bluuebunny/crossref_metadata_2025 huggingface dataset:
Three‐dimensionally resolved NAD(P)H cellular metabolic redox imaging of the in situ cornea with two‐photon excitation laser scanning microscopy
Authors: PISTON D. W. , MASTERS B. R. , WEBB W. W.
Published: August 2011

Three‐dimensional maps of cellular metabolic oxidation/reduction states of rabbit cornea in situ were obtained by imaging the fluorescence of the naturally occurring reduced pyridine nucleotides (both reduced nicotinamide‐adenine dinucleotide, NADH, and reduced nicotinamide‐adenine dinucleotide phosphate, NADPH, denoted here as NAD(P)H). Autofluorescence images with submicrometre lateral resolution were obtained throughout the entire 400 μm thickness of the cornea. Two‐photon excitation scanning laser microscopy with near‐infrared excitation provided high fluorescence collection efficiency, reduced photodamage, and eliminated ultraviolet chromatic aberration, all of which have previously degraded the visualization of pyridine nucleotide fluorescence. Sharp autofluorescence images of the basal epithelium (40 μm within the cornea) show substantial subcellular detail, providing the ability to monitor autofluorescence intensity changes over time, which reflect changes in oxidative metabolism and cellular dynamics necessary for maintenance of the ocular surface. The autofluorescence was confirmed to be mostly of NAD(P)H origin by cyanide exposure, which increased the fluorescence from all cell types in the cornea by about a factor of two. Autofluorescence images of individual keratocytes in the stroma were observed only after cyanide treatment, while in the predominant extracellular collagen (> 90% of the stromal volume), fluorescence was not distinguished from the background. Observation of keratocyte metabolism demonstrates the sensitivity made available by two‐photon microscopy for future redox fluorescence imaging of cellular metabolic states.
A hybrid scanning force and light microscope for surface imaging and three‐dimensional optical sectioning in differential interference contrast
Authors: STEMMER A.
Published: August 2011

The design of a scanned‐cantilever‐type force microscope is presented which is fully integrated into an inverted high‐resolution video‐enhanced light microscope. This set‐up allows us to acquire thin optical sections in differential interference contrast (DIC) or polarization while the force microscope is in place. Such a hybrid microscope provides a unique platform to study how cell surface properties determine, or are affected by, the three‐dimensional dynamic organization inside the living cell.

The hybrid microscope presented in this paper has proven reliable and versatile for biological applications. It is the only instrument that can image a specimen by force microscopy and high‐power DIC without having either to translate the specimen or to remove the force microscope. Adaptation of the design features could greatly enhance the suitability of other force microscopes for biological work.
Maximum entropy reconstruction of compositional depth profiles from electron probe microanalysis data
Authors: SMITH G. C. , PARK D. , COCHONNEAU O.
Published: August 2011

Electron probe microanalysis (EPMA) is a powerful method for the quantitative determination of the elemental composition of micro‐regions of a sample surface. Here, we report on the development of a method of reconstructing compositional depth profiles in thin films from EPMA data measured over a range of electron beam energies, using maximum entropy data processing. The method gives quantitative information on film compositions up to approximately 1 μm in depth, with a lateral spatial resolution of approximately 1 μm. The method is tested using both simulated data and measured experimental data from well‐characterized model sample structures.
Inherent bias in correlation averaged images
Authors: WOODWARD J. T. , KONO C. , MADSEN L. L. , ZASADZINSKI J. A.
Published: August 2011

The correlation averaging algorithm frequently used to enhance micrographs of repeating structures contains an inherent bias that favours images with larger pixel values or positive noise levels. This bias not only skews the composite image toward higher pixel values, but also distorts the image by increasing the value of high‐valued pixels more than that of low‐valued pixels. These errors are especially important in scanning probe microscopy images where the pixel value reflects a distinct height. A similar algorithm that uses a structure function in place of the correlation function eliminates this bias.
An image processing system for cell behaviour studies in subconfluent cultures
Authors: ZICHA D. , DUNN G. A.
Published: August 2011

DRIMAPS (digitally recorded interference microscopy with automatic phase‐shifting) is a system that we have developed for quantifying the behaviour of cells in subconfluent cultures. The primary data generated by the system consist of phase‐shifted interference (PSI) images which are accurate density maps of the distribution of dry mass (non‐aqueous material) inside cells. Time‐lapse sequences of PSI images may be viewed as movie sequences or processed in various ways to reveal many different aspects of the dynamics of cell growth and motile behaviour.

Here we describe the image processing routines that are an integral part of the system and are required for four main functions:

1 initial calculation of the PSI images;

2 compensation of these images for instrumental distortion and instability;

3 identification and tracking of individual cells in a time‐lapse sequence of PSI images;

4 extraction of cell behavioural data from a time‐lapse sequence of PSI images.

The first function converts standard interference microscope images into an image that accurately represents the optical phase‐difference introduced by the specimen. The second function recalibrates a sequence of images by taking the cell‐free region in each image as a reference plane of zero phase‐difference. This is particularly necessary to compensate for the long‐term instability of the Horn type of double‐beam interference microscope, which has several advantages over other types of interference microscope for studying cell behaviour. The third function compares consecutive images in a sequence in order to trace the identity of individual cells throughout the sequence. Semi‐automatic tracking, which allows close interaction with a human operator, is less prone to error than fully automatic tracking. The fourth function automatically extracts dynamic data from the identified cells. These data may include the true mass centroids of cells for translocation analysis and robust morphometric parameters for cell morphology examination. The integrated intensity of a cell is an accurate measure of cell mass and allows the growth (increase in dry mass) of individual cells to be studied. These data may be entered into a relational database of cell behaviour and a rule‐based system allows efficient data access and analysis.

