bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations among work‐related stress, cortisol, inflammation, and metabolic syndrome
Authors: Almadi Tawfiq , Cathers Ian , Chow Chin Moi
Published: June 2013

This cross‐sectional study examined the relationship between work‐related stress, cortisol, and C‐reactive protein (CRP) in predicting metabolic syndrome (MtS). Self‐reported work stress measured by the effort reward imbalance ratio (ERI), anthropometric data, CRP, and saliva cortisol were collected from 204 healthy Jordanian male workers. ERI and cortisol were significantly associated with the presence of MtS (OR = 4.74, 95% CI: 2.13–10.55; OR = 3.03, 95% CI: 2.08–4.40; OR = 11.50, 95% CI: 2.16–59.14, respectively). The odds of MtS in men with high ERI and high cortisol were significantly higher than that of men with low ERI and low cortisol (OR = 11.50, 95% CI: 2.16–59.14). CRP was significantly associated with MtS (OR = 2.51, 95% CI: 1.50–4.20). The odds of MtS were significantly higher in centrally obese men with both high ERI and CRP level. Thus, high ERI along with high cortisol or high CRP increases the risk for MtS, especially among centrally obese men.
A Model of Language Processing as Hierarchic Sequential Prediction
Authors: van Schijndel Marten , Exley Andy , Schuler William
Published: June 2013

Computational models of memory are often expressed as hierarchic sequence models, but the hierarchies in these models are typically fairly shallow, reflecting the tendency for memories of superordinate sequence states to become increasingly conflated. This article describes a broad‐coverage probabilistic sentence processing model that uses a variant of a left‐corner parsing strategy to flatten sentence processing operations in parsing into a similarly shallow hierarchy of learned sequences. The main result of this article is that a broad‐coverage model with constraints on hierarchy depth can process large newspaper corpora with the same accuracy as a state‐of‐the‐art parser not defined in terms of sequential working memory operations.
Transfusion‐related lung injury in children: a case series and review of the literature
Authors: Lieberman Lani , Petraszko Tanya , Yi Qi‐long , Hannach Barbara , Skeate Robert
Published: June 2013

Background

Transfusion‐related acute lung injury (TRALI) is the leading cause of transfusion‐related mortality. The majority of the literature involves adult patients. The main objective of this study was to characterize the demographic features, clinical presentation, patient outcomes, and antibody profiles of TRALI patients reported to the Canadian Blood Service (CBS) and to assess similarities and differences between adult and pediatric TRALI cases.

Study Design and Methods

A retrospective review of cases of TRALI submitted to the CBS from 2001 to 2011 was performed. Information collected included recipient demographics, event details, blood component transfused, morbidity and mortality data, and donor antibody results.

Results

A total of 284 cases of definite, possible, or probable TRALI were reported. Six percent (n = 17) occurred in children. There were no significant differences between pediatric or adult patients with TRALI. Most of the children who presented with TRALI were either teenagers or less than 1 year of age. The incident rate of reported TRALI cases in Canada per 100,000 red blood cell transfusions was estimated at 5.58 for children and 3.75 for adults.

Conclusions

This study is the largest case series of reported TRALI cases in children. Crude modeling suggests that the incidence of TRALI in children is similar to that of adults. Although the numbers are small, there do not appear to be differences in presentation or outcome between adults and children with TRALI. TRALI is associated with significant morbidity and mortality and pediatricians need to consider this diagnosis in children who experience respiratory distress after transfusions.
Assessing transfusion competency in junior doctors: a retrospective cohort study
Authors: Graham Jane , Grant‐Casey John , Alston Robert , Baker Paul , Pendry Kate
Published: June 2013

Background

There is scope to further improve the safety of transfusion practice within the United Kingdom. This study aims to identify the current role of junior doctors in the transfusion process and to assess their competency to appropriately prescribe blood and blood products to patients.

Study Design and Methods

Transfusion competency in junior doctors training in a single region was addressed through anonymized questionnaires assessing factual knowledge, personal reflection, and documented evidence of competency. Factual knowledge comprised 33 true‐false questions (competency score) covering indications for transfusion, special requirements, risks of transfusion, and guidelines for testing in transfusion. Background data on current practice and education in transfusion medicine were addressed using multiple‐choice and single‐response questions.

Results

A total of 787 newly qualified doctors, comprising 79% of first‐year (F1) and 62% of second‐year (F2) Foundation doctors, completed the assessment over a 3‐week period. There was no improvement in competency score between F1 and F2 doctors (p = 0.1). Competency scores correlated most strongly with undergraduate education in transfusion medicine and attendance at hospital induction (p < 0.01). Junior doctors had a high confidence level with regard to prescribing blood, although only 78% were aware they had been competency assessed against national standards.

Conclusion

Junior doctors are involved in sampling, prescribing, consenting, and documenting transfusion practice frequently enough to maintain competency. They are rarely involved in the collection, bedside checking, or administration of blood despite current curriculum requirements. There is scope to significantly improve both the training and the assessment of transfusion competency in doctors.
Alleles of the LAN blood group system: molecular and serologic investigations
Authors: Reid Marion E. , Hue‐Roye Kim , Huang Angela , Velliquette Randall W. , Tani Yoshihiko , Westhoff Connie M. , Lomas‐Francis Christine , Zelinski Teresa
Published: June 2013

Background

Anti‐Lan has been implicated in hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. The LAN blood group system is encoded by ABCB6, whose gene product, ABCB6, belongs to the ATP‐binding cassette (ABC) efflux transporter superfamily. The purpose of this study was to characterize additional alleles by analyzing DNA from 14 (13 unrelated) subjects whose red blood cells were serologically defined as Lan−, Lan+w/−, or Lan+w.

