bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conceptualizing and theorizing EU regulatory networks
Authors: Blauberger Michael , Rittberger Berthold 
Published: September 2014

AbstractEuropean regulatory networks (ERNs) play a central role in the formulation, deliberation, and implementation of EU policies and have, thus, become objects of investigation in a fast‐growing scholarly literature. We identify two shortcomings – one conceptual, one theoretical – in the literature on ERNs: First, we argue that the principal–agent approach, which is conventionally used to conceptualize ERNs, overlooks and even misrepresents central features of ERNs. By introducing and applying the “orchestration” framework to ERNs we demonstrate that it better captures the specific characteristics of ERNs. Secondly, explanations for the choice and design of ERNs have treated functional and power‐based accounts as mutually exclusive. We argue instead that explanatory leverage can be gained by combining these two accounts by specifying their respective domains of application. While functional accounts enable us to illuminate why and under what circumstances ERNs are created in the first place (rather than EU agencies or delegation to the Commission), political accounts help us to shed light on variation in the design of ERNs (i.e. why actors opt for rather close or loose network structures). We illustrate the explanatory value‐added of such an approach through two brief case studies on EU telecommunications and competition policies.
Regulatory capabilities: A normative framework for assessing the distributional effects of regulation
Authors: Cafaggi Fabrizio , Pistor Katharina 
Published: September 2014

AbstractThis paper develops the normative concept of “regulatory capabilities.” It asserts that nobody – individuals, groups, or entities – should be subjected to a regulatory regime without some freedom to determine its nature. Self‐determination in this context means the ability to accept or reject a regulatory regime imposed by others or to develop viable alternative approaches. We use the term “regulatory capabilities” to capture the importance of enabling conditions for regulatory self‐determination. This is particularly important in the transnational context where private, hybrid public–private, and public actors compete for influence, shape domestic regulation, and, in doing so, limit the scope for democratic self‐governance. In short, this paper seeks to contribute to the general debate on the normative foundations of and the requisite conditions for transnational regulation and governance.
On the Nature of Toddlers' Helping: Helping or Interest in Others' Activity?
Authors: Carpendale Jeremy I. M. , Kettner Viktoria A. , Audet Karyn N. 
Published: September 2014

AbstractToddlers' helping has been interpreted as early evidence of cooperation and altruism. We consider whether this important social activity might, instead, be due to toddlers' interest in participating in the activity of others, and we illustrate this possibility with diary observations of infants' social and communicative development. This alternative view of toddlers' helping as one manifestation of a more‐general tendency for social engagement requires a different approach to the explanation of this aspect of social development. We argue for a relational developmental systems account of the emergence and further development of infants' social and emotional engagement leading to toddlers' helping.
Foundations of the Workfare State – Reflections on the Political Transformation of the Welfare State in Britain
Authors: Deeming Christopher 
Published: September 2014

AbstractThe British ‘welfare state’ has been transformed. ‘Welfare’ has been replaced by a new ‘workfare’ regime (the ‘Work Programme’) defined by tougher state regulatory practices for those receiving out‐of‐work benefits. US‐style mandatory community work programmes are being revived and expanded. This article, therefore, considers shifting public attitudes to work and welfare in Britain and changing attitudes to working‐age welfare and out‐of‐work benefits in particular. It also considers the extent to which recent transformations of the state may be explained by declines in traditional labourist politics and class‐based solidarity. Thus, we attempt to develop a richer understanding of changing public attitudes towards welfare and the punitive regulatory ‘workfare’ practices engaged by the modern state in the liberal market economy; reflecting on the nature of the relations between ideology, party policies, popular attitudes and their political impact.
Rhabdomyolysis associated with cytomegalovirus infection in kidney transplant recipients
Authors: Jung H.‐Y. , Kim K.‐H. , Park S.‐C. , Lee J.‐H. , Choi J.‐Y. , Cho J.‐H. , Park S.‐H. , Kim Y.‐L. , Kim H.‐K. , Huh S. , Kim C.‐D. 
Published: September 2014