Experiments with phase‐contrast microscopy have revealed that many of these image processing methods are generally useful for cell behaviour studies using more conventional forms of microscopy.
X‐ray microanalysis of wet biological specimens in the environmental scanning electron microscope. 1. Reduction of specimen distance under different atmospheric conditions
Authors: GILPIN C. , SIGEE D. C.
Published: August 2011

X‐ray microanalysis of non‐biological and biological specimens was carried out in the environmental scanning electron microscope (ESEM) under different conditions of specimen distance (the distance travelled by the electron probe within the specimen chamber) and chamber atmosphere.

Using both water vapour and argon atmospheres, it was shown that reduction in specimen distance had no effect on atmospheric gas X‐ray signal in either case. Unlike water vapour, increased levels of argon (up to 10 torr) caused a marked depression of specimen P/B ratios, with a decrease in both characteristic and background (continuum) counts. These effects in argon were not altered by reduction in specimen distance.

Specimen distance was important in relation to beam skirting and elemental analysis. With an extended assembly (short specimen distance), beam skirting in a water‐vapour atmosphere was much reduced – leading to enhanced element detectability in a discrete biological specimen (Anabaena cyclindrica).
The development of coherent Foucault imaging to investigate magnetic microstructure
Authors: JOHNSTON A. B. , CHAPMAN J. N.
Published: August 2011

We describe coherent Foucault (CF) imaging, a novel TEM technique which we have used successfully to investigate quantitatively micromagnetic structures in thin magnetic films. A simple analytical approach to CF imaging shows how an accurately positioned aperture in the diffraction plane leads to a magnetic interferogram forming in the image plane. Fringes follow lines of magnetic induction and there is one quantum of flux, h/e, between adjacent fringes. The aperture used can either be opaque or phase‐shifting and one‐ and two‐dimensional computer simulations have been performed to investigate how the nature and positioning of the aperture, along with the coherence of the illumination, affect the detailed form of the interferogram. Images recorded on a modified Philips CM20 FEG TEM confirm the simulations and demonstrate the power of the technique. The paper ends with a brief discussion of the broader uses of Foucault imaging.
Miniature magnetic electron lenses with permanent magnets
Authors: ADAMEC P. , DELONG A. , LENCOVÁ B.
Published: August 2011

New permanent magnet materials offer the possibility of designing lenses for applications at lower voltages. This paper briefly presents the finite‐element method (FEM) program for computation of lenses based on permanent magnets. The design of a lens unit for a low‐voltage TEM, realized in Brno, is described together with some design proposals of SEM and STEM lenses and computed results for a rotation‐free projector proposed by Le Poole in 1972.
Approximate expressions for electron lens properties*
Authors: HAWKES P. W. , LENCOVÁ B. , LENC M.
Published: August 2011

New approximate formulae for the focal length and principal aberration coefficients of electrostatic and magnetic lenses have been suggested by Crewe. These are compared with earlier approximate expressions and similarities and differences are indicated; they are also compared with calculated values for some real lenses. These comparisons confirm Crewe's findings and elucidate some unexplained features of these.
Second‐order finite element method and its practical application in charged particle optics
Authors: ZHU X. , MUNRO E.
Published: August 2011

The first‐order finite element method (FOFEM) has been widely used in computing electrostatic and magnetic fields of lenses and deflectors. With the increasing requirement of high‐accuracy field computation and the advances in the power of computers, the second‐order finite element method (SOFEM), which will be demonstrated in this paper to be more accurate than FOFEM, is becoming necessary and practical. In this paper, the concept of SOFEM will be described. Several applications of SOFEM in charged particle optics will also be illustrated, such as the simulation of electrostatic and magnetic lenses and deflectors, the modelling of electron and ion sources, and the evaluation of high‐order geometric and chromatic aberrations of charged particle columns.
Unconventional lens computation
Authors: LENCOVÁ B.
Published: August 2011

Professor Tom Mulvey has contributed significantly to the development of computer‐aided design in electron optics. Some of the problems connected with the computation of unconventional lenses and related test examples proposed by Mulvey are summarized. It is shown what boundary condition and position of boundary has to be selected for reliable results, what types and sizes of mesh should be used for required field accuracy, and which problems in the first‐order finite‐element method remain unsolved.
Double‐layer coating for high‐resolution low‐temperature scanning electron microscopy
Authors: WALTHER P. , WEHRLI E. , HERMANN R. , MÜLLER M.
Published: August 2011

Specimen damage caused by mass loss due to electron beam irradiation is a major limitation in low‐temperature scanning electron microscopy of bulk specimens. At high primary magnifications (e.g. 100 000x) a hydrated sample is usually severely damaged after one slow scan (about 3000 e— nm—2). The consequences of this beam damage are significantly reduced by coating the frozen‐hydrated sample with a 5–10‐nm‐thick carbon layer. Since this layer covers up surface details, the sample is first unidirectionally shadowed with a thin heavy metal layer (e.g. 2 nm of platinum) that is in close contact with the biological surface (double layer coating). This heavy metal layer can be visualized in field‐emission scanning electron microscopy with the material‐dependent backscattered electron signal. The method allows for routine observation of large frozen‐hydrated samples. By use of an in‐lens field‐emission SEM and a sensitive backscattered electron detector, structural information comparable to that obtained with the transmission electron microscopy freeze‐fracture replica technique can be achieved.
Reflection conoscopy and micro‐ellipsometry of isotropic thin film structures
Authors: SHATALIN S. V. , JUŠKAITIS R. , TAN J. B. , WILSON T.
Published: August 2011

