bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe congenital neutropenia resulting from G6PC3 deficiency with increased neutrophil CXCR4 expression and myelokathexis
Authors: McDermott David H. , De Ravin Suk See , Jun Hyun Sik , Liu Qian , Priel Debra A. Long , Noel Pierre , Takemoto Clifford M. , Ojode Teresa , Paul Scott M. , Dunsmore Kimberly P. , Hilligoss Dianne , Marquesen Martha , Ulrick Jean , Kuhns Douglas B. , Chou Janice Y. , Malech Harry L. , Murphy Philip M.
Published: July 2010

Mutations in more than 15 genes are now known to cause severe congenital neutropenia (SCN); however, the pathologic mechanisms of most genetic defects are not fully defined. Deficiency of G6PC3, a glucose-6-phosphatase, causes a rare multisystem syndrome with SCN first described in 2009. We identified a family with 2 children with homozygous G6PC3 G260R mutations, a loss of enzymatic function, and typical syndrome features with the exception that their bone marrow biopsy pathology revealed abundant neutrophils consistent with myelokathexis. This pathologic finding is a hallmark of another type of SCN, WHIM syndrome, which is caused by gain-of-function mutations in CXCR4, a chemokine receptor and known neutrophil bone marrow retention factor. We found markedly increased CXCR4 expression on neutrophils from both our G6PC3-deficient patients and G6pc3−/− mice. In both patients, granulocyte colony-stimulating factor treatment normalized CXCR4 expression and neutrophil counts. In G6pc3−/− mice, the specific CXCR4 antagonist AMD3100 rapidly reversed neutropenia. Thus, myelokathexis associated with abnormally high neutrophil CXCR4 expression may contribute to neutropenia in G6PC3 deficiency and responds well to granulocyte colony-stimulating factor.
Role of Krüppel-like factors in leukocyte development, function, and disease
Authors: Cao Zhuoxiao , Sun Xinghui , Icli Basak , Wara Akm Khyrul , Feinberg Mark W.
Published: July 2010

The Krüppel-like transcription factor (KLF) family participates in diverse aspects of cellular growth, development, differentiation, and activation. Recently, several groups have identified new connections between the function of these factors and leukocyte responses in health and disease. Gene targeting of individual KLFs in mice has uncovered novel and unexpected physiologic roles among myeloid and lymphocyte cell lineage maturation, particularly in the bone marrow niche and blood. In addition, several KLF family members are downstream targets of stimuli and signaling pathways critical to T-cell trafficking, T regulatory cell differentiation or suppressor function, monocyte/macrophage activation or renewal, and B memory cell maturation or activation. Indeed, KLFs have been implicated in subtypes of leukemia, lymphoma, autoimmunity, and in acute and chronic inflammatory disease states, such as atherosclerosis, diabetes, and airway inflammation, raising the possibility that KLFs and their upstream signals are of therapeutic interest. This review focuses on the relevant literature of Krüppel-like factors in leukocyte biology and their implications in clinical settings.
Development of a highly metastatic model that reveals a crucial role of fibronectin in lung cancer cell migration and invasion
Authors: Jia Deshui , Yan Mingxia , Wang Xiaomin , Hao Xiangfang , Liang Linhui , Liu Lei , Kong Hanwei , He Xianghuo , Li Jinjun , Yao Ming
Published: July 2010

Background

The formation of metastasis is the most common cause of death in patients with lung cancer. A major implement to understand the molecular mechanisms involved in lung cancer metastasis has been the lack of suitable models to address it. In this study, we aimed at establishing a highly metastatic model of human lung cancer and characterizing its metastatic properties and underlying mechanisms.

Methods

The human lung adeno-carcinoma SPC-A-1 cell line was used as parental cells for developing of highly metastatic cells byin vivoselection in NOD/SCID mice. After three rounds of selection, a new SPC-A-1sci cell line was established from pulmonary metastatic lesions. Subsequently, the metastatic properties of this cell line were analyzed, including optical imaging ofin vivometastasis, immunofluorescence and immunohistochemical analysis of several epithelial mesenchymal transition (EMT) makers and trans-well migration and invasion assays. Finally, the functional roles of fibronectin in the invasive and metastatic potentials of SPC-A-1sci cells were determined by shRNA analysis.

Results

A spontaneously pulmonary metastatic model of human lung adeno-carcinoma was established in NOD/SCID mice, from which a new lung cancer cell line, designated SPC-A-1sci, was isolated. Initially, the highly metastatic behavior of this cell line was validated by optical imaging in mice models. Further analyses showed that this cell line exhibit phenotypic and molecular alterations consistent with EMT. Compared with its parent cell line SPC-A-1, SPC-A-1sci was more aggressivein vitro, including increased potentials for cell spreading, migration and invasion. Importantly, fibronectin, a mesenchymal maker of EMT, was found to be highly expressed in SPC-A-1sci cells and down-regulation of it can decrease thein vitroandin vivometastatic abilities of this cell line.

