentile. No statistically significant interaction terms were observed for the associations between Cd-B or Cd-U and the other renal markers under study (i.e., μ-Alb and β2-MG). Our findings indicate that Pb increases the impact of Cd exposure on early renal biomarkers. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Duration and Timing of Exposure to Neighborhood Poverty and the Risk of Adolescent Parenthood

Science.gov (United States)

Wodtke, Geoffrey T.

2013-01-01

Theory suggests that the impact of neighborhood poverty depends on both the duration and timing of exposure. Previous research, however, does not properly analyze the sequence of neighborhoods to which children are exposed throughout the early life course. This study investigates the effects of different longitudinal patterns of exposure to disadvantaged neighborhoods on the risk of adolescent parenthood. It follows a cohort of children in the PSID from age 4 to 19 and uses novel methods for time-varying exposures that overcome critical limitations of conventional regression when selection processes are dynamic. Results indicate that sustained exposure to poor neighborhoods substantially increases the risk of becoming a teen parent and that exposure to neighborhood poverty during adolescence may be more consequential than exposure earlier during childhood. PMID:23720166

Response of needle dark respiration of Pinus koraiensis and Pinus sylvestriformis to elevated CO2 concentrations for four growing seasons' exposure

Institute of Scientific and Technical Information of China (English)

ZHOU YuMei; HAN ShiJie; ZHANG HaiSen; XIN LiHua; ZHENG JunQiang

2007-01-01

The long-term effect of elevated CO2 concentrations on needle dark respiration of two coniferous species-Pinus koraiensis and Pinus sylvestriformis on the Changbai Mountain was investigated using open-top chambers. P. Koraiensis and P. Sylvestriformis were exposed to 700,500μmol·mol-1 CO2 and ambient CO2(approx.350 μmol·mol-1)for four growing seasons. Needle dark respiration was measurd during the second, third and fourth growing seasons' exposure to elevated CO2.The results showed that needle dark respiration rate increased for P. Koraiensis and P. Sylvestriformis grown at elevated CO2 concentrations during the second growing season, could be attributed to the change of carbohydrate and/or nitrogen content of needles. Needle dark respiration of P. Koraiensis was stimulated and that of P. Sylvestriformis was inhibited by elevated CO2 concentrations during the third growing season. Different response of the two tree species to elevated CO2 mainly resulted from the difference in the growth rate. Elevated CO2 concentrations inhibited needle dark respiration of both P. Koraiensis and P. Sylvestriformis during the fourth growing season. There was consistent trend between the short-term effect and the long-term effect of elevated CO2 on needle dark respiration in P. Sylvestriformis during the third growing season by changing measurement CO2 concentrations. However, the short-term effect was different from the long-term effect for P. Koraiensis. Response of dark respiration of P. Koraiensis and P. Sylvestriformis to elevated CO2 concentrations was related to the treatment time of CO2 and the stage of growth and development of plant. The change of dark respiration for the two tree species was determined by the direct effect of CO2 and long-term acclimation. The prediction of the long-term response of needle dark respiration to elevated CO2 concentration based on the short-term response is in dispute.

interactive effect of cowpea variety, dose and exposure time

African Journals Online (AJOL)

ACSS

variety (V), exposure time (T) and dose (D) on the tolerance of C. maculatus to both plant materials. The effect ... laboratories and institutions of higher education in several West .... Each value is the mean±S.E of 20 cowpea seeds. Means ...

Exposure to elevated pCO2 does not exacerbate reproductive suppression of Aurelia aurita jellyfish polyps in low oxygen environments

KAUST Repository

Treible, LM

2017-08-15

Eutrophication-induced hypoxia is one of the primary anthropogenic threats to coastal ecosystems. Under hypoxic conditions, a deficit of O2 and a surplus of CO2 will concurrently decrease pH, yet studies of hypoxia have seldom considered the potential interactions with elevated pCO2 (reduced pH). Previous studies on gelatinous organisms concluded that they are fairly robust to low oxygen and reduced pH conditions individually, yet the combination of stressors has only been examined for ephyrae. The goals of this study were to determine the individual and interactive effects of hypoxia and elevated pCO2 on the asexual reproduction and aerobic respiration rates of polyps of the scyphozoan Aurelia aurita during a manipulative experiment that ran for 36 d. pCO2 and pO2 were varied on a diel basis to closely mimic the diel conditions observed in the field. Exposure to low dissolved oxygen (DO) reduced asexual budding of polyps by ~50% relative to control conditions. Under hypoxic conditions, rates of respiration were elevated during an initial acclimation period (until Day 8), but respiration rates did not differ between DO levels under prolonged exposure. There was no significant effect of increased pCO2 on either asexual reproduction or aerobic respiration, suggesting that elevated pCO2 (reduced pH) did not exacerbate the negative reproductive effects of hypoxia on A. aurita polyps.

Exposure to elevated pCO2 does not exacerbate reproductive suppression of Aurelia aurita jellyfish polyps in low oxygen environments

KAUST Repository

Treible, LM; Pitt, KA; Klein, SG; Condon, RH

2017-01-01

Eutrophication-induced hypoxia is one of the primary anthropogenic threats to coastal ecosystems. Under hypoxic conditions, a deficit of O2 and a surplus of CO2 will concurrently decrease pH, yet studies of hypoxia have seldom considered the potential interactions with elevated pCO2 (reduced pH). Previous studies on gelatinous organisms concluded that they are fairly robust to low oxygen and reduced pH conditions individually, yet the combination of stressors has only been examined for ephyrae. The goals of this study were to determine the individual and interactive effects of hypoxia and elevated pCO2 on the asexual reproduction and aerobic respiration rates of polyps of the scyphozoan Aurelia aurita during a manipulative experiment that ran for 36 d. pCO2 and pO2 were varied on a diel basis to closely mimic the diel conditions observed in the field. Exposure to low dissolved oxygen (DO) reduced asexual budding of polyps by ~50% relative to control conditions. Under hypoxic conditions, rates of respiration were elevated during an initial acclimation period (until Day 8), but respiration rates did not differ between DO levels under prolonged exposure. There was no significant effect of increased pCO2 on either asexual reproduction or aerobic respiration, suggesting that elevated pCO2 (reduced pH) did not exacerbate the negative reproductive effects of hypoxia on A. aurita polyps.

A population-based exposure assessment methodology for carbon monoxide: Development of a carbon monoxide passive sampler and occupational dosimeter

Energy Technology Data Exchange (ETDEWEB)

Apte, Michael G. [Univ. of California, Berkeley, CA (United States)

1997-09-01

Two devices, an occupational carbon monoxide (CO) dosimeter (LOCD), and an indoor air quality (IAQ) passive sampler were developed for use in population-based CO exposure assessment studies. CO exposure is a serious public health problem in the U.S., causing both morbidity and mortality (lifetime mortality risk approximately 10{sup -4}). Sparse data from population-based CO exposure assessments indicate that approximately 10% of the U.S. population is exposed to CO above the national ambient air quality standard. No CO exposure measurement technology is presently available for affordable population-based CO exposure assessment studies. The LOCD and IAQ Passive Sampler were tested in the laboratory and field. The palladium-molybdenum based CO sensor was designed into a compact diffusion tube sampler that can be worn. Time-weighted-average (TWA) CO exposure of the device is quantified by a simple spectrophotometric measurement. The LOCD and IAQ Passive Sampler were tested over an exposure range of 40 to 700 ppm-hours and 200 to 4200 ppm-hours, respectively. Both devices were capable of measuring precisely (relative standard deviation <20%), with low bias (<10%). The LOCD was screened for interferences by temperature, humidity, and organic and inorganic gases. Temperature effects were small in the range of 10°C to 30°C. Humidity effects were low between 20% and 90% RH. Ethylene (200 ppm) caused a positive interference and nitric oxide (50 ppm) caused a negative response without the presence of CO but not with CO.

Influence of different anoxic time exposures on active biomass, protozoa and filamentous bacteria in activated sludge.

Science.gov (United States)

Rodriguez-Perez, S; Fermoso, F G; Arnaiz, C

Medium-sized wastewater treatment plants are considered too small to implement anaerobic digestion technologies and too large for extensive treatments. A promising option as a sewage sludge reduction method is the inclusion of anoxic time exposures. In the present study, three different anoxic time exposures of 12, 6 and 4 hours have been studied to reduce sewage sludge production. The best anoxic time exposure was observed under anoxic/oxic cycles of 6 hours, which reduced 29.63% of the biomass production compared with the oxic control conditions. The sludge under different anoxic time exposures, even with a lower active biomass concentration than the oxic control conditions, showed a much higher metabolic activity than the oxic control conditions. Microbiological results suggested that both protozoa density and abundance of filamentous bacteria decrease under anoxic time exposures compared to oxic control conditions. The anoxic time exposures 6/6 showed the highest reduction in both protozoa density, 37.5%, and abundance of filamentous bacteria, 41.1%, in comparison to the oxic control conditions. The groups of crawling ciliates, carnivorous ciliates and filamentous bacteria were highly influenced by the anoxic time exposures. Protozoa density and abundance of filamentous bacteria have been shown as promising bioindicators of biomass production reduction.

Child and adolescent exposure to food and beverage brand appearances during prime-time television programming.

Science.gov (United States)

Speers, Sarah E; Harris, Jennifer L; Schwartz, Marlene B

2011-09-01

The food industry disproportionately markets to young people through product placements. Children and adolescents may be more susceptible to these disguised persuasive attempts. Quantify incidence and youth exposure to food and beverage brand appearances within shows on prime-time TV. Data on the number of food, beverage, and restaurant brand appearances within shows during prime-time programming in 2008 were purchased from Nielsen and analyzed by product category and company in 2010. Exposure to these brand appearances by children, adolescents, and adults were examined and compared with exposure to prime-time TV advertisements for the same categories and companies using additional Nielsen data. Food, beverage, and restaurant brands appeared a total of 35,000 times within prime-time TV programming examined by Nielsen in 2008. Regular soft drinks, traditional restaurants (i.e., not quickserve), and energy/sports drinks made up 60% of all brand appearances. Young people viewed relatively few of these appearances with one notable exception. Coca-Cola products were seen 198 times by the average child and 269 times by the average adolescent during prime-time shows over the year, accounting for 70% of child exposure and 61% of adolescent exposure to brand appearances. One show, American Idol, accounted for more than 95% of these exposures. Exposure of children to Coca-Cola products through traditional advertisements was much less common. Brand appearances for most food industry companies, except for Coca-Cola, are relatively rare during prime-time programming with large youth audiences. Coca-Cola has pledged to refrain from advertising to children, yet the average child views almost four Coke appearances on prime-time TV every week. This analysis reveals a substantial, potential loophole in current food industry self-regulatory pledges to advertise only better-for-you foods to children. Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc

Seasonal response of photosynthetic electron transport and energy dissipation in the eighth year of exposure to elevated atmospheric CO2 (FACE) in Pinus taeda (loblolly pine)

International Nuclear Information System (INIS)

Logan, B.A.; Combs, A.; Kent, R.; Stanley, L.; Myers, K.; Tissue, D.T.; Western Sydney Univ., Richmond, NSW

2009-01-01

This study investigated the biological adaptation of loblolly pine following long-term seasonal exposure to elevated carbon dioxide (CO 2 ) partial pressures (pCO 2 ). Exposure to elevated atmospheric CO 2 (pCO 2 ) usually results in significant stimulation in light-saturated rates of photosynthetic CO 2 assimilation. Plants are protected against photoinhibition by biochemical processes known as photoprotection, including energy dissipation, which converts excess absorbed light energy into heat. This study was conducted in the eighth year of exposure to elevated pCO 2 at the Duke FACE site. The effect of elevated pCO 2 on electron transport and energy dissipation in the pine trees was examined by coupling the analyses of the capacity for photosynthetic oxygen (O 2 ) evolution, chlorophyll fluorescence emission and photosynthetic pigment composition with measurements of net photosynthetic CO 2 assimilation (Asat). During the summer growing season, Asat was 50 per cent higher in current-year needles and 24 per cent higher in year-old needles in elevated pCO 2 in comparison with needles of the same age cohort in ambient pCO 2 . Thus, older needles exhibited greater photosynthetic down-regulation than younger needles in elevated pCO 2 . In the winter, Asat was not significantly affected by growth pCO 2 . Asat was lower in winter than in summer. Growth at elevated pCO 2 had no significant effect on the capacity for photosynthetic oxygen evolution, photosystem 2 efficiencies, chlorophyll content or the size and conversion state of the xanthophyll cycle, regardless of season or needle age. There was no evidence that photosynthetic electron transport or photoprotective energy dissipation responded to compensate for the effects of elevated pCO 2 on Calvin cycle activity. 73 refs., 4 figs

Energy policy formulation and energy administration in South Africa

International Nuclear Information System (INIS)

Du Plessis, S.J.P.

1983-01-01

The evolvement of the governmental energy administrative mechanisms is discussed. Energy policy formulation and the role of the Department of Mineral and Energy Affairs in this regard are outlined. The energy administrative process, with reference to various energy carriers and specific spheres of the South African energy economy is discussed. It is indicated that close co-operation between the public and private energy sectors should result in mutual understanding of each others' practical problems and objectives, and should contribute towards the process of judicious energy policy formulation and administration in the interests of the national well-being

How to statistically analyze nano exposure measurement results: Using an ARIMA time series approach

NARCIS (Netherlands)

Klein Entink, R.H.; Fransman, W.; Brouwer, D.H.

2011-01-01

Measurement strategies for exposure to nano-sized particles differ from traditional integrated sampling methods for exposure assessment by the use of real-time instruments. The resulting measurement series is a time series, where typically the sequential measurements are not independent from each

Exposure Time Distributions reveal Denitrification Rates along Groundwater Flow Path of an Agricultural Unconfined Aquifer

Science.gov (United States)

Kolbe, T.; Abbott, B. W.; Thomas, Z.; Labasque, T.; Aquilina, L.; Laverman, A.; Babey, T.; Marçais, J.; Fleckenstein, J. H.; Peiffer, S.; De Dreuzy, J. R.; Pinay, G.

2016-12-01

Groundwater contamination by nitrate is nearly ubiquitous in agricultural regions. Nitrate is highly mobile in groundwater and though it can be denitrified in the aquifer (reduced to inert N2 gas), this process requires the simultaneous occurrence of anoxia, an electron donor (e.g. organic carbon, pyrite), nitrate, and microorganisms capable of denitrification. In addition to this the ratio of the time groundwater spent in a denitrifying environment (exposure time) to the characteristic denitrification reaction time plays an important role, because denitrification can only occur if the exposure time is longer than the characteristic reaction time. Despite a long history of field studies and numerical models, it remains exceedingly difficult to measure or model exposure times in the subsurface at the catchment scale. To approach this problem, we developed a unified modelling approach combining measured environmental proxies with an exposure time based reactive transport model. We measured groundwater age, nitrogen and sulfur isotopes, and water chemistry from agricultural wells in an unconfined aquifer in Brittany, France, to quantify changes in nitrate concentration due to dilution and denitrification. Field data showed large differences in nitrate concentrations among wells, associated with differences in the exposure time distributions. By constraining a catchment-scale characteristic reaction time for denitrification with water chemistry proxies and exposure times, we were able to assess rates of denitrification along groundwater flow paths. This unified modeling approach is transferable to other catchments and could be further used to investigate how catchment structure and flow dynamics interact with biogeochemical processes such as denitrification.

Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of human lung epithelial cells and macrophages

DEFF Research Database (Denmark)

Jantzen, Kim; Roursgaard, Martin; Madsen, Claus Desler

2012-01-01

Studies in mono-culture of cells have shown that diesel exhaust particles (DEPs) increase the production of reactive oxygen species (ROS) and oxidative stress-related damage to DNA. However, the level of particle-generated genotoxicity may depend on interplay between different cell types, e.g. lung...... treatment with standard reference DEPs, SRM2975 and SRM1650b. The exposure to DEPs did not affect the colony-forming ability of A549 cells in co-culture with THP-1a cells. The DEPs generated DNA strand breaks and oxidatively damaged DNA, measured using the alkaline comet assay as formamidopyrimidine...... relationship between levels of respiration and ROS production. In conclusion, exposure of mono-cultured cells to DEPs generated oxidative stress to DNA, whereas co-cultures with macrophages had lower levels of oxidatively damaged DNA than A549 epithelial cells....

Persistence of Positive Carryover Effects in the Oyster, Saccostrea glomerata, following Transgenerational Exposure to Ocean Acidification.

