bluuebunny/crossref_metadata_2025 huggingface dataset:
TraceAnalyzer: a system for processing performance traces
Authors: Diwan Amer , Hauswirth Matthias , Mytkowicz Todd , Sweeney Peter F.
Published: August 2010

The performance of a program often varies significantly over the course of the program's run. Thus, to understand the performance of a program it is valuable to look not just at end‐to‐end metrics (e.g. total number of cache misses) but also the time‐varying performance of the program. Unfortunately, analyzing time‐varying performance is both cumbersome and difficult. This paper makes three contributions, all geared toward helping others in working with traces. First, it describes a system, the TraceAnalyzer, designed specifically for working with performance traces; a performance trace captures the time‐varying performance of a program run. Second, it describes lessons that we have learned from many years of working with these traces. Finally, it uses a case study to demonstrate how we have used the TraceAnalyzer to understand a performance anomaly. Copyright © 2010 John Wiley & Sons, Ltd.
Synchronization for fast and reentrant operating system kernel tracing
Authors: Desnoyers Mathieu , Dagenais Michel R.
Published: August 2010

To effectively trace an operating system, a performance monitoring and debugging infrastructure needs the ability to trace various execution contexts. These contexts range from kernel running as a thread toNon‐Maskable Interrupt(NMI) contexts. Given that any part of the kernel infrastructure used by a kernel tracer could lead to infinite recursion if traced, and because most kernel primitives require synchronization unsuitable for some execution contexts, all interactions of the tracing code with the existing kernel infrastructure must be considered in order to correctly inter‐operate with the existing operating system kernel. This paper presents a new low overhead tracing mechanism and motivates the choice of synchronization sequences suitable for operating system kernel tracing, namelylocal atomic instructionsas main buffer synchronization primitive and theRead–Copy Update(RCU) mechanism to control tracing. It also proposes a wait‐free algorithm extending the time‐base needed by the tracer to 64‐bit on architectures that lack hardware 64‐bit time‐base support. Copyright © 2010 John Wiley & Sons, Ltd.
Design principles for developing stream processing applications
Authors: Turaga Deepak , Andrade Henrique , Gedik Buğra , Venkatramani Chitra , Verscheure Olivier , Harris Jeffrey David , Cox John , Szewczyk William , Jones Paul
Published: August 2010

Stream processing applications are used to ingest, process, and analyze continuous data streams from heterogeneous sources of live and stored data, generating streams of output results. These applications are, in many cases, complex, large‐scale, low‐latency, and distributed in nature. In this paper, we describe the design principles and architectural underpinnings for stream processing applications. These principles are distilled from our experience in building real‐world applications both for internal use as well as with customers from several industrial and academic domains. We provide principles, guidelines, as well as appropriate implementation examples to highlight the different aspects of stream processing application design and development. Copyright © 2010 John Wiley & Sons, Ltd.
CloudSim: a toolkit for modeling and simulation of cloud computing environments and evaluation of resource provisioning algorithms
Authors: Calheiros Rodrigo N. , Ranjan Rajiv , Beloglazov Anton , De Rose César A. F. , Buyya Rajkumar
Published: August 2010

Cloud computing is a recent advancement wherein IT infrastructure and applications are provided as ‘services’ to end‐users under a usage‐based payment model. It can leverage virtualized services even on the fly based on requirements (workload patterns and QoS) varying with time. The application services hosted under Cloud computing model have complex provisioning, composition, configuration, and deployment requirements. Evaluating the performance of Cloud provisioning policies, application workload models, and resources performance models in a repeatable manner under varying system and user configurations and requirements is difficult to achieve. To overcome this challenge, we propose CloudSim: an extensible simulation toolkit that enables modeling and simulation of Cloud computing systems and application provisioning environments. The CloudSim toolkit supports both system and behavior modeling of Cloud system components such as data centers, virtual machines (VMs) and resource provisioning policies. It implements generic application provisioning techniques that can be extended with ease and limited effort. Currently, it supports modeling and simulation of Cloud computing environments consisting of both single and inter‐networked clouds (federation of clouds). Moreover, it exposes custom interfaces for implementing policies and provisioning techniques for allocation of VMs under inter‐networked Cloud computing scenarios. Several researchers from organizations, such as HP Labs in U.S.A., are using CloudSim in their investigation on Cloud resource provisioning and energy‐efficient management of data center resources. The usefulness of CloudSim is demonstrated by a case study involving dynamic provisioning of application services in the hybrid federated clouds environment. The result of this case study proves that the federated Cloud computing model significantly improves the application QoS requirements under fluctuating resource and service demand patterns. Copyright © 2010 John Wiley & Sons, Ltd.
An advanced certificate validation service and architecture based on XKMS
Authors: Ruiz‐Martínez Antonio , Sánchez‐Martínez Daniel , Marín‐López C. Inmaculada , Gil‐Pérez Manuel , Gómez‐Skarmeta Antonio F.
Published: August 2010