Conclusions

We have successfully established a new human lung cancer cell line with highly metastatic potentials, which is subject to EMT and possibly mediated by increased fibronectin expression. This cell line and its reproducibles.c. mouse model can further be used to identify underlying mechanisms of lung cancer metastasis.
Association of the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio and concentrations of plasma lipids with high-density lipoprotein subclass distribution in the Chinese population
Authors: Tian Li , Liu Yinghui , Qin Yang , Long Shiyin , Xu Yanhua , Fu Mingde
Published: July 2010

Background

To evaluate the relationship between the low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio and HDL subclass distribution and to further examine and discuss the potential impact of LDL-C and HDL-C together with TG on HDL subclass metabolism.

Results

Small-sized preβ1-HDL, HDL3b and HDL3a increased significantly while large-sized HDL2a and HDL2b decreased significantly as the LDL-C/HDL-C ratio increased. The subjects in low HDL-C level (< 1.03 mmol/L) who had an elevation of the LDL-C/HDL-C ratio and a reduction of HDL2b/preβ1-HDL regardless of an undesirable or high LDL-C level. At desirable LDL-C levels (< 3.34 mmol/L), the HDL2b/preβ1-HDL ratio was 5.4 for the subjects with a high HDL-C concentration (≥ 1.55 mmol/L); however, at high LDL-C levels (≥ 3.36 mmol/L), the ratio of LDL-C/HDL-C was 2.8 in subjects, and an extremely low HDL2b/preβ1-HDL value although with high HDL-C concentration.

Conclusion

With increase of the LDL-C/HDL-C ratio, there was a general shift toward smaller-sized HDL particles, which implied that the maturation process of HDL was blocked. High HDL-C concentrations can regulate the HDL subclass distribution at desirable and borderline LDL-C levels but cannot counteract the influence of high LDL-C levels on HDL subclass distribution.
Copy number variation of the SELENBP1 gene in schizophrenia
Authors: Amar Shirly , Ovadia Ofer , Maier Wolfgang , Ebstein Richard , Belmaker RH , Mishmar Dan , Agam Galila
Published: July 2010

Background

Schizophrenia is associated with rare copy-number (CN) mutations. Screening for such alleles genome-wide, though comprehensive, cannot study in-depth the causality of particular loci, therefore cannot provide the functional interpretation for the disease etiology. We hypothesized that CN mutations in the SELENBP1 locus could associate with the disorder and that these mutations could alter the gene product's activity in patients.

Methods

We analyzed SELENBP1 CN variation (CNV) in blood DNA from 49 schizophrenia patients and 49 controls (cohort A). Since CN of genes may vary among tissues, we investigated SELENBP1 CN in age- sex- and postmortem interval-matched cerebellar DNA samples from 14 patients and 14 controls (cohort B). Since CNV may either be de-novo or inherited we analyzed CNV of the SELENBP1 locus in blood DNA from 26 trios of schizophrenia probands and their healthy parents (cohort C). SELENBP1 mRNA levels were measured by real-time PCR.

Results

In cohort A reduced CN of the SELENBP1 locus was found in four patients but in none of the controls. In cohort B we found reduced CN of the SELENBP1 locus in two patients but in none of the controls. In cohort C three patients exhibited drastic CN reduction, not present in their parents, indicating de-novo mutation. A reduction in SELENBP1 mRNA levels in the postmortem cerebellar samples of schizophrenia patients was found.

Conclusions

We report a focused study of CN mutations in the selenium binding-protein1 (SELENBP1) locus previously linked with schizophrenia. We provide evidence for recurrence of decreased CN of the SELENBP1 locus in three unrelated patients' cohorts but not in controls, raising the possibility of functional involvement of these mutations in the etiology of the disease.
SHIP2, a factor associated with diet-induced obesity and insulin sensitivity, attenuates FGF signaling in vivo
Authors: Jurynec Michael J. , Grunwald David Jonah
Published: July 2010

SH2-domain-containing inositol phosphatase 2 (SHIP2) belongs to a small family of phosphoinositide 5-phosphatases that help terminate intracellular signaling initiated by activated receptor tyrosine kinases. Mammalian SHIP2 is viewed primarily as an attenuator of insulin signaling and has become a prominent candidate target for therapeutic agents that are designed to augment insulin signaling. Despite this view, no signaling pathway has yet been demonstrated as being affected directly by SHIP2 function in vivo, and in vitro studies indicate that the protein may function in multiple signaling pathways. Here, we analyze the role of a SHIP2 family member in the early zebrafish embryo where developmental and gene expression defects can be used to assay specific signaling pathways. The zebrafish ship2a transcript is maternally supplied, and inhibiting the expression of its protein product results in the expansion of dorsal tissue fates at the expense of ventral ones. We show that the developmental defects are the result of perturbation of fibroblast growth factor (FGF) signaling in the early embryo. Loss of Ship2a leads to an increased and expanded expression of outputs of FGF-mediated signaling, including FGF-dependent gene expression and activated mitogen-activated protein kinase (MAPK) signaling. Our findings demonstrate that Ship2a attenuates the FGF signaling pathway in vivo and functions in the establishment of normal tissue patterning in the early embryo. We suggest that modulation of FGF signaling may be a principal function of SHIP2 in mammals.
Rgs16 and Rgs8 in embryonic endocrine pancreas and mouse models of diabetes
Authors: Villasenor Alethia , Wang Zhao V. , Rivera Lee B. , Ocal Ozhan , Asterholm Ingrid Wernstedt , Scherer Philipp E. , Brekken Rolf A. , Cleaver Ondine , Wilkie Thomas M.
Published: July 2010

