bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of ambient temperature on the compaction of pharmaceutical powders
Authors: Michrafy A , Haas S , Kadiri M. S. , Sommer K , Dodds J. A.
Published: October 2007

This article presents an experimental study of the effects of raised ambient temperature in dies and punches on the compaction of pharmaceutical powders. The experiments use an instrumented hydraulic press having a temperature-controlled enclosure allowing the ambient temperature of die and punch to be varied from 20 to 57 °C. A pharmaceutical powder was compacted at temperatures in this range and mechanical parameters, such as stress transfer ratio, stress transmission ratio, and die-wall friction, were analysed to examine the effects of heat transfer between tools and powder. In particular, it is shown that increasing the environmental temperature of die and punch increases the transfer ratio and the die-wall friction. The radial pressure is also slightly increased at the first stages of the compaction. However, the stress transmission is reduced by increasing the temperature. This may indicate an increase of shear stress. It is also observed that the particles undergoing compaction are ‘softened’ by increase of the temperature. This softening is certainly due to rise in temperature of the powder generated by the compaction and by the heat flux transfer between the die and the tablet. It is suggested that these effects could be important in industrial tablet production installations without air conditioning and thus subject to variations in ambient temperature.
Understanding the role of corrosion in the degradation of metal-on-metal implants
Authors: Yan Y , Neville A , Dowson D
Published: October 2007

In metal-on-metal joints the primary concerns in terms of long-term durability relate to corrosion, wear, and their joint (tribocorrosion) effects. The release of ions through corrosion processes and nanoscale debris from wear processes can seriously affect joint integrity and can lead to an adverse biological reaction by the host. In this paper an integrated study of corrosion-wear interactions in serum, Dulbecco's Modified Eagle's Medium and 0.3 per cent NaCl has demonstrated that the biological nature of the fluid affects the total degradation rate and also the level of wear-corrosion interactions. The specific action of proteins in corrosion and tribocorrosion for high-carbon Co-Cr-Mo and low-carbon Co-Cr-Mo alloys is discussed.
Cancer incidence and causes of death among total hip replacement patients: A review based on Nordic cohorts with a special emphasis on metal-on-metal bearings
Authors: Visuri TI , Pukkala E , Pulkkinen P , Paavolainen P
Published: October 2007

All patients with total hip arthroplasty (THA) are exposed to soluble or particulate forms of Co and Cr. Adverse effects of these wear products are not known. Data from Nordic registries is used to estimate adverse effects on a large scale, based mostly on metal-on-polyethylene bearings. Cancer incidence was in line with the general population when the patients were operated on for all indications and significantly decreased when the indication was primary osteoarthritis. Stomach cancer and colorectal cancers were significantly reduced and prostate cancer and skin melanoma significantly increased. There was no significant excess of cancer in target organs, i.e. liver, kidney, or haematopoietic cancers. THA patients had reduced mortality and extended life expectancy compared with standard Nordic populations.

All-site cancer incidence of the first-generation metal-on-metal McKee-Farrar patients operated on for primary osteoarthritis was in line with the general population after follow-up for up to 28 years. General mortality of these patients was also reduced and they also had an extended life expectancy.

Temporary increases in haematopoietic cancers at different follow-up periods were seen in some cohorts. This malignancy deserves a special record linkage monitoring while large numbers of young patients are provided with the second generation of metal-on-metal prostheses.
Biological effects of clinically relevant wear particles from metal-on-metal hip prostheses
Authors: Brown C , Fisher J , Ingham E
Published: October 2007

The problems of osteolysis and late aseptic loosening associated with ultra-high molecular weight polyethylene (UHMWPE) particles has lead to a renewed interest in metal-on-metal prostheses. Wear particles generated by modern Co-Cr-on-Co-Cr prostheses are nanometre in size (range: 10-120 nm; mean: about 40 nm), an order of magnitude smaller than the size of UHMWPE known to be critical for activation of osteolytic cytokines by macrophages. Co-Cr wear particles will induce osteolytic cytokine production by human macrophages, but only at high volumetric concentrations. Unlike UHMWPE, Co-Cr particles are not inert. Co-Cr particles have the potential to release metal ions; they may be toxic to cells, induce deoxyribonucleic acid damage or cause host hypersensitivity. The nanometre size range of Co-Cr wear particles means that they may be disseminated widely in the body.

