bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of proton pump inhibitors increased the risk of hip fracture: a population‐based case–control study
Authors: Chiu Hui‐Fen , Huang Ya‐Wen , Chang Chih‐Ching , Yang Chun‐Yuh
Published: September 2010

Purpose

To investigate whether the use of proton pump inhibitor (PPIs) was associated with an increased risk of hip fracture.

Methods

We conducted a population‐based case–control study in Taiwan. Data were retrospectively collected from the Taiwan National health Insurance Research Database. Cases included all patients with a newly diagnosed of hip fracture in 2005 and 2006 (n = 1241). The controls were pair matched to cases by age, sex, and index date. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using multiple logistic regression.

Results

Having been prescribed more than 28 defined daily dose (DDDs) of PPIs was associated with an increased risk for hip fracture in multivariate analyses (adjustments for matching variables and medication use) (at 29–70 DDDs, OR = 1.67, 95% CI = 1.11–2.51 and at >70 DDDs, OR = 2.51, 95% CI = 1.77–3.55). There was a significant trend toward increasing hip fracture risk with increasing cumulative DDDs of PPIs (p for trend <0.0001).

Conclusions

This study provides evidence that PPIs use is associated with an increased risk of hip fracture in a dose–response manner. Copyright © 2010 John Wiley & Sons, Ltd.
Use of herbal products among 392 Italian pregnant women: focus on pregnancy outcome
Authors: Cuzzolin Laura , Francini‐Pesenti Francesco , Verlato Giovanna , Joppi Marco , Baldelli Paola , Benoni Giuseppina
Published: September 2010

Purpose

The present study aimed to explore the use of herbal products among a sample of Italian pregnant women and the possible influence of herbal consumption on pregnancy outcome.

Methods

The study was conducted over a 10‐month period (2 days a week, from January to October 2009) at the Maternity wards of Padua and Rovereto Hospital. Data were collected through a face‐to‐face interview on the basis of a prestructured questionnaire including socio‐demographic characteristics of the enrolled subjects, specific questions on herbal use, information about pregnancy and newborn.

Results

In total, 392 interviews were considered. One hundred and nine out of 392 women (27.8%) reported to have been taking one or more herbal products during pregnancy, in the 36.7% of cases throughout all pregnancy. The most frequently herbs taken by interviewees were chamomile, licorice, fennel, aloe, valerian, echinacea, almond oil, propolis, and cranberry. Four out of 109 women (3.7%) reported side‐effects: constipation after a tisane containing a mix of herbs, rash and itching after local application of aloe or almond oil. The decision to use herbal products was mainly based on personal judgement and on the conviction that these natural substances would be safer than traditional medicines. Users were more often affected by morbidities pregnancy‐related and their neonates were more frequently small for their gestational age. An higher incidence of threatening miscarriages and preterm labours was observed among regular users of chamomile and licorice.

Conclusions

This research underlines that the use of herbal products during pregnancy is common among Italian women, not always appropriate and in some cases potentially harmful. Copyright © 2010 John Wiley & Sons, Ltd.
Identification of gifted students with learning disabilities in a Response‐to‐Intervention era
Authors: Crepeau‐Hobson Franci , Bianco Margarita
Published: September 2010

The identification of children who are twice‐exceptional—those who are gifted and have concomitant learning disabilities (LDs)—has historically posed a number of challenges for school psychologists and other school personnel. With the reauthorization of the Individuals With Disabilities Education Act and the shift to the use of a Response‐to‐Intervention (RtI) model to identify students with LDs, the task of identifying those who are twice exceptional is even more daunting. This article proposes an integrated model for the identification of gifted children with LDs that blends standardized assessment methods with practices consistent with RtI. This balanced approach brings together the best of both worlds to more accurately identify twice‐exceptional students and better meet their educational needs. © 2010 Wiley Periodicals, Inc.
Quality of life and physical performance and activity of breast cancer patients after adjuvant treatments
Authors: Penttinen H. M. , Saarto T. , Kellokumpu‐Lehtinen P. , Blomqvist C. , Huovinen R. , Kautiainen H. , Järvenpää S. , Nikander R. , Idman I. , Luoto R. , Sievänen H. , Utriainen M. , Vehmanen L. , Jääskeläinen A. S. , Elme A. , Ruohola Johanna , Luoma M. , Hakamies‐Blomqvist L.
Published: September 2010

Objective: The study aimed at investigating the quality of life (QoL) and physical performance and activity, and their interrelations, in Finnish female breast cancer patients shortly after adjuvant treatments.

Methods: A total of 537 disease‐free breast cancer survivors aged 35–68 years were surveyed at the beginning of a one year randomized exercise intervention. The patients were interviewed using EORTC QLQ‐C30, FACIT‐F, RBDI, and WHQ (for vasomotor symptoms) questionnaires. Physical performance was tested by a 2 km walking test. Physical activity was measured by a questionnaire and a prospective two‐week diary. Multivariate analysis was used to study the factors associated with QoL.