Diabetes is characterized by the loss, or gradual dysfunction, of insulin-producing pancreatic β-cells. Although β-cells can replicate in younger adults, the available diabetes therapies do not specifically target β-cell regeneration. Novel approaches are needed to discover new therapeutics and to understand the contributions of endocrine progenitors and β-cell regeneration during islet expansion. Here, we show that the regulators of G protein signaling Rgs16 and Rgs8 are expressed in pancreatic progenitor and endocrine cells during development, then extinguished in adults, but reactivated in models of both type 1 and type 2 diabetes. Exendin-4, a glucagon-like peptide 1 (Glp-1)/incretin mimetic that stimulates β-cell expansion, insulin secretion and normalization of blood glucose levels in diabetics, also promoted re-expression of Rgs16::GFP within a few days in pancreatic ductal-associated cells and islet β-cells. These findings show that Rgs16::GFP and Rgs8::GFP are novel and early reporters of G protein-coupled receptor (GPCR)-stimulated β-cell expansion after therapeutic treatment and in diabetes models. Rgs16 and Rgs8 are likely to control aspects of islet progenitor cell activation, differentiation and β-cell expansion in embryos and metabolically stressed adults.
The elastic behaviour of non-sintered metal powder compacts
Authors: Riera M D , Prado J M
Published: July 2010

This work carries out a research about the elastic behaviour of metallic powder compacts. Cylindrical specimens with different levels of density have been submitted to uniaxial compression tests with loading and unloading cycles. The analysis of the elastic loadings shows a non-linear elasticity, which can be mathematically represented by means of a potential law. Results can be explained from two different theoretical approaches: one concerns the initial compression cycles and is based on the development of an internal field of chain forces; the other concerns advanced compression stages in which forces are distributed homogeneously among the contacts between particles.
Numerical Model Assessment of Tidal Stream Energy Resources in the Severn Estuary, UK
Authors: Xia J , Falconer R A , Lin B
Published: July 2010

Tidal stream systems make use of the kinetic energy of tidal movement to power turbines, in a similar manner to the way in which windmills extract energy from the wind. This method of renewable energy generation is gaining in popularity because of the high predictability of tides, the lower investment needed for tidal turbines, and the lower ecological impact, as compared with other schemes involving barrages or lagoons. It is generally considered that a mean spring peak tidal current of at least 2 m/s is required for tidal stream power to be worth exploiting. In the Severn Estuary, the peak tidal current exceeds 2 m/s, with a corresponding minimum depth of greater than 20 m, and it is thereby a potential location for tidal stream power. Previous studies cannot provide the detailed and precise distribution of tidal stream power in this estuary, and it has therefore been deemed appropriate to undertake a numerical model assessment of tidal stream energy resources in the Severn Estuary. In the present study, an existing finite volume numerical model has been refined, with the inclusion of an algorithm for computing the power density and its mean value across the estuary. The refined model has also been validated against (a) measured tidal currents at four sites, using the method of harmonic analysis; (b) measured tide level hydrographs at five tide gauging stations, taken over a 15-day period and covering the full spring—neap cycle; and (c) in situ velocity measurements at two sites. Finally, the validated model has been used to assess the potential tidal stream energy resources without and with the Severn Barrage, including the distributions of the mean power density over a spring—neap cycle in the Severn Estuary and a detailed assessment of the tidal stream energy resources at two sites near the coast of South Wales. The model predictions indicate that at two sites, the annual power output with the presence of barrage could be reduced by 70—80 per cent, as compared with the value without any structure.
Thermodynamic Optimization of Organic Rankine Cycles at Several Condensing Temperatures: Case Study of Waste Heat Recovery in a Natural Gas Compressor Station
Authors: Saavedra I , Bruno J C , Coronas A
Published: July 2010

In this article, the authors performed the thermodynamic optimization of organic Rankine cycles (ORCs) using several working fluids and considered the effect of three heat rejection media in the condenser: cooling water, ambient air, and hot water at high temperature for co- or trigeneration applications. The ORC system was modelled and optimized using the Aspen Hysys process simulator. The objective function is the maximization of turbine power output. Most natural gas compression stations use no heat recovery system. In this study, they applied the optimization procedure to the recovery of waste heat from gas turbines used to drive natural gas compressors in natural gas pumping stations. They used operational data from an existing pumping station to illustrate the potential benefits of ORC systems for this application, taking into account also non-thermodynamic aspects such as toxicity, flammability, and investment cost return. The highest ORC turbine output powers were obtained with aromatic hydrocarbons, then with aromatic fluorocarbons, n-hydrocarbons, and siloxanes (in that order). For the case studied here — a gas turbine of 2.6 MW of mechanical power— the proposed ORC can produce around 1 MWe, with a thermal efficiency of up to 24 per cent depending on the working fluid and condensing temperature.
Multi-Objective Fault-Tolerant Output Tracking Control of a Flexible Air-Breathing Hypersonic Vehicle
Authors: Li H , Wu L , Si Y , Gao H , Hu X
Published: July 2010