The appearance of some laws that make the electronic signature (e‐signature) legally equivalent to the handwritten signature (under some circumstances) has favoured its use in different fields, such as e‐commerce and e‐government. In these fields, the e‐signatures associated to some documents have to remain valid over long periods of time. For these kinds of e‐signatures, Advanced Electronic Signature (AdES) forms have appeared. These forms specify the information to include along with the e‐signature so that it remains valid for a long time after its creation. Basically, this information comprises signers' certificates, a set of certificates up to a trust anchor, certificate validation responses, etc. These data can be gathered by using different Public Key Infrastructure‐compliant protocols. However, the support of different protocols is complex for clients. XML Key Management Specification (XKMS) appeared with the aim of simplifying the certificate management, but it only supports a simple validation mechanism that does not provide the information needed for long‐term validation. As a solution to this problem, we have extended XKMS by defining an advanced certificate validation service to support the obtaining of validation data needed for different scenarios, such as the building of AdES forms or validation data registries. This extension also defines the different components needed to support this kind of a service. Furthermore, the defined service has been implemented and incorporated into an e‐government infrastructure. Copyright © 2010 John Wiley & Sons, Ltd.
Message filters for hardening the Linux kernel
Authors: Nadella Suneetha , Janakiram Dharanipragada
Published: August 2010

Various mechanisms for hardening the Linux kernel (for example, enforcing system call policies, device driver failure recovery, protection against exploitation of bugs in code) are proposed in the literature. The main problem with these mechanisms is that, they require changes in the kernel code leading to the possibility of introducing new bugs and hence increasing the testing time. We propose a message filter model as an extension to object‐oriented wrappers for the Linux kernel, to dynamically provide various filtering capabilities to the kernel. This model works as a comprehensive framework for specifying system call policies, handling device driver faults, protecting the kernel against exploits of bugs in code etc, without modifying the existing kernel code. This considerably reduces the possibility of creating new bugs in the kernel code. We have integrated policies for system call interception and device driver failure handling, into the Linux kernel (2.6.9), using message filter model. Our experiments show that the overhead due to our filter objects is very low, making it a useful mechanism for providing filtering capabilities to the Linux kernel. Copyright © 2010 John Wiley & Sons, Ltd.
Assessing architectural drift in commercial software development: a case study
Authors: Rosik Jacek , Le Gear Andrew , Buckley Jim , Babar Muhammad Ali , Connolly Dave
Published: August 2010

Objectives: Software architecture is perceived as one of the most important artefacts created during a system's design. However, implementations often diverge from their intended architectures: a phenomenon called architectural drift. The objective of this research is to assess the occurrence of architectural drift in the context ofde novosoftware development, to characterize it, and to evaluate whether its detection leads to inconsistency removal.Method: Anin vivo, longitudinal case study was performed during the development of a commercial software system, where an approach based on Reflexion Modelling was employed to detect architectural drift. Observation and think‐aloud data, captured during the system's development, were assessed for the presence and types of architectural drift. When divergences were identified, the data were further analysed to see if identification led to the removal of these divergences.Results: The analysed system diverged from the intended architecture, during the initial implementation of the system. Surprisingly however, this work showed that Reflexion Modelling served to conceal some of the inconsistencies, a finding that directly contradicts the high regard that this technique enjoys as an architectural evaluation tool. Finally, the analysis illustrated that detection of inconsistencies was insufficient to prompt their removal, in the small, informal team context studied.Conclusions: Although the utility of the approach for detecting inconsistencies was demonstrated in most cases, it also served to hide several inconsistencies and did not act as a trigger for their removal. Hence additional efforts must be taken to lessen architectural drift and several improvements in this regard are suggested. Copyright © 2010 John Wiley & Sons, Ltd.
Decision‐making in complex systems: Relationship between scale of change and performance
Authors: Maani Kambiz , Li Anson
Published: August 2010

Empirical research as well as numerous cases studying managers across diverse disciplines, cultures, and industries reveal consistent patterns of counter‐productive decision‐making. In this regard, decision‐makers appear to exhibit an unmistakable tendency to ‘over‐intervene’ in the systems (companies, organizations, cities, communities, etc.) they are responsible for. This suggests an inadequate appreciation and understanding of the dynamics underlying decision‐making, generating unwarranted and excessive fluctuations and instability in organizations. Numerous studies have observed such phenomena in simulated and experimental settings. Research results, as well as in‐depth case studies highlight a number of assumptions and mental models commonly held by decision‐makers and managers with adverse effect on organizational dynamics and performance. This paper reports on extensive empirical research and findings elicited from subjects interacting with realistic simulation models of organizations (microworlds) to investigate the relationship between scale of intervention and performance. The results show that while large‐scale interventions appear to be effective in the start‐up phase of systems (e.g. new products, markets, companies) they are generally counter‐productive in mature systems operating at steady state. The results support findings from organizational case studies, notably, the extensive study of ‘Good to Great’ firms. Copyright © 2010 John Wiley & Sons, Ltd.
Fostering innovation in medical technology with hierarchy theory: Narratives on emergent clinical solutions
Authors: Galbrun Jérôme , Kijima Kyoichi Jim
Published: August 2010

