Educational interventions for preventing vascular catheter bloodstream infections in critical care: Evidence map, systematic review and economic evaluation

Background Bloodstream infections resulting from intravascular catheters (catheter-BSI) in critical care increase patients' length of stay, morbidity and mortality, and the management of these infections and their complications has been estimated to cost the NHS annually £19.1–36.2M. Catheter-BSI are thought to be largely preventable using educational interventions, but guidance as to which types of intervention might be most clinically effective is lacking. Objective To assess the effectiveness and cost-effectiveness of educational interventions for preventing catheter-BSI in critical care units in England. Data sources Sixteen electronic bibliographic databases – including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Cumulative Index to Nursing and Allied Health Literature (CINAHL), NHS Economic Evaluation Database (NHS EED), EMBASE and The Cochrane Library databases – were searched from database inception to February 2011, with searches updated in March 2012. Bibliographies of systematic reviews and related papers were screened and experts contacted to identify any additional references. Review methods References were screened independently by two reviewers using a priori selection criteria. A descriptive map was created to summarise the characteristics of relevant studies. Further selection criteria developed in consultation with the project Advisory Group were used to prioritise a subset of studies relevant to NHS practice and policy for systematic review. A decision-analytic economic model was developed to investigate the cost-effectiveness of educational interventions for preventing catheter-BSI. Results Seventy-four studies were included in the descriptive map, of which 24 were prioritised for systematic review. Studies have predominantly been conducted in the USA, using single-cohort before-and-after study designs. Diverse types of educational intervention appear effective at reducing the incidence density of catheter-BSI (risk ratios statistically significantly < 1.0), but single lectures were not effective. The economic model showed that implementing an educational intervention in critical care units in England would be cost-effective and potentially cost-saving, with incremental cost-effectiveness ratios under worst-case sensitivity analyses of < £5000/quality-adjusted life-year. Limitations Low-quality primary studies cannot definitively prove that the planned interventions were responsible for observed changes in catheter-BSI incidence. Poor reporting gave unclear estimates of risk of bias. Some model parameters were sourced from other locations owing to a lack of UK data. Conclusions Our results suggest that it would be cost-effective and may be cost-saving for the NHS to implement educational interventions in critical care units. However, more robust primary studies are needed to exclude the possible influence of secular trends on observed reductions in catheter-BSI.

Role-based process view derivation and composition

The process view concept deploys a partial and temporal representation to adjust the visible view of a business process according to various perception constraints of users. Process view technology is of practical use for privacy protection and authorization control in process-oriented business management. Owing to complex organizational structure, it is challenging for large companies to accurately specify the diverse perception of different users over business processes. Aiming to tackle this issue, this article presents a role-based process view model to incorporate role dependencies into process view derivation. Compared to existing process view approaches, ours particularly supports runtime updates to the process view perceivable to a user with specific view merging operations, thereby enabling the dynamic tracing of process perception. A series of rules and theorems are established to guarantee the structural consistency and validity of process view transformation. A hypothetical case is conducted to illustrate the feasibility of our approach, and a prototype is developed for the proof-of-concept purpose.

Process Analytical Technology Approach on Fluid Bed Granulation and Drying : Identifying Critical Relationships and Constructing the Design Space

Fluid bed granulation is a key pharmaceutical process which improves many of the powder properties for tablet compression. Dry mixing, wetting and drying phases are included in the fluid bed granulation process. Granules of high quality can be obtained by understanding and controlling the critical process parameters by timely measurements. Physical process measurements and particle size data of a fluid bed granulator that are analysed in an integrated manner are included in process analytical technologies (PAT). Recent regulatory guidelines strongly encourage the pharmaceutical industry to apply scientific and risk management approaches to the development of a product and its manufacturing process. The aim of this study was to utilise PAT tools to increase the process understanding of fluid bed granulation and drying. Inlet air humidity levels and granulation liquid feed affect powder moisture during fluid bed granulation. Moisture influences on many process, granule and tablet qualities. The approach in this thesis was to identify sources of variation that are mainly related to moisture. The aim was to determine correlations and relationships, and utilise the PAT and design space concepts for the fluid bed granulation and drying. Monitoring the material behaviour in a fluidised bed has traditionally relied on the observational ability and experience of an operator. There has been a lack of good criteria for characterising material behaviour during spraying and drying phases, even though the entire performance of a process and end product quality are dependent on it. The granules were produced in an instrumented bench-scale Glatt WSG5 fluid bed granulator. The effect of inlet air humidity and granulation liquid feed on the temperature measurements at different locations of a fluid bed granulator system were determined. This revealed dynamic changes in the measurements and enabled finding the most optimal sites for process control. The moisture originating from the granulation liquid and inlet air affected the temperature of the mass and pressure difference over granules. Moreover, the effects of inlet air humidity and granulation liquid feed rate on granule size were evaluated and compensatory techniques used to optimize particle size. Various end-point indication techniques of drying were compared. The ∆T method, which is based on thermodynamic principles, eliminated the effects of humidity variations and resulted in the most precise estimation of the drying end-point. The influence of fluidisation behaviour on drying end-point detection was determined. The feasibility of the ∆T method and thus the similarities of end-point moisture contents were found to be dependent on the variation in fluidisation between manufacturing batches. A novel parameter that describes behaviour of material in a fluid bed was developed. Flow rate of the process air and turbine fan speed were used to calculate this parameter and it was compared to the fluidisation behaviour and the particle size results. The design space process trajectories for smooth fluidisation based on the fluidisation parameters were determined. With this design space it is possible to avoid excessive fluidisation and improper fluidisation and bed collapse. Furthermore, various process phenomena and failure modes were observed with the in-line particle size analyser. Both rapid increase and a decrease in granule size could be monitored in a timely manner. The fluidisation parameter and the pressure difference over filters were also discovered to express particle size when the granules had been formed. The various physical parameters evaluated in this thesis give valuable information of fluid bed process performance and increase the process understanding.

