bluuebunny/crossref_metadata_2025 huggingface dataset:
VPg of murine norovirus binds translation initiation factors in infected cells
Authors: Daughenbaugh Katie F , Wobus Christiane E , Hardy Michele E
Published: May 2006

Background

Norovirus genomic and subgenomic RNAs are covalently linked at the 5' nucleotide to a 15 kD protein called VPg. VPg of two human norovirus strains binds translation initiation factor eIF3 and other eIFs in vitro, suggesting VPg functions in initiation of protein synthesis on viral RNA. Human norovirus strains are not cultivable, and thus experimental evidence of interactions between VPg and eIFs in infected cells has been lacking. We used the cultivable murine norovirus MNV-1 as a model to study interactions between VPg and eIFs in infected cells.

Results

As shown previously for human norovirus VPg, MNV-1 VPg bound eIF3, eIF4GI, eIF4E, and S6 ribosomal protein in cell extracts by GST pull-down assay. Importantly, MNV-1 VPg co-precipitated eIF4GI and eIF4E from infected macrophages, providing evidence that VPg interacts with components of the translation machinery in norovirus infected cells.

Conclusion

The interactions between MNV-1 VPg and eIFs completely mimic those reported for the human norovirus VPg, illustrating the utility of MNV-1 as a relevant molecular model to study mechanisms of human norovirus replication.
Self-harm in British South Asian women: psychosocial correlates and strategies for prevention
Authors: Husain MI , Waheed W , Husain Nusrat
Published: May 2006

Objective

To review the rates of self-harm in British South Asian women, look into the factors that contribute to these high rates of self-harm and discuss possible strategies for prevention and provision of culturally sensitive service for South Asian women who harm themselves.

Method

Review.

Results

South Asian women are significantly more likely to self harm between ages 16–24 years than white women. Across all age groups the rates of self harm are lower in South Asian men as compared to South Asian women. These women are generally younger, likely to be married and less likely to be unemployed or use alcohol or other drugs. They report more relationship problems within the family. South Asian women are less likely to attend the ER with repeat episode since they hold the view that mainstream services do not meet their needs.

Conclusion

South Asian women are at an increased risk of self harm. Their demographic characteristics, precipitating factors and clinical management are different than whites. There is an urgent need for all those concerned with the mental health services for ethnic minorities to take positive action and eradicate the barriers that prevent British South Asians from seeking help. There is a need to move away from stereotypes and overgeneralisations and start from the user's frame of reference, taking into account family dynamics, belief systems and cultural constraints.
The experience of brace treatment in children/adolescents with scoliosis
Authors: Sapountzi-Krepia Despina , Psychogiou Maria , Peterson Darin , Zafiri Vassiliki , Iordanopoulou Eugenia , Michailidou Fotini , Christodoulou Anastassios
Published: May 2006

Background

Idiopathic scoliosis is a chronic illness with several different braces used for its treatment. Brace treatment during childhood/adolescence can produce stress. There are studies supporting that it can decrease body-image perception while other studies support that it has no such effect.

The purpose of this study was to explore the experience of brace treatment in children/adolescents with scoliosis. The aim was to investigate which feelings are created by the bracing experience in children/adolescents with scoliosis and what are the children/adolescents' with scoliosis opinions of the support provided to them by health-care professionals and by their families.

Methods

We conducted interviews with the help of a semi-structured interview guide in order to address the topic of the experience of brace treatment. A convenient sample of twelve children and adolescents with scoliosis was selected from patients attending follow-up appointments at the Outpatient Scoliosis Clinics of two Greek hospitals. The data was analysed using the method of content analysis.

Results

Patients in the sample were 10–16 years old and they were mainly females (71%). Almost all of the participants reported having to deal with stress, denial, fear, anger, and shame. They were satisfied with the information they received regarding their condition and therapy. However, the information was not accompanied by support from the health care professionals. They reported that they were receiving support mainly from their families, friends, and classmates.

Conclusion

The present study is contributing to the development of a better understanding of significant issues related to the experience of bracing therapy. It is clear that scoliosis children/adolescents have to be provided with support during the long period of bracing. It is apparent that those children/adolescents have unmet needs for care and health professionals and policy makers should try to find a way to address those needs.
Management of acute pancreatitis: current knowledge and future perspectives
Authors: Fantini Lorenzo , Tomassetti Paola , Pezzilli Raffaele
Published: May 2006

In recent years, a number of articles have been published on the treatment of acute pancreatitis in experimental models and most of them concerned animals with mild disease. However, it is difficult to translate these results into clinical practice. For example, infliximab, a monoclonal TNF antibody, was experimentally tested in rats and it was found to significantly reduce the pathologic score and serum amylase activity and also to alleviate alveolar edema and acute respiratory distress syndrome; however, no studies are available in clinical human acute pancreatitis. Another substance, such as interleukin 10, was efficacious in decreasing the severity and mortality of lethal pancreatitis in rats, but seems to have no effect on human severe acute pancreatitis. Thus, the main problem in acute pancreatitis, especially in the severe form of the disease, is the difficulty of planning clinical studies capable of giving reliable statistically significant answers regarding the benefits of the various proposed therapeutic agents previously tested in experimental settings.

