bluuebunny/crossref_metadata_2025 huggingface dataset:
Blending technology in teaching advanced health assessment in a family nurse practitioner program: Using personal digital assistants in a simulation laboratory
Authors: Elliott Lydia , DeCristofaro Claire , Carpenter Alesia
Published: May 2012

Purpose: This article describes the development and implementation of integrated use of personal handheld devices (personal digital assistants, PDAs) and high‐fidelity simulation in an advanced health assessment course in a graduate family nurse practitioner (NP) program. A teaching tool was developed that can be utilized as a template for clinical case scenarios blending these separate technologies.

Data sources: Review of the evidence‐based literature, including peer‐reviewed articles and reviews.

Conclusions: Blending the technologies of high‐fidelity simulation and handheld devices (PDAs) provided a positive learning experience for graduate NP students in a teaching laboratory setting. Combining both technologies in clinical case scenarios offered a more real‐world learning experience, with a focus on point‐of‐care service and integration of interview and physical assessment skills with existing standards of care and external clinical resources. Faculty modeling and advance training with PDA technology was crucial to success.

Implications for practice: Faculty developed a general template tool and systems‐based clinical scenarios integrating PDA and high‐fidelity simulation. Faculty observations, the general template tool, and one scenario example are included in this article.

Disclosure  No relationship exists between any of the authors and any commercial entity or product mentioned in this article that might represent a conflict of interest. No inducements have been made by any commercial entity to submit the manuscript for publication.
Spontaneous intracranial hypotension: A case study
Authors: Tyree Tammy L. , Porter Randall
Published: May 2012

Purpose: To present an illustrative case study of a patient with spontaneous intracranial hypotension (SIH) and to increase awareness of this condition among nurse practitioners (NPs).

Data sources: A literature search was conducted, and deidentified patient information forms the basis of this presentation. The authors’ experience and appropriate images enhance the presentation of the case study.

Conclusions: SIH is a condition that typically occurs without a traumatic event, although it can be associated with minor trauma. It occurs when cerebrospinal fluid (CSF) leaks through a focal weakness in the dural sac or meningeal diverticula, resulting in CSF hypovolemia. Patients usually present with an orthostatic headache. The most common brain magnetic resonance imaging findings are diffuse pachymeningeal enhancement, descent of the cerebellar tonsils, and subdural fluid collections. Treatment options range from management of symptoms to surgical repair of the leak.

Implications for practice: As NPs continue to provide care in a variety of settings, including emergency departments and urgent care areas, they must be familiar with the progression of symptoms that might indicate SIH and be prepared to make appropriate referrals to prevent iatrogenic morbidity.
Foundational Semantics I: Descriptive Accounts
Authors: García‐Carpintero Manuel
Published: May 2012

Descriptive semantic theories purport to characterize the meanings of the expressions of languages in whatever complexity they might have. Foundational semantics purports to identify the kind of considerations relevant to establish that a given descriptive semantics accurately characterizes the language used by a given individual or community. Foundational Semantics I presents three contrasting approaches to the foundational matters, and the main considerations relevant to appraise their merits. These approaches contend that we should look at the contents of speakers’ intuitions; at the deep psychology of users and its evolutionary history, as revealed by our best empirical theories; or at the personal‐level rational psychology of those subjects. Foundational Semantics II examines a fourth view, according to which we should look instead at norms enforced among speakers. The two papers aim to determine in addition the extent to which the approaches are really rival, or rather complementary.
The Concept of Sovereignty in Contemporary Continental Political Philosophy
Authors: Erlenbusch Verena
Published: May 2012

The concept of sovereignty is one of the central concepts of modern political philosophy. However, faced with processes of economic globalization as well as legal and political universalism, contemporary political theory struggles to account for the exercise of state power in terms of the traditional understanding of sovereignty. This survey article reviews the most influential conceptualizations of sovereignty in contemporary continental political philosophy. These include Schmitt’s defense of sovereignty and Agamben’s rejection of sovereign politics as well as a number of theoretical attempts to account for the complexities of sovereignty and its adaptation to new political circumstances.
Is There a Distinctively Feminist Philosophy of Religion?
Authors: Burns Elizabeth D.
Published: May 2012

Feminist philosophers of religion such as Grace Jantzen and Pamela Sue Anderson have endeavoured, firstly, to identify masculine bias in the concepts of God found in the scriptures of the world’s religions and in the philosophical writings in which religious beliefs are assessed and proposed and, secondly, to transform the philosophy of religion, and thereby the lives of women, by recommending new or expanded epistemologies and using these to revision a concept of the divine which will inspire both women and men to work for the flourishing of the whole of humankind. It is argued, firstly, that the philosophies of Jantzen and Anderson are by no means as different from each other as they might, at first, appear. Secondly, it is suggested that their epistemologies are not distinctively feminist, and that the classical divine attributes of the Abrahamic faiths do not necessarily privilege the masculine. Perhaps the only way in which a philosophy of religion might be distinctively feminist is by emphasising the inclusion of women. This might mean being more open to concepts of the divine which are not, even in a metaphorical sense, masculine, and enhancing awareness of the ways in which abstract arguments about the divine could be relevant to the practical aspects of human life which have traditionally been the preserve of women. Insofar as these are increasingly also the responsibility of men, however, a feminist philosophy of religion might now be more appropriately characterised as an inclusivist philosophy of religion.
Agamben’s Fictions
Authors: McQuillan Colin
Published: May 2012

