bluuebunny/crossref_metadata_2025 huggingface dataset:
The Ecological Sensitivity Evaluation in Yellow River Delta National Natural Reserve
Authors: Liang Chen , Li Xiaowen
Published: October 2012

Based on the grid analysis of GIS, with the combination of habitat suitability assessment and human interference analysis, the ecological sensitivity evaluation model was established. Firstly, the endangered water‐birds in Yellow River Delta NNR were prioritized as a database according to IUCN 2007 Red List, and the habitat preference was identified and evaluated through literatures review and field survey. By establishing GIS‐based 200 × 200 m grid system, the existing habitat was evaluated on landscape‐level, and a comprehensive habitat suitability index (CHSI) was developed and calculated by habitat suitability assessment model. Based on CHSI, the habitat suitability was evaluated and graded. Secondly, the typical species cranes was selected from the established database as indicator species and the habitat loss rate of indicator species associated with anthropogenic interference (roads and oil wells) was also analyzed on 200 × 200 m grids by GIS. Finally, on the basis of results from habitat suitability evaluation and human interference analysis, ecological sensitivity analysis was conducted by overlying operation. The results showed that: the ecological sensitivity of study area was quite high on the whole; the overall distribution was high in the coastal region while low in the inland region, ranking in five classes. In the area, extreme sensitivity zone and fair sensitivity zone accounted for about 55.74%, the moderate sensitivity zone was about 16.2%, the sensitivity zone and no sensitivity zone constituted 22.81 and 5.19%, respectively. In addition, compared with existing function zones, related suggestions for adjusting function zones were proposed aiming at enhancing the conservation efficacy of critical habitats.
A Review of Soil Nitrogen Mineralization as Affected by Water and Salt in Coastal Wetlands: Issues and Methods
Authors: Bai Junhong , Gao Haifeng , Xiao Rong , Wang Junjing , Huang Chen
Published: October 2012

The availability of soil nutrients can have significant influence on water quality and wetland productivity. Nitrogen mineralization is the important process transferred from organic nitrogen to plant‐available inorganic forms by soil animals and microorganism. Soil nitrogen mineralization processes in coastal wetlands will be greatly impacted by the significant changes of soil water and salt conditions caused by global climate change in the future. However, further studies concerning the effects of water and salt on soil nitrogen mineralization is still needed. The influences of other soil physical–chemical properties and plant community on soil nitrogen mineralization processes are also concluded. The influencing mechanism of soil nitrogen mineralization can be explained using the laboratory incubation, whereas the in situ incubation can contribute to reflecting the real nitrogen mineralization information in the field. The laboratory and in situ incubation methods combined with 15N tracing‐isotope technique should be combined and applied to better reflect and explain soil nitrogen mineralization processes. Moreover, the applications of modern molecular biology techniques are also very necessary to quantitatively and accurately study nitrogen mineralization.
Lagrangian analysis of hemodynamics data from FSI simulation
Authors: Duvernois Vincent , Marsden Alison L. , Shadden Shawn C.
Published: October 2012

We present the computation of Lagrangian‐based flow characterization measures for time‐dependent, deformable‐wall, finite‐element blood flow simulations. Applicability of the algorithm is demonstrated in a fluid–structure interaction simulation of blood flow through a total cavopulmonary connection (Fontan procedure), and results are compared with a rigid‐vessel simulation. Specifically, we report on several important Lagrangian‐based measures including flow distributions, finite‐time Lyapunov exponent fields, particle residence time, and exposure time calculations. Overall, strong similarity in Lagrangian measures of the flow between deformable and rigid‐vessel models was observed. Copyright © 2012 John Wiley & Sons, Ltd.
Natural networks as thermodynamic systems
Authors: Hartonen Tuomo , Annila Arto
Published: October 2012

Natural networks are considered as thermodynamic systems that evolve from one state to another by consuming free energy. The least‐time consumption of free energy is found to result in ubiquitous scale‐free characteristics. The network evolution will yield the scale‐independent qualities because the least‐time imperative will prefer attachment of nodes that contribute most to the free‐energy consumption. The analysis of evolutionary equation of motion, derived from statistical physics of open systems, reveals that evolution of natural networks is a path‐dependent and nondeterministic process. Despite the noncomputability of evolution, many mathematical models of networks can be recognized as approximations of the least‐time process as well as many measures of networks can be appreciated as practical assessments of the system's thermodynamic status. © 2012 Wiley Periodicals, Inc. Complexity, 2012
A novel low‐spur DDFS utilizing the twice second‐order high‐pass error feedback architecture
Authors: Jeng Shiann‐Shiun , Lin Hsing‐Chen , Jhuang Wei‐Sheng , Lee Yen‐Ching
Published: October 2012

In this paper, the twice second‐order high‐pass error feedback (EF) (twice second‐order high‐pass EF (HPEF)) utilizing re‐feedback process and phase‐bit splitting technique in the second‐order HPEF to design a simplified low‐spur direct digital frequency synthesizer is proposed. The proposed method performs phase‐bit splitting technique and re‐feedback process in order to make the phase change tremendously and scramble the periodicity of the phase sequences violently in the original feedback path. In addition, the noise spectrum power is spread more uniformly in order to effectively suppress the spurs due to phase‐truncated error effect. Thus, the twice second‐order HPEF is implemented on a field programmable gate array development board, the Altera Stratix II EP2S60. The simulation and experimental results show that the proposed method can effectively achieve better spectrum performance, such as spurious‐free dynamic range, as compared to basic phase truncation, first‐order HPEF and second‐order HPEF architectures. Copyright © 2012 John Wiley & Sons, Ltd.
Flow cytometric determination of stem/progenitor content in epithelial tissues: An example from nonsmall lung cancer and normal lung
Authors: Donnenberg Vera S. , Landreneau Rodney J. , Pfeifer Melanie E. , Donnenberg Albert D.
Published: October 2012

