bluuebunny/crossref_metadata_2025 huggingface dataset:
Complex data analysis in high‐resolution SSFP fMRI
Authors: Lee Jongho , Shahram Morteza , Schwartzman Armin , Pauly John M.
Published: April 2007

In transition‐band steady‐state free precession (SSFP) functional MRI (fMRI), functional contrast originates from a bulk frequency shift induced by a deoxygenated hemoglobin concentration change in the activated brain regions. This frequency shift causes a magnitude and/or phase‐signal change depending on the off‐resonance distribution of a voxel in the balanced‐SSFP (bSSFP) profile. However, in early low‐resolution studies, only the magnitude signal activations were shown. In this paper the task‐correlated phase‐signal change is presented in a high‐resolution (1 × 1 × 1 mm3) study. To include this phase activation in a functional analysis, a new complex domain data analysis method is proposed. The results show statistically significant phase‐signal changes in a large number of voxels comparable to that of the magnitude‐activated voxels. The complex‐data analysis method successfully includes these phase activations in the activation map and thus provides wider coverage compared to magnitude‐data analysis results. Magn Reson Med 57:905–917, 2007. © 2007 Wiley‐Liss, Inc.
High‐resolution chemical shift imaging for the assessment of intramuscular lipids
Authors: Newcomer Bradley R. , Lawrence Jeannine C. , Buchthal Steven , den Hollander Jan A.
Published: April 2007

A new high‐resolution MRSI technique was used to measure extracellular lipids (EMCL), intracellular lipids (IMCL), and total muscle lipids (TML). The purpose of this study was to assess the feasibility and reproducibility of this new technique. This study also compared results obtained from small regions of interest (ROIs) vs. a summation of a large ROI of voxels representing the total soleus or anterior tibialis (TA) muscles. Eight volunteers were studied with the use of a conventional single‐slice MR spectroscopic imaging (MRSI) sequence run with the following parameters: TR = 145.9 ms, FOV = 16 cm, slice thickness = 1 cm, and 64 × 64 phase encodes. EMCL, IMCL, and TML values from the small ROIs proved to be reproducible (coefficient of variation (CV) = 7.8–13.8% for soleus, and 8.2–18% for TA). EMCL, IMCL, and TML values from the larger soleus ROI proved to be reproducible (CV = 7.3–16.1%), whereas the larger TA ROIs were less reproducible. The small and larger soleus ROIs produced statistically equivalent measures of EMCL and TML per unit area. However, the small soleus and TA ROIs showed a trend toward yielding different IMCL contents as compared to the larger ROIs. This study demonstrates that high‐resolution 1H MRSI of the calf muscle is feasible and can reproducibly measure EMCL, IMCL, and TML. Magn Reson Med 57:848–858, 2007. © 2007 Wiley‐Liss, Inc.
T2‐prepared SSFP improves diagnostic confidence in edema imaging in acute myocardial infarction compared to turbo spin echo
Authors: Kellman Peter , Aletras Anthony H. , Mancini Christine , McVeigh Elliot R. , Arai Andrew E.
Published: April 2007

T2‐weighted MRI of edema in acute myocardial infarction (MI) provides a means of differentiating acute and chronic MI, and assessing the area at risk of infarction. Conventional T2‐weighted imaging of edema uses a turbo spin‐echo (TSE) readout with dark‐blood preparation. Clinical applications of dark‐blood TSE methods can be limited by artifacts such as posterior wall signal loss due to through‐plane motion, and bright subendocardial artifacts due to stagnant blood. Single‐shot imaging with a T2‐prepared SSFP readout provides an alternative to dark‐blood TSE and may be conducted during free breathing. We hypothesized that T2‐prepared SSFP would be a more reliable method than dark‐blood TSE for imaging of edema in patients with MI. In patients with MI (22 acute and nine chronic MI cases), T2‐weighted imaging with both methods was performed prior to contrast administration and delayed‐enhancement imaging. The T2‐weighted images using TSE were nondiagnostic in three of 31 cases, while six additional cases rated as being of diagnostic quality yielded incorrect diagnoses. In all 31 cases the T2‐prepared SSFP images were rated as diagnostic quality, correctly differentiated acute or chronic MI, and correctly determined the coronary territory. Free‐breathing T2‐prepared SSFP provides T2‐weighted images of acute MI with fewer artifacts and better diagnostic accuracy than conventional dark‐blood TSE. Magn Reson Med 57:891–897, 2007. Published 2007 Wiley‐Liss, Inc.
Spectral phase‐corrected GRAPPA reconstruction of three‐dimensional echo‐planar spectroscopic imaging (3D‐EPSI)
Authors: Zhu Xiaoping , Ebel Andreas , Ji Jim X. , Schuff Norbert
Published: April 2007

