Real-Time PCR : A Molecular Approach to Investigate the Role of Intestinal Microbiota in the Pathophysiology of Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a common multifactorial functional intestinal disorder, the pathogenesis of which is not completely understood. Increasing scientific evidence suggests that microbes are involved in the onset and maintenance of IBS symptoms. The microbiota of the human gastrointestinal (GI) tract constitutes a massive and complex ecosystem consisting mainly of obligate anaerobic microorganisms making the use of culture-based methods demanding and prone to misinterpretation. To overcome these drawbacks, an extensive panel of species- and group-specific assays for an accurate quantification of bacteria from fecal samples with real-time PCR was developed, optimized, and validated. As a result, the target bacteria were detectable at a minimum concentration range of approximately 10 000 bacterial genomes per gram of fecal sample, which corresponds to the sensitivity to detect 0.000001% subpopulations of the total fecal microbiota. The real-time PCR panel covering both commensal and pathogenic microorganisms was assessed to compare the intestinal microbiota of patients suffering from IBS with a healthy control group devoid of GI symptoms. Both the IBS and control groups showed considerable individual variation in gut microbiota composition. Sorting of the IBS patients according to the symptom subtypes (diarrhea, constipation, and alternating predominant type) revealed that lower amounts of Lactobacillus spp. were present in the samples of diarrhea predominant IBS patients, whereas constipation predominant IBS patients carried increased amounts of Veillonella spp. In the screening of intestinal pathogens, 17% of IBS samples tested positive for Staphylococcus aureus, whereas no positive cases were discovered among healthy controls. Furthermore, the methodology was applied to monitor the effects of a multispecies probiotic supplementation on GI microbiota of IBS sufferers. In the placebo-controlled double-blind probiotic intervention trial of IBS patients, each supplemented probiotic strain was detected in fecal samples. Intestinal microbiota remained stable during the trial, except for Bifidobacterium spp., which increased in the placebo group and decreased in the probiotic group. The combination of assays developed and applied in this thesis has an overall coverage of 300-400 known bacterial species, along with the number of yet unknown phylotypes. Hence, it provides good means for studying the intestinal microbiota, irrespective of the intestinal condition and health status. In particular, it allows screening and identification of microbes putatively associated with IBS. The alterations in the gut microbiota discovered here support the hypothesis that microbes are likely to contribute to the pathophysiology of IBS. The central question is whether the microbiota changes described represent the cause for, rather than the effect of, disturbed gut physiology. Therefore, more studies are needed to determine the role and importance of individual microbial species or groups in IBS. In addition, it is essential that the microbial alterations observed in this study will be confirmed using a larger set of IBS samples of different subtypes, preferably from various geographical locations.

A participatory approach to tactical forest planning.

The paper examines the needs, premises and criteria for effective public participation in tactical forest planning. A method for participatory forest planning utilizing the techniques of preference analysis, professional expertise and heuristic optimization is introduced. The techniques do not cover the whole process of participatory planning, but are applied as a tool constituting the numerical core for decision support. The complexity of multi-resource management is addressed by hierarchical decision analysis which assesses the public values, preferences and decision criteria toward the planning situation. An optimal management plan is sought using heuristic optimization. The plan can further be improved through mutual negotiations, if necessary. The use of the approach is demonstrated with an illustrative example, it's merits and challenges for participatory forest planning and decision making are discussed and a model for applying it in general forest planning context is depicted. By using the approach, valuable information can be obtained about public preferences and the effects of taking them into consideration on the choice of the combination of standwise treatment proposals for a forest area. Participatory forest planning calculations, carried out by the approach presented in the paper, can be utilized in conflict management and in developing compromises between competing interests.