The conoscopic image of isotropic thin film structures is discussed, and it is shown that, although the specimens may be optically isotropic, the conoscopic images are generally not angularly symmetric. Theoretical expressions for these patterns are derived and from which full ellipsometric data about the specimen are extracted. In addition, a variety of spatial filters which may be inserted into the optical system in order to enhance specific image contrast are recommended.
Vitrification of articular cartilage by high‐pressure freezing
Authors: STUDER D. , MICHEL M. , WOHLWEND M. , HUNZIKER E. B. , BUSCHMANN M. D.
Published: August 2011

For more than 20 years, high‐pressure freezing has been used to cryofix bulk biological specimens and reports are available in which the potential and limits of this method have been evaluated mostly based on morphological criteria. By evaluating the presence or absence of segregation patterns, it was postulated that biological samples of up to 600 μm in thickness could be vitrified by high‐pressure freezing. The cooling rates necessary to achieve this result under high‐pressure conditions were estimated to be of the order of several hundred degrees kelvin per second. Recent results suggest that the thickness of biological samples which can be vitrified may be much less than previously believed.

It was the aim of this study to explore the potential and limits of high‐pressure freezing using theoretical and experimental methods. A new high‐pressure freezing apparatus (Leiċa EM HPF), which can generate higher cooling rates at the sample surface than previously possible, was used. Using bovine articular cartilage as a model tissue system, we were able to vitrify 150‐μm‐thick tissue samples. Vitrification was proven by subjecting frozen‐hydrated cryosections to electron diffraction analysis and was found to be dependent on the proteoglycan concentration and water content of the cartilage. Only the lower radical zone (with a high proteoglycan concentration and a low water content compared to the other zones) could be fully vitrified. Our theoretical calculations indicated that applied surface cooling rates in excess of 5000 K/s can be propagated into specimen centres only if samples are relatively thin (<200 μm). These calculations, taken together with our zone‐dependent attainment of vitrification in 150‐μm‐thick cartilage samples, suggest that the critical cooling rates necessary to achieve vitrification of biological samples under high‐pressure freezing conditions are significantly higher (1000–100 000 K/s) than previously proposed, but are reduced by about a factor of 100 when compared to cooling rates necessary to vitrify biological samples at ambient pressure.
Electron energy‐loss near‐edge structure of internal interfaces by spatial difference spectroscopy
Authors: MÜLLEJANS H. , BRULEY J.
Published: August 2011

Internal interfaces determine the macroscopic mechanical and electronic properties of materials. Their investigation is therefore essential for an understanding of the relationship between microstructure and the materials properties. Besides the atomic structure, the bonding and electronic structure on an atomic scale are of interest. This information is contained in the interface‐sensitive component of the electron energy‐loss near‐edge structure (ELNES). It can be extracted by the spatial difference method. Such spectra have already been interpreted with respect to the bonding and the local atomic environment of the atoms at the interface. Here we assess critically the application of the spatial difference for the investigation of internal interfaces. The method is subjective because a suitable scaling factor has to be chosen. As a guideline we propose to minimize the number of turning points in the difference spectrum. With this hypothesis we successfully determine the ELNES arising from atoms at two internal interfaces between a metal and a ceramic. This reveals qualitatively which type of bonding is present at the interface and quantitatively how many atoms are involved in it.
Quantitative near‐edge structure analysis of diamond‐like carbon in the electron microscope using a two‐window method
Authors: BRULEY J. , WILLIAMS D. B. , CUOMO J. J. , PAPPAS D. P.
Published: August 2011

To extract quantitative electronic structure information from electron energy‐loss near‐edge structure typically necessitates the separation of spectra into linearly independent components. For this to be accomplished, certain conditions need to be met concerning the localization of chemical bonding and the linear scaling of fine structure with density of states. The dependence of the processing parameters, such as window widths and positions, of the commonly used ‘two‐window intensity‐ratio’ method to determine the distribution of π and σ bonding of diamond‐like carbon films is investigated. It is shown that, although the selection of the integration windows can lead to very large variations in the resultant bonding fractions, the placement of two small windows centred on the edge structures of interest does permit a robust and reliable estimate of bonding. It is demonstrated that the sp3 variations can be reproducibly monitored with a relative accuracy of about ± 5%, and an absolute concentration given with an accuracy of ± 13% for foils of thickness at least up to twice the inelastic mean free path.
A software package for the processing and reconstruction of electron holograms
Authors: VÖLKL E. , ALLARD L. F. , FROST B.
Published: August 2011

