Structurally-related (−)-epicatechin metabolites in humans: assessment using de novo chemically synthesized authentic standards

Accumulating data suggest that diets rich in flavanols and procyanidins are beneficial for human health. In this context, there has been a great interest in elucidating the systemic levels and metabolic profiles at which these compounds occur in humans. While recent progress has been made, there still exist considerable differences and various disagreements with regard to the mammalian metabolites of these compounds, which in turn is largely a consequence of the lack of availability of authentic standards that would allow for the directed development and validation of expedient analytical methodologies. In the present study, we developed a method for the analysis of structurally-related flavanol metabolites using a wide range of authentic standards. Applying this method in the context of a human dietary intervention study using comprehensively characterized and standardized flavanol- and procyanidin-containing cocoa, we were able to identify the structurally-related (−)-epicatechin metabolites (SREM) postprandially extant in the systemic circulation of humans. Our results demonstrate that (−)-epicatechin-3′-β-D-glucuronide, (−)-epicatechin-3′-sulfate, and a 3′-O-methyl(−)-epicatechin-5/7-sulfate are the predominant SREM in humans, and further confirm the relevance of the stereochemical configuration in the context of flavanol metabolism. In addition, we also identified plausible causes for the previously reported discrepancies regarding flavanol metabolism, consisting to a significant extent of inter-laboratory differences in sample preparation (enzymatic treatment and sample conditioning for HPLC analysis) and detection systems. Thus, these findings may also aid in the establishment of consensus on this topic.

Community based ecotourism as a panacea for protected areas: the use of common property theory in its analysis and development

Tourism is the worlds largest employer, accounting for 10% of jobs worldwide (WTO, 1999). There are over 30,000 protected areas around the world, covering about 10% of the land surface(IUCN, 2002). Protected area management is moving towards a more integrated form of management, which recognises the social and economic needs of the worlds finest areas and seeks to provide long term income streams and support social cohesion through active but sustainable use of resources. Ecotourism - 'responsible travel to natural areas that conserves the environment and improves the well- being of local people' (The Ecotourism Society, 1991) - is often cited as a panacea for incorporating the principles of sustainable development in protected area management. However, few examples exist worldwide to substantiate this claim. In reality, ecotourism struggles to provide social and economic empowerment locally and fails to secure proper protection of the local and global environment. Current analysis of ecotourism provides a useful checklist of interconnected principles for more successful initiatives, but no overall framework of analysis or theory. This paper argues that applying common property theory to the application of ecotourism can help to establish more rigorous, multi-layered analysis that identifies the institutional demands of community based ecotourism (CBE). The paper draws on existing literature on ecotourism and several new case studies from developed and developing countries around the world. It focuses on the governance of CBE initiatives, particularly the interaction between local stakeholders and government and the role that third party non-governmental organisations can play in brokering appropriate institutional arrangements. The paper concludes by offering future research directions."

Technological change and the challenges for regional development: building social capital in less-favoured regions

The relevance of regional policy for less favoured regions (LFRs) reveals itself when policy-makers must reconcile competitiveness with social cohesion through the adaptation of competition or innovation policies. The vast literature in this area generally builds on an overarching concept of ‘social capital’ as the necessary relational infrastructure for collective action diversification and policy integration, in a context much influenced by a dynamic of industrial change and a necessary balance between the creation and diffusion of ‘knowledge’ through learning. This relational infrastructure or ‘social capital’ is centred on people’s willingness to cooperate and ‘envision’ futures as a result of “social organization, such as networks, norms and trust that facilitate action and cooperation for mutual benefit” (Putnam, 1993: 35). Advocates of this interpretation of ‘social capital’ have adopted the ‘new growth’ thinking behind ‘systems of innovation’ and ‘competence building’, arguing that networks have the potential to make both public administration and markets more effective as well as ‘learning’ trajectories more inclusive of the development of society as a whole. This essay aims to better understand the role of ‘social capital’ in the production and reproduction of uneven regional development patterns, and to critically assess the limits of a ‘systems concept’ and an institution-centred approach to comparative studies of regional innovation. These aims are discussed in light of the following two assertions: i) learning behaviour, from an economic point of view, has its determinants, and ii) the positive economic outcomes of ‘social capital’ cannot be taken as a given. It is suggested that an agent-centred approach to comparative research best addresses the ‘learning’ determinants and the consequences of social networks on regional development patterns. A brief discussion of the current debate on innovation surveys has been provided to illustrate this point.

