bluuebunny/crossref_metadata_2025 huggingface dataset:
The efficiency frontier approach to economic evaluation of health‐care interventions
Authors: Caro J. Jaime , Nord Erik , Siebert Uwe , McGuire Alistair , McGregor Maurice , Henry David , de Pouvourville Gérard , Atella Vincenzo , Kolominsky‐Rabas Peter
Published: June 2010

Background: IQWiG commissioned an international panel of experts to develop methods for the assessment of the relation of benefits to costs in the German statutory health‐care system.

Proposed methods: The panel recommended that IQWiG inform German decision makers of the net costs and value of additional benefits of an intervention in the context of relevant other interventions in that indication. To facilitate guidance regarding maximum reimbursement, this information is presented in an efficiency plot with costs on the horizontal axis and value of benefits on the vertical. The efficiency frontier links the interventions that are not dominated and provides guidance. A technology that places on the frontier or to the left is reasonably efficient, while one falling to the right requires further justification for reimbursement at that price. This information does not automatically give the maximum reimbursement, as other considerations may be relevant. Given that the estimates are for a specific indication, they do not address priority setting across the health‐care system.

Conclusion: This approach informs decision makers about efficiency of interventions, conforms to the mandate and is consistent with basic economic principles. Empirical testing of its feasibility and usefulness is required. Copyright © 2010 John Wiley & Sons, Ltd.
Special populations with hepatitis B virus infection #
Authors: Peters Marion G.
Published: June 2010

Treatment of patients with chronic hepatitis B virus (HBV) infection who have advanced disease or comorbidities can be challenging, and recommendations may differ from standard guidelines. Among the special populations that merit specific consideration are patients with compensated or decompensated cirrhosis, organ transplantation, acute hepatitis B, pregnancy, coinfection with hepatitis C and/or D virus, chronic renal failure, and children. Major advances have been made in management of many of these special populations because of recent increasing availability of oral nucleosides, which are generally well tolerated and highly effective despite presence of other morbidities or viral infections. Also important have been changes in the management of hepatitis B during the peri-liver transplantation period that allows for prevention of reinfection in the majority of cases. However, much remains to be done to determine which patients should be treated and which should be monitored on no specific therapy. Outcomes of chronic HBV infection in persons with coinfection and in children have varied from different areas of the world, but it is not clear whether these differences are due to host and racial differences or to viral genotypic differences. Further studies are particularly needed in assessing the safety and efficacy of therapy in pregnant women, in children, and in patients with hepatitis D and C virus coinfection. (Hepatology 2009;49:S146–S155.)
Overexpression of the cell adhesion protein neuroligin‐1 induces learning deficits and impairs synaptic plasticity by altering the ratio of excitation to inhibition in the hippocampus
Authors: Dahlhaus Regina , Hines Rochelle M. , Eadie Brennan D. , Kannangara Timal S. , Hines Dustin J. , Brown Craig E. , Christie Brian R. , El‐Husseini Alaa
Published: June 2010

Trans‐synaptic cell‐adhesion molecules have been implicated in regulating CNS synaptogenesis. Among these, the Neuroligin (NL) family (NLs 1–4) of postsynaptic adhesion proteins has been shown to promote the development and specification of excitatory versus inhibitory synapses. NLs form a heterophilic complex with the presynaptic transmembrane protein Neurexin (NRX). A differential association of NLs with postsynaptic scaffolding proteins and NRX isoforms has been suggested to regulate the ratio of excitatory to inhibitory synapses (E/I ratio). Using transgenic mice, we have tested this hypothesis by overexpressing NL1 in vivo to determine whether the relative levels of these cell adhesion molecules may influence synapse maturation, long‐term potentiation (LTP), and/or learning. We found that NL1‐overexpressing mice show significant deficits in memory acquisition, but not in memory retrieval. Golgi and electron microscopy analysis revealed changes in synapse morphology indicative of increased maturation of excitatory synapses. In parallel, electrophysiological examination indicated a shift in the synaptic activity toward increased excitation as well as impairment in LTP induction. Our results demonstrate that altered balance in the expression of molecules necessary for synapse specification and development (such as NL1) can lead to defects in memory formation and synaptic plasticity and outline the importance of rigidly controlled synaptic maturation processes. © 2009 Wiley‐Liss, Inc.
Capital accumulation and growth: a new look at the empirical evidence
Authors: Bond Steve , Leblebicioǧlu Asli , Schiantarelli Fabio
Published: June 2010

Using annual data for 75 countries in the period 1960–2000, we present evidence of a positive relationship between investment as a share of gross domestic product (GDP) and the long‐run growth rate of GDP per worker. This result is robust for our full sample and for the subsample of non‐OECD countries, but not for the subsample of OECD countries. Our analysis controls for time‐invariant country‐specific heterogeneity in growth rates, and for a range of time‐varying control variables. We also address endogeneity issues, and allow for heterogeneity across countries in model parameters and for cross‐section dependence. Copyright © 2010 John Wiley & Sons, Ltd.
Materials characterization of explanted polypropylene, polyethylene terephthalate, and expanded polytetrafluoroethylene composites: Spectral and thermal analysis
Authors: Cozad Matthew J. , Grant David A. , Bachman Sharon L. , Grant Daniel N. , Ramshaw Bruce J. , Grant Sheila A.
Published: June 2010