Directory of Open Access Journals (Sweden)

Laura M Parker

Full Text Available Ocean acidification (OA is predicted to have widespread implications for marine organisms, yet the capacity for species to acclimate or adapt over this century remains unknown. Recent transgenerational studies have shown that for some marine species, exposure of adults to OA can facilitate positive carryover effects to their larval and juvenile offspring that help them to survive in acidifying oceanic conditions. But whether these positive carryover effects can persist into adulthood or the next generation is unknown. Here we tested whether positive carryover effects found in larvae of the oyster, Saccostrea glomerata following transgenerational exposure to elevated CO2, could persist into adulthood and whether subsequent transgenerational exposure of adults to elevated CO2 would facilitate similar adaptive responses in the next generation of larvae and juveniles. Following our previous transgenerational exposure of parental adults and first generation (F1 larvae to ambient (385 μatm and elevated (856 μatm CO2, newly settled F1 juveniles were transferred to the field at ambient CO2 for 14 months, until they reached reproductive maturity. At this time, the F1 adults were returned to the laboratory and the previous transgenerational CO2 exposure was repeated to produce F2 offspring. We found that the capacity of adults to regulate extracellular pH at elevated CO2 was improved if they had a prior history of transgenerational exposure to elevated CO2. In addition, subsequent transgenerational exposure of these adults led to an increase in the resilience of their larval and juvenile offspring. Offspring with a history of transgenerational exposure to elevated CO2 had a lower percentage abnormality, faster development rate, faster shell growth and increased heart rate at elevated CO2 compared with F2 offspring with no prior history of exposure to elevated CO2. Our results suggest that positive carryover effects originating during parental and larval

Spasmolytic effect of traditional herbal formulation on guinea pig ileum

Directory of Open Access Journals (Sweden)

Dushyant Kumar

2015-01-01

Full Text Available Background: The herbal formulation consisting of Andrographis paniculata Nees., Cassia fistula L., Foeniculum vulgare Mill. and Cuminum cyminum L. is widely used by the local traditional practitioners in rural Northern Karnataka for spasmodic abdominal pain. Objective: The present study was undertaken to evaluate safety and spasmolytic effect of poly-herbal formulation. Materials and Methods: Acute toxicity studies were carried out in Swiss mice, as per the Organization for Economic Co-operation and Development (OECD guidelines. The spasmolytic activity of the formulation was studied in isolated guinea pig ileum model using histamine and acetylcholine as agonists. The data were analyzed by one-way ANOVA, followed by Dunnetts post-hoc test and P ≤ 0.05 was considered as significant. Results: The formulation did not show any adverse toxic effects and found to be safe. It also showed significant (P < 0.05 relaxation in different agonist like histamine and acetylcholine-induced contractions in guinea pig ileum. Conclusions: Antispasmodic activity of the herbal formulation can be attributed to its atropine-like activity. The present findings, therefore, support its utility in spasmodic abdominal pain.

Effect of nickel and iron co-exposure on human lung cells

International Nuclear Information System (INIS)

Salnikow, Konstantin; Li Xiaomei; Lippmann, Morton

2004-01-01

Exposure to ambient air particulate matter (PM) is associated with increased mortality and morbidity in susceptible populations. The epidemiological data also suggest a relationship between PM air pollution and impairment of cardiopulmonary function. The mechanisms that may be responsible for these effects are not fully understood and are likely related to perturbations of cellular and molecular functions. One type of PM, residual oil fly ash (ROFA), is of particular interest. ROFA does not contain much organic material, but does contain relatively high quantities of transition metals, predominantly nickel, vanadium, and iron, as well as black carbon and sulfates. In this study, we investigated the effect of two metals (iron and nickel) on the induction of 'hypoxia-like' stress and the production of interleukins (ILs) in minimally transformed human airway epithelial cells (1HAEo - ). We found that exposure to soluble nickel sulfate results in the induction of hypoxia-inducible genes and IL-8 production by the 1HAEo - cells. The simultaneous addition of iron in either ferric or ferrous form and nickel completely inhibited IL-8 production and had no effect on 'hypoxia-like' stress caused by nickel, suggesting the existence of two different pathways for the induction 'hypoxia-like' stress and IL-8 production. The effect of nickel was not related to the blocking of iron entry into cells since the level of intracellular iron was not affected by co-exposure with nickel. The obtained data indicate that nickel can induce different signaling pathways with or without interference with iron metabolism. Our observations suggest that in some cases the excess of iron in PM can cancel the effects of nickel

Bedtime and evening light exposure influence circadian timing in preschool-age children: A field study

Directory of Open Access Journals (Sweden)

Lameese D. Akacem

2016-11-01

Full Text Available Light exposure and sleep timing are two factors that influence inter-individual variability in the timing of the human circadian clock. The aim of this study was to quantify the degree to which evening light exposure predicts variance in circadian timing over and above bedtime alone in preschool children. Participants were 21 children ages 4.5–5.0 years (4.7±0.2 years; 9 females. Children followed their typical sleep schedules for 4 days during which time they wore a wrist actigraph to assess sleep timing and a pendant light meter to measure minute-by-minute illuminance levels in lux. On the 5th day, children participated in an in-home dim-light melatonin onset (DLMO assessment. Light exposure in the 2 h before bedtime was averaged and aggregated across the 4 nights preceding the DLMO assessment. Mean DLMO and bedtime were 19:22±01:04 and 20:07±00:46, respectively. Average evening light exposure was 710.1±1418.2 lux. Children with later bedtimes (lights-off time had more delayed melatonin onset times (r=0.61, p=0.002. Evening light exposure was not independently associated with DLMO (r=0.32, p=0.08; however, a partial correlation between evening light exposure and DLMO when controlling for bedtime yielded a positive correlation (r=0.46, p=0.02. Bedtime explained 37.3% of the variance in the timing of DLMO, and evening light exposure accounted for an additional 13.3% of the variance. These findings represent an important step in understanding factors that influence circadian phase in preschool-age children and have implications for understanding a modifiable pathway that may underlie late sleep timing and the development of evening settling problems in early childhood.

Extended-Release Once-Daily Formulation of Tofacitinib: Evaluation of Pharmacokinetics Compared With Immediate-Release Tofacitinib and Impact of Food.

Science.gov (United States)

Lamba, Manisha; Wang, Rong; Fletcher, Tracey; Alvey, Christine; Kushner, Joseph; Stock, Thomas C

2016-11-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. An extended-release (XR) formulation has been designed to provide a once-daily (QD) dosing option to patients to achieve comparable pharmacokinetic (PK) parameters to the twice-daily immediate-release (IR) formulation. We conducted 2 randomized, open-label, phase 1 studies in healthy volunteers. Study A characterized single-dose and steady-state PK of tofacitinib XR 11 mg QD and intended to demonstrate equivalence of exposure under single-dose and steady-state conditions to tofacitinib IR 5 mg twice daily. Study B assessed the effect of a high-fat meal on the bioavailability of tofacitinib from the XR formulation. Safety and tolerability were monitored in both studies. In study A (N = 24), the XR and IR formulations achieved time to maximum plasma concentration at 4 hours and 0.5 hours postdose, respectively; terminal half-life was 5.9 hours and 3.2 hours, respectively. Area under plasma concentration-time curve (AUC) and maximum plasma concentration (C max ) after single- and multiple-dose administration were equivalent between the XR and IR formulations. In study B (N = 24), no difference in AUC was observed for fed vs fasted conditions. C max increased by 27% under the fed state. On repeat administration, negligible accumulation (Tofacitinib administration as an XR or IR formulation was generally well tolerated in these studies. © 2016, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Exposure time independent summary statistics for assessment of drug dependent cell line growth inhibition.

Science.gov (United States)

Falgreen, Steffen; Laursen, Maria Bach; Bødker, Julie Støve; Kjeldsen, Malene Krag; Schmitz, Alexander; Nyegaard, Mette; Johnsen, Hans Erik; Dybkær, Karen; Bøgsted, Martin

2014-06-05

In vitro generated dose-response curves of human cancer cell lines are widely used to develop new therapeutics. The curves are summarised by simplified statistics that ignore the conventionally used dose-response curves' dependency on drug exposure time and growth kinetics. This may lead to suboptimal exploitation of data and biased conclusions on the potential of the drug in question. Therefore we set out to improve the dose-response assessments by eliminating the impact of time dependency. First, a mathematical model for drug induced cell growth inhibition was formulated and used to derive novel dose-response curves and improved summary statistics that are independent of time under the proposed model. Next, a statistical analysis workflow for estimating the improved statistics was suggested consisting of 1) nonlinear regression models for estimation of cell counts and doubling times, 2) isotonic regression for modelling the suggested dose-response curves, and 3) resampling based method for assessing variation of the novel summary statistics. We document that conventionally used summary statistics for dose-response experiments depend on time so that fast growing cell lines compared to slowly growing ones are considered overly sensitive. The adequacy of the mathematical model is tested for doxorubicin and found to fit real data to an acceptable degree. Dose-response data from the NCI60 drug screen were used to illustrate the time dependency and demonstrate an adjustment correcting for it. The applicability of the workflow was illustrated by simulation and application on a doxorubicin growth inhibition screen. The simulations show that under the proposed mathematical model the suggested statistical workflow results in unbiased estimates of the time independent summary statistics. Variance estimates of the novel summary statistics are used to conclude that the doxorubicin screen covers a significant diverse range of responses ensuring it is useful for biological

Different gene expression of Normal lymphobloastoid cells which exposure to different dose of 60Co γ-ray

International Nuclear Information System (INIS)

Xiao Yao; Yang Jian; Gao Xian; Qin Yanghua; Sun Ding; Hai Ling

2008-01-01

Objective: To study on the gene expression of normal lymphoblastoid cells(AHH-1) which exposure to difference dose of 60 Co γ-ray, analyses the essential different biological effect.. Methods Human AHH-1 normal line was irradiated by 60 Co γ-rays. Used human cDNA microarray to develop the transcriptional levels of the genes by hybridizing the mRNA of cells 8 h after exposured in different dose and the control cells. Cluster analysis, discrimination and bolting were used to filter the effective genes of differential expression. Results The results of data analysis showed 23 genes of differential expression closely related to biological effect of 2.0 Gy radiation, 5 genes express changed only by 0.5 Gy radiation, 5 genes express apparently both in 2.0 Gy and 0.5 Gy radiation. Conclusion: The different dose γ-rays radiation-induced significant changes in gene expression, such as PAPLN, TP53INP1, PTENP1, FOS and TPR seem to be some important components of cellular radioresponse. (authors)

Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation.

Science.gov (United States)

Johannsson, G; Nilsson, A G; Bergthorsdottir, R; Burman, P; Dahlqvist, P; Ekman, B; Engström, B E; Olsson, T; Ragnarsson, O; Ryberg, M; Wahlberg, J; Biller, B M K; Monson, J P; Stewart, P M; Lennernäs, H; Skrtic, S

2012-02-01

Patients with treated adrenal insufficiency (AI) have increased morbidity and mortality rate. Our goal was to improve outcome by developing a once-daily (OD) oral hydrocortisone dual-release tablet with a more physiological exposure-time cortisol profile. The aim was to compare pharmacokinetics and metabolic outcome between OD and the same daily dose of thrice-daily (TID) dose of conventional hydrocortisone tablets. We conducted an open, randomized, two-period, 12-wk crossover multicenter trial with a 24-wk extension at five university hospital centers. The trial enrolled 64 adults with primary AI; 11 had concomitant diabetes mellitus (DM). The same daily dose of hydrocortisone was administered as OD dual-release or TID. We evaluated cortisol pharmacokinetics. Compared with conventional TID, OD provided a sustained serum cortisol profile 0-4 h after the morning intake and reduced the late afternoon and the 24-h cortisol exposure. The mean weight (difference = -0.7 kg, P = 0.005), systolic blood pressure (difference = -5.5 mm Hg, P = 0.0001) and diastolic blood pressure (difference: -2.3 mm Hg; P = 0.03), and glycated hemoglobin (absolute difference = -0.1%, P = 0.0006) were all reduced after OD compared with TID at 12 wk. Compared with TID, a reduction in glycated hemoglobin by 0.6% was observed in patients with concomitant DM during OD (P = 0.004). The OD dual-release tablet provided a more circadian-based serum cortisol profile. Reduced body weight, reduced blood pressure, and improved glucose metabolism were observed during OD treatment. In particular, glucose metabolism improved in patients with concomitant DM.

Population exposure to ultraviolet radiation in Finland 1920-1995: Exposure trends and a time-series analysis of exposure and cutaneous melanoma incidence

International Nuclear Information System (INIS)

Kojo, Katja; Jansen, Christer T.; Nybom, Pia; Huurto, Laura; Laihia, Jarmo; Ilus, Taina; Auvinen, Anssi

2006-01-01

Ultraviolet radiation (UVR) is the principal cause of cutaneous malignant melanoma (CMM). However, the relation between CMM and UVR exposure is not clear. We present the trends of population exposure to UVR and conduct a time-series analysis of the relation between UVR exposure and incidence of CMM. Data on CMM incidence were obtained from the Finnish Cancer Registry. Clothing coverage of the body was scored from archival photographs and the proportion of uncovered skin was used as a measure of solar exposure. Information on the number of sunny resort holidays, duration of annual holidays, and sunscreen sales were obtained from various sources. Exposed skin area doubled from 1920 to 1985. The average duration of annual holidays increased 30-fold. The number of sunny resort holidays and the sales of sunscreens increased rapidly from 1980. CMM was most strongly associated with solar exposure of 5-19 years earlier. There is a considerable decrease in clothing coverage during the 20th century. UVR exposure preceding CMM occurrence 4 years or less does not appear relevant, whereas the period 5-19 years prior to CMM occurrence might be the most relevant period. However, findings of ecological studies may not be applicable at the individual level

Formulation studies on stability of solid-state proteases for detergent applications

DEFF Research Database (Denmark)

Ay, Suzan Biran; Jensen, Anker Degn; Kiil, Søren

2012-01-01

Enzymes are one of the most important components in the laundry detergents. They effectively contribute to the washing process by decreasing energy and water consumption, reducing environmental load of detergent products, leaving non-toxic water effluents and providing fabric care. Ensuring prope...... the antioxidant homogeneously with the enzyme was found to provide a better protection than coating the salt as a separate layer due to crack formation and/or deliquescence of Na2S2O3 at high humidity.......-dried detergent protease, Savinase, were determined in a newly developed experimental setup, providing rapid assessment of solid-state enzyme stability under oxidizing conditions. The method was based on exposure of an enzyme column to known concentrations of H2O2 (g) and humidity in a thermally stabilized...... that, the inactivation was caused by single-oxidation of the enzyme at Met222 residue. Formulation studies revealed that, having an anti-oxidative property,Na2S2O3 had a better activity-preservation effect compared to Na2CO3, retaining 80% and 60% residual activity, respectively. In addition, mixing...

Long term deactivation test of high dust SCR catalysts by straw co-firing

Energy Technology Data Exchange (ETDEWEB)

Weigang Lin; Degn Jensen, A.; Bjerkvig, J.

2009-12-15

The consequences of carbon dioxide induced global warming cause major concern worldwide. The consumption of energy produced with fossil fuels is the major factor that contributes to the global warming. Biomass is a renewable energy resource and has a nature of CO{sub 2} neutrality. Co-combustion of biomass in existing coal fired power plants can maintain high efficiency and reduce the emission of CO{sub 2} at same time. However, one of the problems faced by co-firing is deactivation of the SCR catalysts. Understanding of the mechanisms of deactivation of the catalyst elements at co-firing conditions is crucial for long term runs of the power plants. Twenty six SCR catalyst elements were exposed at two units (SSV3 and SSV4) in the Studstrup Power Plant for a long period. Both units co-fire coal and straw with a typical fraction of 8-10% straw on an energy basis during co-firing. SSV4 unit operated in co-firing mode most of the time; SSV3 unit co-fired straw half of the operating time. The main objective of this PSO-project is to gain knowledge of a long term influence on catalyst activity when co-firing straw in coal-fired power plants, thus, to improve the basis for operating the SCR-plants for NO{sub x}-reduction. The exposure time of the applied catalyst elements (HTAS and BASF) varied from approximately 5000 to 19000 hours in the power plant by exchanging the element two times. The activity of all elements was measured before and after exposure in a bench scale test rig at the Department of Chemical and Biochemical Engineering, Technical University of Denmark. The results show that the activity, estimated by exclusion of channel clogging of the elements, decreases gradually with the total exposure time. It appears that the exposure time under co-firing condition has little effect on the deactivation of the catalyst elements and no sharp decrease of the activity was observed. The average deactivation rate of the catalyst elements is 1.6 %/1000 hours. SEM

Lack of the correlation between biochemical effects on rats and blood carboxyhemoglobin concentrations in various conditions of single acute exposure to carbon monoxide

Energy Technology Data Exchange (ETDEWEB)

Sokal, J.A.