Electron holography is leaving its state of infancy and is rapidly becoming a tool for everyday use. This is due to the increasing availability of field‐emission electron microscopes as well as the increasing use of slow‐scan CCD cameras, which provide the linear image recording so essential to electron holography. At the same time, the continuing boost in performance of desktop computers both in hardware and in software has facilitated the handling of many of the complex reconstruction and processing tasks of electron holography. We describe here the software package ‘HoloWorks©’, recently developed at Oak Ridge National Laboratories. This package is designed for the processing of electron holograms stressing easy‐to‐use functions and is a plug‐in module for Gatan's software DigitalMicrograph®.
Analysis of bonding state in pure and gold‐implanted amorphous SiC by a combination of UHVEM and AES
Authors: YASUDA H. , MORI H.
Published: August 2011

Single crystalline α‐SiC films and Au(target metal)/α‐SiC(substrate) bilayer films were irradiated with 2‐MeV electrons in an ultrahigh‐voltage electron microscope (UHVEM) to form, in situ, pure amorphous SiC (a‐SiC) and gold‐implanted a‐SiC. respectively. In the latter case, sample films were set so that the electron beam was incident on the gold layer. Differences in the bonding state between pure a‐SiC and gold‐implanted a‐SiC were studied by Auger valence electron spectroscopy (AES). In pure a‐SiC. the carbon valence state was markedly different from that of α‐SiC but the silicon valence state was similar to that of α‐SiC. In gold‐implanted α‐SiC. both the carbon and the silicon valence states were different from those of α‐SiC. It is suggested that a high density of molecularized carbon clusters are formed in the amorphous matrix in gold‐enriched a‐SiC.
The effects of total internal reflection on the spread function along the axis in confocal microscopy
Authors: ENTWISTLE A.
Published: August 2011

A broadening and splitting of the axial spread function is observed when high‐numerical‐aperture (NA) oil‐immersion objectives are used on a confocal microscope to examine dielectric interfaces when the refractive index below the boundary is lower than the NA of the objective. The phenomena is due to total internal reflection probably as a consequence of the Goos‐Hänchen shift. If total internal reflection occurs when undertaking confocal microscopy, this shift creates obvious problems when the optical sectioning capabilities must be optimal in reflectance mode and more subtle difficulties can arise when examining fluorescent emission. Alternatively, deliberately inducing total internal reflection can be used to estimate the refractive index in component parts within foams, emulsions and aerated specimens where such measurements can be relatively difficult to make by other means. Furthermore, the examination of total internal reflection with a confocal microscope permits the phenomena of total internal reflection itself to be probed with very high illumination intensities without disturbing the boundary conditions with an external probe. Finally, other changes in the apparent position of the focus were noted to occur when high‐NA oil‐immersion objectives are used to examine specimens such as metal mirrors.
Edge effect in Auger electron microscopy: Quantification of the effect
Authors: FRANK L. , MATÊJKA F.
Published: August 2011

The edge effect in electron microscopical images is proposed to be measured in length units by using a ratio of the edge or near‐to‐edge signal enhancement or depletion integrated over all this feature along a line‐scan across an edge, to the mean signal away from the edge, giving the result in length units. This approach is applied to quantification of the edge effect in Auger electron images, which is examined by using specimens with sharp edge terminated overlayer terraces, both chemically homogeneous and heterogeneous. The following combinations of overlayer/substrate materials were used: Si/Si of three different overlayer thicknesses, W/W and W/Si, and line‐scans across the edges were recorded in both the low‐ and the high‐energy Auger electrons mode, i.e. Si LMM and Si KLL or W NOO and W MNN. The experimental results are presented for the 3‐, 10‐ and 20‐keV primary electron energies. Owing to a low signal‐to‐noise ratio in the measured data, basic relations between the effect appearance and the experimental conditions were revealed only: on both Si and W homogeneous specimens with a surface step, the edge enhancement is the dominating subphenomenon while at the W terrace edge on the Si substrate, the ‘penetration’ of the radiation characteristic to both areas separated by the step, to the neighbouring feature, is observed as the most significant effect. The quantification has shown that the effect is, first of all, proportional to the step height, amounting to one‐third to up to the full height, while the material dependence was weak, equally to the dependence on the Auger electron energy. The primary electron energy dependence is increasing in accordance with expectation. The results indicate that the effect cannot be modelled simply by the interaction volume cut by the surface step but phenomena such as subsurface electron channelling along the sidewall have to be taken into account.
Imaging and nano‐dissection of tobacco mosaic virus by atomic force microscopy
Authors: BUSHELL G. R. , WATSON G. S. , HOLT S. A. , MYHRA S.
Published: August 2011

Tobacco mosaic virus (TMV) has been deposited on freshly cleaved mica substrates. The topography was investigated by contact, non‐contact and lateral‐force microscopy under ambient conditions in air. The results were in accord with known dimensions of TMV (i.e. 18 nm in diameter and 300 nm in length). However, convolution of tip shape with TMV morphology resulted in an apparent width of 80–140 nm in the lateral plane, a factor of 4–7 greater than the known diameter. Other artefacts ‐ broadening and double images ‐ were observed and ascribed to tip anomalies.