The potential for metal-on-metal bearings to induce adverse effects clinically will be dependent upon the rate of wear. What constitutes a safe wear rate for modern metal-on-metal bearings is unknown. However, the wear of metal-on-metal prostheses is critically dependent upon the design and, in particular, the carbon content of the alloy, the radial clearance, and the head diameter. Thus, the potential for adverse biological reactions associated with metal-on-metal bearings can be reduced by selection of appropriately designed implants.
History and modern concepts in surface replacement
Authors: McMinn D , Daniel J
Published: October 2007

Hip resurfacing is not a modern concept. Professor Sir John Charnley attempted the first hip resurfacing procedure in the 1950s. This implant failed as a result of unsatisfactory materials and the same problem has troubled hip resurfacing developments over the subsequent forty years. Modern hip resurfacing using metal-on-metal bearings has shown good medium-term results in the most challenging subgroup - young active patients.
Biological effects of metal-on-metal hip replacements
Authors: Bhamra M S , Case C P
Published: October 2007

The advantages seen by patients receiving total hip arthroplasties and the implications of the release of both metal particles and soluble metal ions are discussed. This paper describes some of the early changes that have been observed in metal-on-metal hip arthroplasties, in terms of both changes in metal levels in blood and chromosome changes.
Biomechanical, morphological, and histological analysis of early failures in hip resurfacing arthroplasty
Authors: Morlock M M , Bishop N , Rüther W , Delling G , Hahn M
Published: October 2007

The present revival of hip resurfacing arthroplasty may be related to an increase in early failures owing to the challenging technique of the procedure. Fifty-five retrieved implants were analysed with respect to wear, cement mantle and cement penetration, fracture and head morphology, as well as standard histology. Femoral neck fractures occurred in median after 102 days. The time to failure was shorter for older women. Major deviations from the suggested cement mantle thickness and cement penetration were found. Indications for high trauma during implantation leading to early failure due to weakening of the femoral neck were also observed. Some failures had signs of pseudarthrosis beneath the implant. Four different fracture patterns with different mean survival times were identified. Observed wear was minor with the exception of that due to alignment mistakes (rim loading). The cups were not damaged by the failures. Histological results indicate that avascular necrosis is not necessarily connected with this kind of endoprosthetic surgery. Most of the failures analysed can probably be attributed to the ‘learning curve’ effect, which is an unsatisfactory situation.
Hip resurfacing arthroplasty: The evolution of contemporary designs
Authors: Grigoris P , Roberts P , Panousis K , Jin Z
Published: October 2007

Metal-on-metal hip resurfacing is considered by many as the most significant recent development in hip arthroplasty. It preserves proximal femoral bone stock, optimizes stress transfer to the proximal femur, and offers inherent stability and optimal range of movement. The early results of hip resurfacing in the 1970s and 1980s were poor and the procedure was largely abandoned by the mid-1980s. The expectation that these prostheses would be easy to revise was not often fulfilled. The large diameter of the articulation combined with thin polyethylene cups or liners resulted in accelerated wear and the production of large volumes of biologically active particulate debris, leading to bone loss and implant loosening. Failure has been attributed to other factors, mainly avascular necrosis of the femoral head. However, this concern has not been confirmed by retrieval studies. The failure of early hip resurfacings was essentially a consequence of the use of inappropriate materials, poor implant design, inadequate instrumentation, and crude surgical technique. It was not an inherent problem with the procedure itself.

The renaissance of metal-on-metal articulations for total hip arthroplasty enabled the introduction of new hip resurfacings and most of the major implant manufacturers have already introduced such systems. Early results are encouraging and complications commonly seen in the 1970s and 1980s, such as early implant loosening and femoral neck fracture, now appear to be rare. Whilst early results should be regarded with caution, modern metal-on-metal hip resurfacing potentially offers the ultimate bone preservation and restoration of function in appropriately selected young patients.
Deformation of press-fitted metallic resurfacing cups. Part 2: Finite element simulation
Authors: Yew A , Jin Z M , Donn A , Morlock M M , Isaac G
Published: October 2007

The deformation of metallic acetabular cups employed for metal-on-metal hip resurfacing procedures was considered theoretically using the finite element method in the present study, following on the experimental investigation reported in Part 1. Three representative cups, characterized by the cup wall thickness as thin, intermediate, and thick, were considered. For the intermediate cup, the effects of both the size and the diametral interference on the cup deformation were investigated. Both two-dimensional axisymmetric and three-dimensional finite element models were developed to examine the important parameters during and after the press-fit procedure, and in particular the deformation of the metallic cup. The theoretical prediction of the cup deformation was in reasonable agreement with the corresponding experimental measurement reported in Part 1. The most significant factor influencing the cup deformation was the cup wall thickness. Both the size and the diametral interference were also shown to influence the cup deformation. It is important to ensure that the cup deformation does not significantly affect the clearance designed and optimized for tribological performances of metal-on-metal hip resurfacing prostheses. Furthermore the contact parameters at the cup and bone interface associated with the press fit were also discussed.
Metal-on-metal hip joint tribology
Authors: Dowson D , Jin Z-M
Published: October 2007

The basic tribological features of metal-on-metal total hip replacements have been reviewed to facilitate an understanding of the engineering science underpinning the renaissance of these hard-on-hard joints.

Metal-on-polymer hip replacements operate in the boundary lubrication regime, thus leading to the design guidance to reduce the femoral head diameter as much as is feasible to minimize frictional torque and volumetric wear. This explains why the gold-standard implant of this form from the past half-century had a diameter of only 22.225 mm (7/8 in).