Single cell analysis and cell sorting has enabled the study of development, growth, differentiation, repair and maintenance of “liquid” tissues and their cancers. The application of these methods to solid tissues is equally promising, but several unique technical challenges must be addressed. This report illustrates the application of multidimensional flow cytometry to the identification of candidate stem/progenitor populations in non‐small cell lung cancer and paired normal lung tissue. Seventeen paired tumor/normal lung samples were collected at the time of surgical excision and processed immediately. Tissues were mechanically and enzymatically dissociated into single cell suspension and stained with a panel of antibodies used for negative gating (CD45, CD14, CD33, glycophorin A), identification of epithelial cells (intracellular cytokeratin), and detection of stem/progenitor markers (CD44, CD90, CD117, CD133). DAPI was added to measure DNA content. Formalin fixed paraffin embedded tissue samples were stained with key markers (cytokeratin, CD117, DAPI) for immunofluorescent tissue localization of populations detected by flow cytometry. Disaggregated tumor and lung preparations contained a high proportion of events that would interfere with analysis, were they not eliminated by logical gating. We demonstrate how inclusion of doublets, events with hypodiploid DNA, and cytokeratin+ events also staining for hematopoietic markers reduces the ability to quantify epithelial cells and their precursors. Using the lung cancer/normal lung data set, we present an approach to multidimensional data analysis that consists of artifact removal, identification of classes of cells to be studied further (classifiers) and the measurement of outcome variables on these cell classes. The results of bivariate analysis show a striking similarity between the expression of stem/progenitor markers on lung tumor and adjacent tumor‐free lung. © 2012 International Society for Advancement of Cytometry
Label‐free somatic cell cytometry in raw milk using acoustophoresis
Authors: Grenvall Carl , Folkenberg Jacob Riis , Augustsson Per , Laurell Thomas
Published: October 2012

A microfluidic system for cell enumeration in raw milk was developed. The new method, preconditions the milk sample using acoustophoresis that removes lipid particles which are larger than a few micrometers. The acoustophoretic preprocessing eliminates the need for conventional sample preparation techniques, which include chemical solvents, cell labeling and centrifugation, and facilitates rapid cell enumeration using microscopy or coulter counter measurements. By introducing an acoustic standing wave with three pressure nodes in a microchannel at the same time as the milk sample is laminated to the channel center, lipids are acoustically driven to the closest pressure antinode at each side of the channel center and the cells in the milk sample are focused in the central pressure node. The extracted center fraction with cells becomes sufficiently clean from lipid vesicles to enable enumeration of somatic cells without any labeling step either by direct light microscopy or by coulter counting. Obtained lipid free milk fractions clearly revealed the cell fraction when analyzed by Coulter Counting. Cell counting as measured by a Coulter Counter after acoustophoretic lipid depletion aligned with the corresponding data obtained by reference measurements based on fluorescence staining and subsequent flow cytometer analysis. © 2012 International Society for Advancement of Cytometry
Equine cellular therapy—from stall to bench to bedside?
Authors: Burk Janina , Badylak Stephen F. , Kelly Jeremy , Brehm Walter
Published: October 2012

Pioneering clinical stem cell research is being performed in the horse, a recipient of cutting edge veterinary medicine as well as a unique animal model, paving the way for human medical applications. Although demonstrable progress has been made on the clinical front, in vitro characterization of equine stem cells is still in comparatively early stages. To translate the promising results of clinical stem cell therapy in the horse, advances must be made in the characterization of equine stem cells. Aiming to improve communication between veterinarians and other natural scientists, this review gives an overview of veterinary “bedside” achievements, focusing on stem cell therapies in equine orthopedics as well as the current state of in vitro characterization of equine multipotent mesenchymal stromal cells (MSCs) and equine embryonic stem cells (ESCs). © 2012 International Society for Advancement of Cytometry
Giardia diagnostic methods in human fecal samples: A comparative study
Authors: El‐Nahas Hala A. , Salem Dalia A. , El‐Henawy Abeer A. , El‐Nimr Hosam I. , Abdel‐Ghaffar Hasan A. , El‐Meadawy Ali M.
Published: October 2012

Several methods were tried for Giardia detection in stool. This study aimed to compare between the results of ordinary microscopy, direct immunofluorescence assay (DIF), and flow cytometry (FC) for the detection of Giardia cyst in human stool samples. The study included 84 children recruited from outpatient clinics of Mansoura University Children Hospital. Fecal samples were processed and examined for Giardia cysts using conventional microscopy, DIF, and FC. Among 84 fecal samples, 40 (47.6%) were diagnosed as Giardia‐positive by saline wet mount, while DIF and FC detected 52 (61.9%), and 38 (45%) Giardia‐positive cases, respectively. When compared with DIF as a gold standard method, ordinary microscopy had 76.9% sensitivity and 100% specificity while the FC had a sensitivity of 73.1% and 100% specificity, with statistically significant differences between DIF and the other two methods (P < 0.05). DIF was able to detect as few as 500 cysts/g of concentrated stool, yielding a threshold higher than ordinary microscopy (1,800 cyst/g) even after concentration. It is concluded that direct microscopic examination is reliable in Giardia diagnosis as a first choice test. DIF is an excellent technique in clinically suspected cases after negative microscopy. FC was found to be less sensitive to obtain accurate organisms' count but it could be an effective alternative method for the detection of Giardia cysts, especially for large‐scale epidemiological studies or extensive surveillance programs as it has the beneficial attribute of speed and do not depend on an experienced microscope viewer. However, DIF remains the gold standard while FC still requires significant technical improvements before it can compete with DIF for Giardia diagnosis. © 2012 International Clinical Cytometry Society
Cybrids for Mitochondrial DNA Pharmacogenomics
Authors: Iglesias Eldris , Llobet Laura , Pacheu‐Grau David , Gómez‐Durán Aurora , Ruiz‐Pesini Eduardo
Published: October 2012