High force loadings and slow repetitive scanning resulted in controlled removal of parts of the TMV structure. Accordingly, it was possible to reveal and image the central core channel of the TMV. The precision and resolution of dissection induced by AFM is currently limited by the shape of the tip, having a 40‐nm radius of curvature for standard Si3N4 tips. It is estimated that sharper tips, with a radius of curvature of less than 10 nm, should be able to resolve, non‐destructively, the protein subunits in the non‐contact mode, and selectively remove single subunits in the contact mode.
Preparation of metal multilayer TEM cross‐sections using ultramicrotomy
Authors: HOWELL D. A. , JR J. W. HECKMAN , CRIMP M. A.
Published: August 2011

Ultramicrotomy is an effective method of sample preparation for TEM of metal multilayer thin‐films. Large, thin, cross‐sectional areas can be obtained for TEM observations from a small amount of thin‐film which has been mechanically removed from its substrate. An example of a TEM cross‐section made from an AuFe0.03/a‐silicon multilayer used in the study of metallic spin‐glass properties illustrates the usefulness of ultramicrotomy in preparing samples that are largely free of the deleterious effects associated with ion‐milling such as irradiation damage, differential thinning and variable thickness.
Recent developments in secondary electron imaging
Authors: HOWIE A.
Published: August 2011

Some recent experimental and theoretical developments in secondary electron (SE) imaging are reviewed. Coincidence experiments identify inner‐shell excitations and single electron valence excitations often as more significant initial events in SE production than the more delocalized process of plasmon generation. Quantitative measurement and interpretation of escape depths in different materials are now becoming possible. Local variations in surface barrier height or work function can be imaged, e.g. at p‐n junctions in semiconductors, especially if the effects of external patch fields are overcome.
Changes in the iron white‐line ratio in the electron energy‐loss spectrum of iron‐copper multilayers
Authors: LLOYD S. J. , BOTTON G. A. , STOBBS W. M.
Published: August 2011

We report changes in the iron L3/L2 white‐line ratio of the electron energy‐loss spectrum of a series of iron‐copper multilayers which we discuss in terms of the lattice plane spacings present in the multilayer system. Momentum‐resolved data from one multilayer is also considered.
Oxygen K near‐edge spectra of amorphous silicon suboxides
Authors: WALLIS D. J. , GASKELL P. H. , BRYDSON R.
Published: August 2011

Chemical disorder in silicon suboxides has been modelled by constructing several small atomic clusters which were used as input for multiple scattering calculations of the energy‐loss near‐edge structure at the oxygen K‐edge. A redistribution of intensity at the O K‐edge is observed as the number of second neighbour oxygen atoms is reduced. Since photoelectrons scattered by second neighbours of oxygen (at least) contribute to the spectra, O K‐edge data provide valuable structural information, additional to that obtained from the Si L23‐edge, which appears to be restricted to the local coordination shell. Comparison with the experimental O K‐edge for a‐SiOx (O < × < 2), prepared by oxidation of amorphous Si, suggests that the material consists of an intimate mixture of a wide range of Si sites with varying proportions of oxygen and silicon in the first neighbour shell.
Virologic factors associated with failure to passive–active immunoprophylaxis in infants born to HBsAg‐positive mothers
Authors: Zou H. , Chen Y. , Duan Z. , Zhang H. , Pan C.
Published: August 2011

Summary.  In infants born to hepatitis B surface antigen (HBsAg)–positive mothers, failure after passive–active immunization still occurs. The role of maternal hepatitis B DNA level and other risk factors in this setting remains unclear. This study retrospectively evaluated virologic and other risk factors associated with immunoprophylaxis failure in infants born to HBsAg‐positive mothers. Between January 2007 and March 2010, we reviewed the clinical and virologic tests in 869 mother–infant pairs. All infants received the identical passive–active immunization schedule after birth. The failure infants (HBsAg positive at 7–12 months of age) were compared to infants who were HBsAg negative when tested during this time period. Among 869 infants, 27 (3.1%) infants were immunoprophylaxis failures and the other 842 (96.9%) infants remained HBsAg negative. When mothers’ pre‐delivery HBV DNA levels were stratified to <6, 6–6.99, 7–7.99 and ≥8 log10 copies/mL, the corresponding rates of immunoprophylaxis failure were 0%, 3.2% (3/95), 6.7% (19/282) and 7.6% (5/66), respectively (P < 0.001 for the trend). All failure infants were born to hepatitis B e antigen (HBeAg)–positive mothers. Multivariate logistic regression analysis identified maternal HBV DNA levels [odds ratio (OR) = 1.88, 95% confidence interval (CI): 1.07–3.30] and detectable HBV DNA in the cord blood (OR = 39.67, 95% CI: 14.22–110.64) as independent risk factors for immunoprophylaxis failure. All failure infants were born to HBeAg‐positive mothers with HBV DNA levels ≥6 log10 copies/mL. The presence of HBV DNA in cord blood predicted failure to passive–active immunization.
Maternal ethnicity and pre‐eclampsia in New York City, 1995–2003
Authors: Gong Jian , Savitz David A. , Stein Cheryl R. , Engel Stephanie M.
Published: August 2011

Gong J, Savitz DA, Stein CR, Engel SM. Maternal ethnicity and pre‐eclampsia in New York City, 1995–2003. Paediatric and Perinatal Epidemiology 2012; 26: 45–52.

