bluuebunny/crossref_metadata_2025 huggingface dataset:
The Ritland impact structure, southwestern Norway
Authors: RIIS F. , KALLESON E. , DYPVIK H. , KRØGLI S. O. , NILSEN O.
Published: April 2011

Abstract– The Ritland structure is a newly discovered impact structure, which is located in southwestern Norway. The structure is the remnant of a simple crater 2.5 km in diameter and 350 m deep, which was excavated in Precambrian gneissic rocks. The crater was filled by sediments in Cambrian times and covered by thrust nappes of the Caledonian orogen in the Silurian–Devonian. Several succeeding events of uplift, erosion, and finally the Pleistocene glaciations, disclosed this well‐preserved structure. The erosion has exposed brecciated rocks of the original crater floor overlain by a thin layer of melt‐bearing rocks and postimpact crater‐filling breccias, sandstones, and shales. Quartz grains with planar deformation features occur frequently within the melt‐bearing unit, confirming the impact origin of the structure. The good exposures of infilling sediments have allowed a detailed reconstruction of the original crater morphology and its infilling history based on geological field mapping.
Separation Control of Axial Compressor Cascade by Fluidic-Based Excitations
Authors: Zheng Xinqian , Zhang Yangjun , Xing Weidong , Zhang Junyue
Published: April 2011

Flow separation control was investigated on a compressor cascade using three types of fluidic-based excitations: steady suction, steady blowing, and synthetic jet. By solving unsteady Reynolds–averaged Navier–Stokes equations, the effect of excitation parameters (amplitude, angle, and location) on performance was addressed. The results show that the separated flow can be controlled by the fluidic-based actuators effectively and the time-averaged performance of the flow field can be improved remarkably. Generally, the improvement can be enhanced when the amplitude of excitation is increased. The optimal direction varies with each type of excitations and is related to physical mechanisms underlying the separation control. For two types of steady excitations, the most effective jet location is at a distance upstream of the time-averaged separation point and the synthetic jet is just at the separation point.
Effect of Density Ratio on Flat Plate Film Cooling With Shaped Holes Using PSP
Authors: Wright Lesley M. , McClain Stephen T. , Clemenson Michael D.
Published: April 2011

Detailed film-cooling effectiveness distributions are obtained on a flat plate using the pressure sensitive paint (PSP) technique. The applicability of the PSP technique is expanded to include a coolant-to-mainstream density ratio of 1.4. The effect of density ratio on the film-cooling effectiveness is coupled with varying blowing ratio (M=0.25–2.0), freestream turbulence intensity (Tu=1–12.5%), and film hole geometry. The effectiveness distributions are obtained on three separate flat plates containing either simple angle, cylindrical holes, simple angle, fanshaped holes (α=10 deg), or simple angle, laidback, fanshaped holes (α=10 deg and γ=10 deg). In all three cases, the film-cooling holes are angled at θ=35 deg from the mainstream flow. Using the PSP technique, the combined effects of blowing ratio, turbulence intensity, and density ratio are captured for each film-cooling geometry. The detailed film-cooling effectiveness distributions, for cylindrical holes, clearly show that the effectiveness at the lowest blowing ratio is enhanced at the lower density ratio (DR=1). However, as the blowing ratio increases, a transition occurs, leading to increased effectiveness with the elevated density ratio (DR=1.4). In addition, the PSP technique captures an upstream shift of the coolant jet reattachment point as the density ratio increases or the turbulence intensity increases (at moderate blowing ratios for cylindrical holes). With the decreased momentum of the shaped film-cooling holes, the greatest film-cooling effectiveness is obtained at the lower density ratio (DR=1.0) over the entire range of blowing ratios considered. In all cases, as the freestream turbulence intensity increases, the film effectiveness decreases; this effect is reduced as the blowing ratio increases for all three film hole configurations.
A Faster Water Cycle
Authors: Bowen Gabriel J.
Published: April 2011

Fossil teeth from marine mammals suggest that the tropical water cycle sped up during the Eocene.
A Cardiac Nonproliferation Treaty
Authors: Schneider Michael D.
Published: April 2011

Two cell signaling pathways converge to restrain the proliferation of muscle cells in the mammalian heart.
On Cancer and People
The Emperor of All Maladies
A Biography of Cancer

by Siddhartha Mukherjee

Scribner, New York, 2010. 595 pp. $30, C$34.99. ISBN 9781439107959.
Authors: Pederson Thoru
Published: April 2011

The winner of the 2011 Pulitzer Prize for General Nonfiction blends a historical survey of cancer and Mukherjee's "coming of age as an oncologist."
EPA in the Crosshairs
Authors: Chameides William L.
Published: April 2011

There are those in the U.S. Congress who seem determined to dismantle the nation's Environmental Protection Agency (EPA) in the name of economic growth and jobs. This despite EPA estimates that last year, the accumulated benefits of the Clean Air Act alone exceeded its costs by more than $1 trillion.
*
The struggle over the EPA has just been played out within the context of the larger budgetary conflict between the Republican-controlled House and the Obama Administration. In the brinkmanship negotiations that kept government doors open, the EPA appears to have escaped more or less intact. The agency will have to absorb $1.6 billion in cuts, or about 16% of its 2010 budget. Although not fatal, those cuts will surely slow the implementation of programs that are under legislative attack, including those that tackle water and air pollution. But the battle is far from over.
Controversy Follows Pricey Space Station Experiment to Launch Pad
Authors: Cho Adrian
Published: April 2011