This study utilized spectral and thermal analysis of explanted hernia mesh materials to determine material inertness and elucidate reasons for hernia mesh explantation. Composite mesh materials, comprised of polypropylene (PP) and expanded polytetrafluoroethylene (ePTFE) mesh surrounded by a polyethylene terephthalate (PET) ring, were explanted from humans. Scanning electron microscopy (SEM) was conducted to visually observe material defects while attenuated total reflectance Fourier transform infrared spectroscopy (ATR‐FTIR) was used to find chemical signs of surface degradation. Modulated differential scanning calorimetry (MDSC) and thermogravimetric analysis (TGA) gave thermal stability profiles that showed changes in heat of fusion and rate of percent weight loss, respectively. ATR‐FTIR scans showed higher carbonyl peak areas as compared to pristine for 91% and 55% of ePTFE and PP explants, respectively. Ninety‐one percent of ePTFE explants also exhibited higher CH stretch peak areas. Seventy‐three percent of ePTFE explants had higher heats of fusion while 64% of PP explants had lower heats of fusion with respect to their corresponding pristines. Only 9% of PET explants exhibited a lower heat of fusion than pristine. Seventy‐three percent of ePTFE explants, 73% of PP explants, and only 18% of PET explants showed a decreased rate of percent weight loss as compared to pristine. The majority of the PP and ePTFE mesh explants demonstrated oxidation and crosslinking, respectively, while the PET ring exhibited breakdown at the sites of high stress. The results showed that all three materials exhibited varied degrees of chemical degradation suggesting that a lack of inertness in vivo contributes to hernia mesh failure. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010.
Cloud computing: Retro revival or the new paradigm?
Authors: Bean LuAnn
Published: June 2010

“Cloud computing” is one of the most recently hyped concepts in information technology (IT). While some argue that it is just the old “time‐sharing” mainframe model transformed, others contend that it is a dramatic change in how we will expand computing possibilities. Which is correct? Is it something that your company should consider? The author explains what cloud computing is and examines its advantages and disadvantages. © 2010 Wiley Periodicals, Inc.
IT: What's the impact of IFRS?
Authors: Burnett Royce D. , Friedman Mark , Murthy Uday
Published: June 2010

Everyone is anticipating the adoption of International Financial Reporting Standards (IFRSs) in the United States. But companies are slowly beginning to realize that conversion to IFRSs will require some complicated, far‐reaching changes for firms' information technology (IT) systems. In fact, this may be more costly and disruptive than Y2K and the Sarbanes‐Oxley Act combined! Senior managers will need a solid understanding of IFRSs and a workable plan to deal with the conversion process for IT. This article provides guidance for both those challenges. © 2010 Wiley Periodicals, Inc.
Information technology control questionnaire
Authors: Reider Rob
Published: June 2010

Most businesses now process their financial transactions through a PC computer system. But there are special control considerations where computers are used to process financial and accounting data. How secure are your firm's PC controls? Answer the information technology control questionnaire in this article and find out. © 2010 Wiley Periodicals, Inc.
The sleeping giant hypocrisy
Authors: Rouse Robert W.
Published: June 2010

In a sharply worded commentary, our SEC columnist declares that it's time to stop pretending that what now passes as “business ethics” will save us from ourselves. © 2010 Wiley Periodicals, Inc.
Toeholds as an M&A strategy?
Authors: Strickland Deon , Martin Dale R. , Cotter James F.
Published: June 2010

“Toeholds” are a merger‐and‐acquisition (M&A) strategy, where a company buys a limited number of shares in a target firm prior to initiating M&A discussions with the target firm. Toeholds can lower the risk and cost of an acquisition. But this strategy carries risks of its own. The authors examine potential positive and negative consequences of using toeholds. © 2010 Wiley Periodicals, Inc.
Four steps to simplify multimeasure performance evaluations using the balanced scorecard
Authors: Albright Thomas L. , Burgess Christopher M. , Hibbets Aleecia R. , Roberts Michael L.
Published: June 2010

Processing complex, unstructured information can be difficult. Since balanced scorecards can include as many as 24 or more measures, this article presents a methodology to help managers manage the complexity. The four‐step process explained here can lead to accurate and consistent evaluations using both quantitative and qualitative performance measures. © 2010 Wiley Periodicals, Inc.
A one‐pot synthesis of the 1‐benzopyrano[2,3‐b]pyridine moiety from 2‐(alkyl/arylamino)‐4‐oxo‐4H‐1‐benzopyran‐3‐carbaldehyde
Authors: Maiti Sourav , Panja Suman Kalyan , Bandyopadhyay Chandrakanta
Published: June 2010

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2‐(Alkyl/arylamino)chromone‐3‐carbaldehyde reacts with Meldrum's acid, hippuric acid, 4‐hydroxycoumarin, diethyl malonate, ethyl acetoacetate, or ethyl benzoylacetate to produce 1‐benzopyrano[2,3‐b]pyridine‐2,5‐dione moiety, but ethyl cyanoacetate and malononitrile react differently. J. Heterocyclic Chem., (2010).
Synthesis and X‐ray crystal structures of chiral, nonracemic 5,6‐dihydro‐4H‐1,3,4‐oxadiazines
Authors: Hitchcock Shawn R. , Dean Melissa A. , Kelley Christopher J. , Edler Kate L. , Ferrence Gregory M.
Published: June 2010

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A series of chiral, nonracemic oxadiazines have been prepared from (1R,2S)‐ephedrine, (1R,2S)‐norephedrine, and L‐phenylalaninol. The synthesis of the Ephedra‐based oxadiazines was accomplished by a process of N‐nitrosation, reduction, acylation, and acid‐catalyzed cyclization. The trans‐ and cis‐diastereomeric oxadiazines derived from (1R,2S)‐ephedrine were analyzed by 1H NMR spectroscopy and by single crystal X‐ray crystallographic analysis. The stereochemistry of the (1R,2S)‐norephedrine–derived oxadiazines was assigned based on 1H NMR spectroscopy and by analogy with the X‐ray crystal structure of the (1R,2S)‐ephedrine–based oxadiazines. In addition, L‐phenylalaninol was used as a template to prepare a series of oxadiazines substituted at the N4‐nitrogen with an isopropyl group. This was accomplished by a reductive alkylation of L‐phenylalaninol with acetone and subsequent hydrazide formation. These hydrazides were reacted with methanesulfonyl chloride to yield the corresponding oxadiazines by a base‐mediated cyclization. J. Heterocyclic Chem., (2010).
Characterizing iron deposition in multiple sclerosis lesions using susceptibility weighted imaging
Authors: Haacke E. Mark , Makki Malek , Ge Yulin , Maheshwari Megha , Sehgal Vivek , Hu Jiani , Selvan Madeswaran , Wu Zhen , Latif Zahid , Xuan Yang , Khan Omar , Garbern James , Grossman Robert I.
Published: June 2010

Purpose

To investigate whether the variable forms of putative iron deposition seen with susceptibility weighted imaging (SWI) will lead to a set of multiple sclerosis (MS) lesion characteristics different than that seen in conventional MR imaging.

