Showing papers by "Cardiff University published in 2006"

Expert consensus document on arterial stiffness: methodological issues and clinical applications

Abstract: In recent years, great emphasis has been placed on the role of arterial stiffness in the development of cardiovascular diseases. Indeed, the assessment of arterial stiffness is increasingly used in the clinical assessment of patients. Although several papers have previously addressed the methodological issues concerning the various indices of arterial stiffness currently available, and their clinical applications, clinicians and researchers still report difficulties in selecting the most appropriate methodology for their specific use. This paper summarizes the proceedings of several meetings of the European Network for Non-invasive Investigation of Large Arteries and is aimed at providing an updated and practical overview of the most relevant methodological aspects and clinical applications in this area.

Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological Fluids

Abstract: Exosomes are small membrane vesicles found in cell culture supernatants and in different biological fluids. Exosomes form in a particular population of endosomes, called multivesicular bodies (MVBs), by inward budding into the lumen of the compartment. Upon fusion of MVBs with the plasma membrane, these internal vesicles are secreted. Exosomes possess a defined set of membrane and cytosolic proteins. The physiological function of exosomes is still a matter of debate, but increasing results in various experimental systems suggest their involvement in multiple biological processes. Because both cell-culture supernatants and biological fluids contain different types of lipid membranes, it is critical to perform high-quality exosome purification. This unit describes different approaches for exosome purification from various sources, and discusses methods to evaluate the purity and homogeneity of the purified exosome preparations.

Guidelines on the management of valvular heart disease The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology

Abstract: Guidelines and Expert Consensus Documents aim to present management recommendations based on all of the relevant evidence on a particular subject in order to help physicians select the best possible management strategies for the individual patient suffering from a specific condition, taking into account the impact on outcome and also the risk–benefit ratio of a particular diagnostic or therapeutic procedure. Numerous studies have demonstrated that patient outcomes improve when guideline recommendations, based on the rigorous assessment of evidence-based research, are applied in clinical practice. A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) and also by other organizations or related societies. The profusion of documents can put at stake the authority and credibility of guidelines, particularly if discrepancies appear between different documents on the same issue, as this can lead to confusion in the minds of physicians. In order to avoid these pitfalls, the ESC and other organizations have issued recommendations for formulating and issuing Guidelines and Expert Consensus Documents. The ESC recommendations for guidelines production can be found on the ESC website.1 It is beyond the scope of this preamble to recall all but the basic rules. In brief, the ESC appoints experts in the field to carry out a comprehensive review of the literature, with a view to making a critical evaluation of the use of diagnostic and therapeutic procedures and assessing the risk–benefit ratio of the therapies recommended for management and/or prevention of a given condition. Estimates of expected health outcomes are included, where data exist. The strength of evidence for or against particular procedures or treatments is weighed according to predefined scales for grading recommendations and levels of evidence, as outlined in what follows. The Task Force members of the writing panels, …

Solvent-Free Oxidation of Primary Alcohols to Aldehydes Using Au-Pd/TiO2 Catalysts

Abstract: The oxidation of alcohols to aldehydes with O2 in place of stoichiometric oxygen donors is a crucial process for the synthesis of fine chemicals. However, the catalysts that have been identified so far are relatively inactive with primary alkyl alcohols. We showed that Au/Pd-TiO2 catalysts give very high turnover frequencies (up to 270,000 turnovers per hour) for the oxidation of alcohols, including primary alkyl alcohols. The addition of Au to Pd nanocrystals improved the overall selectivity and, using scanning transmission electron microscopy combined with x-ray photoelectron spectroscopy, we showed that the Au-Pd nanocrystals were made up of a Au-rich core with a Pd-rich shell, indicating that the Au electronically influences the catalytic properties of Pd.

Polymer conjugates as anticancer nanomedicines

Abstract: Polymers can be conjugated to anticancer drugs and proteins to improve their therapeutic index. Some such conjugates are in routine clinical use and there are exciting advances in development, such as polymer-based combination therapies.