Constructing and negotiating entrepreneurial agency : A social psychological approach to entrepreneurship discourse in the farm context

Entrepreneurship, understood as the autonomous, effective pursuit of opportunities regardless of resources, is currently subject to a multitude of interests, expectations, and facilitation efforts. On the one hand, such entrepreneurial agency has broad appeal to individuals in Western market democracies and resonates with their longing for an autonomous, personally tailored, meaningful, and materially rewarding way of life. On the other hand, entrepreneurship represents a tempting and increasingly popular means of governance and policy making, and thus a model for the re-organization of a variety of societal sectors. This study focuses on the diffusion and reception of entrepreneurship discourse in the context of farming and agriculture, where pressures to adopt entrepreneurial orientations have been increasingly pronounced while, on the other hand, the context of farming has historically enjoyed state protection and adhered to principles that seem at odds with aspects of individualistic entrepreneurship discourse . The study presents an interpretation of the psychologically and politically appealing uses of the notion of entrepreneurial agency , reviews the historical and political background of the current situation of farming and agriculture with regard to entrepreneurship, and examines their relationships in four empirical studies. The study follows and develops a social psychological, situated relational approach that guides the qualitative analyses and interpretations of the empirical studies. Interviews with agents from the farm sector aim to stimulate evaluative responses and comments on the idea of entrepreneurship on farms. Analysis of the interview talk, in turn, detects the variety of evaluative responses and argumentative contexts with which the interviewees relate themselves to the entrepreneurship discourse and adopt, use, resist, or reject it. The study shows that despite the pressures towards entrepreneurialism, the diffusion of entrepreneurship discourse and the construction of entrepreneurial agency in farm context encounter many obstacles. These obstacles can be variably related to aspects dealing with the individual agent, the action situation, the characteristics of the action itself, or to the broader social, institutional and cultural context. Many aspects of entrepreneurial agency, such as autonomy, personal initiative and achievement orientation, are nevertheless familiar to farmers and are eagerly related to one s own farming activities. The idea of entrepreneurship is thus rarely rejected outright. The findings highlight the relational and situational preconditions for the construction of entrepreneurial agency in the farm context: When agents demonstrate entrepreneurial agency, they do so by drawing on available and accessed relational resources characteristic of their action context. Likewise, when agents fail or are reluctant to demonstrate entrepreneurial agency, they nevertheless actively account for their situation and demonstrate personal agency by drawing on the relational resources available to them.

An approach to scenario analysis of the sustainability of an industrial sector applied to clothing and textiles in the UK

Companies aiming to be 'sustainability leaders' in their sector and governments wanting to support their ambitions need a means to assess the changes required to make a significant difference in the impact of their whole sector. Previous work on scenario analysis/scenario planning demonstrates extensive developments and applications, but as yet few attempts to integrate the 'triple bottom line' concerns of sustainability into scenario planning exercises. This paper, therefore, presents a methodology for scenario analysis of large change to an entire sector. The approach includes calculation of a 'triple bottom line graphic equaliser' to allow exploration and evaluation of the trade-offs between economic, environmental and social impacts. The methodology is applied to the UK's clothing and textiles sector, and results from the study of the sector are summarised. In reflecting on the specific study, some suggestions are made about future application of a similar methodology, including a template of candidate solutions that may lead to significant reduction in impacts. © 2007 Elsevier Ltd. All rights reserved.

A probability-based approach to setting annual catch levels.

The requirement of setting annual catch limits to prevent overfishing has been added to the Magnuson-Stevens Fishery Conservation and Management Reauthorization Act of 2006 (MSRA). Because this requirement is new, a body of applied scientific practice for deriving annual catch limits and accompanying targets does not yet exist. This article demonstrates an approach to setting levels of catch that is intended to keep the probability of future overfishing at a preset low level. The proposed framework is based on stochastic projection with uncertainty in population dynamics. The framework extends common projection methodology by including uncertainty in the limit reference point and in management implementation, and by making explicit the risk of overfishing that managers consider acceptable. The approach is illustrated with application to gag (Mycteroperca microlepis), a grouper that inhabits the waters off the southeastern United States. Although devised to satisfy new legislation of the MSRA, the framework has potential application to any fishery where the management goal is to limit the risk of overfishing by controlling catch.

