Showing papers by "Cardiff University published in 2003"

The dawning era of polymer therapeutics

Abstract: As we enter the twenty-first century, research at the interface of polymer chemistry and the biomedical sciences has given rise to the first nano-sized (5-100 nm) polymer-based pharmaceuticals, the 'polymer therapeutics'. Polymer therapeutics include rationally designed macromolecular drugs, polymer-drug and polymer-protein conjugates, polymeric micelles containing covalently bound drug, and polyplexes for DNA delivery. The successful clinical application of polymer-protein conjugates, and promising clinical results arising from trials with polymer-anticancer-drug conjugates, bode well for the future design and development of the ever more sophisticated bio-nanotechnologies that are needed to realize the full potential of the post-genomic age.

Understanding Alternative Food Networks: Exploring the Role of Short Food Supply Chains in Rural Development:

Abstract: In this paper we explore the development and incidence of alternative food networks within a European-wide context. By developing a consistent definition of short food supply chains, we address both the morphology and the dynamics of these, and then examine empirical evidence concerning their incidence and rural development impact across seven EU member states. These developments need to be seen as one significant contribution to the current transitions in rural Europe concerning the crisis of conventional intensive and productivist agriculture and the public consumer pressure for a larger variety of distinctive 'quality' food products.

Can generalist predators be effective biocontrol agents

Abstract: Theoretical developments are helping us to comprehend the basic parameters governing the dynamics of the interactions between generalist predators and their many pest and nonpest prey. In practice, however, inter- and intraspecific interactions between generalist predators, and between the predators and their prey, within multispecies systems under the influence of rapidly changing biotic and abiotic variables are difficult to predict. We discuss trade-offs between the relative merits of specialists and generalists that allow both to be effective, and often complementary, under different circumstances. A review of manipulative field studies showed that in approximately 75% of cases, generalist predators, whether single species or species assemblages, reduced pest numbers significantly. Techniques for manipulating predator numbers to enhance pest control at different scales are discussed. We now need to find ways of disentangling the factors influencing positive and negative interactions within natural enemy communities in order to optimize beneficial synergies leading to pest control.

Genome Scan Meta-Analysis of Schizophrenia and Bipolar Disorder, Part II: Schizophrenia

Abstract: Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.

Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.

Abstract: Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. Background: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. Methods: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case- control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two- sided. Results: Breast cancer risk increased with increasing BMI (P-trend = .002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m(2) increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin- bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. Conclusion: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.

An electrosurgical generator

Abstract: An electrosurgical generator for supplying RF power to an electrosurgical instrument for cutting or vaporising tissue has an RF output stage (42) with an RF power bridge (Q1, Q2, Q3, Q4), a pair of output lines (74) and a series-resonant output network (48). The output impedance of the output stage (42) at the output lines (74) is less than 200/√P ohms, where P is the maximum continuous RF output power of the generator. The generator offers improved cutting and vaporising performance, especially in relation to the reliability with which an arc can be struck when presented with an initial low impedance load. Overloading of the output stage is prevented by rapidly operating protection circuitry responsive to a predetermined electrical condition such as a substantial short-circuit across the output lines. In the preferred embodiment, the output stage is capable of maintaining output pulses at least 1kW peak by supplying the power bridge from a large reservoir capacitor (60). Pulsing is dynamically variable in response to load conditions by controlling the maximum energy per pulse in response to the reservoir capacitor voltage.

Electrosurgical method and apparatus

Abstract: An electrosurgical method and apparatus comprises a probe, at least one temperature sensor, and a controller for generating and controlling electromagnetic energy supplied to the probe. The controller receives signals from the temperature sensor and controls the supply of electromagnetic energy such that the temperature of the probe is ramped up and then maintained at a steady state temperature of between 100° C. and 115° C. In an equilibration phase, between the ramping up and the steady state temperature, the controller holds the temperature of the probe substantially constant for a period of time to allow the temperature of different parts of the probe to equilibrate.

Coordination of Actions and Habits in the Medial Prefrontal Cortex of Rats

Abstract: As animals learn novel behavioural responses, performance is maintained by two dissociable influences. Initial responding is goal-directed and under voluntary control, but overtraining of the same response routine leads to behavioural autonomy and the development of habits that are no longer voluntary or goal-directed. Rats normally show goal-directed performance after limited training, indexed by sensitivity to changes in the value of reward, but this sensitivity to goal value is lost with extended training. Rats with selective lesions of the prelimbic medial prefrontal cortex showed no sensitivity to goal value after either limited or extended training, whereas rats with lesions of the infralimbic region of the medial prefrontal cortex showed the opposite pattern of deficit, a marked sensitivity to goal value after both limited and extended training. This double-dissociation suggests that the prelimbic region is responsible for voluntary response performance and the infralimbic cortex mediates the incremental ability of extended training to override this goal-directed behaviour.