Developing a quality criteria framework for patient decision aids: online international Delphi consensus process

Abstract: Objective To develop a set of quality criteria for patient decision support technologies (decision aids). Design and setting Two stage web based Delphi process using online rating process to enable international collaboration. Participants Individuals from four stakeholder groups (researchers, practitioners, patients, policy makers) representing 14 countries reviewed evidence summaries and rated the importance of 80 criteria in 12 quality domains ona1to9 scale. Second round participants received feedback from the first round and repeated their assessment of the 80 criteria plus three new ones. Main outcome measure Aggregate ratings for each criterion calculated using medians weighted to compensate for different numbers in stakeholder groups; criteria rated between 7 and 9 were retained. Results 212 nominated people were invited to participate. Of those invited, 122 participated in the first round (77 researchers, 21 patients, 10 practitioners, 14 policy makers); 104/122 (85%) participated in the second round. 74 of 83 criteria were retained in the following domains: systematic development process (9/9 criteria); providing information about options (13/13); presenting probabilities (11/13); clarifying and expressing values (3/3); using patient stories (2/5); guiding/coaching (3/5); disclosing conflicts of interest (5/5); providing internet access (6/6); balanced presentation of options (3/3); using plain language (4/6); basing information on up to date evidence (7/7); and establishing effectiveness (8/8). Conclusions Criteria were given the highest ratings where evidence existed, and these were retained. Gaps in research were highlighted. Developers, users, and purchasers of patient decision aids now have a checklist for appraising quality. An instrument for measuring quality of decision aids is being developed.

Randomized Multicenter Trial of Sentinel Node Biopsy Versus Standard Axillary Treatment in Operable Breast Cancer: The ALMANAC Trial

Abstract: BACKGROUND: Sentinel lymph node biopsy in women with operable breast cancer is routinely used in some countries for staging the axilla despite limited data from randomized trials on morbidity and mortality outcomes. We conducted a multicenter randomized trial to compare quality-of-life outcomes between patients with clinically node-negative invasive breast cancer who received sentinel lymph node biopsy and patients who received standard axillary treatment. METHODS: The primary outcome measures were arm and shoulder morbidity and quality of life. From November 1999 to October 2003, 1031 patients were randomly assigned to undergo sentinel lymph node biopsy (n = 515) or standard axillary surgery (n = 516). Patients with sentinel lymph node metastases proceeded to delayed axillary clearance or received axillary radiotherapy (depending on the protocol at the treating institution). Intention-to-treat analyses of data at 1, 3, 6, and 12 months after surgery are presented. All statistical tests were two-sided. RESULTS: The relative risks of any lymphedema and sensory loss for the sentinel lymph node biopsy group compared with the standard axillary treatment group at 12 months were 0.37 (95% confidence interval [CI] = 0.23 to 0.60; absolute rates: 5% versus 13%) and 0.37 (95% CI = 0.27 to 0.50; absolute rates: 11% versus 31%), respectively. Drain usage, length of hospital stay, and time to resumption of normal day-to-day activities after surgery were statistically significantly lower in the sentinel lymph node biopsy group (all P .05). CONCLUSION: Sentinel lymph node biopsy is associated with reduced arm morbidity and better quality of life than standard axillary treatment and should be the treatment of choice for patients who have early-stage breast cancer with clinically negative nodes.

Polymers of intrinsic microporosity (PIMs): organic materials for membrane separations, heterogeneous catalysis and hydrogen storage

Abstract: This tutorial review describes recent research directed towards the synthesis of polymer-based organic microporous materials termed Polymers of Intrinsic Microporosity (PIMs). PIMs can be prepared either as insoluble networks or soluble polymers with both types giving solids that exhibit analogous behaviour to that of conventional microporous materials such as activated carbons. Soluble PIMs may be processed into thin films for use as highly selective gas separation membranes. Preliminary results also demonstrate the potential of PIMs for heterogeneous catalysis and hydrogen storage.