If all goes as planned, next Friday, NASA's space shuttle Endeavor will carry a massive particle detector to the international space station, some 17 years after the mission was proposed.
More Megaquakes on the Way? That Depends on Your Statistics
Authors: Kerr Richard A.
Published: April 2011

Could the earthquake that hit off Indonesia 6 years ago somehow have touched off a cluster of great earthquakes spanning the Pacific, including the magnitude-9.0 "megaquake" that just struck off Japan? And if so, has this cluster played itself out? Experts differ.
A Remedy at Last for the Ailing Ganges?
Authors: Stone Richard
Published: April 2011

After decades of futility, a charismatic civil engineer's campaign to clean the polluted river is poised for a breakthrough.
Inflammatory Profile and Response to Anti-Tumor Necrosis Factor Therapy in Patients with Chronic Pulmonary Sarcoidosis
Authors: Loza Matthew J. , Brodmerkel Carrie , Du Bois Roland M. , Judson Marc A. , Costabel Ulrich , Drent Marjolein , Kavuru Mani , Flavin Susan , Lo Kim Hung , Barnathan Elliot S. , Baughman Robert P.
Published: April 2011

Sarcoidosis is an inflammatory, granulomatous disease of unknown etiology that most commonly afflicts the lungs. Despite aggressive immunosuppressive therapies, many sarcoidosis patients still chronically present significant symptoms. Infliximab, a therapeutic tumor necrosis factor alpha (TNF-α) monoclonal antibody (MAb), produced a small but significant improvement in forced vital capacity (FVC) in sarcoidosis patients in a double-blind, placebo-controlled, phase II clinical trial. In the current study, serum samples from this clinical trial were assessed to evaluate the underlying hypothesis that treatment with infliximab would reduce systemic inflammation associated with sarcoidosis, correlating with the extent of clinical response. A 92-analyte multiplex panel was used to assess the expression of serum proteins in 134 sarcoidosis patients compared with sera from 50 healthy controls. A strong systemic inflammatory profile was associated with sarcoidosis, with 29 analytes significantly elevated in sarcoidosis (false-discovery rate, <0.05 and >50% higher than controls). The associated analytes included chemokines, neutrophil-associated proteins, acute-phase proteins, and metabolism-associated proteins. This profile was evident despite patients receiving corticosteroids and immunosuppressive therapies. Following infliximab treatment, sarcoidosis patients expressing the highest levels of TNF-α, who had more severe disease, had the greatest improvement in FVC and reduction in serum levels of the inflammatory proteins MIP-1β and TNF-RII. This study supports the need for further exploration of anti-TNF therapy for chronic sarcoidosis patients, particularly for those expressing the highest serum levels of TNF-α.
Preliminary experience with the percutaneous embolization of paragangliomas at the carotid bifurcation using only ethylene vinyl alcohol copolymer (EVOH) Onyx
Authors: Shah Hriday M , Gemmete Joseph J , Chaudhary Neeraj , Pandey Aditya S , Ansari Sameer A
Published: April 2011

Background/purpose

Carotid body paragangliomas are rare hypervascular lesions which may benefit from preoperative devascularization to reduce intraoperative blood loss. The optimal method for devascularization of these tumors is not known. Our purpose was to evaluate the extent of angiographic devascularization and intraoperative blood loss using only ethylene vinyl alcohol copolymer (EVOH) for percutaneous glomus tumor embolization.

Methods

A consecutive series of seven paragangliomas located at the carotid bifurcation were treated with percutaneous embolization with EVOH as the sole embolic agent.

Results

Complete devascularization of seven paragangliomas was achieved in all cases percutaneously with only EVOH. There were no complications. The average intraoperative blood loss was 55 ml (range 15–80 ml).

Conclusions

Our preliminary experience suggests that EVOH may offer a higher degree of devascularization when compared with other embolic agents. This may facilitate easier surgical resection with lower blood loss. EVOH seems to be safe when percutaneously injected as the sole embolic agent.
High prevalence of hypovitaminosis D in young healthy adults from the western part of India
Authors: Shivane Vyankatesh K , Sarathi Vijaya , Bandgar Tushar , Menon Padmavathy , Shah Nalini S
Published: April 2011

Objective

Data on the prevalence of hypovitaminosis D in Indians living in the western part of the country are limited. The authors aimed to study the vitamin D status and dietary intake of calcium and phytates in healthy adult volunteers from a city in the western part of India.

Methods

This cross-sectional study was conducted at a tertiary care centre in western India. A total of 1137 young (age: 25–35 years), healthy volunteers of both sexes were included in the study. All subjects were assessed for sun exposure, dietary intake of energy, protein, fat, calcium and phytates. Biochemical investigations included calcium, inorganic phosphorus, alkaline phosphatase, 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (iPTH), total proteins, albumin and creatinine in serum and spot urinary calcium to creatinine ratio.

Results

The serum 25(OH)D concentration for the whole study population was low (17.4±9.1 ng/ml), and that for men and women were 18.9±8.9 ng/ml and 15.8±9.1 ng/ml, respectively. Seventy per cent of the study population had hypovitaminosis D (25(OH)D <20 ng/ml) with a slightly higher prevalence in women (76%). Mean dietary calcium intake of the study population was 322.92±135.17 mg/day and was very low when compared with the recommended dietary allowance (400 mg/day for adults of both sexes) issued by the Indian Council of Medical Research. Dietary phytate was much higher than calcium intake with a dietary phytate to calcium ratio of 2.25±0.76. Serum iPTH had significant negative correlation with 25(OH)D (r=−0.23, p<0.001).