According to the pathophysiology of acute pancreatitis, the efficacy of the drugs already available, such as gabexate mesilate, lexipafant and somatostatin should be re-evaluated and should be probably administered in a different manner. Of course, also in this case, we need adequate studies to test this hypothesis.
Intron gain and loss in segmentally duplicated genes in rice
Authors: Lin Haining , Zhu Wei , Silva Joana C , Gu Xun , Buell C Robin
Published: May 2006

Background

Introns are under less selection pressure than exons, and consequently, intronic sequences have a higher rate of gain and loss than exons. In a number of plant species, a large portion of the genome has been segmentally duplicated, giving rise to a large set of duplicated genes. The recent completion of the rice genome in which segmental duplication has been documented has allowed us to investigate intron evolution within rice, a diploid monocotyledonous species.

Results

Analysis of segmental duplication in rice revealed that 159 Mb of the 371 Mb genome and 21,570 of the 43,719 non-transposable element-related genes were contained within a duplicated region. In these duplicated regions, 3,101 collinear paired genes were present. Using this set of segmentally duplicated genes, we investigated intron evolution from full-length cDNA-supported non-transposable element-related gene models of rice. Using gene pairs that have an ortholog in the dicotyledonous model species Arabidopsis thaliana, we identified more intron loss (49 introns within 35 gene pairs) than intron gain (5 introns within 5 gene pairs) following segmental duplication. We were unable to demonstrate preferential intron loss at the 3' end of genes as previously reported in mammalian genomes. However, we did find that the four nucleotides of exons that flank lost introns had less frequently used 4-mers.

Conclusion

We observed that intron evolution within rice following segmental duplication is largely dominated by intron loss. In two of the five cases of intron gain within segmentally duplicated genes, the gained sequences were similar to transposable elements.
Facial expressions of simplified robot face for health care system
Authors: Takahashi Yoshihiko , Goto Hiroshi , Shigemoto Hiroyuki
Published: May 2006

A new health care system using a simplified robot face has been developed, and the facial expressions have been categorized. Patient’s health care data can be stored in a personal computer and a robotic system can take many actions depending on the stored data. It can tell a patient what time to take his/her medication and warn them if they fail to take their medication at the appropriate time. The robotic system can communicate with a patient using facial expressions, a voice communication system and a personal computer monitor. The robot face was designed using simple mechanisms in order to achieve a low-cost system. Only seven DOF are used to give facial expressions. The facial impressions of the simplified robot have been categorized with a questionnaire by over 500 people.
Robust disturbance rejection via P-D state feedback Example for lane keeping of highway vehicles
Authors: Koumboulis F. N. , Skarpetis M. G. , Panagiotakis G. E.
Published: May 2006

The problem of robust disturbance rejection (RDR) using a Proportional plus Derivative (P-D) state feedback controller is studied for the case of single-input single output (SISO) linear systems with nonlinear uncertain structure. The linear systems are considered to be subjected to nonmeasurable disturbances. Sufficient conditions for the problem to have a solution are established. A family of P-D feedback controllers solving the problem is analytically determined. Sufficient conditions for the solution of the RDR problem with simultaneous robust stability are also established. Furthermore, the latter problem together with normality and asymptotic command matching is solved. The problem of lane keeping of highway vehicles was the motive for the derivation of all the above results. In particular, the problem of zeroing the relative lateral position of a vehicle travelling along a highway is formulated here as an RDR problem. The curvature of the road plays the role of the unknown disturbance. The problem of rejecting robustly the influence of the road curvature to the lateral position is proved to be always solvable, using a P-D feedback controller. The controller is analytically determined using a finite step algorithm. Furthermore, the free responses of the vehicle’s relative lateral position and lateral velocity are proved to be expressed only in terms of arbitrary modes. The general set of P-D feedback controllers solving the problem is proved also to guarantee robust stability of the closed-loop system. Using the infinity norm, the good performance of the rest of the vehicle’s variables, namely the yaw angle, the yaw rate and the front steering angle, is proved. Simulation results illustrate the good performance of the RDR over a wide range of system uncertainties and measurement errors.
Observer-based boundary control for 2D Burgers equation
Authors: Efe Mehmet Önder
Published: May 2006

The 2D Burgers equation has extensively been considered as a benchmark problem by flow control researchers. The flavour of the problem is its multidimensionality and non-linearity, which are the reasons for making the governing equation a good start for developing a well defined understanding of control of flows. This paper demonstrates that an infinite dimensional observer can be designed, and by the aid of the observer, a simple boundary feedback control can be achieved under severe noise and disturbance scenarios. The results are in good compliance with the theoretical claims.
Sensor faults compensation for MIMO fault-tolerant control systems
Authors: Yang S. S. , Chen J.
Published: May 2006

This paper puts forward a model-based sensor fault-tolerant control design framework for multi-input and multi-output systems. This framework facilitates the use of fault indicating residuals to compensate for faulty sensor feedback signals and allows the integrated design of a fault-tolerant control system to be achieved with established robust H methods. A case study to demonstrate the potential of such a design is illustrated via simulation of a space shuttle re-entry manoeuvre control system. In this simulation, different sensor fault situations have been simulated to test the controller tolerance towards sensor faults. Favourable results demonstrate satisfactory operations in the flight control system in the presence of sensor faults.
Fault detection for non-linear non-Gaussian stochastic systems using entropy optimization principle
Authors: Guo L. , Wang H. , Chai T.
Published: May 2006