Metal-on-metal implants can operate in the mild mixed lubrication regime in which much of the applied load is supported by elastohydrodynamic films. Correct tribological design leads to remarkably low steady state wear rates. Promotion of the most effective elastohydrodynamic films calls for the largest possible head diameters and the smallest clearances that can reasonably be adopted, consistent with fine surface finishes, good sphericity and minimal structural elastic deformation of the cup on its foundations. This guidance, which is opposite in form to that developed for metal-on-polymer joints, is equally valid for solid (monolithic) metallic heads on metallic femoral stems and surface replacement femoral shells.

Laboratory measurements of friction and wear in metal-on-metal joints have confirmed their potential to achieve a very mild form of mixed lubrication. The key lies in the generation of effective elastohydrodynamic lubricating films of adequate thickness compared with the composite roughness of the head and cup. The calculation of the film thickness is by no means easy, but the full procedure is outlined and the use of an empirical formula that displays good agreement with calculations based upon the full numerical solutions is explained. The representation of the lambda ratio, A, embracing both film thickness and composite roughness, is described.
Clinical experience with metal-on-metal total joint replacements: Indications and results
Authors: Learmonth I D , Gheduzzi S , Vail T P
Published: October 2007

Survivorship of total joint arthroplasty depends on the durability of fixation and durability of articulation. The metal-on-polyethylene articular couple has been the most widely used. Polyethylene wear (and the associated cytochemical events that culminate in osteolysis) has been identified as a major factor adversely influencing the durability of joint replacement. This stimulated the orthopaedic community to explore the possibility of using alternative bearings with lower wear rates.

Hard-on-hard bearings have been shown to be associated with reduced wear. Metal-on-metal bearings have wear rates that are 20-100 times lower than metal on conventional polyethylene. However, patients with metal-on-metal articulations have increased levels of cobalt and chromium in the serum and urine, and this has raised concerns about toxicity, mutagenesis, and hypersensitivity. At this stage there is no epidemiological evidence to suggest that the risk of carcinogenesis is anything more than theoretical.

Successful long-term results have been reported with the cast cobalt-chromium metal-on-metal couples of the mid-1960s. Tissues retrieved at revision of these implants did not show the giant-cell inflammatory response associated with polyethylene particles. Several researchers have reported excellent mid-term results with the current generation of high-precision metal-on-metal bearings.
Development rationale for an articular surface replacement: A science-based evolution
Authors: Isaac G H , Siebel T , Schmalzried T P , Cobb A G , O'Sullivan T , Oakeshott R D , Flett M , Vail T P
Published: October 2007

Hip resurfacing has an enduring appeal because of the advantages of bone conservation and maximal joint stability. However, a far from satisfactory experience with earlier resurfacing designs led to its virtual disappearance in the 1980s. The concept was reintroduced in the late 1990s. The current generation of resurfacing devices generally consisted of a large-diameter metal-on-metal articulation, the femoral components being cemented and the acetabular components utilizing various forms of cementless fixation. The encouraging medium-term results, with a follow-up of up to 8 years using the current generation of surface replacement joints, combined with favourable reports related to long-term performance of some metal bearings have led to a rapid increase in the use of such components with these devices. This trend is most marked in younger, more active patients who have expectations of restoration of lifestyle in addition to improved mobility and pain relief and in whom failure with conventional total hip replacement is much higher than previously reported with more sedentary patients.

The aim of this paper is, firstly, to highlight a number of areas of improvement and, secondly, to explain how these may be addressed by making modifications to the design of both implants and instrumentation and to the surgical technique. The areas identified for improvement were tissue preservation (thinner components, and reduced steps between sizes), acetabular cup issues (fixation, insertion, and positioning), femoral component issues (design, loading, and cementation), improved bearing surface characteristics, and simplified precise instrumentation with a low-trauma surgical technique.
Deformation of press-fitted metallic resurfacing cups. Part 1: Experimental simulation
Authors: Jin Z M , Meakins S , Morlock M M , Parsons P , Hardaker C , Flett M , Isaac G
Published: October 2007

The interference press fit of a metallic one-piece acetabular cup employed for metal-on-metal hip resurfacing procedures was investigated experimentally under laboratory conditions in the present study, in particular regarding the cup deformation. Tests were carried out in cadavers as well as polyurethane foams of various grades with different elastic moduli to represent different cancellous bone qualities. The cadaver test was used to establish the most suitable configuration of the foam model representing realistic support and geometrical conditions at the pelvis. It was found that a spherical cavity, with two identical areas relieved on opposite sides, was capable of creating a two-point pinching action of the ischeal and ilial columns on the cup as the worst-case scenario. Furthermore, the cup deformation produced from such a two-point loading model with a grade 30 foam was similar to that measured from the cadaver test. Therefore, such a protocol was employed in subsequent experimental tests. For a given size of the outside diameter of the cup of 60 mm, the cup deflection was shown to be dependent largely on the cup wall thickness and the diametral interference between cup and prepared cavity at implantation. For a relatively thin cup with a wall thickness between 2.3 mm (equator) and 4 mm (pole) and with a modest nominal diametral interference of 1 mm, which corresponds to an actual interference of approximately 0.5 mm, the maximum diametral cup deflection (at the rim) was around 60 μm, compared with a diametral clearance of 80-120 μm between the femoral head and the acetabular cup, generally required for fluid-film lubrication and tribological performances. Stiffening of the cup, by both thickening and lateralizing by 1 mm, reduced the cup deformation to between 30 and 50 μm with actual diametral interferences between 0.5 and 1 mm.
Cementing techniques in hip resurfacing
Authors: Chandler M , Z Kowalski R S , Watkins N D , Briscoe A , R New A M
Published: October 2007