Flow of metal in constrained plane-strain extrusion forging- Part II

With many innovations in process technology, forging is establishing itself as a precision manufacturing process: as forging is used to produce complex shapes in difficult materials, it requires dies of complex configuration of high strength and of wear-resistant materials. Extensive research and development work is being undertaken, internationally, to analyse the stresses in forging dies and the flow of material in forged components. Identification of the location, size and shape of dead-metal zones is required for component design. Further, knowledge of the strain distribution in the flowing metal indicates the degree to which the component is being work hardened. Such information is helpful in the selection of process parameters such as dimensional allowances and interface lubrication, as well as in the determination of post-forging operations such as heat treatment and machining. In the presently reported work the effect of aperture width and initial specimen height on the strain distribution in the plane-strain extrusion forging of machined lead billets is observed: the distortion of grids inscribed on the face of the specimen gives the strain distribution. The stress-equilibrium approach is used to optimise a model of flow in extrusion forging, which model is found to be effective in estimating the size of the dead-metal zone. The work carried out so far indicates that the methodology of using the stress-equilibrium approach to develop models of flow in closed-die forging can be a useful tool in component, process and die design.

Using a glow graph to represent data flow and dependency in event logs

The idea of extracting knowledge in process mining is a descendant of data mining. Both mining disciplines emphasise data flow and relations among elements in the data. Unfortunately, challenges have been encountered when working with the data flow and relations. One of the challenges is that the representation of the data flow between a pair of elements or tasks is insufficiently simplified and formulated, as it considers only a one-to-one data flow relation. In this paper, we discuss how the effectiveness of knowledge representation can be extended in both disciplines. To this end, we introduce a new representation of the data flow and dependency formulation using a flow graph. The flow graph solves the issue of the insufficiency of presenting other relation types, such as many-to-one and one-to-many relations. As an experiment, a new evaluation framework is applied to the Teleclaim process in order to show how this method can provide us with more precise results when compared with other representations.

Fiber Bragg Grating Sensors for Real Time Monitoring of Evacuation Process

Fiber bragg grating (FBG) sensors have been widely used for number of sensing applications like temperature, pressure, acousto-ultrasonic, static and dynamic strain, refractive index change measurements and so on. Present work demonstrates the use of FBG sensors in in-situ measurement of vacuum process with simultaneous leak detection capability. Experiments were conducted in a bell jar vacuum chamber facilitated with conventional Pirani gauge for vacuum measurement. Three different experiments have been conducted to validate the performance of FBG sensor in monitoring vacuum creating process and air bleeding. The preliminary results of FBG sensors in vacuum monitoring have been compared with that of commercial Pirani gauge sensor. This novel technique offers a simple alternative to conventional method for real time monitoring of evacuation process. Proposed FBG based vacuum sensor has potential applications in vacuum systems involving hazardous environment such as chemical and gas plants, automobile industries, aeronautical establishments and leak monitoring in process industries, where the electrical or MEMS based sensors are prone to explosion and corrosion.

Modeling of the Effects of Process Variations on Circuit Delay at 65nm

A novel methodology for modeling the effects of process variations on circuit delay performance is proposed by relating the variations in process parameters to variations in delay metric of a complex digital circuit. The delay of a 2-input NAND gate with 65nm gate length transistors is extensively characterized by mixed-mode simulations which is then used as a library element. The variation in saturation current Ionat the device level, and the variation in rising/falling edge stage delay for the NAND gate at the circuit level, are taken as performance metrics. A 4-bit x 4-bit Wallace tree multiplier circuit is used as a representative combinational circuit to demonstrate the proposed methodology. The variation in the multiplier delay is characterized, to obtain delay distributions, by an extensive Monte Carlo analysis. An analytical model based on CV/I metric is proposed, to extend this methodology for a generic technology library with a variety of library elements.