Results: About 26% of the patients were rated as depressed, 20.4% as fatigued, and 82% suffered from menopausal symptoms. The global QoL was lower than in general population (69.4 vs 74.7, p<0.001). About 62% of the walking test results were below the population average. Fatigue (p<0.001), depression (p<0.001), body mass index (p = 0.016) and comorbidity (p = 0.032) impaired, and physical activity (p = 0.003) improved QoL. Physical activity level correlated positively to physical performance (r = −0.274, p<0.0001).

Conclusions: The QoL of the patients shortly after adjuvant treatments was impaired and the physical performance poor as compared to general population. In particular, depression and fatigue were related to impaired QoL. Physical performance and activity level were the only factors that correlated positively to QoL. Thus, physical exercise could be useful in rehabilitation of cancer survivors, especially for depressed and fatigued patients. Copyright © 2010 John Wiley & Sons, Ltd.
The High‐Pressure Characterization of Energetic Materials: 2‐Methyl‐5‐Nitramino‐2H‐Tetrazole
Authors: Ciezak Jennifer A.
Published: September 2010

The isothermal structural properties, equation of state, and vibrational dynamics of 2MNT were studied under high‐pressure using synchrotron XRD and optical Raman and IR microspectroscopy. Analysis of the XRD patterns revealed no indication of a phase transition to near 15 GPa and the pressure‐volume isotherm remained smooth to 15 GPa. Near 15 GPa, significant sample damage was observed from the X‐ray beam which precluded the acquisition of patterns above this pressure. XRD and Raman spectroscopic measurements showed the monoclinic ambient condition phase of 2MNT remains the dominant phase to near 20 GPa, although a shift of the NO2IR active vibrational modes to lower frequencies suggested a subtle geometry modification not reflected in the XRD data.
Changes in stepping response to lateral perturbations immediately following a single bout of physical activity
Authors: Egerton Thorlene , Brauer Sandra G. , Cresswell Andrew G.
Published: September 2010

Background and Purpose. Fatiguing exercise can adversely alter postural stability and therefore may contribute to falling. However, older adults rarely perform exercise to fatigue. This study aimed to determine whether undertaking a single bout of moderate‐intensity physical activity, similar to that experienced during daily activity or rehabilitation, altered the ability to recover balance with an outward step response to a lateral perturbation. Methods. Thirty‐four healthy older adults (mean: 76 ± 5 years) and 31 healthy young adults (29 ± 6 years) underwent a 14‐minute, self‐paced, moderate‐intensity physical activity protocol. Before and immediately after the protocol, their responses to lateral waist‐pull perturbations were recorded. For participants who used a single outward step response before and after the perturbation, the changes to the timing of the step phases and the hip abductor muscle activity onsets were compared. Results. Young adults responded with an outward step in 55% of trials before and 70% after activity, whereas this frequency was 35% before and 36% after among older adults. When performed, the timing of steps and muscle activity onsets were not adversely altered following the physical activity in either group, apart from a slightly later stance limb gluteus medius onset after activity, found in both groups. Conclusions. Before and after activity, older adults responded with a single outward step to arrest a fall less frequently than young adults. This may place older adults at risk of overbalancing. However, when responding with this strategy, both young and older adults demonstrated few changes immediately following moderate‐intensity physical activity compared with before. They appear to be not adversely affected by moderate physical activity. Copyright © 2010 John Wiley & Sons, Ltd.
Stabilization of mutant p53 via alkylation of cysteines and effects on DNA binding
Authors: Kaar Joel L. , Basse Nicolas , Joerger Andreas C. , Stephens Elaine , Rutherford Trevor J. , Fersht Alan R.
Published: September 2010

Oncogenic mutations inactivate the tumor suppressor p53 by lowering its stability or by weakening its binding to DNA. Alkylating agents that reactivate mutant p53 are currently being explored for cancer therapy. We have discovered ligands containing an α,β‐unsaturated double bond, characteristic of Michael acceptors, that bind covalently to generic cysteine sites in the p53 core domain. They raised the melting temperature of the core domain of wild‐type p53 and the hotspot mutants R175H, Y220C, G245S, R249S, and R282 by up to 3°C. Analysis of the relative reactivity of the cysteines in p53 by mass spectrometry found that C124 and C141 react first, followed by C135, C182, and C277, and eventually C176 and C275. Post‐translational modifications of cysteines are known to be involved in regulation of other transcription factors. Modification of C277, which sits on the DNA‐binding surface, may, for example, play a role in regulating p53 activity in cells in response to environmental cues. We found that the modifications progressively reduced DNA‐binding activity of full‐length p53. In light of these results, it is likely that the anticancer activity of the alkylating drugs works via a nontranscriptional activity of p53.
Conformational space search of Neuromedin C using replica exchange molecular dynamics and molecular dynamics
Authors: Sharma Parul , Singh Parvesh , Bisetty Krishna , Rodriguez Alex , Perez Juan J.
Published: September 2010