Chromatin signatures of pluripotent cell lines

Abstract: Epigenetic genome modifications are thought to be important for specifying the lineage and developmental stage of cells within a multicellular organism. Here, we show that the epigenetic profile of pluripotent embryonic stem cells (ES) is distinct from that of embryonic carcinoma cells, haematopoietic stem cells (HSC) and their differentiated progeny. Silent, lineage-specific genes replicated earlier in pluripotent cells than in tissue-specific stem cells or differentiated cells and had unexpectedly high levels of acetylated H3K9 and methylated H3K4. Unusually, in ES cells these markers of open chromatin were also combined with H3K27 trimethylation at some non-expressed genes. Thus, pluripotency of ES cells is characterized by a specific epigenetic profile where lineage-specific genes may be accessible but, if so, carry repressive H3K27 trimethylation modifications. H3K27 methylation is functionally important for preventing expression of these genes in ES cells as premature expression occurs in embryonic ectoderm development (Eed)-deficient ES cells. Our data suggest that lineage-specific genes are primed for expression in ES cells but are held in check by opposing chromatin modifications.

The bees algorithm, a novel tool for complex optimisation problems

Abstract: Publisher Summary This chapter presents a new population-based search algorithm called the Bees Algorithm (BA). This algorithm mimics the food foraging behavior of swarms of honeybees. In its basic version, the algorithm performs a kind of neighborhood search combined with random search and can be used for both combinatorial optimization and functional optimization. This chapter focuses on the latter. Following a description of the algorithm, the chapter presents the results obtained for a number of benchmark problems demonstrating the efficiency and robustness of the new algorithm. The results show that the algorithm can reliably handle complex multi-model optimization problems without being trapped at local solutions. One of the drawbacks of the algorithm is the number of tunable parameters used. However, it is possible to set the parameter values by conducting a small number of trials.

Public Views on Climate Change: European and USA Perspectives

Abstract: If uncontrolled, human influences on the climate system may generate changes that will endanger various aspects of life on Earth. The precise implications of the scientific claims about climate change, and the extent to which they pose dangers to various populations, are becoming intensely debated at many levels in relation to policy. How `danger' is interpreted will ultimately affect which actions are taken. In this paper, we examine how climate change is conceptualised by publics in Europe and in the USA. Although there is widespread concern about climate change, it is of secondary importance in comparison to other issues in people's daily lives. Most individuals relate to climate change through personal experience, knowledge, the balance of benefits and costs, and trust in other societal actors. We analyse these factors through findings from various surveys and studies, which highlight both the distinctiveness and some shared perspectives at a generalised level. We reflect upon these in relation to trust and responsibility for climate change action, and risk communication, supporting the call for discourses about climate change to also be situated in people's locality, as a means of increasing its saliency.

Small Business Champions for Corporate Social Responsibility

Abstract: While Corporate Social Responsibility (CSR) has traditionally been the domain of the corporate sector, recognition of the growing significance of the Small and Medium Sized Enterprise (SME) sector has led to an emphasis on their social and environmental impact, illustrated by an increasing number of initiatives aimed at engaging SMEs in the CSR agenda. CSR has been well researched in large companies, but SMEs have received less attention in this area. This paper presents the findings from a U.K. wide study of socially responsible SMEs. The 24 companies studied were chosen as “exemplars” of␣CSR in SMEs. The aim of this study therefore is to progress understanding of both the limitations on and opportunities for CSR in SMEs through the exploration of exemplary characteristics in the study companies. Key areas of investigation were CSR terminology, the influence of managerial values, the nature of SME CSR activities, motivation for and benefits from engaging in CSR, and the challenges faced. The results of this study demonstrate some of the exemplary goals and principles needed to achieve social responsibility in SMEs, and begin to provide knowledge that could be used to engender learning in other SMEs. In particular, there is evidence that stakeholder theory may provide a framework in which SMEs and CSR can be understood. SMEs prefer to learn through networking and from their peers, so this is a possible avenue for greater SME engagement in CSR. This would require strong leadership or “championing” from individuals such as highly motivated owner–managers and from exemplary companies as a whole.

