bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of NORM Sources in Petroleum Coke Calcining Processes
Authors: Hamilton Ian S. , Halter Donald A. , Haumann Donald F. , Fruchtnicht Erich H. , Arno Matthew G.
Published: December 2010

Petroleum coke, or “petcoke,” is a waste by-product of the oil refining industry. The majority of petcoke consumption is in energy applications; catalyst coke is used as refinery fuel, anode coke for electricity conduction, and marketable coke for heating cement kilns. Roskill has predicted that long-term growth in petroleum coke production will be maintained, and may continue to increase slightly through 2012. Petcoke must first be calcined to drive off any undesirable petroleum by-products that would shorten the coke product-life cycle. As an example, the calcining process can take place in large, rotary kilns heated to maximum temperatures as high as approximately 1400–1540°C. The kilns and combustion/settling chambers, as well as some cooler units, are insulated with refractory bricks and other, interstitial materials, e.g., castable refractory materials, to improve the efficiency of the calcining process. The bricks are typically made of 70–85-percent bauxite, and are slowly worn away by the calcining process; bricks used to line the combustion chambers wear away, as well, but at a slower rate. It has been recognized that the refractory materials contain slight amounts of naturally occurring radioactive materials (NORM) from the uranium- and thorium-decay series. Similarly, low levels of NORM could be present in the petcoke feed stock given the nature of its origin. Neither the petcoke nor the refractory bricks represent appreciable sources of radiation or radioactive waste. However, some of the demolished bricks that have been removed from service because of the aforementioned wearing process have caused portal alarms to activate at municipal disposal facilities. This has lead to the current investigation into whether there is a NORM concentrating mechanism facilitated by the presence of the slightly radioactive feed stock in the presence of the slightly radioactive refractory materials, at calcining-zone temperatures. Research conducted to date has been used to determine the speciation and concentration of nuclides in both the feed stock and the various refractory materials, as well as the slag that forms at the interface of the two materials, as a function of temperature. Further investigation into any potential for generation of a NORM hazard as a result of refractory demolition has been conducted. Aerosol generation (mass loading), particle size distribution, and pulmonary solubility class have been investigated as a function of demolition-task description. In addition, external radiation levels in the kilns, chambers and waste piles, as a function of temperature profile and brick/operating history have been investigated.
The Inventory of Nuclear Liabilities: A Mission of Public Interest
Authors: Cosemans Christian , Cantarella Jacques , Bal Gerda
Published: December 2010

The safe management of a country’s radioactive substances in both the short and the long term implies a cost to its present society and necessitates financial resources to cover these costs. Once they are needed, these financial resources may prove to be insufficient or even completely lacking, leading to a nuclear liability. By virtue of article 9 of the Belgian law of 12th December 1997, the Belgian Government wishes to avoid the occurrence of such nuclear liabilities. This law charges ONDRAF/NIRAS, the Belgian Agency for Radioactive Waste and Enriched Fissile Materials with the mission to draw up a register of the localisation and the state of all nuclear sites and all sites containing radioactive substances, to estimate the costs of their decommissioning and remediation, to evaluate the existence and adequacy of the provisions for financing these future or current operations and to update the resulting inventory of nuclear liabilities on a five-yearly basis. This paper outlines the methodology put in place by ONDRAF/NIRAS to accomplish this assignment and highlights some of the results of this exercise. It than focuses on the main recommendations ONDRAF/NIRAS made to the Belgian Government on the field of avoiding potential nuclear liabilities.
Decommissioning in the United States: Past, Present and Future
Authors: Devgun Jas S.
Published: December 2010

The experience related to decommissioning of nuclear facilities in the United States is very substantial and covers power reactors, research reactors, and many facilities in the Department of Energy complex. The focus of this paper however is on the commercial power plants. With 104 operating reactors, the U.S. fleet of civilian reactors is still the largest in the world. Nuclear power industry in the United States has undergone a dramatic upturn after decades of stalemate. One effect of this nuclear renaissance has been that the plans have changed for several reactors that were initially destined for decommissioning. Instead, the focus now is on relicensing of the reactors and on power uprates. In fact, after the peak period between 1987 and 1998, no additional power reactors have been shutdown. On the contrary, power uprates in the past twenty years have added a cumulative capacity equivalent to five new reactors. Almost all the operating reactors plan to have license extensions, thus postponing the eventual decommissioning. Nevertheless, in addition to the 9 reactors where licenses have been terminated following decommissioning, 12 power and early demonstration reactors and 14 test & research reactors are permanently shutdown and are in decommissioning phase. Substantial experience and lessons learned are available from the U.S. projects that are of value to the international decommissioning projects, especially where such projects are in early stages. These lessons cover a wide array of areas from decommissioning plans, technology applications, large component removal, regulatory and public interface, decommissioning funding and costs, clean up criteria, surveys of the decommissioned site, and license termination. Additionally, because of the unavailability of a national spent fuel disposition facility, most decommissioning sites are constructing above ground interim storage facilities for the spent nuclear fuel. The U.S. nuclear power projects are also gearing up for the design and licensing of new reactors. Lessons from the past are useful in the development of such designs so that along with the other factors, the designs are optimized for eventual decommissioning as well. This paper provides an overview of the past reactor decommissioning, lessons learned from the past experience, and status of the current decommissioning activities and issues. It also presents some long term projections for the future of decommissioning in the United States.
Bioavailability of Mercury in Contaminated Oak Ridge Watershed and Potential Remediation of River/Runoff/Storm Water by an Aquatic Plant
Authors: Su Yi , Han Fengxiang X. , Chen Jian , Xia Yunju , Monts David L.
Published: December 2010

