An investigation into effects of long-distance seed dispersal on organelle population genetic structure and colonization rate: a model analysis

A simulation-based modelling approach is used to examine the effects of stratified seed dispersal (representing the distribution of the majority of dispersal around the maternal parent and also rare long-distance dispersal) on the genetic structure of maternally inherited genomes and the colonization rate of expanding plant populations. The model is parameterized to approximate postglacial oak colonization in the UK, but is relevant to plant populations that exhibit stratified seed dispersal. The modelling approach considers the colonization of individual plants over a large area (three 500 km x 10 km rolled transects are used to approximate a 500 km x 300 km area). Our approach shows how the interaction of plant population dynamics with stratified dispersal can result in a spatially patchy haplotype structure. We show that while both colonization speeds and the resulting genetic structure are influenced by the characteristics of the dispersal kernel, they are robust to changes in the periodicity of long-distance events, provided the average number of long-distance dispersal events remains constant. We also consider the effects of additional physical and environmental mechanisms on plant colonization. Results show significant changes in genetic structure when the initial colonization of different haplotypes is staggered over time and when a barrier to colonization is introduced. Environmental influences on survivorship and fecundity affect both the genetic structure and the speed of colonization. The importance of these mechanisms in relation to the postglacial spread and genetic structure of oak in the UK is discussed.

Transdermal delivery of a tetrapeptide: Evaluation of passive diffusion

Skin penetration of the tetrapeptide Ac-Ala-Ala-Pro-Val-NH2 was assessed. This peptide sequence fits the P-P-1 subsites of elastase and inhibits human neutrophil elastase competitively. Consequently this peptide may be therapeutically useful in a variety of inflammatory disorders, including psoriasis. in which elevated levels of human neutrophil elastase have been reported. Peptide penetration was assessed across whole human skin, whole skin with the stratum corneum removed by tape stripping and epidermis, which had been removed from the dermis by heat separation. The influence of 75% aqueous ethanol as a potential penetration enhancer of the tetrapeptide across epidermis was also assessed. The tetrapeptide did not penetrate whole human skin or epidermis, even under the influence of 75% aqueous ethanol. However, when the stratum corneum was removed tetrapeptide flux of 73.39 mug cm(-2) h(-1) was achieved. The study demonstrates that the stratum corneum is the main barrier to tetrapeptide skin penetration and must be overcome if therapeutically relevant amounts of tetrapeptide are to be delivered to the skin.

Social inclusion, new regionalism and associational governance: The Queensland experience

In recent years there has been a resurgence of decentralized social governance concerned with the spatial dimensions of disadvantage. This article examines aspects of this resurgence in the Australian state of Queensland where, after the hasty birth of 'place management' in response to the rise of 'Hansonism', a plethora of 'joined-up' policy initiatives were undertaken in relation to the regional dimensions of poverty. We propose that these trends reflect in part new ways of thinking about the spatial aspects of disadvantage which have emerged in recent years and which have the potential to take regional policy beyond the narrow confines imposed by neoliberal economic orthodoxy. These new ways of thinking have arisen in social policy through the refraining of disadvantage in terms of social exclusion and in regional economic policy through the influence of the so-called 'new regionalism'. The article shows how together these bodies of theory point us towards a new model of 'associational governance'. The article reviews recent Queensland experience and indicates those features of 'associational governance' which have become characteristic of locality-based social policy ideas in Queensland. 'Joined-up' and regional policy aspirations of the Queensland State government have shown the influence of these new approaches. The political and policy sustainability of these trends, however, is uncertain. The lingering shadow of managerialism and neoliberal policy frameworks remains a significant barrier to the innovation and viability of these approaches. More directly, the inherent limits of the 'local' or 'regional' initiatives in the face of broader national and global factors will significantly constrain the capacity of associational governance systems to deliver positive democratic, social and economic outcomes. The article examines recent Queensland policy refors in light of this complex set of factors and concludes by offering directions for future research and policy development.

A survey of e-mentoring among New Zealand midwives

Mentoring is a strategy that may assist the midwifery profession to support new graduates and midwives working in rural and remote areas. We conducted a survey of 1577 New Zealand midwives about their opinions and experiences of mentoring. The questionnaire comprised 33 questions, nine of which were open questions. There was a 44% response rate. While the telephone was commonly utilized by mentors (37%) and mentored midwives (37%), the Internet and email played only a small part. Participants acknowledged the potential of these avenues for communication, but midwives felt that mentoring could be provided only by immediate, face-to-face contact. Nevertheless, e-mentoring could be a viable option and requires further investigation. About one-third of midwives identified geographical isolation as a barrier to being a mentor (38%) and being mentored (36%). The use of e-mentoring could remove the barrier of location and allow the midwife to chose a mentor who meets her needs, rather than because she is the only mentor available.

Public and private psychiatry: Can they work together and is it worth the effort?