The present study involves the utilization of replica exchange molecular dynamics (REMD) methodology to explore the conformational space of Neuromedin C (NMC) using implicit (REMDimplicit) and explicit (REMDexplicit) water models. Comparison of the structures obtained from these simulations indicate that REMDexplicit trajectory display a greater tendency to induce β‐turns and bent structures as compared to those obtained from the REMDimplicit simulation. Moreover, two additional MD trajectories performed using Langevin (MDLang) and Berendsen (MDBerend) algorithms under generalized born (GB) solvent conditions were also suitably competent to sample similar kinds of conformations, although the extent of beta turns was low compared to those observed in REMDexplicit simulation. Finally, the comparison of results obtained from all the trajectories and those derived from the NMR studies of Ni(II) complex of NMC indicates that the REMD under explicit conditions is more efficient in sampling the conformations, and show good agreement with the experimental results. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.
Solid‐state lighting: ‘The case’ 10 years after and future prospects
Authors: Haitz Roland , Tsao Jeffrey Y.
Published: September 2010

Ten years ago, a white paper titled “The Case for a National Research Program on Semiconductor Lighting” outlined the promise and potential of semiconductor light‐emitting diodes (LEDs) for general illumination. Since then, investments in the now‐renamed field of solid‐state lighting (SSL) have accelerated and considerable progress has been made, not always in the directions envisioned at the time. In this paper, two of the original four authors comment on the white paper's hits and misses, while making the original white paper available archivally as supplemental online material. Finally, we make new predictions for the coming 10–20 years.
Spontaneous emission rate of green strain‐compensated InGaN/InGaN LEDs using InGaN substrate
Authors: Park Seoung‐Hwan , Moon Yong‐Tae , Lee Jeong Sik , Kwon Ho Ki , Park Joong Seo , Ahn Doyeol
Published: September 2010

Optical properties of strain‐compensated InGaN/InGaN quantum well (QW) structures using a InGaN substrate are investigated using the multiband effective mass theory. These results are compared with those of conventional InGaN/GaN QW structures using a GaN substrate. The strain‐compensated QW structure shows that a smaller well thickness is needed to obtain the transition wavelength of 530 nm than the InGaN/GaN QW structure. The spontaneous emission peak of a strain‐compensated QW structure is shown to be much larger than that of a conventional QW structure. This is mainly attributed to the fact that the internal field is reduced due to the decrease in the lattice mismatch with a substrate.
Resistance and mesoscopic fluctuations in graphene
Authors: Mahelona Keoni K. , Kaiser Alan B. , Skákalová Viera
Published: September 2010

We investigate the mesoscopic resistance fluctuations (MRFs) that, as we showed previously, cause the exponentially decaying low‐temperature resistance anomaly in graphene monolayers. We determine autocorrelation functions and power spectra for the MRFs, finding that the fluctuations have shorter periods (as a function of gate voltage) near the neutrality point. We also investigate the origin of the sharp increase of the resistance of graphene on a Si/SiO2 substrate at higher temperatures and at higher charge carrier densities. We show that a very good description of this increase is given by scattering by the experimentally observed graphene zone‐boundary phonons of energy 160 meV (that cause current saturation in carbon nanotubes) and by lower energy phonons (70 meV) that make a smaller contribution.

magnified image

An example of mesoscopic resistance fluctuations as a function of gate voltage measured from the neutrality point (with resistance at temperature 51 K subtracted).
The role of linear wave refraction in the transient eddy–mean flow response to tropical Pacific SST anomalies
Authors: Harnik N. , Seager R. , Naik N. , Cane M. , Ting M.
Published: September 2010

The midlatitude response to tropical Pacific SST anomalies involves changes in transient eddy propagation, but the processes leading to the transient eddy changes are still not clear. In a recent study, we used a series of controlled general circulation model (GCM) experiments in which an imposed tropical Pacific sea‐surface temperature (SST) anomaly is turned on abruptly and the response is analyzed in terms of its high‐ and low‐frequency parts, to show that the changes in transient eddies induced by El Niño Southern Oscillation (ENSO) arise from changes in wave refraction on the altered mean flow. In this work, we use a quasi‐geostrophic linear model and a linear stationary wave model, to interpret the GCM experiments and obtain the sequence of events that lead from a tropical SST anomaly to the quasi‐equilibrium change in the mean and transient atmospheric circulation. The initial direct response of the mean flow is confined to the tropical and subtropical Pacific, similar to what is obtained from a stationary wave model. This tropical–subtropical mean flow change initiates a transient eddy response, which induces a midlatitude mean flow anomaly. The wave–mean flow system evolves towards a state in which the eddy anomalies maintain the mean flow anomalies, allowing them to persist. It is further shown that, while eddy momentum fluxes persistently accelerate and decelerate the subtropical and midlatitude mean flow, the eddy heat flux effect on the zonal mean flow is much more variable, and only marginally significant. The linear quasi‐geostrophic model calculations capture the evolution of eddy momentum flux anomalies equatorwards of 60°N quite well, suggesting linear wave refraction can explain the midlatitude ENSO anomalies. However, other processes, like stationary waves or changes in the nonlinear stage of eddy life cycles, are needed to explain the ENSO‐related anomalies at high latitudes, polewards of around 60°N. Copyright © 2010 Royal Meteorological Society
Two‐dimensional guidelines for measurement system indices
Authors: White T. Kevin , Borror Connie M.
Published: September 2010