AbstractRhabdomyolysis is a pathological syndrome caused by skeletal muscle cell damage that affects the integrity of the cellular membrane and leads to the release of toxic intracellular constituents into the bloodstream. Although cytomegalovirus (CMV) has rarely been reported as a cause of rhabdomyolysis, CMV infection could be considered as a possible cause because of its clinical significance in kidney transplant recipients (KTRs). We report 2 cases of rhabdomyolysis associated with CMV infection in KTRs. A 64‐year‐old woman (Case 1) and a 65‐year‐old man (Case 2), who had each received a kidney from a living unrelated donor, were admitted with complaints of weakness in both legs and myalgia. Laboratory findings revealed highly increased creatine phosphokinase and myoglobinuria. In both cases, no recent alterations of medications had occurred, and other causes of rhabdomyolysis—such as trauma, alcohol, drugs, and electrolyte abnormalities – were excluded. CMV pp65 antigen was positive, and patients were diagnosed with rhabdomyolysis associated with CMV infection. Both patients recovered without complications after ganciclovir treatment. In conclusion, CMV infection should be considered as a possible cause of rhabdomyolysis in KTRs.
Risk factors associated with human Rift Valley fever infection: systematic review and meta‐analysis
Authors: Nicholas Dennis E. , Jacobsen Kathryn H. , Waters Nigel M. 
Published: September 2014

AbstractObjectiveTo identify risk factors for human Rift Valley fever virus (RVFV) infection.MethodsA systematic review identified 17 articles reporting on 16 studies examining risk factors for RVFV. Pooled odds ratios (pOR) were calculated for exposures examined in four or more studies.ResultsBeing male [pOR = 1.4 (1.0, 1.8)], contact with aborted animal tissue [pOR = 3.4 (1.6, 7.3)], birthing an animal [pOR = 3.2 (2.4, 4.2)], skinning an animal [pOR = 2.5 (1.9, 3.2)], slaughtering an animal [pOR = 2.4 (1.4, 4.1)] and drinking raw milk [pOR = 1.8 (1.2, 2.6)] were significantly associated with RVF infection after meta‐analysis. Other potential risk factors include sheltering animals in the home and milking an animal, which may both involve contact with animal body fluids.ConclusionsBased on the identified risk factors, use of personal protective equipment and disinfectants by animal handlers may help reduce RVFV transmission during outbreaks. Milk pasteurisation and other possible preventive methods require further investigation.
A Systematic Scoping Study of the Socio‐Economic Impact of Rift Valley Fever: Research Gaps and Needs
Authors: Peyre M. , Chevalier V. , Abdo‐Salem S. , Velthuis A. , Antoine‐Moussiaux N. , Thiry E. , Roger F. 
Published: September 2014

SummaryRift Valley fever (RVF) is a severe mosquito‐borne disease affecting humans and domestic ruminants. RVF virus has been reported in most African countries, as well as in the Arabic Peninsula. This paper reviews the different types of socio‐economic impact induced by RVF disease and the attempts to evaluate them. Of the 52 papers selected for this review, 13 types of socio‐economic impact were identified according to the sector impacted, the level and temporal scale of the impact. RVF has a dramatic impact on producers and livestock industries, affecting public and animal health, food security and the livelihood of the pastoralist communities. RVF also has an impact on international trade and other agro‐industries. The risk of introducing RVF into disease‐free countries via the importation of an infected animal or mosquito is real, and the consequent restriction of access to export markets may induce dramatic economic consequences for national and local economies. Despite the important threat of RVF, few studies have been conducted to assess the socio‐economic impact of the disease. The 17 studies identified for quantitative analysis in this review relied only on partial cost analysis, with limited reference to mid‐ and long‐term impact, public health or risk mitigation measures. However, the estimated impacts were high (ranging from $5 to $470 million USD losses). To reduce the impact of RVF, early detection and rapid response should be implemented. Comprehensive disease impact studies are required to provide decision‐makers with science‐based information on the best intervention measure to implement ensuring efficient resource allocation. Through the analysis of RVF socio‐economic impact, this scoping study proposes insights into the mechanisms underpinning its often‐underestimated importance. This study highlights the need for comparative socio‐economic studies to help decision‐makers with their choices related to RVF disease management.
Automatic slice selection and diagnosis of breast strain elastography
Authors: Chang Shao‐Chien , Lee Yan‐Wei , Lai Yi‐Chen , Tiu Chui‐Mei , Wang Hsin‐Kai , Chiou Hong‐Jen , Hsu Yu‐Wei , Chou Yi‐Hong , Chang Ruey‐Feng 
Published: September 2014