Historically as part of its national security mission, the U.S. Department of Energy’s Y-12 National Security Facility in Oak Ridge, TN, USA acquired a significant fraction of the world’s supply of elemental mercury. During the 1950’s and 1960’s, a large amount of elemental mercury escaped confinement and is still present in the buildings and grounds of the Y-12 Facility and in the Y-12 Watershed. Because of the adverse effects of elemental mercury and mercury compounds upon human health, the Oak Ridge Site is engaged in an ongoing effort to monitor and remediate the area. The main thrust of the Oak Ridge mercury remediation effort is currently scheduled for implementation in FY09. In order to more cost effectively implement those extensive remediation efforts, it is necessary now to obtain an improved understanding of the role that mercury and mercury compounds play in the Oak Ridge ecosystem. Most recently, concentrations of both total mercury and methylmercury in fish and water of lower East Fork Poplar Creek (LEFPC) of Oak Ridge increased although the majority of mercury in the site is mercury sulfide. This drives the US DOE and the Oak Ridge Site to study the long-term bioavailability of mercury and speciation at the site. The stability and bioavailability of mercury sulfide as affected by various biogeochemical conditions –presence of iron oxides have been studied. We examined the kinetic rate of dissolution of cinnabar from Oak Ridge soils and possible mechanisms and pathways in triggering the most recent increase of mercury solubility, bioavailability and mobility in Oak Ridge site. The effects of pH and chlorine on oxidative dissolution of cinnabar from cinnabar-contaminated Oak Ridge soils is discussed. On the other hand, aquatic plants might be good candidate for phytoremediate contaminated waste water and phytofiltration of collective storm water and surface runoff and river. Our greenhouse studies on uptake of Hg by water lettuce (Pistia stratiotes) show that water lettuce is effectively removing Hg from water solution and Hg was mostly stored in roots. One day of growing could remove 93–98% of Hg from water solutions. However, Hg shows acute toxicity to water lettuce as indicated by decreases in fresh biomass and moisture contents.
Use of Full Recovery Hydrolasing Equipment for Facility Decommissioning
Authors: Martin Scott A. , Adams Scott R.
Published: December 2010

The removal of surface contamination is a major challenge for nearly all nuclear facilities undergoing, or awaiting, decommissioning. Conventional means of surface decontamination can expose workers to unnecessary hazards, and are often not fit-for-purpose due to size constraints or weight restrictions. Additionally, conventional methods are not always easily deployed remotely due to their complexity or required services. The use of ultra high pressure water for surface decontamination, known as hydrolasing, is recognized as a technology which can be used in various applications requiring surface removal. Hydrolasing is an advantageous technology for many reasons including its versatility, overall simplicity and relative ease of remote deployment. For the nuclear industry, one of the largest challenges with regards to the use of hydrolasing is the requirement for the full recovery of the injected water and removed solids. For non-nuclear applications, there is often no requirement for recovery of the liquid and solid waste, which has led to few system designs which will recover the waste in full. S.A. Robotics’ experience with the deployment of ultra high pressure water systems for nuclear applications has shown that full recovery of injected water and removed solids is achievable in both underwater and in-air applications. Innovative equipment and system design have allowed S.A. Robotics’ hydrolasing systems to achieve near 100% solid and liquid recovery during concrete hydrolasing. This technology has been deployed for Fluor Hanford at Hanford’s K-Basins, as well as for UKAEA as part of the Windscale Piles decommissioning project. The purpose of this paper is to provide a short description of the hydrolasing process and the associated waste issues, describe the unique design features of S.A. Robotics’ hydrolasing systems which combat these issues, and provide an overview of two of the hydrolasing projects that S.A. Robotics has completed.
Use of Remote Equipment in Reactor Decommissioning
Authors: Cole Matt , Martin Scott , Adams Scott
Published: December 2010

Nuclear reactor decommissioning continues to remain at the forefront of the energy and defence industries as many reactors built from the 1940s to the 1970s are reaching the end of their life cycles. As demand for decommissioning increases, the focus on worker’s health and safety has become paramount. This focus on worker safety, coupled with the unique challenges faced in reactor decommissioning, continues to promote the use of remote equipment in the decommissioning process. New technologies available in the market today have also created new opportunities for the implementation and application of remote equipment for reactor decommissioning. These technologies include: carbon fibre, high pressure liquid cutting, and advanced control packages. Also, the methods for remote deployment of existing decommissioning technologies such as flame cutting, shearing, and heavy equipment continue to evolve. This paper will focus on the use of this technology at the following facilities: the decommissioning of the Rancho Seco reactor in California, the Brookhaven graphite research reactor in New York, the Windscale Pile 1 Reactor in the United Kingdom, and the Fort St. Vrain HTG Reactor in Colorado. These have all used remote equipment and emerging technologies to solve complex problems in nuclear reactor decommissioning. The purpose is this paper is to outline some of the challenges associated with reactor decommissioning, describe new technologies and deployment techniques being used in the decommissioning field, and to provide an overview of projects using these new technologies.
Altered Crystalline Rock Distributed Along Groundwater Conductive Fractures and the Retardation Capacity in the Orogenic Field of Japan
Authors: Yoshida Hidekazu , Nishimoto Shoji , Metcalfe Richard
Published: December 2010

