bluuebunny/crossref_metadata_2025 huggingface dataset:
On assessing the presence of evaluation‐time bias in progression‐free survival in randomized trials
Authors: Kay Richard , Wu Jane , Wittes Janet
Published: June 2010

Evaluation (or assessment)–time bias can arise in oncology trials that study progression‐free survival (PFS) when randomized groups have different patterns of timing of assessments. Modelling or computer simulation is sometimes used to explore the extent of such bias; valid results require building such simulations under realistic assumptions concerning the timing of assessments. This paper considers a trial that used a logrank test where computer simulations were based on unrealistic assumptions that severely overestimated the extent of potential bias. The paper shows that seemingly small differences in assumptions can lead to dramatic differences in the apparent operating characteristics of logrank tests. Copyright © 2010 John Wiley & Sons, Ltd.
Reference regions for beat‐to‐beat ECG data
Authors: Crimin Kimberly S. , Emerson John W. , Muirhead Robb J.
Published: June 2010

The QT interval is regarded as an important biomarker for the assessment of arrhythmia liability, and evidence of QT prolongation has led to the withdrawal and relabeling of numerous compounds. Traditional methods of assessing QT prolongation correct the QT interval for the length of the RR interval (which varies inversely with heart‐rate) in a variety of ways. These methods often disagree with each other and do not take into account changes in autonomic state. Correcting the QT interval for RR reduces a bivariate observation (RR, QT) to a univariate observation (QTc). The development of automatic electrocardiogram (ECG) signal acquisition systems has made it possible to collect continuous (so called ‘beat‐to‐beat’) ECG data. ECG data collected prior to administration of a compound allow us to define a region for (RR, QT) values that encompasses typical activity. Such reference regions are used in clinical applications to define the ‘normal’ region of clinical or laboratory measurements.

This paper motivates the need for reference regions of (RR, QT) values from beat‐to‐beat ECG data, and describes a way of constructing these. We introduce a measure of agreement between two reference regions that points to the reliability of 12‐lead digital Holter data. We discuss the use of reference regions in establishing baselines for ECG parameters to assist in the evaluation of cardiac risk and illustrate using data from two methodological studies. Copyright © 2010 John Wiley & Sons, Ltd.
The ability of hydroxysafflor yellow a to attenuate lipopolysaccharide‐induced pulmonary inflammatory injury in mice
Authors: Sun Chun‐Yan , Pei Chong‐qiang , Zang Bao‐Xia , Wang Lin , Jin Ming
Published: June 2010

Hydroxysafflor yellow A (HSYA) is a component of the flower of Carthamus tinctorius L. The present study investigated whether HSYA could attenuate acute lung injury (ALI) induced by lipopolysaccharide (LPS) administration. Male Kunming mice were pretreated with HSYA 0.5 h prior to intraperitoneal application of LPS. Arterial blood gas, lung water content index, lung tissue myeloperoxidase (MPO) activity, mRNA expression of inflammatory cytokines, NF‐κBp65, p38 mitogen‐activated protein kinase (MAPK) and pathological changes in lung morphology were assessed. After LPS administration, all animals displayed increased arterial carbon dioxide partial pressure (PaCO2), and decreased arterial oxygen partial pressure (PaO2), arterial oxygen saturation (SO2), HCO3− concentration and pH, which were ameliorated by pretreating the animals with HSYA. HSYA administration significantly attenuated inflammatory cell infiltration and alleviated pulmonary edema induced by LPS. Moreover, HSYA decreased NF‐κB p65 nuclear translocation, inhibited proinflammatory cytokine TNF‐α, IL‐1β and IL‐6 mRNA expression and promoted antiinflammatory cytokine IL‐10 gene expression following LPS injection. Pulmonary p38 MAPK phosphorylation was upregulated 4 h after LPS treatment, which could be suppressed by pretreatment with HSYA. These findings demonstrated the protective effect of HSYA against LPS‐induced acute lung injury, which is suggested to be associated with the inhibition of p38 MAPK, NF‐κB p65 activation and alteration of inflammatory cytokine expression. Copyright © 2010 John Wiley & Sons, Ltd.
Absence of positive effect of black cohosh (Cimicifuga racemosa) on fracture healing in osteopenic rodent model
Authors: Kolios Leila , Daub Florian , Sehmisch Stephan , Frosch Karl‐Heinz , Tezval Mohammed , Stuermer Klaus Michael , Wuttke Wolfgang , Stuermer Ewa Klara
Published: June 2010

The healing of predominantly metaphyseal fractures in postmenopausal osteoporosis is delayed and comparatively poor. Due to the potential side effects of HRT, natural alternatives are appealing. The aim of this study was to determine whether Cimicifuga racemosa extract BNO 1055 improves metaphyseal fracture healing in severe osteopenic bone in rats.

Thirty‐three 12‐week‐old female rats developed severe osteopenia during 10 weeks after ovariectomy. After metaphyseal tibial‐osteotomy and standardized T‐plate‐osteosynthesis, the healing periods in ovariectomized rats (C), 17‐α‐estradiol (E) and Cimicifuga racemosa (CR) supplemented diets were assessed for 35 days. Changes in callus morphology were evaluated qualitatively by biomechanical testing and quantitatively in microradiographies and fluorochrome‐labeled histological sections.