Conclusion

Hypovitaminosis D, low dietary calcium and high phytate consumption are highly prevalent among young healthy adults in the western part of India.
AN INTEGRATED FRAMEWORK FOR SUSPECT INVESTIGATION
Authors: KIM KEEHYUNG , CHOI HYUKGEUN , McKAY RI (BOB)
Published: April 2011

In a complex crime scene with many possible suspects and conflicting evidence, crime investigation requires scientific and logical steps to narrow down the suspects. Since human investigators have difficulty in fully handling all reasoning in this highly complex hypothesis space, we propose a decision support system to aid the investigation process. The system integrates a rule-based reasoner, a Bayesian network for criminal profiling, and an assumption-based truth maintenance system for evidential reasoning to determine the most plausible suspect. The reasoning process reasons about a profiling classification and an alibi credibility measure. It proved effective in a realistic simulation.
PIECEWISE LINEAR REPRESENTATION SEGMENTATION IN NOISY DOMAINS WITH A LARGE NUMBER OF MEASUREMENTS: THE AIR TRAFFIC CONTROL DOMAIN
Authors: GUERRERO JOSÉ LUIS , GARCÍA JESÚS , MOLINA JOSÉ MANUEL
Published: April 2011

The importance of time series segmentation techniques is rapidly expanding, due to the growth in collection and storage technologies. Among them, one of the most used ones is Piecewise Linear Representation, probably due to its ease of use. This work tries to determine the difficulties faced by this technique when the analyzed time series shows noisy data and a large number of measurements and how to introduce the information about the present noise in the segmentation process. Both difficulties are met in the Air Traffic Control domain, which exhibits position measurements of aircraft's trajectories coming from sensor devices (basically surveillance radar and aircraft-derived data), being used as the motivating domain. Results from the three main traditional techniques are presented (sliding window, top down and bottom up approaches) and compared with a new introduced approach, the Hybrid Local Residue Analysis technique.
MODELING OF PARALLELED SERIES-LOADED-RESONANT CONVERTER WITH PHASE SHIFTING CONTROL
Authors: TAUFIK TAUFIK , POLLERI ANGEL ALEJANDRO , ANWARI MAKBUL , TAUFIK MOHAMMAD
Published: April 2011

One topology widely known for use in high-voltage high-power converter in medical equipment is the Series Loaded Resonant (SLR) converter. As the power level required by medical equipment increases, there is a need to parallel the SLR converter for improved efficiency and performance. This paper presents the development of a circuit model for paralleled SLR converter to aid circuit designers evaluate circuit performance before the actual hardware is implemented. Each section of the circuit is modeled individually using sinusoidal approximation and circuit network methods. The derived model is then extended to include the parallel connection of the converter. The validity of the model is then tested by using computer simulation and hardware setup to demonstrate the converter's switching waveforms, output voltage and efficiency. Results from both simulation and hardware show good agreement, which demonstrate the validity of the derived model and its usefulness in the initial design of the converter.
In Situ Observation and Long-Term Reactivity of Si/C/CMC Composites Electrodes for Li-Ion Batteries
Authors: Bridel J-S. , Azaïs T. , Morcrette M. , Tarascon J-M. , Larcher D.
Published: April 2011

Si/C/CMC composite for electrodes (Na-Carboxy-Methyl-Cellulose) appear today as the most promising strategy in view of substituting carbonaceous materials for silicon as negative active material in Li-ion batteries, hence the need to understand their reaction mechanism. By means of solid state Nuclear Magnetic Resonance spectroscopy, we confirmed that CMC chains can bind to Si via covalent or hydrogen bonding depending upon the pH of the mother suspension. Through coupled in situ Scanning Electron Microscopy and Electrochemical Impedance Spectroscopy observations of such electrodes reacting with Li, we demonstrated the ability of their porosity to buffer the Si swelling up to 1.7–2 Li/Si, further lithiation resulting in internal reorganization with either a definitive break of the covalent CMC-Si bond, or preservation of both the texture and electric wiring in the case of weaker Si-CMC hydrogen bonding thanks to a self-healing process. A relationship between the nature of the Si-CMC bonding and the electrode performance was found with a very positive impact of hydrogen interaction as 100 cycles could be achieved with preservation of the initial texture and excellent retention (3000 mAh/g Si after 100 cycles). Besides, we demonstrated that an alteration in the electrode texture/porosity, by a freeze-drying process, also impacts the electrode reversibility.
Properties of the Passive Film on Alloy 22 in Chloride Solutions Obtained by Electrochemical Impedance
Authors: Rodríguez Martín A. , Carranza Ricardo M.
Published: April 2011