MR spectroscopic (MRS) images from a large volume of brain can be obtained using a 3D echo‐planar spectroscopic imaging (3D‐EPSI) sequence. However, routine applications of 3D‐EPSI are still limited by a long scan time. In this communication, a new approach termed “spectral phase‐corrected generalized autocalibrating partially parallel acquisitions” (SPC‐GRAPPA) is introduced for the reconstruction of 3D‐EPSI data to accelerate data acquisition while preserving the accuracy of quantitation of brain metabolites. In SPC‐GRAPPA, voxel‐by‐voxel spectral phase alignment between metabolite 3D‐EPSI from individual coil elements is performed in the frequency domain, utilizing the whole spectrum from interleaved water reference 3D‐EPSI for robust estimation of the zero‐order phase correction. The performance of SPC‐GRAPPA was compared with that of fully encoded 3D‐EPSI and conventional GRAPPA. Analysis of whole‐brain 3D‐EPSI data reconstructed by SPC‐GRAPPA demonstrates that SPC‐GRAPPA with an acceleration factor of 1.5 yields results very similar to those obtained by fully encoded 3D‐EPSI, and is more accurate than conventional GRAPPA. Magn Reson Med 57:815–820, 2007. © 2007 Wiley‐Liss, Inc.
Intuitive design guidelines for fast spin echo imaging with variable flip angle echo trains
Authors: Lebel R. Marc , Wilman Alan H.
Published: April 2007

We present a simple and intuitive means for determining the flip angles (FAs) required for smooth transitions between static pseudo steady states (SPSSs) in fast spin echo (FSE) imaging with variable FA (VFA) echo trains. We demonstrate the effectiveness of single and multiple transition pulses to successfully vary refocusing FAs while retaining high signal levels. The graphical interpretation presented here is consistent with previous analytical techniques and permits accurate signal‐intensity predictions along the echo train. Magn Reson Med 57:972–975, 2007. © 2007 Wiley‐Liss, Inc.
Self‐calibrated GRAPPA method for 2D and 3D radial data
Authors: Arunachalam Arjun , Samsonov Alexey , Block Walter F.
Published: April 2007

A fast parallel MRI (pMRI) reconstruction method is presented for 2D and 3D radial trajectories. A limitation of the radial generalized autocalibrating partially parallel acquisitions (GRAPPA) method is the need to acquire training data prior to the actual scan. This can be eliminated by the use of self‐calibration when synthesizing the missing data for each coil reconstruction. The training data for each coil are estimated by multiplying the conventionally reconstructed composite image, which contains the aliasing artifacts from undersampling, with each coil's spatial sensitivity profile. An estimate of the individual receiver spatial sensitivity profiles is obtained from the k‐space data that fulfill the Nyquist sampling criterion. The frequency domain representation of the training data is then calculated at the acquired k‐space sample points and at the unacquired locations at which we desire to synthesize k‐space data. Fitting the acquired k‐space samples to the unacquired points creates reconstruction weights that are used to synthesize unacquired radial lines. The in vivo feasibility of the method for 2D radial trajectories is illustrated with an example of 2D abdominal imaging. Preliminary results obtained after applying the method on a 3D radial steady‐state free precession (SSFP) data set are also demonstrated. Magn Reson Med 57:931–938, 2007. © 2007 Wiley‐Liss, Inc.
Fast mapping of the T2 relaxation time of cerebral metabolites using proton echo‐planar spectroscopic imaging (PEPSI)
Authors: Tsai Shang‐Yueh , Posse Stefan , Lin Yi‐Ru , Ko Cheng‐Wen , Otazo Ricardo , Chung Hsiao‐Wen , Lin Fa‐Hsuan
Published: April 2007

Metabolite T2 is necessary for accurate quantification of the absolute concentration of metabolites using long‐echo‐time (TE) acquisition schemes. However, lengthy data acquisition times pose a major challenge to mapping metabolite T2. In this study we used proton echo‐planar spectroscopic imaging (PEPSI) at 3T to obtain fast T2 maps of three major cerebral metabolites: N‐acetyl‐aspartate (NAA), creatine (Cre), and choline (Cho). We showed that PEPSI spectra matched T2 values obtained using single‐voxel spectroscopy (SVS). Data acquisition for 2D metabolite maps with a voxel volume of 0.95 ml (32 × 32 image matrix) can be completed in 25 min using five TEs and eight averages. A sufficient spectral signal‐to‐noise ratio (SNR) for T2 estimation was validated by high Pearson's correlation coefficients between logarithmic MR signals and TEs (R2 = 0.98, 0.97, and 0.95 for NAA, Cre, and Cho, respectively). In agreement with previous studies, we found that the T2 values of NAA, but not Cre and Cho, were significantly different between gray matter (GM) and white matter (WM; P < 0.001). The difference between the T2 estimates of the PEPSI and SVS scans was less than 9%. Consistent spatial distributions of T2 were found in six healthy subjects, and disagreement among subjects was less than 10%. In summary, the PEPSI technique is a robust method to obtain fast mapping of metabolite T2. Magn Reson Med 57:859–865, 2007. © 2007 Wiley‐Liss, Inc.
Contrast‐enhanced MRI of right ventricular abnormalities in Cx43 mutant mouse embryos
Authors: Wadghiri Youssef Zaim , Schneider Amanda E. , Gray Emily N. , Aristizabal Orlando , Berrios Cesar , Turnbull Daniel H. , Gutstein David E.
Published: April 2007