Study Design and Methods

Genomic DNA was extracted from blood samples recovered from liquid nitrogen storage. Intronic primers flanking each of the ABCB6 coding exons were used for polymerase chain reaction amplification. Amplicons were sequenced and analyzed by standard methods.

Results

Among the study subjects, we identified five alleles (one with a nonsense change, three with frameshifts, one with a missense change) that encode the Lan− phenotype and four alleles (with missense changes) encoding either Lan+w or Lan+w/− phenotypes.

Conclusions

Of the nine alleles we identified, three were novel and six were previously documented in the dbSNP. Of these six, only one allele was previously associated with Lan negativity. To date, 19 ABCB6 alleles that encode Lan− or Lan+w/−, or Lan+w phenotypes have been described.
Decision Making for Safety Assessment of Mobile Mooring System
Authors: S. Silvianita , Khamidi Mohd Faris , Kurian V. J.
Published: June 2013

Floating structures use mooring system for station keeping in any water depths. Mooring system is a vital component for the safety of floating structures. Mooring accidents can cause serious injury or damage to the vessel, and hence it is necessary to establish a systematic risk–based decision making for safety assessment of mobile mooring system. This study uses the mobile mooring system of a semi submersible pipe laying barge as a case study. The aim of this study is to develop a Methodology for Investigation of Critical Hazards (MIVTA), which is carried out by the development of preliminary risk analysis using HAZOP (Hazard and Operability), to generate the root causes using FTA (Fault Tree Analysis) and to construct the sequence of the consequences using ETA (Event Tree Analysis). HAZOP is a systematic examination of a system helpful to identify and evaluate the risks related to accidents/incidents in mooring system. FTA is a deductive method useful to generate the potential causes of mooring system failure into undesired events. ETA is an inductive method helpful to define all possible outcomes of accidental events. This study conducts risk-based decision making coupled with the knowledge of the experts of mooring system to identify the root causes, to evaluate the frequency of failure and to classify their class of consequences. This study provides a systematic methodology guideline for the risk–based decision making useful to identify the risk of accidents occurring in offshore platforms.
A Review on methods using capnogram signals for detecting asthmatic patients
Authors: Kazemi Mohsen , M. B. Malarvili , A. H. Teo
Published: June 2013

In this paper, a review on methods for detecting the asthmatic conditions by using capnogram is presented. This is included an investigation on capnography as a new approach for monitoring asthma and related researches. Finally, in this preliminary study, a new method based on signal processing approach is developed to automatic detection of asthmatic patients. This developed algorithm is expected to cluster different states of asthmatic conditions by using the RBF (Radial Basis Function) network, instantaneously. However, manual analysis of capnogram is time-consuming and led to erroneous due to human factor such as tiredness and lack of expertise. In the future, this developed algorithm is expected to help heathcare professional involved in respiratory care as it would be possible to monitor severity of asthma automatically and instantaneously.
Sparse Bayesian Learning for Gas Path Diagnostics
Authors: Pu Xingxing , Liu Shangming , Jiang Hongde , Yu Daren
Published: June 2013

A gas path diagnostic method based on sparse Bayesian learning is presented. Most gas path diagnostic problems present the case where there are fewer measurements than health parameters. In addition, the measurement readings can be faulty themselves and need to be determined, which further increases the number of unknown variables. The number of unknown variables exceeds the number of measurements in gas path diagnostics, making the estimation problem underdetermined. For gradual deterioration, it is common to apply a weighted-least-square algorithm to estimate the component health parameters at the same time sensor errors are being determined. However, this algorithm may underestimate the real problem and attribute parts of it to other component faults for accidental single fault events. The accidental single fault events impact at most one or two component(s). This translates mathematically into the search for a sparse solution. In this paper, we proposed a new gas path diagnostic method based on sparse Bayesian learning favoring sparse solutions for accidental single fault events. The sparse Bayesian learning algorithm is applied to a heavy-duty gas turbine considering component faults and sensor biases to demonstrate its capability and improved performance in gas path diagnostics.
Energy Efficiency of an Axial Fan for Various Casing Configurations
Authors: Guedel Alain , Robitu Mirela , Chaulet Vivian
Published: June 2013

The objective of this paper is to compare the measured and predicted performances of a tubeaxial fan for several casing configurations that are commonly proposed by fan manufacturers to their clients. This work is motivated by the European Commission Regulation 327/2011, which will impose target energy efficiency for fans driven by electric motors beginning 1 January 2013. The prediction is made with the computational fluid dynamics (CFD) commercial code STAR-CCM+. The agreement between the experimental and numerical results on fan performance curves is very satisfactory, which confirms that CFD simulations may advantageously replace testing in parametric studies since they predict the quantitative differences of aerodynamic performance observed experimentally between the different casing configurations quite well. Numerical simulations may, therefore, help manufacturers to improve the geometry of their fans in order to fulfill the requirements of the regulation.
Experimental evaluation of flow-induced noise in level flight of the pigeon (Columba livia)
Authors: Wei Qingkai , Zhong Siyang , Huang Xun
Published: June 2013

The experimental method employed in an anechoic wind tunnel to characterize flow-induced noise of the pigeon (Columba livia) during level flight is described in this letter. A live pigeon was managed to maintain a steady level flight at the wind tunnel test flow of 15 m/s. A microphone array was fabricated, and the conventional beamforming method was then adopted to yield the corresponding narrowband acoustic images and broadband sound pressure spectral results. The results justified the experimental method developed in this work. It can be seen that the flight noise of the pigeon is mostly from the wing tips. In addition, the spectral waveform of the pigeon flight suggests a slope of −20 dB/dec between 500 Hz and 5 kHz.
Root Effect Hemoglobin May Have Evolved to Enhance General Tissue Oxygen Delivery
Authors: Rummer Jodie L. , McKenzie David J. , Innocenti Alessio , Supuran Claudiu T. , Brauner Colin J.
Published: June 2013

Holding Your Breath

Hemoglobin and myoglobin are widely responsible for oxygen transport and storage (see the Perspective by

Rezende

). The ability of diving mammals to obtain enough oxygen to support extended dives and foraging is largely dependent on muscle myoglobin (Mb) content.

