bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fractional carbon dioxide laser‐assisted photodynamic therapy for patients with actinic keratosis
Authors: Song Hyo Sang , Jung Soo‐Eun , Jang Yong Hyun , Kang Hee Young , Lee Eun‐So , Kim You Chan 
Published: May 2015

Background/purposeA relatively long incubation time is needed for photosensitizer absorption in conventional photodynamic therapy (PDT) for actinic keratosis (AK). The use of ablative CO2 fractional lasers (AFXLs) to increase drug delivery could shorten the incubation time. Here, we aimed to compare the efficacy between AFXL‐assisted PDT with a short incubation time and conventional PDT for AK.MethodsPatients with histopathologically confirmed facial AK were randomly divided into two groups. The lesions were histopathologically classified into grades I–III. In the AFXL‐assisted PDT group, an ablative fractional laser was used for pretreatment, prior to the application of methyl aminolevulinate, with an incubation time of 90 min. Irradiation was performed with a 630‐nm light‐emitting diode. In the conventional PDT group, the incubation time was 180 min. All the patients received two rounds of PDT at 2‐week intervals and underwent clinical or histological evaluation at 10 weeks after the first PDT course.ResultsTwenty‐two patients underwent conventional PDT and 24 patients underwent AFXL‐assisted PDT. Thirty‐four AKs were included in the conventional PDT group, and 35 AKs were included in the AFXL‐assisted PDT group. The clearance rate was 64.7% in the conventional PDT and 71.4% in the AFXL‐assisted PDT group; no significant differences in the clearance rate were noted between the groups (P = 0.55). The clearance rates for each grade also did not significantly differ between the two groups.ConclusionsThe use of AFXL before PDT reduced the incubation time, but yielded similar treatment efficacy as compared to conventional PDT.
Achilles' heels of governance: Critical capacity deficits and their role in governance failures
Authors: Howlett Michael , Ramesh M. 
Published: May 2015

AbstractThis article assesses the usefulness of conceptions of policy capacity for understanding policy and governance outcomes. In order to shed light on this issue, it revisits the concept of governance, derives a model of basic governance types and discusses their capacity pre‐requisites. A model of capacity is developed combining competences over three levels of activities with analysis of resource capabilities at each level. This analysis is then applied to the common modes of governance. While each mode requires all types of capacity if it is to match its theoretically optimal potential, most on‐the‐ground modes do not attain their highest potential. Moreover, each mode has a critical type of capacity which serves as its principle vulnerability; its “Achilles' heel.” Without high levels of the requisite capacity, the governance mode is unlikely to perform as expected. While some hybrid modes can serve to supplement or reinforce each other and bridge capacity gaps, other mixed forms may aggravate single mode issues. Switching between modes or adopting hybrid modes is, therefore, a non‐trivial issue in which considerations of capacity issues in general andAchilles' heel capacities in particular should be a central concern.
Uniformity of Node Level Conflict Measures in Bayesian Hierarchical Models Based on Directed Acyclic Graphs
Authors: GÅSEMYR JøRUND 
Published: May 2015

AbstractHierarchical models defined by means of directed, acyclic graphs are a powerful and widely used tool for Bayesian analysis of problems of varying degrees of complexity. A simulation‐based method for model criticism in such models has been suggested by O'Hagan in the form of a conflict measure based on contrasting separate local information sources about each node in the graph. This measure is however not well calibrated. In order to rectify this, alternative mutually similar tail probability‐based measures have been proposed independently and have been proved to be uniformly distributed under the assumed model in quite general normal models with known covariance matrices. In the present paper, we extend this result to a variety of models. An advantage of this is that computationally costly pre‐calibration schemes needed for some other suggested methods can be avoided. Another advantage is that non‐informative prior distributions can be used when performing model criticism.
Collaborative study for the characterization of a chikungunya virus RNA reference reagent for use in nucleic acid testing
Authors: Añez G. , Jiang Z. , Heisey D. A. R. , Kerby S. , Rios M. ,   The Chikungunya virus Collaborative Study Group
Published: May 2015