The CR‐supplementation slightly improved callus quality and trabecular bone formation. It significantly enhanced the endosteal callus density compared to C group (Cl.Dn.e C: 59.08 ± 21.89, E: 45.95 ± 18.39, CR: 60.85 ± 18.66*), though most of the other morphological parameters examined showed no improvement. The time course of fracture healing did not change due to CR. Estrogen‐supplementation enhanced the biomechanical properties of the fracture site. Trabecular bone was improved indicating the physiological endosteal healing process.

The CR‐supplementation did not exhibit positive effects in severe (senile) osteopenic fracture healing as seen in early (postmenopausal) osteoporosis in rats. Callus formation was slightly improved under CR. Estrogen improved fracture healing in severe osteopenic bone, while the extent of callus formation played a minor role. Copyright © 2010 John Wiley & Sons, Ltd.
7,3′‐dimethoxy hesperetin induces apoptosis of fibroblast‐like synoviocytes in rats with adjuvant arthritis through caspase 3 activation
Authors: Li Rong , Cai Li , Xie Xue‐feng , Peng Lei , Li Jun
Published: June 2010

Approaches inducing fibroblast‐like synoviocytes (FLS) apoptosis in rheumatoid arthritis (RA) patients have been considered as a promising strategy for treating RA. Here, adjuvant arthritis (AA) in rat was induced by complete Freund's adjuvant and FLS were separated and cultured using a tissue explant cultivation method. The apoptotic effect of 7,3′‐dimethoxy hesperetin (DMHP, a highly antirheumatic active derivative of hesperidin) on AA FLS was evaluated with MTT assay, Hoechst staining and flow cytometry analysis. Bcl‐2, Bax, caspase 3 gene expressions and caspase 3 activity were assayed to identify whether caspase 3 was involved in the apoptosis induced by DMHP. It was found that DMHP significantly decreased AA FLS proliferation in vitro by MTT assay. The AA FLS treated with DMHP displayed typical apoptotic characteristics including irregularity in shape, nuclear shrinkage and chromatin condensation. Flow cytometry analysis indicated that DMHP could obviously increase the AA FLS apoptosis rate. Compared with the AA‐FLS control group, DMHP markedly decreased the mRNA expression of Bcl‐2, whereas those of Bax and caspase 3 were increased. Moreover, DMHP significantly increased caspase 3 activity in a dose‐dependent manner. In aggregate, the results demonstrate that DMHP effectively induces AA FLS apoptosis through caspase 3 activation and can be considered as a possible antirheumatic agent. Copyright © 2010 John Wiley & Sons, Ltd.
Effects of Chlorophytum arundinaceum, Asparagus adscendens and Asparagus racemosus on pro‐inflammatory cytokine and corticosterone levels produced by stress
Authors: Kanwar Anubha Singh , Bhutani Kamlesh Kumar
Published: June 2010

Chlorophytum arundinaceum, Asparagus adscendens and Asparagus racemosus are used in the Indian traditional system of medicine for improving the general state of health and for stress‐related immune disorders. The effects of the methanol and aqueous extracts of the tuberous roots of these plants were examined in an experimental mouse model of stress, induced by swimming. The extracts were shown to exert an inhibitory effect on pro‐inflammatory cytokines, namely interleukin 1β and tumour necrosis factor α, and on the production of nitric oxide in mouse macrophage cells RAW 264.7 stimulated by lipopolysaccharide in vitro. Similar inhibition was also observed in the production of interleukin 2 in EL 4 lymphoma cells stimulated by concanavalin A. Corticosterone levels in serum and adrenal glands were measured. The findings suggest that these plants may be beneficial in the management of stress and inflammatory conditions. Copyright © 2010 John Wiley & Sons, Ltd.
Antiangiogenic phytochemicals and medicinal herbs
Authors: Jeong Soo‐Jin , Koh Wonil , Lee Eun‐Ok , Lee Hyo‐Jung , Lee Hyo‐Jeong , Bae Hyunsu , Lü Junxuan , Kim Sung‐Hoon
Published: June 2010

Medicinal herbs and their phytochemicals are potential novel leads for developing antiangiogenic drugs. This review aims to assess the current status of research with medicinal herbs and their phytochemicals for the development of antiangiogenic agents for cancer and other angiogenesis‐related diseases including inflammation, diabetic retinopathy, endometriosis and obesity. Most studies reviewed have focused on vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR‐2) signaling for endothelial response processes and have led to the identification of many potential antiangiogenic agents. Since human clinical trials with antiangiogenic modalities targeting VEGF/VEGFR‐2 signaling have shown limited efficacy and occasional toxic side effects, screening strategies for herbal phytochemicals based on other signaling pathways important for cancer‐endothelial and stromal crosstalks should be emphasized in the future. Copyright © 2010 John Wiley & Sons, Ltd.
An automated method for ‘clumped‐isotope’ measurements on small carbonate samples
Authors: Schmid Thomas W. , Bernasconi Stefano M.
Published: June 2010