Is Work Good for Your Health and Well-being?

Abstract: Increasing employment and supporting people into work are key elements of the Government's public health and welfare reform agendas. This independent review, 'Is Work Good for Your Health and Well-being?', commissioned by the Department for Work and Pensions, examines scientific evidence on the health benefits of work, focusing on adults of working age and the common health problems that account for two-thirds of sickness absence and long-term incapacity. The study finds that there is a strong evidence base showing that work is generally good for physical and mental health and well-being, taking into account the nature and quality of work and its social context, and that worklessness is associated with poorer physical and mental health. Work can be therapeutic and can reverse the adverse health effects of unemployment, in relation to healthy people of working age, for many disabled people, for most people with common health problems, and for social security beneficiaries

Regional and cellular gene expression changes in human Huntington's disease brain.

Abstract: Huntington's disease (HD) pathology is well understood at a histological level but a comprehensive molecular analysis of the effect of the disease in the human brain has not previously been available. To elucidate the molecular phenotype of HD on a genome-wide scale, we compared mRNA profiles from 44 human HD brains with those from 36 unaffected controls using microarray analysis. Four brain regions were analyzed: caudate nucleus, cerebellum, prefrontal association cortex [Brodmann's area 9 (BA9)] and motor cortex [Brodmann's area 4 (BA4)]. The greatest number and magnitude of differentially expressed mRNAs were detected in the caudate nucleus, followed by motor cortex, then cerebellum. Thus, the molecular phenotype of HD generally parallels established neuropathology. Surprisingly, no mRNA changes were detected in prefrontal association cortex, thereby revealing subtleties of pathology not previously disclosed by histological methods. To establish that the observed changes were not simply the result of cell loss, we examined mRNA levels in laser-capture microdissected neurons from Grade 1 HD caudate compared to control. These analyses confirmed changes in expression seen in tissue homogenates; we thus conclude that mRNA changes are not attributable to cell loss alone. These data from bona fide HD brains comprise an important reference for hypotheses related to HD and other neurodegenerative diseases.

Where tendons and ligaments meet bone: attachment sites (‘entheses’) in relation to exercise and/or mechanical load

Abstract: Entheses (insertion sites, osteotendinous junctions, osteoligamentous junctions) are sites of stress concentration at the region where tendons and ligaments attach to bone. Consequently, they are commonly subject to overuse injuries (enthesopathies) that are well documented in a number of sports. In this review, we focus on the structure-function correlations of entheses on both the hard and the soft tissue sides of the junction. Particular attention is paid to mechanical factors that influence form and function and thus to exploring the relationship between entheses and exercise. The molecular parameters indicative of adaptation to mechanical stress are evaluated, and the basis on which entheses are classified is explained. The application of the 'enthesis organ' concept (a collection of tissues adjacent to the enthesis itself, which jointly serve the common function of stress dissipation) to understanding enthesopathies is considered and novel roles of adipose tissue at entheses are reviewed. A distinction is made between different locations of fat at entheses, and possible functions include space-filling and proprioception. The basic anchorage role of entheses is considered in detail and comparisons are explored between entheses and other biological 'anchorage' sites. The ability of entheses for self-repair is emphasized and a range of enthesopathies common in sport are reviewed (e.g. tennis elbow, golfer's elbow, jumper's knee, plantar fasciitis and Achilles insertional tendinopathies). Attention is drawn to the degenerative, rather than inflammatory, nature of most enthesopathies in sport. The biomechanical factors contributing to the development of enthesopathies are reviewed and the importance of considering the muscle-tendon-bone unit as a whole is recognized. Bony spur formation is assessed in relation to other changes at entheses which parallel those in osteoarthritic synovial joints.

New screening software shows that most recent large 16S rRNA gene clone libraries contain chimeras.