Impedance measurements were performed for alloy 22 in the passive and transpassive range, in 1 M NaCl at 90°C. A RΩ-(R//CPE) circuit model was applied in the full passive range, where R was the film resistance. This model also applied for a wide range of chloride concentrations and pH values, at the open circuit potential. Two time constants were observed at the beginning and at the end of the passive range. In these cases, the resistances for the ion transfer might be located at the film interfaces, and not in the film itself. The protective properties of the film improved with polarization time due to the thickening and ageing of the film. The film resistance and the space charge layer thickness increased with the potential. The oxidation of Cr3+ to Cr6+ occurred in the film at high potentials, followed by the transpassive dissolution. In the pre-transpassive range of potentials, the film showed a p-type electronic character, while the ionic properties were that of a passive film. The passive film of alloy 22 was an n-type semiconductor, which changed to a p-type for the high passive potentials. ND = 2.7 × 1020 cm−3 and EFB = −0.551 VSCE were determined.
Thermal adaptation of the crucian carp (Carassius carassius) cardiac delayed rectifier current, IKs, by homomeric assembly of Kv7.1 subunits without MinK
Authors: Hassinen Minna , Laulaja Salla , Paajanen Vesa , Haverinen Jaakko , Vornanen Matti
Published: April 2011

Ectothermic vertebrates experience acute and chronic temperature changes which affect cardiac excitability and may threaten electrical stability of the heart. Nevertheless, ectothermic hearts function over wide range of temperatures without cardiac arrhythmias, probably due to special molecular adaptations. We examine function and molecular basis of the slow delayed rectifier K+ current ( IKs) in cardiac myocytes of a eurythermic fish ( Carassius carassius L.). IKs is an important repolarizing current that prevents excessive prolongation of cardiac action potential, but it is extremely slowly activating when expressed in typical molecular composition of the endothermic animals. Comparison of the IKs of the crucian carp atrial myocytes with the currents produced by homomeric Kv7.1 and heteromeric Kv7.1/MinK channels in Chinese hamster ovary cells indicates that activation kinetics and pharmacological properties of the IKs are similar to those of the homomeric Kv7.1 channels. Consistently with electrophysiological properties and homomeric Kv7.1 channel composition, atrial transcript expression of the MinK subunit is only 1.6–1.9% of the expression level of the Kv7.1 subunit. Since activation kinetics of the homomeric Kv7.1 channels is much faster than activation of the heteromeric Kv7.1/MinK channels, the homomeric Kv7.1 composition of the crucian carp cardiac IKs is thermally adaptive: the slow delayed rectifier channels can open despite low body temperatures and curtail the duration of cardiac action potential in ectothermic crucian carp. We suggest that the homomeric Kv7.1 channel assembly is an evolutionary thermal adaptation of ectothermic hearts and the heteromeric Kv7.1/MinK channels evolved later to adapt IKs to high body temperature of endotherms.
Emerging role of Akt substrate protein AS160 in the regulation of AQP2 translocation
Authors: Kim Hyo-Young , Choi Hyo-Jung , Lim Jung-Suk , Park Eui-Jung , Jung Hyun Jun , Lee Yu-Jung , Kim Sang-Yeob , Kwon Tae-Hwan
Published: April 2011

AS160, a novel Akt substrate of 160 kDa, contains a Rab GTPase-activating protein (GAP) domain. The present study examined the role of Akt and AS160 in aquaporin-2 (AQP2) trafficking. The main strategy was to examine the changes in AQP2 translocation in response to small interfering RNA (siRNA)-mediated AS160 knockdown in mouse cortical collecting duct cells (M-1 cells and mpkCCDc14 cells). Short-term dDAVP treatment in M-1 cells stimulated phosphorylation of Akt (S473) and AS160, which was also seen in mpkCCDc14 cells. Conversely, the phosphoinositide 3-kinase (PI3K) inhibitor LY 294002 diminished phosphorylation of Akt (S473) and AS160. Moreover, siRNA-mediated Akt1 knockdown was associated with unchanged total AS160 but decreased phospho-AS160 expression, indicating that phosphorylation of AS160 is dependent on PI3K/Akt pathways. siRNA-mediated AS160 knockdown significantly decreased total AS160 and phospho-AS160 expression. Immunocytochemistry revealed that AS160 knockdown in mpkCCDc14 cells was associated with increased AQP2 density in the plasma membrane [135 ± 3% of control mpkCCDc14 cells ( n = 65), P < 0.05, n = 64] despite the absence of dDAVP stimulation. Moreover, cell surface biotinylation assays of mpkCCDc14 cells with AS160 knockdown exhibited significantly higher AQP2 expression [150 ± 15% of control mpkCCDc14 cells ( n = 3), P < 0.05, n = 3]. Taken together, PI3K/Akt pathways mediate the dDAVP-induced AS160 phosphorylation, and AS160 knockdown is associated with higher AQP2 expression in the plasma membrane. Since AS160 contains a GAP domain leading to a decrease in the active GTP-bound form of AS160 target Rab proteins for vesicle trafficking, decreased expression of AS160 is likely to play a role in the translocation of AQP2 to the plasma membrane.
Designing optimal stimuli to control neuronal spike timing
Authors: Ahmadian Yashar , Packer Adam M. , Yuste Rafael , Paninski Liam
Published: April 2011