The subject of the cementing technique in hip resurfacing has been poorly studied to date. The hip resurfacing prosthesis is unique in the family of cemented prostheses because the cement mantle is blind (hidden underneath the implant) and is radiographically obscured. This presents an immediate challenge to the surgeon at the time of surgery, but also has a longer-term implication in terms of lack of post-operative clinical observation. This should be compared with total hip replacement or total knee replacement where the cement mantle can at least be partially observed both intra- and post-operatively. With this in mind, the objective of this review is, firstly, to understand the cement mantles typically achieved in current clinical practice and, secondly, to identify those factors affecting the cement mantle and to consolidate them into an improved and reproducible cementing technique. The outcome of this work shows that the low-viscosity technique can commonly lead to excessive cement penetration in the proximal femoral head and an incompletely seated component, whereas a more consistent controlled cement mantle can be achieved with a high-viscosity cementing technique. Consequently, it is recommended that a high-viscosity technique should be used to minimize the build-up of excessive cement, to reduce the temperature created by the exothermic polymerization, and to help to ensure correct seating of the prosthesis. A combination of these factors is potentially critical to the clinical success of some articular surface replacement (ASR) procedures.

It is important to note that we specifically studied the DePuy ASR system; therefore only the general principles (and not the specifics) of the cementing technique may apply to other resurfacing prostheses, because of differences in internal geometry, clearance, and surgical technique.
The tribology of metal-on-metal total hip replacements
Authors: Scholes S C , Unsworth A
Published: October 2007

Total hip surgery is an effective way of alleviating the pain and discomfort caused by diseased or damaged joints. However, in the majority of cases, these joints have a finite life. The main reason for failure is osteolysis (bone resorption). It is well documented that an important cause of osteolysis, and therefore the subsequent loosening and failure of conventional metal- or ceramic-on-ultra-high molecular weight polyethylene joints, is the body's immunological response to the polyethylene wear particles. To avoid this, interest has been renewed in metal-on-metal joints.

The intention of this paper is to review the studies that have taken place within different laboratories to determine the tribological performance of new-generation metal-on-metal total hip replacements. These types of joint offer a potential solution to enhance the longevity of prosthetic hip systems; however, problems may arise owing to the effects of metal ion release, which are, as yet, not fully understood.
The clinical significance of metal ion release from cobalt-chromium metal-on-metal hip joint arthroplasty
Authors: Cobb A G , Schmalzreid T P
Published: October 2007

Metal-on-metal (MOM) bearings offer extremely low wear and the avoidance of polyethylene but generate metallic wear particles. Although their total volume is dramatically smaller than polyethylene debris, these particles are in the nanometre size range and are many times more numerous. Metallic particles are ingested by macrophages or may be disseminated via lymphatics to the reticuloendothelial system. They corrode, and metal ions are present in the circulation and concentrated in erythrocytes. Excretion of metal ions via the kidneys seems to balance their generation in patients with MOM implants. However, highly sensitive detection methods can be used to show that levels of circulating cobalt and chromium ions are several times the normal level. These concentrations are well within the limits identified as dangerous to health in workers exposed to industrial chemicals, and also considerably lower than the levels found to cause cell toxicity in vitro. The local concentrations of particles and metal ions in the synovial tissue may occasionally exceed these limits and cause tissue necrosis. Clinical experience of lysis is rare in association with MOM bearings, as are hypersensitivity reactions and MOM bearings have had an excellent record over four decades and have a favourable benefit to risk ratio. Further reduction in risk will be achieved by improvement of materials, engineering, and accuracy of insertion.
Metal-on-metal hip simulator study of increased wear particle surface area due to ‘severe’ patient activity
Authors: Bowsher J G , Hussain A , Williams P A , Shelton J C
Published: October 2007