Planning for the reuse of redundant defence estate: disposal processes, policy frameworks and development impacts

This paper reviews recent research and other literature concerning the planning and development of redundant defence estate. It concentrates on UK sources but includes reference to material from Europe and the North America were it is relevant for comparative purposes. It introduces the topic by providing a brief review of the recent restructuring of the UK defence estate and then proceeds to examine the various planning policy issues generated by this process; the policy frameworks used to guide it; comparable approaches to surplus land disposal and the appraisal of impacts; and ending the main body of the review with an analyse of the economic, social and environmental impacts of military base closure and redevelopment. It concludes that there is a significant body of work focusing on the reuse and redevelopment of redundant defence estate in the UK and abroad, but that much of this work is based on limited research or on personal experience. One particular weakness of the current literature is that it does not fully reflect the institutional difficulties posed by the disposal process and the day-to-day pressures which MOD personnel have to deal with. In doing this, it also under-emphasises the embedded cultures of individuals and professional groups who are required to operationalise the policies, procedures and practices for planning and redeveloping redundant defence estate.

Effect of patient age on management decisions in breast cancer: consensus from a national consultation

This qualitative study investigated the attitudes, perceptions, and practices of breast cancer specialists with reference to the effect of patient age on management decisions in breast cancer, and attempted to identify national consensus on this issue. One hundred thirty-three relevant specialists, including 75 surgeons and 43 oncologists, participated in a virtual consultation using e-mailed questionnaires and open-ended discussion documents, culminating in the development of proposed consensus statements sent to participants for validation. A strong consensus was seen in favor of incorporating minimum standards of diagnostic services, treatment, and care for older patients with breast cancer into relevant national guidance, endorsed by professional bodies. Similarly, an overwhelming majority of participants agreed that simple, evidence-based protocols or guidelines on standardizing assessment of biological and chronological age should be produced by the National Institute for Health and Clinical Excellence and the Scottish Medicines Consortium, developed in collaboration with specialist oncogeriatricians, and endorsed by professional bodies. A further recommendation that all breast cancer patient treatment and diagnostic procedures be undertaken in light of up-to-date, relevant scientific data met with majority support. This study was successful in gauging national specialist opinion regarding the effect of patient age on management decisions in breast cancer in the U.K.

Developing consensus on hospital prescribing indicators of potential harms amenable to decision support

Aim: To develop a list of prescribing indicators specific for the hospital setting that would facilitate the prospective collection of high severity and/or high frequency prescribing errors, which are also amenable to electronic clinical decision support (CDS). Method: A three-stage consensus technique (electronic Delphi) was carried out with 20 expert pharmacists and physicians across England. Participants were asked to score prescribing errors using a 5-point Likert scale for their likelihood of occurrence and the severity of the most likely outcome. These were combined to produce risk scores, from which median scores were calculated for each indicator across the participants in the study. The degree of consensus between the participants was defined as the proportion that gave a risk score in the same category as the median. Indicators were included if a consensus of 80% or more was achieved. Results: A total of 80 prescribing errors were identified by consensus as being high or extreme risk. The most common drug classes named within the indicators were antibiotics (n=13), antidepressants (n=8), nonsteroidal anti-inflammatory drugs (n=6), and opioid analgesics (n=6).The most frequent error type identified as high or extreme risk were those classified as clinical contraindications (n=29/80). Conclusion: 80 high risk prescribing errors in the hospital setting have been identified by an expert panel. These indicators can serve as the basis for a standardised, validated tool for the collection of data in both paperbased and electronic prescribing processes, as well as to assess the impact of electronic decision support implementation or development.

Evaluating the interdependencies between managing business change, IT sourcing and IT governance