In this paper, a fault detection (FD) problem is studied for non-linear dynamic stochastic systems with non-Gaussian disturbances and faults (or abrupt changes of system parameters). After a filter is constructed to generate the detected error, the FD problem is reduced to an optimization problem for the error system, which is represented by a non-linear non-Gaussian stochastic system. Since generally (extended) Kalmen filtering approaches are insufficient to characterize the non-Gaussian variables, we propose the entropy optimization principle for the stochastic error system. The design objective is to maximize the entropies of the stochastic detection errors when the faults occur, and to minimize the entropies of the stochastic estimator errors resulting from the other stochastic noises. Following the formulation of the probability density functions of the stochastic error in terms of those of both the disturbances and the faults, new recursive approaches are established to calculate the entropies of the detection errors. By using the novel performance index and the formulations for the entropies, the real-time optimal FD filter design method is provided. Finally, simulations are given to demonstrate the effectiveness of the proposed FD filtering algorithms.
Phase I/II Study of Cetuximab in Combination With Cisplatin or Carboplatin and Fluorouracil in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Authors: Bourhis Jean , Rivera Fernando , Mesia Ricard , Awada Ahmad , Geoffrois Lionel , Borel Christian , Humblet Yves , Lopez-Pousa Antonio , Hitt Ricardo , Vega Villegas M. Eugenia , Duck Lionel , Rosine Dominique , Amellal Nadia , Schueler Armin , Harstrick Andreas
Published: May 2006

Purpose

This was an open, randomized, multicenter, phase I/II study to investigate the safety and tolerability of cetuximab in the first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN).

Patients and Methods

Treatment comprised cetuximab (initial dose 400 mg/m2 with subsequent weekly doses of 250 mg/m2) in combination with 3-week cycles of either cisplatin (100 mg/m2) or carboplatin (area under the curve, 5), each in combination with a 5-day infusion of fluorouracil (FU) at escalating doses of 600, 800, and 1,000 mg/m2/d. The study was divided into two phases: A, the first two cycles (6 weeks) focusing on the safety and tolerability of combination therapy; and B, the remaining time for those benefiting from therapy until disease progression or intolerable toxicity.

Results

Fifty-three patients were enrolled onto the study. The incidence of dose-limiting toxicities in phase A was acceptable. The most common grade 3/4 adverse events in both groups were leucopenia (38%), asthenia (25%), vomiting (14%), and thrombocytopenia (15%), which are consistent with the known safety profiles of cetuximab, cisplatin/carboplatin, and FU. The overall response rate among patients was 36%, with no clear trend toward an increased efficacy at the highest dose of FU, and no impact of the concomitant chemotherapy regimens on cetuximab pharmacokinetics.

Conclusion

The combination of cetuximab, cisplatin/carboplatin, and FU was reasonably well tolerated and active in recurrent/metastatic SCCHN, and merits additional investigation. An FU dose of 1,000 mg/m2/d in combination with cisplatin or carboplatin can be recommended for additional studies.
Bone Marrow Transplantation Versus Prolonged Intensive Chemotherapy for Children With Acute Lymphoblastic Leukemia and an Initial Bone Marrow Relapse Within 12 Months of the Completion of Primary Therapy: Children's Oncology Group Study CCG-1941
Authors: Gaynon Paul S. , Harris Richard E. , Altman Arnold J. , Bostrom Bruce C. , Breneman John C. , Hawks Ria , Steele David , Zipf Theodore , Stram Daniel O. , Villaluna Doodjuen , Trigg Michael E.
Published: May 2006

Purpose

To compare conventional sibling bone marrow transplantation (CBMT), BMT with alternative donor (ABMT), and chemotherapy (CT) for children with acute lymphoblastic leukemia (ALL) and an early first marrow relapse.

Patients and Methods

After informed consent, 214 patients with ALL and early marrow relapse began multiagent induction therapy. One hundred sixty-three patients with fewer than 25% marrow blasts and count recovery at the end of induction (second remission [CR2]) were allocated by donor availability. Fifty patients with sibling donors were allocated to CBMT. Seventy-two patients were randomly allocated between ABMT and CT while 41 patients refused allocation.

Results

Overall, 3-year event free survival from entry is 19% ± 3%. Thirty-two of 50 CBMT patients (64%) and 19 of 37 ABMT patients (51%) underwent transplantation in CR2 with 3-year disease-free survival of 42% ± 7% and 29% ± 7%. The 3-year DFS is 29% ± 7%, 21% ± 7%, and 27% ± 8% for patients allocated to CBMT, ABMT, and CT, respectively. Contrary to protocol, 12 of 35 patients allocated to CT underwent BMT in CR2. Of these, five patients died after BMT and 5 patients relapsed.

