bluuebunny/crossref_metadata_2025 huggingface dataset:
Spinal extradural arteriovenous malformations with parenchymal drainage: venous drainage variability and implications in clinical manifestations
Authors: Clarke Michelle J. , Patrick Todd A. , White J. Bradley , Cloft Harry J. , Krauss William E. , Lindell E. P. , Piepgras David G.
Published: January 2009

Object

Although nontraumatic spinal arteriovenous malformations and fistulas (AVMs and AVFs) restricted to the epidural space are rare, they can lead to significant neurological morbidity. Careful diagnostic imaging is essential to their detection and the delineation of the pathological anatomy. Aggressive endovascular and open operative treatment can provide arrest and reversal of neurological deficits.

Methods

The authors report on 6 cases of extradural AVMs/AVFs causing progressive myelopathy. Clinical findings, diagnostic evaluation, treatment, and outcome are discussed. Special consideration is given to the anatomy of the lesions and the operative techniques used to treat them. A review of the literature concerning extradural vascular malformations is also presented.

Results

All 6 cases of extradural AVMs had an extradural fistulous location with intradural medullary venous drainage. These cases illustrate progressive myelopathy through cord venous congestion (hypertension) that can be caused by an extradural nidus or fistula. In 4 cases, a large epidural lake was identified on angiography. At surgery, the epidural lake was obliterated and medullary drainage interrupted. All patients had stabilization of their neurological deficits and successful obliteration of the AVM/AVF was obtained.

Conclusions

Extradural AVMs and AVFs are a poorly described entity with published clinical experience limited to sporadic case reports and small series. Although these lesions have a purely extradural location of arteriovenous shunting and early venous drainage, they can be responsible for acute and progressive neurological symptoms similar to those caused by their dural-based intradural counterparts. With careful imaging recognition of the pathological anatomy, surgical and endovascular techniques can be used for the treatment of extradural AVMs affording effective and durable obliteration with stabilization or reversal of neurological symptoms. Venous drainage directly correlates the pathologic mechanisms of presentation. Specific attention must be paid intraoperatively to the epidural lake common to both variants so that recurrence is avoided.
Overview of the current role of endovascular and surgical treatment in spinal dural arteriovenous fistulas
Authors: Dehdashti Amir R. , Da Costa Leodante B. , terBrugge Karel G. , Willinsky Robert A. , Tymianski Michael , Wallace M. Christopher
Published: January 2009

Dural arteriovenous fistulas are the most common vascular malformations of the spinal cord. These benign vascular lesions are considered straightforward targets of surgical treatment and possibly endovascular embolization, but the outcome in these cases depends mainly on the extent of clinical dysfunction at the time of the diagnosis. A timely diagnosis is an equally important factor, with early treatment regardless of the type more likely to yield significant improvements in neurological functioning. The outcomes after surgical and endovascular treatment are similar if complete obliteration of the fistulous site is obtained. In the present study, the authors evaluated the current role of each modality in the management of these interesting lesions.
Advanced noninvasive imaging of spinal vascular malformations
Authors: Eddleman Christopher S. , Jeong Hyun , Cashen Ty A. , Walker Matthew , Bendok Bernard R. , Batjer H. Hunt , Carroll Timothy J.
Published: January 2009

Spinal vascular malformations (SVMs) are an uncommon, heterogeneous group of vascular anomalies that can render devastating neurological consequences if they are not diagnosed and treated in a timely fashion. Imaging SVMs has always presented a formidable challenge because their clinical and imaging presentations resemble those of neoplasms, demyelination diseases, and infection. Advancements in noninvasive imaging modalities (MR and CT angiography) have increased during the last decade and have improved the ability to accurately diagnose spinal vascular anomalies. In addition, intraoperative imaging techniques have been developed that aid in the intraoperative assessment before, during, and after resection of these lesions with minimal and/or optimal use of spinal digital subtraction angiography. In this report, the authors review recent advancements in the imaging of SVMs that will likely lead to more timely diagnoses and treatment while reducing procedural risk exposure to the patients who harbor these uncommon spinal lesions.
One‐Pot Synthesis of Highly Substituted Allenylidene Derivatives via Palladium‐ or Nickel‐Catalyzed Tandem Michael Addition–Cyclization Reaction
Authors: Shi Yun , Huang Jing , Yang Yan‐Fang , Wu Lu‐Yong , Niu Yan‐Ning , Huo Peng‐Fei , Liu Xue‐Yuan , Liang Yong‐Min
Published: January 2009

A simple and tandem synthetic approach, which offers an efficient, direct route to highly substituted indenes, has been developed by palladium‐ or nickel‐catalyzed cyclization of propargylic compounds and nitrogen nucleophiles. The reaction takes place under mild conditions, and a possible mechansim is proposed.
Highly Active and Recyclable Heterogeneous Iridium Pincer Catalysts for Transfer Dehydrogenation of Alkanes
Authors: Huang Zheng , Brookhart Maurice , Goldman Alan S. , Kundu Sabuj , Ray Amlan , Scott Susannah L. , Vicente Brian C.
Published: January 2009