Recent advances in experimental stimulation methods have raised the following important computational question: how can we choose a stimulus that will drive a neuron to output a target spike train with optimal precision, given physiological constraints? Here we adopt an approach based on models that describe how a stimulating agent (such as an injected electrical current or a laser light interacting with caged neurotransmitters or photosensitive ion channels) affects the spiking activity of neurons. Based on these models, we solve the reverse problem of finding the best time-dependent modulation of the input, subject to hardware limitations as well as physiologically inspired safety measures, that causes the neuron to emit a spike train that with highest probability will be close to a target spike train. We adopt fast convex constrained optimization methods to solve this problem. Our methods can potentially be implemented in real time and may also be generalized to the case of many cells, suitable for neural prosthesis applications. With the use of biologically sensible parameters and constraints, our method finds stimulation patterns that generate very precise spike trains in simulated experiments. We also tested the intracellular current injection method on pyramidal cells in mouse cortical slices, quantifying the dependence of spiking reliability and timing precision on constraints imposed on the applied currents.
Proangiogenic Factor PlGF Programs CD11b+ Myelomonocytes in Breast Cancer during Differentiation of Their Hematopoietic Progenitors
Authors: Laurent Julien , Hull Eveline Faes-van't , Touvrey Cedric , Kuonen François , Lan Qiang , Lorusso Girieca , Doucey Marie-Agnès , Ciarloni Laura , Imaizumi Natsuko , Alghisi Gian Carlo , Fagiani Ernesta , Zaman Khalil , Stupp Roger , Shibuya Masabumi , Delaloye Jean-François , Christofori Gerhard , Ruegg Curzio
Published: April 2011

Tumor-mobilized bone marrow–derived CD11b+ myeloid cells promote tumor angiogenesis, but how and when these cells acquire proangiogenic properties is not fully elucidated. Here, we show that CD11b+ myelomonocytic cells develop proangiogenic properties during their differentiation from CD34+ hematopoietic progenitors and that placenta growth factor (PlGF) is critical in promoting this education. Cultures of human CD34+ progenitors supplemented with conditioned medium from breast cancer cell lines or PlGF, but not from nontumorigenic breast epithelial lines, generate CD11b+ cells capable of inducing endothelial cell sprouting in vitro and angiogenesis in vivo. An anti–Flt-1 mAb or soluble Flt-1 abolished the generation of proangiogenic activity during differentiation from progenitor cells. Moreover, inhibition of metalloproteinase activity, but not VEGF, during the endothelial sprouting assay blocked sprouting induced by these proangiogenic CD11b+ myelomonocytes. In a mouse model of breast cancer, circulating CD11b+ cells were proangiogenic in the sprouting assays. Silencing of PlGF in tumor cells prevented the generation of proangiogenic activity in circulating CD11b+ cells, inhibited tumor blood flow, and slowed tumor growth. Peripheral blood of breast cancer patients at diagnosis, but not of healthy individuals, contained elevated levels of PlGF and circulating proangiogenic CD11b+ myelomonocytes. Taken together, our results show that cancer cells can program proangiogenic activity in CD11b+ myelomonocytes during differentiation of their progenitor cells in a PlGF-dependent manner. These findings impact breast cancer biology, detection, and treatment. Cancer Res; 71(11); 3781–91. ©2011 AACR.
Small Bowel Perforation Caused by a Retained Percutaneous Endoscopic Gastrostomy Tube Flange
Authors: Brown Jason N. , Borrowdale Roderick C.
Published: April 2011

A method used at some centers to remove or replace percutaneous endoscopic gastrostomy tubes is to cut the tube at the skin level, allowing the internal flange to be eliminated intestinally. This is known as the cut‐and‐push technique. This report describes a case in which the internal flange resulted in intestinal perforation in a patient with no history of underlying intestinal disease or abdominal surgery. This case illustrates the importance of interval abdominal radiographs to confirm extrusion of the internal flange.
SNP-based pathway enrichment analysis for genome-wide association studies
Authors: Weng Lingjie , Macciardi Fabio , Subramanian Aravind , Guffanti Guia , Potkin Steven G , Yu Zhaoxia , Xie Xiaohui
Published: April 2011

Background

Recently we have witnessed a surge of interest in using genome-wide association studies (GWAS) to discover the genetic basis of complex diseases. Many genetic variations, mostly in the form of single nucleotide polymorphisms (SNPs), have been identified in a wide spectrum of diseases, including diabetes, cancer, and psychiatric diseases. A common theme arising from these studies is that the genetic variations discovered by GWAS can only explain a small fraction of the genetic risks associated with the complex diseases. New strategies and statistical approaches are needed to address this lack of explanation. One such approach is the pathway analysis, which considers the genetic variations underlying a biological pathway, rather than separately as in the traditional GWAS studies. A critical challenge in the pathway analysis is how to combine evidences of association over multiple SNPs within a gene and multiple genes within a pathway. Most current methods choose the most significant SNP from each gene as a representative, ignoring the joint action of multiple SNPs within a gene. This approach leads to preferential identification of genes with a greater number of SNPs.

Results

We describe a SNP-based pathway enrichment method for GWAS studies. The method consists of the following two main steps: 1) for a given pathway, using an adaptive truncated product statistic to identify all representative (potentially more than one) SNPs of each gene, calculating the average number of representative SNPs for the genes, then re-selecting the representative SNPs of genes in the pathway based on this number; and 2) ranking all selected SNPs by the significance of their statistical association with a trait of interest, and testing if the set of SNPs from a particular pathway is significantly enriched with high ranks using a weighted Kolmogorov-Smirnov test. We applied our method to two large genetically distinct GWAS data sets of schizophrenia, one from European-American (EA) and the other from African-American (AA). In the EA data set, we found 22 pathways with nominal P-value less than or equal to 0.001 and corresponding false discovery rate (FDR) less than 5%. In the AA data set, we found 11 pathways by controlling the same nominal P-value and FDR threshold. Interestingly, 8 of these pathways overlap with those found in the EA sample. We have implemented our method in a JAVA software package, called SNP Set Enrichment Analysis (SSEA), which contains a user-friendly interface and is freely available at http://cbcl.ics.uci.edu/SSEA.