This study investigated changes in metal-on-metal (MOM) hip wear and wear particle characteristics arising from a more aggressive patient activity level compared with normal walking. The test hypothesis was that ‘severe’-gait conditions will change wear, wear particle sizes, and morphology owing to a decline in joint lubrication. Four carbon MOM hip bearings 40 mm high were subjected to normal-walking and fast-jogging simulations in an orbital hip joint simulator with 25 per cent α-calf serum as a lubricant. Co-Cr-Mo wear particles were extracted using an enzymatic method, and prolate ellipsoid equations were used to estimate particle volume and surface area. Fast-jogging simulations generated a sevenfold increase in volumetric wear, a 33 per cent increase in mean wear particle size, and a threefold increase in the number of larger (needle) particles compared with walking. This resulted in a twentyfold increase in total wear particle surface area per 106 cycles compared with walking, thereby confirming our hypothesis. The clinical significance of this result suggests that highly active MOM patients may exhibit greater ion release than less active patients.
Calculation method of efficiency factor in Alford's force
Authors: Ding X. J. , Yang Y. L. , Chen W , Huang S. H. , Zheng C. G.
Published: October 2007

The mechanism of gas excitation for wheel eccentricity and to calculate Alford's force are introduced. On the basis of the blade-and-flow parameters a new formulation is derived and validated. The calculation results are consistent with current theory and experimental conclusions. The physical meaning of the ranges of numerical values of the efficiency factor are discussed. This gets rid of the difficulty of selecting the efficiency factor in Alford's formulation and lays a theoretical foundation for the stability analysis to increase turbine rotor stability.
Measurement and analysis of three-dimensional flow in a centrifugal fan volute with large volute width and rectangular cross-section
Authors: Qi D , Zhang Y , Wen S , Liu Q
Published: October 2007

Among all the elements of a centrifugal fan, the volute is the one that has the lowest flow efficiency. Therefore, improving the performance of the volute is an efficient way to improve the total performance of a centrifugal fan. To contribute a better understanding of the flow structure in the fan volute, the three-dimensional flow in a centrifugal fan volute with a large volute width and rectangular cross-section has been measured in detail by means of five-hole probe at three different flowrates. The time-average swirling and throughflow velocity, static and total pressure distributions on eight cross-sections in the throughflow direction of the volute are presented. The results show the formation and development of the flow in the fan volute of this type, indicate the variation of flow parameters, and discover some peculiar flow phenomena different from the traditional understanding. On the basis of the experimental results, the main hydraulic losses in this kind of fan volute have been preliminarily classified and analysed. The results show that the traditional one-dimensional design method of the volute should be further improved as it is only based on the law of momentum moment conservation and the ideal assumption that the distribution of flow parameters are uniform at the volute inlet.
Design of an active suspension system for a quarter-car road vehicle model using model reference control
Authors: Parthasarathy S S , Srinivasa Y. G.
Published: October 2007

The use of skyhook damping for reduction of the vibration in the suspension systems is well documented. The drawback is that it is not practically feasible to obtain the equivalent of a reference point in the sky. The alternative method of using a damper between the sprung mass (the vehicle hull) and the unsprung mass (the wheel assembly) leads to a deterioration in the performance of the unsprung mass. In this paper a new method is proposed that tries to overcome the limitation of the practical skyhook damping method by the use of the model reference control (MRC) method, where the control input is utilized to achieve near-ideal skyhook sprung mass performance in a practical skyhook damping set-up. The MRC method is also applied to a quarter-car suspension model, where the control input is used to achieve the response of a system with damping and stiffness values different from those of the actual system. This allows for variation of the system constants as dictated by dynamic response needs. The proposed methods are applied on a typical quarter-car suspension system and the necessary time and frequency domain simulations are carried out to validate the theoretical predictions.
Adaptive control of dynamically substructured systems: The single-input single-output case
Authors: Stoten D P , Hyde R. A.
Published: October 2007

In recent years, there has been much interest in using the principle of dynamic substructuring as a framework for the testing of critical engineering components and systems. The most significant advantage of the method is that it can offer the opportunity to test full-size non-linear components within a laboratory environment. Such a test would be run in parallel with a real-time numerical simulation of the remaining part of the overall system to be emulated. Potentially, the most significant disadvantage of the method is the very high fidelity of control that is required, in order to achieve near-perfect synchronization of the test rig and the numerical model. This problem is further exacerbated by the presence of unknown and changing dynamic parameters, disturbances, and non-linearities in the test rig.

The purpose of this paper is to lay a foundation for the linear control of dynamically sub-structured systems and, leading on from that, robust adaptive control via an extension to the adaptive minimal control synthesis (MCS) algorithm. Comparative simulation results from using the linear and adaptive control strategies are also included in the paper.
Ion current combustion technology for controlled auto-ignition gasoline engines
Authors: Attard P , Micallef J
Published: October 2007

The use of ionization sensors, by means of a standard spark plug, in gasoline engines is well known. This paper focuses on the use of these sensors for controlled auto-ignition (CAI) gasoline engines, where the air-fuel mixture ignites without the need of a spark. The averaged ion current signals obtained are first observed and compared to the heat release rate and then a method to detect with accuracy the location of the 50 per cent mass fraction burned is described. The variation of emissions is studied and the effects of using a pressure sensor (to calculate the heat release rate) or an ion current sensor are portrayed. Thus it is proved possible to keep the emissions under strict control by using an ion current sensor.
Reliability and maintainability allocation to minimize total cost of ownership in a series-parallel system
Authors: Kumar U. Dinesh , Ramírez-Márquez J. E. , Nowicki D , Verma D
Published: October 2007