Background and ObjectivesInfections with the mosquito‐borne chikungunya virus (CHIKV) can cause febrile illness or be asymptomatic. Laboratory diagnosis of CHIKV is often made with laboratory‐developed nucleic acid amplification technology (NAT) assays because there are no U.S. Food and Drug Administration (FDA)‐approved diagnostic or blood screening assays. We aimed to produce a well‐characterized CHIKV RNA reference reagent (CHIKV‐RR) for use in NAT assays.Materials and MethodsA CHIKV RNA‐RR consisting of cell culture‐grown, heat‐inactivated CHIKV diluted in human plasma was assessed by 8 laboratories in a collaborative study. The participants were asked to test the CHIKV‐RR using their NAT assay(s) by qualitative testing (determination of RNA end‐point by testing log and half‐log dilutions followed by calculation of estimated NAT‐detectable units/ml, after adjustment for the sample volume used for testing), and by quantitative testing, when available.ResultsResults from the testing showed that the CHIKV‐RR had an estimated overall mean of 7·56 log10 detectable units/ml, ranging from 6·2 log10 to 8·6 log10.ConclusionsThe Center for Biologics for Evaluation and Research/FDA CHIKV RNA‐RR for NAT was established with a concentration of 7·56 log10 detectable units/ml.
Towards a hydrodynamically enhanced design and operation of primary settling tanks – Results of a long term in situ measurement investigation program
Authors: Patziger Miklós , Kiss Katalin 
Published: May 2015

AbstractIn modern wastewater treatment the function of primary settling tanks (PSTs) has become more complex comprising the control of readily biodegradable carbon between denitrification and biogas production by an optimum performance. This requires detailed investigations in order to obtain exact knowledge of the processes within PSTs. The article shows the results of the investigation of a PST comprising in situ flow measurements and removal efficiency analysis. The measurements were carried out at different surface overflow rates, which ranged from low to even higher values than those recommended by design guidelines. This was done in order to investigate the relationship between hydrodynamic processes and removal efficiency at high hydraulic loads. Inflowing and outflowing suspended solids concentrations and loads were recorded on‐line during the measurements. The measurements provided detailed insight into the flow processes within the PST as a first step towards hydrodynamically driven design and operation control of PSTs.
Perfusion pressure and blood flow determine microvascular apparent viscosity
Authors: Yalcin Ozlem , Ortiz Daniel , Williams Alexander T. , Johnson Paul C. , Cabrales Pedro 
Published: May 2015

New Findings

What is the central question of this study?
The aim was to evaluate the effect of perfusion pressure on blood flow in small arterioles. The hypothesis was that blood flow regulates the thickness of the red‐cell‐free layer and, therefore, blood flow determines blood apparent viscosity and local vascular resistance in vascular networks with limited myogenic or metabolic regulation of blood flow.

What is the main finding and its importance?
Reduced perfusion pressures lowered volumetric flow rates and increased local vascular resistance, due to increased blood apparent viscosity. Thus, the local vascular resistance of small arterioles with limited myogenic or metabolic regulation of blood flow, appeared to be determined by changes in blood rheology rather than blood vessel diameter.

The study of blood flow regulation is important to understand and resolve pathological conditions. As blood is a complex non‐Newtonian multiphase system, the foundations of blood rheological properties have been obtained mostly in viscometers. However, blood rheological behaviour in vivo depends on the concentration of red blood cells (RBCs), their mechanical properties and the RBC hydrodynamics, including RBC migration away from the vessel wall in shear flow. This migration promotes the formation of a RBC‐depleted zone, or cell‐free layer (CFL), which reduces the apparent viscosity of blood. We hypothesize that perfusion pressure determines blood apparent viscosity in microvessels, as shear rate affects axial migration of RBCs by influencing the CFL thickness. In this study, we analysed the effects of perfusion pressure on blood flow in individual arterioles within the rat cremaster muscle preparation. Perfusion pressures to this microvascular bed were controlled by occlusions of the iliac artery using a pressure cuff. Blood flow measurements were obtained from direct measurements of blood flow velocity profile, as well as determination of CFL thickness using intravital microscopy. Our results indicate that perfusion pressure determines shear rates and the CFL thickness and its variations. In addition, blood flow reduction increased local vascular resistance by augmenting blood apparent viscosity rather than vascular hindrance. In conclusion, blood rheology could act as an intrinsic mechanism to further limit blood flow to tissue with limited myogenic and metabolic responses at low perfusion pressures.
Effect of Carbohydrate and Caffeine Ingestion on Badminton Performance
Authors: Clarke Neil D. , Duncan Michael J. 
Published: May 2015