This paper deals with the problem of multi-objective fault-tolerant output tracking control for the longitudinal model of a flexible air-breathing hypersonic vehicle (FAHV). There exist some challenges for control design for the vehicles due to the inherent couplings between the propulsion system, the airframe dynamics, and the presence of strong flexibility effects. This paper addresses the problem of guaranteed cost fault-tolerant output tracking control with regional pole constraints against actuator faults for the FAHV system. A non-linear longitudinal model is adopted for control design because of the complexity of the FAHV systems. First, a linearized model is established around the trim point including the state of altitude, velocity, angle of attack, pitch angle, and pitch rate, etc. for a non-linear, dynamically coupled simulation model of a FAHV with the aim to address the multi-objective fault-tolerant output tracking control problem. Second, the control objective and models of actuator faults are presented. Third, by utilizing the Lyapunov functional approach, a multi-objective analysis condition is proposed in terms of convex optimization problems, that can be easily solved via standard numerical software. Then, a multi-objective fault-tolerant controller is designed such that the resulting closed-loop system is asymptotically stable and satisfies a prescribed performance cost with the simultaneous consideration of poles assignment in spite of possible actuator failure. Finally, the simulation results are given to show the effectiveness of the proposed method, which is verified by an excellent altitude reference and velocity tracking performance.
Reconfiguration control strategy using Takagi–Sugeno model predictive control for network control systems – a magnetic levitation case study
Authors: Benitez-Pérez H , Ortega-Arjona J , Cardenas-Flores F , Quiñones-Reyes P
Published: July 2010

This paper presents a reconfiguration control strategy for network control systems that makes use of a fuzzy Takagi–Sugeno model for predictive control. The dynamic behaviour of a network control system is modelled by using a real-time implementation of the scheduling algorithm. Here, this is applied for a magnetic levitation system, as a plant that is also modelled using a fuzzy Takagi–Sugeno approach. Thus, this paper covers several design issues, such as how to model a computer network, a plant, and a reconfiguration control strategy, as well as how the reconfiguration control strategy is modified using the fuzzy approach.
Convicted to Innovation in Fluid Power
Authors: Achten P
Published: July 2010

In the coming decade, cost reduction and energy efficiency will be the dominating success factors for any industry. Currently, the hydraulic industry is not fit to meet these demands: hydraulic systems and components are simply too expensive and too inefficient. It is important to mention that there are no fundamental reasons for the poor performance and high manufacturing, production, and engineering cost. Without doubt, hydraulics can be efficient and low-cost. However, the niche market in which the hydraulic industry operates simply does not have an alternative for the hydraulic cylinder. Without feeling the heat of competition, the hydraulic industry has not had enough incentive to invest in new products and technologies. However, changes are apparent. Relatively high labour cost already threatens the production industry in Europe and North America. Moreover, the uncertainty about future fuel and energy prices, and CO2 emission demands, will force the industry to change. If it does, it will create unprecedented market opportunities, utilizing the full potential of high power, torque, and force densities, combined with flexibility in control and power management. The fluid power industry really does not have an alternative. It is convicted to innovation.
Improved Profitability of a Pulping Mill through Progressive Controller Structure Expansion
Authors: Nobakhti A
Published: July 2010

It has been well documented that multivariate systems will benefit from application of advanced control strategies. The application of these methods has thus far been hindered for a variety of reasons which range from complexity of the design methodologies to the cost associated with implementation of these solutions. This paper shows that there exist alternative means by which existing control strategies of a multivariate system could be extended, thereby leading to increased efficiency, without the need to remove and implement a new control system installation. A realistic model of an entire pulping mill is used in this paper to show that by careful selection of only a few additional control loops which are added to the existing structure, sizeable profitability and operational gains may be achieved.
Adaptive Selection Routine for Evolutionary Algorithms
Authors: Pham D T , Castellani M
Published: July 2010

This paper presents an adaptive selection scheme for use in evolutionary algorithms (EAs). The proposed algorithm adjusts the stochastic noise level in the determination of the mating pool in order to regulate the selection pressure. This eliminates the fitness scaling problem and allows optimization of the selection pressure throughout the learning phase, overcoming the major pitfalls of most popular EA selection procedures. Experimental evidence is given to prove the superior performance of the proposed technique compared with conventional EA procedures. The results also highlight how the application of windowing techniques to the roulette wheel procedure can increase the likelihood of premature convergence.
Autonomous Swing-Up Control of a Three-Link Robot Gymnast
Authors: Eldukhri E E , Pham D T
Published: July 2010

In this paper the problem of swing-up control of an under-actuated, three-link robot gymnast (Robogymnast) is discussed. Robogymnast mimics the human acrobat who hangs from a high bar and tries to swing-up to an upside-down position with his/her hands still on the bar. Unlike human acrobats, Robogymnast's hands are firmly attached to a freely rotating high bar mounted on ball bearings. Although this helps during the swing-up phase, it poses a great challenge to balancing the robot at the upright position. The motion of Robogymnast was initiated by applying regularly changing sinusoidal torques to the two motors located respectively at its shoulder and hip joints. As the swing angle increases, the amplitudes of the applied sinusoidal torques were increased while their respective frequency was reduced proportionately. Experimental results showed successful swing-up of Robogymnast from the stable downwards position to the inverted configuration.
Performance Analysis of a Robust Proportional—Integral—Derivative Control Technique for the Auto-Focusing Mechanism of an Optical Surface Profile Measurement System
Authors: Islam N , Parkin R M , Jackson M R , Elmas S , Kesy Z , Fan K-C
Published: July 2010