Conclusion

More than one half of patients died, failed reinduction, or relapsed again before 3 months after CR2 (median time to BMT). Intent-to-treat pair-wise comparison of ABMT with CT, CT with CBMT, and CBMT with ABMT yields hazards of 1.2, 1.1, 0.8 with P values of .56, .80, and .36, respectively. Outcomes remain similar and poor for children with ALL and early marrow relapse. BMT is not a complete answer to the challenge of ALL and early marrow relapse.
American Society of Clinical Oncology Guideline for Antiemetics in Oncology: Update 2006
Authors: Kris Mark G. , Hesketh Paul J. , Somerfield Mark R. , Feyer Petra , Clark-Snow Rebecca , Koeller James M. , Morrow Gary R. , Chinnery Lawrence W. , Chesney Maurice J. , Gralla Richard J. , Grunberg Steven M.
Published: May 2006

Purpose

To update the 1999 American Society of Clinical Oncology guideline for antiemetics in oncology.

Update Methodology

The Update Committee completed a review and analysis of data published from 1998 thru February 2006. The literature review focused on published randomized controlled trials, and systematic reviews and meta-analyses of published phase II and phase III randomized controlled trials.

Recommendations

The three-drug combination of a 5-hydroxytryptamine-3 (5-HT3) serotonin receptor antagonist, dexamethasone, and aprepitant is recommended before chemotherapy of high emetic risk. For persons receiving chemotherapy of high emetic risk, there is no group of patients for whom agents of lower therapeutic index are appropriate first-choice antiemetics. These agents should be reserved for patients intolerant of or refractory to 5-HT3serotonin receptor antagonists, neurokinin-1 receptor antagonists, and dexamethasone. The three-drug combination of a 5-HT3receptor serotonin antagonist, dexamethasone, and aprepitant is recommended for patients receiving an anthracycline and cyclophosphamide. For patients receiving other chemotherapy of moderate emetic risk, the Update Committee continues to recommend the two-drug combination of a 5-HT3receptor serotonin antagonist and dexamethasone. In all patients receiving cisplatin and all other agents of high emetic risk, the two-drug combination of dexamethasone and aprepitant is recommended for the prevention of delayed emesis. The Update Committee no longer recommends the combination of a 5-HT3serotonin receptor antagonist and dexamethasone for the prevention of delayed emesis after chemotherapeutic agents of high emetic risk.

Conclusion

The Update Committee recommends that clinicians administer antiemetics while considering patients' emetic risk categories and other characteristics.
Required, tissue-specific roles for Fgf8 in outflow tract formation and remodeling
Authors: Park Eon Joo , Ogden Lisa A. , Talbot Amy , Evans Sylvia , Cai Chen-Leng , Black Brian L. , Frank Deborah U. , Moon Anne M.
Published: May 2006

Fibroblast growth factor 8 (Fgf8) is a secreted signaling protein expressed in numerous temporospatial domains that are potentially relevant to cardiovascular development. However, the pathogenesis of complex cardiac and outflow tract defects observed in Fgf8-deficient mice, and the specific source(s) of Fgf8 required for outflow tract formation and subsequent remodeling are unknown. A detailed examination of the timing and location of Fgf8 production revealed previously unappreciated expression in a subset of primary heart field cells; Fgf8 is also expressed throughout the anterior heart field (AHF) mesoderm and in pharyngeal endoderm at the crescent and early somite stages. We used conditional mutagenesis to examine the requirements for Fgf8 function in these different expression domains during heart and outflow tract morphogenesis. Formation of the primary heart tube and the addition of right ventricular and outflow tract myocardium depend on autocrine Fgf8 signaling in cardiac crescent mesoderm. Loss of Fgf8 in this domain resulted in decreased expression of the Fgf8 target gene Erm,and aberrant production of Isl1 and its target Mef2c in the anterior heart field, thus linking Fgf8 signaling with transcription factor networks that regulate survival and proliferation of the anterior heart field. We further found that mesodermal- and endodermal-derived Fgf8 perform specific functions during outflow tract remodeling: mesodermal Fgf8 is required for correct alignment of the outflow tract and ventricles, whereas activity of Fgf8 emanating from pharyngeal endoderm regulates outflow tract septation. These findings provide a novel insight into how the formation and remodeling of primary and anterior heart field-derived structures rely on Fgf8 signals from discrete temporospatial domains.
Testing hypotheses for the functions of APC family proteins using null and truncation alleles inDrosophila
Authors: McCartney Brooke M. , Price Meredith H. , Webb Rebecca L. , Hayden Melissa A. , Holot Lesley M. , Zhou Mengning , Bejsovec Amy , Peifer Mark
Published: May 2006

Adenomatous polyposis coli (APC) is mutated in colon cancers. During normal development, APC proteins are essential negative regulators of Wnt signaling and have cytoskeletal functions. Many functions have been proposed for APC proteins, but these have often rested on dominant-negative or partial loss-of-function approaches. Thus, despite intense interest in APC, significant questions remain about its full range of cellular functions and about how mutations in the gene affect these. We isolated six new alleles of Drosophila APC2. Two resemble the truncation alleles found in human tumors and one is a protein null. We generated ovaries and embryos null for both APC2 and APC1,and assessed the consequences of total loss of APC function, allowing us to test several previous hypotheses. Surprisingly, although complete loss of APC1 and APC2 resulted in strong activation of Wingless signaling, it did not substantially alter cell viability, cadherin-based adhesion, spindle morphology, orientation or selection of division plane, as predicted from previous studies. We also tested the hypothesis that truncated APC proteins found in tumors are dominant negative. Two mutant proteins have dominant effects on cytoskeletal regulation, affecting Wnt-independent nuclear retention in syncytial embryos. However, they do not have dominant-negative effects on Wnt signaling.
Axis specification in the spider embryo:dppis required for radial-to-axial symmetry transformation andsogfor ventral patterning
Authors: Akiyama-Oda Yasuko , Oda Hiroki
Published: May 2006