Purpose:Generally speaking, breast imaging experts and physicians select a representative slice from the strain elastographic image sequences to diagnose the tumor. Given the strain image qualities, it is difficult to make a successful diagnosis using human eyes only. The main purpose of this study is to develop an automatic and reliable method to select the representative slice from the elastography cine loops and/or video and then diagnose the tumor by means of the elastographic features generated from the selected slice.Methods:In this study, the authors collected 80 biopsy‐proven breast tumors, comprising of 45 benign and 35 malignant lesions, to estimate the performance of the automatic slice selection method. Images chosen using several slice selection criteria (e.g., whole‐image analysis or tumor region analysis) were compared to the physician‐selected images to determine the best selection criterion. The level set tumor segmentation method was applied to the corresponding B‐mode part of the representative elastographic slice to overlap tumor boundaries on strain images and to calculate elastographic features for diagnosis.Results:The experiment showed that the diagnostic performance, in terms of accuracy, sensitivity, and specificity, evaluated by the leave‐one‐out method, based on the elastographic features for the representative slice selected by the proposed slice selection method, was 71.3%, 91.4%, and 55.6%, respectively, while the performance values for the physician‐selected slice were 65.0%, 77.1%, and 55.6%, respectively.Conclusions:Both the sensitivity and accuracy of the proposed slice selection method were better than those of the physician‐selected slice, and the specificity of these two different schemes is similar. According to the statistical analysis of experimental results, the performance of the proposed slice selection method was similar to that of the physician's selection. The authors concluded that the proposed slice selection method could assist the physician in selecting the appropriate representative slice and in decreasing the time of selection.
Phantomless patient‐specific TomoTherapy QA via delivery performance monitoring and a secondary Monte Carlo dose calculation
Authors: Handsfield Lydia L. , Jones Ryan , Wilson David D. , Siebers Jeffery V. , Read Paul W. , Chen Quan 
Published: September 2014