This article argues that Agamben’s conception of fiction is crucial for understanding his recent works. I suggest that the key to understanding Agamben conception of fiction is to be found in a few curious remarks at the end of Language and Death. These remarks explain why the distinctions between life and death, animal life and human life, bare life and political forms of life, the outlaw and the sovereign, and the norm and the exception that continue to preoccupy Agamben are all fictions. After considering Agamben’s account of these fictions and their relation to the relevant passage in Language and Death, the article explores the ways Agamben thinks the fictions that govern human action and social life might be unworked.
Too close and too rigid: Applying the Circumplex Model of Family Systems to First‐Generation Family Firms
Authors: Michael‐Tsabari Nava , Lavee Yoav
Published: May 2012

Despite growing research interest in family businesses, little is known about the characteristics of the families engaging in them. The present paper uses Olson’s (Journal of Psychotherapy & the Family, 1988, 4(12), 7–49; Journal of Family Therapy, 2000, 22, 144–167) Circumplex Model of Marital and Family Systems to look at first‐generation family firms. We describe existing typologies of family businesses and discuss similarities between the characteristics of first‐generation family firms and the rigidly enmeshed family type described in the Circumplex Model. The Steinberg family business (Gibbon & Hadekel (1990) Steinberg: The breakup of a family empire. ON, Canada: MacMillan) serves to illustrate the difficulties of rigidly enmeshed first‐generation family firms. Implications for understanding troubled family businesses are discussed together with guidelines for the assessment of a family business in crisis and for intervention: enhancing open communication; allowing for more flexible leadership style, roles, and rules; and maintaining a balance between togetherness and separateness.
A simulation‐based evaluation of methods for inferring linear barriers to gene flow
Authors: BLAIR CHRISTOPHER , WEIGEL DANA E. , BALAZIK MATTHEW , KEELEY ANNIKA T. H. , WALKER FAITH M. , LANDGUTH ERIN , CUSHMAN SAM , MURPHY MELANIE , WAITS LISETTE , BALKENHOL NIKO
Published: May 2012

Different analytical techniques used on the same data set may lead to different conclusions about the existence and strength of genetic structure. Therefore, reliable interpretation of the results from different methods depends on the efficacy and reliability of different statistical methods. In this paper, we evaluated the performance of multiple analytical methods to detect the presence of a linear barrier dividing populations. We were specifically interested in determining if simulation conditions, such as dispersal ability and genetic equilibrium, affect the power of different analytical methods for detecting barriers. We evaluated two boundary detection methods (Monmonier’s algorithm and WOMBLING), two spatial Bayesian clustering methods (TESS and GENELAND), an aspatial clustering approach (STRUCTURE), and two recently developed, non‐Bayesian clustering methods [PSMIX and discriminant analysis of principal components (DAPC)]. We found that clustering methods had higher success rates than boundary detection methods and also detected the barrier more quickly. All methods detected the barrier more quickly when dispersal was long distance in comparison to short‐distance dispersal scenarios. Bayesian clustering methods performed best overall, both in terms of highest success rates and lowest time to barrier detection, with GENELAND showing the highest power. None of the methods suggested a continuous linear barrier when the data were generated under an isolation‐by‐distance (IBD) model. However, the clustering methods had higher potential for leading to incorrect barrier inferences under IBD unless strict criteria for successful barrier detection were implemented. Based on our findings and those of previous simulation studies, we discuss the utility of different methods for detecting linear barriers to gene flow.
Clinical characteristics of patients with lung cancer and idiopathic pulmonary fibrosis in China
Authors: Xu Yan , Zhong Wei , Zhang Li , Zhao Jing , Li Longyun , Wang Mengzhao
Published: May 2012

Background:  To identify distinguishing characteristics between patients with lung cancer and idiopathic pulmonary fibrosis (IPF‐CA) and patients with IPF alone in China.

Methods:  The medical records of 24 IPF‐CA patients and 80 IPF patients admitted to Peking Union Medical College Hospital (PUMCH) from 1999 to 2009 were reviewed.

Results:  The incidence of lung cancer in IPF patients in our study was 23.1% (24/104), and the percentage of patients who smoked in the IPF‐CA group was higher than the IPF group (87.5% and 55.0%, respectively, P = 0.004). Three symptoms, including productive cough, hemoptysis, and chest pain, were more common in IPF‐CA patients than IPF alone patients. There was no significant difference in the percentage of patients with other abnormal serum tumor markers, except that the percentage of patients with abnormal neuron specific enolase was significantly higher in the IPF‐CA group than in the IPF group (28.6% vs. 7.4%, P = 0.041). The most common histology type was adenocarcinoma (33.3%). The median overall survival for IPF‐CA patients and IPF patients was 7.0 months (95% confidential interval (CI), 2.51–11.49) and 14.0 months (95% CI, 1.26–26.74), respectively, with no significant difference (P = 0.327).

Conclusion:  Due to a high proportion of IPF cases complicated with lung cancer, physicians should closely observe lung cancer incidence during the IPF follow‐up period. Individualized treatment for lung cancer patients with IPF is emphasized. Hence, it is important to ensure the safety of cancer treatments.
Prevalence of restless legs syndrome in Japanese patients with chronic liver disease
Authors: Matsuzaki Toshihisa , Ichikawa Tatsuki , Kondo Hideaki , Taura Naota , Miyaaki Hisamitsu , Isomoto Hajime , Takeshima Fuminao , Nakao Kazuhiko
Published: May 2012

Aim:  Sleep disturbance is a major complication in patients with chronic liver disease, but causes are unclear. The aim of this study was to clarify the prevalence of restless legs syndrome (RLS) in Japanese chronic liver disease patients and investigate the influence on sleep and quality of life.