In the orogenic field Japanese islands, there are wide areas of crystalline rocks that inevitably contain groundwater conductive fractures associated with alteration zones. However, little attention has been given to the formation process and possible influence on the radionuclides migration from radioactive waste repository that might be sited within crystalline rock. In particular, the influences of alteration minerals and microfractures, due to chemical sorption and/or physical retardation are required to assess the realistic barrier function. In order to understand the alteration process and the retardation capacity, detailed mineralogical and physico-chemical characterization of altered crystalline rocks have been carried out. Mineralogical analysis reveals that the altered crystalline rocks have been formed through basically two stages of water-rock interaction during and after uplift. Physico-chemical characteristics including laboratory sorption experiments show that altered crystalline rock has a certain volume of accessible porosity, particularly in plagioclase grains, which would influence on nuclide retardation more than the accessible porosity in other minerals present, such as biotite. These results provide confidence that even altered and fractured parts of any crystalline rock that might be encountered in a site for the disposal of high-level radioactive waste may still play a role of barrier function.
New Safety Concept for Geological Disposal in Japan
Authors: Kitayama Kazumi
Published: December 2010

This paper describes a new safety concept for the Japanese geological disposal program, which is a development of the conventional multi-barrier system concept. The Japanese government established the ‘Nuclear Waste Management Organization of Japan’ (NUMO) as an implementation body in 2000 based on the “Final disposal act” following the publication of the “H-12 Report”, which confirmed the scientific and engineering feasibility of HLW geological disposal in Japan. Since then, NUMO has undertaken further technical developments aimed at achieving safe and efficient implementation of final disposal. The safety concept developed in the “H-12 Report” provides sufficient safety on the basis of site-generic considerations. However, it is considered to be over-conservative and therefore does not represent the most probable performance of the engineered or natural barriers. Recently, concrete measures have been proposed requiring the safety case to be presented in terms of a realistic assessment of the most probable performance. This approach takes into account the safety functions of both engineered and natural barriers as well as the long-term static geochemical equilibrium. In particular, the evolution of the safety performance of engineered and natural barriers can be efficiently augmented by the realistic long-term geochemical equilibrium.
Use of the Safety Case to Focus KMS Applications
Authors: Osawa Hideaki , Hioki Kazumasa , Umeki Hiroyuki , Takase Hiroyasu , McKinley Ian
Published: December 2010

The safety case, as defined in Japan, is an integrated set of arguments to show that a repository is sufficiently safe during both operational and post-closure phases. It explicitly includes the findings of a safety assessment and a demonstration of confidence in these findings. It is developed in a stepwise manner, with provisional cases used to support decisions at major project milestones. Social acceptance is acknowledged to be critical and hence a safety case includes not only technical components, but also the arguments required to explain fundamental issues to all key stakeholders. In the JAEA KMS project, the safety case has been found useful as a framework that allows all supporting R&D to be seen in the context of its applicability. Various tools have been examined to develop associated argumentation models and they have been seen to provide an overview that is valuable to both the users and producers of knowledge. The paper will review progress to date in this work, with illustrative examples of argumentation networks and an outline of future developments and challenges.
Practical Application of the KMS: 2) Site Characterisation
Authors: Semba Takeshi , Osawa Hideaki , Hioki Kazumasa , Tachibana Shoko , Takase Hiroyasu , McKinley Ian
Published: December 2010

The characterisation of potential repository sites will produce huge volumes of information, which must be correlated, quality assured, integrated, analysed, documented and archived in a rigorous and efficient manner. While some of this work involves rather routine data handling that may be easily automated, much of it requires input of tacit knowledge which involves the experience of expert staff. To provide support for the Japanese implementer and also the regulator, a JAEA team is attempting to capture both Japanese and international geosynthesis experience within a Knowledge Management System (KMS) framework, which is termed ISIS. This is a hybrid system that combines “smart” software with human experts, although an aim is to capture tacit knowledge within expert systems to the maximum extent practicable. Initial tests, based mainly on field work carried out by JAEA at the sites of the Mizunami and Horonobe underground research laboratories, have utilised expert systems as modules in a “blackboard system” approach to planning or implementing the processing of field data. Examples are presented of sub-systems where this approach has already been demonstrated and perspectives for more extensive application to integrated geosynthesis management are discussed.
The DIAMOND University Research Consortium: Nuclear Waste Characterisation, Immobilisation and Storage
Authors: Biggs Simon , Fairweather Michael , Young James , Hyatt Neil , Livens Francis
Published: December 2010