Innovating with the goal of conquering disease and injury is one of humanity's most admirable activities. With the variability of patients and diseases, medical innovation often involves complex interactions between the physicians in clinical practice and the rapid technological change from commercial firms. We apply aspects of interpretative hierarchy theory dealing with self‐reflective processes, particularly observation and description, to analyse these complex and dynamic relationships that foster innovation in medical technology. This systemic approach fixes certain parameters that help reduce complexity, (i) the notion of gain to adequately describe the change of observed technological hierarchies over time, and (ii) a systems description that allows clinical innovation to emerge as narratives. Our view of innovation in medical technology as an outcome of a high and low gain system finds its empirical illustration through the emergence of diagnostic solutions in medical imaging in the past decade. Finally, our research suggests epistemological and practical contributions to support the sound technological innovation in clinical practice with emphasis on selection criteria and holism for different stakeholders including physicians, firm managers and policymakers. Copyright © 2010 John Wiley & Sons, Ltd.
Hunting, gathering, investing, globalizing: The biological roots of economic behaviour
Authors: Burd Martin
Published: August 2010

The emerging discipline of behavioural economics has established that humans do not follow the canonical rules of rational utility maximization that were the foundation of neoclassical economics. If people were rational economic agents, their behaviour would be highly predictable. No unifying predictive framework for actual economic behaviour has emerged to replace the canonical assumption of utility maximization. I suggest here that evolutionary biology can play a role in forging a new theoretical framework for behavioural economics. I argue that some apparently irrational economic behaviours can be understood as products of the hunter–gatherer ecology in which humans evolved. I discuss three examples of anomalous behaviour: hyperbolic time discounting, context‐dependent preferences and contribution to public goods. In each case, ‘irrational’ decisions are less surprizing when we recognize the evolutionary roots of the behaviour. Cultural effects remain relevant in an evolutionary account of economic behaviour. Indeed, an evolutionary perspective may help us anticipate economic behaviour and create sustainable societies in the novel, globalized economy that we have created. Copyright © 2010 John Wiley & Sons, Ltd.
Sustainability and livability in the 2007 banking crisis: A failed transition to a low gain system
Authors: Shaw Duncan R.
Published: August 2010

There is a contrast between the role of complexity in enabling value creation and market growth and its role in limiting sustainability. This contrast can be understood by using the concept of low gain systems, which are relatively elaborate and sustainable, and the concept of high gain systems which are concerned with the immediacy of actually living rather than longer‐term sustaining. This paper analyses the recent banking crisis to develop a framework that weaves together the many suggestions that have been made to fix the banking system and to look for a root cause. The root cause of the banking crisis was in the increased complexity of the supply chain that linked more borrowers to more investors. This complexity enabled the aggregation and customization of debt product for specific investors, which grew the market. But it was not elaborate enough to preserve information that was required to manage the quality of these debt products. So the negative feedback of toxic debts poisoned the system in a high gain manner rather than being filtered out in a low gain manner. This was allowed to happen because of missing elements at the global and national levels of the regulation system which did not spot this filtering problem or were unable to constrain the lower levels of the regulation system to options that would fix it. The implications for regulating future system elaboration attempts are also discussed. Copyright © 2010 John Wiley & Sons, Ltd.
Complexity and the productivity of innovation
Authors: Strumsky Deborah , Lobo José , Tainter Joseph A.
Published: August 2010

Innovation underpins the industrial way of life. It is assumed implicitly both that it will continue to do so, and that it will produce solutions to the problems we face involving climate and resources. These assumptions underlie the thinking of many economists and the political leaders whom they influence. Such a view assumes that innovation in the future will be as productive as it has been in the recent past. To test whether this is likely to be so, we investigate the productivity of innovation in the United States using data from the U.S. Patent and Trademark Office. The results suggest that the conventional optimistic view may be unwarranted. Copyright © 2010 John Wiley & Sons, Ltd.
Making livable sustainable systems unremarkable
Authors: Allen Timothy F. H.
Published: August 2010

Livable and sustainable are more than differently scaled considerations, they belong to different qualitative types. Livability is dynamic and unplanned. Sustainability is about rate‐independent planning. Livability trumps sustainability in the present, but it is labile and so sustainability can wait it out until material pressures force a change. Sustainability is constrained but not determined by livability. Livability changes as resources become scarce. High gain systems take in fuel and burn it willy‐nilly, yielding to thermodynamic description. Low gain takes in low quality material and refines it so it can be used as fuel. The refinement has preferred outcomes and yields to descriptions of efficiency. Livability is high gain while sustainability is low gain. The conflict between livability and sustainability makes their consideration juxtaposed a complex system. I recommend that teaching global systems thinking in the early school years will give the next generation a clarity of vision and a flexibility of mind that will help greatly as the vice on resources tightens. Making livable sustainable systems matter of fact to the next generation, making it unremarkable is the only fully promising path forward. Copyright © 2010 John Wiley & Sons, Ltd.
Integrating economic gain in biosocial systems
Authors: Allen Timothy F. H. , Tainter Joseph A. , Flynn John , Steller Rachael , Blenner Elizabeth , Pease Megan , Nielsen Kristina
Published: August 2010

The concept of gain and profit is introduced into ecology as a way of summarizing strategies of biological and social structures. High gain systems can be predicted by flux as they take in fuel at a rate. Low gain systems must refine low‐quality materials in order to acquire fuel. Low gain systems are predictable from their plans and coded behaviour. Changes from high to low gain mode and vice versa represent a reordering of a hierarchy over time. We use a catastrophe pleat as a way to model high gain collapse. Collapse is avoided in low gain by planning. At first, planning enlarges the system through economies of scale, but eventually resources are of such low quality that gathering and refining begins to limit size. We also model shifts from high to low gain with a response surface of resource used against adaptation. There are peaks of high and low gain adaptation with which we analyse termite evolution. Positioning systems on the surface is complicated by valid alternative interpretations of system behaviour. Each low gain phase starts with a burst of high gain so it is possible to reinterpret successive moves to the lower gain as fractal shifts that link successive response surfaces. We propose mathematical protocols for capturing the response surfaces. Copyright © 2010 John Wiley & Sons, Ltd.
Canonical Wnt/β-Catenin Regulation of Liver Receptor Homolog-1 Mediates Pluripotency Gene Expression
Authors: Wagner Ryan T. , Xu Xueping , Yi Fei , Merrill Bradley J. , Cooney Austin J.
Published: August 2010