In this paper, we review two common measurement system indices and a common process capability index. With some simple plots, it will be shown that the traditional guidelines for these measurement system indices can often misdirect improvement efforts. By taking advantage of the relationship between the measurement system indices and the process capability index, two‐dimensional guidelines that can be used as an alternative to the traditional guidelines are developed. These two‐dimensional guidelines are intended to help address adequacy of the measurement system and better direct improvement efforts to where there will be the most benefit. Copyright © 2010 John Wiley & Sons, Ltd.
GPU‐based efficient realistic techniques for bleeding and smoke generation in surgical simulators
Authors: Halic Tansel , Sankaranarayanan Ganesh , De Suvranu
Published: September 2010

Background

In actual surgery, smoke and bleeding due to cauterization processes provide important visual cues to the surgeon, which have been proposed as factors in surgical skill assessment. While several virtual reality (VR)‐based surgical simulators have incorporated the effects of bleeding and smoke generation, they are not realistic due to the requirement of real‐time performance. To be interactive, visual update must be performed at at least 30 Hz and haptic (touch) information must be refreshed at 1 kHz. Simulation of smoke and bleeding is, therefore, either ignored or simulated using highly simplified techniques, since other computationally intensive processes compete for the available Central Processing Unit (CPU) resources.

Methods

In this study we developed a novel low‐cost method to generate realistic bleeding and smoke in VR‐based surgical simulators, which outsources the computations to the graphical processing unit (GPU), thus freeing up the CPU for other time‐critical tasks. This method is independent of the complexity of the organ models in the virtual environment. User studies were performed using 20 subjects to determine the visual quality of the simulations compared to real surgical videos.

Results

The smoke and bleeding simulation were implemented as part of a laparoscopic adjustable gastric banding (LAGB) simulator. For the bleeding simulation, the original implementation using the shader did not incur noticeable overhead. However, for smoke generation, an input/output (I/O) bottleneck was observed and two different methods were developed to overcome this limitation. Based on our benchmark results, a buffered approach performed better than a pipelined approach and could support up to 15 video streams in real time. Human subject studies showed that the visual realism of the simulations were as good as in real surgery (median rating of 4 on a 5‐point Likert scale).

Conclusions

Based on the performance results and subject study, both bleeding and smoke simulations were concluded to be efficient, highly realistic and well suited to VR‐based surgical simulators. Copyright © 2010 John Wiley & Sons, Ltd.
Quasi‐equilibrium conditions of urban gravel‐bed stream channels in southern Ontario, Canada
Authors: Annable W. K. , Watson C. C. , Thompson P. J.
Published: September 2010

Urban gravel‐bed stream channels in southern Ontario, Canada identified to be in a state of quasi‐equilibrium have been studied over the past 15 years and compared against rural gravel bed stream channels of the same hydrophysiographic region. Bankfull width and depth versus bankfull discharge were not found to increase as a function of increasing urbanization as has been found in many other studies. The observed annual frequency of bankfull discharge was typically less than a 1‐year return period with many sites ranging between 2 and 18 bankfull events per year with higher intensity and shorter duration urban flood responses, which further identified significant limitations in using annual peak discharge methods for predicting morphological forming flows in urban watersheds.

The cumulative volume of bankfull and larger flood events from the urban stream channels were very similar to the same annual event volumes in the rural comparison study reaches. Bed material supply was found to decrease with increasing urbanization and the reduction in bed material supply appears to be off‐set by the smaller bankfull channel width, depth and access to floodplains during large flood events. Field evidence may also suggest a even greater reduction in channel width trajectory, relative to the rural setting, with expansive floodplains to maintain quasi‐equilibrium conditions as bed material supply continues to decrease with increased anthropogenic activity. Copyright © 2010 John Wiley & Sons, Ltd.
12‐GHz Thin‐Film Transistors on Transferrable Silicon Nanomembranes for High‐Performance Flexible Electronics
Authors: Sun Lei , Qin Guoxuan , Seo Jung‐Hun , Celler George K. , Zhou Weidong , Ma Zhenqiang
Published: September 2010

Multigigahertz flexible electronics are attractive and have broad applications. A gate‐after‐source/drain fabrication process using preselectively doped single‐crystal silicon nanomembranes (SiNM) is an effective approach to realizing high device speed. However, further downscaling this approach has become difficult in lithography alignment. In this full paper, a local alignment scheme in combination with more accurate SiNM transfer measures for minimizing alignment errors is reported. By realizing 1 μm channel alignment for the SiNMs on a soft plastic substrate, thin‐film transistors with a record speed of 12 GHz maximum oscillation frequency are demonstrated. These results indicate the great potential of properly processed SiNMs for high‐performance flexible electronics.
Engineering Nanocomposite Materials for Cancer Therapy
Authors: Minelli Caterina , Lowe Stuart B. , Stevens Molly M.
Published: September 2010