Pincer‐ligated iridium complexes have proven to be highly effective catalysts for the dehydrogenation and transfer‐dehydrogenation of alkanes. Immobilization onto a solid support offers significant potential advantages in the application of such catalysts particularly with respect to catalyst separation and recycling. We describe three approaches toward such immobilization: (i) covalent attachment to a Merrifield resin, (ii) covalent bonding to silica via a pendant alkoxysilane group, and (iii) adsorption on γ‐alumina (γ‐Al2O3), through basic functional groups on the para‐position of the pincer ligand. The simplest of these approaches, adsorption on γ‐Al2O3, is also found to be the most effective, yielding catalysts that are robust, recyclable, and comparable to or even more active than the corresponding species in solution. Spectroscopic evidence (NMR, IR) and studies of catalytic activity support the hypothesis that binding occurs at the para‐substituent and that this has only a relatively subtle and indirect influence on catalytic behavior.
Binding properties of peptidic affinity ligands for plasmid DNA capture and detection
Authors: Han Ying , Gras Sally , Forde Gareth M.
Published: January 2009

Peptides constructed from α‐helical subunits of the Lac repressor protein (LacI) were designed then tailored to achieve particular binding kinetics and dissociation constants for plasmid DNA purification and detection. Surface plasmon resonance was employed for quantification and characterization of the binding of double stranded Escherichia coli plasmid DNA (pUC19) via the lac operon (lacO) to “biomimics” of the DNA binding domain of LacI. Equilibrium dissociation constants (KD), association (ka), and dissociation rates (kd) for the interaction between a suite of peptide sequences and pUC19 were determined. KD values measured for the binding of pUC19 to the 47mer, 27mer, 16mer, and 14mer peptides were 8.8 ± 1.3 × 10−10 M, 7.2 ± 0.6 × 10−10 M, 4.5 ± 0.5 × 10−8 M, and 6.2 ± 0.9 × 10−6 M, respectively. These findings show that affinity peptides, composed of subunits from a naturally occurring operon–repressor interaction, can be designed to achieve binding characteristics suitable for affinity chromatography and biosensor devices. © 2008 American Institute of Chemical Engineers AIChE J, 2009
BK virus nephropathy after allogeneic stem cell transplantation: A case report and literature review
Authors: Lekakis Lazaros J. , Macrinici Valentina , Baraboutis Ioannis G. , Mitchell Bonnie , Howard Dianna S.
Published: January 2009

Polyomaviruses are increasingly recognized as important human pathogens. Among those, BK virus has been identified as the main cause of polyomavirus‐associated nephropathy (PVAN), a major cause of renal allograft failure. PVAN has also been well described in the setting of non‐renal solid organ transplantation. The reports of PVAN after hematopoietic stem cell transplantation (HCT) are surprisingly very few. Here, we describe a patient with treatment‐related myelodysplastic syndrome who received an unrelated donor HCT after ablative conditioning and in vivo T cell depletion with alemtuzumab. He developed a biopsy‐proven BK nephropathy, which contributed to his renal failure. Leflunomide as well as cidofovir were given at different times, both in combination with intravenous immunoglobulin. Both treatments were effective in reducing the BK viral load, the cystitis symptoms and both stabilized but did not really improved the renal function. The patient was still dialysis‐dependent when he died from Pseudomonas sepsis 13 months after HCT. A critical review of the literature and the treatment modalities for post‐HCT PVAN are provided. Am. J. Hematol. 2009. © 2008 Wiley‐Liss, Inc.
Transfer of the shared epitope through microchimerism in women with rheumatoid arthritis
Authors: Rak J. M. , Maestroni L. , Balandraud N. , Guis S. , Boudinet H. , Guzian M. C. , Yan Z. , Azzouz D. , Auger I. , Roudier C. , Martin M. , Didelot R. , Roudier J. , Lambert N. C.
Published: January 2009

Objective

Rheumatoid arthritis (RA) is an autoimmune disease that affects mostly women and is associated with HLA–DRB1 genes having in common a shared epitope sequence. In parallel, cells and/or DNA originating from pregnancy (microchimerism) persist for decades and could contribute to autoimmunity. The aim of this study was to examine whether microchimerism may be a source of the shared epitope among women with RA.

Methods

Women with RA and healthy women who lacked RA‐associated genes such as HLA–DRB1*01 (n = 33 and n = 46, respectively) and/or HLA–DRB1*04 (n = 48 and n = 64, respectively), were tested for DRB1*01 or DRB1*04 microchimerism by HLA‐specific quantitative polymerase chain reaction assays. As controls, alleles not associated with RA (DQB1*02 and DRB1*15/16) were also analyzed.

Results

Compared with healthy women, women (42% with RA had a higher frequency and higher levels of DRB1*04 microchimerism versus 8%; P = 0.00002) as well as DRB1*01 microchimerism (30% versus 4%; P = 0.0015). Moreover, no difference in microchimerism was observed for alleles not associated with RA.

Conclusion

Women with RA had microchimerism with RA‐associated HLA alleles, but not with non–RA‐associated HLA alleles, more often and at higher levels compared with healthy women. These observations are the first to indicate that microchimerism can contribute to the risk of an autoimmune disease by providing HLA susceptibility alleles.
Compensatory ability to null mutation in metabolic networks
Authors: Jiang Da , Zhou Shuigeng , Chen Yi‐Ping Phoebe
Published: January 2009