Methods:  The study included 149 consecutive outpatients with chronic liver disease at Nagasaki University Hospital between September 2008 and March 2010. The presence of RLS was evaluated by a written survey using the questionnaire for the epidemiological surveillance of the international RLS research group in 2003. In addition, 89 cases, including all RLS patients, were evaluated for sleep quality and health‐related quality of life. Sleep quality was evaluated by using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI), and health‐related quality of life was evaluated by the Japanese SF‐36 Health Survey.

Result:  Twenty‐five of the 149 patients (16.8%) fulfilled the diagnostic criteria for RLS. The median global PSQI score of the RLS group was significantly higher than the non‐RLS group (9 vs 5, P < 0.01). The number of poor sleepers (global PSQI score, >5) in the RLS group was significantly higher than in the non‐RLS group (P < 0.05). In SF‐36, the mental component summary score of the RLS group was 43.8 ± 10.8, which was significantly lower than the non‐RSL group (49.8 ± 10.5; P < 0.05).

Conclusion:  This is the first report that clarifies the prevalence of RLS in Japanese chronic liver disease patients. RLS worsens quality of sleep and life in chronic liver disease patients.
Experimental determination of photostability and fluorescence‐based detection of PAHs on the Martian surface
Authors: DARTNELL Lewis R. , PATEL Manish R. , STORRIE‐LOMBARDI Michael C. , WARD John M. , MULLER Jan‐Peter
Published: May 2012

Abstract– Even in the absence of any biosphere on Mars, organic molecules, including polycyclic aromatic hydrocarbons (PAHs), are expected on its surface due to delivery by comets and meteorites of extraterrestrial organics synthesized by astrochemistry, or perhaps in situ synthesis in ancient prebiotic chemistry. Any organic compounds exposed to the unfiltered solar ultraviolet spectrum or oxidizing surface conditions would have been readily destroyed, but discoverable caches of Martian organics may remain shielded in the subsurface or within surface rocks. We have studied the stability of three representative polycyclic aromatic hydrocarbons (PAHs) in a Mars chamber, emulating the ultraviolet spectrum of unfiltered sunlight under temperature and pressure conditions of the Martian surface. Fluorescence spectroscopy is used as a sensitive indicator of remaining PAH concentration for laboratory quantification of molecular degradation rates once exposed on the Martian surface. Fluorescence‐based instrumentation has also been proposed as an effective surveying method for prebiotic organics on the Martian surface. We find the representative PAHs, anthracene, pyrene, and perylene, to have persistence half‐lives once exposed on the Martian surface of between 25 and 60 h of noontime summer UV irradiation, as measured by fluorescence at their peak excitation wavelength. This equates to between 4 and 9.6 sols when the diurnal cycle of UV light intensity on the Martian surface is taken into account, giving a substantial window of opportunity for detection of organic fluorescence before photodegradation. This study thus supports the use of fluorescence‐based instrumentation for surveying recently exposed material (such as from cores or drill tailings) for native Martian organic molecules in rover missions.
Stochastic Nonlinear Free Vibration Analysis of Piezolaminated Composite Conical Shell Panel Subjected to Thermoelectromechanical Loading With Random Material Properties
Authors: Lal Achchhe , Choski Paras , Singh B. N.
Published: May 2012

This paper presents the effect of randomness in material properties on piezolaminated composite geometrically nonlinear conical shell panel subjected to thermoelectromechanical loading acting simultaneously or individually. Material properties such as modulus ratio, Poisson’s ratio, and thermal expansion coefficients are modeled as independent random variables. The temperature field considered is assumed to be a uniform distribution over the shell panel surface and through the shell thickness and the electric field is assumed to be the transverse component Ez only. It is assumed that the mechanical properties do not depend on temperature and electric fields. The basic formulation is based on higher order shear deformation theory (HSDT) with von-Karman nonlinearity. A C0 nonlinear finite element model based on direct iterative approach in conjunction with mean centered first order perturbation technique (FOPT) used by the present author for plate is now extended for conical shell panel to solve a random nonlinear generalized eigenvalue problem. Parametric studies are carried out to examine the effect of amplitude ratios, stacking sequences, cone angles, circumferential length to thickness ratios, piezoelectric layers, applied voltages, change in temperature, types of thermoelectromechanical loadings, and support boundary conditions on the dimensionless mean and coefficient of variance (COV) of laminated conical shell panels. The present outlined approach has been validated with those available results in literature and independent Monte Carlo simulation (MCS).
Analytic Approximations for the Flow Near the Equator of a Steady Magnetohydrodynamic Boundary Layer Over a Rotating Sphere
Authors: El-Nahhas A.
Published: May 2012

The strongly nonlinear problem for the steady, laminar, viscous incompressible ,and electrically conducting fluid near the equator of the boundary layer flow due to a rotating sphere and in the presence of a uniform radial magnetic field is considered. Analytic approximations for this problem are obtained through the application of the homotopy analysis method and via a fractional basis. Variations for velocity and temperature profiles with the change of the suction/blowing, rotational, and magnetic parameters are studied.
Elementary Ca
2+
Signals Through Endothelial TRPV4 Channels Regulate Vascular Function
Authors: Sonkusare Swapnil K. , Bonev Adrian D. , Ledoux Jonathan , Liedtke Wolfgang , Kotlikoff Michael I. , Heppner Thomas J. , Hill-Eubanks David C. , Nelson Mark T.
Published: May 2012

Blood Pressure Gauge

Endothelial cells line blood vessels and, by interacting with smooth muscle, can help to control blood flow.

Sonkusare
et al.

(p.
597
; see the Perspective by

Lederer
et al.