Abstract: A new computer program, called Mallard, is presented for screening entire 16S rRNA gene libraries of up to 1,000 sequences for chimeras and other artifacts. Written in the Java computer language and capable of running on all major operating systems, the program provides a novel graphical approach for visualizing phylogenetic relationships among 16S rRNA gene sequences. To illustrate its use, we analyzed most of the large libraries of cloned bacterial 16S rRNA gene sequences submitted to the public repository during 2005. Defining a large library as one containing 100 or more sequences of 1,200 bases or greater, we screened 25 of the 28 libraries and found that all but three contained substantial anomalies. Overall, 543 anomalous sequences were found. The average anomaly content per clone library was 9.0%, 4% higher than that previously estimated for the public repository overall. In addition, 90.8% of anomalies had characteristic chimeric patterns, a rise of 25.4% over that found previously. One library alone was found to contain 54 chimeras, representing 45.8% of its content. These figures far exceed previous estimates of artifacts within public repositories and further highlight the urgent need for all researchers to adequately screen their libraries prior to submission. Mallard is freely available from our website at http://www.cardiff.ac.uk/biosi/research/biosoft/.

Accounting, professions and regulation: Locating the sites of professionalization

Abstract: This review paper argues that the institutions and sites of professionalization projects and regulatory processes matter. The institutions and locations where regulation takes place affect both the outcome of the regulatory process and the legitimacy of the rules and practices produced. Changes in regulatory processes affect opportunities for democratic control and legitimacy. A common position in the accounting literature is to examine both the process of professionalization and accounting and audit regulation within and around professional associations and related organizations, such as standard setting bodies and regulatory agencies. We argue that professional firms are increasingly important in professionalization and regulatory processes and have not received the attention that they warrant: an examination of the multi-national professional service firms (currently known as the Big 4) can enhance an understanding of professionalization and professional regulation. We suggest that these are important sites where accounting practices are themselves standardized and regulated, where accounting rules and standards are translated into practice, where professional identities are mediated, formed and transformed, and where important conceptions of personal, professional and corporate governance and management are transmitted.

Keywords in Qualitative Methods

Abstract: An essential companion for students across the social and health sciences, this text provides a wide-ranging coverage of qualitative methods complemented by extended illustration from the array of academic disciplines in which qualitative research is found and employed. Written in a lively and reader-friendly style, the guide covers a comprehensive range of topics, including: - a concise definition of the method - a description of distinctive features - examples to convey the flavour of a technique or principle - a critical and reflective evaluation of the method or approach under consideration - cross references to associated concepts within the dictionary - a list of key readings

New consensus nomenclature for mammalian keratins

Abstract: Keratins are intermediate filament–forming proteins that provide mechanical support and fulfill a variety of additional functions in epithelial cells. In 1982, a nomenclature was devised to name the keratin proteins that were known at that point. The systematic sequencing of the human genome in recent years uncovered the existence of several novel keratin genes and their encoded proteins. Their naming could not be adequately handled in the context of the original system. We propose a new consensus nomenclature for keratin genes and proteins that relies upon and extends the 1982 system and adheres to the guidelines issued by the Human and Mouse Genome Nomenclature Committees. This revised nomenclature accommodates functional genes and pseudogenes, and although designed specifically for the full complement of human keratins, it offers the flexibility needed to incorporate additional keratins from other mammalian species.

Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas

Abstract: In June 2005, an ad hoc Expert Committee formed by the Pituitary Society convened during the 9th International Pituitary Congress in San Diego, California. Members of this committee consisted of invited international experts in the field, and included endocrinologists and neurosurgeons with recognized expertise in the management of prolactinomas. Discussions were held that included all interested participants to the Congress and resulted in formulation of these guidelines, which represent the current recommendations on the diagnosis and management of prolactinomas based upon comprehensive analysis and synthesis of all available data.

Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer.