Imaging of the mammalian cardiac right ventricle (RV) is particularly challenging, especially when a two‐dimensional method such as conventional histology is used to evaluate the morphology of this asymmetric, crescent‐shaped chamber. MRI may improve the characterization of mutants with RV phenotypes by allowing analysis of the samples in any plane and by facilitating three‐dimensional image reconstruction. MRI was used to examine the conditional knockout Cx43‐PCKO mouse line known to have RV malformations. To help delineate the cardiovascular system and facilitate identification of the right ventricular outflow tract (RVOT), embryonic day (E) 17.5 embryos were perfusion fixed through the umbilical vein followed by a gadolinium‐based contrast agent mixed in 7% gelatin. Micro‐MRI experiments were performed at 7 T and followed by paraffin embedding of specimens, histological sectioning and hematoxylin and eosin (H&E) staining. Imaging of up to four embryos simultaneously allowed for higher throughput than traditional individual imaging techniques, while intravascular contrast afforded excellent signal‐to‐noise characteristics. All control embryos (n = 4) and heterozygous Cx43 knockout embryos (n = 4) had normal‐appearing right ventricular outflow tract contours by MRI. Obvious abnormalities in the RVOT, including abnormal bulging and infiltration of contrast into the wall of the RV, were seen in three out of four Cx43‐PCKO mutants with MRI. Furthermore, three‐dimensional reconstruction of MR images with orthogonal projections as well as maximum‐intensity projection allowed for visualization of the relationship of infundibular bulging segments to the pulmonary trunk in Cx43‐PCKO mutant hearts. The addition of MRI to standard histology in the characterization of RV malformations in mutant mouse embryos aids in the assessment and understanding of morphologic abnormalities. Flexibility in the viewing of MR images, which can be retrospectively sectioned in any desired orientation, is particularly useful in the investigation of the RV, an asymmetric chamber that is difficult to analyze with two‐dimensional techniques. Copyright © 2007 John Wiley & Sons, Ltd.
Measurement of nonlinear pO2 decay in mouse lungs using 3He‐MRI
Authors: Cieślar Katarzyna , Alsaid Hasan , Stupar Vasile , Gaillard Sophie , Canet‐Soulas Emmanuelle , Fissoune Rachida , Crémillieux Yannick
Published: April 2007

Spatial and temporal variations in oxygen partial pressure (pO2) during breath‐hold can be exploited to obtain important regional parameters of lung function. In the course of apnea, the oxygen concentration is known to decay exponentially. Therefore, the initial pO2 (p0) can be used to represent local ventilation, and the oxygen depletion time constant can characterize perfusion. The protocol, based on a nonlinear model of pO2 decay, was validated in six healthy mice. Parametric maps of p0 and oxygen depletion time constant were obtained for pure 3He and 3He/air mixture. The mean measured values of p0 were 77 ± 9 mbar for the pure 3He insufflation and 107 ± 5 mbar for 3He/air mixture, in agreement with the predefined p0 values: 75 ± 15 mbar and 123 ± 15 mbar, respectively. The mean measured oxygen depletion time constants were 6.5 ± 0.2 s for pure 3He and 7.1 ± 0.8 s for the 3He/air mixture, in agreement with physiology. Copyright © 2007 John Wiley & Sons, Ltd.
Magnetic resonance imaging and spectroscopy of transgenic models of cancer
Authors: Raman Venu , Pathak Arvind P. , Glunde Kristine , Artemov Dmitri , Bhujwalla Zaver M.
Published: April 2007

The complexity of cancer, where a single genetic alteration can have multiple functional effects, makes it a fascinating but humbling disease to study, and the necessity of investigating it in its entirety is more imperative than ever before. Advances in transgene technology have made it possible to create cancer cells, or mice with specific genetic alterations, and the application of an array of both functional and molecular non‐invasive MR methods to these transgenic cancer cells and mice to characterize their phenotypic traits is revolutionizing our understanding of cancer. With the establishment of multi‐modality molecular imaging centers within barrier or pathogen‐free facilities, multi‐parametric and multi‐modality imaging of transgenic mouse models of human cancer are becoming increasingly prevalent. In this review, we outline some of the methods currently available for generating transgenic mice and cancer cell lines. We also present examples of the application of MR methods to transgenic models that are providing novel insights into the molecular and functional characteristics of cancer and are leading to an era of ‘non‐invasive phenotyping’ of the effects of specific molecular alterations in cancer. Copyright © 2007 John Wiley & Sons, Ltd.
Postmortem delay does not change regional diffusion anisotropy characteristics in mouse spinal cord white matter
Authors: Kim Joong Hee , Trinkaus Kathryn , Ozcan Alpay , Budde Matthew D. , Song Sheng‐Kwei
Published: April 2007

It has been demonstrated previously that water diffusion anisotropy in vivo is equivalent to that observed ex vivo after perfusion fixation in the mouse brain. This finding supports the practice of ex vivo diffusion tensor imaging (DTI) measurement on perfusion‐fixed tissues. However, the validity of extrapolating ex vivo DTI measurements from immersion‐fixed autopsy specimens to the in vivo state is questionable because of variable postmortem delays often encountered before fixation. In this study, we investigated the effect of postmortem delay on the water diffusion anisotropy of ventrolateral spinal cord white matter from mice. Mouse spinal cords, each from the same animal, were examined using DTI in vivo, in situ after death before fixation, and ex vivo immersion fixed 10 h after death. Our results suggest that diffusion anisotropy in mouse spinal cord is preserved up to 10 h after death. Regional characteristics of diffusion anisotropy in mouse spinal cord white matter are equivalent in vivo, in situ after death (up to 10 h before fixation), and ex vivo 15 weeks after immersion fixation. Copyright © 2007 John Wiley & Sons, Ltd.
Application of MRS to mouse models of neurodegenerative illness
Authors: Choi Ji‐Kyung , Dedeoglu Alpaslan , Jenkins Bruce G.
Published: April 2007