Materials and Methods

Twenty‐seven clinically definite MS patients underwent brain scans using magnetic resonance imaging including: pre‐ and postcontrast T1‐weighted imaging, T2‐weighted imaging, FLAIR, and SWI at 1.5 T, 3 T, and 4 T. MS lesions were identified separately in each imaging sequence. Lesions identified in SWI were reevaluated for their iron content using the SWI filtered phase images.

Results

There were a variety of new lesion characteristics identified by SWI, and these were classified into six types. A total of 75 lesions were seen only with conventional imaging, 143 only with SWI, and 204 by both. From the iron quantification measurements, a moderate linear correlation between signal intensity and iron content (phase) was established.

Conclusion

The amount of iron deposition in the brain may serve as a surrogate biomarker for different MS lesion characteristics. SWI showed many lesions missed by conventional methods and six different lesion characteristics. SWI was particularly effective at recognizing the presence of iron in MS lesions and in the basal ganglia and pulvinar thalamus. J. Magn. Reson. Imaging 2009;29:537–544. © 2009 Wiley‐Liss, Inc.
Robust segmentation of mass‐lesions in contrast‐enhanced dynamic breast MR images
Authors: Meinel Lina A. , Buelow Thomas , Huo Dezheng , Shimauchi Akiko , Kose Ursula , Buurman Johannes , Newstead Gillian
Published: June 2010

Purpose:

To develop and evaluate a computerized segmentation method for breast MRI (BMRI) mass‐lesions.

Materials and Methods:

A computerized segmentation algorithm was developed to segment mass‐like‐lesions on breast MRI. The segmentation algorithm involved: (i) interactive lesion selection, (ii) automatic intensity threshold estimation, (iii) connected component analysis, and (iv) a postprocessing procedure for hole‐filling and leakage removal. Seven observers manually traced the borders of all slices of 30 mass‐lesions using the same tools. To initiate the computerized segmentation, each user selected a seed‐point for each lesion interactively using two methods: direct seed‐point and robust region of interest (ROI) selections. The manual and computerized segmentations were compared pair‐wise using the measured size and overlap to evaluate similarity, and the reproducibility of the computerized segmentation was compared with the interobserver variability of the manual delineations.

Results:

The observed inter‐ and intraobserver variations were similar (P > 0.05). Computerized segmentation using the robust ROI selection method was significantly (P < 0.001) more reproducible in measuring lesion size (stDev 1.8%) than either manual contouring (11.7%) or computerized segmentation using directly placed seed‐point method (13.7%).

Conclusion:

The computerized segmentation method using robust ROI selection is more reproducible than manual delineation in terms of measuring the size of a mass‐lesion. J. Magn. Reson. Imaging 2010;32:110–119. © 2010 Wiley‐Liss, Inc.
In vivo vascular hallmarks of diffuse leukoaraiosis
Authors: Uh Jinsoo , Yezhuvath Uma , Cheng Yamei , Lu Hanzhang
Published: June 2010

Purpose:

To characterize multiple patterns of vascular changes in leukoaraiosis using in vivo magnetic resonance imaging (MRI) techniques.

Materials and Methods:

We measured cerebral blood flow (CBF), cerebrovascular reactivity (CVR), and blood–brain‐barrier (BBB) leakage in a group of 33 elderly subjects (age: 72.3 ± 6.8 years, 17 males, 16 females). Leukoaraiosis brain regions were identified in each subject using fluid‐attenuated inversion‐recovery (FLAIR) MRI. Vascular parameters in the leukoaraiosis regions were compared to those in the normal‐appearing white matter (NAWM) regions. Vascular changes in leukoaraiosis were also compared to structural damage as assessed by diffusion tensor imaging.

Results:

CBF and CVR in leukoaraiosis regions were found to be 39.7 ± 5.2% (P < 0.001) and 52.5 ± 11.6% (P = 0.005), respectively, of those in NAWM. In subjects who did not have significant leukoaraiosis, CBF and CVR in regions with high risk for leukoaraiosis showed a slight reduction compared to the other white matter regions. Significant BBB leakage was also detected (P = 0.003) in leukoaraiosis and the extent of BBB leakage was positively correlated with mean diffusivity. In addition, CVR in NAWM was lower than that in white matter of subjects without significant leukoaraiosis.

Conclusion:

Leukoaraiosis was characterized by reduced CBF, CVR, and a leakage in the BBB. J. Magn. Reson. Imaging 2010;32:184–190. © 2010 Wiley‐Liss, Inc.
Reproducibility and correlation between quantitative and semiquantitative dynamic and intrinsic susceptibility‐weighted MRI parameters in the benign and malignant human prostate
Authors: Alonzi Roberto , Taylor N. Jane , Stirling J. James , d'Arcy James A. , Collins David J. , Saunders Michele I. , Hoskin Peter J. , Padhani Anwar R.
Published: June 2010

Purpose:

To assess the reproducibility of relaxivity‐ and susceptibility‐based dynamic contrast‐enhanced magnetic resonance imaging (MRI) in the benign and malignant prostate gland and to correlate the kinetic parameters obtained.

Materials and Methods:

Twenty patients with prostate cancer underwent paired scans before and after androgen deprivation therapy. Quantitative parametric maps for T1‐ and T2*‐weighted parameters were calculated (Ktrans, kep,ve, IAUC60, rBV, rBF, and R2*). The reproducibility of and correlation between each parameter were determined using standard methods at both timepoints.