Organisations need the right business and IT capabilities in order to achieve future business success. It follows that the sourcing of these capabilities is an important decision. Yet, there is a lack of consensus on the approach to decid-ing where and how to source the core operational capabilities. Furthermore, de-veloping its dynamic capability enables an organisation to effectively manage change its operational capabilities. Recent research has proposed that analysing business capabilities is a key pre-requisite to defining its Information Technology (IT) solutions. This research builds on these findings by considering the interde-pendencies between the dynamic business change capability and the sourcing of IT capabilities. Further it examines the decision-making oversight of these areas as implemented through IT governance. There is a good understanding of the direct impact of IT sourcing decision on operational capabilities However, there is a lack of research on the indirect impact to the capability of managing business change. Through a review of prior research and initial pilot field research, a capability framework and three main propositions are proposed, each examining a two-way interdependency. This paper describes the development of the integrated capa-bility framework and the rationale for the propositions. These respectively cover managing business change, IT sourcing and IT governance. Firstly, the sourcing of IT affects both the operational capabilities and the capability to manage business change. Similarly a business change may result in new or revised operational ca-pabilities, which can influence the IT sourcing decision resulting in a two-way rela-tionship. Secondly, this IT sourcing is directed under IT governance, which pro-vides a decision-making framework for the organisation. At the same time, the IT sourcing can have an impact on the IT governance capability, for example by out-sourcing key capabilities; hence this is potentially again a two-way relationship. Finally, there is a postulated two-way relationship between IT governance and managing business change in that IT governance provides an oversight of manag-ing business change through portfolio management while IT governance is a key element of the business change capability. Given the nature and novelty of this framework, a philosophical paradigm of constructivism is preferred. To illustrate and explore the theoretical perspectives provided, this paper reports on the find-ings of a case study incorporating eight high-level interviews with senior execu-tives in a German bank with 2300 employees. The collected data also include or-ganisational charts, annual reports, project and activity portfolio and benchmark reports for the IT budget. Recommendations are made for practitioners. An understanding of the interdependencies can support professionals in improving business success through effectively managing business change. Additionally, they can be assisted to evaluate the impact of IT sourcing decisions on the organisa-tion’s operational and dynamic capabilities, using an appropriate IT governance framework.

Characterizing intuition in information systems research

The study of intuition is an emerging area of research in psychology, social sciences, and business studies. It is increasingly of interest to the study of management, for example in decision-making as a counterpoint to structured approaches. Recently work has been undertaken to conceptualize a construct for the intuitive nature of technology. However to-date there is no common under-standing of the term intuition in information systems (IS) research. This paper extends the study of intuition in IS research by using exploratory research to cate-gorize the use of the word “intuition” and related terms in papers published in two prominent IS journals over a ten year period. The entire text of MIS Quarterly and Information Systems Research was reviewed for the years 1999 through 2008 using searchable PDF versions of these publications. As far as could be deter-mined, this is the first application of this approach in the analysis of the text of IS academic journals. The use of the word “intuition” and related terms was catego-rized using coding consistent with Grounded Theory. The focus of this research was on the first two stages of Grounded Theory analysis - the development of codes and constructs. Saturation of coding was not reached: an extended review of these publications would be required to enable theory development. Over 400 incidents of the use of “intuition”, and related terms were found in the articles reviewed. The most prominent use of the term of “intuition” was coded as “Intui-tion as Authority” in which intuition was used to validate a research objective or finding; representing approximately 37 per cent of codes assigned. The second most common coding occurred in research articles with mathematical analysis, representing about 19 per cent of the codes assigned, for example where a ma-thematical formulation or result was “intuitive”. The possibly most impactful use of the term “intuition” was “Intuition as Outcome”, representing approximately 7 per cent of all coding, which characterized research results as adding to the intui-tive understanding of a research topic or phenomena. This research contributes to a greater theoretical understanding of intuition enabling insight into the use of intuition, and the eventual development of a theory on the use of intuition in academic IS research publications. It also provides potential benefits to practi-tioners by providing insight into and validation of the use of intuition in IS man-agement. Research directions include the creation of reflective and/or formative constructs for intuition in information systems research.

Participatory research approaches in the development of improved management practices in indigenous chickens production systems with smallholder farmers in Kenya

This thesis is concerned with development of improved management practices in indigenous chicken production systems in a research process that includes participatory approaches with smallholder farmers and other stakeholders in Kenya. The research process involved a wide range of activities that included on-station experiments, field surveys, stakeholder consultations in workshops, seminars and visits, and on-farm farmer participatory research to evaluate the effect of some improved management interventions on production performance of indigenous chickens. The participatory research was greatly informed from collective experiences and lessons of the previous activities. The on-station studies focused on hatching, growth and nutritional characteristics of the indigenous chickens. Four research publications from these studies are included in this thesis. Quantitative statistical analyses were applied and they involved use of growth models estimated with non-linear regressions for the growth characteristics, chi-square determinations to investigate differences among different reciprocal crosses of indigenous chickens and general linear models and covariance determination for the nutrition study. The on-station studies brought greater understanding of performance and production characteristics of indigenous chickens and the influence of management practices on these characteristics. The field surveys and stakeholder consultations helped in understanding the overarching issues affecting the productivity of the indigenous chickens systems and their place in the livelihoods of smallholder farmers. These activities created strong networking opportunities with stakeholders from a wide spectrum. The on-farm farmer participatory research involved selection of 200 farmers in five regions followed by training and introduction of interventions on improved management practices which included housing, vaccination, deworming and feed supplementation. Implementation and monitoring was mainly done by individual farmers continuously for close to one and half years. Six quarterly visits to the farms were made by the research team to monitor and provide support for on-going project activities. The data collected has been analysed for 5 consecutive 3-monthly periods. Descriptive and inferential statistics were applied to analyse the data collected involving treatment applications, production characteristics and flock demography characteristics. Out of the 200 farmers initially selected, 173 had records on treatment applications and flock demography characteristics while 127 farmers had records on production characteristics. The demographic analysis with a dissimilarity index of flock size produced 7 distinct farm groups from among the 173 farms. Two of these farm groups were represented in similar numbers in each of the five regions. The research process also involved a number of dissemination and communication strategies that have brought the process and project outcomes into the domain of accessibility by wider readership locally and globally. These include workshops, seminars, field visits and consultations, local and international conferences, electronic conferencing, publications and personal communication via emailing and conventional posting. A number of research and development proposals were also developed based on the knowledge and experiences gained from the research process. The thesis captures the research process activities and outcomes in 8 chapters which include in ascending order – introduction, theoretical concepts underpinning FPR, research methodology and process, on-station research output, FPR descriptive statistical analysis, FPR inferential statistical analysis on production characteristics, FPR demographic analysis and conclusions. Various research approaches both quantitative and qualitative have been applied in the research process indicating the possibilities and importance of combining both systems for greater understanding of issues being studied. In our case, participatory studies of the improved management of indigenous chickens indicates their potential importance as livelihood assets for poor people.