The rapid development of transgenic mouse models of neurodegenerative diseases, in parallel with the rapidly expanding growth of MR techniques for assessing in vivo, non‐invasive, neurochemistry, offers the potential to develop novel markers of disease progression and therapy. In this review we discuss the interpretation and utility of MRS for the study of these transgenic mouse and rodent models of neurodegenerative diseases such as Alzheimer's (AD), Huntington's (HD) and Parkinson's disease (PD). MRS studies can provide a wealth of information on various facets of in vivo neurochemistry, including neuronal health, gliosis, osmoregulation, energy metabolism, neuronal–glial cycling, and molecular synthesis rates. These data provide information on the etiology, natural history and therapy of these diseases. Mouse models enable longitudinal studies with useful time frames for evaluation of neuroprotection and therapeutic interventions using many of the potential MRS markers. In addition, the ability to manipulate the genome in these models allows better mechanistic understanding of the roles of the observable neurochemicals, such as N‐acetylaspartate, in the brain. The argument is made that use of MRS, combined with correlative histology and other MRI techniques, will enable objective markers with which potential therapies can be followed in a quantitative fashion. Copyright © 2007 John Wiley & Sons, Ltd.
In Vivo mouse imaging and spectroscopy in drug discovery
Authors: Beckmann Nicolau , Kneuer Rainer , Gremlich Hans‐Ulrich , Karmouty‐Quintana Harry , Blé François‐Xavier , Müller Matthias
Published: April 2007

Imaging modalities such as micro‐computed tomography (micro‐CT), micro‐positron emission tomography (micro‐PET), high‐resolution MRI, optical imaging, and high‐resolution ultrasound have become invaluable tools in preclinical pharmaceutical research. They can be used to non‐invasively investigate, in vivo, rodent biology and metabolism, disease models, and pharmacokinetics and pharmacodynamics of drugs. The advantages and limitations of each approach usually determine its application, and therefore a small‐rodent imaging laboratory in a pharmaceutical environment should ideally provide access to several techniques. In this paper we aim to illustrate how these techniques may be used to obtain meaningful information for the phenotyping of transgenic mice and for the analysis of compounds in murine models of disease. Copyright © 2007 John Wiley & Sons, Ltd.
Mouse MRI using phased‐array coils
Authors: Gareis Daniel , Wichmann Tobias , Lanz Titus , Melkus Gerd , Horn Michael , Jakob Peter M.
Published: April 2007

The advantages of array coil imaging in human whole‐body MR systems are well known and have gained relevance in many applications and MR techniques. In the field of small‐animal studies, this concept has become increasingly important. In this work, three different phased‐array coils for performing MRI on mice are presented. For imaging at 300 MHz, a four‐channel receive‐only phased‐array coil is introduced. One two‐channel and a four‐channel transmit/receive setup operating at 750 MHz show the feasibility of array coil imaging at 17.6 T. All of these coils show excellent performance and deliver high‐quality MR images of mice. Copyright © 2007 John Wiley & Sons, Ltd.
Quantitative MRI reveals aging‐associated T2 changes in mouse models of Alzheimer's disease
Authors: Falangola M. F. , Dyakin V. V. , Lee S. P. , Bogart A. , Babb J. S. , Duff K. , Nixon R. , Helpern J. A.
Published: April 2007

In this study, we used MRI to analyze quantitative parametric maps of transverse (T2) relaxation times in a longitudinal study of transgenic mice expressing mutant forms of amyloid precursor protein (APP), presenilin (PS1), or both (PS/APP), modeling aspects of Alzheimer's disease (AD). The main goal was to characterize the effects of progressive β‐amyloid accumulation and deposition on the biophysical environment of water and to investigate if these measurements would provide early indirect evidence of AD pathological changes in the brains of these mice. Our results demonstrate that at an early age before β‐amyloid deposition, only PS/APP mice show a reduced T2 in the hippocampus and cortex compared with wild‐type non‐transgenic (NTg) controls, whereas a statistically significant within‐group aging‐associated decrease in T2 values is seen in the cortex and hippocampus of all three transgenic genotypes (APP, PS/APP, and PS) but not in the NTg controls. In addition, for animals older than 12 months, we confirmed our previous report that only the two genotypes that form amyloid plaques (APP and PS/APP) have significantly reduced T2 values compared with NTg controls. Thus, T2 changes in these AD models can precede amyloid deposition or even occur in AD models that do not deposit β‐amyloid (PS mice), but are intensified in the presence of amyloid deposition. Copyright © 2007 John Wiley & Sons, Ltd.
4D cardiac MRI in the mouse
Authors: Feintuch Akiva , Zhu Yonghong , Bishop Jonathan , Davidson Lorinda , Dazai Jun , Bruneau Benoit G. , Henkelman R. Mark
Published: April 2007

With the introduction of mouse models for the study of cardiac morphogenesis, there arises a need for new imaging protocols that can capture both morphological and functional information. High‐resolution 2D cardiac cine MRI has often been used to quantify left and right ventricular function. In this study we propose a 3D isotropic cardiac cine MRI protocol with a voxel size of 200 µm3 as a means of studying cardiac multi‐chamber morphology and function. A black blood sequence was used to enhance blood myocardium contrast. Manual segmentation of the ventricles was used to measure ventricular volumes at end diastole and end systole. This method is demonstrated on an Irx4‐deficient mouse model. We have been able to identify the volumes of both ventricles dynamically and to show differences in ejection fraction in the mutant. We have also identified an abnormality of the papillary muscle in the mutant that had been missed in previous phenotyping with ultrasound and histology. Copyright © 2007 John Wiley & Sons, Ltd.
MRI of mouse models of neurological disorders
Authors: Anderson Stasia A. , Frank Joseph A.
Published: April 2007