Conclusions

The SNP-based pathway enrichment method described here offers a new alternative approach for analysing GWAS data. By applying it to schizophrenia GWAS studies, we show that our method is able to identify statistically significant pathways, and importantly, pathways that can be replicated in large genetically distinct samples.
Complications of childbirth and maternal deaths in Kinshasa hospitals: testimonies from women and their families
Authors: Kabali Eugénie , Gourbin Catherine , De Brouwere Vincent
Published: April 2011

Background

Maternal mortality in Kinshasa is high despite near universal availability of antenatal care and hospital delivery. Possible explanations are poor-quality care and by delays in the uptake of care. There is, however, little information on the circumstances surrounding maternal deaths. This study describes and compares the circumstances of survivors and non survivors of severe obstetric complications.

Method

Semi structured interviews with 208 women who survived their obstetric complication and with the families of 110 women who died were conducted at home by three experienced nurses under the supervision of EK. All the cases were identified from twelve referral hospitals in Kinshasa after admission for a serious acute obstetric complication. Transcriptions of interviews were analysed with N-Vivo 2.0 and some categories were exported to SPSS 14.0 for further quantitative analysis.

Results

Testimonies showed that despite attendance at antenatal care, some women were not aware of or minimized danger signs and did not seek appropriate care. Cost was a problem; 5 deceased and 4 surviving women tried to avoid an expensive caesarean section by delivering in a health centre, although they knew the risk. The majority of surviving mothers (for whom the length of stay was known) had the caesarean section on the day of admission while only about a third of those who died did so. Ten women died before the required caesarean section or blood transfusion could take place because they did not bring the money in time. Negligence and lack of staff competence contributed to the poor quality of care. Interviews revealed that patients and their families were aware of the problem, but often powerless to do anything about it.

Conclusion

Our findings suggest that women with serious obstetric complications have a greater chance of survival in Kinshasa if they have cash, go directly to a functioning referral hospital and have some leverage when dealing with health care staff
Association of high sensitive C-reactive protein (hsCRP) with established cardiovascular risk factors in the Indian population
Authors: Jeemon Panniyammakal , Prabhakaran Dorairaj , Ramakrishnan Lakhmy , Gupta Ruby , Ahmed F , Thankappan KR , Kartha CC , Chaturvedi Vivek , Reddy KS ,   the Sentinel Surveillance in Industrial Populations Study Group
Published: April 2011

Introduction

Inflammation, the key regulator of C-reactive protein (CRP) synthesis, plays a pivotal role in atherothrombotic cardiovascular disease.

Methods

High sensitivity CRP (hsCRP) analysis was carried out in randomly selected 600 individuals from the sentinel surveillance study in Indian industrial population (SSIP). The hsCRP was measured quantitatively by turbid metric test using kits from SPINREACT, Spain. We analyzed the association between hsCRP and traditional CVD risk factors in this sub-sample.

Results

Complete risk factor data and CRP levels were available from 581/600 individuals. One half (51.2%) of the study subjects were males. Mean age of the study group was 39.2 ± 11.2 years. The Pearson correlation coefficients were in the range of 0.12 for SBP (p = 0.004) to 0.55 for BMI (p < 0.001). The linear regression coefficients ranged from 0.01 for SBP, PG and TC (p < 0.001) to 0.55 for logeTAG (p < 0.001) after adjustment for age, sex and education. The mean of logehsCRP significantly increased (P < 0.001) from individuals with ≤1 risk factors (-0.50) to individuals with three or more risk factors (0.60). In the multivariate model, the odds ratios for elevated CRP (CRP ≥ 2.6 mg/dl) were significantly elevated only in females in comparison to males (1.63, 95% CI; 1.02-2.58), overweight individuals in comparison to normal weight individuals (3.90, 95% CI; 2.34-6.44, p < 0.001), and abdominal obese individuals (1.62, 95% CI; 1.02-2.60, p = 0.04) in comparison to non-obese individuals.

Conclusion

Clinical measurements of adiposity (body mass index and abdominal obesity) correlate well and can be surrogate for systemic inflammatory state of individuals.
Activation of the Galanin Receptor 2 in the Periphery Reverses Nerve Injury-Induced Allodynia
Authors: Hulse Richard P , Wynick David , Donaldson Lucy F
Published: April 2011

Background:

Galanin is expressed at low levels in the intact sensory neurons of the dorsal root ganglia with a dramatic increase after peripheral nerve injury. The neuropeptide is also expressed in primary afferent terminals in the dorsal horn, spinal inter-neurons and in a number of brain regions known to modulate nociception. Intrathecal administration of galanin modulates sensory responses in a dose-dependent manner with inhibition at high doses. To date it is unclear which of the galanin receptors mediates the anti-nociceptive effects of the neuropeptide and whether their actions are peripherally and/or centrally mediated. In the present study we investigated the effects of direct administration into the receptive field of galanin and the galanin receptor-2/3-agonist Gal2-11 on nociceptive primary afferent mechanical responses in intact rats and mice and in the partial saphenous nerve injury (PSNI) model of neuropathic pain.