Results:

T1‐derived parameters are more reproducible than T2*‐weighted measures, both becoming more variable following androgen deprivation (variance coefficients for prostate Ktrans and rBF increased from 13.9%–15.8% and 42.5%–90.8%, respectively). Tumor R2* reproducibility improved after androgen ablation (23.3%–11.8%). IAUC60 correlated strongly with Ktrans, ve, and kep (all P < 0.001). R2* did not correlate with other parameters.

Conclusion:

This study is the first to document the variability and repeatability of T1‐ and T2*‐weighted dynamic MRI and intrinsic susceptibility‐weighted MRI for the various regions of the human prostate gland before and after androgen deprivation. These data provide a valuable source of reference for groups that plan to use dynamic contrast‐enhanced MRI or intrinsic susceptibility‐weighted MRI for the assessment of treatment response in the benign or malignant prostate. J. Magn. Reson. Imaging 2010;32:155–164. © 2010 Wiley‐Liss, Inc.
MR elastography of the ex vivo bovine globe
Authors: Litwiller Daniel V. , Lee Sung J. , Kolipaka Arunark , Mariappan Yogesh K. , Glaser Kevin J. , Pulido Jose S. , Ehman Richard L.
Published: June 2010

Purpose:

To evaluate the feasibility of using MR elastography (MRE) to assess the mechanical properties of the eye.

Materials and Methods:

The elastic properties of the corneoscleral shell of an intact, enucleated bovine globe specimen were estimated using MRE and finite element modeling (FEM), assuming linear, isotropic behavior. The two‐dimensional (2D), axisymetric model geometry was derived from a segmented 2D MR image, and estimations of the Young's modulus in both the cornea and sclera were made at various intraocular pressures using an iterative flexural wave speed matching algorithm.

Results:

Estimated values of the Young's moduli of the cornea and sclera varied from 40 to 185 kPa and 1 to 7 MPa, respectively, over an intraocular pressure range of 0.85 to 9.05 mmHg (1.2 to 12.3 cmH2O). They also varied exponentially as functions of both wave speed and intraocular dP/dV, an empirical measure of “ocular rigidity.”

Conclusion:

These results show that it is possible to estimate the intrinsic elastic properties of the corneoscleral shell in an ex vivo bovine globe, suggesting that MRE may provide a useful means to assess the mechanical properties of the eye and its anatomy. Further development of the technique and modeling process will enhance its potential, and further investigations are needed to determine its clinical potential. J. Magn. Reson. Imaging 2010;32:44–51. © 2010 Wiley‐Liss, Inc.
Vital signs and cognitive function are not affected by 23‐sodium and 17‐oxygen magnetic resonance imaging of the human brain at 9.4 T
Authors: Atkinson Ian C. , Sonstegaard Rachel , Pliskin Neil H. , Thulborn Keith R.
Published: June 2010

Purpose:

To evaluate the effect of 23‐sodium (23Na) and 17‐oxygen (17O) magnetic resonance imaging (MRI) at 9.4 (T) on vital signs and cognitive function of the human brain.

Materials and Methods:

Vital sign and cognitive function measurements from healthy volunteers (N = 14) positioned outside and at isocenter of a 9.4 T scanner before and after 23Na and 17O MRI were compared for changes due to exposure to the static magnetic field and to the gradient switching and radiofrequency radiation during MRI.

Results:

Exposure to the 9.4 T static magnetic field and 23Na and 17O MRI at 105.92 MHz and 54.25 MHz, respectively, did not have a statistically significant (P > 0.05) effect on the vital signs or cognitive function of healthy normal adults.

Conclusion:

23Na and 17O MRI of the human brain at 9.4 T does not have any readily demonstrated health risks reflected in vital signs or change in cognitive performance. J. Magn. Reson. Imaging 2010;32:82–87. © 2010 Wiley‐Liss, Inc.
Detecting blood oxygen level‐dependent (BOLD) contrast in the breast
Authors: Rakow‐Penner Rebecca , Daniel Bruce , Glover Gary H.
Published: June 2010

Purpose:

To develop a robust technique for detecting blood oxygenation level‐dependent (BOLD) contrast in the human breast and to evaluate the signal in healthy and malignant breast.

Materials and Methods:

The design of this study focused on determining the optimal pulse sequence and stimulus for detecting BOLD contrast in the breast. For this study a single‐shot fast spin echo (SSFSE) sequence was compared to a gradient echo (GRE) pulse sequence. Also, several hyperoxic stimuli were tested on 15 healthy volunteers to determine the best stimulus for inducing BOLD contrast in the breast: air interleaved with carbogen (95% O2, 5% CO2), air interleaved with oxygen, and oxygen interleaved with carbogen. The stimulus with the most consistent results among the healthy population was tested on three breast cancer patients.

Results:

An SSFSE pulse sequence produced improved BOLD contrast results in the breast compared to a GRE pulse sequence. Oxygen interleaved with carbogen yielded the most consistent results in the healthy population. BOLD contrast in healthy glandular breast tissue positively correlates with carbogen and malignant tissue mostly negatively correlates to carbogen.

Conclusion:

BOLD contrast can consistently be detected in the breast using a robust protocol. This methodology may be used in the future as a noninvasive method for evaluating tumor oxygenation. J. Magn. Reson. Imaging 2010;32:120–129. © 2010 Wiley‐Liss, Inc.
Comparison of dual to single contrast bolus magnetic resonance myocardial perfusion imaging for detection of significant coronary artery disease
Authors: Groothuis Jan G.J. , Kremers Frans P.P.J. , Beek Aernout M. , Brinckman Stijn L. , Tuinenburg Alvin C. , Jerosch‐Herold Michael , van Rossum Albert C. , Hofman Mark B.M.
Published: June 2010

Purpose:

To investigate the incremental diagnostic value of dual‐bolus over single‐contrast‐bolus first pass magnetic resonance myocardial perfusion imaging (MR‐MPI) for detection of significant coronary artery disease (CAD).