Cancer accounted for 13% of all deaths worldwide in 2005. Although early detection is critical for the successful treatment of many cancers, there are sensitivity limitations associated with current detection methodologies. Furthermore, many traditional anticancer drug treatments exhibit limited efficacy and cause high morbidity. The unique physical properties of nanoscale materials can be utilized to produce novel and effective sensors for cancer diagnosis, agents for tumor imaging, and therapeutics for cancer treatment. Functionalizing inorganic nanoparticles with biocompatible polymers and natural or rationally designed biomolecules offers a route towards engineering responsive and multifunctional composite systems. Although only a few such innovations have reached human clinical trial to date, nanocomposite materials based on functionalized metal and semiconductor nanoparticles promise to transform the way cancer is diagnosed and treated. This review summarizes the current state‐of‐the‐art in the development of inorganic nanocomposites for cancer‐related applications.
Perylene‐Labeled Silica Nanoparticles: Synthesis and Characterization of Three Novel Silica Nanoparticle Species for Live‐Cell Imaging
Authors: Blechinger Julia , Herrmann Rudolf , Kiener Daniel , García‐García F. Javier , Scheu Christina , Reller Armin , Bräuchle Christoph
Published: September 2010

The increasing exposure of humans to nanoscaled particles requires well‐defined systems that enable the investigation of the toxicity of nanoparticles on the cellular level. To facilitate this, surface‐labeled silica nanoparticles, nanoparticles with a labeled core and a silica shell, and a labeled nanoparticle network—all designed for live‐cell imaging—are synthesized. The nanoparticles are functionalized with perylene derivatives. For this purpose, two different perylene species containing one or two reactive silica functionalities are prepared. The nanoparticles are studied by transmission electron microscopy, widefield and confocal fluorescence microscopy, as well as by fluorescence spectroscopy in combination with fluorescence anisotropy, in order to characterize the size and morphology of the nanoparticles and to prove the success and homogeneity of the labeling. Using spinning‐disc confocal measurements, silica nanoparticles are demonstrated to be taken up by HeLa cells, and they are clearly detectable inside the cytoplasm of the cells.
Studying software evolution of large object‐oriented software systems using an ETGM algorithm
Authors: Kpodjedo Segla , Ricca Filippo , Galinier Philippe , Antoniol Giuliano , Guéhéneuc Yann‐Gaël
Published: September 2010

Analyzing and understanding the evolution of large object‐oriented software systems is an important but difficult task in which matching algorithms play a fundamental role. An error‐tolerant graph matching (ETGM) algorithm can identify evolving classes that maintain a stable structure of relations (associations, inheritances, and aggregations) with other classes and thus likely constitute the backbone of the system. Therefore, to study the evolution of class diagrams, we first develop a novel ETGM algorithm, which improves the performance of our previous algorithm. Second, we describe the process of building an oracle to validate the results of our approach to solve the class diagram evolution problem. Third, we report for the new algorithm the impact of its parameters on the F‐measure summarizing precision (quantifying the exactness of the solution) and recall (quantifying the completeness of the solution). Finally, with tuned parameters, we carry out and report an extensive empirical evaluation of our algorithm using small (Rhino), medium (Azureus and ArgoUML), and large systems (Mozilla and Eclipse). We thus show that this novel algorithm is scalable, stable and has better time performance than its earlier version. Copyright © 2010 John Wiley & Sons, Ltd.
Highly practical amino acid and alkaloid synthesis using designer chiral phase transfer catalysts as high‐performance organocatalysts
Authors: Maruoka Keiji
Published: September 2010

A series of chiral quaternary ammonium salts derived from commercially available (R)‐ or (S)‐binaphthol have been designed as new C2‐symmetric chiral phase transfer catalysts. In order to realize the flexible design of these phase transfer catalysts, the combinatorial design approach has been developed. These chiral high‐performance organocatalysts have been successfully applied to the highly practical asymmetric synthesis of various amino acid derivatives including α‐alkyl and α,α‐dialkyl‐α‐amino acids in addition to alkaloids. © 2010 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 10: 254–259; 2010: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.201000019
In vitro and in vivo gene delivery with tailor‐designed aminofullerenes
Authors: Nakamura Eiichi , Isobe Hiroyuki
Published: September 2010

Long‐range studies on the chemistry of two strained ring systems, cyclopropanes and fullerenes, converged on a challenge in biology, in vivo gene delivery. The new protocol of gene delivery employing a tailor‐designed amino fullerene represents the third protocol after the two using virus and lipid delivery agents, none of which are universally useful. The amino fullerene delivers an EGFP and an insulin‐2 gene to mice with efficiency superior to and selectivity distinct from those achieved by the conventional lipid‐based delivery agents. The studies demonstrate the power of organic synthesis as driven by scientifically and socially important subjects. © 2010 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 10: 260–270; 2010: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.201000021
Lessons from total synthesis of hybrid natural products
Authors: Suzuki Keisuke
Published: September 2010

There are a vast number of interesting and useful compounds that are readily found in nature. Mother Nature has acquired ingenious ways of generating molecular diversity in living cells responsible for regulation of various biochemical events. This has inspired research into the synthesis of biologically active compounds for use as antibiotics or in cancer therapy, for example. This account provides an overview of the work performed in the total synthesis of hybrid natural products and the interesting synthetic mechanisms encountered along the way. © 2010 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.201000030
Prenatal diagnosis of lobar bronchial atresia
Authors: Bonnefoy C. , Blanc P. , Coste K. , Delabaere A. , Dechelotte P. J. , Laurichesse‐Delmas H. , Labbe A. , Jacquetin B. , Lemery D. , Sapin V. , Gallot D.
Published: September 2010