Legacy waste treatment, storage and disposal, as well as decommissioning and site remediation, from the UK’s civil nuclear programme are estimated at a cost of £70B. Within the UK, the Nuclear Decommissioning Authority (NDA) directs the strategy for all civil nuclear decommissioning and demanding timescales have been set for remediation of all nuclear sites. Additionally, the Committee on Radioactive Waste Management (CoRWM) recently delivered a recommendation, accepted by Government, that geological disposal in a mined repository presents the “best available approach” for long term management of the waste legacy. There is therefore a requirement to decommission all power generation and experimental reactors, and fuel reprocessing plants, to decontaminate land, and to return nuclear licensed sites to brown or green field status. The engineering and scientific challenges that lie ahead in meeting these targets are significant, and many of the ideas required to deliver the final end state have not yet been researched. In recognition of this the UK Research Council’s Energy Programme released a call for research proposals in the area of nuclear waste management and decommissioning valued at £4M. A grant was subsequently awarded in 2008 to a consortium led by the University of Leeds, with member universities from Manchester, Imperial College, Sheffield, Loughborough and University College London. The DIAMOND (Decommissioning, Immobilisation And Management Of Nuclear Wastes For Disposal) consortium will undertake research aligned with the strategic priorities of the NDA and the CoRWM recommendations. Its primary purpose is to be adventurous and to deliver innovation. However, research is also being performed that will be of more immediate benefit to industrial stakeholders, with near-term impact achieved through the adoption of off-the-shelf technology currently implemented by other industries. Currently more than 20 industrial organisations are linked directly to the consortium. The aims of the consortium are to carry out internationally leading research in the areas of decommissioning and waste management that underpins the development of innovative and relevant technologies for industrial use. It will broaden the research base that focuses on relevant technologies, support new links within and between universities, promote multi-disciplinary collaboration and new applications of existing knowledge, and train the next generation of researchers to address a developing skills gap.
Engineering Properties of Nuclear Waste Slurries
Authors: Biggs Simon , Fairweather Michael , Hunter Timothy , Omokanye Qanitalillahi , Peakall Jeffrey
Published: December 2010

The type of particulate systems encountered in legacy nuclear waste slurries is highly complicated, with the aggregation and flow behaviour being at times very variable. However, deconstructing the complex overall slurry activity to singular particle-particle interactions can lead to a greater understanding of the mechanisms involved with particle aggregation, and so to predictions of their settling and flow in nuclear systems. Of particular importance to legacy waste is the role of salts in controlling the attraction of particles (and so in dictating the rheological properties of the system) as sludge may contain a variety of specific ions and generally have high ionic conductivity [1]. In this paper, particle-particle interactions are characterised using a number of complimentary methods, and their influence on resulting flow and bed compression is measured. The methods used to characterise the particle-particle interactions under various salt and pH conditions were electroacoustic analysis (zeta potential) and atomic force microscopy (AFM). Following on from the analysis of particle-particle properties, bulk sediment behaviour was investigated using shear and compressive yield stress measurements, vital parameters in dictating flow and dewatering performance, respectively. Together, these techniques enable the characterisation of a range of particulate systems that may be encountered in legacy wastes, and results point to a number of important factors that can help explain the observed variability in industrial slurry behaviour.
NEC3: Managing Change
Authors: Wilsoncroft Charles
Published: December 2010

The Office of Government Commerce (OGC) has endorsed the use of NEC for all public sector contracts. The reason being is that it stimulates effective project management and enables the parties to manage risk and change more efficiently, which in turn serves to mitigate the cost and time effects of any risk event should it arise under the contract. In essence it facilitates a more collaborative working culture between the parties. The NEC3 contract is gaining in popularity and has been adopted for use in the decommissioning of nuclear power stations and the London Olympics, it also recently received support in the Tenth Special Report on Construction Matters by the House of Commons. It has strict time limits for the notification of compensation events as set out in the core clause 61.3 whereby the Contractor’s contract administration team needs to notify the project manager within an eight week period of becoming aware of the event. The contract also provides for an early warning procedure whereby the Contractor and the project manager will cooperate and proactively discuss how issues can be overcome in a collaborative manner. This NEC3 contract requires both the Contractor and the Employer to act positively and is welcomed as a possible solution to the entrenched disputes which have regularly occurred on major energy projects and if properly administered will hopefully result in an earlier and less fraught final account settlement process for both parties.
Methods of Control of Inaccuracy in Calculation of Nuclear Power Plant Decommissioning Parameters
Authors: Ondra Frantisˇek , Danisˇka Vladimi´r , Reha´k Ivan , Necˇas Vladimi´r
Published: December 2010

The aim of the article is a development of analytical methodology for evaluation of input data inaccuracies impact on calculation of cost and other output decommissioning parameters. This methodology is based on analytical model calculations using the OMEGA code and taking into account the probability of input data inaccuracies occurrence also.
UK Strategy for Nuclear Industry LLW
Authors: Clark Matthew , Fisher Joanne
Published: December 2010