Materials and Methods:

Patients (n = 49) with suspected CAD underwent first pass adenosine stress and rest MR‐MPI and invasive coronary angiography (CA). Gadolinium diethylenetriamine pentaacetic acid (Gd‐DTPA) was injected with a prebolus (1 mL) and a large bolus (0.1 mmol/kg). For the single‐bolus technique, the arterial input function (AIF) was obtained from the large‐contrast bolus. For the dual‐bolus technique, the AIF was reconstructed from the prebolus. Absolute myocardial perfusion was calculated by Fermi‐model constrained deconvolution. Receiver operating characteristic (ROC) analysis was used to investigate diagnostic accuracy of MR myocardial perfusion imaging for detection of significant CAD on CA at vessel‐based analysis.

Results:

The area under the curve (AUC) of the minimal stress perfusion value for the detection of significant CAD using the single‐bolus and dual‐bolus technique was 0.85 ± 0.04 (95% confidence interval [CI], 0.77–0.93) and 0.77 ± 0.05 (95% CI, 0.67–0.86), respectively.

Conclusion:

In this study the dual‐bolus technique had no incremental diagnostic value over single‐bolus technique for detection of significant CAD with the used contrast concentrations. J. Magn. Reson. Imaging 2010;32:88–93. © 2010 Wiley‐Liss, Inc.
Utility of diffusion‐weighted MRI in distinguishing benign and malignant hepatic lesions
Authors: Miller Frank H. , Hammond Nancy , Siddiqi Aheed J. , Shroff Sagar , Khatri Gaurav , Wang Yi , Merrick Laura B. , Nikolaidis Paul
Published: June 2010

Purpose:

To evaluate apparent diffusion coefficient (ADC) values for characterization of a variety of focal liver lesions and specifically for differentiation of solid benign lesions (focal nodular hyperplasia [FNH] and adenomas) from solid malignant neoplasms (metastases and hepatocellular carcinoma [HCC]) in a large case series.

Materials and Methods:

A total of 542 lesions in 382 patients were evaluated. ADC values were measured in 166 hemangiomas, 112 hepatomas, 107 metastases, 95 cysts, 10 abscesses, 43 FNH, and nine adenomas. ADCs of 1.5 and 1.6 (×10−3 mm2/second) were selected as threshold values to separate benign and malignant lesions. Sensitivity, specificity, positive, and negative predictive values (PPV, NPV) were calculated. Comparisons were carried out with studentized range test.

Results:

There was high interobserver agreement in ADC measurements for all lesion types. The mean ADCs for cysts was 3.40 (×10 −3 mm2/second), hemangiomas 2.26, FNH 1.79, adenomas 1.49, abscesses 1.97, HCC 1.53, and metastases 1.50. The mean ADC for benign lesions was 2.50 and for malignant lesions was 1.52. Cysts were easily distinguished from other lesions. There was, however, overlap between solid benign and malignant lesions.

Conclusion:

Benign lesions have higher mean ADC values than malignant lesions. However, ADC values of solid benign lesions (FNH and adenomas) are similar to malignant lesions (metastases, HCC) limiting the value of diffusion weighted imaging (DWI) for differentiating solid liver masses. J. Magn. Reson. Imaging 2010;32:138–147. © 2010 Wiley‐Liss, Inc.
Distribution of human papillomavirus types in the anogenital tract of females and males
Authors: Barzon Luisa , Militello Valentina , Pagni Silvana , Franchin Elisa , Dal Bello Federico , Mengoli Carlo , Palù Giorgio
Published: June 2010

Human papillomavirus (HPV) infection is the most common sexually transmitted infection in both men and women, but there are limited data comparing the prevalence of HPV infection between genders and in different anogenital sites. This cross‐sectional analysis describes the distribution of HPV types in the genital tract of 3,410 consecutive females and 1,033 males undergoing voluntary screening for HPV and referred to a single institution. The relationship between specific HPV types and the presence of anogenital lesions was examined. In both females and males, the overall prevalence of HPV infection was about 40%. A wide variety of HPV types was identified, but the prevalence of different types was remarkably similar in the two genders, even when considering different anatomical sites. HPV‐6 was the most frequent (prevalence 13%) type in all anogenital sites in men followed by HPV‐16 (7%), while HPV‐16 was the most common type in women (about 6%), either in the cervix, vagina, or vulva, followed by HPV‐6. In addition to HPV‐16, HPV‐58, HPV‐33, HPV‐31, and HPV‐56 were the carcinogenic types detected most commonly and were significantly associated with high‐grade squamous intraepithelial cervical lesions, while HPV‐53 and HPV‐66 were the most common among possibly carcinogenic types. In both genders, anogenital warts were associated with HPV‐6 and HPV‐11 infection, and, less frequently, with other types, like HPV‐54, HPV‐62, and HPV‐66. These results show that genital HPV infection involves numerous HPV types, which have similar distribution patterns in females and males and in different anogenital anatomical sites. J. Med. Virol. 82:1424–1430, 2010. © 2010 Wiley‐Liss, Inc.
Allele‐specific conventional reverse‐transcription polymerase chain reaction as a screening assay for discriminating influenza a H1N1 (H275Y) oseltamivir‐resistant and wild‐type viruses
Authors: Ngai Karry L.K. , Lam Wai‐Yip , Lee Nelson , Leung Ting Fan , Hui David S.C. , Chan Paul K.S.
Published: June 2010