Mirceta
et al.

(p.
1303
) found that in mammalian lineages with an aquatic or semiaquatic lifestyle, Mb net charge increases, which may represent an adaptation to inhibit self-association of Mb at high intracellular concentrations. Epistasis results from nonadditive genetic interactions and can affect phenotypic evolution.

Natarajan
et al.

(p.
1324
) found that epistatic interactions were able to explain the increased hemoglobin oxygen-binding affinity observed in deer mice populations at high altitude. In mammals, the offloading of oxygen from hemoglobin is facilitated by a reduction in the blood's pH, driven by metabolically produced CO
2
. However, in fish, a reduction in blood pH reduces oxygen carrying capacity of hemoglobin.

Rummer
et al.

(p.
1327
) implanted fiber optic oxygen sensors within the muscles of rainbow trout and found that elevated CO
2
levels in the water led to acidosis and elevated oxygen tensions.
The Molecular Basis for Attractive Salt-Taste Coding in
Drosophila
Authors: Zhang Yali V. , Ni Jinfei , Montell Craig
Published: June 2013

Too Much or Too Little

An important task of the nervous system is to distribute information appropriately throughout the brain. The olfactory and gustatory systems of
Drosophila
provide good models for understanding these processes and the underlying mechanisms (see the Perspective by

Su and Carlson

).

Lin
et al.

(p.
1338
) mapped out the circuit that detects carbon dioxide (CO
2
), an important environmental and communication signal for fruit flies. Two distinct classes of projection neurons mediate avoidance of high and low concentrations of CO
2
, while a third class, comprising inhibitory neurons, shuts down the low-concentration pathway at high concentrations. In contrast to other basic taste qualities, salt is innately attractive at low concentrations, but aversive at high concentrations. The mechanisms underlying salt detection are poorly understood in any species mainly because of a lack of specific molecular tools.

Zhang
et al.

(p.
1334
) discovered that
Drosophila
uses two types of gustatory receptor neurons to distinguish between high and low concentrations of salt. One type is activated maximally by low salt and induces attractive feeding behavior. The other class of receptors is activated primarily by high salt and leads to avoidance behavior.
Evolution of Mammalian Diving Capacity Traced by Myoglobin Net Surface Charge
Authors: Mirceta Scott , Signore Anthony V. , Burns Jennifer M. , Cossins Andrew R. , Campbell Kevin L. , Berenbrink Michael
Published: June 2013

Holding Your Breath

Hemoglobin and myoglobin are widely responsible for oxygen transport and storage (see the Perspective by

Rezende

). The ability of diving mammals to obtain enough oxygen to support extended dives and foraging is largely dependent on muscle myoglobin (Mb) content.

Mirceta
et al.

(p.
1234192
) found that in mammalian lineages with an aquatic or semiaquatic lifestyle, Mb net charge increases, which may represent an adaptation to inhibit self-association of Mb at high intracellular concentrations. Epistasis results from nonadditive genetic interactions and can affect phenotypic evolution.

Natarajan
et al.

(p.
1324
) found that epistatic interactions were able to explain the increased hemoglobin oxygen-binding affinity observed in deer mice populations at high altitude. In mammals, the offloading of oxygen from hemoglobin is facilitated by a reduction in the blood's pH, driven by metabolically produced CO
2
. However, in fish, a reduction in blood pH reduces oxygen carrying capacity of hemoglobin.

Rummer
et al.

(p.
1327
) implanted fiber optic oxygen sensors within the muscles of rainbow trout and found that elevated CO
2
levels in the water led to acidosis and elevated oxygen tensions.
Parallel Neural Pathways Mediate CO
2
Avoidance Responses in
Drosophila
Authors: Lin Hui-Hao , Chu Li-An , Fu Tsai-Feng , Dickson Barry J. , Chiang Ann-Shyn
Published: June 2013

Too Much or Too Little

An important task of the nervous system is to distribute information appropriately throughout the brain. The olfactory and gustatory systems of
Drosophila
provide good models for understanding these processes and the underlying mechanisms (see the Perspective by

Su and Carlson

).

Lin
et al.

(p.
1338
) mapped out the circuit that detects carbon dioxide (CO
2
), an important environmental and communication signal for fruit flies. Two distinct classes of projection neurons mediate avoidance of high and low concentrations of CO
2
, while a third class, comprising inhibitory neurons, shuts down the low-concentration pathway at high concentrations. In contrast to other basic taste qualities, salt is innately attractive at low concentrations, but aversive at high concentrations. The mechanisms underlying salt detection are poorly understood in any species mainly because of a lack of specific molecular tools.

Zhang
et al.