Robustness is an inherent property of biological system. It is still a limited understanding of how it is accomplished at the cellular or molecular level. To this end, this article analyzes the impact degree of each reaction to others, which is defined as the number of cascading failures of following and/or forward reactions when an initial reaction is deleted. By analyzing more than 800 organism's metabolic networks, it suggests that the reactions with larger impact degrees are likely essential and the universal reactions should also be essential. Alternative metabolic pathways compensate null mutations, which represents that average impact degrees for all organisms are small. Interestingly, average impact degrees of archaea organisms are smaller than other two categories of organisms, eukayote and bacteria, indicating that archaea organisms have strong robustness to resist the various perturbations during the evolution process. The results show that scale‐free feature and reaction reversibility contribute to the robustness in metabolic networks. The optimal growth temperature of organism also relates the robust structure of metabolic network. Biotechnol. Bioeng. 2009;103: 361–369. © 2008 Wiley Periodicals, Inc.
Biofabrication of antibodies and antigens via IgG‐binding domain engineered with activatable pentatyrosine pro‐tag
Authors: Wu Hsuan‐Chen , Shi Xiao‐Wen , Tsao Chen‐Yu , Lewandowski Angela T. , Fernandes Rohan , Hung Chi‐Wei , DeShong Philip , Kobatake Eiry , Valdes James J. , Payne Gregory F. , Bentley William E.
Published: January 2009

We report the assembly of seven different antibodies (and two antigens) into functional supramolecular structures that are specifically designed to facilitate integration into devices using entirely biologically based bottom‐up fabrication. This is enabled by the creation of an engineered IgG‐binding domain (HG3T) with an N‐terminal hexahistidine tag that facilitates purification and a C‐terminal enzyme‐activatable pentatyrosine “pro‐tag” that facilitates covalent coupling to the pH stimuli‐responsive polysaccharide, chitosan. Because we confer pH‐stimuli responsiveness to the IgG‐binding domain, it can be electrodeposited or otherwise assembled into many configurations. Importantly, we demonstrate the loading of both HG3T and antibodies can be achieved in a linear fashion so that quantitative assessment of antibodies and antigens is feasible. Our demonstration formats include: conventional multiwell plates, micropatterned electrodes, and fiber networks. We believe biologically based fabrication (i.e., biofabrication) provides bottom‐up hierarchical assembly of a variety of nanoscale components for applications that range from point‐of‐care diagnostics to smart fabrics. Biotechnol. Bioeng. 2009;103: 231–240. © 2008 Wiley Periodicals, Inc.
Fractionation of β‐Lactoglobulin from whey by mixed matrix membrane ion exchange chromatography
Authors: Saufi Syed M. , Fee Conan J.
Published: January 2009

Mixed matrix membranes (MMMs), which incorporate adsorptive particles during membrane casting, can be prepared simply and have performances that are competitive with other membrane chromatography materials. The application of MMM chromatography for fractionation of β‐Lactoglobulin from bovine whey is described in this article. MMM chromatography was prepared using ethylene vinyl alcohol polymer and lewatit anion exchange resin to form a flat sheet membrane. The membrane was characterized in terms of structure and its static and dynamic binding capacities were measured. The optimum binding for β‐Lactoglobulin was found to be at pH 6.0 using 20 mM sodium phosphate buffer. The MMM had a static binding capacity of 120 mg/g membrane (36 mg/mL membrane) and 90 mg/g membrane (27 mg/mL membrane) for β‐Lactoglobulin and α‐Lactalbumin, respectively. In batch fractionation of whey, the MMM showed selective binding towards β‐Lactoglobulin compared to other proteins. The dynamic binding capacity of β‐Lactoglobulin in whey solution was about 80 mg/g membrane (24 mg β‐Lac/mL of MMM), which is promising for whey fractionation using this technology. This is the first reported application of MMM chromatography to a dairy feed stream. Biotechnol. Bioeng. 2009;103: 138–147. © 2008 Wiley Periodicals, Inc.
“Enzyme Test Bench,” a high‐throughput enzyme characterization technique including the long‐term stability
Authors: Rachinskiy Kirill , Schultze Hergen , Boy Matthias , Bornscheuer Uwe , Büchs Jochen
Published: January 2009

A new high throughput technique for enzyme characterization with specific attention to the long term stability, called “Enzyme Test Bench,” is presented. The concept of the Enzyme Test Bench consists of short term enzyme tests in 96‐well microtiter plates under partly extreme conditions to predict the enzyme long term stability under moderate conditions. The technique is based on the mathematical modeling of temperature dependent enzyme activation and deactivation. Adapting the temperature profiles in sequential experiments by optimal non‐linear experimental design, the long term deactivation effects can be purposefully accelerated and detected within hours. During the experiment the enzyme activity is measured online to estimate the model parameters from the obtained data. Thus, the enzyme activity and long term stability can be calculated as a function of temperature. The engineered instrumentation provides for simultaneous automated assaying by fluorescent measurements, mixing and homogenous temperature control in the range of 10–85 ± 0.5°C. A universal fluorescent assay for online acquisition of ester hydrolysis reactions by pH‐shift is developed and established. The developed instrumentation and assay are applied to characterize two esterases. The results of the characterization, carried out in microtiter plates applying short term experiments of hours, are in good agreement with the results of long term experiments at different temperatures in 1 L stirred tank reactors of a week. Thus, the new technique allows for both: the enzyme screening with regard to the long term stability and the choice of the optimal process temperature regarding such process parameters as turn over number, space time yield or optimal process duration. The comparison of the temperature dependent behavior of both characterized enzymes clearly demonstrates that the frequently applied estimation of long term stability at moderate temperatures by simple activity measurements after exposing the enzymes to elevated temperatures may lead to suboptimal enzyme selection. Thus, temperature dependent enzyme characterization is essential in primary screening to predict its long term behavior. Biotechnol. Bioeng. 2009;103: 305–322. © 2008 Wiley Periodicals, Inc.
A virtual electric machine laboratory for synchronous machine application
Authors: Tanyildizi E. , Orhan A.
Published: January 2009