In early 2008, a sudden increase in oseltamivir (Tamiflu®)‐resistant influenza A H1N1 viruses was reported from several European countries. This resistant virus has spread globally and accounted for more than 95% of H1N1 viruses isolated in the following influenza season. A continuous close monitoring on the prevalence of this resistant virus is necessary to rationalize the choice of antiviral agents. The resistance of this novel strain to oseltamivir is conferred by an amino acid substitution from histidine to tyrosine at position 275 (H275Y) of the neuraminidase protein. This study developed and evaluated allele‐specific conventional reverse‐transcription polymerase chain reaction (cRT‐PCR) assays to provide a simple, rapid, and low‐cost option for discriminating oseltamivir‐resistant influenza A H1N1 (H275Y) mutant from wild‐type viruses. The evaluation was based on 90 nasopharyngeal aspirate specimens collected before, during the initial phase and at the peak of emergence of resistance. Thirty‐six (40%) of these specimens were H275Y mutant, whereas the other 54 (60%) were wild‐type viruses as confirmed by sequencing of the neuraminidase gene. When applied directly on the 90 nasopharyngeal aspirate specimens, the allele‐specific cRT‐PCR assays achieved an unequivocal discrimination for 82 (91%) specimens. Further improvement in performance is expected when applied to cell culture isolates with a higher viral titer. These allele‐specific cRT‐PCR assays can be a simple, low‐cost option for large‐scale screening of influenza isolates. J. Med. Virol. 82:1295–1298, 2010. © 2010 Wiley‐Liss, Inc.
Multiple routes of hepatitis C virus transmission among injection drug users in Hai Phong, Northern Vietnam
Authors: Tanimoto Tomoaki , Cuong Nguyen Hung , Ishizaki Azumi , Chung Phan Thi Thu , Huyen Hoang Thi Thanh , Trung Nguyen Vu , Kageyama Seiji , Oka Shinichi , Thuc Pham Van , Ichimura Hiroshi
Published: June 2010

To identify hepatitis C virus (HCV) transmission routes among injection drug users in Northern Vietnam, plasma samples were collected from 486 drug users in Hai Phong. Plasma viral RNA was extracted from 323 (66.5%) samples that were positive for anti‐HCV antibodies. Portions of the HCV 5′‐untranslated (5′UTR)‐Core and NS5B genes were amplified by reverse‐transcriptase polymerase chain reaction, sequenced directly, and genotyped in 194 and 195 specimens, respectively. Both regions were genotyped in 137 specimens. In the 5′UTR‐Core region, genotype 6a was predominant (32.5%), followed by genotype 1a (23.7%), genotype 1b (20.6%), and genotype 6e (14.4%). In the NS5B region, genotype 1a was predominant (42.6%), followed by genotype 1b (24.1%), genotype 6a (14.4%), genotype 3b (7.2%), and genotype 6e (5.1%). Of the 137 specimens with both regions genotyped, 23 (16.8%) showed discordant genotyping results between the two regions, suggesting possible recombination and/or dual infection. Phylogenetic analysis revealed close associations between Hai Phong strains and strains from Southern China: the Yunnan province for genotype 3b; the Guangxi province for genotype 6e; the USA for genotype 1a; and Southern Vietnam for genotypes 1a and 6e. The human immunodeficiency virus (HIV) infection rate among HCV‐infected injection drug users was 52.6–55.4% and did not differ significantly by HCV genotype. Most drug users infected with HIV‐1 [98.8% (171/173)] were co‐infected with HCV. These results suggest multiple routes of HCV transmission among injection drug users in Northern Vietnam that may also be HIV transmission routes. J. Med. Virol. 82:1355–1363, 2010. © 2010 Wiley‐Liss, Inc.
Characterization of human papillomavirus infection in north Taiwan
Authors: Wang Chin‐Hung , Garvilles Ronald Garingalao , Chen Chung‐Yung
Published: June 2010

The detection of human papillomavirus (HPV) is very important for the evaluation of preventative strategies for cervical cancer. The major objective of this study was to characterize the prevalence of different genotypes of HPV in north Taiwan to contribute to the epidemiological knowledge of HPV infections. Papanicolaou (Pap) cervical smears were collected from 10,543 women aged between 14 and 87 years. The polymerase chain reaction (PCR) and DNA array hybridization techniques were used to genotype 51 different HPV strains. HPV was detected in 1,577 women, which gave an overall HPV prevalence rate of 15%. Forty‐eight different genotypes were found in these patients, which included 9.7% that were high‐risk HPV (HR‐HPV) genotypes. The most common types of HR‐HPV in patients, in descending order of frequency, were HPV 52, 16, 58, 56, 39, 51, 18, 68, 31, 33, 59, 45, and 35. HPV 52 was the most frequent type in every age group. The four most common HR‐HPV types were found in 56.6% of the patients infected with HR‐HPV. In cases that were infected with multiple HPV genotypes, 69.2% had at least one HR‐HPV genotype. The rate of infection with HR‐HPV was higher in the younger age groups than the older ones. In conclusion, 48 HPV genotypes were identified from a large study of cervical screening samples and the prevalence of HPV genotypes in different age groups was very diverse. The formulation of a public health strategy for HPV vaccination should take into account the prevalence of various HR‐HPV/LR‐HPV genotypes. J. Med. Virol. 82:1416–1423, 2010. © 2010 Wiley‐Liss, Inc.
Validity of the rapid strip assay test for detecting HBsAg in patients admitted to hospital in Uganda
Authors: Seremba E. , Ocama P. , Opio C.K. , Kagimu M. , Yuan H.J. , Attar N. , Thomas D.L. , Lee W.M.
Published: June 2010

Commercially available rapid strip assays (RSAs) for hepatitis B surface antigen (HBsAg) are used for most routine clinical testing in sub‐Saharan Africa. This study evaluated the validity of RSA and a more sophisticated enzyme immunoassay (EIA) with confirmation by nucleic acid testing (NAT) in hospitalized patients in Uganda. Sera from 380 consecutive patients collected and tested for HBsAg and anti‐HIV in Kampala, Uganda by RSA were sent frozen to Dallas for EIA including HBsAg, total anti‐hepatitis B core, hepatitis B e antigen, and anti‐HIV. NAT was performed on all HBsAg‐positives and on a random sample of 102 patients that were HBsAg‐negative by both assays. Overall, 31 (8%) were HBsAg positive by RSA while 50 (13%) were HBsAg‐positive by EIA; 26 were concordant between the two assays. Of 55 HBsAg‐positive patients, nearly all showed detectable serum hepatitis B virus (HBV) DNA by bDNA (46) or PCR (4) assay. The 26 patients who were HBsAg positive by both EIA and RSA had significantly higher median serum HBV DNA levels than the 24 patients who were HBsAg positive by EIA alone. An additional 12/102 (12%) HBsAg negative patients had very low serum HBV DNA levels by NAT. Several differences in expected results of serologic testing were observed in this large series of African patients. RSA HBsAg testing is less sensitive than EIA; even EIA failed to detect all HBV DNA positive sera. A more complex testing protocol than RSA alone will be needed in Africa to improve patient care. J. Med. Virol. 82:1334–1340, 2010. © 2010 Wiley‐Liss, Inc.
FasL/Fas pathway is involved in dengue virus induced apoptosis of the vascular endothelial cells
Authors: Liao Hongwu , Xu Juan , Huang Junqi
Published: June 2010