Delineating the signaling pathways that underlie ESC pluripotency is paramount for development of ESC applications in both the research and clinical settings. In culture pluripotency is maintained by leukemia inhibitory factor (LIF) stimulation of two separate signaling axes: Stat3/Klf4/Sox2 and PI3K/Tbx3/Nanog, which converge in the regulation of Oct4 expression. However, LIF signaling is not required in vivo for self-renewal, thus alternate signaling axes likely mediate these pathways. Additional factors that promote pluripotency gene expression have been identified, including the direct regulation of Oct4 by liver receptor homolog-1 (Lrh-1) and β-catenin regulation of Nanog. Here, we present genetic, molecular, and pharmacological studies identifying a signaling axis in which β-catenin promotes pluripotency gene expression in an Lrh-1-dependent manner. Furthermore, Lrh-1 was identified as a novel β-catenin target gene, and Lrh-1 regulation is required for maintaining proper levels of Oct4, Nanog, and Tbx3. Elucidation of this pathway provides an alternate mechanism by which the primary pluripotency axis may be regulated in vivo and may pave the way for small molecule applications to manipulate pluripotency or improve the efficiency of somatic cell reprogramming.
Human Gingiva-Derived Mesenchymal Stem Cells Elicit Polarization of M2 Macrophages and Enhance Cutaneous Wound Healing
Authors: Zhang Qun-Zhou , Su Wen-Ru , Shi Shi-Hong , Wilder-Smith Petra , Xiang Andy Peng , Wong Alex , Nguyen Andrew L. , Kwon Chan Wook , Le Anh D.
Published: August 2010

Increasing evidence has supported the important role of mesenchymal stem cells (MSCs) in wound healing, however, the underlying mechanism remains unclear. Recently, we have isolated a unique population of MSCs from human gingiva (GMSCs) with similar stem cell-like properties, immunosuppressive, and anti-inflammatory functions as human bone marrow-derived MSCs (BMSCs). We describe here the interplay between GMSCs and macrophages and the potential relevance in skin wound healing. When cocultured with GMSCs, macrophages acquired an anti-inflammatory M2 phenotype characterized by an increased expression of mannose receptor (MR; CD206) and secretory cytokines interleukin (IL)-10 and IL-6, a suppressed production of tumor necrosis factor (TNF)-α, and decreased ability to induce Th-17 cell expansion. In vivo, we demonstrated that systemically infused GMSCs could home to the wound site in a tight spatial interaction with host macrophages, promoted them toward M2 polarization, and significantly enhanced wound repair. Mechanistically, GMSC treatment mitigated local inflammation mediated by a suppressed infiltration of inflammatory cells and production of IL-6 and TNF-α, and an increased expression of IL-10. The GMSC-induced suppression of TNF-α secretion by macrophages appears to correlate with impaired activation of NFκB p50. These findings provide first evidence that GMSCs are capable to elicit M2 polarization of macrophages, which might contribute to a marked acceleration of wound healing.
High-Efficiency Induction of Neural Conversion in Human ESCs and Human Induced Pluripotent Stem Cells with a Single Chemical Inhibitor of Transforming Growth Factor Beta Superfamily Receptors
Authors: Zhou Jiaxi , Su Pei , Li Dong , Tsang Stephanie , Duan Enkui , Wang Fei
Published: August 2010

Chemical compounds have emerged as powerful tools for modulating ESC functions and deriving induced pluripotent stem cells (iPSCs), but documentation of compound-induced efficient directed differentiation in human ESCs (hESCs) and human iPSC (hiPSCs) is limited. By screening a collection of chemical compounds, we identified compound C (also denoted as dorsomorphin), a protein kinase inhibitor, as a potent regulator of hESC and hiPSC fate decisions. Compound C suppresses mesoderm, endoderm, and trophoectoderm differentiation and induces rapid and high-efficiency neural conversion in both hESCs and hiPSCs, 88.7% and 70.4%, respectively. Interestingly, compound C is ineffective in inducing neural conversion in mouse ESCs (mESCs). Large-scale kinase assay revealed that compound C targets at least seven transforming growth factor beta (TGF-β) superfamily receptors, including both type I and type II receptors, and thereby blocks both the Activin and bone morphogenesis protein (BMP) signaling pathways in hESCs. Dual inhibition of Activin and BMP signaling accounts for the effects of compound C on hESC differentiation and neural conversion. We also identified muscle segment homeobox gene 2 (MSX2) as a downstream target gene of compound C and a key signaling intermediate of the BMP pathway in hESCs. Our findings provide a single-step cost-effective method for efficient derivation of neural progenitor cells in adherent culture from human pluripotent stem cells. Therefore, it will be uniquely suitable for the production of neural progenitor cells in large scale and should facilitate the use of stem cells in drug screening and regenerative medicine and study of early human neural development.
A Role for Regulatory T Cells in Acceptance of ESC-Derived Tissues Transplanted Across an Major Histocompatibility Complex Barrier
Authors: Lui Kathy O. , Boyd Ashleigh S. , Cobbold Stephen P. , Waldmann Herman , Fairchild Paul J.
Published: August 2010