Engineering education can reach the desired level if practical laboratory works are given together with the theory. In electrical engineering education, if foundation costs are considered the electrical machine labs become very important. Due to the increasing number of students accessing the university educational structures, the cost of laboratories for didactical electric machine applications is going to be very high. In this study, virtual laboratory, which is found to have wide application field in recent years, is introduced. For this purpose, a virtual electrical machine lab for electrical engineering lab courses is developed. An example of application was presented for the control of synchronous motor and no‐load and blocked rotor test of synchronous generator. Moreover, this study explores the learning effect related to different learning styles of web‐based virtual lab that has developed in electric engineering students. © 2008 Wiley Periodicals, Inc. Comput Appl Eng Educ 17: 187–195, 2009; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae20133
A compulsory yet motivating question/answer game to teach computer fundamentals
Authors: Natvig Lasse , Sindre Guttorm , Djupdal Asbjørn
Published: January 2009

Age of Computers is a web‐based multi‐player game for teaching computer fundamentals to undergraduate engineering students. The storyline of the game is linked to the historical periods (epochs) of computers, and the content is organized in rooms or places on a map where the player moves around to answer questions and solve puzzles. This paper reports on the usage of the game in a course with 250 undergraduate students. Both questionnaire surveys and observations of student behavior indicate that the game was positively received even if the students were obliged to use it in the context of the course. © 2008 Wiley Periodicals, Inc. Comput Appl Eng Educ 17: 167–179, 2009; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae20173
Emotional reactions, coping and long‐term consequences of perceived discrimination among the Mapuche people of Chile
Authors: Mellor David , Merino María Eugenia , Saiz José L. , Quilaqueo Daniel
Published: January 2009

Although a substantial body of research has now documented the negative mental and physical health impacts of discrimination on various minority/non‐dominant groups, little has been reported on the impacts of such discrimination on indigenous populations. In this study, we investigated the self‐reported emotional reactions, coping responses and long‐term impacts of discriminatory experiences among 50 Mapuche adults in Chile. The limited literature suggests that a substantial proportion of the Chilean majority society is prejudiced and discriminatory towards the indigenous Mapuche population, and that the Mapuche experience discrimination. Interviews with participants indicated that discrimination was psychologically wounding, and aroused anger, undifferentiated bad feelings, shame and a sense of powerlessness. Participants responded with self‐protective, self‐controlled or confronting actions. Although negative long‐term effects were reported, ethnic re‐affirmation and strengthening of bonds within the Mapuche community were positive outcomes that seem to provide resilience for the participants. This does not discount however, the need for more research assessing the impacts of discrimination in Chile nor the need for anti‐discrimination measures to be implemented. Copyright © 2008 John Wiley & Sons, Ltd.
Ex vivo Activities of β‐Lapachone and α‐Lapachone on Macrophages: A Quantitative Pharmacological Analysis Based on Amperometric Monitoring of Oxidative Bursts by Single Cells
Authors: Ferreira Danielle C. M. , Tapsoba Issa , Arbault Stéphane , Bouret Yann , Alexandre Moreira Magna Suzana , Ventura Pinto Antônio , Goulart Marília O. F. , Amatore Christian
Published: January 2009

Artificial synapses for femtomolar detection: Amperometry at platinized carbon fibre electrodes has been used to unravel the complexity of β‐lapachone's effects on cellular oxidative stress. α‐Lapachone, the pharmacologically inactive para‐quinone isomer, did not display such characteristics, but over longer incubation periods both quinones induced apoptosis. The observed effects were interpreted in terms of two mechanisms involving opposite reactivities of quinones in living cells.

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β‐Lapachone (1) has been widely used for its pharmacological activity, particularly against cancer. However, its mechanism of action at the cellular level remains unclear, although a common major hypothesis involves its prooxidant properties. Electrochemical measurements with microelectrodes were taken in order to quantitatively investigate the activity of 1 at different concentrations and several incubation times, on the oxidative bursts released by single macrophages. The exact natures of the electroactive reactive oxygen species (ROS) and reactive nitrogen species (RNS) released by macrophages under the effect of 1 were characterized, and their fluxes were measured quantitatively. This allowed the reconstruction of the primary O2.− and NO production by the cells. In the first hour, at 10 μM, the decrease in the oxidative burst involved mainly RNS, while the amount of H2O2 was found to be higher than in controls. After a longer incubation time—that is, 4 h—at 1 μM, the total amount of ROS and RNS had increased, with significant enhancements of H2O2 and NO. In contrast, α‐lapachone, the pharmacologically inactive para‐quinone isomer, was unable to increase the production of RONS by macrophages significantly. Over much longer incubation periods (about one day), however, each quinone induced cell death by apoptosis. All these effects were interpreted by consideration of two different mechanisms involving opposite reactivities of quinones in living cells.
Isolation of Phospholipase D Mutants Having Phosphatidylinositol‐Synthesizing Activity with Positional Specificity on myo‐Inositol
Authors: Masayama Atsushi , Tsukada Kaori , Ikeda Chika , Nakano Hideo , Iwasaki Yugo
Published: January 2009

Enzyme‐mediated synthesis of phosphatidylinositol: Engineered phospholipase D enzymes enable the synthesis of phosphatidylinositol by transphosphatidylation. The 1‐ or 3‐hydroxy group of myo‐inositol is selectively reacted.