The hallmark of the dengue hemorrhagic fever/dengue shock syndrome is hematologic abnormality. The pathogenesis of dengue hemorrhagic fever/dengue shock syndrome remains unknown. Our work showed that the dengue virus serotype‐2 induced apoptosis in human umbilical vein endothelial cells. Fas (CD95), Tumor Necrosis Factor receptors, and Tumor Necrosis Factor‐related apoptosis‐inducing ligand receptors are the most common death receptors, which can induce apoptosis. Compared with the untreated human umbilical vein endothelial cells, Fas expression was increased both in the mRNA level and on the surface of infected human umbilical vein endothelial cells. FasL was expressed at similar levels on human umbilical vein endothelial cells over a course of dengue virus serotype‐2 infection, but the expression in mRNA level was increased in infected human umbilical vein endothelial cells. It is possible that there is soluble FasL secreted from human umbilical vein endothelial cells in the supernatant. Tumor Necrosis Factor‐related apoptosis‐inducing ligand receptor 1 and Tumor Necrosis Factor receptors 1–2 were constantly very low, whereas Tumor Necrosis Factor‐related apoptosis‐inducing ligand receptors 2–4 decreased after dengue virus serotype‐2 infection. This result suggested that dengue virus serotype‐2 may inhibit Tumor Necrosis Factor‐related apoptosis‐inducing ligand receptors‐induced apoptosis. The apoptotic rates in human umbilical vein endothelial cells were decreased upon the addition of caspase family inhibitors. In addition, activated caspase 8 and caspase 3 were also observed by Western blot following dengue virus serotype‐2 infection. Thus, it is shown that the Fas/FasL pathway may participate in dengue virus‐induced apoptosis of vascular endothelial cells in vitro. J. Med. Virol. 82:1392–1399, 2010. © 2010 Wiley‐Liss, Inc.
Newly identified respiratory viruses in children with asthma exacerbation not requiring admission to hospital
Authors: Arden Katherine E. , Chang Anne B. , Lambert Stephen B. , Nissen Michael D. , Sloots Theo P. , Mackay Ian M.
Published: June 2010

There are few data describing the comprehensive identification in and influence of newly identified respiratory viruses on asthma exacerbations. Most studies focus on inpatients. In this preliminary study, the point prevalence and the associations of picornavirus species described recently and human bocavirus (HBoV) with the recovery from exacerbations in non‐hospitalized asthmatic children (median age 5.1 years) were examined. Human rhinoviruses (HRVs) were present in 52.6% of specimens, HBoV‐1 was in 7.7%. Viral co‐detections occurred in 25.6% of children and were associated (P = 0.04) with lower asthma quality of life scores upon presentation than were single viral detections. The undifferentiated presence or absence of virus did not influence the severity of asthma or recovery however when virus species were examined individually, specific clinical associations emerged. HRV species C (HRV‐Cs) were the viruses most frequently detected as single virus detections. Among 41 genotyped HRVs, more HRV‐Cs (n = 23) were identified than HRV‐As (n = 16) however HRV‐A detection was associated (P = 0.01) with worse asthma symptoms and cough for longer than was HRV‐C detection. Larger, PCR‐based studies are required to elucidate further the true impact of HRV species in childhood asthma exacerbations of both hospitalized and non‐hospitalized cohorts. J. Med. Virol. 82:1458–1461, 2010. © 2010 Wiley‐Liss, Inc.
Virological and immunological features of active cytomegalovirus infection in nonimmunosuppressed patients in a surgical and trauma intensive care unit
Authors: Chilet Marifina , Aguilar Gerardo , Benet Isabel , Belda Javier , Tormo Nuria , Carbonell José Antonio , Clari María Ángeles , Costa Elisa , Navarro David
Published: June 2010

Cytomegalovirus (CMV) reactivation occurs frequently in critically ill patients. The natural course of CMV infection and the interaction between CMV and the adaptive immune system in this setting remain poorly defined. Fifty‐three CMV‐seropositive patients in a surgical and trauma intensive care unit were included in this study. The CMV DNA load in tracheal aspirates (TA) and plasma (PL) was monitored by qPCR. CMV‐specific T‐cell immunity was assessed by intracellular cytokine staining. Plasma TNF‐α levels were determined by ELISA. CMV reactivation occurred in 39.7% of patients (23% had CMV DNA detected only in TA). The analysis of TA allowed an earlier diagnosis in 28% of patients. Clearance of CMV DNAemia preceded that of CMV DNA in TA in some episodes. Peak CMV DNA levels were significantly higher in TA than in PL (P = 0.02). CMV reactivation developed in the presence of CMV‐specific T cells. Termination of CMV reactivation was associated with an expansion of functional CMV‐specific T cells. Plasma levels of TNF‐α did not allow for the prediction of the occurrence of CMV reactivation. CMV‐specific T‐cell immunity is preserved in most critically ill patients experiencing CMV reactivation. Analysis of respiratory specimens is imperative for an optimal monitoring of CMV reactivation in this setting. J. Med. Virol. 82:1384–1391, 2010. © 2010 Wiley‐Liss, Inc.
Surveillance of norovirus infections in the state of Rio De Janeiro, Brazil 2005–2008
Authors: Ferreira M.S.R. , Victoria M. , Carvalho‐Costa F.A. , Vieira C.B. , Xavier M.P.T.P. , Fioretti J.M. , Andrade J. , Volotão E.M. , Rocha M. , Leite J.P.G. , Miagostovich M.P.
Published: June 2010