Results:

Exogenous galanin altered the responses of mechano-nociceptive C-fibre afferents in a dose-dependent manner in both naive and nerve injured animals, with low concentrations facilitating and high concentrations markedly inhibiting mechano-nociceptor activity. Further, use of the galanin fragment Gal2-11 confirmed that the effects of galanin were mediated by activation of galanin receptor-2 (GalR2). The inhibitory effects of peripheral GalR2 activation were further supported by our demonstration that after PSNI, mechano-sensitive nociceptors in galanin over-expressing transgenic mice had significantly higher thresholds than in wild type animals, associated with a marked reduction in spontaneous neuronal firing and C-fibre barrage into the spinal cord.

Conclusions:

These findings are consistent with the hypothesis that the high level of endogenous galanin in injured primary afferents activates peripheral GalR2, which leads to an increase in C-fibre mechanical activation thresholds and a marked reduction in evoked and ongoing nociceptive responses.
De novo assembly of potential linear artificial chromosome constructs capped with expansive telomeric repeats
Authors: Lin Li , Koo Dal-Hoe , Zhang Wenli , St Peter Joseph , Jiang Jiming
Published: April 2011

Background

Artificial chromosomes (ACs) are a promising next-generation vector for genetic engineering. The most common methods for developing AC constructs are to clone and combine centromeric DNA and telomeric DNA fragments into a single large DNA construct. The AC constructs developed from such methods will contain very short telomeric DNA fragments because telomeric repeats can not be stably maintained in Escherichia coli.

Results

We report a novel approach to assemble AC constructs that are capped with long telomeric DNA. We designed a plasmid vector that can be combined with a bacterial artificial chromosome (BAC) clone containing centromeric DNA sequences from a target plant species. The recombined clone can be used as the centromeric DNA backbone of the AC constructs. We also developed two plasmid vectors containing short arrays of plant telomeric DNA. These vectors can be used to generate expanded arrays of telomeric DNA up to several kilobases. The centromeric DNA backbone can be ligated with the telomeric DNA fragments to generate AC constructs consisting of a large centromeric DNA fragment capped with expansive telomeric DNA at both ends.

Conclusions

We successfully developed a procedure that circumvents the problem of cloning and maintaining long arrays of telomeric DNA sequences that are not stable in E. coli. Our procedure allows development of AC constructs in different eukaryotic species that are capped with long and designed sizes of telomeric DNA fragments.
Effect of the dual endothelin receptor antagonist bosentan on untreatable skin ulcers in a patient with diabetes: a case report
Authors: Álvarez Reyes Fátima , Luna Gómez Cristina , Brito Suárez Manuel
Published: April 2011

Introduction

Refractory skin ulcers are a major burden in patients with diabetes. Their pathogenesis is multifactorial, and data increasingly implicate endothelin as a mediator of diabetic macro- and microvasculopathy. Here we describe the first reported case of an endothelin receptor antagonist being used to successfully treat refractory skin ulcers in a patient with diabetes.

Case presentation

An 85-year-old Caucasian man with a 30-year history of type 2 diabetes developed multiple skin ulcerations, including a right heel ulcer. Despite appropriate treatment, the ulcer showed little improvement and the risk of amputation was high. The patient was treated with the dual endothelin receptor antagonist bosentan. After three weeks of treatment, major improvements were observed, and after 21 weeks, all ulcers had healed. No abnormalities were observed during monitoring of blood pressure, erythrocyte sedimentation rate or serum aminotransferase levels.

Conclusion

In patients with refractory ulceration associated with diabetes, bosentan may be of real benefit, especially in terms of amputation prevention. This case supports the proposed role for endothelin in the pathogenesis of skin ulceration in diabetes and is suggestive of a potential benefit of bosentan in this patient type. This case report is of interest to diabetologists and dermatologists.
A comparison of ankle foot orthoses with foot abduction orthoses to prevent recurrence following correction of idiopathic clubfoot by the Ponseti method
Authors: Janicki J. A. , Wright J. G. , Weir S. , Narayanan U. G.
Published: April 2011

The Ponseti method of clubfoot management requires a period of bracing in order to maintain correction. This study compared the effectiveness of ankle foot orthoses and Denis Browne boots and bar in the prevention of recurrence following successful initial management. Between 2001 and 2003, 45 children (69 feet) with idiopathic clubfeet achieved full correction following Ponseti casting with or without a tenotomy, of whom 17 (30 clubfeet) were braced with an ankle foot orthosis while 28 (39 clubfeet) were prescribed with Denis Browne boots and bar. The groups were similar in age, gender, number of casts and tenotomy rates. The mean follow-up was 60 months (50 to 72) in the ankle foot orthosis group and 47 months (36 to 60) in the group with boots and bars. Recurrence requiring additional treatment occurred in 25 of 30 (83%) of the ankle foot orthosis group and 12 of 39 (31%) of the group with boots and bars (p < 0.001). Additional procedures included repeat tenotomy (four in the ankle foot orthosis group and five in the group treated with boot and bars), limited posterior release with or without tendon transfers (seven in the ankle foot orthosis group and two in the group treated with boots and bars), posteromedial releases (nine in the orthosis group) and midfoot osteotomies (five in the orthosis group, p < 0.001).