A control system is regarded as the vital component of a process loop. For centuries, various control techniques have been employed to control actuators or process parameters in an effective manner to obtain the desired response. The field of control engineering has seen phenomenal changes in the past two decades or so, epitomized by the rise of ever-more sophisticated modern intelligent control techniques. However, despite such massive improvements in control techniques, century-old proportional—integral—derivative (PID) controllers are still widely used in industry and research alike owing to the simplicity of fabricating and tuning such devices. Many studies in the literature have shown that a particular variant of the PID controller, namely a robust PID, is even more effective in achieving better performance of the closed-loop system. This paper investigates the performance enhancement of the response of the auto-focusing mechanism of a surface profile measurement system using a robust PID controller as opposed to a controller tuned using the conventional Ziegler—Nichols (ZN) method. It can be observed through the reported results that the use of the former technique helps to achieve the highly desired closed-loop response of fast settling time, reasonable overshoot, loop disturbance rejection, and high system bandwidth of the focusing mechanism.
Finite-Time Continuous Gain-Scheduled Control on Stochastic Hyperchaotic Systems
Authors: Yin Y Y , Liu F , Shi P
Published: July 2010

In the present paper, a finite-time continuous gain-scheduled control problem is studied for a class of stochastic Markov jump hyperchaotic systems with state delays. By means of the gradient linearization method, the non-linear jump system is constructed by a series of linear jump models at selected working states. Then, based on the stochastic Lyapunov—Krasovskii functional approach, a new robust stochastic finite-time stabilization criterion is established and the finite-time H∞ controller is formulated for each linear jump model in the form of linear matrix inequalities. Finally, for such stochastic non-linear hyperchaotic system, the continuous gain-scheduled method is adopted and continuous finite-time gain-scheduled H∞ controllers are designed. The simulation example shows the effectiveness of the proposed techniques.
Optimal Initial Positioning of Excavators in Digging Processes
Authors: Papachristou A , Valsamos H , Dentsoras A
Published: July 2010

Excavators comprise a category of construction equipment and are used in a wide range of applications of varying scale. Regarding their usage in digging processes, the relevant literature records few analytical methods which, when combined with the available empirical knowledge, provide certain analytical tools, rules, and guidelines. In the present work, an approach for obtaining optimal initial positioning of excavators in digging processes is proposed. First, constraints and assumptions regarding excavator and dig geometries are stated. The excavator work space is correlated to its kinematics and the geometric locus of optimal positioning points that correspond to maximal length of the boom—arm pair is located. Then the problem of determining the volume of removed soil is analysed and subsequently reduced to the solution of the corresponding two-dimensional problem. Simple mathematical formulae are provided that relate dig and excavator geometries. Finally, Euclidean and/or Manhattan distance calculations are used for locating the point that offers the shortest path to the point of initial location of the excavator.
Direct unavailability computation of a maintained highly reliable system
Authors: Briš R , Byczanski P
Published: July 2010

The paper presents a new analytical algorithm which is able to carry out exact reliability quantification of highly reliable systems with maintenance (both preventive and corrective). A directed acyclic graph is used as a system representation. The algorithm allows highly reliable and maintained input components to be taken into account. A new model of a repairable component undergoing hidden failures, i.e. a model when a failure is identified only at special deterministically assigned times, is analytically deduced within the paper. All considered models are implemented into the new algorithm. The algorithm is based on a special new procedure which permits only summarization between two or more non-negative numbers that can be very different. If the summarization of very small positive numbers transformed into the machine code is performed effectively, there is no error at the operation. Unavailability quantification is demonstrated on a test system from references and on its highly reliable modifications. Improvement of the reliability quantification by the new method in comparison to the simulation method is demonstrated on real reliability problem from practice, i.e. the decision-making problem related to reliability of the supply of electric power to consumers.
Human reliability: Benchmark and prediction
Authors: Duffey R B , Ha T
Published: July 2010

A straightforward, general, and simple methodology is given for evaluating and predicting the human error probability (HEP) in transients for accident risk prediction and reduction purposes. The result is validated against all the available data, producing a completely independent assessment of the uncertainty in HEP for safety and risk analysis, and a new validated prediction method. Previous published work established the technical basis for the existence of learning curves for predicting human performance, system outcomes, and accident rates, which was derived and validated against extensive system outcomes and human learning trial data. This latest second-generation minimum error rate equation (MERE)/universal learning curve (ULC) prediction is based on the well-known and proven learning hypothesis. It is therefore applicable to transient and accident analysis, providing the probability of failure or success for individuals as well as for systems. In this paper, new simulator data and three major existing human reliability analysis (HRA) methods used in safety and risk analysis (e.g. technique of human error rate prediction (THERP), human error and assessment technique (HEART), and human cognitive reliability (HCR)) are benchmarked against the new prediction derived directly from the general ULC. Since these existing methods utilize empirical factors, expert judgement and task analysis, the paper demonstrates a totally new objective approach to benchmark human reliability analysis.
Efficiency of tuned mass dampers with uncertain parameters on the performance of structures under stochastic excitation
Authors: Schmelzer B , Oberguggenberger M , Adam C
Published: July 2010