We have previously reported that ESC-derived tissues are subject to some level of immune privilege, which might facilitate induction of immune tolerance. Herein, we further demonstrate that fully allogeneic ESC-derived tissues are accepted with a regimen of coreceptor blockade even in recipients known to be relatively resistant to such a tolerizing protocol. Moreover, ESC-derived tissues could be spontaneously accepted across a class I major histocompatibility complex disparity. We further show that CD4+FoxP3+ regulatory T cells (Treg) appear to be essential for this natural “privileged” state as their ablation with an anti-CD25 mAb results in rejection of ESC-derived tissue. This same treatment exposes activation of macrophages and effector CD8+ T cells, suggesting that these cells are subject to regulatory T cell control. Thus, spontaneous acceptance of ESC-derived tissues mimics the acquired immune privilege induced by coreceptor blockade and is determined by Treg-mediated suppression.
Test data regeneration: generating new test data from existing test data
Authors: Yoo S. , Harman M.
Published: August 2010

Existing automated test data generation techniques tend to start from scratch, implicitly assuming that no pre‐existing test data are available. However, this assumption may not always hold, and where it does not, there may be a missed opportunity; perhaps the pre‐existing test cases could be used to assist the automated generation of additional test cases. This paper introduces search‐based test data regeneration, a technique that can generate additional test data from existing test data using a meta‐heuristic search algorithm. The proposed technique is compared to a widely studied test data generation approach in terms of both efficiency and effectiveness. The empirical evaluation shows that test data regeneration can be up to 2 orders of magnitude more efficient than existing test data generation techniques, while achieving comparable effectiveness in terms of structural coverage and mutation score. Copyright © 2010 John Wiley & Sons, Ltd.
Automated functional testing of online search services
Authors: Zhou Zhi Quan , Zhang ShuJia , Hagenbuchner Markus , Tse T. H. , Kuo Fei‐Ching , Chen T. Y.
Published: August 2010

Search services are the main interface through which people discover information on the Internet. A fundamental challenge in testing search services is the lack of oracles. The sheer volume of data on the Internet prohibits testers from verifying the results. Furthermore, it is difficult to objectively assess the ranking quality because different assessors can have very different opinions on the relevance of a Web page to a query. This paper presents a novel method for automatically testing search services without the need of a human oracle. The experimental findings reveal that some commonly used search engines, including Google, Yahoo!, and Live Search, are not as reliable as what most users would expect. For example, they may fail to find pages that exist in their own repositories, or rank pages in a way that is logically inconsistent. Suggestions are made for search service providers to improve their service quality. Copyright © 2010 John Wiley & Sons, Ltd.
Automated verification and testing of user‐interactive undo features in database applications
Authors: Ngo Minh Ngoc , Tan Hee Beng Kuan
Published: August 2010

User‐interactive undo is a recovery facility that enables users to correct mistakes easily by canceling or re‐executing operations that have already been executed. This paper presents an interesting common structural property that has been discovered in programs that implementing user‐interactive undo features. The property shows that there is a one‐to‐one correspondence between program statements that raise erroneous effects and those statements that can undo these effects. Statistical validation has been conducted which gives evidences to show that this property holds for 99 per cent of all the cases. An approach for automated verification of user‐interactive undo features in database applications through the use of this empirical property is further proposed. Based on the verification results, test cases are automatically generated to confirm the correctness of these features. A case study has been conducted to evaluate the performance of the proposed verification and testing approach in terms of fault detection capability. Copyright © 2010 John Wiley & Sons, Ltd.
Subchronic effects of perfluorooctanesulfonate exposure on inflammation in adult male C57BL/6 mice
Authors: Dong Guang‐Hui , Zhang Ying‐Hua , Zheng Li , Liang Zai‐Fu , Jin Yi‐He , He Qin‐Cheng
Published: August 2010

Previous studies indicate that exposure to perfluorooctanesulfonate (PFOS), a ubiquitous and highly persistent environmental contaminant, induces immunotoxicity in mice. However, few studies have specifically assessed the effects of PFOS on inflammation. This study utilized a standard 60‐day oral exposure period to assess the effects of PFOS on the response of inflammatory cytokines [tumor necrosis factor α (TNF‐α), interleukin‐1 β (IL‐1β), and interleukin‐6 (IL‐6)]. Adult male C57BL/6 mice were dosed daily by oral gavage with PFOS at 0, 0.0083, 0.0167, 0.0833, 0.4167, 0.8333 or 2.0833 mg/kg/day to yield a targeted Total Administered Dose (TAD) over 60 days of 0, 0.5, 1, 5, 25, 50, or 125 mg PFOS/kg, respectively. The percentage of peritoneal macrophages (CD11b+ cells) was significantly increased at concentrations ≥1 mg PFOS/kg TAD in a dose‐dependent manner. Ex vivo IL‐1β production by peritoneal macrophages was elevated substantially at concentrations of ≥5 mg PFOS/kg TAD. Moreover, PFOS exposure markedly enhanced the ex vivo production of TNF‐α, IL‐1β and IL‐6 by peritoneal and splenic macrophages when stimulated either in vitro or in vivo with lipopolysaccharide (LPS). The serum levels of these inflammatory cytokines observed in response to in vivo stimulation with LPS were elevated substantially by exposure to PFOS. PFOS exposure elevated the expression of pro‐inflammatory cytokines TNF‐α, IL‐1β, IL‐6, and proto‐oncogene, c‐myc, in the spleen. These data suggest that exposure to PFOS modulates the inflammatory response, and further research is needed to determine the mechanism of action. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.
Environmental nitration processes enhance the mutagenic potency of aromatic compounds
Authors: Bonnefoy Aurélie , Chiron Serge , Botta Alain
Published: August 2010