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Phospholipase D (PLD) mutants that have phosphatidylinositol (PI)‐synthesizing activity with positional selectivity towards 1‐ or 3‐OH groups of myo‐inositol have been isolated. A mutant PLD library, in which site‐directed saturation mutations were introduced in vitro at positions 187, 191, and 385 of the wild‐type PLD of Streptomyces antibioticus, was screened for PI‐synthesizing mutants. TLC and HPLC analyses of the PI synthesized by the isolated mutant PLDs revealed that three mutants, namely 187D/191Y/385R (DYR), 187A/191Y/385R (AYR), and 187M/191Y/385R (MYR), selectively generated 1‐ or 3‐PI among the other possible PI positional isomers. Taking into account the consensus sequence of the three mutants, a series of mutants, 187X/191Y/385R (XYR), was constructed and analyzed. Almost all the XYR mutants generated 1(3)‐PI selectively, thus suggesting that the Y385R mutation contributed to the selectivity for the 1(3)‐PI synthesis. The XYR mutants showed similar phosphatidylcholine‐hydrolyzing activity among the mutants, but the PI‐synthesizing activities were different depending on the amino acid at position 187. In particular, aromatic amino acids at position 187 greatly reduced the PI‐synthesizing activity. The ratios of 1‐PI versus 3‐PI in the PIs synthesized with the XYR mutants were analyzed by selective hydrolysis with PI‐specific phospholipase C. It was found that 187H/191Y/385R (HYR) generated 1‐PI more than 3‐PI (ratio=7:3), whereas 187T/191Y/385R (TYR) generated 1‐PI less than 3‐PI (ratio=2:8). This confirmed that the amino acid at position 187 determined the selectivity between 1‐PI and 3‐PI formation.
Left coronary artery thrombus characterized by a fully automatic three‐dimensional gated reconstruction
Authors: Schoonenberg Gert A.F. , Garcia Joel A. , Carroll John D.
Published: January 2009

Rotational coronary angiography and subsequent automatic modeling or reconstruction can result in clinically valuable three‐dimensional (3D) representations of the coronaries. From these 3D representations information can be derived for specific coronary segments, such as lesion length, vessel diameter, bifurcation angles, and optimal viewing angles. In this case report, we highlight the characterization of a left coronary artery thrombus by a fully automatic 3D gated reconstruction. This case also shows that detailed 3D morphology of a lesion can be assessed during percutaneous coronary interventions using rotational coronary angiography and subsequent automated image processing. © 2009 Wiley‐Liss, Inc.
Clinical outcomes using aggressive approach to anatomic screening and endovascular revascularization in a veterans affairs population with critical limb ischemia
Authors: Shah Alap P. , Klein Andrew J. , Sterrett Andrew , Messenger John C. , Albert Stephen , Nehler Mark R. , Hiatt William R. , Casserly Ivan P.
Published: January 2009

Background: This study sought to examine the impact of an aggressive approach to anatomic screening and endovascular revascularization in a veterans administration population with critical limb ischemia (CLI) on the primary treatments received and overall clinical outcomes. Methods: The baseline clinical and angiographic characteristics and clinical outcomes of the first consecutive fifty veterans who were referred for the evaluation and treatment of CLI using the strategy outlined were assessed by retrospective review of the computerized medical record and angiographic data. Results: Among the entire cohort, the primary treatments received were as follows – revascularization n = 44 (88%), primary amputation n = 1 (2%), medical treatment n = 3 (6%), and primary minor amputation n = 2 (4%). Endovascular revascularization was the dominant mode of revascularization (94%), with a procedural success rate of 91%. Repeat revascularization was required in 19% of patients who had an initially successful endovascular procedure. A total of eight deaths and four major amputations occurred in the entire cohort over a mean follow‐up of 397 ± 190 days. The 1‐year Kaplan‐Meier estimates for survival and amputation‐free survival for the entire cohort were 90 and 81%, respectively. Resolution of rest pain or complete wound healing was achieved in 85% of patients at a mean of 157 ±126 days. Conclusions: An aggressive approach to anatomic screening and contemporary endovascular treatment of CLI resulted in a higher rate of revascularization as the primary treatment for CLI than previously reported, and was associated with high rates of overall and amputation‐free survival. © 2009 Wiley‐Liss, Inc.
Nanoparticle‐Supported and Magnetically Recoverable Ruthenium Hydroxide Catalyst: Efficient Hydration of Nitriles to Amides in Aqueous Medium
Authors: Polshettiwar Vivek , Varma Rajender S.
Published: January 2009

Magnetic attraction not filtration: A magnetic nanoparticle‐supported ruthenium hydroxide catalyst (see figure) was readily prepared from inexpensive starting materials and shown to catalyze the hydration of nitriles with excellent yield in a benign aqueous medium. Catalyst recovery using an external magnetic field, superior activity, and the inherent stability of the catalyst system are additional sustainable attributes of this protocol.

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No Abstract
Highly Enantioselective Conjugate Additions of Aldehydes to Vinyl Sulfones
Authors: Landa Aitor , Maestro Miguel , Masdeu Carme , Puente Ángel , Vera Silvia , Oiarbide Mikel , Palomo Claudio
Published: January 2009

Joined together, organocatalysts aldehydes and sulfones: A diaryl prolinol silyl ether was found to catalyse efficiently and enantioselectively the conjugate addition of aldehydes to vinyl sulfones (see scheme). The ample synthetic utility of the resulting adducts is illustrated.