MRI has contributed to significant advances in the understanding of neurological diseases in humans. It has also been used to evaluate the spectrum of mouse models spanning from developmental abnormalities during embryogenesis, evaluation of transgenic and knockout models, through various neurological diseases such as stroke, tumors, degenerative and inflammatory diseases. The MRI techniques used clinically are technically more challenging in the mouse because of the size of the brain; however, mouse imaging provides researchers with the ability to explore cellular and molecular imaging that one day may translate into clinical practice. This article presents an overview of the use of MRI in mouse models of a variety of neurological disorders and a brief review of cellular imaging using magnetically tagged cells in the mouse central nervous system. Published in 2007 by John Wiley & Sons, Ltd.
Liver biopsy results in patients with sickle cell disease on chronic transfusions: Poor correlation with ferritin levels
Authors: Karam Lina B. , Disco Deborah , Jackson Sherron M. , Lewin David , Mckie Virgil , Baker Robert D. , Baker Susan S. , Laver Joseph H. , Nietert Paul J. , Abboud Miguel R.
Published: April 2007

Background:

Chronic transfusions are effective in preventing stroke and other complications of sickle cell disease. The aim of this study was to determine whether serum ferritin levels correlated with liver iron content in sickle cell patients on chronic transfusion.

Procedure:

Forty‐four liver biopsy specimens from 38 patients with homozygous sickle cell anemia (HbSS) and one patient with sickle thalassemia receiving chronic transfusions were studied. Five patients underwent a second liver biopsy for follow up. Three ferritin measurements were used to calculate a mean for each patient. The association between serum ferritin levels and liver iron quantitation was measured using the Spearman rank correlation, and sensitivity and specificity were determined for selected threshold values of serum ferritin.

Results:

Serum ferritin levels ranged from 515 to 6076 ng/ml, liver iron concentration ranged from 1.8 to 67.97 mg/g dry weight. The amount of iron per gram liver dry weight was moderately correlated with serum ferritin values (r = 0.46). The correlation of duration of transfusion with serum ferritin (r = 0.40) and with liver iron content (r = 0.41) also indicated moderate correlation. Liver biopsy results led to changes in the management after 29/44 (66%) of the biopsies. Serum ferritin ≥2500 ng/ml predicted high liver iron content (≥7 mg/g), with a sensitivity of 62.5% and a specificity of 77.8%.

Conclusion:

We found a poor correlation between serum ferritin levels and liver iron content (LIC). Despite being on chelation therapy, many patients on chronic transfusion had high levels of liver iron. Measurement of LIC is highly recommended in these patients. Pediatr Blood Cancer 2008;50:62–65. © 2007 Wiley‐Liss, Inc.
The absence of donor‐derived IL‐13 exacerbates the severity of acute graft‐versus‐host disease following allogeneic bone marrow transplantation
Authors: Hildebrandt Gerhard C. , Choi Sung W. , Mueller Gunnar , Olkiewicz Krystyna M. , Moore Bethany B. , Cooke Kenneth R.
Published: April 2007

Acute graft versus host disease (aGVHD) after allogeneic bone marrow transplantation (allo‐BMT) predominantly involves a Th1‐type cytokine response. Interestingly, the Th2‐cytokine, Interleukin‐13 (IL‐13), produced by alloreactive donor T cells in vitro was recently shown to correlate with clinical aGVHD severity. Using an established mouse model, we show that the systemic cytokine milieu following allo‐BMT with IL‐13−/− donors is characterized by decreases in serum Th2 cytokines and an increase in serum TNFα, and ultimately correlates with higher aGVHD mortality compared to allogeneic controls. In vitro studies further demonstrate that both exogenous and T cell‐derived IL‐13 can regulate TNFα production by macrophages following lipopolysaccharide stimulation. Thus, donor‐derived IL‐13 may have a role in modulating inflammatory cytokine release that is associated with aGVHD. Pediatr Blood Cancer 2008;50:911–914. © 2007 Wiley‐Liss, Inc.
Application of QF‐PCR for the prenatal assessment of discordant monozygotic twins for fetal sex
Authors: Fernández‐Martínez F. J. , Galindo A. , Moreno‐Izquierdo A. , Gómez‐Rodríguez M. J. , Moreno‐García M. , Grañeras A. , Barreiro E.
Published: April 2007

Objective

To establish the utility of quantitative fluorescent polymerase chain reaction (QF‐PCR) in order to determine the zygosity of multiple pregnancies, as well as to define the origin of the most frequent aneuploidies in amniotic fluid samples.

Methods

We describe the case of a monochorionic (MC) diamniotic (DA) pregnancy with phenotypically discordant twins (nuchal cystic hygroma and non‐immune hydrops in twin A and no anomalies in twin B). QF‐PCR was performed for rapid prenatal diagnosis in uncultured amniocytes and subsequently in cultured cells. Polymorphic markers for chromosomes X, Y, 13, 18 and 21 were used for determination of zygosity as well as sex chromosome aneuploidy.