This work is an attempt to establish if aromatic nitration processes are always associated with an increase of genotoxicity. We determined the mutagenic and genotoxic effects of Benzene (B), Nitrobenzene (NB), Phenol (P), 2‐Nitrophenol (2‐NP), 2,4‐Dinitrophenol (2,4‐DNP), Pyrene (Py), 1‐Nitropyrene (1‐NPy), 1,3‐Dinitropyrene (1,3‐DNPy), 1,6‐Dinitropyrene (1,6‐DNPy), and 1,8‐Dinitropyrene (1,8‐DNPy). The mutagenic activities were evaluated with umuC test in presence and in absence of metabolic activation with S9 mix. Then, we used both cytokinesis‐blocked micronucleus (CBMN) assay, in combination with fluorescent in situ hybridization (FISH) of human pan‐centromeric DNA probes on human lymphocytes in order to evaluate the genotoxic effects. Analysis of all results shows that nitro polycyclic aromatic hydrocarbons (PAHs) are definitely environmental genotoxic/mutagenic hazards and confirms that environmental aromatic nitration reactions lead to an increase in genotoxicity and mutagenicity properties. Particularly 1‐NPy and 1,8‐DNPy can be considered as human potential carcinogens. They seem to be significant markers of the genotoxicity, mutagenicity, and potential carcinogenicity of complex PAHs mixtures present in traffic emission and industrial environment. In prevention of environmental carcinogenic risk 1‐NPy and 1,8‐DNPy must therefore be systematically analyzed in environmental complex mixtures in association with combined umuC test, CBMN assay, and FISH on cultured human lymphocytes. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.
Can syndromic macrocephaly be diagnosed in utero?
Authors: Malinger G. , Lev D. , Ben‐Sira L. , Hoffmann C. , Herrera M. , Viñals F. , Vinkler H. , Ginath S. , Biran‐Gol Y. , Kidron D. , Lerman‐Sagie T.
Published: August 2010

Objectives

To compare the outcomes of fetuses with apparently isolated macrocephaly and those with associated findings, and to compare prenatal findings with postnatal diagnoses in children with syndromic macrocephaly.

Methods

We reviewed the files of all patients referred for suspected fetal macrocephaly, during a 10‐year period from 2000, to a large prenatal diagnosis unit with expertise in fetal neurology counseling. Macrocephaly was defined as head circumference (HC) > 2 SDs of the norm. Patients with confirmed HC > 2 SD were identified and contacted, and their development was evaluated.

Results

Adequate data for analysis were available for 98 patients, in 82 of whom the fetal macrocephaly was considered isolated (Group A), and in 16 of whom associated fetal anomalies were identified (Group B). Macrocephaly was diagnosed earlier in Group B patients (28.4 vs. 32.3 weeks, P = 0.069), and the HC in Group B patients was larger (Z‐score 2.95 vs. 2.3, P < 0.001). From Group A there were 81 liveborn; one of whom was diagnosed as having infantile autism. From Group B, there were nine liveborn. The associated central nervous system findings, as demonstrated by ultrasound and magnetic resonance imaging, included mild ventriculomegaly, malformations of cortical development, callosal abnormalities, overdeveloped sulcation, large cavum septi pellucidi, large subarachnoid spaces, mega cisterna magna, periventricular pseudocyst, open operculum and vermian dysgenesis. Syndromic diagnosis was made in utero in five fetuses and after birth in three. In eight patients, associated malformations were confirmed after birth but a specific diagnosis was not reached.

Conclusions

When fetal macrocephaly is associated with other brain or systemic anomalies, syndromic macrocephaly can be diagnosed in utero. Fetuses with syndromic macrocephaly have a significantly larger HC, usually > 2.5 SD above the mean. Isolated macrocephaly, particularly when the HC is < 2.5 SD above the norm, may be clinically benign. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
Inhibin A, activin A, placental growth factor and uterine artery Doppler pulsatility index in the prediction of pre‐eclampsia
Authors: Yu J. , Shixia C. Z. , Wu Y. , Duan T.
Published: August 2010

Objectives

To evaluate whether the measurement of maternal serum inhibin A, activin A and placental growth factor (PlGF) at 12 + 0 to 16 + 0 weeks of gestation alone or in combination with second‐trimester uterine artery Doppler pulsatility index (PI) is useful in predicting pre‐eclampsia.