Clumped‐isotope geochemistry deals with the state of ordering of rare isotopes in molecules, in particular with their tendency to form bonds with other rare isotopes rather than with the most abundant ones. Among its possible applications, carbonate clumped‐isotope thermometry is the one that has gained most attention because of the wide potential of applications in many disciplines of earth sciences. Clumped‐isotope thermometry allows reconstructing the temperature of formation of carbonate minerals without knowing the isotopic composition of the water from which they were formed. This feature enables new approaches in paleothermometry. The currently published method is, however, limited by sample weight requirements of 10–15 mg and because measurements are performed manually. In this paper we present a new method using an automated sample preparation device coupled to an isotope ratio mass spectrometer. The method is based on the repeated analysis (n = 6–8) of 200 µg aliquots of sample material and completely automated measurements. In addition, we propose to use precisely calibrated carbonates spanning a wide range in Δ47 instead of heated gases to correct for isotope effects caused by the source of the mass spectrometer, following the principle of equal treatment of the samples and standards. We present data for international standards (NBS 19 and LSVEC) and different carbonates formed at temperatures exceeding 600°C to show that precisions in the range of 10 to 15 ppm (1 SE) can be reached for repeated analyses of a single sample. Finally, we discuss and validate the correction procedure based on high‐temperature carbonates instead of heated gases. Copyright © 2010 John Wiley & Sons, Ltd.
Identification of a uromodulin fragment for diagnosis of IgA nephropathy
Authors: Wu Jie , Wang Na , Wang Jie , Xie Yuansheng , Li Yan , Liang Tingting , Wang Jianzhong , Yin Zhong , He Kun , Chen Xiangmei
Published: June 2010

IgA nephropathy (IgAN) is one of the most common types of glomerulonephritis worldwide and is diagnosed only with a renal biopsy. The purpose of the present studies was to identify the potential biomarkers for the non‐invasive diagnosis of IgAN. The combination of a magnetic bead separation system with matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS) was used to analyze urinary peptides of IgAN patients, other glomerulopathy patients, and healthy controls. ClinProTools v.2.0 software was also applied to establish a diagnostic model for IgAN. Our results demonstrated that 11 features had optimal discriminatory performance (p <0.00001). Among these features, the peptide with m/z 1913.14 was identified as a fragment of uromodulin. Receiver operating characteristic (ROC) analysis for m/z 1913.14 showed that the area under the curve (AUC) was 0.998 for distinguishing IgAN versus healthy controls, and 0.815 for distinguishing IgAN versus other glomerulopathy. Analysis of urine peptides patterns by the magnetic bead separation system and MALDI‐TOF‐MS was a non‐invasive diagnostic tool. We conclude that the urinary peptide with m/z 1913.14, which was identified as a uromodulin fragment, may be used as a biomarker for the non‐invasive diagnosis of IgAN clinically. Copyright © 2010 John Wiley & Sons, Ltd.
Accurate ultra‐low‐energy secondary ion mass spectrometry analysis of wide bandgap GaN/InxGa1–xN structures using optical conductivity enhancement
Authors: Morris R. J. H. , Dowsett M. G. , Beanland R. , Parbrook P. J. , McConville C. F.
Published: June 2010

Ultra‐low‐energy secondary ion mass spectrometry has been used to undertake a structural analysis of GaN–InxGa1–xN (x ∼0.25) quantum wells used in optoelectronic devices. The high resistivity of intrinsic GaN–InxGa1–xN restricts the necessary electrical path between the analyzed area and the instrument ground potential resulting in surface charge accumulation. Consequently, unstable and unrepresentative depth profiles tend to be produced. A technique known as optical conductivity enhancement (OCE) has been used during depth profiling to reduce the material resistivity. This creates an electrical path between the sample and holder, eliminating charge build up and resulting in accurate depth profiles. Copyright © 2010 John Wiley & Sons, Ltd.
Surface characterization and monitoring of surface changes after conservation treatments of silver gelatin photographic papers using confocal microscopy
Authors: Ravines Patrick , Chen Jiuan‐jiuan , Wichern Christian M.
Published: June 2010

Surface metrology techniques that are non‐perturbing (non‐contact, non‐invasive, and non‐destructive) are well suited to in situ surface studies of historical and fine art photographs. They allow for the quantitative examination of the microstructure of the photograph surface, thereby, offering an important advancement in the examination, documentation, and characterization of silver gelatin photographs and other modern and/or historic imaging materials. This article presents the application of an optical confocal scanning disk microscopy system to the qualitative and quantitative characterization and assessment of a silver gelatin photographic paper, Ilford Glossy, submitted to different humidification and flattening protocols. SCANNING 32: 122–133, 2010. © 2010 Wiley Periodicals, Inc.
MNEs and corruption: the impact of national institutions and subsidiary strategy
Authors: Spencer Jennifer , Gomez Carolina
Published: June 2010

We argue that the pressure MNE subsidiaries face to engage in corrupt practices in their host country varies positively with the institutionalization of corrupt practices in both host and home country environments. We further argue that the relationship between an MNE's home country environment and the pressure it faces in the host country is moderated by its localization strategy. Results suggest a positive relationship between the host country corruption environment and the pressure subsidiaries face to engage in bribery locally. Mixed results emerged concerning MNEs from home countries participating in the OECD Convention for Combating Bribery. Results concerning the impact of the home country corruption environment are best viewed in light of significant moderating effects. When MNEs did not have local partners, firms from less corrupt home countries reported less pressure to engage in corrupt practices locally; however, the presence of local partners eliminated this relationship. Results will help managers understand the pressures their firm is likely to face when operating in corrupt host country environments, and also offer guidance concerning how the firm might reduce its exposure to those local institutional pressures. Copyright © 2010 John Wiley & Sons, Ltd.
Positional rigidity: low performance and resource acquisition in large and small firms
Authors: Greve Henrich R.
Published: June 2010

Past research has given contradictory answers to the question of how strategic change is linked to firm size and performance. This paper resolves the contradictory predictions of performance feedback theory and threat rigidity theory by positing that small and large firms have distinct responses to performance because of differences in risk aversion and internal rigidity. To examine these differences, it is necessary to distinguish risk taking from rigidity in the strategic position, which is accomplished by separate analysis of the amount of resource acquisition and the difference of acquired and existing resources. Analysis of data from the shipping industry supports the predicted interactions of firm size and performance. Copyright © 2010 John Wiley & Sons, Ltd.
Nanodiamond as the pH‐Responsive Vehicle for an Anticancer Drug
Authors: Guan Bo , Zou Fei , Zhi Jinfang
Published: June 2010