The mechanism by which Decapentaplegic (Dpp) and its antagonist Short gastrulation (Sog) specify the dorsoventral pattern in Drosophilaembryos has been proposed to have a common origin with the mechanism that organizes the body axis in the vertebrate embryo. However, DrosophilaSog makes only minor contributions to the development of ventral structures that hypothetically correspond to the vertebrate dorsum where the axial notochord forms. In this study, we isolated a homologue of the Drosophila sog gene in the spider Achaearanea tepidariorum, and characterized its expression and function. Expression of sog mRNA initially appeared in a radially symmetrical pattern and later became confined to the ventral midline area, which runs axially through the germ band. RNA interference-mediated depletion of the spider sog gene led to a nearly complete loss of ventral structures, including the axial ventral midline and the central nervous system. This defect appeared to be the consequence of dorsalization of the ventral region of the germ band. By contrast, the extra-embryonic area formed normally. Furthermore, we showed that embryos depleted for a spider homologue of dpp failed to break the radial symmetry, displaying evenly high levels of sog expression except in the posterior terminal area. These results suggest that dppis required for radial-to-axial symmetry transformation of the spider embryo and sog is required for ventral patterning. We propose that the mechanism of spider ventral specification largely differs from that of the fly. Interestingly, ventral specification in the spider is similar to the process in vertebrates in which the antagonism of Dpp/BMP signaling plays a central role in dorsal specification.
Drosophilatalin and integrin genes are required for maintenance of tracheal terminal branches and luminal organization
Authors: Levi Boaz P. , Ghabrial Amin S. , Krasnow Mark A.
Published: May 2006

Epithelial tubes that compose many organs are typically long lasting,except under specific developmental and physiological conditions when network remodeling occurs. Although there has been progress elucidating mechanisms of tube formation, little is known of the mechanisms that maintain tubes and destabilize them during network remodeling. Here, we describe Drosophila tendrils mutations that compromise maintenance of tracheal terminal branches, fine gauge tubes formed by tracheal terminal cells that ramify on and adhere tightly to tissues in order to supply them with oxygen. Homozygous tendrils terminal cell clones have fewer terminal branches than normal but individual branches contain multiple convoluted lumens. The phenotype arises late in development: terminal branches bud and form lumens normally early in development, but during larval life lumens become convoluted and mature branches degenerate. Their lumens, however, are retained in the remaining branches, resulting in the distinctive multi-lumen phenotype. Mapping and molecular studies demonstrate that tendrils is allelic to rhea, which encodes Drosophila talin, a large cytoskeletal protein that links integrins to the cytoskeleton. Terminal cells mutant for myospheroid, the major Drosophila β-integrin, or doubly mutant for multiple edematous wings and inflatedα-integrins, also show the tendrils phenotype, and localization of myospheroid β-integrin protein is disrupted in tendrils mutant terminal cells. The results provide evidence that integrin-talin adhesion complexes are necessary to maintain tracheal terminal branches and luminal organization. Similar complexes may stabilize other tubular networks and may be targeted for inactivation during network remodeling events.
Mechanisms of elongation in embryogenesis
Authors: Keller Ray
Published: May 2006

Here, I discuss selected examples of elongation in embryogenesis to identify common and unique mechanisms, useful questions for further work, and new systems that offer opportunities for answering these questions. Fiber-wound, hydraulic mechanisms of elongation highlight the importance of biomechanical linkages of otherwise unrelated cellular behaviors during elongation. Little-studied examples of elongation by cell intercalation offer opportunities to study new aspects of this mode of elongation. Elongation by oriented cell division highlights the problem of mitotic spindle orientation and the maintenance of cell-packing patterns in anisotropic force environments. The balance of internal cell-adhesion and external traction forces emerges as a key issue in the formation of elongate structures from compact ones by directed migration.
Fgf8is required for anterior heart field development
Authors: Ilagan Roger , Abu-Issa Radwan , Brown Doris , Yang Yu-Ping , Jiao Kai , Schwartz Robert J. , Klingensmith John , Meyers Erik N.
Published: May 2006