Preclinical Research

Several key components of the oxidative phosphorylation system are coded in mitochondrial DNA. In humans, the mutation rate of the mitochondrial genome is higher than that of nuclear DNA. Some of these mutations can modify the interaction of mitochondrial DNA‐encoded products with different therapeutic drugs. Several of these mutations have survived evolution, therefore generating different mitochondrial DNA genetic backgrounds. Thus, personalized medicine approaches must consider these particular interactions. However, before incorporating this knowledge into patient treatments, cellular and molecular studies are required. In this review, we discuss the cybrid model as a tool for this type of analysis, along with the pitfalls and improvements that are necessary before the translation of such models to medical practice.
Pharmacogenomics of Central Nervous System (CNS) Drugs
Authors: Cacabelos Ramón
Published: October 2012

Preclinical Research

Central nervous system (CNS) disorders represent a major problem of health in developed countries, with important consequences in disability and health economics. Recent findings in CNS genomics and pharmacogenomics suggest that the introduction of pharmacogenomic procedures in clinical practice may help to optimize therapeutics (efficacy and safety issues). The genes involved in the pharmacogenomics of CNS drugs fall into five categories: (i) genes associated with CNS pathogenesis; (ii) genes associated with the mechanism of action of drugs; (iii) genes associated with drug metabolism; (iv) genes associated with drug transporters; and (v) pleiotropic genes involved in multifaceted cascades and metabolic reactions. Pharmacogenomics accounts for 30–90% variability in pharmacokinetics and pharmacodynamics. Only 20–30% of the Caucasian population processes normally approximately 60% of the current drugs that are metabolized via CYP2D6, CYP2C9, and CYP2C19. Clinical pharmacogenomics may contribute to personalizing pharmacological treatment, predicting patient/drug‐dose selection, minimizing drug interactions, increasing drug efficacy, and reducing unnecessary costs.
Biological, Chemical, and Omics Research of Taxus Medicinal Resources
Authors: Hao Da‐Cheng , Xiao Pei‐Gen , Ge Guang‐Bo , Liu Ming
Published: October 2012

Preclinical Research

Taxus is a botanical source for the anticancer drug taxol (paclitaxel), first reported in 1971 as a result of bioassay guided fractionation of active extracts from stem bark samples of T. brevifolia. This led to additional discoveries of pharmacologically active taxoids in other Taxus species and to investigations on their biosynthetic precursors, analogues, and derivatives. In continuation with our studies on Taxus biochemistry, we review the genomics, transcriptomics, proteomics, metabolomics, and bioinformatics of Taxus and their endophytic fungi. The bibliometric method is used to quantify and characterize the global scientific effort in the omics technologies being applied. We conclude that systems biology and omics technologies will play an increasingly important role in future medical research involving bioactive compounds of Taxus and other natural products.
Benefits and Limitations of Infrared Technologies in Omics Research and Development of Natural Drugs and Pharmaceutical Products
Authors: Cozzolino Daniel
Published: October 2012

Preclinical Research

Properties related to individual or bioactive compounds that constitute the matrix of pharmaceutical and natural drug products (e.g., essential oils, terpenoids, flavonoids, volatile compounds, and other chemicals) are present at low concentrations (e.g., parts per million or parts per billion). Classical separation, chromatographic, and spectrometric techniques such as high‐performance liquid chromatography, gas chromatography, liquid chromatography, and mass spectrometry have been used for the elucidation of isolated compounds in research and development (R&D) of drugs and pharmaceutical products. Hence, the use of standard separation, chromatographic, and spectrometric methods were found useful for fingerprinting and comparing natural and synthetic samples, as well as for identifying single active compounds. However, these methods are time consuming and require some level of preprocessing of the sample before analysis. Over the last four decades, infrared (IR) spectroscopy became one of the most attractive and used methods for analysis of agricultural‐related products and plant materials providing simultaneous, rapid, and nondestructive tool to quantify major constituents in such samples. This review describes the benefits and limitations of IR spectroscopy combined with multivariate data analysis for high‐throughput screening and R&D of natural drugs and pharmaceutical products.
Role of Epigenomics in Drug Discovery and Therapies
Authors: Shastry Barkur S.
Published: October 2012