A fundamental approach to phase noise reduction in hybrid Si/III-V lasers

Spontaneous emission into the lasing mode fundamentally limits laser linewidths. Reducing cavity losses provides two benefits to linewidth: (1) fewer excited carriers are needed to reach threshold, resulting in less phase-corrupting spontaneous emission into the laser mode, and (2) more photons are stored in the laser cavity, such that each individual spontaneous emission event disturbs the phase of the field less. Strong optical absorption in III-V materials causes high losses, preventing currently-available semiconductor lasers from achieving ultra-narrow linewidths. This absorption is a natural consequence of the compromise between efficient electrical and efficient optical performance in a semiconductor laser. Some of the III-V layers must be heavily doped in order to funnel excited carriers into the active region, which has the side effect of making the material strongly absorbing.

This thesis presents a new technique, called modal engineering, to remove modal energy from the lossy region and store it in an adjacent low-loss material, thereby reducing overall optical absorption. A quantum mechanical analysis of modal engineering shows that modal gain and spontaneous emission rate into the laser mode are both proportional to the normalized intensity of that mode at the active region. If optical absorption near the active region dominates the total losses of the laser cavity, shifting modal energy from the lossy region to the low-loss region will reduce modal gain, total loss, and the spontaneous emission rate into the mode by the same factor, so that linewidth decreases while the threshold inversion remains constant. The total spontaneous emission rate into all other modes is unchanged.

Modal engineering is demonstrated using the Si/III-V platform, in which light is generated in the III-V material and stored in the low-loss silicon material. The silicon is patterned as a high-Q resonator to minimize all sources of loss. Fabricated lasers employing modal engineering to concentrate light in silicon demonstrate linewidths at least 5 times smaller than lasers without modal engineering at the same pump level above threshold, while maintaining the same thresholds.

Towards a Comprehensive Approach to Quantifying and Mapping Ecosystem Services Flows

25 p.

A multi-scale approach to shaping carbon nanotube structures for hollow microneedles

The concept of a carbon nanotube microneedle array is explored in this thesis from multiple perspectives including microneedle fabrication, physical aspects of transdermal delivery, and in vivo transdermal drug delivery experiments. Starting with standard techniques in carbon nanotube (CNT) fabrication, including catalyst patterning and chemical vapor deposition, vertically-aligned carbon nanotubes are utilized as a scaffold to define the shape of the hollow microneedle. Passive, scalable techniques based on capillary action and unique photolithographic methods are utilized to produce a CNT-polymer composite microneedle. Specific examples of CNT-polyimide and CNT-epoxy microneedles are investigated. Further analysis of the transport properties of polymer resins reveals general requirements for applying arbitrary polymers to the fabrication process.

The bottom-up fabrication approach embodied by vertically-aligned carbon nanotubes allows for more direct construction of complex high-aspect ratio features than standard top-down fabrication approaches, making microneedles an ideal application for CNTs. However, current vertically-aligned CNT fabrication techniques only allow for the production of extruded geometries with a constant cross-sectional area, such as cylinders. To rectify this limitation, isotropic oxygen etching is introduced as a novel fabrication technique to create true 3D CNT geometry. Oxygen etching is utilized to create a conical geometry from a cylindrical CNT structure as well as create complex shape transformations in other CNT geometries.

CNT-polymer composite microneedles are anchored onto a common polymer base less than 50 µm thick, which allows for the microneedles to be incorporated into multiple drug delivery platforms, including modified hypodermic syringes and silicone skin patches. Cylindrical microneedles are fabricated with 100 µm outer diameter and height of 200-250 µm with a central cavity, or lumen, diameter of 30 µm to facilitate liquid drug flow. In vitro delivery experiments in swine skin demonstrate the ability of the microneedles to successfully penetrate the skin and deliver aqueous solutions.