Allocation of system level requirements is most effective when performed early in the system's design phase. This holds especially true for two critical and fundamental design characteristics: reliability and maintainability. Traditional reliability allocation models are developed to either maximize system reliability under a cost constraint or minimize cost subject to a system-level, target reliability constraint. Cost, in these traditional allocation models, is represented solely by unit cost. Unit cost, by itself, is an inadequate measure of a system's operational effectiveness. In fact, the underlying economic metric used to properly describe the operational effectiveness of a system is total cost of ownership (TCO). TCO includes not only the upstream unit cost but the downstream operations, maintenance, and support costs. In this paper, new allocation models are developed based on TCO that simultaneously allocate both reliability and maintainability for a series-parallel system subject to meeting a system-level availability target. A non-linear representation of a mathematical model is defined that simultaneously allocates both system-level reliability and maintainability targets in a manner that minimizes TCO. This non-linear model is then transformed into a surrogate linear model that can be solved using existing commercial software. Examples are then discussed to illustrate the solution procedure and to show the sensitivity of allocation design decisions to fluctuations in economic factors such as discount rates, and design factors such as the life of the system.
Simulation of human performance in time-pressured scenarios
Authors: Kozine I
Published: October 2007

This paper reports on the application of the single-channel theory of selective attention to the simulation of human actions in time-pressured scenarios. The paper demonstrates the applicability and benefits of using computer discrete event simulation tools to imitate hazardous scenarios possibly taking place at a potentially hazardous installation with a focus on operators' performance. One of the outcomes of the modelling is the probability of action failure, and this probability is thought of as being dependent on the characteristics of the incoming tasks to be attended to and operated on by the actor and also on the actor's individual abilities, which are in turn influenced by performance-shaping factors. A case study on the simulation of operators' performance under a medium loss of coolant accident scenario at a nuclear power plant is briefly described in the paper.
Adaptive-loop method for non-deterministic design optimization
Authors: Youn B. D.
Published: October 2007

In the last two decades, significant attention has been paid to developing nondeterministic design optimization methodologies: reliability-based design optimization (RBDO), possibility-based design optimization (PBDO), and evidence-based design optimization (EBDO). As a result, numerous methods for non-deterministic design optimization have been proposed. They are categorized as: parallel-loop method, serial-loop method, and single-loop method. It has been reported that each method has its own strong and weak points. The current paper attempts to understand better the various methods, and proposes to develop an integrated framework for non-deterministic design optimization. In short, the integrated design framework adaptively involves different loop methods (deterministic design optimization, parallel-loop method, single-loop method) to maximize numerical efficiency and stability without losing numerical accuracy in the non-deterministic design optimization process. While deterministic design optimization and the single-loop method will improve numerical efficiency at the beginning and end of non-deterministic design optimization, the parallel-loop method maintains good numerical stability in the middle. Thus, the proposed method is referred to as the adaptive-loop method. It will be shown that the adaptive-loop method is applicable for nondeterministic design optimization, such as RBDO, PBDO. Examples are used to demonstrate the effectiveness of the adaptive-loop method in terms of numerical efficiency and stability.
Thiostrepton inhibition of tRNA delivery to the ribosome
Authors: Gonzalez Ruben L. , Chu Steven , Puglisi Joseph D.
Published: October 2007

Ribosome-stimulated hydrolysis of guanosine-5′-triphosphate (GTP) by guanosine triphosphatase (GTPase) translation factors drives protein synthesis by the ribosome. Allosteric coupling of GTP hydrolysis by elongation factor Tu (EF-Tu) at the ribosomal GTPase center to messenger RNA (mRNA) codon:aminoacyl-transfer RNA (aa-tRNA) anticodon recognition at the ribosomal decoding site is essential for accurate and rapid aa-tRNA selection. Here we use single-molecule methods to investigate the mechanism of action of the antibiotic thiostrepton and show that the GTPase center of the ribosome has at least two discrete functions during aa-tRNA selection: binding of EF-Tu(GTP) and stimulation of GTP hydrolysis by the factor. We separate these two functions of the GTPase center and assign each to distinct, conserved structural regions of the ribosome. The data provide a specific model for the coupling between the decoding site and the GTPase center during aa-tRNA selection as well as a general mechanistic model for ribosome-stimulated GTP hydrolysis by GTPase translation factors.
Cloning and expression profiling of small RNAs expressed in the mouse ovary
Authors: Ro Seungil , Song Rui , Park Chanjae , Zheng Huili , Sanders Kenton M. , Yan Wei
Published: October 2007