Preclinical Research

Recent studies suggest that the mammalian genome alone cannot completely explain many physiological and pathophysiological phenomena including variability in phenotypes, drug responses, discordance between monozygotic twins for the same trait or disorder, and disease susceptibility of an individual. The missing link could be epigenetic modifications of genome such as DNA methylation, numerous posttranslational modifications of histone proteins and regulation of expression of microRNAs. Epigenetic modifications are well known and are involved in normal mammalian development. They are modulated globally and in a gene‐specific manner by environmental factors including nutrition, hormones, toxins, and drugs. Age also plays an important role in gene–environmental interactions. Epigenomic pathways are essential for normal cellular functions with abnormalities in their programming leading to complex disorders including psychiatric diseases. Epigenetic factors can thus serve as molecular markers to predict the responsiveness of diseases to therapy. Further knowledge of epigenomic changes and identification of factors that mediate alterations in the epigenome may lead to new drug targets and therapies. In this overview the importance of epigenomics in drug development and therapies has been highlighted.
Issues in Omics Data Integration for Gene Set Analysis and Aberrant Pathway Identification
Authors: Ochs Michael F.
Published: October 2012

Preclinical Research

The impact of omics technologies, from microarrays to next‐generation sequencing, on drug development has been limited by our inability to integrate the data meaningfully for pathway analysis. Here we discuss the relationship between biomolecules and pathway activity, focusing on metabolic and signaling pathways. We discuss how each type of pathway requires a different approach to the generation of pathway statistics from omics data and provide guidance for the creation of appropriate gene sets for pathway analysis.
The effects of sand abrasion of a predominantly stable stream bed on periphyton biomass losses
Authors: Luce J. J. , Lapointe M. F. , Roy A. G. , Ketterling D. B.
Published: October 2012

Periphytic algae are a rich food resource that sustains the upper trophic levels of stream ecosystems. These algae are susceptible to loss through hydraulic shear and abrasion by mobile sediments, but there are few documented linkages between periphyton biomass and sediment transport regimes. In this study, we use both a large set of field observations and an in situ experiment to document the relationship between periphyton biomass and sand transport rate. The in situ experimental design investigates the response of diatom‐dominated periphyton biomass to abrasion from fine and coarse sand in transport over low‐lying and higher protruding host rocks. Our results showed that periphyton biomass decreased with increasing transport rates in a threshold‐type response (transport rates > 0·04–1·8 g m−1 s−1) quantified using classification and regression trees. The in situ experiment revealed that low‐lying rocks lost more biomass for a given transport rate than the higher, protruding ones. Saltating coarse sand abraded surfaces more effectively than fine sand travelling primarily in suspension. The observed pattern of biomass loss was similar to that reported in flume studies of the effects of suspended sediment on periphyton. The negative relationship between sand transport rate and post‐flow event biomass was nearly identical to that found on the Skona River, Norway, for larger flow events. Sand constitutes a large percentage of the bedload of gravel‐bed rivers and is susceptible to transport during frequent flow events. Even small increases in sand loadings to the gravel‐cobble river bed can cause large increases in streambed abrasion. Copyright © 2012 John Wiley & Sons, Ltd.
How Nonequivalency of the Flexibility of the Ligand Bridges Leads to Anisotropy of Perturbation Transmission in a 3D Spin‐Crossover Coordination Network
Authors: Białońska Agata , Bronisz Robert , Kusz Joachim , Weselski Marek , Zubko Maciej
Published: October 2012

The role of the covalent connections of iron(II) spin‐crossover centres in the transmission of perturbation produced by the HS ↔ LS transition has been investigated for the new 3D coordination polymer {[Fe(qbtr)3](ClO4)2}∞ [qbtr = 1,5‐di(1,2,3‐triazol‐1‐yl)pentane]. In this complex, a sequence of structural phase transitions occurs. A Ph1 (HS,HS) → Ph2 (HS,HS,HS) transition precedes spin crossover and is associated with an increased number of crystallographically unique iron(II) ions, whereas the change of spin state Ph2 (HS,HS,HS) → Ph3 (HS,LS) triggers another structural phase transition accompanied by a reduction in the number of the unique iron(II) sites. Iron(II) ions occupying two crystallographically unique Fe1 and Fe2 sites form the nodes of a coordination network in the Ph1 phase. The characteristic feature of the polymeric skeleton is the presence of three kinds of ligand bridges tethering the Fe1···Fe1, Fe1···Fe2 and Fe2···Fe2 sites. The ligand linkages differ from each other in rigidity, and the diversification of their properties arises from the susceptibility of the ligand molecules to undergo conformational changes. The high rigidity of the bridge established in the Ph2 phase between iron(II) ions occupying Fe2 sites allows for the propagation of the perturbation produced by the HS (Fe2) → LS (Fe2) transition through the crystal lattice. A strong compression along the Fe2···Fe2 bridging direction occurs. In contrast, the ligand molecules that form the two remaining types of bridge are disordered in the Ph2 phase and the change of spin state for the iron(II) ions occupying Fe2 sites induces their ordering, which leads to an increase in the separation between donor atoms. In effect, perturbation cannot be effectively transmitted along the Fe1···Fe1 and Fe1···Fe2 linkage directions because the “elongation” of conformationally labile ligand molecules compensates for the shortening of the Fe2–N bond lengths.
Perpendicular versus Coplanar Conformation of the SeCl2Moiety in T‐Shaped Selenyl Chloride Adducts – Propeller‐Like Free Rotation in Solution
Authors: Khrustalev Victor N. , Ismaylova Sheyda R. , Aysin Rinat R. , Matsulevich Zhanna V. , Osmanov Vladimir K. , Peregudov Alexander S. , Borisov Alexander V.
Published: October 2012