(p.
1334
) discovered that
Drosophila
uses two types of gustatory receptor neurons to distinguish between high and low concentrations of salt. One type is activated maximally by low salt and induces attractive feeding behavior. The other class of receptors is activated primarily by high salt and leads to avoidance behavior.
Two Two-Dimensional Materials Are Better than One
Authors: Hamm Joachim M. , Hess Ortwin
Published: June 2013

Combining 2D materials and 2D metasurfaces enables the fabrication of photonic devices based on extreme interactions between electrons and light.

[Also see Report by

Britnell
et al.

]
NSF Cedes Little Ground on Political Science Reviews
Authors: Mervis Jeffrey
Published: June 2013

NSF has responded to a congressional order to scrutinize political science grants.
LIFE SCIENCE TECHNOLOGIES: Biology Watches the Cloud
Authors: Dove Alan
Published: June 2013

As genome sequencers churn out terabytes of new data daily, researchers are increasingly turning to an information-handling strategy already favored by internet companies: cloud computing.
Intranasal Immunization of Lambs with Serine/Threonine Phosphatase 2A against Gastrointestinal Nematodes
Authors: Mohamed Fawzi Elshaima , Cruz Bustos Teresa , Gómez Samblas Mercedes , González-González Gloria , Solano Jenifer , González-Sánchez María Elena , De Pablos Luis Miguel , Corral-Caridad María Jesús , Cuquerella Montserrat , Osuna Antonio , Alunda José María
Published: June 2013

Seven 3-month-old, female, helminth-free lambs were immunized intranasally with three doses (1 mg total) of a recombinant part of the catalytic region of the serine/threonine phosphatase 2A (PP2Ar) (group 1 [G1]). In addition, four lambs were used as an adjuvant control group (G2), four as unimmunized, infected controls (G3), and four as unimmunized, uninfected controls (G4). Fifteen days after the last immunization, lambs from G1, G2, and G3 were challenged with 10,000 larval stage 3 (L3) organisms in a plurispecific nematode infection composed of ca. 40%Trichostrongylus colubriformis, 40%Haemonchus contortus, and 20%Teladorsagia circumcincta. All the lambs were clinically monitored throughout the experiment. Parasitological (fecal egg output and immunological response), biopathological (packed-cell volume and leukocyte and eosinophil counts), and zootechnical (live-weight gain) analyses were conducted. On day 105 of the experiment, all the animals were slaughtered and the adult worm population in their abomasa examined. Intranasal administration of PP2Ar with bacterial walls as an adjuvant elicited a strong immune response in the immunized lambs, as evidenced by their humoral immune response. Immunized animals and animals receiving the adjuvant shed significantly (P< 0.001) fewer numbers of parasites' eggs in their feces. The immunization significantly reduced the helminth burden in the abomasa by the end of the experiment (>68%), protection being provided against bothHaemonchusandTeladorsagia. Live-weight gain in the immunized lambs was similar to that in the uninfected controls versus the infected or adjuvanted animal groups. Our results suggest that heterologous immunization of ruminants by intranasal administration may be efficacious in the struggle to control gastrointestinal helminths in these livestock.
Rifampin Drug Resistance Tests for Tuberculosis: Challenging the Gold Standard
Authors: Van Deun Armand , Aung Kya J. M. , Bola Valentin , Lebeke Rossin , Hossain Mohamed Anwar , de Rijk Willem Bram , Rigouts Leen , Gumusboga Aysel , Torrea Gabriela , de Jong Bouke C.
Published: June 2013

The rapid diagnosis of rifampin resistance is hampered by a reported insufficient specificity of molecular techniques for detection of
rpoB
mutations. Our objective for this study was to document the prevalence and prognostic value of
rpoB
mutations with unclear phenotypic resistance. The study design entailed sequencing directly from sputum of first failure or relapse patients without phenotypic selection and comparison of the standard retreatment regimen outcome, according to the mutation present. We found that among all
rpoB
mutations, the best-documented “disputed” rifampin resistance mutations (511Pro, 516Tyr, 526Asn, 526Leu, 533Pro, and 572Phe) made up 13.1% and 10.6% of all mutations in strains from Bangladesh and Kinshasa, respectively. Except for the 511Pro and 526Asn mutations, most of these strains with disputed mutations tested rifampin resistant in routine Löwenstein-Jensen medium proportion method drug susceptibility testing (DST; 78.7%), but significantly less than those with common, undisputed mutations (96.3%). With 63% of patients experiencing failure or relapse in both groups, there was no difference in outcome of first-line retreatment between patients carrying a strain with disputed versus common mutations. We conclude that rifampin resistance that is difficult to detect by the gold standard, phenotypic DST, is clinically and epidemiologically highly relevant. Sensitivity rather than specificity is imperfect with any rifampin DST method. Even at a low prevalence of rifampin resistance, a rifampin-resistant result issued by a competent laboratory may not warrant confirmation, although the absence of a necessity for confirmation needs to be confirmed for molecular results among new cases. However, a result of rifampin susceptibility should be questioned when suspicion is very high, and further DST using a different system (i.e., genotypic after phenotypic testing) would be fully justified.
Extra-Aortic Mycotic Aneurysm Due to Group A Streptococcus after Pharyngitis
Authors: Biswas Jason S. , Lyons Oliver T. A. , Bell Rachel E. , Price Nicholas
Published: June 2013