An in vivo study was performed to assess the ability of the CNT-polymer microneedles to deliver drugs transdermally. CNT-polymer microneedles are attached to a hand actuated silicone skin patch that holds a liquid reservoir of drugs. Fentanyl, a potent analgesic, was administered to New Zealand White Rabbits through 3 routes of delivery: topical patch, CNT-polymer microneedles, and subcutaneous hypodermic injection. Results demonstrate that the CNT-polymer microneedles have a similar onset of action as the topical patch. CNT-polymer microneedles were also vetted as a painless delivery approach compared to hypodermic injection. Comparative analysis with contemporary microneedle designs demonstrates that the delivery achieved through CNT-polymer microneedles is akin to current hollow microneedle architectures. The inherent advantage of applying a bottom-up fabrication approach alongside similar delivery performance to contemporary microneedle designs demonstrates that the CNT-polymer composite microneedle is a viable architecture in the emerging field of painless transdermal delivery.

A feasible approach to optical-electrical hybrid data storage using phase change material

We present our experimental results supporting optical-electrical hybrid data storage by optical recording and electrical reading using Ge2Sb2Te5as recording medium. The sheet resistance of laser- irradiated Ge2Sb2Te5. lms exhibits an abrupt change of four orders of magnitude ( from 10 7 to 10 3./ sq) with increasing laser power, current- voltage curves of the amorphous area and the laser- crystallized dots, measured by a conductive atomic force microscope ( C- AFM), show that their resistivities are 2.725 and 3.375 x 10- 3., respectively, the surface current distribution in the. lms also shows high and low resistance states. All these results suggest that the laser- recorded bit can be read electrically by measuring the change of electrical resistivity, thus making optical electrical hybrid data storage possible.

An approach to the assessment of the finfish fisheries of the Caribbean Community

This paper briefly outlines the implications of making a decision on the most appropriate alternative for carrying out stock assessments and the reasons for previous failures to conserve finfish stocks for sustainable use. The Mathews (1987) approach utilizing Age-Length Catch-Effort Keys (ALCEK) is briefly reviewed, and a suggested overall approach for the assessment of the finfish resources of the Caribbean community is outlined. With recent initiatives towards use of the precautionary approach and reference points, Carribean community countries are advised to revisit the question of the models to be utilized for the assessment of their fish stocks, paying due attention to the quantity, quality and applicability of data now being collected.

Report of the training programme on Essential Ecosystem Approach to Fisheries Management (EAFM): developing capacity in the EAFM, Chennai, India, 11-16 August, 2014

Participants were exposed to concepts and information about EAFM using a structured, participatory method of delivery. The learning strategy involved specifically designed exercises, using real examples, to consolidate learning. Daily monitoring and reviews were conducted together with pre-and post-course assessment.

A Computer integrated unified modelling approach to responsive manufacturing

Computer modelling approaches have significant potential to enable decision-making about various aspects of responsive manufacturing. In order to understand the system prior to the selection of any responsiveness strategy, multiple process segments of organisations need to be modelled. The article presents a novel systematic approach for creating coherent sets of unified enterprise, simulation and other supporting models that collectively facilitate responsiveness. In this approach, enterprise models are used to explicitly define relatively enduring relationships between (i) production planning and control (PPC) processes, that implement a particular strategy and (ii) process-oriented elements of production systems, that are work loaded by the PPC processes. Coherent simulation models, can in part be derived from the enterprise models, so that they computer execute production system behaviours. In this way, time-based performance outcomes can be simulated; so that the impacts of alternative PPC strategies on the planning and controlling historical or forecasted patterns of workflow, through (current and possible future) production system models, can be analysed. The article describes the unified modelling approach conceived and its application in a furniture industry case study small and medium enterprise (SME). Copyright © 2010 Inderscience Enterprises Ltd.

A structured modelling approach to simulating dynamic behaviours in complex organisations

This article reports a case study application of a systematic approach to modelling complex organisations, centred on simulation modelling (SM). The approach leads to populated instances of complementary model types, in ways that systematically capture, validate and facilitate various uses of organisational understandings, knowledge and data normally distributed amongst multiple knowledge holders. The model-driven approach to decision making enables improved manufacturing responsiveness. Literature on modelling technologies relevant to manufacturing systems organisation design and change is presented, as is literature on production planning and control. This provides a rationale for the development of a new modelling methodology which combines the use of enterprise, causal loop and SM. Subsequently, this article describes how in the case of a specific manufacturing enterprise the combined modelling techniques have informed the choice of alternative production planning and control policies. An example enterprise model of a capacitor manufacturing company is illustrated as derivative causal-loop models that structure and enable the design and use of a general purpose simulation model.