1975-01-01

The relationship between conditions of exposure to carbon monoxide (CO) and biochemical effects was investigated in experiments on rats. The magnitude and the time of biochemical disturbances in the tissues resulting from two different exposures consisting of 1 vol. percent CO for 4 min and 0.4 vol. percent CO for 40 min respectively were compared. In both cases, at the end of exposure the same level of blood carboxyhemoglobin (COHb) (about 50 percent) was reached. The biochemical determinations in the blood (pH, glucose, lactate, pyruvate) and brain tissue (lactate, pyruvate) were carried out immediately after termination of the exposure and after the time periods of restitution. CO exposure resulted in a decreased blood pH, increased level of blood glucose, as well as that of lactate and pyruvate both in blood and brain tissue. These changes were much more pronounced following the longer-lesser exposure than after the shorter-intense one, although blood concentrations of COHb was the same. The observed phenomenon puts some light on the frequently encountered lack of the correlation between COHb level in blood and severity of CO intoxication in clinical practice.

Odors: appetizing or satiating? Development of appetite during odor exposure over time

NARCIS (Netherlands)

Ramaekers, M.G.; Boesveldt, S.; Lakemond, C.M.M.; Boekel, van M.A.J.S.; Luning, P.A.

2014-01-01

Background: Exposure to palatable food odors influences appetite responses, either promoting or inhibiting food intake. Possibly, food odors are appetizing after a short exposure (of circa 1–3¿min), but become satiating over time (circa 10–20¿min). Objective: To investigate the effect of odor

Formulating viscous hydrodynamics for large velocity gradients

International Nuclear Information System (INIS)

Pratt, Scott

2008-01-01

Viscous corrections to relativistic hydrodynamics, which are usually formulated for small velocity gradients, have recently been extended from Navier-Stokes formulations to a class of treatments based on Israel-Stewart equations. Israel-Stewart treatments, which treat the spatial components of the stress-energy tensor τ ij as dynamical objects, introduce new parameters, such as the relaxation times describing nonequilibrium behavior of the elements τ ij . By considering linear response theory and entropy constraints, we show how the additional parameters are related to fluctuations of τ ij . Furthermore, the Israel-Stewart parameters are analyzed for their ability to provide stable and physical solutions for sound waves. Finally, it is shown how these parameters, which are naturally described by correlation functions in real time, might be constrained by lattice calculations, which are based on path-integral formulations in imaginary time

Exploring the potential role of tungsten carbide cobalt (WC-Co) nanoparticle internalization in observed toxicity toward lung epithelial cells in vitro.

Science.gov (United States)

Armstead, Andrea L; Arena, Christopher B; Li, Bingyun

2014-07-01

Tungsten carbide cobalt (WC-Co) has been recognized as a workplace inhalation hazard in the manufacturing, mining and drilling industries by the National Institute of Occupational Safety and Health. Exposure to WC-Co is known to cause "hard metal lung disease" but the relationship between exposure, toxicity and development of disease remain poorly understood. To better understand this relationship, the present study examined the role of WC-Co particle size and internalization on toxicity using lung epithelial cells. We demonstrated that nano- and micro-WC-Co particles exerted toxicity in a dose- and time-dependent manner and that nano-WC-Co particles caused significantly greater toxicity at lower concentrations and shorter exposure times compared to micro-WC-Co particles. WC-Co particles in the nano-size range (not micron-sized) were internalized by lung epithelial cells, which suggested that internalization may play a key role in the enhanced toxicity of nano-WC-Co particles over micro-WC-Co particles. Further exploration of the internalization process indicated that there may be multiple mechanisms involved in WC-Co internalization such as actin and microtubule based cytoskeletal rearrangements. These findings support our hypothesis that WC-Co particle internalization contributes to cellular toxicity and suggest that therapeutic treatments inhibiting particle internalization may serve as prophylactic approaches for those at risk of WC-Co particle exposure. Copyright © 2014 Elsevier Inc. All rights reserved.

Metal dust exposure and lung function deterioration among steel workers: an exposure-response relationship.

Science.gov (United States)

Hamzah, Nurul Ainun; Mohd Tamrin, Shamsul Bahri; Ismail, Noor Hassim

2016-07-01

Metallic dust is a heterogeneous substance with respiratory sensitizing properties. Its long term exposure adversely affected lung function, thus may cause acute or chronic respiratory diseases. A cross-sectional study was conducted in a steel factory in Terengganu, Malaysia to assess the metal dust exposure and its relationship to lung function values among 184 workers. Metal dust concentrations values (Co, Cr, and Ni) for each worker were collected using air personal sampling. Lung function values (FEV 1 , FVC, and %FEV 1 /FVC) were determined using spirometer. Exposure to cobalt and chromium were 1-3 times higher than permissible exposure limit (PEL) while nickel was not exceeding the PEL. Cumulative of chromium was the predictor to all lung function values (FEV 1 , FVC, and %FEV 1 /FVC). Frequency of using mask was positively associated with FVC (Adj b = 0.263, P = 0.011) while past respiratory illnesses were negatively associated with %FEV 1 /FVC (Adj b = -1.452, P = 0.026). Only few workers (36.4%) were found to wear their masks all times during the working hours. There was an exposure-response relationship of cumulative metal dust exposure with the deterioration of lung function values. Improvement of control measures as well as proper and efficient use or personal protection equipment while at work could help to protect the respiratory health of workers.

Response of needle dark respiration of Pinus koraiensis and Pinus sylvestriformis to elevated CO2 concentra-tions for four growing seasons’ exposure

Institute of Scientific and Technical Information of China (English)

2007-01-01

The long-term effect of elevated CO2 concentrations on needle dark respiration of two coniferous spe- cies—Pinus koraiensis and Pinus sylvestriformis on the Changbai Mountain was investigated using open-top chambers. P. koraiensis and P. sylvestriformis were exposed to 700, 500 μmol·mol-1 CO2 and ambient CO2 (approx. 350 μmol·mol-1) for four growing seasons. Needle dark respiration was meas- ured during the second, third and fourth growing seasons’ exposure to elevated CO2. The results showed that needle dark respiration rate increased for P. koraiensis and P. sylvestriformis grown at elevated CO2 concentrations during the second growing season, could be attributed to the change of carbohydrate and/or nitrogen content of needles. Needle dark respiration of P. koraiensis was stimu- lated and that of P. sylvestriformis was inhibited by elevated CO2 concentrations during the third growing season. Different response of the two tree species to elevated CO2 mainly resulted from the difference in the growth rate. Elevated CO2 concentrations inhibited needle dark respiration of both P. koraiensis and P. sylvestriformis during the fourth growing season. There was consistent trend be- tween the short-term effect and the long-term effect of elevated CO2 on needle dark respiration in P. sylvestriformis during the third growing season by changing measurement CO2 concentrations. How- ever, the short-term effect was different from the long-term effect for P. koraiensis. Response of dark respiration of P. koraiensis and P. sylvestriformis to elevated CO2 concentrations was related to the treatment time of CO2 and the stage of growth and development of plant. The change of dark respiration for the two tree species was determined by the direct effect of CO2 and long-term acclimation. The prediction of the long-term response of needle dark respiration to elevated CO2 concentration based on the short-term response is in dispute.

Multi function Finishing and Pigment Printing of UV Cured Cotton/Polyester Fabrics Coated with Plasticized Epoxy Resin/ZnO Formulation

International Nuclear Information System (INIS)

Hassan, M.S.; Mousaa, I.M.; Ali, N.M.

2015-01-01

Cotton/ Polyester fabrics were coated with epoxy acrylate (EA) formulations plasticized by castor oil (CO), in the presence of benzophenone as initiator, ZnO (antibacterial agent) and pigment printing. Ultra violet (UV) irradiation was used as a curing system. The effect of UV irradiation time and CO percentage on the mechanical and crease recovery properties were investigated. The effect of the coating process on the cross-section feature by using scanning electron microscope (SEM), the antibacterial properties, water retardance, colour difference and the durability for washing of the coated fabrics were also investigated. From the results, it was found that the crease recovery and antibacterial properties were enhanced. Also, the colour durability against multiple washing cycles gave adequate results after application of the investigated coating formulation. The most fitting castor oil per cent was found to be 45%, while the 3% ZnO recorded the best antibacterial and mechanical properties. The pigment per cent that gave the highest durability and adequate colour strength was 0.6%.

Effects of day-time exposure to different light intensities on light-induced melatonin suppression at night.

Science.gov (United States)

Kozaki, Tomoaki; Kubokawa, Ayaka; Taketomi, Ryunosuke; Hatae, Keisuke

2015-07-04

Bright nocturnal light has been known to suppress melatonin secretion. However, bright light exposure during the day-time might reduce light-induced melatonin suppression (LIMS) at night. The effective proportion of day-time light to night-time light is unclear; however, only a few studies on accurately controlling both day- and night-time conditions have been conducted. This study aims to evaluate the effect of different day-time light intensities on LIMS. Twelve male subjects between the ages of 19 and 23 years (mean ± S.D., 20.8 ± 1.1) gave informed consent to participate in this study. They were exposed to various light conditions (day-time light conditions). They were then exposed to bright light (300 lx) again between 01:00 and 02:30 (night-time light exposure). They provided saliva samples before (00:55) and after night-time light exposure (02:30). A one-tailed paired t test yielded significant decrements of melatonin concentration after night-time light exposure under day-time dim, 100- and 300-lx light conditions. No significant differences exist in melatonin concentration between pre- and post-night-time light exposure under day-time 900- and 2700-lx light conditions. Present findings suggest the amount of light exposure needed to prevent LIMS caused by ordinary nocturnal light in individuals who have a general life rhythm (sleep/wake schedule). These findings may be useful in implementing artificial light environments for humans in, for example, hospitals and underground shopping malls.

Estimating Time-Varying PCB Exposures Using Person-Specific Predictions to Supplement Measured Values: A Comparison of Observed and Predicted Values in Two Cohorts of Norwegian Women.

Science.gov (United States)

Nøst, Therese Haugdahl; Breivik, Knut; Wania, Frank; Rylander, Charlotta; Odland, Jon Øyvind; Sandanger, Torkjel Manning

2016-03-01

Studies on the health effects of polychlorinated biphenyls (PCBs) call for an understanding of past and present human exposure. Time-resolved mechanistic models may supplement information on concentrations in individuals obtained from measurements and/or statistical approaches if they can be shown to reproduce empirical data. Here, we evaluated the capability of one such mechanistic model to reproduce measured PCB concentrations in individual Norwegian women. We also assessed individual life-course concentrations. Concentrations of four PCB congeners in pregnant (n = 310, sampled in 2007-2009) and postmenopausal (n = 244, 2005) women were compared with person-specific predictions obtained using CoZMoMAN, an emission-based environmental fate and human food-chain bioaccumulation model. Person-specific predictions were also made using statistical regression models including dietary and lifestyle variables and concentrations. CoZMoMAN accurately reproduced medians and ranges of measured concentrations in the two study groups. Furthermore, rank correlations between measurements and predictions from both CoZMoMAN and regression analyses were strong (Spearman's r > 0.67). Precision in quartile assignments from predictions was strong overall as evaluated by weighted Cohen's kappa (> 0.6). Simulations indicated large inter-individual differences in concentrations experienced in the past. The mechanistic model reproduced all measurements of PCB concentrations within a factor of 10, and subject ranking and quartile assignments were overall largely consistent, although they were weak within each study group. Contamination histories for individuals predicted by CoZMoMAN revealed variation between study subjects, particularly in the timing of peak concentrations. Mechanistic models can provide individual PCB exposure metrics that could serve as valuable supplements to measurements.

Spatially selective Er/Yb-doped CaF2 crystal formation by CO2 laser exposure

International Nuclear Information System (INIS)

Kim, Dong-Seon; Lee, Jin-Ho; Lim, Ki-Soo

2014-01-01

Highlights: • Oxyfluoride glass–ceramics containing CaF 2 nanocrystals doped with Er 3+ and Yb 3+ ions were formed on the glass surface by CO 2 laser and a heat gun exposure. • Most of Er and Yb ions were distributed inside CaF 2 nanocrystals and fluorine loss was observed in the EDS element maps. • IR-to-VIS upconversion emission efficiency of laser annealed glass ceramics was much increased and compared with that of the furnace-annealed glass ceramics. • Distributed volume of the glass ceramics were estimated by a confocal fluorescence microscope imaging. - Abstract: We report the glass–ceramic precipitation on the oxyfluoride glass surface by spatially selective annealing with a CO 2 laser and a heat gun exposure. X-ray diffraction analysis showed the formation of major CaF 2 and miner Ca 2 SiO 4 nanoparticles. We observed ∼100 nm nanoparticle aggregation by tunneling electron microscopy and element distribution in glass and crystal phases. Spatial distribution of glass ceramics near the glass surface was probed by confocal fluorescence microscope by using much enhanced emission from the Er ions in the laser-treated area. Strong emissions at 365 nm excitation and visible up-conversion emissions at 980 nm excitation also indicated well incorporation of Er and Yb ions into a crystalline environment

Spatially selective Er/Yb-doped CaF2 crystal formation by CO2 laser exposure

International Nuclear Information System (INIS)

Kim, Dong-Seon; Lee, Jin-Ho; Lim, Ki-Soo

2015-01-01

Highlights: • Oxyfluoride glass–ceramics containing CaF 2 nanocrystals doped with Er 3+ and Yb 3+ ions were formed on the glass surface by CO 2 laser and a heat gun exposure. • Most of Er and Yb ions were distributed inside CaF 2 nanocrystals and fluorine loss was observed in the EDS element maps. • IR-to-VIS upconversion emission efficiency of laser annealed glass ceramics was much increased and compared with that of the furnace-annealed glass ceramics. • Distributed volume of the glass ceramics were estimated by a confocal fluorescence microscope imaging. - Abstract: We report the glass–ceramic precipitation on the oxyfluoride glass surface by spatially selective annealing with a CO 2 laser and a heat gun exposure. X-ray diffraction analysis showed the formation of major CaF 2 and miner Ca 2 SiO 4 nanoparticles. We observed ∼100 nm nanoparticle aggregation by tunneling electron microscopy and element distribution in glass and crystal phases. Spatial distribution of glass ceramics near the glass surface was probed by confocal fluorescence microscope by using much enhanced emission from the Er ions in the laser-treated area. Strong emissions at 365 nm excitation and visible up-conversion emissions at 980 nm excitation also indicated well incorporation of Er and Yb ions into a crystalline environment

Relative bioavailability of three formulations of galunisertib administered as monotherapy in patients with advanced or metastatic cancer

Directory of Open Access Journals (Sweden)

Ivelina Gueorguieva

2016-12-01

Full Text Available Objective: Galunisertib (LY2157299 monohydrate, an inhibitor of the transforming growth factor β (TGFβ pathway, is currently under investigation in several clinical trials involving multiple tumor types. The primary objective of this study was to assess relative bioavailability of two new galunisertib formulations developed using the roller compaction (RC dry-milled (RCD and RC slurry-milled (RCS processes, compared with the existing formulation developed using the high-sheer wet granulation (HSWG process. The secondary objective was to report the safety profile after a single dose of the three formulations. Methods: Patients with advanced or metastatic cancer were enrolled into this single-center, 3-period, 6-sequence crossover study. Patients were assigned sequentially to 1 of 6 sequences in blocks of 6 to ensure that all 6 sequences have the same number of completers. A patient entering a sequence received a different galunisertib formulation as a single 150 mg dose orally during each of the 3 periods. Each period was separated from the next by a washout interval of at least 48 hours. Pharmacokinetic (PK parameters, including area under curve (AUC and Cmax, were computed using standard non-compartmentalized methods of analysis. For comparison of exposures between formulations, log-transformed AUC and Cmax values were analyzed using a linear mixed-effects model. Safety assessments included adverse event monitoring, physical examinations, and laboratory tests. Results: Of the 14 patients who entered and completed the study, 13 patients were included in the final statistical analysis. AUC(0-tlast, AUC(0-48 h, and AUC(0-∞ for the RC formulations and the HSWG formulation were similar. Cmax was reduced by approximately 22% and tmax was longer by at least 1.00 h for the RCD and RCS formulations compared with the HSWG formulation. The RC formulations demonstrated a safety profile after a single dose similar to the HSWG formulation. Conclusions

Integration of image exposure time into a modified laser speckle imaging method

Energy Technology Data Exchange (ETDEWEB)

RamIrez-San-Juan, J C; Salazar-Hermenegildo, N; Ramos-Garcia, R; Munoz-Lopez, J [Optics Department, INAOE, Puebla (Mexico); Huang, Y C [Department of Electrical Engineering and Computer Science, University of California, Irvine, CA (United States); Choi, B, E-mail: jcram@inaoep.m [Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA (United States)

2010-11-21

Speckle-based methods have been developed to characterize tissue blood flow and perfusion. One such method, called modified laser speckle imaging (mLSI), enables computation of blood flow maps with relatively high spatial resolution. Although it is known that the sensitivity and noise in LSI measurements depend on image exposure time, a fundamental disadvantage of mLSI is that it does not take into account this parameter. In this work, we integrate the exposure time into the mLSI method and provide experimental support of our approach with measurements from an in vitro flow phantom.