Cis‐dichlorodiammineplatinum(II) (CDDP, cisplatin), a widely used anticancer drug, is successfully loaded onto nanodiamond (ND) by adsorption and complexation. The CDDP–ND composite is characterized by IR spectroscopy, atomic absorption spectroscopy, thermogravimetric analysis, energy‐dispersive X‐ray spectroscopy, and X‐ray photoelectron spectroscopy. CDDP is released from the composite in phosphate‐buffered saline (PBS) of pH 6.0 at a rate higher than in PBS of pH 7.4. Therefore, it is predicted that the ND vehicle would deliver low concentrations of CDDP in the blood, but release much more drug after integration into the acidic cytoplasm, thereby reducing toxic side effects. The complexation between CDDP and the carboxyl groups on the ND surface is responsible for the pH‐responsive release property. The drug released from the composite retains the same cytotoxicity as free CDDP against human cervical cancer cells.
New Mixing Rules for Composite Polymer Materials
Authors: Holcman Vladimír , Grmela Lubomír , Liedermann Karel
Published: June 2010

This paper studies the dielectric properties of an elastomer filled with spherical Ni particles of different sizes the range 35–115 µm. The experimental analysis is followed by an examination of the permittivity/conductivity mixing rules. A new mixing formula for the composite system consisting of spherical metallic particles and the polymer matrix is presented. This formula includes both Ni particle content and Ni particle size as two independent variables. Copyright © 2010 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Space Charge Distribution Measurement in Complex Insulating Structures
Authors: Holé Stéphane
Published: June 2010

Electrical insulation involves more and more complex structures in which the electric field or the material can be heterogeneous. For testing space charge buildup in such structures, one‐dimensional measurements are still often used owing to their simplicity. The sample complexity may, however, induce spurious effects that can be confused with space charge. In this paper, from the underlying physics of the pressure‐wave propagation (PWP) and the electro‐acoustic (PEA) methods, limitations of the one‐dimensional model are shown and an analysis procedure is given. Copyright © 2010 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Refractive Index Control of Polymer Film by Plasma CVD for designing an Optical Waveguide
Authors: Sato Tetsuji , Moriki Kazunori , Yumoto Motoshige
Published: June 2010

Refractive index control of a polymer film is an important issue in the fabrication of an optical polymer waveguide by using plasma‐enhanced polymerization. In a conventional approach, one attempts to control the same by changing the molecular structure by controlling the plasma conditions, for example, the applied power, pressure, and plasma potential. In another approach, elements other than carbon and hydrogen can be incorporated into the film. However, this approach unfortunately causes an increased optical absorption due to excess radicals, e.g. dangling bonds in the film and the unpredictable and undesirable bases produced during the reaction. We have proposed to control the amount of double bonding by varying the source monomer without changing the plasma conditions, where we used C6H6 and C6H10 as the source monomers. In the present paper, we investigate how the refractive index changes by varying the amount of double bonds by controlling the ratio of C6H6 and C6H10 in a mixture. Moreover, we discuss how the CF4 plasma atmosphere affects the refractive index and the molecular structure of the film. Consequently, increasing the ratio of C6H6 in the mixture increases the refractive index of the film linearly. The refractive index decreases until the ratio of CF4 is less than 0.4, and beyond this value the refractive index remains almost constant. Additionally, the deposition rate using CF4 as the atmosphere is much larger than when using Ar. Copyright © 2010 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Relationship between Contact Voltage Drop and Frictional Coefficient under High‐current Sliding Contact
Authors: Ueno Takahiro , Kadono Kenichi , Yamaguchi Shinji , Aoyagi Minoru , Tanaka Akio , Morita Noboru
Published: June 2010

Large DC motors are used in various industrial applications. These motors repeatedly generate arcs between the brush and commutator, because the load change is intense and the current value is also large. In particular, for the case in which the current is concentrated on a part of the brush, brush burnout may occur as a result of overcurrent. Therefore, excellent brushes to withstand arc generation and with good electrical properties are required. In the present paper, we discuss the relation between contact voltage drop and frictional wear for electrical sliding contacts when high currents flow to the brush. Specifically, we investigate the means by which to prevent brush burnout when high‐current flows to the brush. Copyright © 2010 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
A Simple Method for Detecting Oil–Water Interface Level and Oil Level
Authors: Lu Gui‐Rong , Hu Hao , Chen Shu‐Yue
Published: June 2010

A new and simple method for monitoring two levels of oil‐water interface and oil is proposed. The method aims to estimate the two levels of liquids stored up and layered in a single tank. A parallel‐plate capacitance sensor, one electrode of which has been divided into two parts by a diagonal line through a small crack, has been developed. According to relationships between capacitances and the two levels, two formulas for estimating the oil‐water interface level and oil level have been derived and tested theoretically. The results indicate that the proposed method is possible and the designed sensor can deliver important information for practical engineers. Copyright © 2010 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Field Experiments of an OFDMA/TDD System for Mobile WiMAX
Authors: Yamazaki Satoshi , Asano David K.
Published: June 2010

Mobile worldwide interoperability for microwave access (WiMAX) is a technology that has received much attention for next‐generation mobile broadband systems. In this paper, we focused on the physical layer of mobile WiMAX and performed field experiments. We show the performance of a WiMAX base station in the field using the error vector magnitude (EVM) performance measure experimentally and theoretically. Copyright © 2010 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
A new population‐based term prediction model vs. two traditional sample‐based models: validation on 9046 ultrasound examinations
Authors: Økland I. , Gjessing H. K. , Grøttum P. , Eggebø T. M. , Eik‐Nes S. H.
Published: June 2010

Objectives

To compare results of predictions of date of delivery from a new population‐based model with those from two traditional regression models.