Studies on ethnic differences in the risk of pre‐eclampsia are limited. We linked birth records for 902 460 singleton births for the period 1995–2003 in New York City with hospital discharge data to evaluate the association between ethnicity and the risk of pre‐eclampsia and compare risks between US‐born and foreign‐born women. Logistic regression models adjusted for maternal age, maternal education, parity, self‐reported pre‐pregnancy maternal weight, smoking during pregnancy and year of delivery were used to compare each ethnic group with non‐Hispanic White women. The prevalence of pre‐eclampsia in this study population was 3.2%. Among the major ethnic groups considered in our study, East Asian women had the lowest risk of pre‐eclampsia (1.4%) and Mexican women had the highest risk (5.0%). Compared with non‐Hispanic White women, there was a slightly decreased risk for East Asian women (adjusted OR = 0.8, [95% CI 0.7, 0.8]), similar risk for North African women (adjusted OR = 1.1, [95% CI 0.9, 1.3]), and increased risk for all other major ethnic groups (adjusted ORs: 1.3, 2.9), with the highest risk for Mexican women (adjusted OR = 2.9, [95% CI 2.7, 3.1]). No difference in risks was observed for US‐ vs. foreign‐born women with the exception that foreign‐born South‐East Asian and Pacific Islanders had an increased risk of pre‐eclampsia (adjusted OR = 1.8, [95% CI 1.0, 3.1]) relative to those born in the US. We concluded that there was ethnic heterogeneity in the development of pre‐eclampsia among women in New York City and that Asian subgroups should be examined separately in future studies on ethnicity. Our results should contribute to screening for pre‐eclampsia taking ethnic variation into account, and may help to suggest leads for the study of the aetiology of the condition.
Accuracy of pastoralists’ memory‐based kinship assignment of Ankole cattle: a microsatellite DNA analysis
Authors: Kugonza D.R. , Kiwuwa G.H. , Mpairwe D. , Jianlin H. , Nabasirye M. , Okeyo A.M. , Hanotte O.
Published: August 2011

This study aimed to estimate the level of relatedness within Ankole cattle herds using autosomal microsatellite markers and to assess the accuracy of relationship assignment based on farmers’ memory. Eight cattle populations (four from each of two counties in Mbarara district in Uganda) were studied. Cattle in each population shared varying degrees of relatedness (first‐, second‐ and third‐degree relatives and unrelated individuals). Only memory‐based kinship assignments which farmers knew with some confidence were tested in this experiment. DNA isolated from the blood of a subsample of 304 animals was analysed using 19 microsatellite markers. Average within population relatedness coefficients ranged from 0.010 ± 0.005 (Nshaara) to 0.067 ± 0.004 (Tayebwa). An exclusion probability of 99.9% was observed for both sire–offspring and dam–offspring relationships using the entire panel of 19 markers. Confidence from likelihood tests performed on 292 dyads showed that first‐degree relatives were more easily correctly assigned by farmers than second‐degree ones (p < 0.01), which were also easier to assign than third‐degree relatives (p < 0.01). Accuracy of kinship assignment by the farmers was 91.9% ± 5.0 for dam–offspring dyads, 85.5% ± 3.4 for sire–offspring dyads, 75.6% ± 12.3 for half‐sib and 60.0% ± 5.0 for grand dam–grand offspring dyads. Herd size, number of dyads assigned and length of time spent by the herder with their cattle population did not correlate with error in memorizing relationships. However, herd size strongly correlated with number of dyads assigned by the herder (r = 0.967, p < 0.001). Overall, we conclude that memorized records of pastoralists can be used to trace relationships and for pedigree reconstruction within Ankole cattle populations, but with the awareness that herd size constrains the number of kinship assignments remembered by the farmer.
A critical realist approach to knowledge: implications for evidence‐based practice in and beyond nursing
Authors: Nairn Stuart
Published: August 2011

NAIRN S. Nursing Inquiry 2012; 19: 6–17 A critical realist approach to knowledge: implications for evidence‐based practice in and beyond nursing

This paper will identify some of the key conceptual tools of a critical realist approach to knowledge. I will then apply these principles to some of the competing epistemologies that are prevalent within nursing. There are broadly two approaches which are sometimes distinct from each other and sometimes inter‐related. On one side, there is the view that all healthcare interventions should be judged on the principles of randomised controlled trials and the other is a preoccupation with language in which healthcare interventions are subjected to a discursive interrogation. These debates are configured through the idea of a hierarchy of knowledge that is accorded uncritical acceptance by some and virulent distaste by others. I will argue that the notion of hierarchy is problematic and is largely argued for in unproductive epistemological terms. What is required is a shift towards a theory that emphasises the contextual nature of the ways that knowledge is produced and disseminated. In other words, there is no single hierarchy of knowledge, but there are multiple hierarchies of knowledge.
Effect of disability level on response to pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis
Authors: KOZU RYO , JENKINS SUE , SENJYU HIDEAKI
Published: August 2011

Background and objective:  It is unclear whether the severity of functional limitation resulting from IPF affects the response to pulmonary rehabilitation. The aim of this study was to compare the outcomes of rehabilitation in patients with IPF, who were grouped according to the Medical Research Council (MRC) dyspnoea scale.

Methods:  Sixty‐five subjects (46, 71% men) with stable IPF were enrolled in an 8‐week pulmonary rehabilitation programme. Subjects with MRC dyspnoea grades 2, 3 and 4 undertook a supervised outpatient programme, whereas subjects with MRC dyspnoea grade 5 participated in an unsupervised, home‐based programme, with review every 2 weeks. The outcome measures included functional exercise capacity (6MWD), health status (Medical Outcomes Study Short Form 36 (SF‐36)) and dyspnoea (transition dyspnoea index), which were measured at baseline and immediately after the programme. Hospitalizations for respiratory exacerbations were compared for the 12 months preceding and following the programme.