Methods

This was a case–control study of pre‐eclampsia. From pregnant women attending their first antenatal examination at 12–16 weeks we collected serum samples and stored them at − 80 °C. All patients also underwent uterine artery Doppler examination to measure the PI at 22–24 weeks' gestation. We retrieved for analysis frozen samples from women who then developed pre‐eclampsia, as well as three control samples per woman, matched for gestational age and storage time. Inhibin A, activin A and PlGF were measured using an enzyme‐linked immunosorbent assay (ELISA) by an examiner who was blinded to the pregnancy outcome.

Results

There were 31 cases with pre‐eclampsia and 93 controls. Second‐trimester uterine artery PI and marker levels were expressed as multiples of the median (MoM). The uterine artery PI was increased in pregnancies with pre‐eclampsia compared with controls (mean ± SD, 1.45 ± 0.31 MoM vs. 1.02 ± 0.25 MoM, P < 0.001), as were the level of inhibin A (mean ± SD, 1.57 ± 0.34 MoM vs. 1.08 ± 0.43 MoM, P < 0.001) and the level of activin A (mean ± SD, 1.68 ± 0.38 MoM vs. 1.06 ± 0.42 MoM, P < 0.001). The level of PlGF was decreased in pre‐eclampsia compared with controls (mean ± SD, 0.69 ± 0.23 MoM vs. 1.00 ± 0.26 MoM, P < 0.001). Receiver–operating characteristics curves were analyzed for controls and cases and areas under the curve (AUC) were 0.796 (95% CI, 0.712–0.880, P < 0.001) for inhibin A, 0.823 (95% CI, 0.746–0.899, P < 0.001) for activin A, 0.831 (95% CI, 0.752–0.910, P < 0.001) for PlGF and 0.851 (95% CI, 0.783–0.920, P < 0.001) for uterine artery PI. The combination of activin A, inhibin A and PI using logistic regression analysis yielded an AUC of 0.907 (95% CI, 0.830–0.938, P < 0.001) with a sensitivity of 87% and a specificity of 80%. The combination of activin A, PlGF and PI gave an AUC of 0.925 (95% CI, 0.852–0.978, P < 0.001) with a sensitivity of 90% and a specificity of 80%. Combining all four markers gave an AUC of 0.941 (95% CI, 0.891–0.990, P < 0.001) with a sensitivity of 93% and a specificity of 80%.

Conclusion

Early second‐trimester serum inhibin A, activin A, PlGF and second‐trimester uterine artery Doppler PI may add further information for the prediction of pre‐eclampsia. The combination of the three serum markers and uterine artery Doppler PI has the highest prediction value for pre‐eclampsia. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
Gastrointestinal stromal tumors presenting as gynecological masses: usefulness of multidetector computed tomography
Authors: Teoh W. C. , Teo S. Y. , Ong C. L.
Published: August 2010

Large extraluminal gastrointestinal tumors (GISTs) may present as pelvic masses and thus mimic gynecological neoplasms in female patients. On clinical examination and pelvic ultrasound, these tumors resemble pedunculated fibroids or ovarian tumors. Multidetector computed tomography (CT), with its ability to perform isotropic multiplanar reconstruction, is useful in differentiating GISTs from true gynecological masses by demonstrating the pedicle sign connecting a pelvic GIST to its organ of origin. This allows a preoperative diagnosis to be made, which may be helpful in guiding therapeutic options and management. We present two cases of GISTs presenting as pelvic masses in which ultrasound findings suggested a gynecological cause, but multidetector CT with multiplanar reconstruction was able to determine their true organ of origin. Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd.
Outcome prediction in monochorionic diamniotic twin pregnancies with moderately discordant amniotic fluid
Authors: Van Mieghem T. , Eixarch E. , Gucciardo L. , Done E. , Gonzales I. , Van Schoubroeck D. , Lewi L. , Gratacos E. , Deprest J.
Published: August 2010

Objective

The aim of this study was to identify predictors of twin‐to‐twin transfusion syndrome (TTTS) and selective intrauterine growth restriction (sIUGR) in monochorionic diamniotic (MCDA) twin pregnancies with moderate amniotic fluid discordance (mAFD).

Methods

Monochorionic twins with mAFD (n = 45; gestational age, 15–29 weeks) were assessed for extent of fluid discordance, fetal growth discordance and fetal cardiac dysfunction, and were followed longitudinally. A prediction algorithm was constructed for TTTS and sIUGR and validated in an unrelated cohort (n = 52).

Results

Cardiac dysfunction could not predict TTTS or sIUGR. Twins below 20 weeks of gestation with a fluid discordance of ≥ 3.1 cm had a risk of TTTS of 85.7%. Sensitivity for TTTS was nevertheless only 55%. An intertwin weight discordance of ≥ 25% had 63% sensitivity and 76% specificity for sIUGR without TTTS.

Conclusion

The outcome of MCDA twins with mAFD remains unpredictable, yet high‐risk and low‐risk subgroups for TTTS can be identified based on severity of fluid discordance and gestational age. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
Ultrasound‐guided tru‐cut biopsy of abdominal and pelvic tumors in gynecology
Authors: Zikan M. , Fischerova D. , Pinkavova I. , Dundr P. , Cibula D.
Published: August 2010

Objective

To analyze the safety, adequacy and accuracy of tru‐cut biopsy and to evaluate factors potentially affecting adequacy.