Integration of image exposure time into a modified laser speckle imaging method

International Nuclear Information System (INIS)

RamIrez-San-Juan, J C; Salazar-Hermenegildo, N; Ramos-Garcia, R; Munoz-Lopez, J; Huang, Y C; Choi, B

2010-01-01

Speckle-based methods have been developed to characterize tissue blood flow and perfusion. One such method, called modified laser speckle imaging (mLSI), enables computation of blood flow maps with relatively high spatial resolution. Although it is known that the sensitivity and noise in LSI measurements depend on image exposure time, a fundamental disadvantage of mLSI is that it does not take into account this parameter. In this work, we integrate the exposure time into the mLSI method and provide experimental support of our approach with measurements from an in vitro flow phantom.

Using exposure bands for rapid decision making in the ...

Science.gov (United States)

The ILSI Health and Environmental Sciences Institute (HESI) Risk Assessment in the 21st Century (RISK21) project was initiated to address and catalyze improvements in human health risk assessment. RISK21 is a problem formulation-based conceptual roadmap and risk matrix visualization tool, facilitating transparent evaluation of both hazard and exposure components. The RISK21 roadmap is exposure-driven, i.e. exposure is used as the second step (after problem formulation) to define and focus the assessment. This paper describes the exposure tiers of the RISK21 matrix and the approaches to adapt readily available information to more quickly inform exposure at a screening level. In particular, exposure look-up tables were developed from available exposure tools (European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) Targeted Risk Assessment (TRA) for worker exposure, ECETOC TRA, European Solvents Industry Group (ESIG) Generic Exposure Scenario (GES) Risk and Exposure Tool (EGRET) for consumer exposure, and USEtox for indirect exposure to humans via the environment) were tested in a hypothetical mosquito bed netting case study. A detailed WHO risk assessment for a similar mosquito net use served as a benchmark for the performance of the RISK21 approach. The case study demonstrated that the screening methodologies provided suitable conservative exposure estimates for risk assessment. The results of this effort showed that the RISK21 approach is useful f

Investigating the American Time Use Survey from an Exposure Modeling Perspective

Science.gov (United States)

This paper describes an evaluation of the U.S. Bureau of Labor Statistics' American Time Use Survey (ATUS) for potential use in modeling human exposures to environmental pollutants. The ATUS is a large, on-going, cross-sectional survey of where Americans spend time and what activ...

Estimating time-varying exposure-outcome associations using case-control data: logistic and case-cohort analyses.

Science.gov (United States)

Keogh, Ruth H; Mangtani, Punam; Rodrigues, Laura; Nguipdop Djomo, Patrick

2016-01-05

Traditional analyses of standard case-control studies using logistic regression do not allow estimation of time-varying associations between exposures and the outcome. We present two approaches which allow this. The motivation is a study of vaccine efficacy as a function of time since vaccination. Our first approach is to estimate time-varying exposure-outcome associations by fitting a series of logistic regressions within successive time periods, reusing controls across periods. Our second approach treats the case-control sample as a case-cohort study, with the controls forming the subcohort. In the case-cohort analysis, controls contribute information at all times they are at risk. Extensions allow left truncation, frequency matching and, using the case-cohort analysis, time-varying exposures. Simulations are used to investigate the methods. The simulation results show that both methods give correct estimates of time-varying effects of exposures using standard case-control data. Using the logistic approach there are efficiency gains by reusing controls over time and care should be taken over the definition of controls within time periods. However, using the case-cohort analysis there is no ambiguity over the definition of controls. The performance of the two analyses is very similar when controls are used most efficiently under the logistic approach. Using our methods, case-control studies can be used to estimate time-varying exposure-outcome associations where they may not previously have been considered. The case-cohort analysis has several advantages, including that it allows estimation of time-varying associations as a continuous function of time, while the logistic regression approach is restricted to assuming a step function form for the time-varying association.

Cadmium and mercury exposure over time in Swedish children

Energy Technology Data Exchange (ETDEWEB)

Lundh, T., E-mail: Thomas.Lundh@med.lu.se [Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, SE−22185 Lund (Sweden); Axmon, A., E-mail: Anna.Axmon@med.lu.se [Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, SE−22185 Lund (Sweden); Skerfving, S., E-mail: Staffan.Skerfving@med.lu.se [Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, SE−22185 Lund (Sweden); Broberg, K., E-mail: Karin.Broberg@ki.se [Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, SE−22185 Lund (Sweden); Unit of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, SE-171 77 Stockholm (Sweden)

2016-10-15

Purpose: Knowledge about changes in exposure to toxic metals over time remains very sparse, in particular for children, the most vulnerable group. Here, we assessed whether a reduction in environmental pollution with cadmium (Cd) and mercury (Hg) caused a change in exposure over time. In total, 1257 children (age 4–9) in two towns in Sweden were sampled once in 1986–2013. Blood concentrations of Cd (b-Cd; n=1120) and Hg (b-Hg; n=560) were determined. Results: The median b-Cd was 0.10 (geometric mean 0.10; range 0.010–0.61) μg/L and b-Hg was 0.91 (geometric mean 0.83; range 0.021–8.2) μg/L. Children living close to a smelter had higher b-Cd and b-Hg than those in urban and rural areas. There was no sex difference in b-Cd or b-Hg, and b-Cd and b-Hg showed no significant accumulation by age. b-Cd decreased only slightly (0.7% per year, p<0.001) over the study period. In contrast, b-Hg did show a clear decrease over the study period (3% per year, p<0.001). Conclusions: The exposure to Cd was very low but still might increase the risk of disease later in life. Moreover, b-Cd only showed a minor decrease, indicating that Cd pollution should be further restricted. b-Hg was relatively low and decreasing, probably because of reduced use of dental amalgam and lower Hg intake from fish. The b-Cd and b-Hg levels decreased much less than the levels of lead in the blood as previously found in the same children. - Highlights: • There are few studies of time trends for exposure to toxic metals, except for lead. • 1986–2013 we studied blood levels of cadmium and mercury in 1257 Swedish children. • The median blood concentration of cadmium was 0.10 μg/L, of mercury 0.83 μg/L. • Cadmium perhaps decreased by 0.7% per year, mercury by 3% per year. • Cadmium accumulation may result in toxic levels in elderly women.

Chronic ethanol exposure produces time- and brain region-dependent changes in gene coexpression networks.

Directory of Open Access Journals (Sweden)

Elizabeth A Osterndorff-Kahanek

Full Text Available Repeated ethanol exposure and withdrawal in mice increases voluntary drinking and represents an animal model of physical dependence. We examined time- and brain region-dependent changes in gene coexpression networks in amygdala (AMY, nucleus accumbens (NAC, prefrontal cortex (PFC, and liver after four weekly cycles of chronic intermittent ethanol (CIE vapor exposure in C57BL/6J mice. Microarrays were used to compare gene expression profiles at 0-, 8-, and 120-hours following the last ethanol exposure. Each brain region exhibited a large number of differentially expressed genes (2,000-3,000 at the 0- and 8-hour time points, but fewer changes were detected at the 120-hour time point (400-600. Within each region, there was little gene overlap across time (~20%. All brain regions were significantly enriched with differentially expressed immune-related genes at the 8-hour time point. Weighted gene correlation network analysis identified modules that were highly enriched with differentially expressed genes at the 0- and 8-hour time points with virtually no enrichment at 120 hours. Modules enriched for both ethanol-responsive and cell-specific genes were identified in each brain region. These results indicate that chronic alcohol exposure causes global 'rewiring' of coexpression systems involving glial and immune signaling as well as neuronal genes.

Novel microemulsion-based gel formulation of tazarotene for therapy of acne.

Science.gov (United States)

Patel, Mrunali Rashmin; Patel, Rashmin Bharatbhai; Parikh, Jolly R; Patel, Bharat G

2016-12-01

The objective of this study was to develop and evaluate a novel microemulsion based gel formulation containing tazarotene for targeted topical therapy of acne. Psudoternary phase diagrams were constructed to obtain the concentration range of oil, surfactant, and co-surfactant for microemulsion formation. The optimized microemulsion formulation containing 0.05% tazarotene was formulated by spontaneous microemulsification method consisting of 10% Labrafac CC, mixed emulsifiers 15% Labrasol-Cremophor-RH 40 (1:1), 15% Capmul MCM, and 60% distilled water (w/w) as an external phase. All plain and tazarotene-loaded microemulsions were clear and showed physicochemical parameters for desired topical delivery and stability. The permeation profiles of tazarotene through rat skin from optimized microemulsion formulation followed the Higuchi model for controlled permeation. Microemulsion-based gel was prepared by incorporating Carbopol®971P NF in optimized microemulsion formulation having suitable skin permeation rate and skin uptake. Microemulsion-based gel showed desired physicochemical parameters and demonstrated advantage over marketed formulation in improving the skin tolerability of tazarotene indicating its potential in improving its topical delivery. The developed microemulsion-based gel may be a potential drug delivery vehicle for targeted topical delivery of tazarotene in the treatment of acne.

Solidified self-nanoemulsifying formulation for oral delivery of combinatorial therapeutic regimen

DEFF Research Database (Denmark)

Jain, Amit K; Thanki, Kaushik; Jain, Sanyog

2014-01-01

formulation in contrast to that of clinically available tamoxifen citrate when measured as function of hepatotoxicity markers and histopathological changes. CONCLUSIONS: In nutshell, co-encapsulation of quercetin with tamoxifen in solid SNEDDS poses great potential in improving the therapeutic efficacy...

Time characteristics of distortion product otoacoustic emissions recovery function after moderate sound exposure

DEFF Research Database (Denmark)

de Toro, Miguel Angel Aranda; Ordoñez, Rodrigo Pizarro; Hammershøi, Dorte

2006-01-01

Exposure to sound of moderate level temporarily attenuates the amplitude of distortion product otoacoustic emissions (DPOAEs). These changes are similar to the changes observed in absolute hearing thresholds after similar sound exposures. To be able to assess changes over time across a broad...

Preliminary Formulation of Finite Element Solution for the 1-D, 1-G Time Dependent Neutron Diffusion Equation without Consideration about Delay Neutron

Energy Technology Data Exchange (ETDEWEB)

Ryu, Eun Hyun; Song, Yong Mann; Park, Joo Hwan [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2013-05-15

If time-dependent equation is solved with the FEM, the limitation of the input geometry will disappear. It has often been pointed out that the numerical methods implemented in the RFSP code are not state-of-the-art. Although an acceleration method such as the Coarse Mesh Finite Difference (CMFD) for Finite Difference Method (FDM) does not exist for the FEM, one should keep in mind that the number of time steps for the transient simulation is not large. The rigorous formulation in this study will richen the theoretical basis of the FEM and lead to an extension of the dynamics code to deal with a more complicated problem. In this study, the formulation for the 1-D, 1-G Time Dependent Neutron Diffusion Equation (TDNDE) without consideration of the delay neutron will first be done. A problem including one multiplying medium will be solved. Also several conclusions from a comparison between the numerical and analytic solutions, a comparison between solutions with various element orders, and a comparison between solutions with different time differencing will be made to be certain about the formulation and FEM solution. By investigating various cases with different values of albedo, theta, and the order of elements, it can be concluded that the finite element solution is agree well with the analytic solution. The higher the element order used, the higher the accuracy improvements are obtained.

[Formulation optimization of panax notoginsenoside orally fast disintegration tablets].

Science.gov (United States)

Wang, Zhi; Wei, Li; Chen, Ting

2008-07-01

To optimize the formulation of panax notoginsenoside orally fast disintegrating tablets. Mannitol, microcrystalline cellulose (PH 102) and lactose 80 were used as diluent. A polynomial regression algorithm was used to evaluate the relationship between the controlling factor, compacting pressure and diluent ratio, and disintegration time, tensile strength of tablets. Optimum formulation and process parameters could be determined by contrast the contour plot of tensile strength to that of disintegration time. The disintegration time and tensile strength of panax notoginsenoside oral disintegrating tablets were good, and the taste was satisfactory. Panax notoginsenoside oral disintegrating tablets achieve the goal of design and this method can be fairly used in formulation screening.

Formulation and Evaluation of New Glimepiride Sublingual Tablets

Directory of Open Access Journals (Sweden)

Wafa Al-Madhagi

2017-01-01

Full Text Available Oral mucosal delivery of drugs promotes rapid absorption and high bioavailability, with a subsequent immediate onset of pharmacological effect. However, many oral mucosal deliveries are compromised by the possibility of the patient swallowing the active substance before it has been released and absorbed locally into the systemic circulation. The aim of this research was to introduce a new glimepiride formula for sublingual administration and rapid drug absorption that can be used in an emergency. The new sublingual formulation was prepared after five trials to prepare the suitable formulation. Two accepted formulations of the new sublingual product were prepared, but one of them with disintegration time of 1.45 min and searching for preferred formulation, the binder, is changed with Flulac and starch slurry to prepare formula with disintegration time of 21 seconds that supports the aim of research to be used in an emergency. The five formulations were done, after adjusting to the binder as Flulac and aerosil with disintegration time of 21 seconds and accepted hardness as well as the weight variation. The assay of a new product (subglimepiride is 103% which is a promising result, confirming that the formula succeeded. The new product (subglimepiride is accepted in most quality control tests and it is ready for marketing.

Co-exposure to fumonisins and aflatoxins in maize-based foods in central america: guatemala as a case study

Science.gov (United States)

Aflatoxin B1 (AFB1) is a human liver carcinogen having a genotoxic mechanism of action. The ceramide synthase inhibitor fumonisin B1 (FB1) is a liver cancer promoter in rats and trout. Both mycotoxins are found in maize so that the possibility of co-exposure is a health concern, especially in Centra...

Non-conforming finite-element formulation for cardiac electrophysiology: an effective approach to reduce the computation time of heart simulations without compromising accuracy

Science.gov (United States)

Hurtado, Daniel E.; Rojas, Guillermo

2018-04-01

Computer simulations constitute a powerful tool for studying the electrical activity of the human heart, but computational effort remains prohibitively high. In order to recover accurate conduction velocities and wavefront shapes, the mesh size in linear element (Q1) formulations cannot exceed 0.1 mm. Here we propose a novel non-conforming finite-element formulation for the non-linear cardiac electrophysiology problem that results in accurate wavefront shapes and lower mesh-dependance in the conduction velocity, while retaining the same number of global degrees of freedom as Q1 formulations. As a result, coarser discretizations of cardiac domains can be employed in simulations without significant loss of accuracy, thus reducing the overall computational effort. We demonstrate the applicability of our formulation in biventricular simulations using a coarse mesh size of ˜ 1 mm, and show that the activation wave pattern closely follows that obtained in fine-mesh simulations at a fraction of the computation time, thus improving the accuracy-efficiency trade-off of cardiac simulations.

Novel gas sensor with dual response under CO(g) exposure: Optical and electrical stimuli

Science.gov (United States)

Rocha, L. S. R.; Cilense, M.; Ponce, M. A.; Aldao, C. M.; Oliveira, L. L.; Longo, E.; Simoes, A. Z.