Methods

We included 9046 fetal biparietal diameter (BPD) measurements and 8776 femur length (FL) measurements from the routine ultrasound examinations at Stavanger University Hospital between 2001 and 2007. The prediction models to be validated were applied to the data, and the resulting predictions were compared with the actual time of the subsequent deliveries. The primary measure was the median bias (the difference between the true and the predicted date of delivery), calculated for each method, for the study population as a whole and for three subgroups of BPD/FL measurements. We also assessed the proportion of births within ± 14 days of the predicted day, and rates of preterm and post‐term deliveries, which were regarded as secondary measures.

Results

For the population‐based model, the median bias was −0.15 days (95% confidence interval (CI), −0.43 to 0.12) for the BPD‐based, and −0.48 days (95% CI, −0.86 to −0.46) for the FL‐based predictions, and both biases were stable over the inclusion ranges. The biases of the traditional regression models varied, depending on the fetal size at the time of the examination; the extremes were −3.2 and + 4.5 days for the BPD‐based, and −1.0 and + 5.0 days for the FL‐based predictions.

Conclusions

The overall biases, as well as the biases for the subgroups, were all smaller with the population‐based model than with the traditional regression models, which exhibited substantial biases in some BPD and FL subcategories. For the population‐based model, the FL‐based predictions were in accordance with the BPD‐based predictions. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
Out with the Old, In with the New: A Novel Approach to Treating Pain Associated with Rib Fractures
Authors: Truitt Michael S. , Mooty R. Clark , Amos Joseph , Lorenzo Manuel , Mangram Alicia , Dunn Ernest
Published: June 2010

Background

Rib fractures continue to be a challenging problem from both a pulmonary and analgesia standpoint. As a result, numerous modalities have been used to treat this condition, but none has proven universally available and efficacious. The objective of this pilot study was to assess the efficacy of a novel technique for placing an elastomeric infusion pump (EIP) catheter (On‐Q; Lake Forest, CA, USA) in the extrathoracic paraspinous space to create a continuous intercostal nerve block.

Methods

This was a prospective, nonrandomized study conducted in the surgical intensive care unit (SICU) of an urban level II trauma center. We developed a novel technique for placing EIP catheters in the extrathoracic paraspinous space to provide continuous intercostal nerve blockade. We subsequently evaluated 30 consecutive blunt trauma patients with three or more unilateral rib fractures. The catheters were infused with local anesthetic, and the dose was titrated to achieve adequate analgesia. For each patient, preplacement numeric pain scale scores (NPSs) and sustained maximum inspiration (SMI) lung volumes were determined. Sixty minutes following placement of the catheters, the NPS and SMI were repeated. The patients were monitored for any procedural or drug‐related complications.

Results

The mean age of the patients was 65 years (22–92 years); the mean ISS was 14 (9–16); and the mean number of rib fractures was 4.4 (3–8). Overall, the mean NPS significantly improved (preplacement NPS 9.03, postplacement NPS 3.06;p< 0.05) and was associated with a significant increase in the SMI (preplacement SMI 0.40 L, postplacement SMI 1.1 L;p< 0.05). The catheters remained in place for an average of 98 h (72–146 h), and there were no procedural‐ or drug‐related complications.

Conclusions

These pilot data indicate that the placement of EIP catheters in the extrathoracic paraspinous space may be a safe, viable, and efficacious procedure for ameliorating pain secondary to rib fractures.
Does Pringle Maneuver Affect Survival in Patients with Colorectal Liver Metastases?
Authors: Ferrero Alessandro , Russolillo Nadia , Viganò Luca , Lo Tesoriere Roberto , Muratore Andrea , Capussotti Lorenzo
Published: June 2010

Background

The purpose of this original article was to evaluate the impact of the Pringle maneuver on the survival of patients with colorectal liver metastases.

Methods

Eighty patients with colorectal liver metastases were randomized to undergo hepatectomy with (39 patients, HPC group) or without (41 patients, NHPC group) pedicle clamping.

Results

The two groups were homogeneous. Mortality and morbidity rates were similar. Blood transfusions rates were higher in HPC group (p = 0.010). Median follow‐up was 67.1 ± 20 months in the HPC group and 77.5 ± 16.6 months in the other group (p = 0.07). Overall survival at 1, 3, and 5 years was 100%, 86.1%, and 49.4% in HPC group vs. 92.6%, 65.8%, and 48.2% in NHPC group (p = 0.704). Disease‐free survival was similar between the two groups: 1‐, 3‐ and 5‐year survival rates were 85.7%, 51.4%, and 34.3% in the HPC group vs. 84%, 51.5%, and 37.9% in NHPC group (p = 0.943). The incidence of hepatic recurrence was similar in the two groups (p = 0.506). Median time to hepatic recurrence was similar in the two groups (p = 0.482). Overall and disease‐free survival rates were similar even when the Pringle maneuver was longer than 45 min (p = 0.571 and 0.948) and in patients with liver steatosis (p = 0.779 and 0.412).