Methods

We analyzed retrospectively a group of patients who had undergone tru‐cut biopsy for either primary suboptimally operable tumors, recurrence or suspected non‐genital or secondary tumor. Tru‐cut biopsy was performed either transvaginally or transabdominally, using an automatic biopsy gun with disposable needle and needle guide attached to the probe. The adequacy, i.e. obtaining a sample sufficient for identification of the origin of the tumor and performance of immunohistochemistry; accuracy, i.e. agreement between biopsy and final postoperative histology; and safety, as determined by complication rate, were assessed. Variables potentially influencing adequacy were analyzed using the orthogonal projections to latent structure method.

Results

A total of 195 biopsies were performed on 190 patients. An adequate sample was obtained in 178 (91.3%) biopsies. The final histology was not in agreement with the result from tru‐cut biopsy in two out of 118 patients who underwent subsequent surgery (accuracy 98.3%). There were complications in two cases out of the 195 biopsies performed (1.0%). Ascites, elevated CA 125, primary suboptimal operable tumor, serous epithelial ovarian cancer histology, carcinomatosis and vaginal approach were significant positive predictors for the achievement of an adequate sample, while recurrence as an indication, non‐serous and non‐ovarian histotypes and transabdominal approach were negative predictors.

Conclusion

Ultrasound‐guided tru‐cut biopsy is an efficient, minimally invasive, accurate and safe diagnostic method in the management of advanced, recurrent or atypical abdominal and pelvic tumors of probable non‐genital origin, where unnecessary laparotomy or laparoscopy can be avoided. The adequacy of tru‐cut biopsy is mainly influenced by indication group, histology, site of biopsy and approach. Our analysis can help in counseling the patient before the procedure and helps to explain the possible causes of failure of the procedure. Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd.
Prenatal diagnosis of fetal left pulmonary artery sling
Authors: Yorioka H. , Kasamatsu A. , Kanzaki H. , Kawataki M. , Yoo S.‐J.
Published: August 2010

Left pulmonary artery (LPA) sling is a very rare anomaly in which the LPA arises distally, far from the right pulmonary artery on the right side of the distal trachea, turns sharply leftwards around the trachea and courses to the left lung hilum through the space between the trachea and esophagus. LPA sling is often associated with distal tracheal narrowing, due to either intrinsic stenosis or secondary compression by the anomaly itself. To our knowledge, prenatal diagnosis of LPA sling has not been reported so far. We report a case in which LPA sling was diagnosed during fetal ultrasound examination. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
Antenatal embolization of a large chorioangioma by percutaneous Glubran 2 injection
Authors: Gajewska K. , Herinckx A. , Holoye A. , D'Haene N. , Massez A. , Cassart M. , Van Rysselberge M. , Donner C.
Published: August 2010

We describe a case of a large chorioangioma diagnosed at 18 weeks' gestation. Because of advanced fetal heart failure at 23 weeks' gestation, embolization of the chorioangioma's vessels was performed by percutaneous injection of Glubran 2 surgical glue. There was no immediate secondary effect of treatment. Devascularization was complete and durable. Signs of fetal cardiac failure normalized after 1 month and a healthy infant was delivered at 38 weeks. To our knowledge this is the first reported case of perinatal survival after successful embolization of a chorioangioma using tissue glue. Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd.
Fetal cardiac function between 11 and 35 weeks' gestation and nuchal translucency thickness
Authors: Clur S. A. B. , Oude Rengerink K. , Mol B. W. J. , Ottenkamp J. , Bilardo C. M.
Published: August 2010

Objectives

The pathophysiological background of an increased nuchal translucency (NT) is still poorly understood. Cardiac dysfunction has been proposed as a cause. The aim of this study was to determine if, in fetuses with normal hearts, the NT thickness is related to cardiac function throughout gestation.

Methods

The NT was measured in 191 karyotypically/phenotypically normal fetuses with structurally normal hearts and was increased (≥ 95th centile) in 104. All fetuses had been referred for fetal echocardiography and were prospectively included between October 1 2003 and April 1 2009. Three‐hundred and ten echocardiograms were performed between 11 and 35 weeks' gestation. The E‐ and A‐wave velocity, E/A velocity ratio, E/time velocity integral (TVI) ratio over the atrioventricular (AV) valves, myocardial performance index, acceleration time (AT) and peak velocity over the semilunar valves, stroke volume (SV) and cardiac output (CO) as well as the ductus venosus pulsatility index for veins at 11–14 weeks' gestation (DV‐PIV), were measured. A multilevel analysis was performed using the NT multiples of the median (MoM) as a continuous variable.

Results

AV‐E‐ and A‐wave velocities, E/A velocity ratios, semilunar valve peak velocity, SV, CO and aortic valve (AoV) AT increased significantly with advancing gestation. At 11–14 weeks' gestation, the AoV‐AT, tricuspid valve (TV)‐E/A, TV‐E/TVI ratios and DV‐PIV increased, and the pulmonary valve (PV) AT decreased, with increasing NT‐MoMs. After midgestation, the PV‐AT increased and the AoV‐AT, TV‐E/A and TV‐E/TVI ratios decreased with increasing NT‐MoMs.

Conclusions

NT thickness is related to right ventricular diastolic function and semilunar valve AT. Our findings suggest improved first‐trimester, but later reduced, right ventricular relaxation and discordant ventricular afterload in fetuses with an increased NT. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.