2018-05-01

In this work, a lanthanum (La) doped ceria (CeO2) film, which depicted a dual gas sensing response (electric and optical) for CO(g) detection, was obtained by the microwave-assisted hydrothermal (HAM) synthesis and deposited by the screen-printing technique, in order to prevent deaths by intoxication with this life-threatening gas. An electric response under CO(g) exposure was obtained, along with an extremely fast optical response for a temperature of 380 °C, associated with Ce+4 reduction and vacancy generation. A direct optical gap was found to be around 2.31 eV from UV-Vis results, which corresponds to a transition from valence band to 4f states. Due to the anomalous electron configuration of cerium atoms with 4f electrons in its reduced state, they are likely to present an electric conduction based on the small polaron theory with a hopping mechanism responsible for its dual sensing response with a complete reversible behaviour.

Influence of Differing Analgesic Formulations of Aspirin on Pharmacokinetic Parameters

Directory of Open Access Journals (Sweden)

Kunal Kanani

2015-08-01

Full Text Available Aspirin has been used therapeutically for over 100 years. As the originator and an important marketer of aspirin-containing products, Bayer’s clinical trial database contains numerous reports of the pharmacokinetics of various aspirin formulations. These include evaluations of plain tablets, effervescent tablets, granules, chewable tablets, and fast-release tablets. This publication seeks to expand upon the available pharmacokinetic information concerning aspirin formulations. In the pre-systemic circulation, acetylsalicylic acid (ASA is rapidly converted into its main active metabolite, salicylic acid (SA. Therefore, both substances are measured in plasma and reported in the results. The 500 mg strength of each formulation was chosen for analysis as this is the most commonly used for analgesia. A total of 22 studies were included in the analysis. All formulations of 500 mg aspirin result in comparable plasma exposure to ASA and SA as evidenced by AUC. Tablets and dry granules provide a consistently lower Cmax compared to effervescent, granules in suspension and fast release tablets. Effervescent tablets, fast release tablets, and granules in suspension provide a consistently lower median Tmax compared to dry granules and tablets for both ASA and SA. This report reinforces the importance of formulation differences and their impact on pharmacokinetic parameters.

Contrast characteristics of barium preparations and the timing of exposure

OpenAIRE

渋谷, 光一; 中桐, 義忠; 東, 義晴; 杉田, 勝彦; 小橋, 高郎; 大倉, 保彦; 丹谷, 延義; 三上, 泰隆; 平木, 祥夫

1995-01-01

We studied the relationship between the contrast characteristics of barium suspension and timing of exposure. We poured several kinds of barium preparations on the phantom manufactured by ourselves, and took X-ray pictures continuously by a DSA system. We analyzed each of the characteris-tics of the contrast. The time which was reguired for the contrast to reach the peak (Contrast Peak Time ; CPT) was unrelated with the kind of barium preparations used. It depended on the viscosity of the con...

Information technology in developing countries: a study to guide policy formulation

NARCIS (Netherlands)

de Boer, S.J.; Walbeek, M.M.

1999-01-01

This article discusses the information gap between industrialised and developing countries. In view of this gap, the Dutch Ministry of Development Co-operation decided to finance research aimed at formulating policy recommendations on the removal of bottlenecks preventing or slowing down the growth

Effects of decadal exposure to interacting elevated CO2 and/or O3 on paper birch (Betula papyrifera) reproduction

International Nuclear Information System (INIS)

Darbah, Joseph N.T.; Kubiske, Mark E.; Nelson, Neil; Oksanen, Elina; Vapaavuori, Elina; Karnosky, David F.

2008-01-01

We studied the effects of long-term exposure (nine years) of birch (Betula papyrifera) trees to elevated CO 2 and/or O 3 on reproduction and seedling development at the Aspen FACE (Free-Air Carbon Dioxide Enrichment) site in Rhinelander, WI. We found that elevated CO 2 increased both the number of trees that flowered and the quantity of flowers (260% increase in male flower production), increased seed weight, germination rate, and seedling vigor. Elevated O 3 also increased flowering but decreased seed weight and germination rate. In the combination treatment (elevated CO 2 + O 3 ) seed weight is decreased (20% reduction) while germination rate was unaffected. The evidence from this study indicates that elevated CO 2 may have a largely positive impact on forest tree reproduction and regeneration while elevated O 3 will likely have a negative impact. - In this study, we found that elevated CO 2 enhances and elevated O 3 decreases birch reproduction and early seedling growth

An econometric time-series analysis of global CO2 concentrations and emissions

International Nuclear Information System (INIS)

Cohen, B.C.; Labys, W.C.; Eliste, P.

2001-01-01

This paper extends previous work on the econometric modelling of CO 2 concentrations and emissions. The importance of such work rests in the fact that models of the Cohen-Labys variety represent the only alternative to scientific or physical models of CO 2 accumulations whose parameters are inferred rather than estimated. The stimulation for this study derives from the recent discovery of oscillations and cycles in the net biospheric flux of CO 2 . A variety of time series tests is thus used to search for the presence of normality, stationarity, cyclicality and stochastic processes in global CO 2 emissions and concentrations series. Given the evidence for cyclicality of a short-run nature in the spectra of these series, both structural time series and error correction model are applied to confirm the frequency and amplitude of these cycles. Our results suggest new possibilities for determining equilibrium levels of CO 2 concentrations and subsequently revising stabilization policies. (Author)

Estimating time-varying exposure-outcome associations using case-control data: logistic and case-cohort analyses

Directory of Open Access Journals (Sweden)

Ruth H. Keogh

2016-01-01

Full Text Available Abstract Background Traditional analyses of standard case-control studies using logistic regression do not allow estimation of time-varying associations between exposures and the outcome. We present two approaches which allow this. The motivation is a study of vaccine efficacy as a function of time since vaccination. Methods Our first approach is to estimate time-varying exposure-outcome associations by fitting a series of logistic regressions within successive time periods, reusing controls across periods. Our second approach treats the case-control sample as a case-cohort study, with the controls forming the subcohort. In the case-cohort analysis, controls contribute information at all times they are at risk. Extensions allow left truncation, frequency matching and, using the case-cohort analysis, time-varying exposures. Simulations are used to investigate the methods. Results The simulation results show that both methods give correct estimates of time-varying effects of exposures using standard case-control data. Using the logistic approach there are efficiency gains by reusing controls over time and care should be taken over the definition of controls within time periods. However, using the case-cohort analysis there is no ambiguity over the definition of controls. The performance of the two analyses is very similar when controls are used most efficiently under the logistic approach. Conclusions Using our methods, case-control studies can be used to estimate time-varying exposure-outcome associations where they may not previously have been considered. The case-cohort analysis has several advantages, including that it allows estimation of time-varying associations as a continuous function of time, while the logistic regression approach is restricted to assuming a step function form for the time-varying association.

Exposure to household air pollution from wood combustion and association with respiratory symptoms and lung function in nonsmoking women: results from the RESPIRE trial, Guatemala.

Science.gov (United States)

Pope, Daniel; Diaz, Esperanza; Smith-Sivertsen, Tone; Lie, Rolv T; Bakke, Per; Balmes, John R; Smith, Kirk R; Bruce, Nigel G

2015-04-01

With 40% of the world's population relying on solid fuel, household air pollution (HAP) represents a major preventable risk factor for COPD (chronic obstructive pulmonary disease). Meta-analyses have confirmed this relationship; however, constituent studies are observational, with virtually none measuring exposure directly. We estimated associations between HAP exposure and respiratory symptoms and lung function in young, nonsmoking women in rural Guatemala, using measured carbon monoxide (CO) concentrations in exhaled breath and personal air to assess exposure. The Randomized Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) Guatemala study was a trial comparing respiratory outcomes among 504 women using improved chimney stoves versus traditional cookstoves. The present analysis included 456 women with data from postintervention surveys including interviews at 6, 12, and 18 months (respiratory symptoms) and spirometry and CO (ppm) in exhaled breath measurements. Personal CO was measured using passive diffusion tubes at variable times during the study. Associations between CO concentrations and respiratory health were estimated using random intercept regression models. Respiratory symptoms (cough, phlegm, wheeze, or chest tightness) during the previous 6 months were positively associated with breath CO measured at the same time of symptom reporting and with average personal CO concentrations during the follow-up period. CO in exhaled breath at the same time as spirometry was associated with lower lung function [average reduction in FEV1 (forced expiratory volume in 1 sec) for a 10% increase in CO was 3.33 mL (95% CI: -0.86, -5.81)]. Lung function measures were not significantly associated with average postintervention personal CO concentrations. Our results provide further support for the effects of HAP exposures on airway inflammation. Further longitudinal research modeling continuous exposure to particulate matter against lung function will

Effects of decadal exposure to interacting elevated CO2 and/or O3 on paper birch (Betula papyrifera) reproduction.

Science.gov (United States)

Darbah, Joseph N T; Kubiske, Mark E; Nelson, Neil; Oksanen, Elina; Vapaavuori, Elina; Karnosky, David F

2008-10-01

We studied the effects of long-term exposure (nine years) of birch (Betula papyrifera) trees to elevated CO(2) and/or O(3) on reproduction and seedling development at the Aspen FACE (Free-Air Carbon Dioxide Enrichment) site in Rhinelander, WI. We found that elevated CO(2) increased both the number of trees that flowered and the quantity of flowers (260% increase in male flower production), increased seed weight, germination rate, and seedling vigor. Elevated O(3) also increased flowering but decreased seed weight and germination rate. In the combination treatment (elevated CO(2)+O(3)) seed weight is decreased (20% reduction) while germination rate was unaffected. The evidence from this study indicates that elevated CO(2) may have a largely positive impact on forest tree reproduction and regeneration while elevated O(3) will likely have a negative impact.

Exhaled CO, a predictor of lung function?

DEFF Research Database (Denmark)

Fabricius, Peder; Scharling, Henrik; Løkke, Anders

2007-01-01

and whether CO could provide additional information to usual measures of smoking regarding prediction of present lung function and decline in lung function over an extended period of time. METHOD: Cigarette smokers from the Copenhagen City Heart Study with valid measures of lung function and exhaled CO......; in total 3738 subjects, 2096 women and 1642 men. RESULTS: Subjects not inhaling had slightly lower exhaled CO values than those inhaling, but substantially higher values than non-smokers (PSmokers of plain cigarettes had slightly lower CO values than smokers of filter cigarettes (P...BACKGROUND: Smoking is associated with an accelerated loss of lung function and inhalation accelerates the decline further. Exhaled CO reflects the exposure of smoke to the lungs. AIM: To investigate whether self-reported inhalation and type of cigarette influenced the level of exhaled CO...

Co-ordinate variations in methylmalonyl-CoA mutase and methionine synthase, and the cobalamin cofactors in human glioma cells during nitrous oxide exposure and the subsequent recovery phase.

Science.gov (United States)

Riedel, B; Fiskerstrand, T; Refsum, H; Ueland, P M

1999-07-01

We investigated the co-ordinate variations of the two cobalamin (Cbl)-dependent enzymes, methionine synthase (MS) and methylmalonyl-CoA mutase (MCM), and measured the levels of their respective cofactors, methylcobalamin (CH3Cbl) and adenosylcobalamin (AdoCbl) in cultured human glioma cells during nitrous oxide exposure and during a subsequent recovery period of culture in a nitrous oxide-free atmosphere (air). In agreement with published data, MS as the primary target of nitrous oxide was inactivated rapidly (initial rate of 0.06 h(-1)), followed by reduction of CH3Cbl (to ordinate distribution of Cbl cofactors during depletion and repletion.

Chronic CO2 exposure markedly increases the incidence of cataracts in juvenile Atlantic cod Gadus morhua L

DEFF Research Database (Denmark)

Moran, Damian; Tubbs, Lincoln; Støttrup, Josianne G.

2012-01-01

A study was undertaken to test the affect of chronic exposure to elevated dissolved carbon dioxide on juvenile Atlantic cod. The CO2 treatment concentrations were designated as low (1–2mgL−1, 1000μatm), medium (8mgL−1, 3500μatm) and high (18mgL−1, 8500μatm), and the fish were reared at 10°C and 2...

Time series models of environmental exposures: Good predictions or good understanding.

Science.gov (United States)

Barnett, Adrian G; Stephen, Dimity; Huang, Cunrui; Wolkewitz, Martin

2017-04-01

Time series data are popular in environmental epidemiology as they make use of the natural experiment of how changes in exposure over time might impact on disease. Many published time series papers have used parameter-heavy models that fully explained the second order patterns in disease to give residuals that have no short-term autocorrelation or seasonality. This is often achieved by including predictors of past disease counts (autoregression) or seasonal splines with many degrees of freedom. These approaches give great residuals, but add little to our understanding of cause and effect. We argue that modelling approaches should rely more on good epidemiology and less on statistical tests. This includes thinking about causal pathways, making potential confounders explicit, fitting a limited number of models, and not over-fitting at the cost of under-estimating the true association between exposure and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Non-linear behaviour of power density and exposure time of argon laser on ocular tissues

Energy Technology Data Exchange (ETDEWEB)

El-Sayed, E M; Talaat, M S; Salem, E F [Physics Department, Faculty of Science, Ain Shams University, Cairo (Egypt)

1997-12-31

In ophthalmology, the thermal effect of argon laser is the most widely used category of laser- tissue interaction. The rise in tissue temperature has to exceed a threshold value for photo coagulation of retinal blood vessels. This value mainly depends on the laser. The most suitable argon laser power P and exposure time (t) which would be more effective for thermal and electrical behaviour of chicken eye was studied. This was achieved by measuring the variations in ocular temperature in electroretinogram (ERG) records under the effect of argon experiment, while power density (P) and exposure time (t) were varied in four different ways for each dose (pt). Results indicated that for the same laser dose, the temperature distribution of the eye, using low power density and high exposure time was higher than that high power density and low exposure time, indicating non-linearity of the laser dose. This finding was confirmed by ERG records which showed similar variations in b-wave latency, amplitude and duration, for the laser exposure conditions. This indicates variations in retinal function due to laser-dependent temperature variations. 5 figs., 3 tabs.

Performance, acute health symptoms and physiological responses during exposure to high air temperature and carbon dioxide concentration

DEFF Research Database (Denmark)

liu, weiwei; Zhong, Weidi; Wargocki, Pawel

2017-01-01

saturation decreased significantly, while the percentage of adjacent inter-beat cardiac intervals differing by > 50 m (pNN50) decreased significantly, indicating elevated stress. The performance of addition and subtraction tasks decreased significantly during this exposure, as well. Increasing CO2 to 3000......Human subjects were exposed for 3 h in a climate chamber to the air temperature of 35 °C that is an action level, at which the working time needs to be diminished in China. The purpose was to put this action level to test by measuring physiological responses, subjective ratings and cognitive...... performance, and compare them with responses at temperature of 26 °C (reference exposure). Moreover, CO2 was increased to 3000 ppm (CO2 exposure) at 35 °C to further examine, whether this change will have any effect on the measured responses. Compared with the reference exposure, exposure to 35 °C caused...

Time and frequency characteristics of temporary threshold shifts caused by pure tone exposures

DEFF Research Database (Denmark)

Ordoñez, Rodrigo Pizarro; Hammershøi, Dorte

2011-01-01

The time-frequency characteristics of Temporary Threshold Shifts (TTS) caused by pure tones were determined using the Békésy audiometric method with narrow-band noise of short duration as the probe stimuli. Two experiments were done using exposures of 3 min at 100 dB above threshold. In the first....... In the second experiment, the TTS recovery curve produced by a 1 kHz pure tone exposure was assessed at 1.5 kHz, at approximately 15 s intervals for the first 5 min and at regularly increasing intervals up to 45 min after the exposure. The results showed a maximum in the recovery around 2 min after the exposure....... The data gathered in these experiments were used to construct a mathematical model of TTS recovery. The model describes both the 1/2-octave shift and the 2 min bounce and it can be used in the comparison of temporary changes in auditory function, assessed at different times and frequencies....

EXPOSURE ANALYSIS MODELING SYSTEM (EXAMS): USER MANUAL AND SYSTEM DOCUMENTATION

Science.gov (United States)

The Exposure Analysis Modeling System, first published in 1982 (EPA-600/3-82-023), provides interactive computer software for formulating aquatic ecosystem models and rapidly evaluating the fate, transport, and exposure concentrations of synthetic organic chemicals - pesticides, ...

Combination of a higher-tier flow-through system and population modeling to assess the effects of time-variable exposure of isoproturon on the green algae Desmodesmus subspicatus and Pseudokirchneriella subcapitata.