Purpose:To investigate the effect of ingesting carbohydrate and caffeine solutions on measures that are central to success in badminton.Methods:Twelve male badminton players performed a badminton serve-accuracy test, coincidence-anticipation timing (CAT), and a choice reaction-time sprint test 60 min before exercise. Participants then consumed 7 mL/kg body mass of either water (PLA), 6.4% carbohydrate solution (CHO), a solution containing a caffeine dose of 4 mg/kg, or 6.4% carbohydrate and 4 mg/kg caffeine (C+C). All solutions were flavored with orange-flavored concentrate. During the 33-min fatigue protocol, participants were provided with an additional 3 mL/kg body mass of solution, which was ingested before the end of the protocol. As soon as the 33-min fatigue protocol was completed, all measures were recorded again.Results:Short-serve accuracy was improved after the ingestion of CHO and C+C compared with PLA (P = .001, ηp2 = .50). Long-serve accuracy was improved after the ingestion of C+C compared with PLA (P < .001, ηp2 = .53). Absolute error in CAT demonstrated smaller deteriorations after the ingestion of C+C compared with PLA (P < .05; slow, ηp2 = .41; fast, ηp2 = .31). Choice reaction time improved in all trials with the exception of PLA, which demonstrated a reduction (P < .001, ηp2 = .85), although C+C was faster than all trials (P < .001, ηp2 = .76).Conclusion:These findings suggest that the ingestion of a caffeinated carbohydrate solution before and during a badminton match can maintain serve accuracy, anticipation timing, and sprinting actions around the court.
Dengue Antibody-Dependent Enhancement: Knowns and Unknowns
Authors: Halstead Scott B. 
Published: May 2015

ABSTRACTDengue provides the most abundant example in human medicine and the greatest human illness burden caused by the phenomenon of intrinsic antibody-dependent infection enhancement (iADE). In this immunopathological phenomenon infection of monocytes or macrophages using infectious immune complexes suppresses innate antiviral systems, permitting logarithmic intracellular growth of dengue virus. The four dengue viruses evolved from a common ancestor yet retain similar ecology and pathogenicity, but although infection with one virus provides short-term cross-protection against infection with a different type, millions of secondary dengue infections occur worldwide each year. When individuals are infected in the virtual absence of cross-protective dengue antibodies, the dengue vascular permeability syndrome (DVPS) may ensue. This occurs in around 2 to 4% of second heterotypic dengue infections. A complete understanding of the biologic mechanism of iADE, dengue biology, and the mechanism of host responses to dengue infection should lead to a comprehensive and complete understanding of the pathogenesis of DVPS. A crucial emphasis must be placed on understanding ADE. Clinical and epidemiological observations of DVPS define the research questions and provide research parameters. This article will review knowledge related to dengue ADE and point to areas where there has been little research progress. These observations relate to the two stages of dengue illnesses: afferent phenomena are those that promote the success of the microorganism to infect and survive; efferent phenomena are those mounted by the host to inhibit infection and replication and to eliminate the infectious agent and infected tissues. Data will be discussed as “knowns” and “unknowns.”
Phage and Yeast Display
Authors: Sheehan Jared , Marasco Wayne A. 
Published: May 2015