We report three cases of fetal lobar bronchial atresia referred to our Fetal Medicine Center during the mid‐trimester of pregnancy over the last 15 years. Lobar bronchial atresia can mimic a main stem bronchial atresia on mid‐trimester ultrasound examination as it induces extensive lobar enlargement, major mediastinal shift and eversion of the diaphragm. It was associated with severe pulmonary hypoplasia in all three cases, even though polyhydramnios and ascites were absent in two. Termination of pregnancy was performed at parental request after extensive counseling in each of the cases and necropsy confirmed one or two enlarged lung lobes leading to major compression of the remaining lobe(s) of the ipsilateral lung, the contralateral lung and the heart. No other anomalies were observed and the karyotype was normal in all cases. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
First‐trimester Down syndrome screening: pregnant women's knowledge
Authors: Dahl K. , Hvidman L. , Jørgensen F. S. , Henriques C. , Olesen F. , Kjaergaard H. , Kesmodel U. S.
Published: September 2010

Objectives

The primary aim of this study was to assess pregnant women's knowledge of first‐trimester combined Down syndrome screening in a setting of required informed consent. As the secondary aim, we wanted to identify relevant differences in knowledge level among subgroups of pregnant women, including those informed in different ways about prenatal examinations.

Methods

Data stem from a population‐based cross‐sectional questionnaire study including 15 multiple‐choice questions assessing knowledge of different aspects of screening. Included were 6427 first‐trimester pregnant women from three Danish obstetric departments offering prenatal screening free of charge. Both participants and non‐participants in the screening program were included. The results are based on 4095 responders (64%). Differences between subgroups were examined using chi‐squared tests and logistic regression analysis. Estimates are stated with 95% CI.

Results

The majority of the participants (87.6 (86.6–88.6)% to 92.6 (91.7–93.3)%) correctly identified the test concept and the main condition being screened for. Fewer participants (16.4 (15.3–17.6)% to 43.3 (41.8–44.8)%) correctly recognized test accuracy and the potential risk of adverse findings other than Down syndrome. Knowledge level was positively associated with length of education (adjusted ORs 1.0 (0.8–1.4) to 3.9 (2.4–6.4)) and participation in the screening program (adjusted OR 0.9 (0.6–1.3) to 5.9 (3.9–8.8)). Participation in an individual information session was weakly associated with more knowledge.

Conclusion

The majority of the pregnant women correctly identified the test concept and the main condition being screened for. The pregnant women were found less knowledgeable on test accuracy and drawbacks. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
Four‐chamber view and ‘swing technique’ (FAST) echo: a novel and simple algorithm to visualize standard fetal echocardiographic planes
Authors: Yeo L. , Romero R. , Jodicke C. , Oggè G. , Lee W. , Kusanovic J. P. , Vaisbuch E. , Hassan S.
Published: September 2010

Objective

To describe a novel and simple algorithm (four‐chamber view and ‘swing technique’ (FAST) echo) for visualization of standard diagnostic planes of fetal echocardiography from dataset volumes obtained with spatiotemporal image correlation (STIC) and applying a new display technology (OmniView).

Methods

We developed an algorithm to image standard fetal echocardiographic planes by drawing four dissecting lines through the longitudinal view of the ductal arch contained in a STIC volume dataset. Three of the lines are locked to provide simultaneous visualization of targeted planes, and the fourth line (unlocked) ‘swings’ through the ductal arch image (swing technique), providing an infinite number of cardiac planes in sequence. Each line generates the following plane(s): (a) Line 1: three‐vessels and trachea view; (b) Line 2: five‐chamber view and long‐axis view of the aorta (obtained by rotation of the five‐chamber view on the y‐axis); (c) Line 3: four‐chamber view; and (d) ‘swing line’: three‐vessels and trachea view, five‐chamber view and/or long‐axis view of the aorta, four‐chamber view and stomach. The algorithm was then tested in 50 normal hearts in fetuses at 15.3‐40 weeks' gestation and visualization rates for cardiac diagnostic planes were calculated. To determine whether the algorithm could identify planes that departed from the normal images, we tested the algorithm in five cases with proven congenital heart defects.

Results

In normal cases, the FAST echo algorithm (three locked lines and rotation of the five‐chamber view on the y‐axis) was able to generate the intended planes (longitudinal view of the ductal arch, pulmonary artery, three‐vessels and trachea view, five‐chamber view, long‐axis view of the aorta, four‐chamber view) individually in 100% of cases (except for the three‐vessels and trachea view, which was seen in 98% (49/50)) and simultaneously in 98% (49/50). The swing technique was able to generate the three‐vessels and trachea view, five‐chamber view and/or long‐axis view of the aorta, four‐chamber view and stomach in 100% of normal cases. In the abnormal cases, the FAST echo algorithm demonstrated the cardiac defects and displayed views that deviated from what was expected from the examination of normal hearts. The swing technique was useful for demonstrating the specific diagnosis due to visualization of an infinite number of cardiac planes in sequence.