In the mouse embryo, the splanchnic mesodermal cells of the anterior heart field (AHF) migrate from the pharynx to contribute to the early myocardium of the outflow tract (OT) and right ventricle (RV). Recent studies have attempted to distinguish the AHF from other precardiac populations, and to determine the genetic and molecular mechanisms that regulate its development. Here, we have used an Fgf8lacZ allele to demonstrate that Fgf8is expressed within the developing AHF. In addition, we use both a hypomorphic Fgf8 allele (Fgf8neo) and Cre-mediated gene ablation to show that Fgf8 is essential for the survival and proliferation of the AHF. Nkx2.5Cre is expressed in the AHF, primary heart tube and pharyngeal endoderm, while TnT-Cre is expressed only within the specified heart tube myocardium. Deletion of Fgf8 by Nkx2.5Cre results in a significant loss of the Nkx2.5Cre lineage and severe OT and RV truncations by E9.5, while the remaining heart chambers (left ventricle and atria) are grossly normal. These defects result from significant decreases in cell proliferation and aberrant cell death in both the pharyngeal endoderm and splanchnic mesoderm. By contrast, ablation of Fgf8 in the TnT-Cre domain does not result in OT or RV defects, providing strong evidence that Fgf8 expression is crucial in the pharyngeal endoderm and/or overlying splanchnic mesoderm of the AHF at a stage prior to heart tube elongation. Analysis of downstream signaling components, such as phosphorylated-Erk and Pea3, identifies the AHF splanchnic mesoderm itself as a target for Fgf8 signaling.
Getting to the guts of enteric nervous system development
Authors: Heuckeroth Robert O. , Pachnis Vassilis
Published: May 2006

Scientists from around the world gathered in New York City recently to discuss the latest research on enteric nervous system development at a meeting organised by Alan Burns and Heather Young. The participants enjoyed 3 days of presentations that spurred active conversations and highlighted the rapidly advancing research in this field.
Finite Element Analysis of Interface Cracks Using Multiple Point Constraints
Authors: Liu C H , Lin Jui-Hsiang
Published: May 2006

A finite element technique to analyse closed-mode interface cracks is proposed in this study. Stress boundary conditions for a closed-tip model are transformed into multiple point constraints (MPCs) for nodal displacements. These constraints are imposed upon the finite element solutions to simulate closed-tip stress fields in crack-tip elements. This technique can deal with small as well as large crack-tip contact zones, and no special elements other than the standard quarter-point elements are needed. Since stresses approach infinity at the crack tip in a quarter-point element, dominant terms are used in deriving MPCs for nodal displacements. Fracture parameters are obtained by using the virtual crack extension method, and numerical results are in good agreement with analytical results.
An Automated Procedure for Determining Asymptotic Elastic Stress Fields at Singular Points
Authors: Lee Donghee , Barber J. R
Published: May 2006

The paper describes an analytical tool in MATLAB for determining the nature of the stress and displacement fields near a fairly general singular point in linear elasticity. The user is prompted to input the local geometry of the system, the material properties, and the boundary conditions (and interface conditions in the case of composite bodies or problems involving contact between two or more bodies). The tool then computes the dominant eigenvalue and provides as output the equations defining the singular stress and displacement fields and contour plots of these fields. No knowledge of the asymptotic analysis procedure is required of the user.

The tool is tested against previously published results where available and proves to be robust and accurate. It is potentially useful for the development of special finite elements for singular points or for characterizing failure at such points. It can be downloaded from the website http://www-personal.umich.edu/∼jbarber/asymptotics/intro.html
Axial and Diametral Cyclic Stress—Strain Response in Plain and Circumferentially Notched Cylindrical Bars at 550 °C
Authors: Skelton R. P , Webster G. A
Published: May 2006

Cyclic stress-strain tests were undertaken at 550 °C on plain specimens and notched specimens of different notch acuities in several low- and high-alloy ferritic steels (1Cr-Mo-V, NF616, TB12M, and HCM12A). Integrated axial strains were measured between the minimum sections of the notches using a longitudinal extensometer, while surface hoop strains were measured by means of a diametral extensometer with probes located across the notch root. The same extensometry was employed in plain specimens. Over a period of 100 cycles, softening occurred in all plain specimens. These effects were also demonstrated in notched specimens in both axial and diametral directions, although to a lesser degree. From hysteresis loops determined in the notch tests, the cyclic deformation response of the notched regions was expressed in terms of an ‘equivalent gauge length’.

Deviations from elastic-plastic behaviour in plain specimens were noted in that the commonly used ‘effective Poisson's ratiO' was greater than calculated. The effect was investigated further by exploring the characteristics of a very shallow notch, induced by straining a plain specimen to the onset of necking and beyond. The implications of observed behaviour in strain-control low-cycle fatigue tests is discussed.
The Application of Plasticity Principles to Friction
Authors: Churchman C. M , Korsunsky A. M , Hills D. A
Published: May 2006

This paper presents a compelling analogy between the ideas of plastic shakedown and frictional shakedown. It introduces the frictional equivalent of the Bree diagram and classifies the different possible responses of a simple system to typical periodic or cyclic loading.
Patellar resurfacing in total knee replacement
Authors: Campbell D. G. , Duncan W. W. , Ashworth M. , Mintz A. , Stirling J. , Wakefield L. , Stevenson T. M.
Published: May 2006

A series of 100 consecutive osteoarthritic patients was randomised to undergo total knee replacement using a Miller-Galante II prosthesis, with or without a cemented polyethylene patellar component. Knee function was evaluated using the American Knee Society score, Western Ontario and McMaster University Osteoarthritis index, specific patellofemoral-related questions and radiographic evaluation until the fourth post-operative year, then via questionnaire until ten years post-operatively. A ten-point difference in the American Knee Society score between the two groups was considered a significant change in knee performance, with α and β levels of 0.05.

The mean age of the patients in the resurfaced group was 71 years (53 to 88) and in the non-resurfaced group was 73 years (54 to 86).