Results

Twin A showed a Turner Syndrome (TS) mosaicism pattern by QF‐PCR in uncultured amniocytes. The monozygotic origin of the pregnancy was determined. Interphase fluorescence in situ hybridization (I‐FISH) in this sample showed a mosaicism X0/XY (83/17%). Cytogenetic analysis revealed a 45,X0 karyotype in twin A and a 46,XY karyotype in twin B.

Conclusions

QF‐PCR is a reliable tool for the determination of the zygosity independently of the chorionicity and the fetal sex in case of twin pregnancy. Testing both direct and cultured cells can provide useful results for genetic counselling in chromosomal mosaicisms. Copyright © 2007 John Wiley & Sons, Ltd.
The Influence of Pulse Frequency and Duty on the Deposition Rate in Pulsed Magnetron Sputtering
Authors: Kelly Peter J. , Onifade Ayokola A. , Zhou Yanwen , Clarke Gregory C. B. , Audronis Martynas , Bradley James W.
Published: April 2007

This paper investigates the influence of pulse frequency and duty on the deposition rate during the pulsed magnetron sputtering process. Whilst deposition rates increased with duty, they also showed a very marked decrease with pulse frequency. Detailed analysis of the data implies that there is a ‘dead time’ of the order of at least 500 ns at the beginning of each pulse‐on cycle, during which negligible sputtering takes place. As pulse frequency increases, the ‘dead time’ becomes a greater proportion of the total on‐time, thus leading to a fall in the deposition rate. Other factors also contributing to this effect include a reduction in the average power delivered to the target as pulse frequency is increased, and significant differences with frequency in the rate of change of target voltage at the beginning of each pulse on cycle.

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Trends in Combining Techniques for the Deposition of New Application‐Tailored Thin Films
Authors: Dinescu Gheorghe , Ruset Cristian , Dinescu Maria
Published: April 2007

A modern approach for the development of thin film deposition technology is to combine the classical principles of PVD and CVD techniques, and to assist them with the recent progress in plasma sources and reactors. The power of inter‐combining the deposition methods with new ideas and tools is discussed for a particular number of cases, such as the combination of magnetron sputtering with pulsed ion implantation, of pulsed laser deposition with low‐pressure radiofrequency directional plasma beams, and of magnetron sputtering with plasma‐beam‐enhanced chemical vapor deposition. The discussed cases are complemented with examples from literature, highlighting the recent trends in combining plasma based deposition techniques, and the need for an improvement in the terminology.

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Helianthos: Roll‐to‐Roll Deposition of Flexible Solar Cell Modules
Authors: Hamers Edward A. G. , van den Donker Menno N. , Stannowski Bernd , Schlatmann Rutger , Jongerden Gert J.
Published: April 2007

In the development of the roll‐to‐roll deposition of amorphous silicon by means of plasma enhanced chemical vapor deposition, a number of different plasma aspects have been of importance. First, the understanding of process windows in terms of a dust free plasma has led to the formulation of an empirical scaling law for the dust free to dust forming transition in terms of the crucial process parameters such as, e.g., power and gas flows. Second, the homogeneity of deposition on an effective width of 30 cm has been demonstrated to be better than 5%. Increasing the deposition rate might be achieved by increasing the power density, but it scales only as (power density)0.77. A last important issue in roll‐to‐roll processing of long runs is process stability and on‐line quality control. The accurate measurement of self bias voltage and optical thickness of the deposited stacks have proven to be very useful in this context.

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Immobilization of Tungsten Catalysts on Plasma Modified Membranes
Authors: Lopez Linda C. , Buonomenna Maria G. , Fontananova Enrica , Drioli Enrico , Favia Pietro , d'Agostino Riccardo
Published: April 2007

Novel catalytic membranes were developed by coupling low‐temperature plasma treatments with the chemical immobilization of W‐based catalysts. Poly(vinylidene fluoride) membranes were pre‐treated with Ar, and then treated with NH3 radiofrequency glow discharges in order to obtain a surface rich in amino groups, which are suitable anchor sites for the immobilization of tungsten‐based heterogeneous catalysts. In particular, we have focused our interest on tungstate ions (WO), which catalyze the oxidation of secondary amines to nitrones, and on decatungstate (W10O) and phosphotungstate (W12PO) ions, which can both be used as catalysts for the degradation of organic pollutants such as phenol.

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A new model for ordinal pain data from a pharmaceutical study
Authors: Chuang Christy , Agresti Alan
Published: April 2007

For the pain data analysed previously by Cox and Chuang. This paper proposes a new model that assumes monotone scores for ordered response categories. This proposed model possesses several attractive features and allows a stochastic ordering of the drugs under comparison. Such a model also provides insight regarding the ordinal scale used to classify response. Estimation of the parameters in the model is obtained by use of BMDP3R.
Choosing the number of controls in a matched case‐control study, some sample size, power and efficiency considerations
Authors: Taylor Jeremy M. G.
Published: April 2007

This paper investigates the efficiency of using multiple controls in a case‐control study, when there is a single binary exposure variable. Specifically, we consider the asymptotic power of the Cochran1 test statistic against non‐local alternatives of interest. When it is desirable to take multiple controls per case, we show that the marginal return rapidly diminishes as the number of controls per case increases. The effect is as strong, if not stronger, for non‐local alternatives as it is for local alternatives. Hence, it is rarely worth choosing more than three controls per case. We also provide a table of sample sizes necessary to achieve 80 per cent power for some odds ratios not equal to one. We extend the results to a special case when there are two binary exposure variables.
Box‐jenkins modelling of some viral infectious diseases
Authors: Helfenstein Ulrich
Published: April 2007

During the last few years Box‐Jenkins models have become of increasing importance in such fields as economics and industry. They have been used for forecasting and for detecting relations between different time series. Similar applications are also relevant in epidemiology.

