Drug delivery strategies for the treatment of Helicobacter pylori infections

Helicobacter pylori is one of the most common pathogenic bacterial infections, colonising an estimated half of all humans. It is associated with the development of serious gastroduodenal disease - including peptic ulcers, gastric lymphoma and acute chronic gastritis. Current recommended regimes are not wholly effective and patient compliance, side-effects and bacterial resistance can be problematic. Drug delivery to the site of residence in the gastric mucosa may improve efficacy of the current and emerging treatments. Gastric retentive delivery systems potentially allow increased penetration of the mucus layer and therefore increased drug concentration at the site of action. Proposed gastric retentive systems for the enhancement of local drug delivery include floating systems, expandable or swellable systems and bioadhesive systems. Generally, problems with these formulations are lack of specificity, limited to mucus turnover or failure to persist in the stomach. Gastric mucoadhesive systems are hailed as a promising technology to address this issue, penetrating the mucus layer and prolonging activity at the mucus-epithelial interface. This review appraises gastroretentive delivery strategies specifically with regard to their application as a delivery system to target Helicobacter. As drug-resistant strains emerge, the development of a vaccine to eradicate and prevent reinfection is an attractive proposition. Proposed prophylactic and therapeutic vaccines have been delivered using a number of mucosal routes using viral and non-viral vectors. The delivery form, inclusion of adjuvants, and delivery regime will influence the immune response generated. © 2005 Bentham Science Publishers Ltd.

Using process mapping and business process simulation to support a process-based approach to change in a public sector organisation

A case study demonstrates the use of a process-based approach to change regarding the implementation of an information system for road traffic accident reporting in a UK police force. The supporting tools of process mapping and business process simulation are used in the change process and assist in communicating the current process design and people's roles in the overall performance of that design. The simulation model is also used to predict the performance of new designs incorporating the use of information technology. The approach is seen to have a number of advantages in the context of a public sector organisation. These include the ability for personnel to move from a traditional grouping of staff in occupational groups with relationships defined by reporting requirements to a view of their role in a process, which delivers a performance to a customer. By running the simulation through time it is also possible to gauge how changes at an operational level can lead to the meeting of strategic targets over time. Also the ability of simulation to proof new designs was seen as particularly important in a government agency were past failures of information technology investments had contributed to a more risk averse approach to their implementation. © 2004 Elsevier Ltd. All rights reserved.

Behaviour of concrete frame structures under localised fire scenarios

This thesis encompasses an investigation of the behaviour of concrete frame structure under localised fire scenarios by implementing a constitutive model using finite-element computer program. The investigation phase included properties of material at elevated temperature, description of computer program, thermal and structural analyses. Transient thermal properties of material have been employed in this study to achieve reasonable results. The finite-element computer package of ANSYS is utilized in the present analyses to examine the effect of fire on the concrete frame under five various fire scenarios. In addition, a report of full-scale BRE Cardington concrete building designed to Eurocode2 and BS8110 subjected to realistic compartment fire is also presented. The transient analyses of present model included additional specific heat to the base value of dry concrete at temperature 100°C and 200°C. The combined convective-radiation heat transfer coefficient and transient thermal expansion have also been considered in the analyses. For the analyses with the transient strains included, the constitutive model based on empirical formula in a full thermal strain-stress model proposed by Li and Purkiss (2005) is employed. Comparisons between the models with and without transient strains included are also discussed. Results of present study indicate that the behaviour of complete structure is significantly different from the behaviour of individual isolated members based on current design methods. Although the current tabulated design procedures are conservative when the entire building performance is considered, it should be noted that the beneficial and detrimental effects of thermal expansion in complete structures should be taken into account. Therefore, developing new fire engineering methods from the study of complete structures rather than from individual isolated member behaviour is essential.

Complementary methods to investigate the development of clogging within a horizontal sub-surface flow tertiary treatment wetland

A combination of experimental methods was applied at a clogged, horizontal subsurface flow (HSSF) municipal wastewater tertiary treatment wetland (TW) in the UK, to quantify the extent of surface and subsurface clogging which had resulted in undesirable surface flow. The three dimensional hydraulic conductivity profile was determined, using a purpose made device which recreates the constant head permeameter test in-situ. The hydrodynamic pathways were investigated by performing dye tracing tests with Rhodamine WT and a novel multi-channel, data-logging, flow through Fluorimeter which allows synchronous measurements to be taken from a matrix of sampling points. Hydraulic conductivity varied in all planes, with the lowest measurement of 0.1 md1 corresponding to the surface layer at the inlet, and the maximum measurement of 1550 md1 located at a 0.4m depth at the outlet. According to dye tracing results, the region where the overland flow ceased received five times the average flow, which then vertically short-circuited below the rhizosphere. The tracer break-through curve obtained from the outlet showed that this preferential flow-path accounted for approximately 80% of the flow overall and arrived 8 h before a distinctly separate secondary flow-path. The overall volumetric efficiencyof the clogged system was 71% and the hydrology was simulated using a dual-path, dead-zone storage model. It is concluded that uneven inlet distribution, continuous surface loading and high rhizosphere resistance is responsible for the clog formation observed in this system. The average inlet hydraulic conductivity was 2 md1, suggesting that current European design guidelines, which predict that the system will reach an equilibrium hydraulic conductivity of 86 md1, do not adequately describe the hydrology of mature systems.