Conclusions

The Pringle maneuver does not seem to affect the survival of patients with liver metastases.
Nationwide survey of extended newborn screening by tandem mass spectrometry in Taiwan
Authors: Niu Dau‐Ming , Chien Yin‐Hsiu , Chiang Chuan‐Chi , Ho Hui‐Chen , Hwu Wuh‐Liang , Kao Shu‐Min , Chiang Szu‐Hui , Kao Chuan‐Hong , Liu Tze‐Tze , Chiang Hung , Hsiao Kwang‐Jen
Published: June 2010

In Taiwan, during the period March 2000 to June 2009, 1,495,132 neonates were screened for phenylketonuria (PKU) and homocystinuria (HCU), and 1,321,123 neonates were screened for maple syrup urine disease (MSUD), methylmalonic academia (MMA), medium‐chain acyl‐coenzyme A (CoA) dehydrogenase (MCAD) deficiency, isovaleric academia (IVA), and glutaric aciduria type 1 (GA‐1) using tandem mass spectrometry (MS/MS). In a pilot study, 592,717 neonates were screened for citrullinemia, 3‐methylcrotonyl‐CoA carboxylase deficiency (3‐MCC) and other fatty acid oxidation defects in the MS/MS newborn screening. A total of 170 newborns and four mothers were confirmed to have inborn errors of metabolism. The overall incidence was approximately 1/5,882 (1/6,219 without mothers). The most common inborn errors were defects of phenylalanine metabolism [five classic PKU, 20 mild PKU, 40 mild hyperphenylalaninemia (HPA), and 13 6‐pyruvoyl‐tetrahydropterin synthase (PTPS) deficiency]. MSUD was the second most common amino acidopathy and, significantly, most MSUD patients (10/13) belonged to the Austronesian aboriginal tribes of southern Taiwan. The most frequently detected among organic acid disorders was 3‐MCC deficiency (14 newborns and four mothers). GA‐1 and MMA were the second most common organic acid disorders (13 and 13 newborns, respectively). In fatty acid disorders, five carnitine transport defect (CTD), five short‐chain acyl‐CoA dehydrogenase deficiency (SCAD), and two medium‐chain acyl‐CoA dehydrogenase (MCAD) deficiency were confirmed. This is the largest case of MS/MS newborn screening in an East‐Asian population to date. We hereby report the incidences and outcomes of metabolic inborn error diseases found in our nationwide MS/MS newborn screening program.
Vascular presentation of cystathionine beta‐synthase deficiency in adulthood
Authors: Magner Martin , Krupková Lucie , Honzík Tomáš , Zeman Jiří , Hyánek Josef , Kožich Viktor
Published: June 2010

Several recent studies describing a solely vascular presentation of cystathionine beta‐synthase (CBS) deficiency in adulthood prompted us to analyze the frequency of patients manifesting with vascular complications in the Czech Republic. Between 1980 and 2009, a total of 20 Czech patients with CBS deficiency have been diagnosed yielding an incidence of 1:311,000. These patients were divided into three groups based on symptoms leading to diagnosis: those with vascular complications, with connective tissue manifestation and with neurological presentation. A vascular event such as a clinical feature leading to diagnosis of homocystinuria was present in five patients, while two of them had no other symptoms typical for CBS deficiency at the time of diagnosis. All patients with the vascular manifestation were diagnosed only during the past decade. The median age of diagnosis was 29 years in the vascular, 11.5 years in the connective tissue and 4.5 years in the neurological group. The ratio of pyridoxine responsive to nonresponsive patients was higher in the vascular (4 of 5 patients) and connective tissue groups (6 of 7 patients) than in the neurological group (2 of 8 patients). Mutation c.833T>C (p.I278T) was frequent in patients with vascular (6/10 alleles) and connective tissue presentation (8/14 alleles), while it was not present in patients with neurological involvement (0/16 alleles). During the last decade, we have observed patients with homocystinuria diagnosed solely due to vascular events; this milder form of homocystinuria usually manifests at greater ages, has a high ratio of pyridoxine responsiveness/nonresponsiveness, and the mutation c.833T>C (p.I278T) is often present.
The homocysteine controversy
Authors: Smulders Yvo M. , Blom Henk J.
Published: June 2010

Mild to moderate hyperhomocysteinemia has been identified as a strong predictor of cardiovascular disease, independent from classical atherothrombotic risk factors. In the last decade, a number of large intervention trials using B vitamins have been performed and have shown no benefit of homocysteine‐lowering therapy in high‐risk patients. In addition, Mendelian randomization studies failed to convincingly demonstrate that a genetic polymorphism commonly associated with higher homocysteine levels (methylenetetrahydrofolate reductase 677 C>T) is a risk factor for cardiovascular disease. Together, these findings have cast doubt on the role of homocysteine in cardiovascular disease pathogenesis, and the homocysteine hypothesis has turned into a homocysteine controversy. In this review, we attempt to find solutions to this controversy. First, we explain that the Mendelian randomization analyses have limitations that preclude final conclusions. Second, several characteristics of intervention trials limit interpretation and generalizability of their results. Finally, the possibility that homocysteine lowering is in itself beneficial but is offset by adverse side effects of B vitamins on atherosclerosis deserves serious attention. As we explain, such side effects may relate to direct adverse effects of the B‐vitamin regimen (in particular, the use of high‐dose folic acid) or to proinflammatory and proproliferative effects of B vitamins on advanced atherosclerotic lesions.
Acyl‐CoA Binding Protein Gene Ablation Induces Pre‐implantation Embryonic Lethality in Mice
Authors: Landrock Danilo , Atshaves Barbara P. , McIntosh Avery L. , Landrock Kerstin K. , Schroeder Friedhelm , Kier Ann B.
Published: June 2010