After ten years 22 patients had died, seven were suffering from dementia, three declined further participation and ten were lost to follow-up. Two patients in the non-resurfaced group subsequently had their patellae resurfaced. In the resurfaced group one patient had an arthroscopic lateral release. There was no significant difference between the two treatment groups: both had a similar deterioration of scores with time, and no further patellofemoral complications were observed in either group.

We are unable to recommend routine patellar resurfacing in osteoarthritic patients undergoing total knee replacement on the basis of our findings.
The effects of operative delay on the relief of neuropathic pain after injury to the brachial plexus
Authors: Kato N. , Htut M. , Taggart M. , Carlstedt T. , Birch R.
Published: May 2006

We investigated the effect of delay before nerve repair on neuropathic pain after injury to the brachial plexus. We studied 148 patients, 85 prospectively and 63 retrospectively. The mean number of avulsed spinal nerves was 3.2 (1 to 5). Pain was measured by a linear visual analogue scale and by the peripheral nerve injury scale. Early repair was more effective than delayed repair in the relief from pain and there was a strong correlation between functional recovery and relief from pain.
Methicillin-resistant Staphylococcus aureus in an Irish orthopaedic centre
Authors: Roche S. J. , Fitzgerald D. , O’Rourke A. , McCabe J. P.
Published: May 2006

This prospective five-year study analyses the impact of methicillin-resistant Staphylococcus aureus (MRSA) on an Irish orthopaedic unit. We identified 318 cases of MRSA, representing 0.76% of all admissions (41 971). A total of 240 (76%) cases were colonised with MRSA, while 120 (37.7%) were infected. Patients were admitted from home (218; 68.6%), nursing homes (72; 22.6%) and other hospitals (28; 8.8%). A total of 115 cases (36.6%) were colonised or infected on admission. Many patients were both colonised and infected at some stage. The length of hospital stay was almost trebled because of the presence of MRSA infection.

Encouragingly, overall infection rates have not risen significantly over the five years of the study despite increased prevalence of MRSA. However, the financial burden of MRSA is increasing, highlighting the need for progress in understanding how to control this resistant pathogen more effectively.
Factors affecting the cohesion of impaction bone graft
Authors: Oakley J. , Kuiper J. H.
Published: May 2006

The role of bone-graft extenders in impaction revision surgery is becoming increasingly important. Tricalcium phosphate and hydroxyapatite have been shown to be both biocompatible and osteoconductive, yet many surgeons remain reluctant to use them. The difficulty in handling bone-graft extenders can be partly alleviated by using porous particles and adding clotted blood.

In an in vitro model we measured the cohesive properties of various impaction graft mixes. Several factors were evaluated including the use of pure bone graft compared with mixes with extender, washing the bone and the addition of clotted blood.

Our findings showed that pure allograft bone particles had significantly higher cohesion than when mixed with extender (p < 0.001). Washing had no effect on cohesion. The addition of clotted blood significantly increased the cohesion of both pure bone (p < 0.019) and mixes with pure bone and with porous graft extender (p < 0.044).
Determinants of functional outcome after simple and complex acetabular fractures involving the posterior wall
Authors: Kreder H. J. , Rozen N. , Borkhoff C. M. , Laflamme Y. G. , McKee M. D. , Schemitsch E. H. , Stephen D. J. G.
Published: May 2006

We have evaluated the functional, clinical and radiological outcome of patients with simple and complex acetabular fractures involving the posterior wall, and identified factors associated with an adverse outcome.

We reviewed 128 patients treated operatively for a fracture involving the posterior wall of the acetabulum between 1982 and 1999. The Musculoskeletal Functional Assessment and Short-Form 36 scores, the presence of radiological arthritis and complications were assessed as a function of injury, treatment and clinical variables.

The patients had profound functional deficits compared with the normal population. Anatomical reduction alone was not sufficient to restore function. The fracture pattern, marginal impaction and residual displacement of > 2 mm were associated with the development of arthritis, which related to poor function and the need for hip replacement. It may be appropriate to consider immediate total hip replacement for patients aged > 50 years with marginal impaction and comminution of the wall, since 7 of 13 (54%) of these required early hip replacement.
The early response to major trauma and intramedullary nailing
Authors: White T. O. , Clutton R. E. , Salter D. , Swann D. , Christie J. , Robinson C. M.
Published: May 2006

The stress response to trauma is the summation of the physiological response to the injury (the ‘first hit’) and by the response to any on-going physiological disturbance or subsequent trauma surgery (the ‘second hit’).