Thyroid hormone can increase estrogen-mediated transcription from a consensus estrogen response element in neuroblastoma cells

Thyroid hormones (T) and estrogens (E) are nuclear receptor ligands with at least two molecular mechanisms of action: (i) relatively slow genomic effects, such as the regulation of transcription by cognate T receptors (TR) and E receptors (ER); and (ii) relatively rapid nongenomic effects, such as kinase activation and calcium release initiated at the membrane by putative membrane receptors. Genomic and nongenomic effects were thought to be disparate and independent. However, in a previous study using a two-pulse paradigm in neuroblastoma cells, we showed that E acting at the membrane could potentiate transcription from an E-driven reporter gene in the nucleus. Because both T and E can have important effects on mood and cognition, it is possible that the two hormones can act synergistically. In this study, we demonstrate that early actions of T via TRalpha1 and TRbeta1 can potentiate E-mediated transcription (genomic effects) from a consensus E response element (ERE)-driven reporter gene in transiently transfected neuroblastoma cells. Such potentiation was reduced by inhibition of mitogen-activated protein kinase. Using phosphomutants of ERalpha, we also show that probable mitogen-activated protein kinase phosphorylation sites on the ERalpha, the serines at position 167 and 118, are important in TRbeta1-mediated potentiation of ERalpha-induced transactivation. We suggest that crosstalk between T and E includes potential interactions through both nuclear and membrane-initiated molecular mechanisms of hormone signaling.

Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies

Chromosomal microarray (CMA) is increasingly utilized for genetic testing of individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA). Performing CMA and G-banded karyotyping on every patient substantially increases the total cost of genetic testing. The International Standard Cytogenomic Array (ISCA) Consortium held two international workshops and conducted a literature review of 33 studies, including 21,698 patients tested by CMA. We provide an evidence-based summary of clinical cytogenetic testing comparing CMA to G-banded karyotyping with respect to technical advantages and limitations, diagnostic yield for various types of chromosomal aberrations, and issues that affect test interpretation. CMA offers a much higher diagnostic yield (15%-20%) for genetic testing of individuals with unexplained DD/ID, ASD, or MCA than a G-banded karyotype (similar to 3%, excluding Down syndrome and other recognizable chromosomal syndromes), primarily because of its higher sensitivity for submicroscopic deletions and duplications. Truly balanced rearrangements and low-level mosaicism are generally not detectable by arrays, but these are relatively infrequent causes of abnormal phenotypes in this population (<1%). Available evidence strongly supports the use of CMA in place of G-banded karyotyping as the first-tier cytogenetic diagnostic test for patients with DD/ID, ASD, or MCA. G-banded karyotype analysis should be reserved for patients with obvious chromosomal syndromes (e.g., Down syndrome), a family history of chromosomal rearrangement, or a history of multiple miscarriages.