Unique among the intracellular lipid binding proteins, acyl‐CoA binding protein (ACBP) exclusively binds long‐chain fatty acyl‐CoAs (LCFA‐CoAs). To test if ACBP is an essential protein in mammals, the ACBP gene was ablated by homologous recombination in mice. While ACBP heterozygotes appeared phenotypically normal, intercrossing of the heterozygotes did not produce any live homozygous deficient (null) ACBP(−/−) pups. Heterozygous and wild type embryos were detected at all post‐implantation stages, but no homozygous ACBP‐null embryos were obtained—suggesting that an embryonic lethality occurred at a pre‐implantation stage of development, or that embryos never formed. While ACBP‐null embryos were not detected at any blastocyst stage, ACBP‐null embryos were detected at the morula (8‐cell), cleavage (2‐cell), and zygote (1‐cell) pre‐implantation stages. Two other LCFA‐CoA binding proteins, sterol carrier protein‐2 (SCP‐2) and sterol carrier protein‐x (SCP‐x) were significantly upregulated at these stages. These findings demonstrate for the first time that ACBP is an essential protein required for embryonic development and its loss of function may be initially compensated by concomitant upregulation of two other LCFA‐CoA binding proteins, but only at the earliest pre‐implantation stages. The fact that ACBP is the first known intracellular lipid binding protein whose deletion results in embryonic lethality suggests its vital importance in mammals.
The Europe 2020 Strategy: Time for Europe to Think Again
Authors: Erixon Fredrik
Published: June 2010

In March 2010, the Europe 2020 strategy was released as the follow-up to the very ambitious Lisbon Strategy. Like its predecessor, the strategy aims to increase Europe's competitiveness in the world economy. Also like its predecessor, Europe 2020 is likely to be ineffectual. The strategy focuses too much on areas that are outside the EU's legal competence, it lacks recourse for non-compliance and it contains goals that have very little to do with increasing competitiveness. The probable failure of Europe 2020 could have been avoided had the European Commission focused on policy areas over which the EU has competence, and had been given the tools to accomplish the goals that were outside its competence.
The Kyoto Protocol and European energy policy
Authors: De Filippis Fabrizio , Scarano Giovanni
Published: June 2010

During the lead up to and assessment of the Copenhagen Climate Conference in November 2009, the effects of the celebrated Kyoto Protocol were often overlooked. Although the aims of the Kyoto Protocol can be relegated to the dustbin of history, the targets set out in the agreement allowed Europe to put itself in a dominant position. Not only did the Kyoto Protocol force Europe to invest heavily in green technologies, but in addition it led to the creation of a European energy policy with the aim of reducing Europe's dependence on fossil fuels which can be seen, from a strategic point of view, as an undesirable dependence on sources abroad.
A quasi‐experimental evaluation of parents as sexual health educators resulting in delayed sexual initiation and increased access to condoms ⋆
Authors: Campero Lourdes , Walker Dilys , Atienzo Erika E. , Gutierrez Juan Pablo
Published: June 2010

Objective

To evaluate the effectiveness of an educational intervention for parents of first year high school students in the State of Morelos, Mexico, whose aim was to impact adolescents’ sexual behavior, knowledge and access to contraception.

Material and methods

Quasi‐experimental prospective study with eleven control and eleven intervention schools using self‐administered questionnaires for parents and adolescents pre‐ and post‐intervention. Parent–child dyads in the control and intervention schools were matched according to parents’ propensity score; the average treatment effect (ATE) was estimated for adolescent’s outcome variables.

Results

At follow‐up, we found significant differences for adolescents in the intervention schools: 6.8% delayed initiation of sexual intercourse, 14.4% had correct knowledge about emergency contraception (EC), and 164% reported having received condoms from their parents, when comparing with students in control schools.

Conclusions

Our results suggest that parent‐focused interventions could be an innovative and effective strategy to promote adolescents sexual health.
Schizoaffective disorder–an ongoing challenge for psychiatric nosology
Authors: Jäger M. , Haack S. , Becker T. , Frasch K.
Published: June 2010

Objective

Schizoaffective disorder is a common diagnosis in mental health services. The present article aims to provide an overview of diagnostic reliability, symptomatology, outcome, neurobiology and treatment of schizoaffective disorder.

Method

Literature was identified by searches in “Medline” and “Cochrane Library”.

Results

The diagnosis of schizoaffective disorder has a low reliability. There are marked differences between the current diagnostic systems. With respect to psychopathological symptoms, no clear boundaries were found between schizophrenia, schizoaffective disorder and affective disorders. Common neurobiological factors were found across the traditional diagnostic categories. Schizoaffective disorder according to ICD-10 criteria, but not to DSM-IV criteria, shows a more favorable outcome than schizophrenia. With regard to treatment, only a small and heterogeneous database exists.