) describe how signaling in endothelial cells controls contraction of surrounding smooth muscle cells, which provides an important mechanism for control of blood pressure. A calcium-sensitive fluorescent protein was expressed in endothelial cells of mouse arteries to image small changes in calcium concentration that appear to represent opening of single TRPV4 ion channels and consequent influx of calcium into the cell. Clustering of the channels allowed cooperative activation of a handful of channels, which appeared to produce a sufficient calcium signal to open another set of calcium-sensitive potassium channels. The resulting depolarization of the endothelial cells then passes an electrical connection to smooth muscle cells through gap junctions.
Regional Sea-Level Projection
Authors: Willis Josh K. , Church John A.
Published: May 2012

More accurate projections of regional sea levels are needed to inform adaptation and mitigation planning.
Ancient Impact and Aqueous Processes at Endeavour Crater, Mars
Authors: Squyres S. W. , Arvidson R. E. , Bell J. F. , Calef F. , Clark B. C. , Cohen B. A. , Crumpler L. A. , de Souza P. A. , Farrand W. H. , Gellert R. , Grant J. , Herkenhoff K. E. , Hurowitz J. A. , Johnson J. R. , Jolliff B. L. , Knoll A. H. , Li R. , McLennan S. M. , Ming D. W. , Mittlefehldt D. W. , Parker T. J. , Paulsen G. , Rice M. S. , Ruff S. W. , Schröder C. , Yen A. S. , Zacny K.
Published: May 2012

Martian Veins

After more than 7 years of traveling across the Meridiani Planum region of Mars, the Mars Exploration rover Opportunity reached the Endeavour Crater, a 22-km-impact crater made of materials older than those previously investigated by the rover.

Squyres
et al.

(p.
570
) present a comprehensive analysis of the rim of this crater. Localized zinc enrichments that provide evidence for hydrothermal alteration and gypsum-rich veins that were precipitated from liquid water at a relatively low temperature provide a compelling case for aqueous alteration processes in this area at ancient times.
The Environment Makes History
The Republic of Nature
An Environmental History of the United States

by Mark Fiege

University of Washington Press, Seattle, 2012. 600 pp. $34.95. ISBN 9780295991672. Weyerhaeuser Environmental Books.
Authors: McNeill J. R.
Published: May 2012

Through unconventional environmental perspectives on nine familiar episodes in U.S. history, Fiege demonstrates the importance of the natural world for understanding the past.
One H5N1 Paper Finally Goes to Press; Second Greenlighted
Authors: Enserink Martin , Cohen Jon
Published: May 2012

One of two controversial studies that shows how to make H5N1 avian influenza more transmissible in mammals is now up on
Nature
's Web site for all the world to scrutinize.
First Spinoff of African Math Institute Takes Root in Senegal
Authors: Enserink Martin
Published: May 2012

The African Institute for Mathematical Sciences Senegal is part of a story that has captivated mathematicians and triggered an outpouring of support in money, time, and brainpower.
Search for Pore-fection
Authors: Pennisi Elizabeth
Published: May 2012

At long last, nanopore sequencing seems poised to leave the lab, promising a new and better way to decode DNA.
Going Solid-State
Authors: Pennisi Elizabeth
Published: May 2012

The first nanopore sequencers will depend on protein pores, but many in the field envision replacing these biological channels with solid-state ones.
How the Modern Body Shaped Up
Authors: Gibbons Ann
Published: May 2012

A remarkably comprehensive analysis of more than 2000 European skeletons presented at the meeting reveals how cultural changes have altered our physiques.
Intranasal Immunization with a Formalin-Inactivated Human Influenza A Virus Whole-Virion Vaccine Alone and Intranasal Immunization with a Split-Virion Vaccine with Mucosal Adjuvants Show Similar Levels of Cross-Protection
Authors: Okamoto Shigefumi , Matsuoka Sumiko , Takenaka Nobuyuki , Haredy Ahmad M. , Tanimoto Takeshi , Gomi Yasuyuki , Ishikawa Toyokazu , Akagi Takami , Akashi Mitsuru , Okuno Yoshinobu , Mori Yasuko , Yamanishi Koichi
Published: May 2012

The antigenicity of seasonal human influenza virus changes continuously; thus, a cross-protective influenza vaccine design needs to be established. Intranasal immunization with an influenza split-virion (SV) vaccine and a mucosal adjuvant induces cross-protection; however, no mucosal adjuvant has been assessed clinically. Formalin-inactivated intact human and avian viruses alone (without adjuvant) induce cross-protection against the highly pathogenic H5N1 avian influenza virus. However, it is unknown whether seasonal human influenza formalin-inactivated whole-virion (WV) vaccine alone induces cross-protection against strains within a subtype or in a different subtype of human influenza virus. Furthermore, there are few reports comparing the cross-protective efficacy of the WV vaccine and SV vaccine-mucosal adjuvant mixtures. Here, we found that the intranasal human influenza WV vaccine alone induced both the innate immune response and acquired immune response, resulting in cross-protection against drift variants within a subtype of human influenza virus. The cross-protective efficacy conferred by the WV vaccine in intranasally immunized mice was almost the same as that conferred by a mixture of SV vaccine and adjuvants. The level of cross-protective efficacy was correlated with the cross-reactive neutralizing antibody titer in the nasal wash and bronchoalveolar fluids. However, neither the SV vaccine with adjuvant nor the WV vaccine induced cross-reactive virus-specific cytotoxic T-lymphocyte activity. These results suggest that the intranasal human WV vaccine injection alone is effective against variants within a virus subtype, mainly through a humoral immune response, and that the cross-protection elicited by the WV vaccine and the SV vaccine plus mucosal adjuvants is similar.
Immunogenicity and Safety of a Meningococcal Quadrivalent Conjugate Vaccine in Saudi Arabian Adolescents Previously Vaccinated with One Dose of Bivalent and Quadrivalent Meningococcal Polysaccharide Vaccines: a Phase III, Controlled, Randomized, and Modified Blind-Observer Study
Authors: Al-Mazrou Yagob , Khalil Mohamed , Findlow Helen , Chadha Helen , Bosch Castells Valerie , Johnson David R. , Borrow Ray
Published: May 2012