A 4‐year (2005–2008) norovirus (NoV) surveillance study was conducted in the state of Rio Janeiro, Brazil, to demonstrate the role of these viruses in outbreaks and sporadic cases of acute gastroenteritis. A cohort of 1,687 fecal samples was obtained from patients with gastroenteritis; 324 were rotavirus‐positive. Of the remainder 1,363 rotavirus‐negative samples, 1,087 samples were tested for NoV RNA in this study. The study enrolled 267 outpatients from Municipal Public Health Centers and 820 inpatients, whose samples were obtained by active surveillance in Public Hospitals. Fecal samples were tested by reverse transcription (RT) followed by polymerase chain reaction (PCR) using the MON 431–434 set of degenerate primers for NoV GI and GII detection, and there were 35.1% (381/1,087) positive samples for NoV, consisting of 30.2% (248/820) and 49.8% (133/267) from inpatient and outpatient, respectively. Children infected by NoV had significantly more frequent mucus in feces, vomiting and fever. No seasonal pattern in NoV infections was observed in patients admitted to hospital; however, two peaks of NoV infections were observed from ambulatory cases, suggesting that there was an occurrence of outbreaks in those time periods. Molecular characterization revealed GII to be the most prevalent genogroup, totaling 96.3% (104/108) of all sequences analyzed, and GII.4 was the genotype detected most frequently (80.7%), followed by GII.6, 3, 14, 7, and 8. Two GI strains, GI.2 and GI.3, were also observed. The number of outbreaks and sporadic cases described in this study highlights the need to implement diagnosis of NoV in surveillance laboratories. J. Med. Virol. 82:1442–1448, 2010. © 2010 Wiley‐Liss, Inc.
Testing for human papillomavirus and measurement of viral load of HPV 16 and 18 in self‐collected vaginal swabs of women who do not undergo cervical cytological screening in Southern France
Authors: Tamalet Catherine , Richet Hervé , Carcopino Xavier , Henry Mireille , Leretraite Laurence , Heid Patrice , Leandri François‐Xavier , Sancho‐Garnier Hélène , Piana Lucien
Published: June 2010

Self‐sampling using vaginal swabs could be a valuable alternative to screen for cervical cancer for women who do not attend regular cytological screening. The aim of this study was to determine the prevalence of high and low‐risk HPV types and of HPV type 16 and 18 DNA load in self‐collected vaginal swabs from 35‐ to 69‐year‐old Southern French women of low socioeconomic level or migrant populations who do not attend regular cervical screening. A good concordance (93.1%) was found between cervical brush and vaginal swabs in 29 samples. Self‐collected vaginal swabs were examined from 120 women. HPV infection was found in 28 women (23.3%; median age 48 years), 17 (14.1%) of whom harbored high‐risk HPV types. HPV type 16 was the high risk type found most frequently, followed by types 53, 31, 18, 58, and 66. The low‐risk type detected most frequently was HPV type 6, followed by types 61, 70, and 81. The mean HPV 16 and 18 load was 6.3 log10 copies/106 cells and 2.4 log10 copies/106 cells, respectively. These results suggest that vaginal self‐swabs can be a reliable tool for cervical cancer screening in non‐attending and inadequately screened elderly women. J. Med. Virol. 82:1431–1437, 2010. © 2010 Wiley‐Liss, Inc.
Quantitative and qualitative assay of rubella IgA antibody in breast milk
Authors: Hayakawa Yuko , Zhou Yumei , Mizuguchi Masashi , Frey Teryl K. , Ushijima Hiroshi
Published: June 2010

Breast milk contains immunological factors, such as IgA antibody, which help to prevent infectious diseases. A total of 197 paired samples of colostrum and breast milk was collected from postpartum mothers in Gunma City, Japan, and examined for anti‐rubella IgA antibody by enzyme‐linked immunosorbent assay (ELISA) and Western blotting (WB). The anti‐rubella virus IgA ranged from 0.5 to 78.5 U/ml with a mean of 6.05 U/ml and a median of 3.6 U/ml in colostrum, and from 0.5 to 32.7 U/ml with a mean of 2.74 U/ml and a median of 2 U/ml in milk. The differences between the means of titers of total IgA and anti‐rubella virus IgA in colostrum and in milk were significant statistically. The levels of anti‐rubella virus IgA in both colostrum and breast milk correlated positively with the anti‐rubella virus hemagglutination inhibition (HI) titers in the sera of mother, indicating that the levels of these different classes of antibodies correlated. Based on WB, anti‐rubella virus IgA in both colostrum and breast milk reacted with the rubella viral protein E1 and C, but not with the E2 protein. J. Med. Virol. 82:1475–1479, 2010. © 2010 Wiley‐Liss, Inc.
Effect of the autoregulator from Streptomyces griseus JA 5142 on surface cultures of blocked mutant ZIMET 43682
Authors: Gräfe U. , Reinhardt G. , Krebs D. , Eritt I. , Steudel A.
Published: June 2010

Zero time addition of the autoregulator (L‐factor) from S. griseus (Lkm+ Amy+) to surface cultures of its bald mutant ZIMET 43682 (Amy−Lkm−) restored the capacity to form both anthracycline‐type antibiotic leukaemomycin and aerial mycelium. The pertinent mycelia displayed the same growth rate and cellular levels of nucleic acid as the asporogeneous phenotype but the composition of fatty acids and phospholipids as well as the ratio of cytochromes b and c were altered. These differences indicate alterations in the cellular architecture of substrate and aerial hyphae. The result suggest that the autoregulator triggers the onset of a complex programme of differentiation at a very early stage.