Since many people who are concerned with the analysis of medical data are not familiar with this subject, a short non‐technical introduction to Box‐Jenkins models is given. The model‐building process is demonstrated in some detail using monthly case reports of the two seasonal endemic diseases chicken‐pox and mumps, and the relation between these two time series is investigated. It is found that both diseases may be represented by simple models which have basically the same statistical structure and that they are related at time‐lag O but not at other time‐lags.
Statistical methods for relating several exposure factors to several diseases in case‐heterogeneity studies
Authors: Thomas D. C. , Goldberg M. , Dewar R. , Siemiatycki J.
Published: April 2007

Statistical methods for characterizing risks are now well‐developed, although little attention has focussed on the problem of risk identification, as in the surveillance of adverse drug reactions or occupational cancers. In this paper we consider the analysis of studies in which one ascertains and compares cases of several disease groups in terms of exposure histories. We address the problem of adjusting each risk for the confounding effects of all the other risks in the data. Data analysis consists of multidimensional contingency tables or polychotomous logistic regression. The latter approach focuses attention on the exposure‐disease relations of primary interest rather than on those among the exposure factors and higher‐order interactions, and applies easily to many exposure variables and to continuous exposure variables. We describe a stepwise approach to selecting effects for inclusion in the model. Application to preliminary data from a study aimed at identification of hitherto unsuspected occupational carcinogens illustrates the general approach.
Prediction of sudden infant death syndrome: An independent evaluation of four scoring methods
Authors: Peters Tim J. , Golding Jean
Published: April 2007

The performances of four published risk prediction systems for sudden infant death syndrome (SIDS) were compared for the 34 cases of SIDS and 48 explained deaths among a cohort of all births in the U.K. during one week in April 1970.

With cut‐points for the scores which would include about 20 per cent of the population, the sensitivities of the scoring methods ranged from identifying 40 per cent of the explained deaths to 70 per cent of SIDS. The highest sensitivities were achieved with the Sheffield ‘at birth’ system and a system based on both data from Oxford and general observations from the literature, with the latter system providing the most powerful predictor of SIDS for the study sample.
The use of logit models to investigate social and biological factors in infant mortality. III: Neonatal mortality
Authors: Machin D. , Murrells T. J. , Catford J. C. , Smith T. M. F.
Published: April 2007

Infant mortality data for England and Wales, cross‐classified by mother's age, parity and social class have been published on two occasions, the first giving the relevant data for 1949/50, the second for 1975, some 25 years later. Published analyses of these separate data sets have been based on graphical and tabular analysis. This paper develops the methodology from an earlier paper by Murrells et al.1 to the analysis of the neonatal data.
A proposal for interpreting and reporting negative studies
Authors: Hauck Walter W. , Anderson Sharon
Published: April 2007

An issue of continuing interest is the interpretation and reporting of ‘negative’ studies, namely studies that do not find statistically significant differences. The most common approach is the design‐power method which determines, irrespective of the observed difference, what differences the study could have been expected to detect. We propose an alternative approach, the application of equivalence testing methods, where we define equivalence to mean that the actual difference lies within some specified limits. This approach, in contrast to the design‐power approach, provides a way of quantifying (with p‐values) what was actually determined from the study instead of saying what the study may or may not have accomplished with some degree of certainty (power). For example, a possible outcome of the equivalence testing approach is the conclusion at the 5 per cent level that two means (or proportions) do not differ by more than some specified amount.

The equivalence testing approach applies to any study design. We illustrate the method with a cancer clinical trial and an epidemiologic case‐control study. In addition, for those studies in which one cannot specify limits a priori, we propose the use of equivalence curves to summarize and present the study results.
Sequential treatment allocation procedures in clinical trials‐with particular attention to the analysis of results for the biased coin design
Authors: Halpern Jerry , Brown Byron Wm.
Published: April 2007

We discuss the advantages and problems of using sequential allocation procedures for assigning treatments in a clinical trial. We use Monte Carlo methods to study the exact distribution of the fourfold chi‐squared statistic for the case of no stratifying variables except sequence of entry. We display situations in which the distribution is well‐approximated by the chi‐squared distribution or by Efron's adjusted chi‐squared and situations where these approximations fail. We provide suggestions for recognition and handling of situations in which both approaches fail.
Psychiatric admissions and choice of abortion
Authors: Andersen Per Kragh , Rasmussen Niels Kr.
Published: April 2007

A statistical analysis is presented of the intensities of admissions to psychiatric hospitals among women in Denmark who either gave birth to a child in the year 1975 or had an induced abortion in the same year. The models used are time‐continuous Markov and semi‐Markov processes, and the methods employed include non‐parametric and semi‐parametric analysis of counting processes. The influence of prior psychiatric admissions on the choice of terminating the pregnancy with an induced abortion is also studied.
Case‐control studies and bayesian inference
Authors: Zelen M. , Parker R. A.
Published: April 2007