Science.gov (United States)

Weber, Denis; Schaefer, Dieter; Dorgerloh, Michael; Bruns, Eric; Goerlitz, Gerhard; Hammel, Klaus; Preuss, Thomas G; Ratte, Hans Toni

2012-04-01

A flow-through system was developed to investigate the effects of time-variable exposure of pesticides on algae. A recently developed algae population model was used for simulations supported and verified by laboratory experiments. Flow-through studies with Desmodesmus subspicatus and Pseudokirchneriella subcapitata under time-variable exposure to isoproturon were performed, in which the exposure patterns were based on the results of FOrum for Co-ordination of pesticide fate models and their USe (FOCUS) model calculations for typical exposure situations via runoff or drain flow. Different types of pulsed exposure events were realized, including a whole range of repeated pulsed and steep peaks as well as periods of constant exposure. Both species recovered quickly in terms of growth from short-term exposure and according to substance dissipation from the system. Even at a peak 10 times the maximum predicted environmental concentration of isoproturon, only transient effects occurred on algae populations. No modified sensitivity or reduced growth was observed after repeated exposure. Model predictions of algal growth in the flow-through tests agreed well with the experimental data. The experimental boundary conditions and the physiological properties of the algae were used as the only model input. No calibration or parameter fitting was necessary. The combination of the flow-through experiments with the algae population model was revealed to be a powerful tool for the assessment of pulsed exposure on algae. It allowed investigating the growth reduction and recovery potential of algae after complex exposure, which is not possible with standard laboratory experiments alone. The results of the combined approach confirm the beneficial use of population models as supporting tools in higher-tier risk assessments of pesticides. Copyright © 2012 SETAC.

Variations with time and age in the relative risks of solid cancer incidence after radiation exposure

International Nuclear Information System (INIS)

Little, M.P.; Muirhead, C.R.; de Vathaire, F.; Charles, M.W.

1997-01-01

The Japanese atomic bomb survivor cancer incidence dataset and data on five groups exposed to radiation for medical reasons in childhood are analysed and evidence found for a reduction in the radiation-induced relative risk of cancers other than leukaemia with increasing time since exposure and age at exposure. The rate of the reductions in relative risk with time since exposure are not significantly different for those exposed in childhood and for those exposed in adulthood, if adjustment is made for the effects on the relative risk of age at exposure. For those irradiated in childhood, there is a statistically significant annual reduction of 5.8% (95% Cl 2.8, 8.9) in excess relative risk, and there are no strong indications of inter-cohort heterogeniety in the speed of reduction of relative risk. After adjustment for the effects of age at exposure, there is a significant annual reduction of 3.6% (95% Cl 1.6, 5.6) in excess relative risk in all age-at-exposure groups. There are significant reductions of 5.2% (95% Cl 3.7, 6.8) in excess relative risk per year of age at exposure. There are statistically significant (P = 0.04) interactions between the exponential adjustments to the excess relative risk for age at exposure and time since exposure in the Japanese data, but no indications (P = 0.38) of such interactions when powers of time since exposure and attained age are used to adjust the excess relative risk, so that the fit of the model with power adjustments is to be preferred to that of the model with exponential adjustments. (author)

The co-solvent Cremophor EL limits absorption of orally administered paclitaxel in cancer patients.

Science.gov (United States)

Malingré, M M; Schellens, J H; Van Tellingen, O; Ouwehand, M; Bardelmeijer, H A; Rosing, H; Koopman, F J; Schot, M E; Ten Bokkel Huinink, W W; Beijnen, J H

2001-11-16

The purpose of this study was to investigate the effect of the co-solvents Cremophor EL and polysorbate 80 on the absorption of orally administered paclitaxel. 6 patients received in a randomized setting, one week apart oral paclitaxel 60 mg m(-2) dissolved in polysorbate 80 or Cremophor EL. For 3 patients the amount of Cremophor EL was 5 ml m(-2), for the other three 15 ml m(-2). Prior to paclitaxel administration patients received 15 mg kg(-1) oral cyclosporin A to enhance the oral absorption of the drug. Paclitaxel formulated in polysorbate 80 resulted in a significant increase in the maximal concentration (C(max)) and area under the concentration-time curve (AUC) of paclitaxel in comparison with the Cremophor EL formulations (P = 0.046 for both parameters). When formulated in Cremophor EL 15 ml m(-2), paclitaxel C(max) and AUC values were 0.10 +/- 0.06 microM and 1.29 +/- 0.99 microM h(-1), respectively, whereas these values were 0.31 +/- 0.06 microM and 2.61 +/- 1.54 microM h(-1), respectively, when formulated in polysorbate 80. Faecal data revealed a decrease in excretion of unchanged paclitaxel for the polysorbate 80 formulation compared to the Cremophor EL formulations. The amount of paclitaxel excreted in faeces was significantly correlated with the amount of Cremophor EL excreted in faeces (P = 0.019). When formulated in Cremophor EL 15 ml m(-2), paclitaxel excretion in faeces was 38.8 +/- 13.0% of the administered dose, whereas this value was 18.3 +/-15.5% for the polysorbate 80 formulation. The results show that the co-solvent Cremophor EL is an important factor limiting the absorption of orally administered paclitaxel from the intestinal lumen. They highlight the need for designing a better drug formulation in order to increase the usefulness of the oral route of paclitaxel

Erythrocyte osmotic fragility and lipid peroxidation following chronic co-exposure of rats to chlorpyrifos and deltamethrin, and the beneficial effect of alpha-lipoic acid

Directory of Open Access Journals (Sweden)

Chidiebere Uchendu

2014-01-01

Full Text Available The present study aimed to evaluate the effect of chronic co-exposure to chlorpyrifos (CPF and deltamethrin (DLT on erythrocyte osmotic fragility, lipid peroxidation and the ameliorative effect of alpha-lipoic acid (ALA on erythrocyte fragility. Thirty-six male Wistar rats divided into six groups of six rats each were used for the study. Groups I (S/oil and II (ALA were given soya oil (2 ml/kg and ALA (60 mg/kg, respectively. Rats in group III (DLT and IV (CPF were exposed to DLT (6.25 mg/kg and CPF (4.75 mg/kg (1/20th of the previously determined LD50 of 125 mg/kg and 95 mg/kg, respectively, over a period of 48 h. Rats in group V (CPF + DLT were co-exposed to CPF (4.75 mg/kg and DLT (6.25 mg/kg, while those in group VI (ALA + CPF + DLT were pretreated with ALA (60 mg/kg and then co-exposed to CPF and DLT, 45 min later. The treatments were administered by gavage once daily for a period of 16 weeks. Blood collected at the end of the experimental period were analyzed for erythrocyte osmotic fragility and malondialdehyde (MDA concentration. The study showed that chronic co-exposure to CPF and DLT resulted in an increase in erythrocyte fragility and MDA concentration which were ameliorated by supplementation with alpha-lipoic acid. The study concluded that repeated co-exposure to CPF and DLT elevated erythrocyte fragility probably due to increased lipid peroxidation, and pretreatment with alpha-lipoic acid ameliorated these alterations.

CoMik : a predictable and cycle-accurately composable real-time microkernel

NARCIS (Netherlands)

Nelson, A.T.; Nejad, A.B.; Molnos, A.M.; Koedam, M.L.P.J.; Goossens, K.G.W.

2014-01-01

The functionality of embedded systems is ever increasing. This has lead to mixed time-criticality systems, where applications with a variety of real-time requirements co-exist on the same platform and share resources. Due to inter-application interference, verifying the real-time requirements of

Tactile friction of topical formulations.

Science.gov (United States)

Skedung, L; Buraczewska-Norin, I; Dawood, N; Rutland, M W; Ringstad, L

2016-02-01

The tactile perception is essential for all types of topical formulations (cosmetic, pharmaceutical, medical device) and the possibility to predict the sensorial response by using instrumental methods instead of sensory testing would save time and cost at an early stage product development. Here, we report on an instrumental evaluation method using tactile friction measurements to estimate perceptual attributes of topical formulations. Friction was measured between an index finger and an artificial skin substrate after application of formulations using a force sensor. Both model formulations of liquid crystalline phase structures with significantly different tactile properties, as well as commercial pharmaceutical moisturizing creams being more tactile-similar, were investigated. Friction coefficients were calculated as the ratio of the friction force to the applied load. The structures of the model formulations and phase transitions as a result of water evaporation were identified using optical microscopy. The friction device could distinguish friction coefficients between the phase structures, as well as the commercial creams after spreading and absorption into the substrate. In addition, phase transitions resulting in alterations in the feel of the formulations could be detected. A correlation was established between skin hydration and friction coefficient, where hydrated skin gave rise to higher friction. Also a link between skin smoothening and finger friction was established for the commercial moisturizing creams, although further investigations are needed to analyse this and correlations with other sensorial attributes in more detail. The present investigation shows that tactile friction measurements have potential as an alternative or complement in the evaluation of perception of topical formulations. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Quantitative monitoring of CO2 injection at Sleipner using seismic full waveform inversion in the time lapse mode and rock physics modeling

International Nuclear Information System (INIS)

Queisser, M.P.

2012-01-01

Carbon capture and sequestration is a technology to achieve a considerable deceleration of CO 2 emission promptly. Since 1996 one of the largest CO 2 storage projects is taking place at Sleipner in the Norwegian North Sea. In order to monitor injected CO 2 , time lapse seismic monitoring surveys have been carried out. Estimating subsurface parameters from the Sleipner seismic data is a challenging problem due to the specific geology of the storage reservoir, which is further complicated by injected CO 2 . Most seismic imaging methods enable only qualitative insights into the subsurface. Motivated by the need for a quantitative seismic monitoring of the injected CO 2 , I have applied 2D seismic full waveform inversion to seismic data sets from Sleipner from 1994 (baseline), 1999 and 2006 along three seismic lines to infer subsurface parameters and parameter changes in the storage reservoir. The P-wave velocity is the major parameter, as it is the most sensitive to CO 2 injection. An energy preconditioning of the gradient has been implemented. The usual source wavelet calibration did not prove to be reliable. An alternative source calibration has been successfully applied. By comparing seismic images with inversion results, I found that using seismic images to locate CO 2 accumulations in the subsurface may be misleading. The quantitative imaging approach using full waveform inversion resulted in a consistent evolution of the model parameter with time. Major reductions in P-wave velocity and hence the CO 2 accumulations could be quantitatively imaged down to a resolution of 10 m. Observed travel time shifts due to CO 2 injection are comparable to those derived from the inversion result. In order to estimate CO 2 saturations, rock physical concepts have been combined and extended to arrive at a rock physical formulation of the subsurface at Sleipner. I used pseudo Monte Carlo rock physics modeling to assess the influence of lithologic heterogeneity on the CO 2

A review of the additive health risk of cannabis and tobacco co-use.

Science.gov (United States)

Meier, Ellen; Hatsukami, Dorothy K

2016-09-01

Cannabis and tobacco are the most widely used substances, and are often used together. The present review examines the toxicant exposure associated with co-use (e.g., carbon monoxide, carcinogens), co-use via electronic nicotine delivery systems (ENDS), and problematic methodological issues present across co-use studies. An extensive literature search through PubMed was conducted and studies utilizing human subjects and in vitro methods were included. Keywords included tobacco, cigarette, e-cigarette, ENDS, smoking, or nicotine AND marijuana OR cannabis OR THC. Co-use may pose additive risk for toxicant exposure as certain co-users (e.g., blunt users) tend to have higher breath carbon monoxide levels and cannabis smoke can have higher levels of some carcinogens than tobacco smoke. Cannabis use via ENDS is low and occurs primarily among established tobacco or cannabis users, but its incidence may be increasing and expanding to tobacco/cannabis naïve individuals. There are several methodological issues across co-use research including varying definitions of co-use, sample sizes, lack of control for important covariates (e.g., time since last cigarette), and inconsistent measurement of outcome variables. There are some known additive risks for toxicant exposure as a result of co-use. Research utilizing consistent methodologies is needed to further establish the additive risk of co-use. Future research should also be aware of novel technologies (e.g., ENDS) as they likely alter some toxicant exposure when used alone and with cannabis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Sunlight stability and rain-fastness of formulations of Baculovirus heliothis

International Nuclear Information System (INIS)

Ignoffo, C.M.; Garcia, C.; Saathoff, S.G.

1997-01-01

Sunlight-Ultraviolet, with an activity spectrum from 290 to 400 nm, is the most destructive factor affecting the persistence of baculoviruses. Benzopurpurin (a disazo dye) and carbon provided the best protection when polyhedral inclusion bodies (PIB) of Baculovirus heliothis were exposed to an artificial spectrum simulating sunlight-UV (UV). Greater than 75% of the original PIB activity was still present after 48 h of sunlight-UV. When sprayed on soybeans and exposed to natural sunlight, only formulations with carbon provided significant protection of PIB. The half-life of formulations were PIB-only 4.9 +/- 1.4 h (mean +/- SE), PIB + polymer (pyrrolidone-based sticker) 3.3 +/- 0.6 h, PIB + polymer + benzopurpurin 3.4 +/- 0.7 h, and PIB + polymer + carbon 27.7 +/- 5.2 h. PIB of B. heliothis tenaciously adhere to soybean, Glycine max (L.) Merrill, leaflets after spraying and drying. Less than 6% of the PIB activity of nonformulated PIB was lost after a drenching, simulated rainfall. More than 97% of the original PIB activity of carbon formulations was still present on soybean leaflets after 10 h of exposure to sunlight-UV. In contrast, 20% was present for formulations without carbon

Quality evaluation of extemporaneous delayed-release liquid formulations of lansoprazole.

Science.gov (United States)

Melkoumov, Alexandre; Soukrati, Amina; Elkin, Igor; Forest, Jean-Marc; Hildgen, Patrice; Leclair, Grégoire

2011-11-01

The quality attributes of extemporaneous delayed-release liquid formulations of lansoprazole for oral administration were evaluated. A novel liquid formulation (3 mg/mL) of Prevacid FasTab in an Ora-Blend vehicle was prepared and compared with the Prevacid FasTab 30 mg and Prevacid-sodium bicarbonate 1 M formulation (3 mg/mL). The latter formulation was combined with hydrochloric acid 0.1 N, and the remaining lansoprazole content was assayed by high-performance liquid chromatography (HPLC). A batch of delayed-release liquid formulation was prepared to evaluate content uniformity. For content assay, three samples were prepared for each evaluated condition and each sample was analyzed in triplicate by HPLC. The lansoprazole in the sodium bicarbonate formulation was extensively degraded by quantities of hydrochloric acid 0.1 N in excess of 100 mL. Storage time and temperature had a significant effect on lansoprazole stability in the Ora-Blend formulation. The drug remained stable for seven days when the formulation was stored at 4.5-5.5 °C, but storage at 21-22 °C or the reduction of pH with citric acid accelerated lansoprazole degradation. The amount of lansoprazole released from the Ora-Blend formulation during the buffer stage of the dissolution test decreased with increases in formulation storage time, in formulation storage temperature, and in the amount of lansoprazole released and degraded during the acid stage of the test. An extemporaneous formulation consisting of lansoprazole microgranules in Ora-Blend maintained acceptable quality attributes when stored for three days at 4.5-5.5 °C.

High drug load, stable, manufacturable and bioavailable fenofibrate formulations in mesoporous silica: a comparison of spray drying versus solvent impregnation methods.

Science.gov (United States)

Hong, Shiqi; Shen, Shoucang; Tan, David Cheng Thiam; Ng, Wai Kiong; Liu, Xueming; Chia, Leonard S O; Irwan, Anastasia W; Tan, Reginald; Nowak, Steven A; Marsh, Kennan; Gokhale, Rajeev

2016-01-01

Encapsulation of drugs in mesoporous silica using co-spray drying process has been recently explored as potential industrial method. However, the impact of spray drying on manufacturability, physiochemical stability and bioavailability in relation to conventional drug load processes are yet to be fully investigated. Using a 2(3) factorial design, this study aims to investigate the effect of drug-loading process (co-spray drying and solvent impregnation), mesoporous silica pore size (SBA-15, 6.5 nm and MCM-41, 2.5 nm) and percentage drug load (30% w/w and 50% w/w) on material properties, crystallinity, physicochemical stability, release profiles and bioavailability of fenofibrate (FEN) loaded into mesoporous silica. From the scanning electronic microscopy (SEM) images, powder X-ray diffraction and Differential scanning calorimetry measurements, it is indicated that the co-spray drying process was able to load up to 50% (w/w) FEN in amorphous form onto the mesoporous silica as compared to the 30% (w/w) for solvent impregnation. The in vitro dissolution rate of the co-spray dried formulations was also significantly (p = 0.044) better than solvent impregnated formulations at the same drug loading. Six-month accelerated stability test at 40 °C/75 RH in open dish indicated excellent physical and chemical stability of formulations prepared by both methods. The amorphous state of FEN and the enhanced dissolution profiles were well preserved, and very low levels of degradation were detected after storage. The dog data for the three selected co-spray-dried formulations revealed multiple fold increment in FEN bioavailability compared to the reference crystalline FEN. These results validate the viability of co-spray-dried mesoporous silica formulations with high amorphous drug load as potential drug delivery systems for poorly water soluble drugs.