Mycotic aneurysms, especially outside the aorta, are uncommon, with group A
Streptococcus
a particularly rare cause. We report a case of extra-aortic mycotic aneurysm following a sore throat without demonstrable bacteremia where identification of the pathological organism was made by molecular diagnostic techniques after a standard laboratory culture was negative.
Broad-Spectrum Biosensor Capable of Detecting and Identifying Diverse Bacterial and Candida Species in Blood
Authors: Metzgar David , Frinder Mark , Lovari Robert , Toleno Donna , Massire Christian , Blyn Lawrence B. , Ranken Raymond , Carolan Heather E. , Hall Thomas A. , Moore David , Hansen Christian J. , Sampath Rangarajan , Ecker David J.
Published: June 2013

We describe an assay which uses broad-spectrum, conserved-site PCR paired with mass spectrometry analysis of amplicons (PCR/electrospray ionization-mass spectrometry [ESI-MS]) to detect and identify diverse bacterial and
Candida
species in uncultured specimens. The performance of the assay was characterized using whole-blood samples spiked with low titers of 64 bacterial species and 6
Candida
species representing the breadth of coverage of the assay. The assay had an average limit of detection of 100 CFU of bacteria or
Candida
per milliliter of blood, and all species tested yielded limits of detection between 20 and 500 CFU per milliliter. Over 99% of all detections yielded correct identifications, whether they were obtained at concentrations well above the limit of detection or at the lowest detectable concentrations. This study demonstrates the ability of broad-spectrum PCR/ESI-MS assays to detect and identify diverse organisms in complex natural matrices that contain high levels of background DNA.
Multicenter Clinical Evaluation of VRESelect Agar for Identification of Vancomycin-Resistant Enterococcus faecalis and Enterococcus faecium
Authors: Anderson Neil W. , Buchan Blake W. , Young Carol L. , Newton Duane W. , Brenke Connie , Lapsley Linda , Granato Paul A. , Ledeboer Nathan A.
Published: June 2013

A chromogenic medium for identification of vancomycin-resistant
Enterococcus faecalis
and
Enterococcus faecium
, VRE
Select
, was compared to bile esculin azide agar with 6 μg/ml vancomycin (BEAV) for the isolation of vancomycin-resistant enterococci (VRE) from stool specimens. At 24 to 28 h, VRE
Select
demonstrated 98.7% (confidence interval [CI], 96.1 to 99.7%) sensitivity and 99.0% (CI, 98.0 to 99.6%) specificity versus 85.1% (CI, 79.8 to 89.5%) and 90.1% (CI, 79.8 to 89.5%) sensitivity and specificity, respectively, for BEAV.
Preliminary Laboratory Report of Fungal Infections Associated with Contaminated Methylprednisolone Injections
Authors: Lockhart Shawn R. , Pham Cau D. , Gade Lalitha , Iqbal Naureen , Scheel Christina M. , Cleveland Angela A. , Whitney Anne M. , Noble-Wang Judith , Chiller Tom M. , Park Benjamin J. , Litvintseva Anastasia P. , Brandt Mary E.
Published: June 2013

In September 2012, the Centers for Disease Control and Prevention (CDC) initiated an outbreak investigation of fungal infections linked to injection of contaminated methylprednisolone acetate (MPA). Between 2 October 2012 and 14 February 2013, the CDC laboratory received 799 fungal isolates or human specimens, including cerebrospinal fluid (CSF), synovial fluid, and abscess tissue, from 469 case patients in 19 states. A novel broad-range PCR assay and DNA sequencing were used to evaluate these specimens. Although
Aspergillus fumigatus
was recovered from the index case,
Exserohilum rostratum
was the primary pathogen in this outbreak and was also confirmed from unopened MPA vials.
Exserohilum rostratum
was detected or confirmed in 191 specimens or isolates from 150 case patients, primarily from Michigan (
n
= 67 patients), Tennessee (
n
= 26), Virginia (
n
= 20), and Indiana (
n
= 16). Positive specimens from Michigan were primarily abscess tissues, while positive specimens from Tennessee, Virginia, and Indiana were primarily CSF.
E. rostratum
antifungal susceptibility MIC
50
and MIC
90
values were determined for voriconazole (1 and 2 μg/ml, respectively), itraconazole (0.5 and 1 μg/ml), posaconazole (0.5 and 1 μg/ml), isavuconazole (4 and 4 μg/ml), and amphotericin B (0.25 and 0.5 μg/ml). Thirteen other mold species were identified among case patients, and four other fungal genera were isolated from the implicated MPA vials. The clinical significance of these other fungal species remains under investigation. The laboratory response provided significant support to case confirmation, enabled linkage between clinical isolates and injected vials of MPA, and described significant features of the fungal agents involved in this large multistate outbreak.
Rifampin Resistance Missed in Automated Liquid Culture System for Mycobacterium tuberculosis Isolates with Specific
rpoB
Mutations
Authors: Rigouts Leen , Gumusboga Mourad , de Rijk Willem Bram , Nduwamahoro Elie , Uwizeye Cécile , de Jong Bouke , Van Deun Armand
Published: June 2013