Simvastatin Induced Neurite Outgrowth Unveils Role of Cell Surface Cholesterol and Acetyl CoA Carboxylase in SH-SY5Y Cells

Statins are known to modulate cell surface cholesterol (CSC) and AMP-activated protein kinase (AMPK) in nonneural cells; however no study demonstrates whether CSC and AMPK may regulate simvastatin induced neuritogenesis (SIN). We found that simvastatin (SIM) maintains CSC as shown by Fillipin III staining, Flotillin-2 protein expression / localization and phosphorylation of various receptor tyrosine kinases (RTKs) in the plasma membrane. Modulation of CSC revealed that SIN is critically dependent on this CSC. Simultaneously, phospho array for mitogen activated protein kinases (MAPKs) revealed PI3K / Akt as intracellular pathway which modulates lipid pathway by inhibiting AMPK activation. Though, SIM led to a transient increase in AMPK phosphorylation followed by a sudden decline; the effect was independent of PI3K. Strikingly, AMPK phosphorylation was regulated by protein phosphatase 2A (PP2A) activity which was enhanced upon SIM treatment as evidenced by increase in threonine phosphorylation. Moreover, it was observed that addition of AMP analogue and PP2A inhibitor inhibited SIN. Biocomposition of neurites shows that lipids form a major part of neurites and AMPK is known to regulate lipid metabolism majorly through acetyl CoA carboxylase (ACC). AMPK activity is negative regulator of ACC activity and we found that phosphorylation of ACC started to decrease after 6 hrs which becomes more pronounced at 12 hrs. Addition of ACC inhibitor showed that SIN is dependent on ACC activity. Simultaneously, addition of Fatty acid synthase (FAS) inhibitor confirmed that endogenous lipid pathway is important for SIN. We further investigated SREBP-1 pathway activation which controls ACC and FAS at transcriptional level. However, SIM did not affect SREBP-1 processing and transcription of its target genes likes ACC1 and FAS. In conclusion, this study highlights a distinct role of CSC and ACC in SIN which might have implication in process of neuronal differentiation induced by other agents.

Direct numerical simulation of transition and turbulence in compressible mixing layer

The three-dimensional compressible Navier-Stokes equations are approximated by a fifth order upwind compact and a sixth order symmetrical compact difference relations combined with three-stage Ronge-Kutta method. The computed results are presented for convective Mach number Mc = 0.8 and Re = 200 with initial data which have equal and opposite oblique waves. From the computed results we can see the variation of coherent structures with time integration and full process of instability, formation of Lambda-vortices, double horseshoe vortices and mushroom structures. The large structures break into small and smaller vortex structures. Finally, the movement of small structure becomes dominant, and flow field turns into turbulence. It is noted that production of small vortex structures is combined with turning of symmetrical structures to unsymmetrical ones. It is shown in the present computation that the flow field turns into turbulence directly from initial instability and there is not vortex pairing in process of transition. It means that for large convective Mach number the transition mechanism for compressible mixing layer differs from that in incompressible mixing layer.

Report of the workshop on process monitoring and significant change. Bangkok, Thailand 26-28 June 2002

The STREAM Initiative is a process rather than a project, and its focus is on learning and building on learning, not the achievement of pre-determined objectives. An overarching goal of STREAM is to facilitate changes that support poor people who manage aquatic resources. A key objective of STREAM is policy change, which in itself is complex and difficult to monitor. Two further layers of complexity relate to the regional scope of the Initiative and the collaborative involvement of stakeholders, all of which need to be accountable for their work. The objectives of this workshop are consistent with the aims of the STREAM Initiative and can be summerized as follows: 1- Familiarizing everyone in the regional STREAM Initiative with work being done in process monitoring and significant change. 2- Discussion and development of a practical information system that enables (i) the monitoring of development processes and significant changes occurring within the STREAM Initiative, and (ii) learning to inform STREAM implementation and other stakeholders. (PDF has 59 pages.)

A novel fast lock-in phase-locked loop frequency synthesizer with direct frequency presetting circuit

This paper proposes a novel, fast lock-in, phase-locked loop (PLL) frequency synthesizer. The synthesizer includes a novel mixed-signal voltage-controlled oscillator (VCO) with a direct frequency presetting circuit. The frequency presetting circuit can greatly speed up the lock-in process by accurately the presetting oscillation frequency of the VCO. We fully integrated the synthesizer in standard 0.35 mu m, 3.3 V complementary metal-oxide-semiconductors (CMOS) process. The entire chip area is only 0.4 mm(2). The measured results demonstrate that the synthesizer can speed up the lock-in process significantly and the lock-in time is less than 10 mu s over the entire oscillation frequency range. The measured phase noise of the synthesizer is -85 dBc/Hz at 10 kHz offset. The synthesizer avoids the tradeoff between the lock-in speed and the phase noise/spurs. The synthesizer monitors the chip temperature and automatically compensates for the variation in frequency with temperature.