Reduced immune responses to repeated polysaccharide vaccination have been previously reported, but there are limited immunogenicity data on the use of meningococcal polysaccharide vaccine (PSV) followed by meningococcal conjugate vaccine. Saudi Arabian adolescents (aged 16 to 19 years) who had previously been vaccinated with ≥1 dose of bivalent meningococcal polysaccharide vaccine and 1 dose of quadrivalent meningococcal polysaccharide (MPSV4) were enrolled in a controlled, randomized, and modified observer-blind study (collectively termed the PSV-exposed group). The PSV-exposed group was randomized to receive either quadrivalent meningococcal conjugate vaccine (MCV4) (n= 145 PSV-exposed/MCV4 group) or MPSV4 (n= 142 PSV-exposed/MPSV4 group), and a PSV-naïve group received MCV4 (n= 163). Serum samples collected prevaccination and 28 days postvaccination were measured by baby rabbit serum bactericidal antibody (rSBA) assay, and vaccine tolerability and safety were also evaluated. For each serogroup, the postvaccination geometric mean titers (GMTs) were significantly higher in the PSV-naïve group than in either group comprised of the PSV-exposed participants. The postvaccination serogroup C rSBA GMT was significantly higher in the PSV-MCV4 group than in the PSV-MPSV4 group after adjusting for prevaccination GMTs. Although not statistically significant, similar differences were observed for serogroups A, Y, and W-135. No worrisome safety signals were detected. This study demonstrated MCV4 to be safe and immunogenic in those who had previously received polysaccharide vaccination, and it suggests that conjugate vaccine can partially compensate for the hyporesponsiveness seen with repeated doses of polysaccharide vaccine.
Impact of Human Granulocyte and Monocyte Isolation Procedures on Functional Studies
Authors: Zhou Lu , Somasundaram Rajesh , Nederhof Rosa F. , Dijkstra Gerard , Faber Klaas Nico , Peppelenbosch Maikel P. , Fuhler Gwenny M.
Published: May 2012

One of the first lines of defense against infection is the activation of the innate immune system. It is becoming clear that autoimmune diseases, such as rheumatoid arthritis and Crohn's disease, may be caused by disturbed innate immunity, and relating granulocyte and monocyte functions to the patient genotype has become an important part of contemporary research. Although it is essential to move this field forward, a systematic study comparing the efficacy and suitability for functional studies of the various available protocols for the isolation of these immune cells has not been performed. Here, we compare human granulocyte functionality under three enrichment protocols: (i) Ficoll density gradient centrifugation, (ii) anti-CD15 antibody-conjugated microbeads (positive selection), and (iii) Polymorphoprep. Primary monocytes were isolated in parallel using (i) anti-CD14 magnetic microbeads, (ii) non-monocyte depletion by antibody-conjugated magnetic microbeads (negative selection), (iii) RosetteSep antibody cocktail, and (iv) the classical adherence protocol. The best results in terms of purity and cell functionality were obtained with positive selection by magnetic microbeads for both human granulocytes and monocytes. Whereas phagocytosis ofEscherichia colibacteria was identical in all isolation procedures tested, the granulocyte respiratory burst was higher in positively selected cells. In addition, different granulocyte enrichment procedures affect cell surface receptor expression to different extents.In toto, we propose that positive selection of granulocytes and monocytes be adopted as the procedure of choice for studies of human granulocyte and monocyte functions but caution investigators to be aware of possible alterations in cell phenotypes with different isolation procedures.
Continuous Spread of HIV-1 Subtypes D and CRF01_AE in France from 2003 to 2009
Authors: Brand Denys , Cazein Françoise , Lot Florence , Brunet Sylvie , Thierry Damien , Moreau Alain , Pillonel Josiane , Semaille Caroline , Barin Francis
Published: May 2012

Among 61 and 35 patients who were infected in France by viruses of the rare clades D and CRF01_AE, respectively, approximately half of them originated from areas where HIV-1 is endemic, but the data showed that both clades have spread in the French indigenous population, particularly in men having sex with men (MSM).
Culture and PCR Detection of Haemophilus influenzae and Haemophilus haemolyticus in Australian Indigenous Children with Bronchiectasis
Authors: Hare K. M. , Binks M. J. , Grimwood K. , Chang A. B. , Leach A. J. , Smith-Vaughan H.
Published: May 2012

A PCR for protein D (hpd#3) was used to differentiate nontypeable
Haemophilus influenzae
(NTHI) from
Haemophilus haemolyticus
. While 90% of nasopharyngeal specimens and 100% of lower-airway specimens from 84 Indigenous Australian children with bronchiectasis had phenotypic NTHI isolates confirmed as
H. influenzae
, only 39% of oropharyngeal specimens with phenotypic NTHI had
H. influenzae
. The nasopharynx is therefore the preferred site for NTHI colonization studies, and NTHI is confirmed as an important lower-airway pathogen.
First Report of Vancomycin-Intermediate Resistance in Sequence Type 72 Community Genotype Methicillin-Resistant Staphylococcus aureus
Authors: Chung Doo Ryeon , Baek Jin Yang , Kim Hyun Ah , Lim Min Hee , Kim So Hyun , Ko Kwan Soo , Kang Cheol-In , Peck Kyong Ran , Lee Nam Yong , Song Jae-Hoon
Published: May 2012