In March 2007 the UK Government and devolved administrations (for Scotland, Wales and Northern Ireland, from here on referred to as ‘Government’) published their policy for the management of solid low level waste (‘the Policy’). The Policy sets out a number of core principles for the management of low level waste (LLW) and charges the Nuclear Decommissioning Authority with developing a UK-wide strategy in the case of LLW from nuclear sites. The UK Nuclear Industry LLW Strategy has been developed within the framework of the principles set out in the policy. A key factor in the development of this strategy has been the strategic partnership the NDA shares with the Low Level Waste Repository near Drigg (LLWR), who now have a role in developing strategy as well as delivering an optimised waste management service at the LLWR. The strategy aims to support continued hazard reduction and decommissioning by ensuring uninterrupted capability and capacity for the management and disposal of LLW in the UK. The continued availability of a disposal route for LLW is considered vital by both the nuclear industry and non-nuclear industry low level waste producers. Given that the UK will generate significantly more low level waste (∼ 3.1 million m3) than there is capacity at the LLWR (∼0.75 million m3), developing alternative effective ways to manage LLW is critical. The waste management hierarchy is central to the strategy, which includes strategic goals at all levels of the hierarchy to improve its application across the industry.
IAEA Decommissioning Safety Activities
Authors: Ljubenov Vladan , Warnecke Ernst , Hannan Mark
Published: December 2010

This paper presents a summary of the recent, ongoing and planned safety related IAEA activities on planning, implementation and termination of decommissioning. Work related to the “Joint Convention on the Safety of Spent Fuel Management and on the Safety of Radioactive Waste Management” and to the development of the international safety standards for decommissioning of facilities using radioactive materials is described. The IAEA activities on the technical assistance to the Member States in the development and review of decommissioning plans through national and international Technical Cooperation Programme projects and through other projects (FaSa project, R2D2P Project, decommissioning of the Iraq former nuclear complex) are presented. Recently established IAEA peer review services on decommissioning are addressed, as well as the international decommissioning forum.
Phosphoproteomic Analysis Reveals Interconnected System-Wide Responses to Perturbations of Kinases and Phosphatases in Yeast
Authors: Bodenmiller Bernd , Wanka Stefanie , Kraft Claudine , Urban Jörg , Campbell David , Pedrioli Patrick G. , Gerrits Bertran , Picotti Paola , Lam Henry , Vitek Olga , Brusniak Mi-Youn , Roschitzki Bernd , Zhang Chao , Shokat Kevan M. , Schlapbach Ralph , Colman-Lerner Alejandro , Nolan Garry P. , Nesvizhskii Alexey I. , Peter Matthias , Loewith Robbie , von Mering Christian , Aebersold Ruedi
Published: December 2010

A system-wide analysis of protein phosphorylation in yeast reveals robustness in the network of kinases and phosphatases.
The Mammalian MAPK/ERK Pathway Exhibits Properties of a Negative Feedback Amplifier
Authors: Sturm Oliver E. , Orton Richard , Grindlay Joan , Birtwistle Marc , Vyshemirsky Vladislav , Gilbert David , Calder Muffy , Pitt Andrew , Kholodenko Boris , Kolch Walter
Published: December 2010

Analysis of ERK pathway circuitry suggests appropriate targets for inhibition, providing a guide for drug development.
Dermal Light Detectors
Authors: Gough Nancy R.
Published: December 2010

Fly larvae detect high-intensity light all over their bodies, not just with their primitive eyes.
When Breaking Up Is Not Depressing
Authors: Adler Elizabeth M.
Published: December 2010

Disruption of the dopamine D1-D2 receptor complex may provide a therapeutic strategy against depression.
Migrating Cells Need TORC
Authors: Foley John F.
Published: December 2010

Cells lacking mTORC2 activity exhibit defects in polarization and chemotaxis.
Beyond the Greatwall
Authors: Ray L. Bryan
Published: December 2010

The protein kinase Greatwall controls cell division by phosphorylating and activating inhibitors of protein phosphatase 2A.
Size Matters
Authors: Zahn Laura M.
Published: December 2010

The central nervous system and the hormone ecdysone govern wing-size scaling in the tobacco hornworm.
Science Signaling
Podcast: 21 December 2010
Authors: Bodenmiller Bernd , Aebersold Ruedi , VanHook Annalisa M.
Published: December 2010

Targeted removal of individual enzymes elicits changes throughout the entire network of kinases and phosphatases in yeast.
T Cell Receptor Signaling Kinetics Takes the Stage
Authors: Sykulev Yuri
Published: December 2010

The kinetics of TCR signaling influence the quality of the T cell response.
Concentrations of Tenofovir and Emtricitabine in Breast Milk of HIV-1-Infected Women in Abidjan, Côte d'Ivoire, in the ANRS 12109 TEmAA Study, Step 2
Authors: Benaboud Sihem , Pruvost Alain , Coffie Patrick A. , Ekouévi Didier K. , Urien Saïk , Arrivé Elise , Blanche Stéphane , Théodoro Frédéric , Avit Divine , Dabis François , Tréluyer Jean-Marc , Hirt Déborah
Published: December 2010