Elevated Levels of Epidermal Growth Factor Receptor/c-erbB2 Heterodimers Mediate an Autocrine Growth Regulatory Pathway in Tamoxifen-Resistant MCF-7 Cells

Abstract: The development of acquired resistance to antihormonal agents in breast cancer is a major therapeutic problem. We have developed a tamoxifen-resistant (TAM-R) MCF-7 breast cancer cell line to investigate the mechanisms behind this condition. Both epidermal growth factor receptor (EGFR) and c-erbB2 mRNA and protein expression were increased in TAM-R compared with wild-type MCF-7 cells, whereas comparable levels of c-erbB3 mRNA and protein were expressed in both cell lines. Under basal conditions, phosphorylated EGFR/c-erbB2, EGFR/c-erbB3 but not c-erbB2/c-erbB3 receptor heterodimers were detected in TAM-R cells in association with increased levels of phosphorylated extracellular-signal regulated kinase 1/2 (ERK1/2). Both cell lines were capable of generating a range of EGFR-specific ligands and increased expression of transforming growth factor α was observed in TAM-R cells. Treatment of TAM-R cells with ZD1839 (Iressa) or trastuzumab (Herceptin) blocked c-erbB receptor heterodimer formation and phosphorylation, reduced ERK1/2 activity, and strongly inhibited cell growth. The MAPK kinase inhibitor PD098059 specifically reduced phosphorylated ERK1/2 levels and inhibited TAM-R growth. All three agents abolished ERK1/2 activity in wild-type cells but caused only small reductions in cell proliferation. These results demonstrate that TAM-R MCF-7 cell growth is mediated by the autocrine release and action of an EGFR-specific ligand inducing preferential EGFR/c-erbB2 dimerization and downstream activation of the ERK pathway.

Sources of Public Service Improvement: A Critical Review and Research Agenda

Abstract: Evidence from sixty-five empirical studies of the determinants of public service performance is critically reviewed. The statistical results are grouped on the basis of five theoretical perspectives: resources, regulation, markets, organization, and management. The analysis suggests that the most likely sources of service improvement are extra resources and better management. A research agenda for further work is identified, and recommendations are made to enhance the theoretical and methodological quality of studies of public service improvement. Governments across the globe are searching for ways to improve public services. During the last twenty years there has been a pandemic of public-sector reforms, many of which are associated with the new public management (Pollitt and Bouckaert 2000). Which, if any, of the existing approaches to public service improvement actually work? How much empirical evidence is there on the impact of the various reform strategies, and how valid is the evidence? What are the main issues that need to be resolved in future work on the sources of public service improvement? The intent of this article is to answer these questions. In the first section of the article, the meaning of public service improvement is analyzed and criteria for evaluating the effects of different routes toward this “Holy Grail” of public administration theory and practice are identified. In the second section, five major theoretical perspectives on the sources of improvement are outlined. These cover resources, regulation, markets, organization, and management. Taken together, these five perspectives offer the basis for a more comprehensive theoretical model of how to provide better public services. In the third section of the article, the methods and results of empirical studies that have tested the five theories are critically reviewed. This leads to conclusions about the extent of our knowledge of how to achieve service improvement and about an agenda for the substance and methods of the vast research program that is required on this topic.

Older adults' use of information and communications technology in everyday life

Abstract: Social commentators in countries such as the United Kingdom and the United States are beginning to recognise that encouraging older adults' use of information and communication technologies (ICTs) is essential for the creation of bona fide information societies. To date, however, few studies have examined in detail older adults' access to and use of ICTs. This important aspect of the interaction between population ageing and societal change is more complex than the published literature's portrayal of a dichotomy between ‘successful users’ and ‘unsuccessful non-users’. The paper examines the extent and nature of ICT access and use by older adults in their everyday lives. Information was collected from a sub-sample of 352 adults aged 60 or more years taken from a large household survey of ICT use in England and Wales among 1,001 people. The findings suggest that using a computer is not only a minority activity amongst older adults but also highly stratified by gender, age, marital status and educational background. Conversely, non-use of computers can be attributed to their low relevance and ‘relative advantage’ to older people. The paper concludes by considering how political and academic assumptions about older people and ICTs might be refocused, away from trying to ‘change’ older adults, and towards involving them in changing ICT.