Vancomycin-intermediate resistance has not been previously reported among sequence type 72 (ST72) methicillin-resistant
Staphylococcus aureus
(MRSA) isolates of SCC
mec
type IV (ST72-MRSA-IV), which are distinctive community genotype strains in Korea. We report the first case of vancomycin treatment failure due to development of vancomycin-intermediate resistance in infection caused by an ST72-MRSA-IV isolate.
Sustained Reduction of Microbial Burden on Common Hospital Surfaces through Introduction of Copper
Authors: Schmidt Michael G. , Attaway Hubert H. , Sharpe Peter A. , John Joseph , Sepkowitz Kent A. , Morgan Andrew , Fairey Sarah E. , Singh Susan , Steed Lisa L. , Cantey J. Robert , Freeman Katherine D. , Michels Harold T. , Salgado Cassandra D.
Published: May 2012

The contribution of environmental surface contamination with pathogenic organisms to the development of health care-associated infections (HAI) has not been well defined. The microbial burden (MB) associated with commonly touched surfaces in intensive care units (ICUs) was determined by sampling six objects in 16 rooms in ICUs in three hospitals over 43 months. At month 23, copper-alloy surfaces, with inherent antimicrobial properties, were installed onto six monitored objects in 8 of 16 rooms, and the effect that this application had on the intrinsic MB present on the six objects was assessed. Census continued in rooms with and without copper for an additional 21 months. In concert with routine infection control practices, the average MB found for the six objects assessed in the clinical environment during the preintervention phase was 28 times higher (6,985 CFU/100 cm
2
;
n
= 3,977 objects sampled) than levels proposed as benign immediately after terminal cleaning (<250 CFU/100 cm
2
). During the intervention phase, the MB was found to be significantly lower for both the control and copper-surfaced objects. Copper was found to cause a significant (83%) reduction in the average MB found on the objects (465 CFU/100 cm
2
;
n
= 2714 objects) compared to the controls (2,674 CFU/100 cm
2
;
n
= 2,831 objects [
P
< 0.0001]). The introduction of copper surfaces to objects formerly covered with plastic, wood, stainless steel, and other materials found in the patient care environment significantly reduced the overall MB on a continuous basis, thereby providing a potentially safer environment for hospital patients, health care workers (HCWs), and visitors.
Early Serum Galactomannan Trend as a Predictor of Outcome of Invasive Aspergillosis
Authors: Chai Louis Y. A. , Kullberg Bart-Jan , Johnson Elizabeth M. , Teerenstra Steven , Khin Lay Wai , Vonk Alieke G. , Maertens Johan , Lortholary Olivier , Donnelly Peter J. , Schlamm Haran T. , Troke Peter F. , Netea Mihai G. , Herbrecht Raoul
Published: May 2012

The monitoring and prediction of treatment responses to invasive aspergillosis (IA) are difficult. We determined whether serum galactomannan index (GMI) trends early in the course of disease may be useful in predicting eventual clinical outcomes. For the subjects recruited into the multicenter Global Aspergillosis Study, serial GMIs were measured at baseline and at weeks 1, 2, and 4 following antifungal treatment. Clinical response and survival at 12 weeks were the outcome measures. GMI trends were analyzed by using the generalized estimation equation approach. GMI cutoffs were evaluated by using receiver-operating curve analyses incorporating pre- and posttest probabilities. Of the 202 study patients diagnosed with IA, 71 (35.1%) had a baseline GMI of ≥0.5. Week 1 GMI was significantly lower for the eventual responders to treatment at week 12 than for the nonresponders (GMIs of 0.62 ± 0.12 and 1.15 ± 0.22, respectively;
P
= 0.035). A GMI reduction of >35% between baseline and week 1 predicted a probability of a satisfactory clinical response. For IA patients with pretreatment GMIs of <0.5 (
n
= 131; 64.9%), GMI ought to remain low during treatment, and a rising absolute GMI to >0.5 at week 2 despite antifungal treatment heralded a poor clinical outcome. Here, every 0.1-unit increase in the GMI between baseline and week 2 increased the likelihood of an unsatisfactory clinical response by 21.6% (
P
= 0.018). In summary, clinical outcomes may be anticipated by charting early GMI trends during the first 2 weeks of antifungal therapy. These findings have significant implications for the management of IA.
Glycoprotein G of Herpes Simplex Virus 2 as a Novel Vaccine Antigen for Immunity to Genital and Neurological Disease
Authors: Görander Staffan , Harandi Ali M. , Lindqvist Madelene , Bergström Tomas , Liljeqvist Jan-Åke
Published: May 2012