Abstract: Cytokine receptors, which exist in membrane-bound and soluble forms, bind their ligands with comparable affinity. Although most soluble receptors are antagonists and compete with their membrane-associated counterparts for the ligands, certain soluble receptors are agonists. In these cases, complexes of ligand and soluble receptor bind on target cells to second receptor subunits and initiate intracellular signaling. The soluble receptors of the interleukin (IL)-6 family of cytokines (sIL-6R, sIL-11R, soluble ciliary neurotrophic factor receptor) are agonists capable of transmitting signals through interaction with the universal signal-transducing receptor for all IL-6 family cytokines, gp130. In vivo, the IL-6/sIL-6R complex stimulates several types of cells, which are unresponsive to IL-6 alone, as they do not express the membrane IL-6R. We have named this process trans-signaling. The generation of soluble cytokine receptors occurs via two distinct mechanisms-limited proteolysis and translation-from differentially spliced mRNA. We have demonstrated that a soluble form of the IL-6 family signaling receptor subunit gp130, which is generated by differential splicing, is the natural inhibitor of IL-6 trans-signaling responses. We have shown that in many chronic inflammatory diseases, including chronic inflammatory bowel disease, peritonitis, rheumatoid arthritis, asthma, as well as colon cancer, IL-6 trans-signaling is critically involved in the maintenance of a disease state, by promoting transition from acute to chronic inflammation. Moreover, in all these models, the course of the disease can be disrupted by specifically interfering with IL-6 trans-signaling using the soluble gp130 protein. The pathophysiological mechanisms by which the IL-6/sIL-6R complex regulates the inflammatory state are discussed.

Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD)

Abstract: Molecular genetic investigations of attention deficit hyperactivity disorder (ADHD) have found associations with a variable number of tandem repeat (VNTR) situated in the 3'-untranslated region of dopamine transporter gene (DAT1), a VNTR in exon 3 of dopamine receptor 4 gene (DRD4) and a microsatellite polymorphism located at 18.5 kb from the 5' end of dopamine receptor 5 gene (DRD5). A number of independent studies have attempted to replicate these findings but the results have been mixed, possibly reflecting inadequate statistical power and the use of different populations and methodologies. In an attempt to clarify this inconsistency, we have combined all the published studies of European and Asian populations up to October 2005 in a meta-analysis to give a comprehensive picture of the role of the three dopamine-related genes using multiple research methods and models. The DRD4 7-repeat (OR=1.34, 95% CI 1.23-1.45, P= 2 x 10(-12)) and 5-repeat (OR=1.68, 95% CI 1.17-2.41, P=0.005) alleles as well as the DRD5 148-bp allele (OR=1.34, 95% CI 1.21-1.49, P= 8 x 10(-8)) confer increased risk of ADHD, whereas the DRD4 4-repeat (OR=0.90, 95% CI 0.84-0.97, P=0.004) and DRD5 136-bp (OR=0.57, 95% CI 0.34-0.96, P=0.022) alleles have protective effects. In contrast, we found no compelling evidence for association with the 480-bp allele of DAT (OR=1.04, 95% CI 0.98-1.11, P=0.20). No significant publication bias was detected in current studies. In conclusion, there is a statistically significant association between ADHD and dopamine system genes, especially DRD4 and DRD5. These findings strongly implicate the involvement of brain dopamine systems in the pathogenesis of ADHD.

The Heartbeat of the Oligocene Climate System

Abstract: A 13-million-year continuous record of Oligocene climate from the equatorial Pacific reveals a pronounced “heartbeat” in the global carbon cycle and periodicity of glaciations. This heartbeat consists of 405,000-, 127,000-, and 96,000-year eccentricity cycles and 1.2-million-year obliquity cycles in periodically recurring glacial and carbon cycle events. That climate system response to intricate orbital variations suggests a fundamental interaction of the carbon cycle, solar forcing, and glacial events. Box modeling shows that the interaction of the carbon cycle and solar forcing modulates deep ocean acidity as well as the production and burial of global biomass. The pronounced 405,000-year eccentricity cycle is amplified by the long residence time of carbon in the oceans.