The structures of two new T‐shaped selenyl chloride adducts studied by experimental (multinuclear NMR, IR, and Raman spectroscopy and X‐ray diffraction analysis) and theoretical (ab initio and DFT quantum chemical calculations) methods clearly demonstrate the possibility of propeller‐like free rotation of the SeCl2moiety around the C–Se bond and indicate the absence of any significant double‐bond character.
Contactless conductivity detection for analytical techniques: Developments from 2010 to 2012
Authors: Kubáň Pavel , Hauser Peter C.
Published: October 2012

The developments in the field of capacitively coupled contactless conductivity detection in the approximate period from July 2010 to June 2012 are traced. Few reports concerning fundamental studies or new detector designs have appeared. On the other hand, applications in standard CZE are flourishing and contactless conductivity measurements are increasingly being employed as part of novel or more sophisticated experimental systems. Work on the lab‐on‐chip devices integrating contactless conductivity detection is continuing. A range of reports on the use of the simple yet powerful detection technique of contactless conductivity measurements in chromatographic separation as well as for analytical methods not including a separation step have also appeared.
A review of developments in the methodology and application of microemulsion electrokinetic chromatography
Authors: Ryan Richie , Altria Kevin , McEvoy Eamon , Donegan Sheila , Power Joe
Published: October 2012

MEEKC is a mode of CE, which utilizes microemulsion (ME) as the BGE to achieve separation of a diverse range of analytes. MEs are composed of nanometer‐sized oil droplets suspended in aqueous buffer which are stabilized by the presence of a surfactant and co‐surfactant. These MEs are commonly referred to as oil‐in‐water MEs and their application in MEEKC has been extensively examined. This review details advances in the theory, methodology, and application of MEEKC during the period 2010–2012. Areas covered include online sample concentration, advances in chiral separations, use of coated capillaries, chemometric approaches, and the use of novel additives to the ME system. This review also provides the reader with an introduction to MEEKC and a presentation of recent applications.
Tort immunity for cyber attacks through SAFETY Act
Authors: Carpentier Deborah A. , Finch Brian E.
Published: October 2012

The Federal Energy Regulatory Commission (FERC) has repeatedly stated that cyber and other national security threats pose an increasing risk to the reliability of the US electric grid, which “undergirds our government and economy and helps ensure the health and welfare of our citizens.”1
Nuclear generation: Costly, interminable delays continue for nuclear spent‐fuel storage
Authors:   Nuclear Waste Strategy Coalition
Published: October 2012

For Nuclear Waste Strategy Coalition (NWSC) members and others following nuclear waste policy developments, 2012 opened with more promise than usual.
Natural gas & electricity pricing: A midsummer night's dream: Why natural gas prices still sleep
Authors: Bodell Tanya
Published: October 2012

For those crushed by falling natural gas prices last spring, the summer offered an opportunity for hope that prices would recover. Although prices did creep up from their April lows, Henry Hub barely broke the $3.00‐a‐million‐Btu threshold. Forces tempering price recovery this past summer portend what may happen this winter in the absence of extreme weather conditions.
Natural gas matters: All industry segments working for success in growing gas‐fired generation
Authors: Smead Richard G.
Published: October 2012

This summer, the US natural gas industry celebrated an important milestone. It has been no secret that power generation is the most important growth market for the industry, with natural gas largely competing with coal as the preferred fuel. It was announced this summer by the Energy Information Administration that in April 2012, for the first time in history, the nation generated as much power with natural gas as it did with coal. Exhibit 1 shows the month‐by‐month convergence of the two fuels' total megawatts generated, from the beginning of 2010 until April.
VALUING QALY GAINS BY APPLYING A SOCIETAL PERSPECTIVE
Authors: Bobinac Ana , van Exel N. Job A. , Rutten Frans F. H. , Brouwer Werner B. F.
Published: October 2012

Interpreting the outcomes of cost utility analyses requires an appropriately defined threshold for costs per quality‐adjusted life year (QALY). A common view is that the threshold should represent the (consumption) value a society attaches to a QALY. So far, individual valuations of personal health gains have mainly been studied rather than potentially relevant social values. In this study, we present the first direct empirical estimates of the willingness to pay for a QALY from a societal perspective. We used the contingent valuation approach, valuing QALYs under uncertainty and correcting for probability weighting. The estimates obtained in a representative sample of the Dutch population (n = 1004) range from €52,000 to €83,000, depending on the specification of the societal perspective. The scale sensitivity was weak, however. Copyright © 2012 John Wiley & Sons, Ltd.
LATINO IMMIGRANT FAMILIES’ SOCIAL SUPPORT NETWORKS: STRENGTHS AND LIMITATIONS DURING A TIME OF STRINGENT IMMIGRATION LEGISlATION AND ECONOMIC INSECURITY
Authors: Ayón Cecilia , Naddy Michela Bou Ghosn
Published: October 2012

Focus group data (N = 52) was used to examine the sources of support available to Latino immigrant families within their social network, the role support agents play, and families’ access to formal sources of advocacy within a context of anti‐immigration legislation and economic precariousness. Results indicate that Latinos rely heavily on their family, friends, neighbors, and community entities for emotional, moral, instrumental, and financial support. Families are in need of formal sources of advocacy, particularly in regards to their experiences as immigrants and documentation status. Service providers have the potential to play a vital role in filling the gaps present in Latino immigrant families’ social network and linking families to much needed services and resources.
Interleukin‐27 expression modifies prostate cancer cell crosstalk with bone and immune cells in vitro
Authors: Zolochevska Olga , Diaz‐Quiñones Adriana O. , Ellis Jayne , Figueiredo Marxa L.
Published: October 2012