Small noncoding RNAs have been suggested to play important roles in the regulation of gene expression across all species from plants to humans. To identify small RNAs expressed by the ovary, we generated mouse ovarian small RNA complementary DNA (srcDNA) libraries and sequenced 800 srcDNA clones. We identified 236 small RNAs including 122 microRNAs (miRNAs), 79 piwi-interacting RNAs (piRNAs), and 35 small nucleolar RNAs (snoRNAs). Among these small RNAs, 15 miRNAs, 74 piRNAs, and 21 snoRNAs are novel. Approximately 70% of the ovarian piRNAs are encoded by multicopy genes located within the repetitive regions, resembling previously identified repeat-associated small interference RNAs (rasiRNAs), whereas the remaining ∼30% of piRNA genes are located in nonrepetitive regions of the genome with characteristics similar to the majority of piRNAs originally cloned from the testis. Since these two types of piRNAs display different structural features, we categorized them into two classes: repeat-associated piRNAs (rapiRNAs, equivalent of the rasiRNAs) and non-repeat-associated piRNAs (napiRNAs). Expression profiling analyses revealed that ovarian miRNAs were either ubiquitously expressed in multiple tissues or preferentially expressed in a few tissues including the ovary. Ovaries appear to express more rapiRNAs than napiRNAs, and sequence analyses support that both may be generated through the “ping-pong” mechanism. Unique expression and structural features of these ovarian small noncoding RNAs suggest that they may play important roles in the control of folliculogenesis and female fertility.
Change in the Governance of Medicine: the politics of self-regulation
Authors: Salter Brian
Published: October 2007

English

This article develops and applies an analytical framework which shows how the political forces at work in the triangular relationship between medicine, society and the State interact to guide and constrain change in medicine’s system of governance. Under pressure from society and the State, the medical profession is now obliged to reform itself and accept a higher degree of public accountability. This article explores the dimensions of the changes required, their likely impact on the political benefits which historically have sustained the triangular relationship, and hence the complex politics which must inevitably accompany such reforms.
The Development of Domiciliary Care: mission accomplished?
Authors: Wistow Gerold , Hardy Brian
Published: October 2007

English

The development of domiciliary care through the independent sector was central to the successful implementation of the 1993 community care changes. A considerable degree of success has been achieved: there has been substantial growth in the volume of home care hours funded by local authorities, all of it concentrated in the independent sector. As a result, the sector now provides more than two fifths of all local authority-funded home care. This pattern of development has not been unproblematic, however. Purchaser–provider relationships have created some provider instability and threatened continuity of care for users. The continuing task for local authorities as purchasers is to develop relationships with their providers which ensure that the quality of care services, and the way they are delivered, are consistent with user-defined standards.
Staff Qualifications and Ratios in Children’s Homes: are they the key to the outcomes of care?
Authors: Sinclair Ian , Gibbs Ian
Published: October 2007

English

Official reports into methods of improving the performance of children’s homes have focused on staff training, staff ratios and size. This article tests these conclusions on 48 children’s homes. It develops a measure of performance based on the social climate of a home and relates this to size, to the proportion of qualified staff, to whether the head of home was qualified and to staff ratios. The analysis supports the importance of size but finds no relationship between staff ratios and qualifications on the one hand and performance on the other.
Use of Halogenated Precursors for Simultaneous DNA and RNA Detection by Means of Immunoelectron and Immunofluorescence Microscopy
Authors: Vecchio Lorella , Solimando Liliana , Biggiogera Marco , Fakan Stanislav
Published: October 2007

We have developed a novel approach for in situ labeling and detection of nucleic acids in cultured cells. It is based on in vivo incorporation of chlorouridine (ClU) or iododeoxyuridine (IdU) into Chinese hamster ovary cells with the aim of labeling RNA and DNA, respectively. The halogenated nucleotides are immunolabeled on ultrathin sections with anti-bromodeoxyuridine (BrdU) monoclonal antibodies that specifically react with either IdU or ClU. Furthermore, we combined ClU and IdU incubation to label simultaneously RNA and DNA in the same cell. Both were visualized by means of anti-BrdU antibodies exhibiting strong affinity for one of the two halogenated epitopes. Confocal imaging of interphase nuclei and electron microscopic analysis showed evidence of a partial colocalization of newly synthesized DNA and RNA inside the cell nucleus. RNase and DNase digestion of ultrathin sections after formaldehyde fixation and acrylic resin embedding confirmed the specificity of incorporation. Consequently, this method allows us to differentially label DNA and RNA on the same section. Using short pulses with the precursors, we could show that newly synthesized DNA and RNA both preferentially occur within the perichromatin region at the border of condensed chromatin domains.
Chondroitin Sulfate Sulfation Motifs as Putative Biomarkers for Isolation of Articular Cartilage Progenitor Cells
Authors: Hayes Anthony J. , Tudor Debbie , Nowell Mari A. , Caterson Bruce , Hughes Clare E.
Published: October 2007