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No Abstract
Cost‐effectiveness analysis of lapatinib in HER‐2–positive advanced breast cancer
Authors: Le Quang A. , Hay Joel W.
Published: January 2009

BACKGROUND:

A recent clinical trial demonstrated that the addition of lapatinib to capecitabine in the treatment of HER‐2–positive advanced breast cancer (ABC) significantly increases median time to progression. The objective of the current analysis was to assess the cost‐effectiveness of this therapy from the US societal perspective.

METHODS:

A Markov model comprising 4 health states (stable disease, respond‐to‐therapy, disease progression, and death) was developed to estimate the projected‐lifetime clinical and economic implications of this therapy. The model used Monte Carlo simulation to imitate the clinical course of a typical patient with ABC and updated with response rates and major adverse effects. Transition probabilities were estimated based on the results from the EGF100151 and EGF20002 clinical trials of lapatinib. Health state utilities, direct and indirect costs of the therapy, major adverse events, laboratory tests, and costs of disease progression were obtained from published sources. The model used a 3% discount rate and reported in 2007 US dollars.

RESULTS:

Over a lifetime, the addition of lapatinib to capecitabine as combination therapy was estimated to cost an additional $19,630, with an expected gain of 0.12 quality‐adjusted life years (QALY) or an incremental cost‐effectiveness ratio (ICER) of $166,113 per QALY gained. The 95% confidence limits of the ICER ranged from $158,000 to $215,000/QALY. A cost‐effectiveness acceptability curve indicated less than 1% probability that the ICER would be lower than $100,000/QALY.

CONCLUSIONS:

Compared with commonly accepted willingness‐to‐pay thresholds in oncology treatment, the addition of lapatinib to capecitabine is not clearly cost‐effective; and most likely to result in an ICER somewhat higher than the societal willingness‐to‐pay threshold limits. Cancer 2009. © 2008 American Cancer Society.
Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas
Authors: Chang Daniel T. , Schellenberg Devin , Shen John , Kim Jeff , Goodman Karyn A. , Fisher George A. , Ford James M. , Desser Terry , Quon Andrew , Koong Albert C.
Published: January 2009

BACKGROUND:

The authors report on the local control and toxicity of stereotactic body radiotherapy (SBRT) for patients with unresectable pancreatic adenocarcinoma.

METHODS:

Seventy‐seven patients with unresectable adenocarcinoma of the pancreas received 25 gray (Gy) in 1 fraction. Forty‐five patients (58%) had locally advanced disease, 11 patients (14%) had medically inoperable disease, 15 patients (19%) had metastatic disease, and 6 patients (8%) had locally recurrent disease. Nine patients (12%) had received prior chemoradiotherapy. Sixteen patients (21%) received between 45 to 54 Gy of fractionated radiotherapy and SBRT. Various gemcitabine‐based chemotherapy regimens were received by 74 patients (96%), but 3 patients (4%) did not receive chemotherapy until they had distant failure.

RESULTS:

The median follow‐up was 6 months (range, 3‐31 months) and, among surviving patients, it was 12 months (range, 3‐31 months). The overall rates of freedom from local progression (FFLP) at 6 months and 12 months were 91% and 84%, respectively. The 6‐ and 12‐month isolated local recurrence rates were 5% and 5%, respectively. There was no difference in the 12‐month FFLP rate based on tumor location (head/uncinate, 91% vs body/tail, 86%; P = .52). The progression‐free survival (PFS) rates at 6 months and 12 months were 26% and 9%, respectively. The PFS rate at 6 months was superior for patients who had nonmetastatic disease versus patients who had metastatic disease (28% vs 15%; P = .05). The overall survival (OS) rates at 6 months and 12 months from SBRT were 56% and 21%, respectively. Four patients (5%) experienced grade ≥2 acute toxicity. Three patients (4%) experienced grade 2 late toxicity, and 7 patients (9%) experienced grade ≥3 late toxicity. At 6 months and 12 months, the rates of grade ≥2 late toxicity were 11% and 25%, respectively.

CONCLUSIONS:

SBRT for pancreatic adenocarcinoma was effective for local control with associated risk of toxicity and should be used with rigorous attention to quality assurance. Efforts to reduce complications are warranted. Distant metastases account for the vast majority of disease‐related mortality. Cancer 2009. © 2008 American Cancer Society.
Autoantibodies in autoimmune polyglandular syndrome type I patients react with major brain neurotransmitter systems
Authors: Fetissov Sergueï O. , Bensing Sophie , Mulder Jan , Le Maitre Erwan , Hulting Anna‐Lena , Harkany Tibor , Ekwall Olov , Sköldberg Filip , Husebye Eystein S. , Perheentupa Jaakko , Rorsman Fredrik , Kämpe Olle , Hökfelt Tomas
Published: January 2009