Prostate cancer is frequently associated with bone metastases, where the crosstalk between tumor cells and key cells of the bone microenvironment (osteoblasts, osteoclasts, immune cells) amplifies tumor growth. We have explored the potential of a novel cytokine, interleukin‐27 (IL‐27), for inhibiting this malignant crosstalk, and have examined the effect of autocrine IL‐27 on prostate cancer cell gene expression, as well as the effect of paracrine IL‐27 on gene expression in bone and T cells. In prostate tumor cells, IL‐27 upregulated genes related to its signaling pathway while downregulating malignancy‐related receptors and cytokine genes involved in gp130 signaling, as well as several protease genes. In both undifferentiated and differentiated osteoblasts, IL‐27 modulated upregulation of genes related to its own signaling pathway as well as pro‐osteogenic genes. In osteoclasts, IL‐27 downregulated several genes typically involved in malignancy and also downregulated osteoclastogenesis‐related genes. Furthermore, an osteogenesis‐focused real‐time PCR array revealed a more extensive profile of pro‐osteogenic gene changes in both osteoblasts and osteoclasts. In T‐lymphocyte cells, IL‐27 upregulated several activation‐related genes and also genes related to the IL‐27 signaling pathway and downregulated several genes that could modulate osteoclastogenesis. Overall, our results suggest that IL‐27 may be able to modify interactions between prostate tumor and bone microenvironment cells and thus could be used as a multifunctional therapeutic for restoring bone homeostasis while treating metastatic prostate tumors. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.
Reduction of choroidal neovascularization in mice by adeno‐associated virus‐delivered anti‐vascular endothelial growth factor short hairpin RNA
Authors: Askou Anne Louise , Pournaras Jean‐Antoine C. , Pihlmann Maria , Svalgaard Jesper D. , Arsenijevic Yvan , Kostic Corinne , Bek Toke , Dagnæs‐Hansen Frederik , Mikkelsen Jacob Giehm , Jensen Thomas Gryesten , Corydon Thomas J.
Published: October 2012

Background

Strategies leading to the long‐term suppression of inappropriate ocular angiogenesis are required to avoid the need for repetitive monthly injections for treatment of diseases of the eye, such as age‐related macular degeneration (AMD). The present study aimed to develop a strategy for the sustained repression of vascular endothelial growth factor (VEGF), which is identified as the key player in exudative AMD.

Methods

We have employed short hairpin (sh)RNAs combined with adeno‐associated virus (AAV) delivery to obtain the targeted expression of potent gene‐regulatory molecules. Anti‐VEGF shRNAs were analyzed in human retinal pigment epithelial (RPE) cells using Renilla luciferase screening. For in vivo delivery of the most potent shRNA, self‐complementary AAV vectors were packaged in serotype 8 capsids (scAAV2/8‐hU6‐sh9). In vivo efficacy was evaluated either by injection of scAAV2/8‐hU6‐sh9 into murine hind limb muscles or in a laser‐induced murine model of choroidal neovascularization (CNV) following scAAV2/8‐hU6‐sh9 subretinal delivery.

Results

Plasmids encoding anti‐VEGF shRNAs showed efficient knockdown of human VEGF in RPEs. Intramuscular administration led to localized expression and 91% knockdown of endogenous murine (m)VEGF. Subsequently, the ability of AAV2/8‐encoded shRNAs to impair vessel formation was evaluated in the murine model of CNV. In this model, the sizes of the CNV were significantly reduced (up to 48%) following scAAV2/8‐hU6‐sh9 subretinal delivery.

Conclusions

Using anti‐VEGF vectors, we have demonstrated efficient silencing of endogenous mVEGF and showed that subretinal administration of scAAV2/8‐hU6‐sh9 has the ability to impair vessel formation in an AMD animal model. Thus, AAV‐encoded shRNA can be used for the inhibition of neovascularization, leading to the development of sustained anti‐VEGF therapy. Copyright © 2012 John Wiley & Sons, Ltd.
Can serum procalcitonin levels help interpret indeterminate chest radiographs in patients hospitalized with acute respiratory illness?
Authors: Walsh Edward E. , Swinburne Andrew J. , Becker Kenneth L. , Nylen Eric S. , Snider Richard H. , Baran Andrea , Peterson Derick R. , Falsey Ann R.
Published: October 2012

BACKGROUND

Clinical diagnosis of pneumonia is difficult and chest radiographs often indeterminate, leading to incorrect diagnoses and antibiotic overuse.

OBJECTIVE

To determine if serum procalcitonin (ProCT) could assist in managing patients with respiratory illness and indeterminate radiographs.

DESIGN

Subjects were prospectively enrolled during 2 consecutive winters.

SETTING

A 520‐bed hospital in Rochester, NY.

PATIENTS

Five hundred twenty‐eight adults admitted with acute respiratory illness were enrolled.

MEASUREMENTS

Serum ProCT, admission diagnoses, and chest radiographic findings were used to derive receiver operating characteristics curves to assess predictive accuracy of ProCT for the presence of infiltrates.

RESULTS

Subjects with pneumonia had higher ProCT (median 0.27 ng/ml) than those with exacerbations of chronic obstructive pulmonary disease (0.08 ng/ml), acute bronchitis (0.09 ng/ml), or asthma (0.06 ng/ml). ProCT had moderate accuracy for the presence of infiltrates (area under curve [AUC] 0.72), when indeterminate radiographs were independently classified as infiltrates by a pulmonologist evaluating patients.