Conclusion

Due to the low reliability and questionable validity there is a substantial need for revision and unification of the current diagnostic concepts of schizoaffective disorder. If future diagnostic systems return to Kraepelin's dichotomous classification of non-organic psychosis or adopt a dimensional diagnostic approach, schizoaffective disorder will disappear from the psychiatric nomenclature. A nosological model with multiple diagnostic entities, however, would be compatible with retaining the diagnostic category of schizoaffective disorder.
OGFOD1, a member of the 2‐oxoglutarate and iron dependent dioxygenase family, functions in ischemic signaling
Authors: Saito Ken , Adachi Noritaka , Koyama Hideki , Matsushita Masayuki
Published: June 2010

The 2‐oxoglutarate and iron dependent dioxygenase family are crucial for cellular adaptation to changes in oxygen concentration. We found that cells with OGFOD1 gene silencing in this family showed resistance to cell death under ischemia, and cDNA microarray analysis of OGFOD1 knockout human cells revealed downregulation of ATPAF1. Although reintroduction of the OGFOD1 wild‐type gene to OGFOD1 KO cells restored ATPAF1 mRNA levels, the catalytically inactive OGFOD1 mutants did not. Furthermore, introduction of ATPAF1 gene to OGFOD1 KO cells induced ischemic cell death. Thus, OGFOD1 plays an important role in ischemic cell survival and an OGFOD1 iron binding residue is required for ATPAF1 gene expression.
Defending the end zone: Studying the players involved in protecting chromosome ends
Authors: Chan Suzanne S. , Chang Sandy
Published: June 2010

The linear nature of eukaryotic chromosomes leaves natural DNA ends susceptible to triggering DNA damage responses. Telomeres are specialized nucleoprotein structures that comprise the “end zone” of chromosomes. Besides having specialized sequences and structures, there are six resident proteins at telomeres that play prominent roles in protecting chromosome ends. In this review, we discuss this team of proteins, termed shelterin, and how it is involved in regulating DNA damage signaling, repair and replication at telomeres.
An intention‐to‐treat study of total laparoscopic hysterectomy
Authors: Heaton Richard L. , Walid M. Sami
Published: June 2010

Objective

To present the experience of a single provider with total laparoscopic hysterectomy (TLH) for benign gynecological pathology in order to promote awareness of the feasibility and merits of this minimally‐invasive procedure.

Methods

An intention‐to‐treat prospective study was conducted in a suburban gynecological practice in Central Georgia, USA. The study data were collected over a 7‐year period.

Results

From March 2003 to December 2009, 623 total laparoscopic hysterectomies including 379 pure laparoscopic hysterectomies (without additional procedures) were performed and 12 patients were referred to a gyn‐oncologist. The majority of our patients (93.6%) had a uterine weight of less than 500 g. The median operative time was 60 minutes for pure total laparoscopic hysterectomies. There were 14 intraoperative organ injuries of which 13 were repaired intraoperatively and no returns to the operation room within the first 24 hours. The average hospital charges for TLH were US $13 468 with an average length of stay of 1 day. The average charges for total abdominal hysterectomy were US $12 514 with an average length of stay of 2.3 days.

Conclusion

An advanced laparoscopist can replace the majority of inpatient total abdominal hysterectomies performed for benign indications with outpatient total laparoscopic hysterectomy.
Impact of ALSO training on the management of prolonged labor and neonatal care at Kagera Regional Hospital, Tanzania
Authors: Sorensen Bjarke Lund , Rasch Vibeke , Massawe Siriel , Nyakina Juma , Elsass Peter , Nielsen Birgitte Bruun
Published: June 2010

Objective

To evaluate the management of prolonged labor and neonatal care before and after Advanced Life Support in Obstetrics (ALSO) training.

Methods

Staff involved in childbirth at Kagera Regional Hospital, Tanzania, attended a 2‐day ALSO provider course. In this prospective intervention study conducted between July and November 2008, the management and outcomes of 558 deliveries before and 550 after the training were observed.

Results

There was no significant difference in the rate of cesarean deliveries owing to prolonged labor, and vacuum delivery was not practiced after the intervention. During prolonged labor, action was delayed for more than 3 hours in half of the cases. The stillbirth rate, Apgar scores, and frequency of neonatal resuscitation did not change significantly. After the intervention, there was a significant increase in newborns given to their mothers within 10 minutes, from 5.6% to 71.5% (RR 12.71; 95% CI, 9.04–17.88). There was a significant decrease from 6 to 0 neonatal deaths before discharge among those born with an Apgar score after 1 minute of 4 or more (P = 0.03).

Conclusion

ALSO training had no effect on the management of prolonged labor. Early contact between newborn and mother was more frequently practiced after ALSO training and the immediate neonatal mortality decreased.
Cox‐2 gene expression in chemically induced skin papillomas cannot predict subsequent tumor fate
Authors: Ishikawa Tomo-o , Jain Naveen K. , Herschman Harvey R.
Published: June 2010

Elevated cyclooxygenase‐2 (COX‐2) expression is observed in a variety of premalignant neoplastic tissues, suggesting COX‐2 expression might serve as a potential indicator of subsequent tumor development. However, it has not been possible to compare the relationship between Cox‐2 gene expression in premalignant lesions and their subsequent fate, because conventional studies require tissue destruction for analysis of gene expression. To monitor COX‐2 expression non‐invasively during tumor development, we created a Cox‐2 luciferase knock‐in mouse, Cox‐2luc, in which the firefly luciferase coding region replaces the Cox‐2 coding region. Luciferase activity was non‐invasively, quantitatively and repeatedly monitored in Cox‐2luc/+ mice subjected to DMBA/TPA multistage skin tumor induction. Luciferase activity is significantly higher in all papillomas than in surrounding skin. However, the magnitude of Cox‐2 promoter‐driven luciferase activity in small papillomas cannot predict subsequent papilloma regression or growth. Elevated Cox‐2 promoter‐driven luciferase signal can be detected when papillomas first become visible, but not before this time.