Conclusions

This novel and simple algorithm can be used to visualize standard fetal echocardiographic planes in normal fetal hearts. The FAST echo algorithm may simplify examination of the fetal heart and could reduce operator dependency. Using this algorithm, inability to obtain expected views or the appearance of abnormal views in the generated planes should raise the index of suspicion for congenital heart disease. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
Simple targeted arterial rendering (STAR) technique: a novel and simple method to visualize the fetal cardiac outflow tracts
Authors: Yeo L. , Romero R. , Jodicke C. , Kim S. K. , Gonzalez J. M. , Oggè G. , Lee W. , Kusanovic J. P. , Vaisbuch E. , Hassan S.
Published: September 2010

Objective

To describe a novel and simple technique—simple targeted arterial rendering (STAR)—to visualize the fetal cardiac outflow tracts from dataset volumes obtained with spatiotemporal image correlation (STIC) and applying a new display technology (OmniView).

Methods

We developed a technique to image the outflow tracts by drawing three dissecting lines through the four‐chamber view of the heart contained in a STIC volume dataset. Each line generated the following plane: (a) Line 1: ventricular septum en face with both great vessels (pulmonary artery anterior to the aorta); (b) Line 2: pulmonary artery with continuation into the longitudinal view of the ductal arch; and (c) Line 3: long‐axis view of the aorta arising from the left ventricle. The pattern formed by all three lines intersecting approximately through the crux of the heart resembles a star. The technique was then tested in 50 normal fetal hearts at 15.3–40.4 weeks' gestation. To determine whether the technique could identify planes that departed from the normal images, we tested the technique in four cases with proven congenital heart defects (ventricular septal defect (VSD), transposition of great vessels, tetralogy of Fallot and pulmonary atresia with intact ventricular septum).

Results

The STAR technique was able to generate the intended planes in all 50 normal cases. In the abnormal cases, the STAR technique allowed identification of the VSD, demonstrated great vessel anomalies and displayed views that deviated from what was expected from the examination of normal hearts.

Conclusions

This novel and simple technique can be used to visualize the outflow tracts and ventricular septum en face in normal fetal hearts. Inability to obtain expected views or the appearance of abnormal views in the generated planes should raise the index of suspicion for congenital heart disease involving the great vessels and/or the ventricular septum. The STAR technique may simplify examination of the fetal heart and could reduce operator dependency. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
Ultrasound bioeffects in rats: quantification of cellular damage in the fetal liver after pulsed Doppler imaging
Authors: Pellicer B. , Herraiz S. , Táboas E. , Felipo V. , Simon C. , Pellicer A.
Published: September 2010

Objective

To determine whether pulsed Doppler examination of the ductus venosus in rat fetuses could damage exposed tissue.

Methods

On gestational day 18, the livers of a mean of approximately five fetuses per mother (n = 5.14, SD = 1.6), in a cohort of 35 pregnant female rats, were exposed individually to pulsed Doppler and these were considered the ‘exposed group’. The remaining fetuses in each pregnant rat (n = 5.16, SD = 2.1) formed the ‘control group’. We tested for 600, 300, 60, 20, 15, 10 and 3 s of exposure of the fetal ductus venosus and the damage was evaluated measuring a cell death index of apoptotic activity at 7 h post‐exposure (n = 16). In addition, subgroups of mothers were sacrificed at 2, 4, 5, 7, 12 and 24 h post‐exposure to determine when the damage appeared and disappeared and whether this depended on the exposure time.

Results

After exposure of 20 s or more, we observed significant damage, as assessed by caspase 3 activity (a marker of apoptotic activity related to tissue damage), in all cases; after 15 s of exposure, some samples presented damage (P = 0.4); there was no damage after 10 s or 3 s of exposure (P = 0.87 and P = 0.3, respectively). There was a positive linear correlation between apoptotic index and pulsed Doppler exposure time, (Pearson's coefficient = 0.324, P < 0.01). No liver still showed significant damage at 12 or 24 h post‐exposure (P > 0.05 and P > 0.4).

Conclusions

We observed reversible damage after pulsed Doppler imaging in an in‐vivo fetal liver tissue rat model and found that longer exposure times produced more tissue damage. We established that 10 s was the maximum exposure time to ensure absence of damage to tissue in this model. It would appear sensible to recommend expert supervision of pulsed Doppler imaging and to have intervals between subsequent examinations. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
Prenatal treatment of meconium peritonitis with urinary trypsin inhibitor
Authors: Izumi Y. , Sato Y. , Kakui K. , Tatsumi K. , Fujiwara H. , Konishi I.
Published: September 2010

We describe a case of congenital meconium peritonitis with progressive fetal ascites and polyhydramnios. Fetal ascites could be only partially reduced on paracentesis at 29 weeks' gestation, and it subsequently increased. Urinary trypsin inhibitor (UTI), a physiological anti‐inflammatory substance, was administered into the fetal abdominal cavity at a second paracentesis performed at 35 weeks' gestation. There was a significant amount of fetal ascites remaining 1 day after the second paracentesis, but this completely resolved within 5 days. A healthy infant was delivered vaginally and no surgical intervention was required. The case suggests that UTI can reduce meconium‐induced chemical peritonitis and thereby facilitate intrauterine remission of fetal ascites. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
A reassessment of biochemical marker distributions in trisomy 21‐affected and unaffected twin pregnancies in the first trimester
Authors: Madsen H. N. , Ball S. , Wright D. , Tørring N. , Petersen O. B. , Nicolaides K. H. , Spencer K.
Published: September 2010

Objective

To estimate the difference between levels of the two biochemical markers pregnancy‐associated plasma protein‐A (PAPP‐A) and maternal serum free β‐human chorionic gonadotropin (free β‐hCG) in twin pregnancies relative to singleton pregnancies and establish an improved screening procedure for chromosomal abnormalities such as trisomy 21 in twin pregnancies.