CONCLUSIONS

ProCT may be useful in diagnosing pneumonia when chest radiographs are indeterminate. Journal of Hospital Medicine 2013;8:61–67. © 2012 Society of Hospital Medicine
qMRI relaxometry of mandibular bone marrow: A monomodal distribution in sickle cell disease
Authors: Liao Joseph H. , Jara Hernan , Nadgir Rohini , Elias Elliott , Nowrouzi Nekou , Saito Naoko , Steinberg Martin H. , Sakai Osamu
Published: October 2012

Purpose:

To identify and characterize sickle cell disease (SCD)‐related changes in the composition of mandibular bone marrow using qMRI relaxometry histograms.

Materials and Methods:

Thirteen SCD patients and 17 controls underwent brain MR imaging with the mixed turbo spin‐echo (TSE) pulse sequence at 1.5T. The mandible was manually segmented and divided into body, angle, ramus, and condyle. T1 and T2 histograms of each mandible were modeled with Gaussian functions. The relaxation time histogram peaks were calculated, and the number of monomodal versus bimodal curves was compared.

Results:

SCD patients exhibited monomodal distributions on both T1 and T2 histograms, consistent with a composition of predominantly red hematopoietic marrow. Eighty‐eight percent of mandibles in control subjects exhibited a bimodal distribution in T1 and all showed a bimodal distribution in T2, indicating mixed but predominantly yellow marrow composition. The second peak in control subjects was shorter in T1 and longer in T2, consistent with yellow marrow composition.

Conclusion:

Instead of physiological fatty replacement, SCD patients exhibit red marrow persistence in the mandible, likely due to the increased demand for hematopoiesis. This phenomenon can be manifested by a monomodal curve in both T1 and T2 relaxometric histograms. J. Magn. Reson. Imaging 2013;37:1182–1188. © 2012 Wiley Periodicals, Inc.
Low prevalence of transmitted genetic drug resistance in a cohort of HIV infected naïve patients entering antiretroviral treatment programs at two sites in northern South Africa
Authors: Nwobegahay Julius , Selabe Gloria , Ndjeka Norbert O. , Manhaeve Cecile , Bessong Pascal Obong
Published: October 2012

Infection with drug resistant viruses influences the outcome of antiretroviral therapy (ART). This study was carried out to determine the transmitted genetic drug resistance profile in a cohort of patients prior to initiation of treatment at two treatment sites in northern South Africa. These study sites were among the first to benefit from antiretroviral drugs in this region. Data on HIV drug resistance are also limited in northern South Africa; and resistance testing prior to initiation of treatment is not undertaken. In 2008, 80 protease and 80 reverse transcriptase nucleotide sequences obtained from 80 patients were analyzed for genetic drug resistance using the calibrated population resistance tool for transmitted drug resistance. Viral genetic subtypes were determined by phylogenetic analysis. Two drug resistance mutations (M41L and K103N) were detected in two different patients (2.5%; 95% CI: 0.0077–0.0863). Twenty‐three sequences (29%) harbored at least one secondary mutation in the reverse transcriptase gene; while all sequences had at least one minor mutation in the protease gene. Phylogenetic analysis of the protease and reverse transcriptase genes showed that 79 out of 80 viruses were HIV‐1 subtype C, and one was an A1/C recombinant. The observations suggest that after 4 and 8 years access to ART in Mankweng and the Bela Bela communities respectively, drug resistance mutations in the naïve population was low. Regular studies are needed to update information on drug resistant viruses in treatment naïve patients to inform better treatment policies. J. Med. Virol. 84:1839–1843, 2012. © 2012 Wiley Periodicals, Inc.
Molecular study of human herpesvirus 6 and 8 involvement in coronary atherosclerosis and coronary instability
Authors: Magnoni Marco , Malnati Mauro , Cristell Nicole , Coli Stefano , Russo Domenico , Ruotolo Giacomo , Cianflone Domenico , Alfieri Ottavio , Lusso Paolo , Maseri Attilio
Published: October 2012

Several lines of evidence suggest the involvement of infectious agents in the pathogenesis of atherosclerosis. Furthermore, a correlation between infection‐driven inflammatory burden and acute manifestation of coronary artery disease has been hypothesized. The aim of this work was to assess whether human herpesvirus (HHV)‐6 and HHV‐8, two DNA viruses with a distinct tropism for endothelium and lymphocytes, may be associated with coronary instability. An age‐ and gender‐matched cross‐sectional study was undertaken in 70 patients with testing of plasma HHV‐6 and HHV‐8 DNA load in different cardiovascular clinical settings: 29 patients with acute myocardial infarction, 21 patients with stable coronary artery disease, and 20 patients without coronary and carotid artery atherosclerosis subjected to cardiac valve replacement. In all patients, HHV‐6 and HHV‐8 plasma DNA was tested by using highly sensitive, calibrated quantitative real‐time PCR assays which employ a synthetic DNA calibrator to adjust for DNA extraction and amplification efficiency. HHV‐8 viremia was undetectable in all three groups. HHV‐6 viremia was detected in a substantial fraction of the samples examined (18.6%) without significant differences among the three groups (ST segment elevation myocardial infarction: 17.2%; stable coronary artery disease: 14.3%; patients without coronary and carotid artery atherosclerosis: 25%). Furthermore, no significant differences in plasma HHV‐6 load were observed amongst the three groups of patients. These findings indicate that coronary instability is not associated specifically with active HHV‐6 or HHV‐8 infection. However, an unusually high rate of active HHV‐6 infection was documented among patients without atherosclerosis admitted to hospital with cardiac disease. J. Med. Virol. 84:1961–1966, 2012. © 2012 Wiley Periodicals, Inc.
Phylogenetic analysis of probable Non‐human genes of group A rotaviruses isolated from children with acute gastroenteritis in Belém, Brazil
Authors: Maestri Régis Piloni , Kaiano Jane Haruko Lima , Neri Darivaldo Luz , Soares Luana da Silva , Guerra Sylvia de Fatima dos Santos , Oliveira Darleise de Souza , Farias Yasmin Nascimento , Gabbay Yvone Benchimol , Leite José Paulo Gagliardi , Linhares Alexandre da Costa , Mascarenhas Joana D'Arc Pereira
Published: October 2012