DNA markers reveal the complexity of livestock domestication

Abstract: A series of recent genetic studies has revealed the remarkably complex picture of domestication in both New World and Old World livestock. By comparing mitochondrial and nuclear DNA sequences of modern breeds with their potential wild and domestic ancestors, we have gained new insights into the timing and location of domestication events that produced the farm animals of today. The real surprise has been the high number of domestication events and the diverse locations in which they took place — factors which could radically change our approach to conserving livestock biodiversity resources in the future.

Activity and mechanisms of action of selected biocidal agents on Gram-positive and -negative bacteria.

Abstract: S.E. W ALSH, J .-Y. M AILLARD, A .D. R USSELL, C .E. C ATRENICH, D .L. C HARBONNEAU A ND R . G . B A R T O L O . 2003. Aims: This study investigates the antimicrobial activity and mode of action of two natural products, eugenol and thymol, a commonly utilized biostatic agent, triclocarban (TCC), and two surfactants, didecyldimethylammonium chloride (DDDMAC) and C10–C16 alkyldimethyl amine N-oxides (ADMAO). Methods and Results: Methods used included: determination of minimum inhibitory concentrations (MICs), lethal effect studies with suspension tests and the investigation of sub-MIC concentrations on growth of E. coli, Staph. aureus and Ps. aeruginosa using a Bioscreen microbiological analyser. Leakage of intracellular constituents and the effects of potentiating agents were also investigated. Only DDDMAC was bactericidal against all of the organisms tested. Eugenol, thymol and ADMAO showed bacteriostatic and bactericidal activity, but not against Ps. aeruginosa. TCC was only bacteristatic against Staph. aureus, but like the other agents, it did affect the growth of the other organisms in the Bioscreen experiments. All of the antimicrobial agents tested were potentiated by the permeabilizers to some extent and leakage of potassium was seen with all of the agents except TCC. Conclusions: DDDMAC was bactericidal against all organisms tested and all compounds had some bacteriostatic action. Low level static effects on bacterial growth were seen with sub-MIC concentrations. Membrane damage may account for at least part of the mode of action of thymol, eugenol, DDDMAC and ADMAO. Significance and Impact of the Study: The ingredients evaluated demonstrated a range of bactericidal and bacteriostatic properties against the Gram-negative and -positive organisms evaluated and the membrane (leakage of intracellular components) was implicated in the mode of action for most (except TCC). Sub-MIC levels of all ingredients did induce subtle effects on the organisms which impacted bacterial growth, even for those which had no true inhibitory effects.

The Consequences of Dysfunctional Customer Behavior

Abstract: Christopher Lovelock (1994) coined the term jaycustomers to refer to dysfunctional customers who deliberately or unintentionally disrupt service in a manner that negatively affects the organization...

Cultivation-dependent and -independent approaches for determining bacterial diversity in heavy-metal-contaminated soil.

Abstract: In recent years, culture-independent methods have been used in preference to traditional isolation techniques for microbial community analysis. However, it is questionable whether uncultured organisms from a given sample are important for determining the impact of anthropogenic stress on indigenous communities. To investigate this, soil samples were taken from a site with patchy metal contamination, and the bacterial community structure was assessed with a variety of approaches. There were small differences in microscopic epifluorescence bacterial counts. Denaturing gradient gel electrophoresis (DGGE) profiles of 16S rRNA gene fragments (16S-DGGE) amplified directly from soil samples were highly similar. A clone library generated from the most contaminated sample revealed a diverse bacterial community, which showed similarities to pristine soil communities from other studies. However, the proportion of bacteria from the soil samples that were culturable on standard plate-counting media varied between 0.08 and 2.2%, and these values correlated negatively with metal concentrations. The culturable communities from each sample were compared by 16S-DGGE of plate washes and by fatty acid profiling of individual isolates. Each approach indicated that there were considerable differences between the compositions of the culturable communities from each sample. DGGE bands from both culture-based and culture-independent approaches were sequenced and compared. These data indicated that metal contamination did not have a significant effect on the total genetic diversity present but affected physiological status, so that the number of bacteria capable of responding to laboratory culture and their taxonomic distribution were altered. Thus, it appears that plate counts may be a more appropriate method for determining the effect of heavy metals on soil bacteria than culture-independent approaches.