An investigation of production workers' performance variations and the potential impact of attitudes

In most manufacturing systems the contribution of human labour remains a vital element that affects overall performance and output. Workers’ individual performance is known to be a product of personal attitudes towards work. However, in current system design processes, worker performance variability is assumed to be largely insignificant and the potential impact of worker attitudes is ignored. This paper describes a field study that investigated the extent to which workers’ production task cycle times vary and the degree to which such variations are associated with attitude differences. Results show that worker performance varies significantly, much more than is assumed by contemporary manufacturing system designers and that this appears to be due to production task characteristics. The findings of this research and their implications are discussed.

Polycystic ovary syndrome as a proinflammatory state:the role of adipokines

Background: Polycystic Ovary Syndrome (PCOS) is a complex heterogeneous disorder and the most common endocrinopathy amongst women of reproductive age. It is characterized by androgen excess, chronic anovulation and an altered cardiometabolic profile. PCOS is linked to impaired adipose tissue (AT) physiology and women with this disorder present with greater risk for insulin resistance (IR), hyperinsulinemia, central adiposity, nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) than matched for age and body mass index (BMI) women without PCOS. Hyperandrogenaemia appears to be driving adipocyte hypertrophy observed in PCOS under the influence of a hyperinsulinaemic state. Changes in the function of adipocytes have an impact on the secretion of adipokines, adipose tissue-derived proinflammatory factors promoting susceptibility to low grade inflammation. Methods: In this article, we review the existing knowledge on the interplay between hyperandrogenaemia, insulin resistance, impaired adipocyte biology, adipokines and chronic low-grade inflammation in PCOS. Results: In PCOS, more than one mechanisms have been suggested in the development of a chronic low-grade inflammation state with the most prevalent being that of a direct effect of the immune system on adipose tissue functions as previously reported in obese women without PCOS. Despite the lack of conclusive evidence regarding a direct mechanism linking hyperandrogenaemia to pro-inflammation in PCOS, there have been recent findings indicating that hyperandrogenaemia might be involved in chronic inflammation by exerting an effect on adipocytes morphology and attributes. Conclusion: Increasing evidence suggests that there is an important connection and interaction between proinflammatory pathways, hyperinsulinemia, androgen excess and adipose tissue hypertrophy and, dysfunction in PCOS. While lifestyle changes and individualized prescription of insulin-sensitizing drugs are common in managing PCOS, further studies are warranted to eventually identify an adipokine that could serve as an indirect marker of adipocyte dysfunction in PCOS, used as a reliable and pathognomic sign of metabolic alteration in this syndrome.

Integrated manufacturing systems design in a multi-product company

Using a hydraulic equipment manufacturing plant as the case study, this work explores the problems of systems integration in manufacturing systems design, stressing the behavioural aspects of motivation and participation, and the constraints involved in the proper consideration of the human sub-system. The need for a simple manageable modular organisation structure is illustrated, where it is shown, by reference to systems theory, how a business can be split into semi-autonomous operating units. The theme is the development of a manufacturing system based on an analysis of the business, its market, product, technology and constraints, coupled with a critical survey of modern management literature to develop an integrated systems design to suit a specific company in the current social environment. Society currently moves through a socio-technical revolution with man seeking higher levels of motivation. The transitory environment from an autocratic/paternalistic to a participative operating mode demands systems parameters only found to a limited extent in manufacturing systems today. It is claimed, that modern manufacturing systems design needs to be based on group working, job enrichment, delegation of decision making and reduced job monotony. The analysis shows how negative aspects of cellular manufacture such as lack of flexibility and poor fixed asset utilisation are relatively irrelevant and misleading in the broader context of the need to come to terms with the social stresses imposed on a company operating in the industrial environment of the present and the immediate future.

Current capacity limits and activities within the EU project MODE-GAP to overcome them

In this presentation we will discuss the implications of the so called Nonlinear Shannon Limit. We will compare technologies including new fibres for long haul transmission and techniques to expand the capacity of existing standard single mode fibres.

Design of few-mode fibers with up to 12 modes and low differential mode delay

In this paper, we investigate the design of few-mode fibers (FMFs) guiding 4 to 12 non-degenerate linearly polarized (LP) modes with low differential mode delay (DMD) over the C-band, suitable for long-haul transmission. The refractive index profile considered is composed by a graded-core with a cladding trench (GCCT). The optimization of the profile parameters aims the lowest possible DMD and macro-bend losses (MBL) lower than the ITU-T standard recommendation. The optimization results show that the optimum DMD and the MBL scale with the number of modes. Additionally, it is shown that the refractive-index relative difference at the core center is one of the most preponderant parameters, allowing to reduce the DMD at the expense of increasing MBL. Finally, the optimum DMD obtained for 12 LP modes is lower than 3 ps/km. © 2014 IEEE.