ABSTRACT

Despite the availability of antimicrobial drugs, the continued development of microbial resistance—established through escape mutations and the emergence of resistant strains—limits their clinical utility. The discovery of novel, therapeutic, monoclonal antibodies (mAbs) offers viable clinical alternatives in the treatment and prophylaxis of infectious diseases. Human mAb-based therapies are typically nontoxic in patients and demonstrate high specificity for the intended microbial target. This specificity prevents negative impacts on the patient microbiome and avoids driving the resistance of nontarget species. The
in vitro
selection of human antibody fragment libraries displayed on phage or yeast surfaces represents a group of well-established technologies capable of generating human mAbs. The advantage of these forms of microbial display is the large repertoire of human antibody fragments present during a single selection campaign. Furthermore, the
in vitro
selection environments of microbial surface display allow for the rapid isolation of antibodies—and their encoding genes—against infectious pathogens and their toxins that are impractical within
in vivo
systems, such as murine hybridomas. This article focuses on the technologies of phage display and yeast display, as these strategies relate to the discovery of human mAbs for the treatment and vaccine development of infectious diseases.
Escherichia coli
O104:H4 Pathogenesis: an Enteroaggregative
E. coli
/Shiga Toxin-Producing
E. coli
Explosive Cocktail of High Virulence
Authors: Navarro-Garcia Fernando 
Published: May 2015

ABSTRACT

A major outbreak caused by
Escherichia coli
of serotype O104:H4 spread throughout Europe in 2011. This large outbreak was caused by an unusual strain that is most similar to enteroaggregative
E. coli
(EAEC) of serotype O104:H4. A significant difference, however, is the presence of a prophage encoding the Shiga toxin, which is characteristic of enterohemorrhagic
E. coli
(EHEC) strains. This combination of genomic features, associating characteristics from both EAEC and EHEC, represents a new pathotype. The 2011
E. coli
O104:H4 outbreak of hemorrhagic diarrhea in Germany is an example of the explosive cocktail of high virulence and resistance that can emerge in this species. A total of 46 deaths, 782 cases of hemolytic-uremic syndrome, and 3,128 cases of acute gastroenteritis were attributed to this new clone of EAEC/EHEC. In addition, recent identification in France of similar O104:H4 clones exhibiting the same virulence factors suggests that the EHEC O104:H4 pathogen has become endemically established in Europe after the end of the outbreak. EAEC strains of serotype O104:H4 contain a large set of virulence-associated genes regulated by the AggR transcription factor. They include, among other factors, the pAA plasmid genes encoding the aggregative adherence fimbriae, which anchor the bacterium to the intestinal mucosa (stacked-brick adherence pattern on epithelial cells). Furthermore, sequencing studies showed that horizontal genetic exchange allowed for the emergence of the highly virulent Shiga toxin-producing EAEC O104:H4 strain that caused the German outbreak. This article discusses the role these virulence factors could have in EAEC/EHEC O104:H4 pathogenesis.
Overview and Historical Perspectives
Authors: Kaper James B. , O'Brien Alison D. 
Published: May 2015

ABSTRACT

In this overview, we describe the history of Shiga toxin (Stx)-producing
Escherichia coli
(STEC) in two phases. In phase one, between 1977 and 2011, we learned that
E. coli
could produce Shiga toxin and cause both hemorrhagic colitis and the hemolytic-uremic syndrome in humans and that the prototype STEC—
E. coli
O157:H7—adheres to and effaces intestinal epithelial cells by a mechanism similar to that of enteropathogenic
E. coli
. We also recognized that the genes for Stx are typically encoded on a lysogenic phage; that STEC O157:H7 harbors a large pathogenicity island that encodes the elements needed for the characteristic attaching and effacing lesion; and that the most severe cases of human disease are linked to production of Stx type 2a, not Stx type 1a. Phase two began with a large food-borne outbreak of hemorrhagic colitis and hemolytic-uremic syndrome in Germany in 2011. That outbreak was caused by a novel strain consisting of enteroaggregative
E. coli
O104:H4 transduced by a Stx2a-converting phage. From this outbreak we learned that any
E. coli
strain that can adhere tightly to the human bowel (either by a biofilm-like mechanism as in
E. coli
O104:H4 or by an attaching and effacing mechanism as in
E. coli
O157:H7) can cause severe diarrheal and systemic illness when it acquires the capacity to produce Stx2a. This overview provides the basis for the review of current information regarding these fascinating and complex pathogens.
c-di-GMP and its Effects on Biofilm Formation and Dispersion: a
Pseudomonas Aeruginosa
Review
Authors: Ha Dae-Gon , O'Toole George A. 
Published: May 2015