Enhanced integrated modelling approach to reconfiguring manufacturing enterprises

Dynamism and uncertainty are real challenges for present day manufacturing enterprises (MEs). Reasons include: an increasing demand for customisation, reduced time to market, shortened product life cycles and globalisation. MEs can reduce competitive pressure by becoming reconfigurable and change-capable. However, modern manufacturing philosophies, including agile and lean, must complement the application of reconfigurable manufacturing paradigms. Choosing and applying the best philosophies and techniques is very difficult as most MEs deploy complex and unique configurations of processes and resource systems, and seek economies of scope and scale in respect of changing and distinctive product flows. It follows that systematic methods of achieving model driven reconfiguration and interoperation of component based manufacturing systems are required to design, engineer and change future MEs. This thesis, titled Enhanced Integrated Modelling Approach to Reconfiguring Manufacturing Enterprises , introduces the development and prototyping a model-driven environment for the design, engineering, optimisation and control of the reconfiguration of MEs with an embedded capability to handle various types of change. The thesis describes a novel systematic approach, namely enhanced integrated modelling approach (EIMA), in which coherent sets of integrated models are created that facilitates the engineering of MEs especially their production planning and control (PPC) systems. The developed environment supports the engineering of common types of strategic, tactical and operational processes found in many MEs. The EIMA is centred on the ISO standardised CIMOSA process modelling approach. Early study led to the development of simulation models during which various CIMOSA shortcomings were observed, especially in its support for aspects of ME dynamism. A need was raised to structure and create semantically enriched models hence forming an enhanced integrated modelling environment. The thesis also presents three industrial case examples: (1) Ford Motor Company; (2) Bradgate Furniture Manufacturing Company; and (3) ACM Bearings Company. In order to understand the system prior to realisation of any PPC strategy, multiple process segments of any target organisation need to be modelled. Coherent multi-perspective case study models are presented that have facilitated process reengineering and associated resource system configuration. Such models have a capability to enable PPC decision making processes in support of the reconfiguration of MEs. During these case studies, capabilities of a number of software tools were exploited such as Arena®, Simul8®, Plant Simulation®, MS Visio®, and MS Excel®. Case study results demonstrated effectiveness of the concepts related to the EIMA. The research has resulted in new contributions to knowledge in terms of new understandings, concepts and methods in following ways: (1) a structured model driven integrated approach to the design, optimisation and control of future reconfiguration of MEs. The EIMA is an enriched and generic process modelling approach with capability to represent both static and dynamic aspects of an ME; and (2) example application cases showing benefits in terms of reduction in lead time, cost and resource load and in terms of improved responsiveness of processes and resource systems with a special focus on PPC; (3) identification and industrial application of a new key performance indicator (KPI) known as P3C the measuring and monitoring of which can aid in enhancing reconfigurability and responsiveness of MEs; and (4) an enriched modelling concept framework (E-MUNE) to capture requirements of static and dynamic aspects of MEs where the conceptual framework has the capability to be extended and modified according to the requirements. The thesis outlines key areas outlining a need for future research into integrated modelling approaches, interoperation and updating mechanisms of partial models in support of the reconfiguration of MEs.

A conceptual approach to integrated coastal management

This paper focuses on the concept of Integrated Coastal Management (ICM) putting the theoretical basis of Chapter 17, Agenda 21 (UN Conference on Environment and Development, UNCED), in relation to the theoretical backgrounds on which the development of coastal area programmes have been founded. Reasoning leads us to think that the general system theory is the proper conceptual basis to stimulate ICM and that, in this theoretical context, integration is to be pursued between (i) the claiming of national maritime jurisdictional belts and the protection of the coastal ecosystem, (ii) the coastal system and its external environment, (iii) the decision making systems acting at all levels (international, regional, national and local). Integration, therefore, should be thought of as a political process.