Tuned mass dampers serve the purpose of damping vibrations of structures such as earthquake-induced vibrations. In their design, two types of uncertainty are relevant: the stochastic excitation (e.g. earthquake record) and the inherent uncertainty of internal parameters of the devices themselves. This paper presents a new framework that admits the combination of stochastic processes and interval-type parameter uncertainty, modelled by random sets. The approach is applied to show how the efficiency of tuned mass dampers can be realistically assessed in the presence of uncertainty.
Bayesian linear inspection planning for large-scale physical systems
Authors: Randell D , Goldstein M , Hardman G , Jonathan P
Published: July 2010

Modelling of complex corroding industrial systems is critical to effective inspection and maintenance for assurance of system integrity. Wall thickness and corrosion rate are modelled for multiple dependent corroding components, given observations of minimum wall thickness per component. At each inspection, partial observations of the system are considered. A Bayes linear approach is adopted simplifying parameter estimation and avoiding often unrealistic distributional assumptions. Key system variances are modelled, making exchangeability assumptions to facilitate analysis for sparse inspection time series. A utility-based criterion is used to assess quality of inspection design and aid decision making. The model is applied to inspection data from pipework networks on a full-scale offshore platform.
Staged carotid endarterectomy under local anaesthetic in patients requiring cardiac surgery
Authors: Birchley David , Villaquiran Jaime , Akowuah Enoch , Lewis Terence , Ashley Simon
Published: July 2010

INTRODUCTION

There is no clear guidance as to the management of carotid stenotic disease prior to cardiac surgery. We aimed to review the results of a single centre performing carotid endarterectomy (CEA) under local anaesthesia prior to cardiac surgery.

PATIENTS AND METHODS

All patients referred for cardiac surgery in our tertiary referral unit between January 1998 and August 2008 were identified and data relating to those 100 undergoing CEA prior to cardiac surgery were reviewed. Eighty had coronary artery bypass grafting (CABG) alone, 15 combined valve surgery and CABG and three underwent isolated valve surgery. Two patients died prior to cardiac surgery.

RESULTS

One hundred patients were prospectively identified after screening by clinical features and carotid duplex scanning to require CEA from a total of 11,394. The stroke rate was 1% between CEA and cardiac surgery, 2% following cardiac surgery and 3% in total. Ninety-eight patients proceeded to cardiac surgery (two deaths post-CEA). The cumulative event rate (stroke, myocardial infarct [included in view of the nature of the patients in our cohort] and/or death) was 10.2% following all cardiac surgery (CABG and valve). In 80 patients undergoing CABG only, the cumulative event rate was 7.5% after CABG. Including the two deaths pre-cardiac surgery, the rates were 12% and 8%. The risk of peri-operative stroke and 30-day mortality were reduced to that of patients undergoing cardiac surgery without significant carotid arterial disease, 3% versus 3.3% and 5.1% versus 6.5%, respectively.

CONCLUSIONS

This study demonstrates that a policy of selective screening for significant carotid artery disease in cardiac surgical patients combined with a strategy of CEA under local anaesthesia prior to unselected cardiac surgery (CABG with or without valve surgery) leads to rates of peri-operative CVA, myocardial infarction and death comparable to rates published for CEA prior to isolated CABG surgery. Furthermore, it reduces the risk of peri-operative stroke and 30-day mortality to that observed in patients undergoing cardiac surgery without significant carotid arterial disease.
Leucocyte count and oral temperature are a useful guide to selecting women with right iliac fossa pain for diagnostic laparoscopy
Authors: Singh-Ranger D , Ogadegbe A
Published: July 2010

INTRODUCTION

In women, negative appendicectomy rates can be as high as 34%. A 5-fold reduction is possible with diagnostic laparoscopy. A selective policy is favoured as indiscriminate use may increase postoperative morbidity. Scoring systems are helpful but not used widely du to their complexity. The value of leucocyte count and temperature in selecting women with right iliac fossa pain for diagnostic laparoscopy is investigated.

PATIENTS AND METHODS

Over a 12-month period, admission leucocyte count and temperature data were obtained from women undergoing appendicectomy. Cohorts were sub-categorised by age (< 20, 21–40 and > 40 years) and the proportion of negative (normal appendix) and positive (inflamed, gangrenous or perforated appendix) appendicectomies compared.

RESULTS

In 100 women, 11% had leucocyte counts and temperature ≥ 11 × 109/l and 38°C, respectively; all had appendicitis. In 50%, leucocyte counts and temperature were ≥ 11 × 109/l and < 38°C; negative appendicectomies occurred in 13.8% < 20 years, 10% > 40 years (P < 0.01) and 27.3% aged 21–40 years (P = 0.086). In 39%, the negative appendicectomy rate was ≥ 36.8% when leucocyte count and temperature were < 11 × 109/l and 38°C (P = 0.1).