WHO-endorsed phenotypic drug susceptibility testing (DST) methods for
Mycobacterium tuberculosis
are assumed to be the gold standard for identifying rifampin (RMP) resistance. However, previous results indicated that low-level, yet probably clinically relevant, RMP resistance linked to specific
rpoB
mutations is easily missed by some growth-based methods. We aimed to compare the level of resistance detected on Löwenstein-Jensen (LJ) medium with resistance detected by the Bactec MGIT 960 automated DST (MGIT-DST) system for various
rpoB
mutants. Full agreement between LJ and MGIT-DST was observed for mutations located at codons 513 (Lys or Pro) and 531 (Leu, Trp), which were always resistant by both methods. For mutations 511Pro, 516Tyr, 533Pro, 572Phe, and several 526 mutations, LJ and MGIT results were highly discordant, with MGIT-DST failing to give a result or declaring the strains susceptible. Our data show that phenotypic RMP resistance testing of
M. tuberculosis
is not a binary phenomenon for some
rpoB
mutations and that the widely used automated MGIT 960 system is prone to miss some RMP resistance-conferring mutations, while careful DST on LJ missed hardly any. Given the association of these mutations with poor clinical outcome, our findings suggest that the gold standard for rifampin resistance should be reconsidered, in order to address the present confusion caused by discrepancies between phenotypic and genotypic results. The impacts of these mutations will depend on the frequency of their occurrence, which may vary from one setting to another.
Control the Host Cell Cycle: Viral Regulation of the Anaphase-Promoting Complex
Authors: Fehr Anthony R. , Yu Dong
Published: June 2013

Viruses commonly manipulate cell cycle progression to create cellular conditions that are most beneficial to their replication. To accomplish this feat, viruses often target critical cell cycle regulators in order to have maximal effect with minimal input. One such master regulator is the large, multisubunit E3 ubiquitin ligase anaphase-promoting complex (APC) that targets effector proteins for ubiquitination and proteasome degradation. The APC is essential for cells to progress through anaphase, exit from mitosis, and prevent a premature entry into S phase. These far-reaching effects of the APC on the cell cycle are through its ability to target a number of substrates, including securin, cyclin A, cyclin B, thymidine kinase, geminin, and many others. Recent studies have identified several proteins from a number of viruses that can modulate APC activity by different mechanisms, highlighting the potential of the APC in driving viral replication or pathogenesis. Most notably, human cytomegalovirus (HCMV) protein pUL21a was recently identified to disable the APC via a novel mechanism by targeting APC subunits for degradation, both during virus infection and in isolation. Importantly, HCMV lacking both viral APC regulators is significantly attenuated, demonstrating the impact of the APC on a virus infection. Work in this field will likely lead to novel insights into viral replication and pathogenesis and APC function and identify novel antiviral and anticancer targets. Here we review viral mechanisms to regulate the APC, speculate on their roles during infection, and identify questions to be addressed in future studies.
Genetic Determinants of Reovirus Pathogenesis in a Murine Model of Respiratory Infection
Authors: Nygaard Rachel M. , Lahti Linse , Boehme Karl W. , Ikizler Mine , Doyle Joshua D. , Dermody Terence S. , Schiff Leslie A.
Published: June 2013

Many viruses invade mucosal surfaces to establish infection in the host. Some viruses are restricted to mucosal surfaces, whereas others disseminate to sites of secondary replication. Studies of strain-specific differences in reovirus mucosal infection and systemic dissemination have enhanced an understanding of viral determinants and molecular mechanisms that regulate viral pathogenesis. After peroral inoculation, reovirus strain type 1 Lang replicates to high titers in the intestine and spreads systemically, whereas strain type 3 Dearing (T3D) does not. These differences segregate with the viral S1 gene segment, which encodes attachment protein σ1 and nonstructural protein σ1s. In this study, we define genetic determinants that regulate reovirus-induced pathology following intranasal inoculation and respiratory infection. We report that two laboratory isolates of T3D, T3D
C
and T3D
F
, differ in the capacity to replicate in the respiratory tract and spread systemically; the T3D
C
isolate replicates to higher titers in the lungs and disseminates, while T3D
F
does not. Two nucleotide polymorphisms in the S1 gene influence these differences, and both S1 gene products are involved. T3D
C
amino acid polymorphisms in the tail and head domains of σ1 protein influence the sensitivity of virions to protease-mediated loss of infectivity. The T3D
C
polymorphism at nucleotide 77, which leads to coding changes in both S1 gene products, promotes systemic dissemination from the respiratory tract. A σ1s-null virus produces lower titers in the lung after intranasal inoculation and disseminates less efficiently to sites of secondary replication. These findings provide new insights into mechanisms underlying reovirus replication in the respiratory tract and systemic spread from the lung.
Autocrine CCL3 and CCL4 Induced by the Oncoprotein LMP1 Promote Epstein-Barr Virus-Triggered B Cell Proliferation
Authors: Tsai Shu-Chun , Lin Sue-Jane , Lin Cheau-Jye , Chou Ya-Ching , Lin Jiun-Han , Yeh Te-Huei , Chen Mei-Ru , Huang Li-Min , Lu Meng-You , Huang Ya-Chi , Chen Huan-Yun , Tsai Ching-Hwa
Published: June 2013

Epstein-Barr virus (EBV) alters the regulation and expression of a variety of cytokines in its host cells to modulate host immune surveillance and facilitate viral persistence. Using cytokine antibody arrays, we found that, in addition to the cytokines reported previously, two chemotactic cytokines, CCL3 and CCL4, were induced in EBV-infected B cells and were expressed at high levels in all EBV-immortalized lymphoblastoid cell lines (LCLs). Furthermore, EBV latent membrane protein 1 (LMP1)-mediated Jun N-terminal protein kinase activation was responsible for upregulation of CCL3 and CCL4. Inhibition of CCL3 and CCL4 in LCLs using a short hairpin RNA approach or by neutralizing antibodies suppressed cell proliferation and caused apoptosis, indicating that autocrine CCL3 and CCL4 are required for LCL survival and growth. Importantly, significant amounts of CCL3 were detected in EBV-positive plasma from immunocompromised patients, suggesting that EBV modulates this chemokinein vivo. This study reveals the regulatory mechanism and a novel function of CCL3 and CCL4 in EBV-infected B cells. CCL3 might be useful as a therapeutic target in EBV-associated lymphoproliferative diseases and malignancies.
Caveolar Endocytosis Is Required for Human PSGL-1-Mediated Enterovirus 71 Infection
Authors: Lin Hsiang-Yin , Yang Ya-Ting , Yu Shu-Ling , Hsiao Kuang-Nan , Liu Chia-Chyi , Sia Charles , Chow Yen-Hung
Published: June 2013