Purpose:To describe the validation and implementation of a novel quality assurance (QA) system for TomoTherapy using a Monte Carlo (MC)‐based secondary dose calculation and CT detector‐based multileaf collimator (MLC) leaf opening time measurement QA verification. This system is capable of detecting plan transfer and delivery errors and evaluating the dosimetric impact of those errors.Methods:The authors’ QA process, MCLogQA, utilizes an independent pretreatment MC secondary dose calculation and postdelivery TomoTherapy exit detector‐based MLC sinogram comparison and log file examination to confirm accurate dose calculation, accurate dose delivery, and to verify machine performance. MC radiation transport simulations are performed to estimate patient dose utilizing prestored treatment machine‐specific phase‐space information, the patient's planning CT, and MLC sinogram data. Sinogram data are generated from both the treatment planning system (MC_TPS) and from beam delivery log files (MC_Log). TomoTherapy treatment planning dose (DTPS) is compared with DMC_TPS and DMC_Log via dose–volume metrics and mean region of interest dose statistics. For validation, in‐phantom ionization chamber dose measurements (DIC) for ten sample patient plans are compared with the computed values.Results:Dose comparisons to in‐phantom ion chamber measurements validate the capability of the MCLogQA method to detect delivery errors. DMC_Log agreed with DIC within 1%, while DTPS values varied by 2%–5% compared to DIC. The authors demonstrated that TomoTherapy treatments can be vulnerable to MLC deviations and interfraction output variations during treatment delivery. Interfractional Linac output variations for each patient were approximately 2% and average output was 1%–1.5% below the gold standard. While average MLC leaf opening time error from patient to patient varied from −0.6% to 1.6%, the MLC leaf errors varied little between fractions for the same patient plan, excluding one patient.Conclusions:MCLogQA is a new TomoTherapy QA process that validates the planned dose before delivery and analyzes the delivered dose using the treatment exit detector and log file data. The MCLogQA procedure is an effective and efficient alternative to traditional phantom‐based TomoTherapy plan‐specific QA because it allows for comprehensive 3D dose verification, accounts for tissue heterogeneity, uses patient CT density tables, reduces total QA time, and provides for a comprehensive QA methodology for each treatment fraction.
Refining the Balance of Attenuation and Immunogenicity of Respiratory Syncytial Virus by Targeted Codon Deoptimization of Virulence Genes
Authors: Meng Jia , Lee Sujin , Hotard Anne L. , Moore Martin L. 
Published: September 2014

ABSTRACT

Respiratory syncytial virus (RSV) is the most important pathogen for lower respiratory tract illness in children for which there is no licensed vaccine. Live-attenuated RSV vaccines are the most clinically advanced in children, but achieving an optimal balance of attenuation and immunogenicity is challenging. One way to potentially retain or enhance immunogenicity of attenuated virus is to mutate virulence genes that suppress host immune responses. The NS1 and NS2 virulence genes of the RSV A2 strain were codon deoptimized according to either human or virus codon usage bias, and the resulting recombinant viruses (dNSh and dNSv, respectively) were rescued by reverse genetics. RSV dNSh exhibited the desired phenotype of reduced NS1 and NS2 expression. RSV dNSh was attenuated in BEAS-2B and primary differentiated airway epithelial cells but not in HEp-2 or Vero cells. In BALB/c mice, RSV dNSh exhibited a lower viral load than did A2, and yet it induced slightly higher levels of RSV-neutralizing antibodies than did A2. RSV A2 and RSV dNSh induced equivalent protection against challenge strains A/1997/12-35 and A2-line19F. RSV dNSh caused less STAT2 degradation and less NF-κB activation than did A2
in vitro
. Serial passage of RSV dNSh in BEAS-2B cells did not result in mutations in the deoptimized sequences. Taken together, RSV dNSh was moderately attenuated, more immunogenic, and equally protective compared to wild-type RSV and genetically stable.

IMPORTANCE
Respiratory syncytial virus (RSV) is the leading cause of infant viral death in the United States and worldwide, and no vaccine is available. Live-attenuated RSV vaccines are the most studied in children but have suffered from genetic instability and low immunogenicity. In order to address both obstacles, we selectively changed the codon usage of the RSV nonstructural (NS) virulence genes NS1 and NS2 to the least-used codons in the human genome (deoptimization). Compared to parental RSV, the codon-deoptimized NS1/NS2 RSV was attenuated
in vitro
and in mice but induced higher levels of neutralizing antibodies and equivalent protection against challenge. We identified a new attenuating module that retains immunogenicity and is genetically stable, achieved through specific targeting of nonessential virulence genes by codon usage deoptimization.
An ABC Transporter Is Required for Secretion of Peptide Sex Pheromones in Enterococcus faecalis
Authors: Varahan Sriram , Harms Nathan , Gilmore Michael S. , Tomich John M. , Hancock Lynn E. 
Published: September 2014