Intratracheal exposure of common marmosets to MERS-CoV Jordan-n3/2012 or MERS-CoV EMC/2012 isolates does not result in lethal disease

Energy Technology Data Exchange (ETDEWEB)

Johnson, Reed F., E-mail: johnsonreed@mail.nih.gov [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Via, Laura E. [Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Kumar, Mia R.; Cornish, Joseph P. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Yellayi, Srikanth; Huzella, Louis; Postnikova, Elena; Oberlander, Nicholas; Bartos, Christopher; Ork, Britini L.; Mazur, Steven; Allan, Cindy; Holbrook, Michael R. [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Solomon, Jeffrey [Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD (United States); Johnson, Joshua C. [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Pickel, James [Transgenic Core Facility, National Institute of Mental Health, National Institutes of Health, Bethesda, MD (United States); Hensley, Lisa E. [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Jahrling, Peter B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States)

2015-11-15

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to be a threat to human health in the Middle East. Development of countermeasures is ongoing; however, an animal model that faithfully recapitulates human disease has yet to be defined. A recent study indicated that inoculation of common marmosets resulted in inconsistent lethality. Based on these data we sought to compare two isolates of MERS-CoV. We followed disease progression in common marmosets after intratracheal exposure with: MERS-CoV-EMC/2012, MERS-CoV-Jordan-n3/2012, media, or inactivated virus. Our data suggest that common marmosets developed a mild to moderate non-lethal respiratory disease, which was quantifiable by computed tomography (CT), with limited other clinical signs. Based on CT data, clinical data, and virological data, MERS-CoV inoculation of common marmosets results in mild to moderate clinical signs of disease that are likely due to manipulations of the marmoset rather than as a result of robust viral replication. - Highlights: • Common marmosets infected with MERS-EMC and MERS-JOR did not develop lethal disease. • Infected subjects developed transient signs of clinical disease. • CT indicated few differences between the infected and control groups. • Marmosets do not faithfully replicate human MERS pathogenesis.

Intratracheal exposure of common marmosets to MERS-CoV Jordan-n3/2012 or MERS-CoV EMC/2012 isolates does not result in lethal disease

International Nuclear Information System (INIS)

Johnson, Reed F.; Via, Laura E.; Kumar, Mia R.; Cornish, Joseph P.; Yellayi, Srikanth; Huzella, Louis; Postnikova, Elena; Oberlander, Nicholas; Bartos, Christopher; Ork, Britini L.; Mazur, Steven; Allan, Cindy; Holbrook, Michael R.; Solomon, Jeffrey; Johnson, Joshua C.; Pickel, James; Hensley, Lisa E.; Jahrling, Peter B.

2015-01-01

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to be a threat to human health in the Middle East. Development of countermeasures is ongoing; however, an animal model that faithfully recapitulates human disease has yet to be defined. A recent study indicated that inoculation of common marmosets resulted in inconsistent lethality. Based on these data we sought to compare two isolates of MERS-CoV. We followed disease progression in common marmosets after intratracheal exposure with: MERS-CoV-EMC/2012, MERS-CoV-Jordan-n3/2012, media, or inactivated virus. Our data suggest that common marmosets developed a mild to moderate non-lethal respiratory disease, which was quantifiable by computed tomography (CT), with limited other clinical signs. Based on CT data, clinical data, and virological data, MERS-CoV inoculation of common marmosets results in mild to moderate clinical signs of disease that are likely due to manipulations of the marmoset rather than as a result of robust viral replication. - Highlights: • Common marmosets infected with MERS-EMC and MERS-JOR did not develop lethal disease. • Infected subjects developed transient signs of clinical disease. • CT indicated few differences between the infected and control groups. • Marmosets do not faithfully replicate human MERS pathogenesis.

Effects of time-variable exposure regimes of the insecticide chlorpyrifos on freshwater invertebrate communities in microcosms

NARCIS (Netherlands)

Zafar, M.I.; Wijngaarden, van R.; Roessink, I.; Brink, van den P.J.

2011-01-01

The present study compared the effects of different time-variable exposure regimes having the same time-weighted average (TWA) concentration of the organophosphate insecticide chlorpyrifos on freshwater invertebrate communities to enable extrapolation of effects across exposure regimes. The

Ozone co-exposure modifies cardiac responses to fine and ultrafine ambient particulate matter in mice: concordance of electrocardiogram and mechanical responses

Science.gov (United States)

BackgroundStudies have shown a relationship between air pollution and increased risk of cardiovascular morbidity and mortality. Due to the complexity of ambient air pollution composition, recent studies have examined the effects of co-exposure, particularly particulate matter (PM...

Field Tests of Real-time In-situ Dissolved CO2 Monitoring for CO2 Leakage Detection in Groundwater

Science.gov (United States)

Yang, C.; Zou, Y.; Delgado, J.; Guzman, N.; Pinedo, J.

2016-12-01

Groundwater monitoring for detecting CO2 leakage relies on groundwater sampling from water wells drilled into aquifers. Usually groundwater samples are required be collected periodically in field and analyzed in the laboratory. Obviously groundwater sampling is labor and cost-intensive for long-term monitoring of large areas. Potential damage and contamination of water samples during the sampling process can degrade accuracy, and intermittent monitoring may miss changes in the geochemical parameters of groundwater, and therefore signs of CO2 leakage. Real-time in-situ monitoring of geochemical parameters with chemical sensors may play an important role for CO2 leakage detection in groundwater at a geological carbon sequestration site. This study presents field demonstration of a real-time in situ monitoring system capable of covering large areas for detection of low levels of dissolved CO2 in groundwater and reliably differentiating natural variations of dissolved CO2 concentration from small changes resulting from leakage. The sand-alone system includes fully distributed fiber optic sensors for carbon dioxide detection with a unique sensor technology developed by Intelligent Optical Systems. The systems were deployed to the two research sites: the Brackenridge Field Laboratory where the aquifer is shallow at depths of 10-20 ft below surface and the Devine site where the aquifer is much deeper at depths of 140 to 150 ft. Groundwater samples were periodically collected from the water wells which were installed with the chemical sensors and further compared to the measurements of the chemical sensors. Our study shows that geochemical monitoring of dissolved CO2 with fiber optic sensors could provide reliable CO2 leakage signal detection in groundwater as long as CO2 leakage signals are stronger than background noises at the monitoring locations.

The molecular basis of simple relationships between exposure concentration and toxic effects with time.

Science.gov (United States)

Tennekes, Henk A; Sánchez-Bayo, Francisco

2013-07-05

Understanding the toxicity of chemicals to organisms requires considering the molecular mechanisms involved as well as the relationships between exposure concentration and toxic effects with time. Our current knowledge about such relationships is mainly explained from a toxicodynamic and toxicokinetic perspective. This paper re-introduces an old approach that takes into account the biochemical mode of action and their resulting biological effects over time of exposure. Empirical evidence demonstrates that the Druckrey-Küpfmüller toxicity model, which was validated for chemical carcinogens in the early 1960s, is also applicable to a wide range of toxic compounds in ecotoxicology. According to this model, the character of a poison is primarily determined by the reversibility of critical receptor binding. Chemicals showing irreversible or slowly reversible binding to specific receptors will produce cumulative effects with time of exposure, and whenever the effects are also irreversible (e.g. death) they are reinforced over time; these chemicals have time-cumulative toxicity. Compounds having non-specific receptor binding, or involving slowly reversible binding to some receptors that do not contribute to toxicity, may also be time-dependent; however, their effects depend primarily on the exposure concentration, with time playing a minor role. Consequently, the mechanism of toxic action has important implications for risk assessment. Traditional risk approaches cannot predict the impacts of toxicants with time-cumulative toxicity in the environment. New assessment procedures are needed to evaluate the risk that the latter chemicals pose on humans and the environment. An example is shown to explain how the risk of time-dependent toxicants is underestimated when using current risk assessment protocols. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Exposure to carbon monoxide, fine particle mass, and ultrafine particle number in Jakarta, Indonesia: effect of commute mode.

Science.gov (United States)

Both, Adam F; Westerdahl, Dane; Fruin, Scott; Haryanto, Budi; Marshall, Julian D

2013-01-15

We measured real-time exposure to PM(2.5), ultrafine PM (particle number) and carbon monoxide (CO) for commuting workers school children, and traffic police, in Jakarta, Indonesia. In total, we measured exposures for 36 individuals covering 93 days. Commuters in private cars experienced mean (st dev) exposures of 22 (9.4) ppm CO, 91 (38) μg/m(3)PM(2.5), and 290 (150)×10(3) particles cm(-3). Mean concentrations were higher in public transport than in private cars for PM(2.5) (difference in means: 22%) and particle counts (54%), but not CO, likely reflecting in-vehicle particle losses in private cars owing to air-conditioning. However, average commute times were longer for private car commuters than public transport commuters (in our sample, 24% longer: 3.0 vs. 2.3 h per day). Commute and traffic-related exposures experienced by Jakarta residents are among the highest in the world, owing to high on-road concentrations and multi-hour commutes. Copyright © 2012 Elsevier B.V. All rights reserved.

Bioavailability of two oral formulations of triazolam using radioreceptor assay

Energy Technology Data Exchange (ETDEWEB)

Lapka, R; Cepelakova, H; Rejholec, V; Franc, Z

1986-04-01

The radioreceptor assay (RRA) was used to quantitate plasma triazolam concentration in eight female volunteers following single 0.5 mg doses of two tablet formulations in a cross-over study. Bioavailability in terms of area under the plasma concentration versus time curve, maximum plasma concentration, time to maximum, and mean residence time was not statistically significantly different from one formulation to the other.

Radiation exposure in transcatheter patent ductus arteriosus closure: time to tune?

Science.gov (United States)

Villemain, Olivier; Malekzadeh-Milani, Sophie; Sitefane, Fidelio; Mostefa-Kara, Meriem; Boudjemline, Younes

2018-05-01

The aims of this study were to describe radiation level at our institution during transcatheter patent ductus arteriosus occlusion and to evaluate the components contributing to radiation exposure. Transcatheter occlusion relying on X-ray imaging has become the treatment of choice for patients with patent ductus arteriosus. Interventionists now work hard to minimise radiation exposure in order to reduce risk of induced cancers. We retrospectively reviewed all consecutive children who underwent transcatheter closure of patent ductus arteriosus from January 2012 to January 2016. Clinical data, anatomical characteristics, and catheterisation procedure parameters were reported. Radiation doses were analysed for the following variables: total air kerma, mGy; dose area product, Gy.cm2; dose area product per body weight, Gy.cm2/kg; and total fluoroscopic time. A total of 324 patients were included (median age=1.51 [Q1-Q3: 0.62-4.23] years; weight=10.3 [6.7-17.0] kg). In all, 322/324 (99.4%) procedures were successful. The median radiation doses were as follows: total air kerma: 26 (14.5-49.3) mGy; dose area product: 1.01 (0.56-2.24) Gy.cm2; dose area product/kg: 0.106 (0.061-0.185) Gy.cm2/kg; and fluoroscopic time: 2.8 (2-4) min. In multivariate analysis, a weight >10 kg, a ductus arteriosus width <2 mm, complications during the procedure, and a high frame rate (15 frames/second) were risk factors for an increased exposure. Lower doses of radiation can be achieved with subsequent recommendations: technical improvement, frame rate reduction, avoidance of biplane cineangiograms, use of stored fluoroscopy as much as possible, and limitation of fluoroscopic time. A greater use of echocardiography might even lessen the exposure.

Bioavailability of syrup and tablet formulations of cefetamet pivoxil.

Science.gov (United States)

Ducharme, M P; Edwards, D J; McNamara, P J; Stoeckel, K

1993-12-01

Two studies examining the bioavailability of cefetamet pivoxil in healthy male subjects were conducted. In the first, the bioavailabilities of the 250-mg (M250) and M500 tablet formulations of cefetamet pivoxil to be marketed were compared with that of a tablet used in clinical trials. All products were given with food at a dose of 500 mg. In the second study, the bioavailability of the syrup formulation was evaluated under both fasting and nonfasting conditions and compared with that of the M500 tablet formulation given with food. The absolute bioavailabilities of the M500 and M250 tablets (55.0% +/- 8.0% and 55.7% +/- 7.0%, respectively) were not significantly different from that of the clinical-trial formulation (49.8% +/- 8.5%). The newer tablet formulations exhibited faster absorption as evidenced by higher peak concentrations (3.8 [M500] and 3.9 [M250] mg/liter compared with 3.2 mg/liter for the clinical-trial formulation), a shorter time to peak concentration, and a shorter mean absorption time. The syrup formulation was found to have significantly lower absolute bioavailability (37.9% +/- 6.0%) compared with that of the M500 tablet (58.4% +/- 9.0%) when both were given with food. Food had no significant effect on the bioavailability of the syrup, which averaged 34.0% +/- 8.6% under fasting conditions, although absorption was delayed by food (mean absorption time increased from 2.2 to 3.9 h). This contrasts with the results of previous studies documenting significant increases in tablet bioavailability with food. Despite the lower bioavailability of the syrup, unbound-cefetamet concentrations are expected to remain above the MICs for 90% of the strains tested for susceptible organisms for approximately 10 h of the usual 12-h dosing interval with both syrup and tablet formulations of cefetamet pivoxil given with food.

Formulation of best-fit hydrophile/lipophile balance-dielectric permittivity demulsifiers for treatment of crude oil emulsions

Directory of Open Access Journals (Sweden)

C.M. Ojinnaka

2016-12-01

Full Text Available The commerce of crude oil depends heavily on its water and salt contents usually referred to as Basic Sediments and Water (BS&W, which is co-produced with the crude oil in the form of emulsion. The lower the BS&W, the higher the market value of the crude. The presence of water in crude oil causes corrosion, lowers capacity utilization of production and processing plant parts and pipelines, reduces oil recovery and increases the oil content of the effluent water. The stabilizing factors of crude oil emulsions vary from one oil field to the other and with time in the same well as co-produced water increases, or after a well treatment and Enhanced Oil Recovery Operations (EOR. Periodical assessment and possible change of demulsifiers employed is therefore necessary at certain stages of crude oil productions, but this is not encouraged due to lack of general formulation procedures and the rigorous nature of bottle test method that is currently being used for assessment and selection. In this paper, the factors that affect the stability of crude oil emulsions are presented. Efforts of researchers in formulating demulsifiers based on these factors and their screening methods were reviewed. The context sets the stage for further exploration of possible relationship(s between the physical parameters of the crude oil and the demulsifiers, and exploiting same in the formulation of new demulsifiers capable of resolving crude oil emulsions using chemicals with improved surface activity and crude extracts of indigenous plants.

Formulation and evaluation of biodegradable nanoparticles for the oral delivery of fenretinide.

Science.gov (United States)

Graves, Richard A; Ledet, Grace A; Glotser, Elena Y; Mitchner, Demaurian M; Bostanian, Levon A; Mandal, Tarun K

2015-08-30

Fenretinide is an anticancer drug with low water solubility and poor bioavailability. The goal of this study was to develop biodegradable polymeric nanoparticles of fenretinide with the intent of increasing its apparent aqueous solubility and intestinal permeability. Three biodegradable polymers were investigated for this purpose: two different poly lactide-co-glycolide (PLGA) polymers, one acid terminated and one ester terminated, and one poly lactide-co-glycolide/polyethylene glycol (PLGA/PEG) diblock copolymer. Nanoparticles were obtained by using an emulsification solvent evaporation technique. The formulations were characterized by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and particle size analysis. Dissolution studies and Caco-2 cell permeation studies were also carried out for all formulations. Ultra high performance liquid chromatography coupled with mass spectrometry (UPLC/MS) and ultraviolet detection was used for the quantitative determination of fenretinide. Drug loading and the type of polymer affected the nanoparticles' physical properties, drug release rate, and cell permeability. While the acid terminated PLGA nanoparticles performed the best in drug release, the ester terminated PLGA nanoparticles performed the best in the Caco-2 cell permeability assays. The PLGA/PEG copolymer nanoparticles performed better than the formulations with ester terminated PLGA in terms of drug release but had the poorest performance in terms of cell permeation. All three categories of formulations performed better than the drug alone in both drug release and cell permeation studies. Copyright © 2015 Elsevier B.V. All rights reserved.