Enterovirus 71 (EV71) causes hand, foot, and mouth disease and severe neurological disorders in children. Human scavenger receptor class B member 2 (hSCARB2) and P-selectin glycoprotein ligand-1 (PSGL-1) are identified as receptors for EV71. The underling mechanism of PSGL-1-mediated EV71 entry remains unclear. The endocytosis required for EV71 entry were investigated in Jurkat T and mouse L929 cells constitutively expressing human PSGL-1 (PSGL-1-L929) or human rhabdomyosarcoma (RD) cells displaying high SCARB2 but no PSGL-1 by treatment of specific inhibitors or siRNA. We found that disruption of clathrin-dependent endocytosis prevented EV71 infection in RD cells, while there was no influence in Jurkat T and PSGL-1-L929 cells. Disturbing caveolar endocytosis by specific inhibitor or caveolin-1 siRNA in Jurkat T and PSGL-1-L929 cells significantly blocked EV71 infection, whereas it had no effect on EV71 infection in RD cells. Confocal immunofluorescence demonstrated caveola, and EV71 was directly colocalized. pH-dependent endosomal acidification and intact membrane cholesterol were important for EV71 infection, as judged by the pretreatment of inhibitors that abrogated the infection. A receptor-dominated endocytosis of EV71 infection was observed: PSGL-1 initiates caveola-dependent endocytosis and hSCARB2 activates clathrin-dependent endocytosis.
Capsid Antibodies to Different Adeno-Associated Virus Serotypes Bind Common Regions
Authors: Gurda Brittney L. , DiMattia Michael A. , Miller Edward B. , Bennett Antonette , McKenna Robert , Weichert Wendy S. , Nelson Christian D. , Chen Wei-jun , Muzyczka Nicholas , Olson Norman H. , Sinkovits Robert S. , Chiorini John A. , Zolotutkhin Sergei , Kozyreva Olga G. , Samulski R. Jude , Baker Timothy S. , Parrish Colin R. , Agbandje-McKenna Mavis
Published: June 2013

Interactions between viruses and the host antibody immune response are critical in the development and control of disease, and antibodies are also known to interfere with the efficacy of viral vector-based gene delivery. The adeno-associated viruses (AAVs) being developed as vectors for corrective human gene delivery have shown promise in clinical trials, but preexisting antibodies are detrimental to successful outcomes. However, the antigenic epitopes on AAV capsids remain poorly characterized. Cryo-electron microscopy and three-dimensional image reconstruction were used to define the locations of epitopes to which monoclonal fragment antibodies (Fabs) against AAV1, AAV2, AAV5, and AAV6 bind. Pseudoatomic modeling showed that, in each serotype, Fabs bound to a limited number of sites near the protrusions surrounding the 3-fold axes of the T=1 icosahedral capsids. For the closely related AAV1 and AAV6, a common Fab exhibited substoichiometric binding, with one Fab bound, on average, between two of the three protrusions as a consequence of steric crowding. The other AAV Fabs saturated the capsid and bound to the walls of all 60 protrusions, with the footprint for the AAV5 antibody extending toward the 5-fold axis. The angle of incidence for each bound Fab on the AAVs varied and resulted in significant differences in how much of each viral capsid surface was occluded beyond the Fab footprints. The AAV-antibody interactions showed a common set of footprints that overlapped some known receptor-binding sites and transduction determinants, thus suggesting potential mechanisms for virus neutralization by the antibodies.
Reinvestigating the Role of IgM in Rabies Virus Postexposure Vaccination
Authors: Dorfmeier Corin L. , Shen Shixue , Tzvetkov Evgeni P. , McGettigan James P.
Published: June 2013

B cells secreting IgG antibodies, but not IgM, are thought to be solely responsible for vaccine-induced protection against rabies virus (RABV) infections in postexposure settings. In this report, we reinvestigated the potential for IgM to mediate protection in a mouse model of RABV vaccination. Immunocompetent mice immunized with an experimental live replication-deficient RABV-based vaccine produced virus neutralizing antibodies (VNAs) within 3 days of vaccination. However, mice unable to produce soluble IgM (sIgM−/−) did not produce VNAs until 7 days postimmunization. Furthermore, sIgM−/−mice were not protected against RABV infection when challenged 3 days postimmunization, while all wild-type mice survived challenge. Consistent with the lack of protection against pathogenic RABV challenge, approximately 50- to 100-fold higher viral loads of challenge virus were detected in the muscle, spinal cord, and brain of immunized sIgM−/−mice compared to control mice. In addition, IgG antibody titers in vaccinated wild-type and sIgM−/−mice were similar at all time points postimmunization, suggesting that protection against RABV challenge is due to the direct effects of IgM and not the influence of IgM on the development of effective IgG antibody titers. In all, early vaccine-induced IgM can limit dissemination of pathogenic RABV to the central nervous system and mediate protection against pathogenic RABV challenge. Considering the importance for the rapid induction of VNAs to protect against RABV infections in postexposure prophylaxis settings, these findings may help guide the development of a single-dose human rabies vaccine.
Characterization of a Critical Interaction between the Coronavirus Nucleocapsid Protein and Nonstructural Protein 3 of the Viral Replicase-Transcriptase Complex
Authors: Hurst Kelley R. , Koetzner Cheri A. , Masters Paul S.
Published: June 2013