Methods

4843 unaffected and 47 trisomy 21‐affected twin pregnancies were included in the study. Chorionicity‐specific medians were generated for PAPP‐A and free β‐hCG from gestational ages 8 to 14 weeks. Multiple of the median values for each of the biochemical markers were calculated. Detection rates and false‐positive rates were estimated for screening tests incorporating nuchal translucency and maternal age, with and without biochemistry.

Results

Medians for the two biochemical markers for monochorionic and dichorionic twins in unaffected pregnancies show a gestational age‐specific increase relative to singleton medians. Allowing for gestation and chorionicity, twin pregnancies affected with trisomy 21 had higher levels of free β‐hCG and lower levels of PAPP‐A. Adding biochemistry into the risk assessment using a fixed risk cut‐off of 1 in 100 increased the detection rate for fetal trisomy 21 in dizygotic twin pregnancies from 78 to 90%, and decreased the false‐positive rate from 8.0 to 5.9%.

Conclusion

Generation of chorionicity‐specific medians for the biochemical markers and their use in risk assessment can improve the performance of first‐trimester screening for chromosomal abnormalities in twins to a level comparable with that in singleton pregnancies. Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd.
Ultrasound predictors of mortality in monochorionic twins with selective intrauterine growth restriction
Authors: Ishii K. , Murakoshi T. , Hayashi S. , Saito M. , Sago H. , Takahashi Y. , Sumie M. , Nakata M. , Matsushita M. , Shinno T. , Naruse H. , Torii Y.
Published: September 2010

Objectives

The aim of this study was to evaluate the use of ultrasound assessment to predict risk of mortality in expectantly managed monochorionic twin fetuses with selective intrauterine growth restriction (sIUGR).

Methods

This was a retrospective study of 101 monochorionic twin pregnancies diagnosed with sIUGR before 26 weeks of gestation. All patients were under expectant management during the observation period. At the initial evaluation, the presence or absence of each of the following abnormalities was documented: oligohydramnios; stuck twin phenomenon; severe IUGR < 3rd centile of estimated fetal weight; abnormal Doppler in the umbilical artery; and polyhydramnios in the larger twin. The relationships between these ultrasound findings and mortality of sIUGR fetuses were evaluated using multiple logistic regression analysis.

Results

Of 101 sIUGR twins, 22 (21.8%) fetuses suffered intrauterine demise and nine (8.9%) suffered neonatal death; 70 (69.3%) survived the neonatal period. Multiple logistic regression analysis revealed that the stuck twin phenomenon (odds ratio (OR): 14.5; 95% CI: 2.2–93.2; P = 0.006) and constantly absent diastolic flow in the umbilical artery (OR: 29.4; 95% CI: 3.3–264.0; P = 0.003) were significant risk factors for mortality.

Conclusions

Not only abnormal Doppler flow in the umbilical artery but also severe oligohydramnios should be recognized as important indicators for mortality in monochorionic twins with sIUGR. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
Uterine artery Doppler screening for pre‐eclampsia: comparison of the lower, mean and higher first‐trimester pulsatility indices
Authors: Napolitano R. , Rajakulasingam R. , Memmo A. , Bhide A. , Thilaganathan B.
Published: September 2010

Objectives

A previous study suggested that the lower uterine artery pulsatility index (PI) is a better predictor of pre‐eclampsia than is either the mean or higher indices. The aim of this study was to assess the relative value of these three indices for the prediction of pre‐eclampsia in the first trimester of pregnancy.

Methods

This was a prospective study of 6221 singleton pregnancies. Uterine artery PI was obtained at the time of the 11–14‐week nuchal translucency scan and receiver–operating characteristics curves for the lower, mean and higher PI value of the two uterine arteries in the prediction of pre‐eclampsia were calculated.

Results

There were 178 cases of pre‐eclampsia. The associations between uterine artery PI and pre‐eclampsia were stronger for early (requiring delivery < 34 weeks' gestation) and preterm (requiring delivery < 37 weeks) pre‐eclampsia compared to pre‐eclampsia at any gestation. There was no significant difference in the strength of the association between lower, mean and higher PI for pre‐eclampsia at any gestation.

Conclusions

First‐trimester uterine artery PI is strongly associated with the development of early and preterm pre‐eclampsia. Lower, mean and higher uterine artery PIs are comparable in screening for pre‐eclampsia. Any differences that exist between the lower, mean and higher uterine artery indices are unlikely to have a significant impact on screening sensitivities. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.