Oxidation of glycerol using supported Pt, Pd and Au catalysts

Abstract: The oxidation of aqueous solutions of glycerol is described and discussed for Pd, Pt and Au nanoparticles supported on graphite and activated carbon. The oxidation in a batch reactor at 60 °C and 1 bar pressure using air as oxidant was initially investigated. Under these conditions, supported Pd and Pt catalysts give some selectivity to glyceric acid, but the main reaction products are considered to be non-desired C1 by-products, e.g. CO2, HCHO and HCOOH. In addition, under these conditions, supported Au catalysts were totally inactive. Using an autoclave with pure oxygen at 3 bar pressure gave a significant improvement in reactivity and, for Pt and Au catalysts, the formation of C1 by-products was eliminated when NaOH was added. In particular, it was noted that, in the absence of NaOH, the Au/C catalyst was inactive. For 1 wt.% Au/graphite or activated carbon, 100% selectivity to glyceric acid at high conversion was readily achieved. The role of the base is discussed and it is proposed that the base aids the initial dehydrogenation via H-abstraction of one of the primary OH groups of glycerol and, in this way, the rate limiting step in the oxidation process is overcome.

Biocide use and antibiotic resistance: the relevance of laboratory findings to clinical and environmental situations

Abstract: Antibiotics are used as chemotherapeutic drugs, and biocides are used as antiseptics, disinfectants, and preservatives. Several factors affect biocidal activity, notably concentration, period of contact, pH, temperature, the presence of interfering material, and the types, numbers, location, and condition of microorganisms. Bacterial cells as part of natural or artificial (laboratory) biofilm communities are much less susceptible than planktonic cells to antibiotics and biocides. Assessment of biocidal activity by bactericidal testing is more relevant than by determination of minimum inhibitory concentrations. Biocides and antibiotics may show some similarities in their mechanisms of action and common mechanisms of bacterial insusceptibility may apply, but there are also major differences. In the laboratory, bacteria can become less susceptible to some biocides. Decreased resistance may be stable or unstable and may be accompanied by a low-level increase in antibiotic resistance. Laboratory studies are useful for examining stress responses and basic mechanisms of action and of bacterial insusceptibility to antibacterial agents. Translation of such findings to the clinical and environmental situations to provide evidence of a possible relation between biocide use and clinical antibiotic resistance is difficult and should be viewed with caution.

Belief, knowledge and expertise: the emergence of the lay expert in medical sociology.

Abstract: The paper has three main aims. First, to trace--through the pages of Sociology of Health and Illness--the changing ways in which lay understandings of health and illness have been represented during the 1979-2002 period. Second, to say something about the limits of lay knowledge (and particularly lay expertise) in matters of health and medicine. Third, to call for a re-assessment of what lay people can offer to a democratised and customer-sensitive system of health care and to attempt to draw a boundary around the domain of expertise. In following through on those aims, the author calls upon data derived from three current projects. These latter concern the diagnosis of Alzheimer's disease in people with Down's syndrome; the development of an outcome measure for people who have suffered a traumatic brain injury; and a study of why older people might reject annual influenza vaccinations.

Origin of ocean island basalts: A new perspective from petrology, geochemistry, and mineral physics considerations

Abstract: Consideration of petrology, geochemistry, and mineral physics suggests that ancient subducted oceanic crusts cannot be the source materials supplying ocean island basalts (OIB). Melting of oceanic crusts cannot produce high-magnesian OIB lavas. Ancient oceanic crusts (>1 Ga) are isotopically too depleted to meet the required values of most OIB. Subducted oceanic crusts that have passed through subduction zone dehydration are likely to be depleted in water-soluble incompatible elements (e.g., Ba, Rb, Cs, U, K, Sr, Pb) relative to water-insoluble incompatible elements (e.g., Nb, Ta, Zr, Hf, Ti). Melting of residual crusts with such trace element composition cannot produce OIB. Oceanic crusts, if subducted into the lower mantle, will be >2% denser than the ambient mantle at shallow lower mantle depths. This negative buoyancy will impede return of the subducted oceanic crusts into the upper mantle. If subducted oceanic crusts melt at the base of the mantle, the resultant melts are even denser than the ambient peridotitic mantle, perhaps by as much as similar to15%. Neither in the solid state nor in melt form can bulk oceanic crusts subducted into the lower mantle return to upper mantle source regions of oceanic basalts. Deep portions of recycled oceanic lithosphere are important geochemical reservoirs hosting volatiles and incompatible elements as a result of metasomatism taking place at the interface between the low-velocity zone and the cooling and thickening oceanic lithosphere. These metasomatized and recycled deep portions of oceanic lithosphere are the most likely candidates for OIB sources in terms of petrology, geochemistry and mineral physics.

Neural transplantation for the treatment of Parkinson's disease.

Abstract: trials showed unequivocally that human fetal dopaminergicneurons can survive and function for more than 10 years inthe striatum of patients with PD and show no signs of beingaffected by the ongoing disease process. These studies have also provided a clear indication that grafted fetaldopaminergic neurons can be therapeutically effective. On thebasis of the limited, but encouraging, observations in theseearly open-label trials,