Design of few-mode fibers with M-modes and low differential mode delay

In this paper, we investigate the design of few-mode fibers (FMFs) guiding 2 to 12 linearly polarized (LP) modes with low differential mode delay (DMD) over the C-band, suitable for long-haul transmission. Two different types of refractive index profile have been considered: a graded-core with a cladding trench (GCCT) profile and a multi-step-index (MSI) profile. The profiles parameters are optimized in order to achieve: the lowest possible DMD and macro-bend losses (MBL) lower than the ITU-T standard recommendation. The optimization results show that the MSI profiles present lower DMD than the minimum achieved with a GCCT profile. Moreover, it is shown that the optimum DMD and the MBL scale with the number of modes for both profiles. The optimum DMD obtained for 12 LP modes is lower than 3 ps/km using a GCCT profile and lower than 2.5 ps/km using a MSI profile. The optimization results reveal that the most preponderant parameter of the GCCT profile is the refractive index relative difference at the core center, Δnco. Reducing Δn co, the DMD is reduced at the expense of increasing the MBL. Regarding the MSI profiles, it is shown that 64 steps are required to obtain a DMD improvement considering 12 LP modes. Finally, the impact of the fabrication margins on the optimum DMD is analyzed. The probability of having a manufactured FMF with 12 LP modes and DMD lower than 12 ps/km is approximately 68% using a GCCT profile and 16% using a MSI profile. © 2013 IEEE.

Design of few-mode fibers with arbitrary and flattened differential mode delay

This letter proposes the use of a refractive index profile with a graded core and a cladding trench for the design of few-mode fibers, aiming an arbitrary differential mode delay (DMD) flattened over the C+ L band. By optimizing the core grading exponent and the dimensioning of the trench, a deviation lower than 0.01 ps/km from a target DMD is observed over the investigated wavelength range. Additionally, it is found that the dimensioning of the trench is almost independent of the target DMD, thereby enabling the use of a simple design rule that guarantees a maximum DMD deviation of 1.8 ps/km for a DMD target between-200 and 200 ps/km. © 2012 IEEE.

Design and applications of in-cavity pulse shaping by spectral sculpturing in mode-locked fibre lasers

We review our recent progress on the realisation of pulse shaping in passively-mode-locked fibre lasers by inclusion of an amplitude and/or phase spectral filter into the laser cavity. We numerically show that depending on the amplitude transfer function of the in-cavity filter, various regimes of advanced waveform generation can be achieved, including ones featuring parabolic-, flat-top- and triangular-profiled pulses. An application of this approach using a flat-top spectral filter is shown to achieve the direct generation of high-quality sinc-shaped optical Nyquist pulses with a widely tunable bandwidth from the laser oscillator. We also present the operation of an ultrafast fibre laser in which conventional soliton, dispersion-managed soliton (stretched-pulse) and dissipative soliton mode-locking regimes can be selectively and reliably targeted by adaptively changing the dispersion profile and bandwidth programmed on an in-cavity programmable filter. The results demonstrate the strong potential of an in-cavity spectral pulse shaper for achieving a high degree of control over the dynamics and output of mode-locked fibre lasers.

Practice based learning approaches in collaborative design and engineering education:a case study investigation into the benefits of a crossdisciplinary practice based learning strategy

This study explores the ongoing pedagogical development of a number of undergraduate design and engineering programmes in the United Kingdom. Observations and data have been collected over several cohorts to bring a valuable perspective to the approaches piloted across two similar university departments while trialling a number of innovative learning strategies. In addition to the concurrent institutional studies the work explores curriculum design that applies the principles of Co-Design, multidisciplinary and trans disciplinary learning, with both engineering and product design students working alongside each other through a practical problem solving learning approach known as the CDIO learning initiative (Conceive, Design Implement and Operate) [1]. The study builds on previous work presented at the 2010 EPDE conference: The Effect of Personality on the Design Team: Lessons from Industry for Design Education [2]. The subsequent work presented in this paper applies the findings to mixed design and engineering team based learning, building on the insight gained through a number of industrial process case studies carried out in current design practice. Developments in delivery also aligning the CDIO principles of learning through doing into a practice based, collaborative learning experience and include elements of the TRIZ creative problem solving technique [3]. The paper will outline case studies involving a number of mixed engineering and design student projects that highlight the CDIO principles, combined with an external industrial design brief. It will compare and contrast the learning experience with that of a KTP derived student project, to examine an industry based model for student projects. In addition key areas of best practice will be presented, and student work from each mode will be discussed at the conference.