Results:  The number of subjects with MRC dyspnoea grades 2, 3, 4 and 5 were 16 (25%), 17 (26%), 17 (26%) and 15 (23%), respectively. There were differences between these groups in the magnitude of change in 6MWD, SF‐36 and transition dyspnoea index (all P < 0.05). Specifically, subjects with MRC dyspnoea grade 2 or 3 demonstrated clinically and statistically significant improvements in 6MWD and SF‐36 following rehabilitation (all P < 0.05). In contrast, for all measures, subjects with MRC dyspnoea grade 4 or 5 showed little or no improvement, or deteriorated following rehabilitation. Hospitalizations were reduced following rehabilitation only in subjects with MRC dyspnoea grade 2, 3 or 4 (P < 0.05).

Conclusions:  The response to pulmonary rehabilitation in subjects with IPF varies depending on the MRC grade of dyspnoea, with little benefit being observed in subjects with severe functional limitation.
Global histone H3 lysine 27 (H3K27) methylation levels and their prognostic relevance in renal cell carcinoma
Authors: Rogenhofer Sebastian , Kahl Philip , Mertens Claudia , Hauser Stefan , Hartmann Wolfgang , Büttner Reinhard , Müller Stefan C. , von Ruecker Alexander , Ellinger Jörg
Published: August 2011

What’s known on the subject? and What does the study add?

Epigenetic alterations are important during carcinogenesis, and earlier studies suggested that global histone modification levels are predictive for patients’ outcome in various tumor entities.

We demonstrate that H3K27me1 and H3K27me3 are markers of progression‐free survival in patients with renal cell carcinoma.

OBJECTIVE

• To evaluate if histone H3 lysine 27 (H3K27) methylation plays a role in renal cell carcinoma (RCC) tissue and whether its expression is a predictor of cancer recurrence in RCC.

MATERIALS AND METHODS

• A tissue microarray (TMA) with 193 RCC specimens (comprising 142 clear‐cell, 31 papillary, 10 chromophobe and 10 sarcomatoid RCC), 10 oncocytoma tissue specimens and a TMA with 30 benign renal tissue samples were stained with antibodies against H3K27‐monomethyl (H3K27me1), H3K27‐dimethyl (H3K27me2) and H3K27‐trimethyl (H3K27me3).

• Sections were scored according to staining intensity and the proportion of epithelial cells showing nuclear staining.

• H3K27 methylation levels were correlated with established clinical‐pathological variables (tumour‐node‐metastasis [TNM] stage, Fuhrman grade) and progression‐free/cancer‐specific survival.

RESULTS

• H3K27me1/‐me2/‐me3 staining was significantly more intense in papillary RCC then in clear‐cell RCC.

• H3K27me3 levels were higher in oncocytoma than in RCC.

• H3K27me1/‐me2/‐me3 methylation levels were inversely correlated with Fuhrman grading and pT‐stage.

• Global H3K27me1/‐me2/‐me3 methylation levels were always higher in benign renal tissue than in RCC with tumour relapse (H3K27me1 P < 0.001, H3K27me2 P= 0.032, H3K27me3 P= 0.004).

• Progression‐free survival was shorter in patients with lower levels of H3K27me1 and H3K27me3 in the univariate analysis. The newly created H3K27me score (combining the staining levels of the single modifications) was a significant and independent predictor of RCC progression‐free survival.

CONCLUSION

• The present study on H3K27‐methylation supports the hypothesis that global histone modifications are potential markers of cancer prognosis in RCC. One reason could be that decreased H3K27 indicates transcriptional activation and therefore predicts cancer activation.
Survival after radical cystectomy of non‐bilharzial squamous cell carcinoma vs urothelial carcinoma: a competing‐risks analysis
Authors: Abdollah Firas , Sun Maxine , Jeldres Claudio , Schmitges Jan , Thuret Rodolphe , Djahangirian Orchidee , Tian Zhe , Shariat Shahrokh F. , Perrotte Paul , Montorsi Francesco , Karakiewicz Pierre I.
Published: August 2011

Study Type – Therapy (case series)

Level of Evidence 4

What's known on the subject? and What does the study add?

To date, there is controversy about the impact of histological subtype of bladder cancer (nonbilharzial squanous cell carcinoma vs. urothelial carcinoma) on cancer control outcomes.

Our study shows that the histological subtype may have an impact on the stage of bladder cancer at presentation. However, after adjusting to stage, the histological subtype has no impact on cancer control outcomes.

OBJECTIVES

To test the effect of histological subtype (NBSCC vs UC) on cancer‐specific mortality (CSM), after adjusting for other‐cause mortality (OCM).

In Western countries, non‐bilharzial squamous cell carcinoma (NBSCC) is the second most common histological subtype in bladder cancer (BCa) after urothelial carcinoma (UC).

PATIENTS AND METHODS

We identified 12 311 patients who were treated with radical cystectomy (RC) between 1988 and 2006, within 17 Surveillance, Epidemiology and End Results (SEER) registries.

Univariable and multivariable competing‐risks analyses tested the relationship between histological subtype and CSM, after accounting for OCM.

Covariates consisted of age, sex, year of surgery, race, pathological T and N stages, as well as tumour grade.

RESULTS

Histological subtype was NBSCC in 614 (5%) patients vs UC in 11 697 (95%) patients.