Patients with autoimmune polyglandular syndrome type I (APS1) often display high titers of autoantibodies (autoAbs) directed against aromatic L‐amino acid decarboxylase (AADC), tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), and glutamic acid decarboxylase (GAD). Neurological symptoms, including stiff‐man syndrome and cerebellar ataxia, can occur in subjects with high levels of GAD autoAbs, particularly when patient sera can immunohistochemically stain γ‐aminobutyric acid (GABA) neurons. However, it was not known if APS1 sera can also stain major monoamine systems in the brain. Therefore, in this work we applied sera from 17 APS1 patients known to contain autoAbs against AADC, TH, TPH, and/or GAD to rat brain sections and processed the sections according to the sensitive immunohistochemical tyramide signal amplification method. We found that autoAbs in sera from 11 patients were able to stain AADC‐containing dopaminergic, serotonergic, and noradrenergic as well as AADC only (D‐group) neurons and fibers in the rat brain, in several cases with a remarkably high quality and sensitivity (dilution up to 1:1,000,000); and, since they are human antibodies, they offer a good opportunity for performing multiple‐labeling experiments using antibodies from other species. Six APS1 sera also stained GABAergic neuronal circuitries. Similar results were obtained in the mouse and primate brain. Our data demonstrate that many APS1 sera can immunostain the major monoamine and GABA systems in the brain. Only in a few cases, however, there was evidence that these autoAbs can be associated with neurological manifestations in APS1 patients, as,, e.g.,, shown in stiff‐man syndrome. J. Comp. Neurol. 513:1–20, 2009. © 2008 Wiley‐Liss, Inc.
An investigation of pulsatile flow in a model cavo‐pulmonary vascular system
Authors: Chitra K. , Vengadesan S. , Sundararajan T. , Nithiarasu P.
Published: January 2009

The complexities in the flow pattern in a cavo‐pulmonary vascular system—after application of the Fontan procedure in the vicinity of the superior vena cava, inferior vena cava, and the confluence at the T‐junction—are analysed. A characteristic‐based split (CBS) finite element scheme involving the artificial compressibility approach is employed to compute the resulting flow. Benchmarking of the CBS scheme is carried out using standard problems and with the flow features observed in an experimental model with the help of a dye visualization technique in model scale. The transient flow variations in a total cavo‐pulmonary connection (TCPC) under pulsatile conditions are investigated and compared with flow visualization studies. In addition to such qualitative flow investigations, quantitative analysis of energy loss and haemodynamic stresses have also been performed. The comparisons show good agreement between the numerical and experimental flow patterns. The numerically predicted shear stress values indicate that the pulsatile flow condition is likely to be more severe than steady flow, with regard to the long‐term health of the surgically corrected TCPC. Copyright © 2008 John Wiley & Sons, Ltd.
Discrepancies of energy values in dynamics of three intersecting plates
Authors: Chróścielewski J. , Witkowski W.
Published: January 2009

In this paper we discuss the discrepancies between results reported in the literature in the context of dynamics of shell structure composed of three intersecting plates. The shell structure is subjected to a system of spatially uniformly distributed dead loads of prescribed time variation. Once the forces die out, the structure experiences free motion. The comparison of reported solutions from the literature shows that the total energy in free motion has different values, despite the fact that the same material, geometry and loads have been used. The aim of study is to address the issue by referring own results to that known from the literature. Copyright © 2008 John Wiley & Sons, Ltd.
The challenge of mass conservation in the solution of free‐surface flows with the fractional‐step method: Problems and solutions
Authors: Idelsohn Sergio R. , Oñate Eugenio
Published: January 2009

The purpose of this paper is to put in evidence that the fractional‐step method (FSM) used to solve the incompressible transient Euler and Navier–Stokes equations for free‐surface flows has a problem inherent to the method that may produce unacceptable variations of the domain volume. A simple modification of the free‐surface boundary term is introduced in order to reduce considerably the volume loss and preserve the computational advantages of the FSM. Copyright © 2008 John Wiley & Sons, Ltd.
The IRG mouse: A two‐color fluorescent reporter for assessing Cre‐mediated recombination and imaging complex cellular relationships in situ
Authors: De Gasperi Rita , Rocher Anne B. , Sosa Miguel A. Gama , Wearne Susan L. , Perez Gissel M. , Friedrich Victor L. , Hof Patrick R. , Elder Gregory A.
Published: January 2009

Fluorescent image of CA1 pyramidal cell layer in the hippocampus of an adult IRG/Nestin‐Cre double transgenic mouse. The new IRG transgenic mouse line expresses DsRed‐Express fluorescent protein but upon cre‐mediated recombination expresses green fluorescent protein. Recombined pyramidal cells are green and non‐recombined blood vessels are red. See the paper by De Gasperi et al. in this issue.
Generation and characterization of Csrp1 enhancer‐driven tissue‐restricted Cre‐recombinase mice
Authors: Snider Paige , Fix Jana L. , Rogers Rhonda , Peabody‐Dowling Goldie , Ingram David , Lilly Brenda , Conway Simon J.
Published: January 2009

Histological section showing beta‐galactosidase staining (blue) of embryonic day 12.5 heart from a new cysteine‐rich protein (Cspr1) transgenic mouse strain crossed to the R26R cre reporter mouse. Staining is found specifically in the outflow tract cushions and myocardial cuff. See the paper by Snider et al. in the March 2008 issue.
3,5‐Disubstituted Isoxazolines as Potential Molecular Kits for Liquid‐Crystalline Materials
Authors: Tavares Aline , Schneider Paulo H. , Merlo Aloir A.
Published: January 2009

A collection of 3,5‐disubstituted isoxazolines have been synthesized by 1,3‐dipolar [3+2] cycloaddition reactions. Some isoxazolines were selected and transformed into liquid crystals. These new liquid crystals exhibit nematic and smectic C mesophases. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Sweets for Catalysis – Facile Optimisation of Carbohydrate‐Based Bis(oxazoline) Ligands
Authors: Minuth Tobias , Irmak Mustafa , Groschner Annika , Lehnert Tobias , Boysen Mike M. K.
Published: January 2009