We outline the methods of Bayesian inference for applications to case‐control studies. These methods appear as the natural way of making inferences, since much of the controversy that surrounds a specific case‐control study is subjective. We derive conjugate prior distributions of exposure, posterior distributions of the ratio of the odds of being incident with a disease both with and without exposure to a potential causal agent, and convenient approximations. In particular, we show how one may carry out ‘case‐control studies’ without necessarily having a control group. We illustrate these ideas with the data that first showed the relationship betweenin uteroexposure to diethylstilbestrol and cancer of the vagina in young girls.
A statistical test for contact among individuals in an epidemic and a pattern among cases of acquired immune deficiency syndrome
Authors: Grimson Roger C. , Groshen Susan
Published: April 2007

In investigating an epidemic or outbreak of a disease in which patient contact (appropriately defined) is hypothesized to be a factor, investigators may ask patients to provide names of people with whom they have had contact. This paper provides statistical methods for assessing whether or not the number of named contacts who are themselves cases is significantly large. Survey data on the epidemiology of acquired immune deficiency syndrome illustrate the methods.
Allocation designs in cohort and case‐control studies
Authors: Moussa Mohamed A. A.
Published: April 2007

Four unequal allocation designs for cohort and case‐control studies that incorporate cost and power are considered and compared with the equal allocation design, with the aim of providing researchers some flexibility in planning their studies. It is found that the type of design to be adopted depends on available resources and projected needs. In the case of tight expenditure, the minimized cost design is the optimal, whereas the maximized power design may be sought if the researcher intends to ensure a high chance of detecting any clinically significant relative risk of disease.
A clinical trial with an interim analysis
Authors: Chi P. Y. , Bristol D. R. , Castellana J. V.
Published: April 2007

We consider a fixed‐sample parallel‐group clinical trial with an interim analysis that tests Ho: μx = μy against H1: μx < μy. If we do not reject at the interim analysis, then the probability of making a type I error by rejecting Ho in favour of H2: μx > μy and the power at the final analysis are not appreciably affected by performing the interim analysis for certain relevant critical regions.
Statistical comparison of two handwashing protocols
Authors: Le Chap T.
Published: April 2007

This paper describes statistical procedures for use in an experiment that compares two handwashing protocols. The evaluation of a handwashing protocol entails collection of the wash effluent. Colony counts for the effluent reflect the number of flora removed by the wash protocol. The analysis aims to formulate and estimate an odds ratio that represents the relative efficacy of a test as compared with a standard protocol.
Sample sizes for phase II and phase III clinical trials: An integrated approach
Authors: Whitehead John
Published: April 2007

In this paper the following problem of clinical research is explored. Several potential new treatments are available for use against a certain disease. These are evaluated in a series of pilot studies which will constitute phase II clinical trials. The most promising will then be compared with a standard treatment in a phase III trial. Of interest will be the number of patients needed for the complete research programme, the proportions of these that should be involved in each phase, and the number of treatments which should be tried. Optimal strategies are found which maximize the probability that the overall programme identifies a treatment which is significantly better than the standard.
Life‐table methods for contraceptive research
Authors: Farley T. M. M.
Published: April 2007

Life‐table methods used for the analysis and interpretation of contraceptive follow‐up studies differ from those used in other areas of medical research. The historical development of these methods in the contraceptive literature is outlined and the two main methods are discussed, compared and shown to differ mainly in their nomenclature; their results are very similar in practice. The daily life‐table method is simpler to apply and interpret, and facilitates analysis using the logrank statistic as well as powerful regression modelling techniques for survival data.
Intelligent dialogue based on statistical models of clinical decision‐making
Authors: McSherry D. M. G.
Published: April 2007

The independence Bayesian model has been used widely in computer programs designed to support clinical decision‐making. A reasoning strategy has been developed to enable these programs to conduct clinically pertinent dialogue and explain their reasoning. It has been implemented in a program for the diagnosis of acute abdominal pain based on the Bayesian model of de Dombal et al. Several features of the dialogue design have been adopted from artificial intelligence research, including shared initiative and critiquing. The program adopts a flexible goal‐driven strategy, attempting to confirm the clinician's diagnosis or rule out the likeliest alternative. Symptoms and signs are selected in order of their expected weights of evidence in favour of the hypothesized disease.
Partitioning methods for classification and decision making in medicine
Authors: Marshall R. J.
Published: April 2007

The use of partitioning methods for classification is discussed. A brief outline of the method of recursive partitioning is given and a note is made of some of its potential drawbacks. An alternative approach is outlined in which a particular class of dichotomous partitions is considered. The class incorporates prior knowledge concerning the nature of an association. Strategies to choose a partition from this class are suggested. The method is illustrated by an analysis of data from patients with gastrointestinal cancer and benign disease. A partition to discriminate between cancer and benign disease is obtained using symptoms, age and tumour marker data.
Some recent statistical analyses of two long‐term studies of exposure to ionizing radiation
Authors: Darby Sarah C.
Published: April 2007

Two long‐term studies of cancer mortality in populations exposed to high doses of ionizing radiation are described briefly. Statistical analysis plays a key role in establishing to what extent it is appropriate to generalize from the experience of these populations to that of other populations who have been exposed, usually at lower doses. Two examples of recent analyses are given. First, a detailed comparison of the cancer mortality experience in the two studies has been carried out; this has shown a high level of agreement between them. In the second example the relation between the radiogenic risk and the baseline age‐specific cancer risk in the two populations has been studied. Results are again in good agreement and show that for a group of epithelial tumours of non‐sex‐specific sites exposure to radiation multiplies the baseline risk.