The aim was to evaluate emtricitabine (FTC) and tenofovir (TFV) neonatal ingestion through breast milk. Median TFV and FTC breast milk doses represented 0.03% and 2%, respectively, of the proposed oral infant doses. Neonatal simulated plasma concentrations were extremely low for TFV but between the half-maximal inhibitory concentration and the adult minimal expected concentration for FTC. The rare children who will acquire HIV despite TDF-FTC therapy will need to be monitored for viral resistance acquisition.
Nonoptimal DNA Topoisomerases Allow Maintenance of Supercoiling Levels and Improve Fitness of
Streptococcus pneumoniae
Authors: Balsalobre Luz , Ferrándiz María José , de Alba Gabriela , de la Campa Adela G.
Published: December 2010

Fluoroquinolones, which target gyrase and topoisomerase IV, are used for treating
Streptococcus pneumoniae
infections. Fluoroquinolone resistance in this bacterium can arise via point mutation or interspecific recombination with genetically related streptococci. Our previous study on the fitness cost of resistance mutations and recombinant topoisomerases identified GyrAE85K as a high-cost change. However, this cost was compensated for by the presence of a recombinant topoisomerase IV (
parC
and
parE
recombinant genes) in strain T14. In this study, we purified wild-type and mutant topoisomerases and compared their enzymatic activities. In strain T14, both gyrase carrying GyrAE85K and recombinant topoisomerase IV showed lower activities (from 2.0- to 3.7-fold) than the wild-type enzymes. These variations of
in vitro
activity corresponded to changes of
in vivo
supercoiling levels that were analyzed by two-dimensional electrophoresis of an internal plasmid. Strains carrying GyrAE85K and nonrecombinant topoisomerases had lower (11.1% to 14.3%) supercoiling density (σ) values than the wild type. Those carrying GyrAE85K and recombinant topoisomerases showed either partial or total supercoiling level restoration, with σ values being 7.9% (recombinant ParC) and 1.6% (recombinant ParC and recombinant ParE) lower than those for the wild type. These data suggested that changes acquired by interspecific recombination might be selected because they reduce the fitness cost associated with fluoroquinolone resistance mutations. An increase in the incidence of fluoroquinolone resistance, even in the absence of further antibiotic exposure, is envisaged.
Increased Mortality with Accessory Gene Regulator (
agr
) Dysfunction in
Staphylococcus aureus
among Bacteremic Patients
Authors: Schweizer Marin L. , Furuno Jon P. , Sakoulas George , Johnson J. Kristie , Harris Anthony D. , Shardell Michelle D. , McGregor Jessina C. , Thom Kerri A. , Perencevich Eli N.
Published: December 2010

Accessory gene regulator (
agr
) dysfunction in
Staphylococcus aureus
has been associated with a longer duration of bacteremia. We aimed to assess the independent association between
agr
dysfunction in
S. aureus
bacteremia and 30-day in-hospital mortality. This retrospective cohort study included all adult inpatients with
S. aureus
bacteremia admitted between 1 January 2003 and 30 June 2007. Severity of illness prior to culture collection was measured using the modified acute physiology score (APS).
agr
dysfunction in
S. aureus
was identified semiquantitatively by using a δ-hemolysin production assay. Cox proportional hazard models were used to measure the association between
agr
dysfunction and 30-day in-hospital mortality, statistically adjusting for patient and pathogen characteristics. Among 814 patient admissions complicated by
S. aureus
bacteremia, 181 (22%) patients were infected with
S. aureus
isolates with
agr
dysfunction. Overall, 18% of patients with
agr
dysfunction in
S. aureus
died, compared to 12% of those with functional
agr
in
S. aureus
(
P
= 0.03). There was a trend toward higher mortality among patients with
S. aureus
with
agr
dysfunction (adjusted hazard ratio [HR], 1.34; 95% confidence interval [CI], 0.87 to 2.06). Among patients with the highest APS (scores of >28),
agr
dysfunction in
S. aureus
was significantly associated with mortality (adjusted HR, 1.82; 95% CI, 1.03 to 3.21). This is the first study to demonstrate an independent association between
agr
dysfunction and mortality among severely ill patients. The δ-hemolysin assay examining
agr
function may be a simple and inexpensive approach to predicting patient outcomes and potentially optimizing antibiotic therapy.
Characterization of the Biosynthesis Gene Cluster for the Pyrrole Polyether Antibiotic Calcimycin (A23187) in
Streptomyces chartreusis
NRRL 3882
Authors: Wu Qiulin , Liang Jingdan , Lin Shuangjun , Zhou Xiufen , Bai Linquan , Deng Zixin , Wang Zhijun
Published: December 2010

The pyrrole polyether antibiotic calcimycin (A23187) is a rare ionophore that is specific for divalent cations. It is widely used as a biochemical and pharmacological tool because of its multiple, unique biological effects. Here we report on the cloning, sequencing, and mutational analysis of the 64-kb biosynthetic gene cluster from
Streptomyces chartreusis
NRRL 3882. Gene replacements confirmed the identity of the gene cluster, and
in silico
analysis of the DNA sequence revealed 27 potential genes, including 3 genes for the biosynthesis of the α-ketopyrrole moiety, 5 genes that encode modular type I polyketide synthases for the biosynthesis of the spiroketal ring, 4 genes for the biosynthesis of 3-hydroxyanthranilic acid, an
N
-methyltransferase tailoring gene, a resistance gene, a type II thioesterase gene, 3 regulatory genes, 4 genes with other functions, and 5 genes of unknown function. We propose a pathway for the biosynthesis of calcimycin and assign the genes to the biosynthesis steps. Our findings set the stage for producing much desired calcimycin derivatives using genetic modification instead of chemical synthesis.
Miconazole Oral Gel Increases Exposure to Oral Oxycodone by Inhibition of CYP2D6 and CYP3A4
Authors: Grönlund Juha , Saari Teijo I. , Hagelberg Nora , Neuvonen Pertti J. , Olkkola Klaus T. , Laine Kari
Published: December 2010