The envelope glycoproteins of herpes simplex virus 1 (HSV-1) and HSV-2, with the exception of glycoprotein G, elicit cross-reactive B- and T-cell responses. Human vaccine trials, using the cross-reactive glycoproteins B and D, have shown no protection against genital HSV-2 infection or disease. In this study, the mature form of glycoprotein G (mgG-2) of HSV-2 was used for immunization of mice, either alone or in combination with adjuvant CpG, followed by an intravaginal challenge with a lethal dose of a fully virulent HSV-2 strain. Mice immunized with mgG-2 plus CpG showed low disease scores and a significantly higher survival rate (73%) than mice immunized with mgG-2 alone (20%) or controls (0%). Accordingly, limited numbers of infectious HSV-2 particles were detected in the spinal cord of mice immunized with mgG-2 plus CpG. The observed protection was associated with a gamma interferon (IFN-γ) response by splenic CD4+T cells upon antigen restimulationin vitroand in vaginal washes 1 day postinfection. The majority of sera collected from mice immunized with mgG-2 plus CpG showed macrophage-mediated antibody-dependent cellular cytotoxicity and antibody-dependent complement-mediated cytolysis, while no neutralization activity was observed. In conclusion, we have shown that immunization with the type-specific mgG-2 protein in combination with CpG could elicit protective immunity against an otherwise lethal vaginal HSV-2 challenge. The mgG-2 protein may therefore constitute a promising HSV-2 vaccine antigen to be considered for future human trials.
LuIII Parvovirus Selectively and Efficiently Targets, Replicates in, and Kills Human Glioma Cells
Authors: Paglino Justin C. , Ozduman Koray , van den Pol Anthony N.
Published: May 2012

Because productive infection by parvoviruses requires cell division and is enhanced by oncogenic transformation, some parvoviruses may have potential utility in killing cancer cells. To identify the parvovirus(es) with the optimal oncolytic effect against human glioblastomas, we screened 12 parvoviruses at a high multiplicity of infection (MOI). MVMi, MVMc, MVM-G17, tumor virus X (TVX), canine parvovirus (CPV), porcine parvovirus (PPV), rat parvovirus 1A (RPV1A), and H-3 were relatively ineffective. The four viruses with the greatest oncolytic activity, LuIII, H-1, MVMp, and MVM-G52, were tested for the ability, at a low MOI, to progressively infect the culture over time, causing cell death at a rate higher than that of cell proliferation. LuIII alone was effective in all five human glioblastomas tested. H-1 progressively infected only two of five; MVMp and MVM-G52 were ineffective in all five. To investigate the underlying mechanism of LuIII's phenotype, we used recombinant parvoviruses with the LuIII capsid replacing the MVMp capsid or with molecular alteration of the P4 promoter. The LuIII capsid enhanced efficient replication and oncolysis in MO59J gliomas cells; other gliomas tested required the entire LuIII genome to exhibit enhanced infection. LuIII selectively infected glioma cells over normal glial cells
in vitro
. In mouse models, human glioblastoma xenografts were selectively infected by LuIII when administered intratumorally; LuIII reduced tumor growth by 75%. LuIII also had the capacity to selectively infect subcutaneous or intracranial gliomas after intravenous inoculation. Intravenous or intracranial LuIII caused no adverse effects. Intracranial LuIII caused no infection of mature mouse neurons or glia
in vivo
but showed a modest infection of developing neurons.
Seasonal Trivalent Inactivated Influenza Vaccine Protects against 1918 Spanish Influenza Virus Infection in Ferrets
Authors: Pearce Melissa B. , Belser Jessica A. , Gustin Kortney M. , Pappas Claudia , Houser Katherine V. , Sun Xiangjie , Maines Taronna R. , Pantin-Jackwood Mary J. , Katz Jacqueline M. , Tumpey Terrence M.
Published: May 2012

The influenza virus H1N1 pandemic of 1918 was one of the worst medical catastrophes in human history. Recent studies have demonstrated that the hemagglutinin (HA) protein of the 1918 virus and 2009 H1N1 pandemic virus [A(H1N1)pdm09], the latter now a component of the seasonal trivalent inactivated influenza vaccine (TIV), share cross-reactive antigenic determinants. In this study, we demonstrate that immunization with the 2010-2011 seasonal TIV induces neutralizing antibodies that cross-react with the reconstructed 1918 pandemic virus in ferrets. TIV-immunized ferrets subsequently challenged with the 1918 virus displayed significant reductions in fever, weight loss, and virus shedding compared to these parameters in nonimmune control ferrets. Seasonal TIV was also effective in protecting against the lung infection and severe lung pathology associated with 1918 virus infection. Our data demonstrate that prior immunization with contemporary TIV provides cross-protection against the 1918 virus in ferrets. These findings suggest that exposure to A(H1N1)pdm09 through immunization may provide protection against the reconstructed 1918 virus which, as a select agent, is considered to pose both biosafety and biosecurity threats.
Corneal Replication Is an Interferon Response-Independent Bottleneck for Virulence of Herpes Simplex Virus 1 in the Absence of Virion Host Shutoff
Authors: Pasieka Tracy Jo , Menachery Vineet D. , Rosato Pamela C. , Leib David A.
Published: May 2012

Herpes simplex viruses lacking the virion host shutoff function (Δvhs) are avirulent and hypersensitive to type I and type II interferon (IFN). In this study, we demonstrate that even in the absence of IFN responses in AG129 (IFN-αβγR−/−) mice, Δvhs remains highly attenuated via corneal infection but is fully virulent via intracranial infection. The data demonstrate that the interferon-independent inherent replication defect of Δvhs has a significant impact upon peripheral replication and neuroinvasion.
Partial Escape of HIV-1 from Cytotoxic T Lymphocytes during Chronic Infection
Authors: Lewis Martha J. , Dagarag Mirabelle , Khan Basim , Ali Ayub , Yang Otto O.
Published: May 2012