At RC, the rate of non‐organ confined (NOC) BCa was higher in NBSCC patients than in their UC counterparts (71.7% vs 52.2%; P < 0.001).

After adjustment for OCM, The 5‐year cumulative CSM rates were 25.0% vs 19.8% (P= 0.2) for patients with NBSCC vs UC organ confined (OC) BCa, respectively. The same rates were 46.3% vs 49.3% in patients with NOC BCa (P= 0.1).

In multivariable competing‐risks analyses, histological subtype (NBSCC vs UC) failed to achieve independent predictor status of CSM in patients with OC (hazard ratio, 1.2; P= 0.06) or NOC BCa (hazard ratio, 1.1; P= 0.1).

CONCLUSIONS

At RC, the rate of NOC BCa is higher in NBSCC patients than in their UC counterparts.

Despite a more advanced stage at surgery, NBSCC histological subtype is not associated with a less favourable CSM than UC histological subtype, after accounting for OCM and the extent of the disease (OC vs NOC).
RESIGNED BUT SATISFIED: THE NEGATIVE IMPACT OF PUBLIC SERVICE MOTIVATION AND RED TAPE ON WORK SATISFACTION
Authors: GIAUQUE DAVID , RITZ ADRIAN , VARONE FRÉDÉRIC , ANDERFUHREN‐BIGET SIMON
Published: August 2011

This article examines the relationship between red tape, Public Service Motivation (PSM) and a particular work outcome labelled ‘resigned satisfaction’. Using data from a national survey of over 3754 public servants working at the municipal level in Switzerland, this study shows the importance of looking more closely at the concept of work satisfaction and, furthermore, of thoroughly investigating the impact of the different PSM dimensions on work outcomes. Unsurprisingly, research findings show that red tape is the most important predictor of resignation. Nevertheless, when PSM dimensions are analysed separately, results demonstrate that ‘commitment to public interest/civic duty’ and, to a lesser extent, ‘attraction to policy‐making’ decrease resignation, whereas ‘compassion’ and ‘self‐sacrifice’ increase it. This study thus highlights some of the negative (or undesirable) effects of PSM that have not been previously addressed in PSM literature.
VOICE AND CHOICE IN HEALTH CARE IN ENGLAND: UNDERSTANDING CITIZEN RESPONSES TO DISSATISFACTION
Authors: DOWDING KEITH , JOHN PETER
Published: August 2011

Using data from a five‐year online survey the paper examines the effects of relative satisfaction with health services on individuals' voice‐and‐choice activity in the English public health care system. Voice is considered in three parts – individual voice (complaints), collective voice voting and participation (collective action). Exercising choice is seen in terms of complete exit (not using health care), internal exit (choosing another public service provider) and private exit (using private health care). The interaction of satisfaction and forms of voice and choice are analysed over time. Both voice and choice are correlated with dissatisfaction with those who are unhappy with the NHS more likely to privately voice and to plan to take up private health care. Those unable to choose private provision are likely to use private voice. These factors are not affected by items associated with social capital – indeed, being more trusting leads to lower voice activity.
Conservation Laws, Hamiltonian Structure, Modulational Instability Properties and Solitary Wave Solutions for a Higher‐Order Model Describing Nonlinear Internal Waves
Authors: Swaters G. E. , Dosser H. V. , Sutherland B. R.
Published: August 2011

Recent theoretical advances in connecting the wave‐induced mean flow with the conserved pseudomomentum per unit mass has permitted the first rational derivation of a model that describes the weakly nonlinear propagation of internal gravity plane waves in a continuously stratified fluid. Depending on the particular parameter regime examined the new model corresponds to an extended bright or dark derivative nonlinear Schrödinger equation or an extended complex‐valued modified Korteweg‐de Vries or Sasa–Satsuma equation. Mass, momentum, and energy conservation laws are derived. A noncanonical infinite‐dimensional Hamiltonian formulation of the model is introduced. The modulational stability characteristics associated with the Stokes wave solution of the model are described. The bright and dark solitary wave solutions of the model are obtained.
National Externalities and Path‐dependence in Technological Change: An Empirical Test
Authors: Mancusi Maria Luisa
Published: August 2011

This paper provides an empirical assessment of the relevance of the hypothesis of increasing returns and path‐dependence in technological development by looking at its implications on the evolution of the technological specialization profiles of advanced countries. A recontracting process is used to formalize the idea that when national externalities are strong, countries should display the tendency to specialize in selected technologies. No evidence of such tendency towards increasing specialization is found in the data.
Reflections on the Architecture of the EU after the Treaty of Lisbon: The European Judicial Approach to Fundamental Rights
Authors: Morano‐Foadi Sonia , Andreadakis Stelios
Published: August 2011

This paper, based on an overarching project, focuses on the role of the Court of Justice of the EU (CJEU) (also known as the Luxembourg Court) in shaping legal integration in Europe. The entry into force of the Lisbon Treaty, the new legally binding nature of the EU Charter of Fundamental Rights and the future EU's accession to the European Convention for the Protection of Human Rights and Fundamental Freedoms (ECHR) bring significant changes to the fundamental rights discourse within the European Union. These developments allow the enhancement of human rights protection within the EU. Based on empirical data collected through interviews with the Court of Justice's judges and Advocates General and recent case‐law, the paper offers original insights into the post‐Lisbon era of regional integration and reflects on the impact of the Charter on the CJEU jurisprudence.