Time series pCO2 at a coastal mooring: Internal consistency, seasonal cycles, and interannual variability

Science.gov (United States)

Reimer, Janet J.; Cai, Wei-Jun; Xue, Liang; Vargas, Rodrigo; Noakes, Scott; Hu, Xinping; Signorini, Sergio R.; Mathis, Jeremy T.; Feely, Richard A.; Sutton, Adrienne J.; Sabine, Christopher; Musielewicz, Sylvia; Chen, Baoshan; Wanninkhof, Rik

2017-08-01

Marine carbonate system monitoring programs often consist of multiple observational methods that include underway cruise data, moored autonomous time series, and discrete water bottle samples. Monitored parameters include all, or some of the following: partial pressure of CO2 of the water (pCO2w) and air, dissolved inorganic carbon (DIC), total alkalinity (TA), and pH. Any combination of at least two of the aforementioned parameters can be used to calculate the others. In this study at the Gray's Reef (GR) mooring in the South Atlantic Bight (SAB) we: examine the internal consistency of pCO2w from underway cruise, moored autonomous time series, and calculated from bottle samples (DIC-TA pairing); describe the seasonal to interannual pCO2w time series variability and air-sea flux (FCO2), as well as describe the potential sources of pCO2w variability; and determine the source/sink for atmospheric pCO2. Over the 8.5 years of GR mooring time series, mooring-underway and mooring-bottle calculated-pCO2w strongly correlate with r-values > 0.90. pCO2w and FCO2 time series follow seasonal thermal patterns; however, seasonal non-thermal processes, such as terrestrial export, net biological production, and air-sea exchange also influence variability. The linear slope of time series pCO2w increases by 5.2 ± 1.4 μatm y-1 with FCO2 increasing 51-70 mmol m-2 y-1. The net FCO2 sign can switch interannually with the magnitude varying greatly. Non-thermal pCO2w is also increasing over the time series, likely indicating that terrestrial export and net biological processes drive the long term pCO2w increase.

Mendelian randomization analysis of a time-varying exposure for binary disease outcomes using functional data analysis methods.

Science.gov (United States)

Cao, Ying; Rajan, Suja S; Wei, Peng

2016-12-01

A Mendelian randomization (MR) analysis is performed to analyze the causal effect of an exposure variable on a disease outcome in observational studies, by using genetic variants that affect the disease outcome only through the exposure variable. This method has recently gained popularity among epidemiologists given the success of genetic association studies. Many exposure variables of interest in epidemiological studies are time varying, for example, body mass index (BMI). Although longitudinal data have been collected in many cohort studies, current MR studies only use one measurement of a time-varying exposure variable, which cannot adequately capture the long-term time-varying information. We propose using the functional principal component analysis method to recover the underlying individual trajectory of the time-varying exposure from the sparsely and irregularly observed longitudinal data, and then conduct MR analysis using the recovered curves. We further propose two MR analysis methods. The first assumes a cumulative effect of the time-varying exposure variable on the disease risk, while the second assumes a time-varying genetic effect and employs functional regression models. We focus on statistical testing for a causal effect. Our simulation studies mimicking the real data show that the proposed functional data analysis based methods incorporating longitudinal data have substantial power gains compared to standard MR analysis using only one measurement. We used the Framingham Heart Study data to demonstrate the promising performance of the new methods as well as inconsistent results produced by the standard MR analysis that relies on a single measurement of the exposure at some arbitrary time point. © 2016 WILEY PERIODICALS, INC.

Chromosome damage and clinical manifestation in a fetus and the mother after accidental 60Co exposure in Xinzhou

International Nuclear Information System (INIS)

Wang Jiajing; Mu Ying; Wang Shanmi

1995-01-01

The authors present the clinical effect and chromosome damage sustained by a fetus and the four months pregnant mother in an accidental 60 Co exposure in November of 1992 in Xinzhou, Shanxi Province. The mother suffered from a moderate acute radiation sickness with ratardation of fetal development. After delivery, the infant's body length, body weight and head circumference were all lowered by three percentiles compared with the normals. Four months after the exposure, the assay of the mother's peripheral lymphocytes showed a chromosome aberration rate of 36%, while concomitant examination of the baby failed to reveal any chromosome abnormality although the sister chromatid exchange rate was remarkably higher than that of the mother and the normal control

Exploring the potential role of tungsten carbide cobalt (WC-Co) nanoparticle internalization in observed toxicity toward lung epithelial cells in vitro

Energy Technology Data Exchange (ETDEWEB)

Armstead, Andrea L. [Biomaterials, Bioengineering and Nanotechnology Laboratory, Department of Orthopaedics, School of Medicine, West Virginia University, Morgantown, WV 26506 (United States); Pharmaceutical and Pharmacological Sciences Graduate Program, School of Pharmacy, West Virginia University, Morgantown, WV 26506 (United States); Arena, Christopher B. [Biomaterials, Bioengineering and Nanotechnology Laboratory, Department of Orthopaedics, School of Medicine, West Virginia University, Morgantown, WV 26506 (United States); E.J. Van Liere Research Program, School of Medicine, West Virginia University, Morgantown, WV 26506 (United States); Li, Bingyun, E-mail: bili@hsc.wvu.edu [Biomaterials, Bioengineering and Nanotechnology Laboratory, Department of Orthopaedics, School of Medicine, West Virginia University, Morgantown, WV 26506 (United States); Pharmaceutical and Pharmacological Sciences Graduate Program, School of Pharmacy, West Virginia University, Morgantown, WV 26506 (United States); E.J. Van Liere Research Program, School of Medicine, West Virginia University, Morgantown, WV 26506 (United States); Mary Babb Randolph Cancer Center, Morgantown, WV 26506 (United States)

2014-07-01

Tungsten carbide cobalt (WC-Co) has been recognized as a workplace inhalation hazard in the manufacturing, mining and drilling industries by the National Institute of Occupational Safety and Health. Exposure to WC-Co is known to cause “hard metal lung disease” but the relationship between exposure, toxicity and development of disease remain poorly understood. To better understand this relationship, the present study examined the role of WC-Co particle size and internalization on toxicity using lung epithelial cells. We demonstrated that nano- and micro-WC-Co particles exerted toxicity in a dose- and time-dependent manner and that nano-WC-Co particles caused significantly greater toxicity at lower concentrations and shorter exposure times compared to micro-WC-Co particles. WC-Co particles in the nano-size range (not micron-sized) were internalized by lung epithelial cells, which suggested that internalization may play a key role in the enhanced toxicity of nano-WC-Co particles over micro-WC-Co particles. Further exploration of the internalization process indicated that there may be multiple mechanisms involved in WC-Co internalization such as actin and microtubule based cytoskeletal rearrangements. These findings support our hypothesis that WC-Co particle internalization contributes to cellular toxicity and suggest that therapeutic treatments inhibiting particle internalization may serve as prophylactic approaches for those at risk of WC-Co particle exposure. - Highlights: • Hard metal (WC-Co) particle toxicity was established in lung epithelial cells. • Nano-WC-Co particles caused greater toxicity than micro-WC-Co particles. • Nano- and micro-WC-Co particles were capable of inducing cellular apoptosis. • Nano-WC-Co particles were internalized by lung epithelial cells. • WC-Co particle internalization was mediated by actin dynamics.

Exploring the potential role of tungsten carbide cobalt (WC-Co) nanoparticle internalization in observed toxicity toward lung epithelial cells in vitro

International Nuclear Information System (INIS)

Armstead, Andrea L.; Arena, Christopher B.; Li, Bingyun

2014-01-01

Tungsten carbide cobalt (WC-Co) has been recognized as a workplace inhalation hazard in the manufacturing, mining and drilling industries by the National Institute of Occupational Safety and Health. Exposure to WC-Co is known to cause “hard metal lung disease” but the relationship between exposure, toxicity and development of disease remain poorly understood. To better understand this relationship, the present study examined the role of WC-Co particle size and internalization on toxicity using lung epithelial cells. We demonstrated that nano- and micro-WC-Co particles exerted toxicity in a dose- and time-dependent manner and that nano-WC-Co particles caused significantly greater toxicity at lower concentrations and shorter exposure times compared to micro-WC-Co particles. WC-Co particles in the nano-size range (not micron-sized) were internalized by lung epithelial cells, which suggested that internalization may play a key role in the enhanced toxicity of nano-WC-Co particles over micro-WC-Co particles. Further exploration of the internalization process indicated that there may be multiple mechanisms involved in WC-Co internalization such as actin and microtubule based cytoskeletal rearrangements. These findings support our hypothesis that WC-Co particle internalization contributes to cellular toxicity and suggest that therapeutic treatments inhibiting particle internalization may serve as prophylactic approaches for those at risk of WC-Co particle exposure. - Highlights: • Hard metal (WC-Co) particle toxicity was established in lung epithelial cells. • Nano-WC-Co particles caused greater toxicity than micro-WC-Co particles. • Nano- and micro-WC-Co particles were capable of inducing cellular apoptosis. • Nano-WC-Co particles were internalized by lung epithelial cells. • WC-Co particle internalization was mediated by actin dynamics

[Optimization of formulations for dietetic pastry products].

Science.gov (United States)

Villarroel, M; Uquiche, E; Brito, G; Cancino, M

2000-03-01

Optimized formulations of dietetic pastry products such as cake and sponge cake premixes were formulated using the surface response methodology. % Emulsifier agent and baking time were the selected independent variables for cake, as well as % emulsifier agent % chlorinated flour the variables selected for sponge cake. Three different level of each variable summing up thirteen experimental formulae of each product were assessed to optimize the variables that could have some influence in the sensory characteristics of these dietetic products. The total sensory quality was determined for both dietetic products using the composite scoring test and a panel of 18 trained judges. Looking at the contour graphic and considering economic aspects the best combination of variables for cake formulation was 2% emulsifier agent and 48 minutes for baking time, With respect to sponge cake, the best combination was 6% emulsifier agent and 48% chlorinated flour. Shelf life studies showed that both dietetic formulations remained stable during storage conditions of 75 days at 30 degrees C. During this period, significant differences in sensory characteristics were not found (p pastry products had good acceptability, and open up marketing opportunities for new products with potential health benefits to consumers.

Co-exposure to titanium dioxide nanoparticles does not affect cadmium toxicity in radish seeds (Raphanus sativus).

Science.gov (United States)

Manesh, R Roshan; Grassi, G; Bergami, E; Marques-Santos, L F; Faleri, C; Liberatori, G; Corsi, I

2018-02-01

decrease on root elongation was observed against controls (p germination %, GI and root elongation was observed in seeds co-exposed to n-TiO 2 and CdCl 2 at the highest concentrations (1000mg/L n-TiO 2 and 250mg/L CdCl 2 ) compared to co-exposed seeds at low concentration (1mg/L n-TiO 2 and 1mg/L CdCl 2 ) and controls (p seeds exposed to single high n-TiO 2 concentration (1000mg/L) was observed while n-TiO 2 (1mg/L), CdCl 2 (1 and 250mg/L) and co-exposure resulted significantly decreased compared to controls (p seeds exposed to 1000mg/L n-TiO 2 but no significantly was observed, however both n-TiO 2 and CdCl 2 alone (1 and 250mg/L, respectively) or in combinations caused a significant decrease in GST activity (p seeds. Morphological alterations in nuclei, vacuoles and shape of radish root cells were observed upon single Cd exposure and not abolished in the presence of n-TiO 2 . Nevertheless, although n-TiO 2 seems not to reduce Cd toxicity at high concentration (up to 250mg/L), interactions cannot be excluded based on obtained results. Copyright © 2017 Elsevier Inc. All rights reserved.

Pharmacokinetic and pharmacodynamic characteristics of a new pediatric formulation of artemether-lumefantrine in African children with uncomplicated Plasmodium falciparum malaria.

Science.gov (United States)

Djimdé, Abdoulaye A; Tekete, Mamadou; Abdulla, Salim; Lyimo, John; Bassat, Quique; Mandomando, Inacio; Lefèvre, Gilbert; Borrmann, Steffen

2011-09-01

The pharmacokinetic and pharmacodynamic properties of a new pediatric formulation of artemether-lumefantrine, dispersible tablet, were determined within the context of a multicenter, randomized, parallel-group study. In an exploratory approach, we compared a new pediatric formulation with the tablet formulation administered crushed in the treatment of African children with uncomplicated Plasmodium falciparum malaria. Patients were randomized to 3 different dosing groups (weights of 5 to DHA), were determined at 1 and 2 h after the first dose of dispersible (n = 91) and crushed (n = 93) tablets. A full pharmacokinetic profile of lumefantrine was reconstituted on the basis of 310 (dispersible tablet) and 315 (crushed tablet) plasma samples, collected at 6 different time points (1 sample per patient). Dispersible and crushed tablets showed similar artemether and DHA maximum concentrations in plasma (C(max)) for the different body weight groups, with overall means of 175 ± 168 and 190 ± 168 ng/ml, respectively, for artemether and 64.7 ± 58.1 and 63.7 ± 65.0 ng/ml, respectively, for DHA. For lumefantrine, the population C(max) were 6.3 μg/ml (dispersible tablet) and 7.7 μg/ml (crushed tablet), whereas the areas under the concentration-time curves from time zero to the time of the last quantifiable plasma concentration measured were 574 and 636 μg · h/ml, respectively. For both formulations, descriptive quintile analyses showed no apparent association between artemether/DHA C(max) and parasite clearance time or between the lumefantrine C(max) and the occurrence of adverse events or corrected QT interval changes. The results suggest that the dispersible tablet provides adequate systemic exposure to artemether, DHA, and lumefantrine in African children with uncomplicated P. falciparum malaria.

Effects of continuous exposure to carbon monoxide on auditory vigilance in man

Energy Technology Data Exchange (ETDEWEB)

Davies, D.M.; Jolly, E.J.; Pethybridge, R.J.; Colquhoun, W.P.

1981-02-01

Six different groups of non-smoking young male subjcts were stutied separately for 18 consecutive days each in a closed controlled-environment human exposure chamber. Each group was subjected to a 5-day control period in fresh air followed successively by an 8-day period of continuous exposure to 50 ppm, 15 ppm or 0 ppm (controll) by volume of carbon monoxide (CO) in air, and a 5-day recovery period in fresh air. The subjects performed a 1-h auditory vigilance task every day at the same time of day in a fixed qualitative, quantitative, and temporal relationship with food intake, consumption of stimulating beverages, physical activity, and sleep. It was concluded that such CO exposure, involving the continuous carriage of carboxyhaemoglobin loads up to 70%, was without significant effect on auditory vigilance.

Long term exposure to respirable volcanic ash on Montserrat: a time series simulation

Science.gov (United States)

Hincks, T. K.; Aspinall, W. P.; Baxter, P. J.; Searl, A.; Sparks, R. S. J.; Woo, G.

2006-01-01

Frequent ash fallout from long-lived eruptions (with active phases greater than 5 years) may lead to local populations experiencing unacceptably high cumulative exposures to respirable particulate matter. Ash from Montserrat has been shown to contain significant levels of cristobalite and other reactive agents that are associated with an increased risk of developing pneumoconiosis (including silicosis) and other long-term health problems. There are a number of difficulties associated with estimating risks in populations due to uncertain and wide ranging individual exposures, change in behaviour with time and the natural variation in individual response. Present estimates of risk in workers and other population groups are simplifications based on a limited number of exposure measurements taken on Montserrat (1996-1999), and exposure-response curves from epidemiological studies of coal workers exposed to siliceous dust. In this paper we present a method for calculating the long-term cumulative exposure to cristobalite from volcanic ash by Monte Carlo simulation. Code has been written to generate synthetic time series for volcanic activity, rainfall, ash deposition and erosion to give daily ash deposit values and cristobalite fraction at a range of locations. The daily mean personal exposure for PM10 and cristobalite is obtained by sampling from a probability distribution, with distribution parameters dependent on occupation, ground deposit depth and daily weather conditions. Output from multiple runs is processed to calculate the exceedance probability for cumulative exposure over a range of occupation types, locations and exposure periods. Results are interpreted in terms of current occupational standards, and epidemiological exposure-response functions for silicosis are applied to quantify the long-term health risk. Assuming continuing volcanic activity, median risk of silicosis (profusion 1/0 or higher) for an average adult after 20 years continuous exposure is