Viral mutational escape from CD8+cytotoxic T lymphocytes (CTLs) is typically considered to be a dichotomous process and uncommon during chronic HIV-1 infection.Ex vivopassaging of HIV-1 from persons with chronic infection, however, revealed the evolution of many fixed substitutions within and around CTL-targeted regions, with an associated increase in replicative capacity. This indicates an evolution of mutations during chronic HIV-1 infection that trade replicative fitness for incomplete evasion of CTLs, or “partial escape.”
Recombinant Canine Distemper Virus Strain Snyder Hill Expressing Green or Red Fluorescent Proteins Causes Meningoencephalitis in the Ferret
Authors: Ludlow M. , Nguyen D. T. , Silin D. , Lyubomska O. , de Vries R. D. , von Messling V. , McQuaid S. , De Swart R. L. , Duprex W. P.
Published: May 2012

The propensity of canine distemper virus (CDV) to spread to the central nervous system is one of the primary features of distemper. Therefore, we developed a reverse genetics system based on the neurovirulent Snyder Hill (SH) strain of CDV (CDV
SH
) and show that this virus rapidly circumvents the blood-brain and blood-cerebrospinal fluid (CSF) barriers to spread into the subarachnoid space to induce dramatic viral meningoencephalitis. The use of recombinant CDV
SH
(rCDV
SH
) expressing enhanced green fluorescent protein (EGFP) or red fluorescent protein (dTomato) facilitated the sensitive pathological assessment of routes of virus spread
in vivo
. Infection of ferrets with these viruses led to the full spectrum of clinical signs typically associated with distemper in dogs during a rapid, fatal disease course of approximately 2 weeks. Comparison with the ferret-adapted CDV
5804P
and the prototypic wild-type CDV
R252
showed that hematogenous infection of the choroid plexus is not a significant route of virus spread into the CSF. Instead, viral spread into the subarachnoid space in rCDV
SH
-infected animals was triggered by infection of vascular endothelial cells and the hematogenous spread of virus-infected leukocytes from meningeal blood vessels into the subarachnoid space. This resulted in widespread infection of cells of the pia and arachnoid mater of the leptomeninges over large areas of the cerebral hemispheres. The ability to sensitively assess the
in vivo
spread of a neurovirulent strain of CDV provides a novel model system to study the mechanisms of virus spread into the CSF and the pathogenesis of acute viral meningitis.
Simian Immunodeficiency Virus-Induced Alterations in Monocyte Production of Tumor Necrosis Factor Alpha Contribute to Reduced Immune Activation in Sooty Mangabeys
Authors: Mir Kiran D. , Bosinger Steven E. , Gasper Melanie , Ho On , Else James G. , Brenchley Jason M. , Kelvin David J. , Silvestri Guido , Hu Shiu-lok , Sodora Donald L.
Published: May 2012

Human immunodeficiency virus type 1 (HIV-1) infection is characterized by persistent viral replication in the context of CD4+T cell depletion and elevated immune activation associated with disease progression. In contrast, simian immunodeficiency virus (SIV) infection of African-origin sooty mangabeys (SM) generally does not result in simian AIDS despite high viral loads and therefore affords a unique model in which to study the immunologic contributions to a nonpathogenic lentiviral disease outcome. A key feature of these natural SIV infections is the maintenance of low levels of immune activation during chronic infection. Our goal was to delineate the contribution of monocytes to maintaining low levels of immune activation in SIV-infected SM. Utilizing anex vivowhole-blood assay, proinflammatory cytokine production was quantified in monocytes in response to multiple Toll-like receptor (TLR) ligands and a specific, significant reduction in the tumor necrosis factor alpha (TNF-α) response to lipopolysaccharide (LPS) was observed in SIV-infected SM. In contrast, monocytes from hosts of pathogenic infections (HIV-infected humans and SIV-infected Asian macaques) maintained a robust TNF-α response. In SIV-infected SM, monocyte TNF-α responses to low levels of LPS could be augmented by the presence of plasma from uninfected control animals. The impact of LPS-induced TNF-α production on immune activation was demonstratedin vitro, as TNF-α blocking antibodies inhibited downstream CD8+T cell activation in a dose-dependent manner. These data demonstrate an association between nonpathogenic SIV infection of SM and a reduced monocyte TNF-α response to LPS, and they identify a role for monocytes in contributing to the suppressed chronic immune activation observed in these natural hosts.
Autophagic Clearance of Sin Nombre Hantavirus Glycoprotein Gn Promotes Virus Replication in Cells
Authors: Hussein Islam T. M. , Cheng Erdong , Ganaie Safder S. , Werle Michael J. , Sheema Sheema , Haque Absarul , Mir Muhammad A.
Published: May 2012

Hantavirus glycoprotein precursor (GPC) is posttranslationally cleaved into two glycoproteins, Gn and Gc. Cells transfected with plasmids expressing either GPC or both Gn and Gc revealed that Gn is posttranslationally degraded. Treatment of cells with the autophagy inhibitors 3-methyladenine, LY-294002, or Wortmanin rescued Gn degradation, suggesting that Gn is degraded by the host autophagy machinery. Confocal microscopic imaging showed that Gn is targeted to autophagosomes for degradation by an unknown mechanism. Examination of autophagy markers LC3-I and LC3-II demonstrated that both Gn expression and Sin Nombre hantavirus (SNV) infection induce autophagy in cells. To delineate whether induction of autophagy and clearance of Gn play a role in the virus replication cycle, we downregulated autophagy genes BCLN-1 and ATG7 using small interfering RNA (siRNA) and monitored virus replication over time. These studies revealed that inhibition of host autophagy machinery inhibits Sin Nombre virus replication in cells, suggesting that autophagic clearance of Gn is required for efficient virus replication. Our studies provide mechanistic insights into viral pathogenesis and reveal that SNV exploits the host autophagy machinery to decrease the intrinsic steady-state levels of an important viral component for efficient replication in host cells.