Our animal model was developed in order to allow the study of each of these components of the stress response to major trauma. High-energy, comminuted fracture of the long bones and severe soft-tissue injuries in this model resulted in a significant tropotropic (depressor) cardiovascular response, transcardiac embolism of medullary contents and activation of the coagulation system. Subsequent stabilisation of the fractures using intramedullary nails did not significantly exacerbate any of these responses.
Spinal injuries in Irish rugby
Authors: Shelly M. J. , Butler J. S. , Timlin M. , Walsh M. G. , Poynton A. R. , O’Byrne J. M.
Published: May 2006

This study assessed the frequency of acute injury to the spinal cord in Irish Rugby over a period of ten years, between 1995 and 2004. There were 12 such injuries; 11 were cervical and one was thoracic. Ten occurred in adults and two in schoolboys. All were males playing Rugby Union and the mean age at injury was 21.6 years (16 to 36). The most common mechanism of injury was hyperflexion of the cervical spine and the players injured most frequently were playing at full back, hooker or on the wing. Most injuries were sustained during the tackle phase of play. Six players felt their injury was preventable. Eight are permanently disabled as a result of their injury.
Biomechanical reconstruction of the hip
Authors: Girard J. , Lavigne M. , Vendittoli P.-A. , Roy A. G.
Published: May 2006

We have compared the biomechanical nature of the reconstruction of the hip in conventional total hip arthroplasty (THA) and surface replacement arthroplasty (SRA) in a randomised study involving 120 patients undergoing unilateral primary hip replacement. The contralateral hip was used as a control.

Post-operatively, the femoral offset was significantly increased with THA (mean 5.1 mm; −2.8 to 11.6) and decreased with SRA (mean −3.3 mm; −8.9 to 8.2). Femoral offset was restored within sd 4 mm in 14 (25%) of those with THA and in 28 (57%) of the patients receiving SRA (p < 0.001). In the THA group, the leg was lengthened by a mean of 2.6 mm (−6.04 to +12.9), whereas it was shortened by a mean of 1.9 mm (−7.1 to +2.05) in the SRA group, compared with the contralateral side. Leg-length inequality was restored within sd 4 mm in 42 (86%) of the SRA and 33 (60%) of the THA patients. The radiological parameters of acetabular reconstruction were similar in both groups.

Restoration of the normal proximal femoral anatomy was more precise with SRA. The enhanced stability afforded by the use of a large-diameter femoral head avoided over-lengthening of the limb or increased offset to improve soft-tissue tension as occurs sometimes in THA. In a subgroup of patients with significant pre-operative deformity, restoration of the normal hip anatomy with lower pre-operative femoral offset or significant shortening of the leg was still possible with SRA.
Survivorship and clinical outcome of modular endoprosthetic reconstruction for neoplastic disease of the lower limb
Authors: Ahlmann E. R. , Menendez L. R. , Kermani C. , Gotha H.
Published: May 2006

We reviewed retrospectively the results in 211 consecutive patients who had undergone limb salvage for bone neoplasia with endoprosthetic reconstruction of the proximal femur (96), distal femur (78), proximal tibia (30) and total femur (7). Their mean age was 50 years (11 to 86) and the mean follow-up period was 37.3 months (1 to 204). A total of 35 (16.6%) prostheses failed. Overall, implant survival was 78% (95% confidence interval (CI) 0.29 to 0.54) at five years, 60% (95% CI 0.93 to 2.35) at ten years and 60% (95% CI 1.27 to 3.88) at 15 years. Survivorship of the limb was 97.6% (95% CI 1.73 to 3.35) at ten years. The gender, age, diagnosis and location of the tumour were not prognostic variables for failure. Modular endoprosthetic replacement in the lower limb is a durable long-term reconstructive option, with the implants generally outlasting the patient.
Methicillin-resistant Staphylococcus aureus on orthopaedic wards
Authors: Nixon M. , Jackson B. , Varghese P. , Jenkins D. , Taylor G.
Published: May 2006

We examined the rates of infection and colonisation by methicillin-resistant Staphylococcus aureus (MRSA) between January 2003 and May 2004 in order to assess the impact of the introduction of an MRSA policy in October 2003, which required all admissions to be screened. Emergency admissions were treated prophylactically and elective beds ring-fenced. A total of 5594 admissions were cross-referenced with 22 810 microbiology results. The morbidity, mortality and cost of managing MRSA-carrying patients, with a proximal fracture of the femur were compared, in relation to age, gender, American Society of Anaesthesiologists grade and residential status, with a group of matched controls who were MRSA-negative.

In 2004, we screened 1795 of 1796 elective admissions and MRSA was found in 23 (1.3%). We also screened 1122 of 1447 trauma admissions and 43 (3.8%) were carrying MRSA. All ten ward transfers were screened and four (40%) were carriers (all p < 0.001). The incidence of MRSA in trauma patients increased by 2.6% per week of inpatient stay (r = 0.97, p < 0.001). MRSA developed in 2.9% of trauma and 0.2% of elective patients during that admission (p < 0.001). The implementation of the MRSA policy reduced the incidence of MRSA infection by 56% in trauma patients (1.57% in 2003 (17 of 1084) to 0.69% in 2004 (10 of 1447), p = 0.035). Infection with MRSA in elective patients was reduced by 70% (0.56% in 2003 (7 of 1257) to 0.17% in 2004 (3 of 1806), p = 0.06). The cost of preventing one MRSA infection was £3200.

Although colonisation by MRSA did not affect the mortality rate, infection by MRSA more than doubled it. Patients with proximal fractures of the femur infected with MRSA remained in hospital for 50 extra days, had 19 more days of vancomycin treatment and 26 more days of vacuum-assisted closure therapy than the matched controls. These additional costs equated to £13 972 per patient.

From this experience we have been able to describe the epidemiology of MRSA, assess the impact of infection-control measures on MRSA infection rates and determine the morbidity, mortality and economic cost of MRSA carriage on trauma and elective orthopaedic wards.