ABSTRACT

Since its initial discovery as an allosteric factor regulating cellulose biosynthesis in
Gluconacetobacter xylinus
, the list of functional outputs regulated by c-di-GMP has grown. We have focused this article on one of these c-di-GMP-regulated processes, namely, biofilm formation in the organism
Pseudomonas aeruginosa
. The majority of diguanylate cyclases and phosphodiesterases encoded in the
P. aeruginosa
genome still remain uncharacterized; thus, there is still a great deal to be learned about the link between c-di-GMP and biofilm formation in this microbe. In particular, while a number of c-di-GMP metabolizing enzymes have been identified that participate in reversible and irreversible attachment and biofilm maturation, there is a still a significant knowledge gap regarding the c-di-GMP output systems in this organism. Even for the well-characterized Pel system, where c-di-GMP-mediated transcriptional regulation is now well documented, how binding of c-di-GMP by PelD stimulates Pel production is not understood in any detail. Similarly, c-di-GMP-mediated control of swimming, swarming and twitching also remains to be elucidated. Thus, despite terrific advances in our understanding of
P. aeruginosa
biofilm formation and the role of c-di-GMP in this process since the last version of this book (indeed there was no chapter on c-di-GMP!) there is still much to learn.
Everyman's Guide to Bacterial Insertion Sequences
Authors: Siguier Patricia , Gourbeyre Edith , Varani Alessandro , Ton-Hoang Bao , Chandler Mick 
Published: May 2015

ABSTRACT
The number and diversity of known prokaryotic insertion sequences (IS) have increased enormously since their discovery in the late 1960s. At present the sequences of more than 4000 different IS have been deposited in the specialized ISfinder database. Over time it has become increasingly apparent that they are important actors in the evolution of their host genomes and are involved in sequestering, transmitting, mutating and activating genes, and in the rearrangement of both plasmids and chromosomes. This review presents an overview of our current understanding of these transposable elements (TE), their organization and their transposition mechanism as well as their distribution and genomic impact. In spite of their diversity, they share only a very limited number of transposition mechanisms which we outline here. Prokaryotic IS are but one example of a variety of diverse TE which are being revealed due to the advent of extensive genome sequencing projects. A major conclusion from sequence comparisons of various TE is that frontiers between the different types are becoming less clear. We detail these receding frontiers between different IS-related TE. Several, more specialized chapters in this volume include additional detailed information concerning a number of these.
In a second section of the review, we provide a detailed description of the expanding variety of IS, which we have divided into families for convenience. Our perception of these families continues to evolve and families emerge regularly as more IS are identified. This section is designed as an aid and a source of information for consultation by interested specialist readers.
Tyrosine Recombinase Retrotransposons and Transposons
Authors: Poulter Russell T. M. , Butler Margi I. 
Published: May 2015

ABSTRACT

Retrotransposons carrying tyrosine recombinases (YR) are widespread in eukaryotes. The first described tyrosine recombinase mobile element, DIRS1, is a retroelement from the slime mold
Dictyostelium discoideum
. The YR elements are bordered by terminal repeats related to their replication via free circular dsDNA intermediates. Site-specific recombination is believed to integrate the circle without creating duplications of the target sites. Recently a large number of YR retrotransposons have been described, including elements from fungi (mucorales and basidiomycetes), plants (green algae) and a wide range of animals including nematodes, insects, sea urchins, fish, amphibia and reptiles. YR retrotransposons can be divided into three major groups: the DIRS elements, PAT-like and the Ngaro elements. The three groups form distinct clades on phylogenetic trees based on alignments of reverse transcriptase/ribonuclease H (RT/RH) and YR sequences, and also having some structural distinctions. A group of eukaryote DNA transposons, cryptons, also carry tyrosine recombinases. These DNA transposons do not encode a reverse transcriptase. They have been detected in several pathogenic fungi and oomycetes. Sequence comparisons suggest that the crypton YRs are related to those of the YR retrotransposons. We suggest that the YR retrotransposons arose from the combination of a crypton-like YR DNA transposon and the RT/RH encoding sequence of a retrotransposon. This acquisition must have occurred at a very early point in the evolution of eukaryotes.