CONCLUSION

Diagnostic laparoscopy should be considered in all women when leucocyte counts and temperature are ≥ 11 × 109/l and 38°C and for females aged 21–40 years when these values are ≥ 11 × 109/l and < 38°C.
High incidence of absent nerve conduction in older patients with bilateral carpal tunnel syndrome
Authors: Povlsen BO
Published: July 2010

INTRODUCTION

Carpal tunnel syndrome has been reported by some to have a less satisfactory outcome in older patients following surgery. However, this impression is not supported by other investigators but no objective explanation has been suggested for these differences. In our department, such patients are routinely treated with night wrist splints and, if this is unsatisfactory, they are investigated with nerve conduction studies prior to surgery.

PATIENTS AND METHODS

This paper reports the neurophysiological outcome in a young (< 40 years of age) and an older (> 60 years of age) group of patients with clinical bilateral carpal tunnel syndrome who did not benefit from splints.

RESULTS

The results showed that both the motor and sensory conduction speeds are significantly lower in the older age group. More importantly in the older group, half had one or more hands where the sensory conduction was absent. In four out of these 10 patients this finding was bilateral and three patients had unilateral absent motor conduction. In the younger group, no patient had absent conduction.

CONCLUSIONS

Poor surgical outcome in some older patients may be because of irreversibly damaged nerves prior to surgery and pre-operative neurophysiology is, therefore, recommended both for clinical and medicolegal reasons.
Amputation and the assessment of limb viability: perceptions of two hundred and thirty two orthopaedic trainees
Authors: Eardley WGP , Taylor DM , Parker PJ
Published: July 2010

INTRODUCTION

The management of complex extremity injury, which may require assessment of limb viability and performance of amputation, is a challenge to those involved in its emergent and definitive care. Concern exists regarding the exposure of orthopaedic trainees to such cases due both to changes in training and centralisation of trauma services.

SUBJECTS AND METHODS

This is a web-based observational study by survey, investigating the confidence and perceived adequacy of training of UK orthopaedic specialist trainees in the assessment of limb viability and amputation surgery. 222 responses from 888 trainees were required to achieve a < 5% error rate with 90% confidence; 232 surveys were completed.

RESULTS

Trainee confidence in dealing with the assessment of limb viability is high despite infrequent exposure to cases. The majority of trainees perceive their training in limb viability assessment as adequate. For performance of amputation, exposure is minimal, confidence is lower and 36% of trainees regard their training as inadequate.

CONCLUSIONS

Limb viability assessment is an area in which trainees feel confident and well trained. There is, however, a perceived training inadequacy in amputation surgery and a corresponding lack of confidence for many trainees, irrespective of training year. This is the first study to offer an insight into specific training experiences of junior orthopaedic surgeons at a national level and it should drive the development of opportunities for trainees to develop skills in amputation surgery.
Does the two-week rule pathway improve the diagnosis of soft tissue sarcoma? A retrospective review of referral patterns and outcomes over five years in a regional sarcoma centre
Authors: Pencavel Tim D , Strauss Dirk C , Thomas Greg P , Thomas J Meirion , Hayes Andrew J
Published: July 2010

INTRODUCTION

The NHS Cancer Plan was introduced in 2000 and included guidelines for the rapid assessment and referral of cases of suspected malignancy. We wished to assess the efficiency and appropriateness of patients referred under the Department of Health's general practitioner referral guidelines implemented for sarcomas in December 2000.

PATIENTS AND METHODS

A retrospective case-note review was performed of all patients referred to our regional soft tissue sarcoma unit between 1 January 2004 and 31 December 2008. Patients referred under the two-week guidelines and all patients referred routinely were analysed. The main outcome measures were the total number of patients referred on the basis of the two-week guidelines and the proportion they constitute of all referrals. The referring criteria were noted and compared to the observed criteria recorded. The final histo-logical diagnosis of patients referred on the basis of the two-week guidelines are documented.

RESULTS

A total of 2746 referrals for suspected sarcoma were made from January 2004 to December 2008. Of these, 154 referrals were made under the two-week rule of which 102 were referred purely on the clinical criteria for suspected soft tissue sarcoma. The remaining patients were referred after non-urgent special investigations indicated the possibility of sarcoma. Twelve patients referred under the two-week rule were proved to have sarcoma, nine after specific investigations including imaging or histological diagnosis. Of the 102 patients referred on clinical suspicion of a sarcoma, two patients had proven soft tissue sarcomas and one patient a cutaneous sarcoma. Between 2004 and 2008, the number of 2-week referrals rose 25-fold but accounted for an increase of less than 1% of the sarcomas treated in this unit.

CONCLUSIONS

The numbers of all referrals for suspected sarcoma are increasing; however, the rate of increase of 2-week referrals is increasing faster than routine referrals and will exceed it in 2012 if current trends continue. There has not been a commensurate rise in the detection of sarcoma or, more specifically, diagnosis of the deep sarcomas associated with worse prognosis. Current clinical guidelines have essentially had no impact on the early diagnosis and treatment of soft tissue sarcoma, and may negatively impact on the treatment of patients with proven sarcoma by delaying treatment within a regional centre because of redirection of a large number of patients with benign abnormalities to such centres.
The diagnosis and management of femoro-acetabular impingement
Authors: Macfarlane Robert J , Haddad Fares S
Published: July 2010

INTRODUCTION

Femoro-acetabular impingement (FAI) was first described in 1999 as abnormal abutment between the acetab-ulum and the femoral head and neck. Since then, it has been shown to be responsible for many acetabular labral tears and is implicated in the aetiology of osteoarthritis of the hip. This review introduces the concept of FAI and reports the key aspects of its diagnosis and management.