Following initial correction by the Ponseti method, children managed with boots and bars had far fewer recurrences than those managed with ankle foot orthoses. Foot abduction appears to be important to maintain correction of clubfeet treated by the Ponseti method, and this cannot be achieved with an ankle foot orthosis.
A new uncemented hydroxyapatite-coated femoral component for the treatment of femoral neck fractures
Authors: Sköldenberg O. G. , Salemyr M. O. , Bodén H. S. , Lundberg A. , Ahl T. E. , Adolphson P. Y.
Published: April 2011

Our aim in this pilot study was to evaluate the fixation of, the bone remodelling around, and the clinical outcome after surgery of a new, uncemented, fully hydroxyapatite-coated, collared and tapered femoral component, designed specifically for elderly patients with a fracture of the femoral neck.

We enrolled 50 patients, of at least 70 years of age, with an acute displaced fracture of the femoral neck in this prospective single-series study. They received a total hip replacement using the new component and were followed up regularly for two years.

Fixation was evaluated by radiostereometric analysis and bone remodelling by dual-energy x-ray absorptiometry. Hip function and the health-related quality of life were assessed using the Harris hip score and the EuroQol-5D.

Up to six weeks post-operatively there was a mean subsidence of 0.2 mm (−2.1 to +0.5) and a retroversion of a mean of 1.2° (−8.2° to +1.5°). No component migrated after three months. The patients had a continuous loss of peri-prosthetic bone which amounted to a mean of 16% (−49% to +10%) at two years. The mean Harris hip score was 82 (51 to 100) after two years.

The two-year results from this pilot study indicate that this new, uncemented femoral component can be used for elderly patients with osteoporotic fractures of the femoral neck.
Ice-cream cone reconstruction of the pelvis: a new type of pelvic replacement
Authors: Fisher N. E. , Patton J. T. , Grimer R. J. , Porter D. , Jeys L. , Tillman R. M. , Abudu A. , Carter S. R.
Published: April 2011

Endoprosthetic replacement of the pelvis is one of the most challenging types of limb-salvage surgery, with a high rate of complications. In an attempt to reduce this and build greater versatility into the reconstruction process, a new type of pelvic endoprosthesis was developed in 2003, based on the old McKee-Farrar prosthesis. This study reviews the outcomes in 27 patients who had an ice-cream cone pelvic prosthesis inserted at two different specialist bone tumour centres in the United Kingdom over the past six years. The indications for treatment included primary bone tumours in 19 patients and metastatic disease in two, and six implants were inserted following failure of a previous pelvic reconstruction. Most of the patients had a P2+P3 resection as classified by Enneking, and most had resection of the ilium above the sciatic notch. The mean age of the patients at operation was 49 years (13 to 81). Complications occurred in ten patients (37.0%), of which dislocation was the most common, affecting four patients (14.8%). A total of three patients (11.1%) developed a deep infection around the prosthesis but all were successfully controlled by early intervention and two patients (7.4%) developed a local recurrence, at the same time as widespread metastases appeared. In one patient the prosthesis was removed for severe pain.

This method of treatment is still associated with high morbidity, but early results are promising. Complications are diminishing with increasing experience.
Distal femoral physeal growth arrest secondary to a cemented proximal femoral endoprosthetic replacement
Authors: Gaston C. L. , Tillman R. M. , Grimer R. J.
Published: April 2011

We report a case of spontaneous physeal growth arrest of the distal femur in a nine-year-old child with Ewing’s sarcoma of the proximal femur treated with chemotherapy and endoprosthetic replacement. Owing to the extent of disuse osteoporosis at the time of surgery, the entire intramedullary canal up to the distal femoral physis was filled with cement. Three years later, the femur remained at its pre-operative length of 19 cm. Pre-operative calculations of further growth failed to account for the growth arrest, and the initial expandable growing prosthesis inserted has been revised to a longer one in order to address the leg-length discrepancy.

To our knowledge, this is the only reported case of distal femoral physeal growth arrest following cemented endoprosthetic replacement of the proximal femur.
The centenary of John Charnley’s birth
Authors: Faux J. C.
Published: April 2011

This year is the centenary of the birth of John Charnley. Some of his legacy to Orthopaedic Surgery is described in this editorial.
Das Portal VD 18: Konzeption und Realisierung. Mit einer Einleitung von Heiner Schnelling
Authors: Schmidt Mirjam
Published: April 2011

Gefördert von der Deutschen Forschungsgemeinschaft arbeiten seit November 2009 fünf Bibliotheken in Kooperation mit dem Institut für Historisch-Kulturwissenschaftliche Informationsverarbeitung der Universität zu Köln am Verzeichnis der im deutschen Sprachraum erschienenen Drucke des 18. Jahrhunderts (VD 18): die Staatsbibliothek zu Berlin – Preußischer Kulturbesitz, die Sächsische Landesbibliothek – Staats- und Universitätsbibliothek Dresden, die Niedersächsische Staats-und Universitätsbibliothek Göttingen, die Universitäts- und Landesbibliothek in Halle, die Bayerische Staatsbibliothek in München. Neben der nationalbibliographischen Verzeichnung sind Digitalisierung und vertiefte Erschließung der Drucke zentrale Elemente des Projekts. Um diesen Mehrwert unter einer einheitlichen Oberfläche verfügbar zu machen, wurde an der ULB Halle im Rahmen eines sechsmonatigen Projektes an der konzeptionellen Entwicklung einer Portallösung für das VD 18 gearbeitet.