Osteoarthritis is a chronic, debilitating joint disease characterized by progressive destruction of articular cartilage. Recently, a number of studies have identified a chondroprogenitor cell population within articular cartilage with significant potential for repair/regeneration. As yet, there are few robust biomarkers of these cells. In this study, we show that monoclonal antibodies recognizing novel chondroitin sulfate sulfation motif epitopes in glycosaminoglycans on proteoglycans can be used to identify metabolically distinct subpopulations of cells specifically within the superficial zone of the tissue and that flow cytometric analysis can recognize these cell subpopulations. Fluorochrome colocalization analysis suggests that the chondroitin sulfate sulphation motifs are associated with a range of cell and extracellular matrix proteoglycans within the stem cell niche that include perlecan and aggrecan but not versican. The unique distributions of these sulphation motifs within the microenvironment of superficial zone chondrocytes, seems to designate early stages of stem/progenitor cell differentiation and is consistent with these molecules playing a functional role in regulating aspects of chondrogenesis. The isolation and further characterization of these cells will lead to an improved understanding of the role novel chondroitin sulfate sulfation plays in articular cartilage development and may contribute significantly to the field of articular cartilage repair.
Regeneration of Reinnervated Rat Soleus Muscle Is Accompanied by Fiber Transition Toward a Faster Phenotype
Authors: Mendler Luca , Pintér Sándor , Kiricsi Mónika , Baka Zsuzsanna , Dux László
Published: October 2007

The functional recovery of skeletal muscles after peripheral nerve transection and microsurgical repair is generally incomplete. Several reinnervation abnormalities have been described even after nerve reconstruction surgery. Less is known, however, about the regenerative capacity of reinnervated muscles. Previously, we detected remarkable morphological and motor endplate alterations after inducing muscle necrosis and subsequent regeneration in the reinnervated rat soleus muscle. In the present study, we comparatively analyzed the morphometric properties of different fiber populations, as well as the expression pattern of myosin heavy chain isoforms at both immunohistochemical and mRNA levels in reinnervated versus reinnervated-regenerated muscles. A dramatic slow-to-fast fiber type transition was found in reinnervated soleus, and a further change toward the fast phenotype was observed in reinnervated-regenerated muscles. These findings suggest that the (fast) pattern of reinnervation plays a dominant role in the specification of fiber phenotype during regeneration, which can contribute to the long-lasting functional impairment of the reinnervated muscle. Moreover, because the fast II fibers (and selectively, a certain population of the fast IIB fibers) showed better recovery than did the slow type I fibers, the faster phenotype of the reinnervated-regenerated muscle seems to be actively maintained by selective yet undefined cues.
Clinicopathologic Factors and Nuclear Morphometry as Independent Prognosticators in KIT-positive Gastrointestinal Stromal Tumors
Authors: Steigen Sonja E. , Straume Bjørn , Turbin Dmitry , Chan Andy K. W. , Leung Samuel , Nielsen Torsten O. , Lindal Sigurd
Published: October 2007

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms found in the gastrointestinal tract. The purpose of this study was to evaluate whether morphometric measurements could complement tumor size and mitotic activity in risk evaluation. Nuclear roundness and ellipse axis ratio were found to correlate with tumor size, mitotic activity, nuclear atypia, and hemorrhage. Morphometric variables in 422 GISTs were significant for overall survival in univariate analyses but did not retain independent significance in multivariate analyses incorporating mitotic count and tumor size. Traditional variables, together with sex, location of primary tumor, and nuclear atypia, seem to be the best parameters for prognostic evaluation.
Mass Spectrometry–Based Detection of Hemoglobin E Mutation by Allele-Specific Base Extension Reaction
Authors: Tsang Jason CH , Charoenkwan Pimlak , Chow Katherine CK , Jin Yongjie , Wanapirak Chanane , Sanguansermsri Torpong , Lo YM Dennis , Chiu Rossa WK
Published: October 2007

Background: The specific detection of a minor population of mutant DNA molecules requires methods of high specificity and sensitivity. While the single-allele base extension reaction (SABER) was shown to be useful for the detection of certain beta-thalassemia mutations, we encountered problems with false positivity during development of SABER for the noninvasive prenatal diagnosis of the hemoglobin E (HbE) disease. Systematic optimization resulted in an alternative protocol, the allele-specific base extension reaction (ASBER).

Methods: An artificial model was established by mixing genomic DNA of HbE carriers and normal individuals. Effects of terminator concentration and annealing temperature on the nonspecificity of SABER were then studied. The use of a single relevant terminator and the other 3 types of dideoxynucleotide as competing terminators were also compared in the development of the ASBER protocol. Thirteen cases of HbE-susceptible pregnancies were tested to compare the SABER and the ASBER protocols.

Results: Decreasing the single relevant terminator concentration and increasing the annealing temperature in SABER were found to improve specificity. The use of the other 3 types of dideoxynucleotide as competing terminators was shown to offer better detection sensitivity than a single terminator in ASBER. Genotyping results were all correctly determined by ASBER, except one false-negative detection (sensitivity: 80%, specificity: 100%).

Conclusions: An alternative mass spectrometry–based protocol for noninvasive prenatal diagnosis, ASBER, has been successfully developed to allow the detection of a minor DNA population with a point mutation.