Rotaviruses (RVs) are the main cause of acute viral gastroenteritis in both humans and young animals of various species such as calves, horses, pigs, dogs, cats, and birds. The genetic diversity of RVs is related to a variety of evolutionary mechanisms, including point mutation, and genome reassortment. The objective of this study was to characterize molecularly genes that encode structural and nonstructural proteins in unusual RV strains. The clinical specimens selected for this study were obtained from children and newborn with RV gastroenteritis, who participated in research projects on viral gastroenteritis conducted at the Evandro Chagas Institute. Structural (VP1‐VP4, VP6, and VP7) and nonstructural (NSP1‐NSP6) genes were amplified from stool samples by the polymerase chain reaction and subsequently sequenced. Eight unusual RV strains isolated from children and newborn with gastroenteritis were studied. Reassortment between genes of animal origin were observed in 5/8 (62.5%) strains analyzed. These results demonstrate that, although rare, interspecies (animal–human) transmission of RVs occurs in nature, as observed in the present study in strains NB150, HSP034, HSP180, HST327, and RV10109. This study is the first to be conducted in the Amazon region and supports previous data showing a close relationship between genes of human and animal origin, representing a challenge to the large‐scale introduction of RV vaccines in national immunization programs. J. Med. Virol. 84:1993–2002, 2012. © 2012 Wiley Periodicals, Inc.
Surveillance of 16 respiratory viruses in patients with influenza‐like illness in Nanjing, China
Authors: Huo Xiang , Qin Yuanfang , Qi Xian , Zu Rongqiang , Tang Fenyang , Li Liang , Hu Zhibin , Zhu Fengcai
Published: October 2012

Much less is known about the etiology of influenza‐like illness in China. A continuous surveillance of 16 respiratory viruses was conducted from November 2010 to October 2011 of outpatients with influenza‐like illness in Nanjing, China. The two largest general hospitals and a provincial virus laboratory in Nanjing participated in this study. Throat swabs were collected from outpatients during medical visits for influenza‐like illness and were tested for 16 respiratory viruses using PCR. Three hundred seventeen viruses were detected in samples from 246 (50.6%) patients with influenza‐like illness. The viruses found mostly commonly were influenza, rhinovirus, hCoV HKU1, and adenovirus. The identification rates of respiratory viruses differed significantly among different sampling seasons (P = 0.0002). The rates of influenza A and hCoV HKU1 were much higher during the influenza‐like illness winter peak than during the influenza‐like illness summer peak and other months. Co‐infections were detected in 57 (11.7%) patients and were found most commonly in adults older than 60 years. RSV was detected in 5.9% and 2.6% of patients who were 0–5 and 6–15 years old, respectively, but was not detected in other age groups. This study confirmed that multiple respiratory viruses may circulate concurrently in the population and account for a large proportion of influenza‐like illness. In addition to influenza virus, hCoV HKU1 may be associated with the influenza‐like illness winter peak in Nanjing, China. J. Med. Virol. 84:1980–1984, 2012. © 2012 Wiley Periodicals, Inc.
Comparative study of molecular and antigenic characterization for intratypic differentiation (ITD) of poliovirus strains
Authors: Adedeji A.O. , Okonko I.O. , Adu F.D.
Published: October 2012

This study was designed to compare the sensitivity of a Sabin vaccine strain‐specific PCR assay and an enzyme‐linked immunosorbent assay with polyclonal cross‐absorbed antisera (PAb‐E) for intratypic differentiation (ITD) of polioviruses (PVs). These were used for the definitive characterization of the strains. Poliovirus strains isolated in L20B and RD cell lines were subjected to both PCR and ELISA. Both PCR and ELISA identified 3 (13.6%) out of 22 isolates, respectively as poliovirus Sabin 1. PCR identified 4 (18.2%) out of 22 isolates as poliovirus Sabin 2 and ELISA identified 2 (9.1%) out of 22 isolates as poliovirus Sabin 2. None of the two assay identified poliovirus Sabin 3. Both PCR and ELISA identified 12 (54.5%) out of 22 isolates, respectively as wild poliovirus (WPV) 1. None of the assays identified any of the isolates as WPV 2 and 3. Only PCR assay was able to identify the mixture of two poliovirus Sabin serotypes (a mixture of Sabin 1 and 2) and two mixtures of poliovirus Sabin 2 and 3. In this study, only ELISA was able to identified two invalid results. Invalid results observed in this study are of important practical implication to the emergence of vaccine‐derived poliovirus. This may have epidemic potential. Hence, the two ITD assays are of paramount importance for identification of PVs. It is therefore recommended in line with WHO guideline that at least two methods be used for the ITD of poliovirus isolates, and each method should be based on a different principle (i.e., antigenic and genetic properties). J. Med. Virol. 84:1975–1979, 2012. © 2012 Wiley Periodicals, Inc.