A novel fast lock-in phase-locked loop frequency synthesizer with direct frequency presetting circuit

This paper proposes a novel, fast lock-in, phase-locked loop (PLL) frequency synthesizer. The synthesizer includes a novel mixed-signal voltage-controlled oscillator (VCO) with a direct frequency presetting circuit. The frequency presetting circuit can greatly speed up the lock-in process by accurately the presetting oscillation frequency of the VCO. We fully integrated the synthesizer in standard 0.35 mu m, 3.3 V complementary metal-oxide-semiconductors (CMOS) process. The entire chip area is only 0.4 mm(2). The measured results demonstrate that the synthesizer can speed up the lock-in process significantly and the lock-in time is less than 10 mu s over the entire oscillation frequency range. The measured phase noise of the synthesizer is -85 dBc/Hz at 10 kHz offset. The synthesizer avoids the tradeoff between the lock-in speed and the phase noise/spurs. The synthesizer monitors the chip temperature and automatically compensates for the variation in frequency with temperature.

A qualitative temporal information system for process control

A general system is presented in this paper which supports the expression of relative temporal knowledge in process control and management. This system allows knowledge of Allen's temporal relations over time elements, which may be both intervals and points. The objectives and characteristics of two major temporal attributes, i.e. ‘transaction time’ and ‘valid time’, are described. A graphical representation for the temporal network is presented, and inference over the network may be made by means of a consistency checker in terms of the graphical representation. An illustrative example of the system as applied to process control and management is provided.

Optimizing the operation of straight-grate iron-ore pellet induration systems using process models

Mathematical models of straight-grate pellet induration processes have been developed and carefully validated by a number of workers over the past two decades. However, the subsequent exploitation of these models in process optimization is less clear, but obviously requires a sound understanding of how the key factors control the operation. In this article, we show how a thermokinetic model of pellet induration, validated against operating data from one of the Iron Ore Company of Canada (IOCC) lines in Canada, can be exploited in process optimization from the perspective of fuel efficiency, production rate, and product quality. Most existing processes are restricted in the options available for process optimization. Here, we review the role of each of the drying (D), preheating (PH), firing (F), after-firing (AF), and cooling (C) phases of the induration process. We then use the induration process model to evaluate whether the first drying zone is best to use on the up- or down-draft gas-flow stream, and we optimize the on-gas temperature profile in the hood of the PH, F, and AF zones, to reduce the burner fuel by at least 10 pct over the long term. Finally, we consider how efficient and flexible the process could be if some of the structural constraints were removed (i.e., addressed at the design stage). The analysis suggests it should be possible to reduce the burner fuel lead by 35 pct, easily increase production by 5+ pct, and improve pellet quality.

Microwave curing of thermosetting polymer materials in microelectronics applications

Thermosetting polymer materials are widely utilised in modern microelectronics packaging technology. These materials are used for a number of functions, such as for device bonding, for structural support applications and for physical protection of semiconductor dies. Typically, convection heating systems are used to raise the temperature of the materials to expedite the polymerisation process. The convection cure process has a number of drawbacks including process durations generally in excess of 1 hour and the requirement to heat the entire printed circuit board assembly, inducing thermomechanical stresses which effect device reliability. Microwave energy is able to raise the temperature of materials in a rapid, controlled manner. As the microwave energy penetrates into the polymer materials, the heating can be considered volumetric – i.e. the rate of heating is approximately constant throughout the material. This enables a maximal heating rate far greater than is available with convection oven systems which only raise the surface temperature of the polymer material and rely on thermal conductivity to transfer heat energy into the bulk. The high heating rate, combined with the ability to vary the operating power of the microwave system, enables the extremely rapid cure processes. Microwave curing of a commercially available encapsulation material has been studied experimentally and through use of numerical modelling techniques. The material assessed is Henkel EO-1080, a single component thermosetting epoxy. The producer has suggested three typical convection oven cure options for EO1080: 20 min at 150C or 90 min at 140C or 120 min at 110C. Rapid curing of materials of this type using advanced microwave systems, such as the FAMOBS system [1], is of great interest to microelectronics system manufacturers as it has the potential to reduce manufacturing costs, increase device reliability and enables new device designs. Experimental analysis has demonstrated that, in a realistic chip-on-board encapsulation scenario, the polymer material can be fully cured in approximately one minute. This corresponds to a reduction in cure time of approximately 95 percent relative to the convection oven process. Numerical assessment of the process [2] also suggests that cure times of approximately 70 seconds are feasible whilst indicating that the decrease in process duration comes at the expense of variation in degree of cure within the polymer.