A new type of carbohydrate‐based bis(oxazoline) ligands was prepared from inexpensive D‐glucosamine and tested in asymmetric cyclopropanation reactions. For optimisation, modified ligands with 3‐O substituents of varying size and electronic properties were prepared as well as a 3‐OH unprotected and a perpivaloylated derivative. All new ligands were tested in asymmetric cyclopropanation, revealing a strong dependence of enantioselectivity on steric demand and electronic properties of the 3‐O residue. Also, a significant influence of the pyranose conformation, which is determined by the presence or absence of the cyclic acetal group, was observed. Thus, it was easily possible to tune the new carbohydrate bis(oxazoline) ligands to a given reaction.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
The application of a novel flame retardant on viscose fiber
Authors: Hu Jiang‐tao , Yao Yong‐nan , Liu Xiu‐sen , Ao Yu‐hui , Zhang Hui‐xuan
Published: January 2009

The paper is mainly about a novel organophosphorus flame‐retardant N‐1‐chloroisopropyl alcohol‐3‐dimethylphosphonopropionamide. Dimethyl phosphate, acrylamide and epichlorohydrin were used as raw materials. The mechanisms of synthesis and molecule structure of the flame retardant were discussed. The fiber was treated using the pad‐dry‐cure‐wash method. The limiting oxygen index value of the modified sample was 31%, higher than that of the sample treated with MDPA (Pyrovatex CP). After 50 laundry cycles, it still had some flame retardancy left. Thermogravimetry (TG) and Differentiate TG analyses confirmed that the flame retardant caused fiber to decompose below its ignition temperature and formed carbonaceous residue or char when exposed to fire. The treatment had an obvious effect on the denier of the fiber; the tensile strength of fiber slightly decreased, but that effect could be negligible. Copyright © 2008 John Wiley & Sons, Ltd.
Can CSF biomarkers or pre‐treatment progression rate predict response to cholinesterase inhibitor treatment in Alzheimer's disease?
Authors: Wallin Å. K. , Hansson O. , Blennow K. , Londos E. , Minthon L.
Published: January 2009

Objective

The main objective of this study was to investigate possible predictors of response to cholinesterase inhibitor (ChEI) treatment, including pre‐treatment progression rates and levels of the cerebrospinal fluid (CSF) biomarkers. A secondary objective was to evaluate whether treatment with ChEI changed progression.

Methods

Out‐patient individuals (n = 191) with the clinical diagnosis of Alzheimer's disease received ChEI treatment and were part of the Swedish Alzheimer Treatment Study (SATS), a prospective, longitudinal, non‐randomised study in a routine clinical setting. Patients were assessed with MMSE, ADAS‐cog and a global rating (CIBIC) at baseline, 2 months and every 6 months for a total period of 3 years. The following potential predictors of treatment response were investigated: age, gender, APOE ε4 carrier, education, duration of disease, cognitive level, pre‐treatment progression rate (in MMSE) and the levels of the CSF biomarkers Aβ42, T‐tau and P‐tau.

Results

Fast pre‐treatment progression rate was a predictor of treatment response even after adjusting for baseline severity, another positive predictor of response. Patients in the fastest quartile of pre‐treatment progression rates were significantly more prone to be responders at 2 months (adjusted OR 6.6, p = 0.001) and 6 months (adjusted OR 10.4, p < 0.001) than those in the slowest progressing quartile. Moreover, the linearity of progression was significantly changed by ChEI treatment at 6 months compared to the pre‐treatment period.

Conclusion

The rate of pre‐treatment progression was the most consistent positive predictor of ChEI treatment response in the routine clinical setting. The progression rate was significantly changed by ChEI treatment. Copyright © 2009 John Wiley & Sons, Ltd.
Increased self‐focus in major depressive disorder is related to neural abnormalities in subcortical‐cortical midline structures
Authors: Grimm Simone , Ernst Jutta , Boesiger Peter , Schuepbach Daniel , Hell Daniel , Boeker Heinz , Northoff Georg
Published: January 2009

Patients with major depressive disorder (MDD) often show a tendency to strongly introspect and reflect upon their self, which has been described as increased self‐focus. Although subcortical‐cortical midline structures have been associated with reflection and introspection of oneself in healthy subjects, the neural correlates of the abnormally increased attribution of negative emotions to oneself, i.e. negative self‐attribution, as hallmark of the increased self‐focus in MDD remain unclear. The aim of the study was, therefore, to investigate the neural correlates during judgment of self‐relatedness of positive and negative emotional stimuli thereby testing for emotional self‐attribution. Using fMRI, we investigated 27 acute MDD patients and compared them with 25 healthy subjects employing a paradigm that focused on judgment of self‐relatedness when compared with mere perception of the very same emotional stimuli. Behaviourally, patients with MDD showed significantly higher degrees of self‐relatedness of specifically negative emotional stimuli when compared with healthy subjects. Neurally, patients with MDD showed significantly lower signal intensities in various subcortical and cortical midline regions like the dorsomedial prefrontal cortex (DMPFC), supragenual anterior cingulate cortex, precuneus, ventral striatum (VS), and the dorsomedial thalamus (DMT). Signal changes in the DMPFC correlated with depression severity and hopelessness whereas those in the VS and the DMT were related to judgment of self‐relatedness of negative emotional stimuli. In conclusion, we present first evidence that the abnormally increased negative self‐attribution as hallmark of the increased self‐focus in MDD might be mediated by altered neural activity in subcortical‐cortical midline structures. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.