Our aim was to assess the effect of miconazole oral gel on the pharmacokinetics of oral oxycodone. In an open crossover study with two phases, 12 healthy volunteers took a single oral dose of 10 mg of immediate-release oxycodone with or without thrice-daily 85-mg miconazole oral gel treatment. The plasma concentrations of oxycodone and its oxidative metabolites were measured for 48 h. Pharmacological effects of oxycodone were recorded for 12 h. Pharmacokinetic parameters were compared by use of the geometric mean ratios (GMRs) and their 90% confidence interval (CIs). Pretreatment with miconazole oral gel caused a strong inhibition of the CYP2D6-dependent metabolism and moderate inhibition of the CYP3A4-dependent metabolism of oxycodone. The mean area under the concentration-time curve (AUC) from time zero to infinity (AUC0-∞; GMR, 1.63; 90% CI, 1.48 to 1.79) and the peak concentration of oxycodone (GMR, 1.31; 90% CI, 1.19 to 1.44) were increased. The AUC of the CYP2D6-dependent metabolite oxymorphone was greatly decreased (GMR, 0.17; 90% CI, 0.09 to 0.31) by miconazole gel, whereas that of the CYP3A4-dependent metabolite noroxycodone was increased (GMR, 1.30; 90% CI, 1.15 to 1.47) by miconazole gel. Differences in the pharmacological response to oxycodone between phases were insignificant. Miconazole oral gel increases the exposure to oral oxycodone, but the clinical relevance of the interaction is moderate. Miconazole oral gel produces a rather strong inhibitory effect on CYP2D6, which deserves further study.
Comparative Efficacy and Safety of Moxifloxacin and Clindamycin in the Treatment of Odontogenic Abscesses and Inflammatory Infiltrates: a Phase II, Double-Blind, Randomized Trial
Authors: Cachovan Georg , Böger Rainer H. , Giersdorf Ina , Hallier Olaf , Streichert Thomas , Haddad Munif , Platzer Ursula , Schön Gerhard , Wegscheider Karl , Sobottka Ingo
Published: December 2010

Moxifloxacin penetrates well into oromaxillary tissue and covers the causative pathogens that show an increasing resistance to standard antibiotics. Clinical reports suggest that moxifloxacin may be effective for the treatment of odontogenic infections that can lead to serious complications. The objective of this prospective, randomized, double-blind, multicenter study was to compare the efficacies and safeties of moxifloxacin and clindamycin for the medical treatment of patients with gingival inflammatory infiltrates and as an adjuvant therapy for patients with odontogenic abscesses requiring surgical treatment. Patients received either 400 mg moxifloxacin
per os
once daily or 300 mg clindamycin
per os
four times daily for 5 days consecutively. The primary efficacy endpoint was the percent reduction in patients' perceived pain on a visual analogue scale at days 2 to 3 from baseline. Primary analysis included 21 moxifloxacin- and 19 clindamycin-treated patients with infiltrates and 15 moxifloxacin- and 16 clindamycin-treated patients with abscesses. The mean pain reductions were 61.0% (standard deviation [SD], 46.9%) with moxifloxacin versus 23.4% (SD, 32.1%) with clindamycin (
P
= 0.006) for patients with infiltrates and 55.8% (SD, 24.8%) with moxifloxacin versus 42.7% (SD, 48.5%) with clindamycin (
P
= 0.358) for patients with abscesses. A global efficacy assessment at days 2 to 3 and 5 to 7 showed faster clinical responses with moxifloxacin in both abscess and infiltrate patients. Rates of adverse events were lower in moxifloxacin- than in clindamycin-treated patients. In patients with inflammatory infiltrates, moxifloxacin was significantly more effective in reducing pain at days 2 to 3 of therapy than clindamycin. No significant differences between groups were found for patients with odontogenic abscesses.
Systematic Review and Meta-Analysis of the Effectiveness and Safety of Tigecycline for Treatment of Infectious Disease
Authors: Cai Yun , Wang Rui , Liang Beibei , Bai Nan , Liu Youning
Published: December 2010