ABSTRACT

Enterococci are leading causes of hospital-acquired infection in the United States and continue to develop resistances to new antibiotics. Many
Enterococcus faecalis
isolates harbor pheromone-responsive plasmids that mediate horizontal transfer of even large blocks of chromosomal genes, resulting in hospital-adapted strains over a quarter of whose genomes consist of mobile elements. Pheromones to which the donor cells respond derive from lipoprotein signal peptides. Using a novel bacterial killing assay dependent on the presence of sex pheromones, we screened a transposon mutant library for functions that relate to the production and/or activity of the effector pheromone. Here we describe a previously uncharacterized, but well-conserved, ABC transporter that contributes to pheromone production. Using three distinct pheromone-dependent mating systems, we show that mutants defective in expressing this transporter display a 5- to 6-order-of-magnitude reduction in conjugation efficiency. In addition, we demonstrate that the ABC transporter mutant displays an altered biofilm architecture, with a significant reduction in biofilm biomass compared to that of its isogenic parent, suggesting that pheromone activity also influences biofilm development. The conservation of this peptide transporter across the
Firmicutes
suggests that it may also play an important role in cell-cell communication in other species within this important phylum.

IMPORTANCE
Enterococcus faecalis
ranks as one of the leading causes of hospital-associated infections. Strains possessing resistance to multiple antibiotics are becoming all too common in clinical settings. Pheromone-responsive plasmids play an important role in harboring and disseminating these antibiotic resistance genes. Here we have identified a novel ABC transporter that is responsible for the secretion of peptide pheromones, which enables communication between cells to mediate plasmid transfer. We have also shown that this transporter is important for biofilm formation, providing a strong rationale for its use as a viable therapeutic target which could be targeted to curb infection, as well as the spread of existing drug resistance.
Identification of a Novel Conjugative Plasmid in Mycobacteria That Requires Both Type IV and Type VII Secretion
Authors: Ummels Roy , Abdallah Abdallah M. , Kuiper Vincent , Aâjoud Anouar , Sparrius Marion , Naeem Raeece , Spaink Herman P. , van Soolingen Dick , Pain Arnab , Bitter Wilbert 
Published: September 2014

ABSTRACT

Conjugative plasmids have been identified in a wide variety of different bacteria, ranging from proteobacteria to firmicutes, and conjugation is one of the most efficient routes for horizontal gene transfer. The most widespread mechanism of plasmid conjugation relies on different variants of the type IV secretion pathway. Here, we describe the identification of a novel type of conjugative plasmid that seems to be unique for mycobacteria. Interestingly, while this plasmid is efficiently exchanged between different species of slow-growing mycobacteria, including
Mycobacterium tuberculosis
, it could not be transferred to any of the fast-growing mycobacteria tested. Genetic analysis of the conjugative plasmid showed the presence of a locus containing homologues of three type IV secretion system components and a relaxase. In addition, a new type VII secretion locus was present. Using transposon insertion mutagenesis, we show that in fact both these secretion systems are essential for conjugation, indicating that this plasmid represents a new class of conjugative plasmids requiring two secretion machineries. This plasmid could form a useful new tool to exchange or introduce DNA in slow-growing mycobacteria.

IMPORTANCE
Conjugative plasmids play an important role in horizontal gene transfer between different bacteria and, as such, in their adaptation and evolution. This effect is most obvious in the spread of antibiotic resistance genes. Thus far, conjugation of natural plasmids has been described only rarely for mycobacterial species. In fact, it is generally accepted that
M. tuberculosis
does not show any recent sign of horizontal gene transfer. In this study, we describe the identification of a new widespread conjugative plasmid that can also be efficiently transferred to
M. tuberculosis
. This plasmid therefore poses both a threat and an opportunity. The threat is that, through the acquisition of antibiotic resistance markers, this plasmid could start a rapid spread of antibiotic resistance genes between pathogenic mycobacteria. The opportunity is that we could use this plasmid to generate new tools for the efficient introduction of foreign DNA in slow-growing mycobacteria.