The coronavirus nucleocapsid protein (N) plays an essential structural role in virions through a network of interactions with positive-strand viral genomic RNA, the envelope membrane protein (M), and other N molecules. Additionally, N protein participates in at least one stage of the complex mechanism of coronavirus RNA synthesis. We previously uncovered an unanticipated interaction between N and the largest subunit of the viral replicase-transcriptase complex, nonstructural protein 3 (nsp3). This was found through analysis of revertants of a severely defective mutant of murine hepatitis virus (MHV) in which the N gene was replaced with that of its close relative, bovine coronavirus (BCoV). In the work reported here, we constructed BCoV chimeras and other mutants of MHV nsp3 and obtained complementary genetic evidence for its association with N protein. We found that the N-nsp3 interaction maps to the amino-terminal ubiquitin-like domain of nsp3, which is essential for the virus. The interaction does not require the adjacent acidic domain of nsp3, which is dispensable. In addition, we demonstrated a complete correspondence between N-nsp3 genetic interactions and the ability of N protein to enhance the infectivity of transfected coronavirus genomic RNA. The latter function of N was shown to depend on both of the RNA-binding domains of N, as well as on the serine- and arginine-rich central region of N, which binds nsp3. Our results support a model in which the N-nsp3 interaction serves to tether the genome to the newly translated replicase-transcriptase complex at a very early stage of infection.
A pilot study of an Enhanced Mental Health Assessment during routine and discharge medicals in the British Armed Forces
Authors: Aguirre Marcela , Greenberg N , Sharpley J , Simpson R , Wall C
Published: June 2013

Objectives

A pilot study to assess the practicality of introducing an enhanced mental health assessment (EMHA) into all routine and discharge medicals of the UK Armed Forces in order to facilitate treatment prior to and on return to civilian life.

Methods

A pilot study was conducted using an EMHA questionnaire with questions about depression, anxiety, post-traumatic stress disorder, alcohol use, sleep and anger/irritability. At pilot sites, the EMHA was completed during all routine and discharge medicals between May 2011 and July 2011. At the end of the study period, qualitative data were collected from participating medical officers and practice managers regarding their opinions about the pilot study.

Results

The quantitative data revealed an average pick-up rate for mental health (MH) problems. Out of the four military medical centres who participated and the 325 questionnaires collected, one referral to a Department of Community Mental Health was made. 26 (8%) patients were categorised as ‘some concern and patient offered advice and/or reassurance’. The vast majority of patients were found to have no evidence of MH problems. However, using a validated alcohol screening tool, 64% of service personnel were found to have a score indicating ‘higher risk drinking’. Analysis of the qualitative data suggests that the EMHA is an easy tool to implement with minimal additional time and resources needed. The interviewees pointed out a number of limitations and suggestions for possible further studies.

Conclusions

The pilot study successfully demonstrated that the EMHA questionnaire is easy to administer, does not take up a large amount of additional resources or manpower and provides a useful check of MH status. The study picked up an average number of MH cases and the questions on alcohol consumption highlighted that military personnel may be at a ‘higher risk of drinking’.
Mud and debris flows and associated earth dam failures in the Okanagan region of British Columbia
Authors: Tannant Dwayne D. , Skermer Nigel
Published: June 2013

A review of debris and mud flows occurring over the past 100 years in the Okanagan region of British Columbia, Canada, reveals that most events have been associated with late spring snowmelt, spring rains occurring on the snowpack or intense localized convective rain storms in the summer. A troubling finding is that many of the most destructive debris and mud flows were triggered by failure of earth dams located high above the valley floor. The dam failures were caused by either seepage-related piping or water flowing over the top of the dam. Dam breaches can occur on hot sunny days in the spring, when snowmelt and saturated ground conditions occur in the headwaters of creeks flowing into the Okanagan valley. The record shows that there is a risk not only of property damage, but also of loss of life associated with these events. Comparison is made to similar mud flow events in western USA.
Geon 12 crustal extension in the central Grenville Province, implications for the orogenic architecture, and potential influence on the emplacement of anorthosites
Authors: Indares Aphrodite , Moukhsil Abdelali
Published: June 2013

Remnants of a ca. 1.24 Ga old volcanic belt formed in a within-plate setting (Manicouagan Crustal Extension Belt) are exposed over several tens of kilometres in the hinterland of the central Grenville Province, and can be recognized despite granulite-facies Grenvillian metamorphism and deformation. This belt mainly consists of layered felsic–mafic rock units, some of which are documented here for the first time. In the vicinity of the 1.24 Ga belt, a Geon 14 arc-related mafic suite and a Geon 15 metasedimentary package were pervasively injected by felsic (and mafic) material, show evidence of a Geon 12 thermal event, and therefore may represent remnants of rifted crust. Following Geon 12 crustal extension, lithospheric-scale magmatic activity in the immediate region continued intermittently, producing mafic dykes at 1.17 Ga and anorthosite at 1.16 and 1.05 Ga. A close association to 1.16 Ga or younger anorthosite is conspicuous to several Geon 12 rock units known in the central and eastern Grenville Province. We therefore suggest that subsequent anorthositic magmatism was focused on zones of lithospheric weakness inherited from Geon 12 crustal extension and remained active intermittently until the end of the Grenvillian orogeny.