EXPRESSION OF COCAINE- AND AMPHETAMINE-REGULATED TRANSCRIPT IN THE RAT FOREBRAIN DURING POSTNATAL DEVELOPMENT

Cocaine- and amphetamine-regulated transcript (CART) is widespread in the rodent brain. CART has been implicated in many different functions including reward, feeding, stress responses, sensory processing, learning and memory formation. Recent studies have suggested that CART may also play a role in neural development. Therefore, in the present study we compared the distribution pattern and levels of CART mRNA expression in the forebrain of male and female rats at different stages of postnatal development: P06, P26 and P66. At 6 days of age (P06), male and female rats showed increased CART expression in the somatosensory and piriform cortices, indusium griseum, dentate gyrus, nucleus accumbens, and ventral premammillary nucleus. Interestingly, we found a striking expression of CART mRNA in the ventral posteromedial and ventral posterolateral thalamic nuclei. This thalamic expression was absent at P26 and P66. Contrastingly, at P06 CART mRNA expression was decreased in the arcuate nucleus. Comparing sexes, we found increased CART mRNA expression in the anteroventral periventricular nucleus of adult females. In other regions including the CA1, the lateral hypothalamic area and the dorsomedial nucleus of the hypothalamus, CART expression was not different comparing postnatal ages and sexes. Our findings indicate that CART gene expression is induced in a distinct temporal and spatial manner in forebrain sites of male and female rats. They also suggest that CART peptide participate in the development of neural pathways related to selective functions including sensory processing, reward and memory formation. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Acoustic Design in Urban Development : analysis of urban soundscapes and acoustic ecology research in New York City

The world is urbanizing rapidly with more than half of the global population now living in cities. Improving urban environments for the well-being of the increasing number of urban citizens is becoming one of the most important challenges of the 21st century. Even though it is common that city planners have visions of a ’good urban milieu’, those visions are concerning visual aesthetics or practical matters. The qualitative perspective of sound, such as sonic diversity and acoustic ecology are neglected aspects in architectural design. Urban planners and politicians are therefore largely unaware of the importance of sounds for the intrinsic quality of a place. Whenever environmental acoustics is on the agenda, the topic is noise abatement or noise legislation – a quantitative attenuation of sounds. Some architects may involve acoustical aspects in their work but sound design or acoustic design has yet to develop to a distinct discipline and be incorporated in urban planning.My aim was to investigate to what extent the urban soundscape is likely to improve if modern architectural techniques merge with principles of acoustics. This is an important, yet unexplored, research area. My study explores and analyses the acoustical aspects in urban development and includes interviews with practitioners in the field of urban acoustics, situated in New York City. My conclusion is that to achieve a better understanding of the human living conditions in mega-cities, there is a need to include sonic components into the holistic sense of urban development.

The Evolution of a Responsibility to Protect in Africa : The African Unions Emerging Peace and Security Regime

The thesis focuses on, and tries to evaluate, the role that the African Union (AU) plays in protecting the peace and security on the African continent. The thesis takes an interdisciplinary approach to the topic by both utilizing international relations and international law theories. The two disciplines are combined in an attempt to understand the evolution of the AU’s commitment to the pragmatist doctrine: responsibility to protect (R2P). The AU charter is considered to be the first international law document to cover R2P as it allows the AU to interfere in the internal affairs of its member states. The R2P doctrine was evolved around the notion of a need to arrive at a consensus in regard to the right to intervene in the face of humanitarian emergencies. A part of the post-Cold War shift in UN behaviour has been to support local solutions to local problems. Hereby the UN acts in collaboration with regional organizations, such as the AU, to achieve the shared aspirations to maintain international peace and security without getting directly involved on the ground. The R2P takes a more holistic and long-term approach to interventions by including an awareness of the need to address the root causes of the crisis in order to prevent future resurrections of conflicts. The doctrine also acknowledges the responsibility of the international community and the intervening parties to actively participate in the rebuilding of the post-conflict state. This requires sustained and well planned support to ensure the development of a stable society.While the AU is committed to implementing R2P, many of the AU’s members are struggling, both ideologically and practically, to uphold the foundations on which legitimate intervention rests, such as the protection of human rights and good governance. The fact that many members are also among the poorest countries in the world adds to the challenges facing the AU. A lack of human and material resources leads to a situation where few countries are willing, or able, to support a long-term commitment to humanitarian interventions. Bad planning and unclear mandates also limit the effectiveness of the interventions. This leaves the AU strongly dependent on regional powerbrokers such as Nigeria and South Africa, which in itself creates new problems in regard to the motivations behind interventions. The current AU charter does not provide sufficient checks and balances to ensure that national interests are not furthered through humanitarian interventions. The lack of resources within the AU also generates worries over what pressure foreign nations and other international actors apply through donor funding. It is impossible for the principle of “local solutions for local problems? to gain ground while this donor conditionality exists.The future of the AU peace and security regime is not established since it still is a work in progress. The direction that these developments will take depends on a wide verity of factors, many of which are beyond the immediate control of the AU.