The aim of this study was to compare the efficacy and safety of tigecycline, a newly developed glycylcycline antibiotic, with those of empirical antibiotic regimens which have been reported to possess good efficacy for complicated skin and skin structure infections (cSSSIs), complicated intra-abdominal infections (cIAIs), community-acquired pneumonia (CAP), and other infections caused by methicillin-resistant
Staphylococcus aureus
(MRSA) or vancomycin-resistant
Enterococcus
(VRE). A meta-analysis of randomized controlled trials (RCTs) identified in PubMed, the Cochrane Library, and Embase was performed. Eight RCTs involving 4,651 patients were included in the meta-analysis. Compared with therapy with empirical antibiotic regimens, tigecycline monotherapy was associated with similar clinical treatment success rates (for the clinically evaluable [CE] population, odds ratio [OR] = 0.92, 95% confidence interval [CI] = 0.76 to 1.12,
P
= 0.42; for the clinical modified intent-to-treat [c-mITT] population, OR = 0.86, 95% CI = 0.74 to 1.01,
P
= 0.06) and similar microbiological treatment success rates (for the microbiologically evaluable [ME] population, OR = 0.86, 95% CI = 0.69 to 1.07,
P
= 0.19). The incidence of adverse events in the tigecycline group was significantly higher than that in the other therapy groups with a statistical margin (for the modified intent-to-treat [mITT] population, OR = 1.33, 95% CI = 1.17 to 1.52,
P
< 0.0001), especially in the digestive system (mITT population, OR = 2.41, 95% CI = 1.67 to 3.46,
P
< 0.00001). No difference regarding all-cause mortality and drug-related mortality between tigecycline and the other regimens was found, although numerically higher mortality was found in the tigecycline group. This meta-analysis provides evidence that tigecycline monotherapy may be used as effectively as the comparison therapy for cSSSI, cIAIs, CAP, and infections caused by MRSA/VRE. However, because of the high risk of mortality, AEs, and emergence of resistant isolates, prudence with the clinical use of tigecycline monotherapy in infections is required.
Oxidative Stress Induction of the MexXY Multidrug Efflux Genes and Promotion of Aminoglycoside Resistance Development in
Pseudomonas aeruginosa
Authors: Fraud Sebastien , Poole Keith
Published: December 2010

Exposure to reactive oxygen species (ROS) (e.g., peroxide) was shown to induce expression of the PA5471 gene, which was previously shown to be required for antimicrobial induction of the MexXY components of the MexXY-OprM multidrug efflux system and aminoglycoside resistance determinant in
Pseudomonas aeruginosa. mexXY
was also induced by peroxide exposure, and this too was PA5471 dependent. The prospect of ROS promoting
mexXY
expression and aminoglycoside resistance recalls
P. aeruginosa
infection of the chronically inflamed lungs of cystic fibrosis (CF) patients, where the organism is exposed to ROS and where MexXY-OprM predominates as the mechanism of aminoglycoside resistance. While ROS did not enhance aminoglycoside resistance
in vitro
, long-term (8-day) exposure of
P. aeruginosa
to peroxide (mimicking chronic
in vivo
ROS exposure) increased aminoglycoside resistance frequency, dependent upon PA5471 and
mexXY
. This enhanced resistance frequency was also seen in a mutant strain overexpressing PA5471, in the absence of peroxide, suggesting that induction of PA5471 by peroxide was key to peroxide enhancement of aminoglycoside resistance frequency. Resistant mutants selected following peroxide exposure were typically pan-aminoglycoside-resistant, with
mexXY
generally required for this resistance. Moreover, PA5471 was required for
mexXY
expression and aminoglycoside resistance in these as well as several CF isolates examined.
Enhancement of Experimental Cutaneous Leishmaniasis byLeishmaniaMolecules Is Dependent on Interleukin-4, Serine Protease/Esterase Activity, and Parasite and Host Genetic Backgrounds
Authors: Silva Virgínia M. G. , Larangeira Daniela F. , Oliveira Pablo R. S. , Sampaio Romina B. , Suzart Paula , Nihei Jorge S. , Teixeira Márcia C. A. , Mengel José O. , dos-Santos Washington L. C. , Pontes-de-Carvalho Lain
Published: December 2010

Most inbred strains of mice, like the BALB/c strain, are susceptible toLeishmania amazonensisinfections and resistant toLeishmania braziliensisinfections. This parasite-related difference could result from the activity of anL. amazonensis-specific virulence factor. In agreement with this hypothesis, it is shown here that the intravenous injection of BALB/c mice withL. amazonensisamastigote extract (LaE) but not theL. braziliensisextract confers susceptibility toL. braziliensisinfection. This effect was associated with high circulating levels of IgG1 anti-L. amazonensisantibodies and with an increase in interleukin-4 (IL-4) production and a decrease in gamma interferon production by draining lymph node cells. Moreover, the effect was absent in IL-4-knockout mice. The biological activity in theLaE was not mediated by amphiphilic molecules and was inhibited by pretreatment of the extract with irreversible serine protease inhibitors. These findings indicate that theLaE contains a virulence-related factor that (i) enhances theLeishmaniainfection by promoting Th2-type immune responses, (ii) is not one of the immunomodulatoryLeishmaniamolecules described so far, and (iii) is either a serine protease or has an effect that depends on that protease activity. In addition to beingLeishmaniaspecies specific, the infection-enhancing activity was also shown to depend on the host genetic makeup, asLaE injections did not affect the susceptibility of C57BL/6 mice toL. braziliensisinfection. The identification ofLeishmaniamolecules with infection-enhancing activity could be important for the development of a vaccine, since the up- or downmodulation of the immune response against a virulence factor could well contribute to controlling the infection.