MATERIALS AND METHODS

A comprehensive search of the literature was conducted using the Pubmed database. Articles relating to the aetiology, pathophysiology, clinical features, diagnosis and treatment of FAI were reviewed. Search terms included femoro-acetabular impingement, arthroscopic treatment, open treatment, aetiology, pathophysiology. The search was limited to articles published in English. All articles were read in full by the authors and selected for inclusion based on relevance to the article.

RESULTS

An increasing number of studies relating to FAI have been produced in the 10 years since its recognition. A range of clinical and radiological features have been described. Surgical management can be performed using a number of techniques, with promising results from various studies. Early treatment with open surgery has paved the way for less invasive and arthroscopic approaches, with short-to-medium term data demonstrating favourable functional results for arthroscopic treatment of FAI.

CONCLUSIONS

A greater awareness of the diagnostic features of FAI, and the various management options available, will allow timely diagnosis and treatment of a relatively newly recognised syndrome. Early treatment may then help to prevent progression to end-stage osteoarthritis of the hip.
Thoracobilia: a rare complication of gallstone disease
Authors: Frampton Adam E , Williams Annabelle , Wilkerson Paul M , Paterson Iain M
Published: July 2010

Thoracobilia and pleurobiliary fistulae secondary to obstructed choledocholithiasis are rare complications of gallstone disease. We present the case of a 64-year-old man with gallstone pancreatitis who developed a pleurobiliary fistula secondary to an obstructing ductal calculus, and was successfully managed non-operatively.
Successful management of short gut due to vanishing gastroschisis – case report and review of the literature
Authors: Khalil BA , Gillham JC , Foresythe L , Harding R , Johnston T , Wright C , Morabito A
Published: July 2010

Vanishing gastroschisis is a rare in utero complication of gastroschisis. It is associated with a high mortality. We present a case report of an infant with vanishing gastroschisis that was managed with a combination of reconstructive bowel surgery and hepatosparing parenteral nutrition. The technique is described and a review of the literature is provided.
Intermittent small bowel obstruction caused by Meckel’s enterolith
Authors: Jones RP , McWhirter D
Published: July 2010

A 56-year-old man presented with small bowel obstruction after a 6-week history of intermittent resolving subacute small bowel obstruction. After investigations, he underwent laparotomy. A mobile, narrow-necked Meckel’s diverticulum packed with enteroliths pressing against proximal small bowel was discovered. A small bowel resection was performed.
Congenital vascular malformation associated with multiple cranial, vertebral and upper limb skeletal abnormalities
Authors: Marsden N , Shokrollahi K , Maw K , Sierakowski A , Bhat FA , Mathur B
Published: July 2010

The association between congenital vascular malformations and altered bone growth, the so-called vascular bone syndrome, is well documented. Various eponymous syndromes each with their individual traits, such as Klippel–Trenaunay, Parkes–Weber and Servelle–Martorell syndrome have been described, along with variations. We report on a previously undescribed case of congenital vascular malformation associated with multiple skeletal abnormalities affecting the skull, vertebrae and right upper limb, and discuss the literature.
Is laparotomy the unavoidable step to diagnose caecal volvulus?
Authors: Pulvirenti Elia , Palmieri Laura , Toro Adriana , Di Carlo Isidoro
Published: July 2010

Caecal volvulus is the axial twist of the caecum, ascending colon and terminal ileum around the mesenteric pedicle. This infrequently encountered clinical entity is responsible for 1–1.5% of all intestinal obstruction with a mortality of 10–40% depending on the presence of colon viability or intestinal gangrene. Many factors have been referred as correlated to caecal volvulus development, mainly anatomical predisposition and previous abdominal operations. Pre-operative diagnosis plays an important role in the management of such patients. Unfortunately, clinical signs, symptoms and laboratory tests are never specific enough to lead to a prompt diagnosis. Abdominal radiography and computed tomography may allow a diagnosis if typical signs are present. However, up to 30% of patients do not show these radiographic peculiarities, making the diagnosis difficult or impossible. Moreover, the low incidence of this disease is often responsible of a wrong or imprecise diagnosis, especially for radiologists who work with low volume of patients. We report a case of a patient with caecal volvulus, in which laparotomy was unavoidable to reach a diagnosis.
Upper limb deep vein thrombosis: a potentially fatal complication of a clavicle fracture
Authors: Jones REK , McCann PA , Clark DA , Sarangi P
Published: July 2010

We present a case a 48-year-old man who was diagnosed with an upper limb deep vein thrombosis post clavicle fracture. He was successfully investigated with a computed tomography (CT) venogram, thrombophilia was excluded, and he was subsequently treated with a 3-month course of anticoagulation. We illustrate this case with photographs and a three-dimensional colour reconstruction of a CT venogram to raise awareness of the condition. A suitable level of clinical suspicion should be maintained by the orthopaedic surgeon; delayed arm swelling with venous congestion following a clavicle fracture should be investigated with CT venography and thrombophilia should be excluded.