Objective: Partnerships in mental health care, particularly between public and private psychiatric services, are being increasingly recognized as important for optimizing patient management and the efficient organization of services. However, public sector mental health services and private psychiatrists do not always work well together and there seem to be a number of barriers to effective collaboration. This study set out to investigate the extent of collaborative 'shared care' arrangements between a public mental health service and private psychiatrists practising nearby. It also examined possible barriers to collaboration and some possible solutions to the identified problems. Method: A questionnaire examining the above factors was sent to all public sector mental health clinicians and all private psychiatrists in the area. Results: One hundred and five of the 154 (68.2%) public sector clinicians and 103 of the 194 (53.1%) private psychiatrists returned surveys. The main barriers to successful collaboration identified by members of both sectors were: 'Difficulty communicating' endorsed by 71.4% of public clinicians and 72% of private psychiatrists, 'Confusion of roles and responsibilities' endorsed by 62.9% and 66%, respectively, and 'Different treatment approach' by 47.6% and 45.6%, respectively. Over 60% of private psychiatrists identified problems with access to the public system as a barrier to successful shared care arrangements. It also emerged, as hypothesized, that the public and private systems tend to manage different patient populations and that public clinicians in particular are not fully aware of the private psychiatrists' range of expertise. This would result in fewer referrals for shared care across the sectors. Conclusions: A number of barriers to public sector clinicians and private psychiatrists collaborating in shared care arrangements were identified. The two groups surveyed identified similar barriers. Some of these can potentially be addressed by changes to service systems. Others require cultural shifts in both sectors. Improved communications including more opportunities for formal and informal meetings between people working in the two sectors would be likely to improve the understanding of the complementary sector's perspective and practice. Further changes would be expected to require careful work between the sectors on training, employment and practice protocols and initiatives, to allow better use of the existing services and resources.

Effectiveness of topical skin care provided in aged care facilities

Background The 2001 Australian census revealed that adults aged 65 years and over constituted 12.6% of the population, up from 12.1% in 1996. It is projected that this figure will rise to 21% or 5.1 million Australians by 2031. In 1998, 6% (134 000) of adults in Australia aged 65 years and over were residing in nursing homes or hostels and this number is also expected to rise. As skin ages, there is a decreased turnover and replacement of epidermal skin cells, a thinning subcutaneous fat layer and a reduced production of protective oils. These changes can affect the normal functions of the skin such as its role as a barrier to irritants and pathogens, temperature and water regulation. Generally, placement in a long-term care facility indicates an inability of the older person to perform all of the activities of daily living such as skin care. Therefore, skin care management protocols should be available to reduce the likelihood of skin irritation and breakdown and ultimately promote comfort of the older person. Objectives The objective of this review was to determine the best available evidence for the effectiveness and safety of topical skin care regimens for older adults residing in long-term aged care facilities. The primary outcome was the incidence of adverse skin conditions with patient satisfaction considered as a secondary outcome. Search strategy A literature search was performed using the following databases: PubMed (NLM) (1966–4/2003), Embase (1966–4/2003), CINAHL (1966–4/2003), Current Contents (1993–4/2003), Cochrane Library (1966–2/2003), Web of Science (1995–12/2002), Science Citation Index Expanded and ProceedingsFirst (1993–12/2002). Health Technology Assessment websites were also searched. No language restrictions were applied. Selection criteria Systematic reviews of randomised controlled trials, randomised and non-randomised controlled trials evaluating any non-medical intervention or program that aimed to maintain or improve the integrity of skin in older adults were considered for inclusion. Participants were 65 years of age or over and residing in an aged care facility, hospital or long-term care in the community. Studies were excluded if they evaluated pressure-relieving techniques for the prevention of skin breakdown. Data collection and analysis Two independent reviewers assessed study eligibility for inclusion. Study design and quality were tabulated and relative risks, odds ratios, mean differences and associated 95% confidence intervals were calculated from individual comparative studies containing count data. Results The resulting evidence of the effectiveness of topical skin care interventions was variable and dependent upon the skin condition outcome being assessed. The strongest evidence for maintenance of skin condition in incontinent patients found that disposable bodyworn incontinence protection reduced the odds of deterioration of skin condition compared with non-disposable bodyworns. The best evidence for non-pressure relieving topical skin care interventions on pressure sore formation found the no-rinse cleanser Clinisan to be more effective than soap and water at maintaining healthy skin (no ulcers) in elderly incontinent patients in long-term care. The quality of studies examining the effectiveness of topical skin care interventions on the incidence of skin tears was very poor and inconclusive. Topical skin care for prevention of dermatitis found that Sudocrem could reduce the redness of skin compared with zinc cream if applied regularly after each pad change, but not the number of lesions. Topical skin care on dry skin found the Bag Bath/Travel Bath no-rinse skin care cleanser to be more effective at preventing overall skin dryness and most specifically flaking and scaling when compared with the traditional soap and water washing method in residents of a long-term care facility. Information on the safety of topical skin care interventions is lacking. Therefore, because of the lack of evidence, no recommendation on the safety on any intervention included in this review can be made.

Epidermal penetration of a therapeutic peptide by lipid conjugation; Stereo-selective peptide availability of a topical diastereomeric lipopeptide

In inflammatory disorders (e.g. psoriasis), local concentrations of human neutrophil elastase (HNE), also known as polymorphonuclear leukocyte elastase (HLE), possibly overwhelm its natural inhibitors leading to extracellular matrix degradation. Elevated levels of HNE have been reported in a variety of inflammatory disorders, including psoriasis. Peptidic HNE inhibitors have a common hydrophobic sequence (Ala-Ala-Pro-Val). This peptide sequence inhibits HNE competitively; however the stratum corneum presents an effective barrier to the delivery of this tetrapeptide across the skin. The current work investigates the delivery of the modified peptide whereby the tetrapeptide was lipidated to enhance its ability to penetrate the stratum The tetrapeptide Was Coupled to a racaemic mixture of a short chain lipoamino acid (LAA) resulting in two diastereomers of the lipoamino acid-modified tetrapeptide. The penetration of the lipopeptide mixture was assessed across human epidermis in vitro. The percentage of applied dose penetrating to the receptor over 8 h following administration was 2.53% for the D-LAA conjugate and 1.47% for the L-diastereomer, compared to 0% for the peptide. The D-diastereomer appears to be relatively stable but the L-diastereomer appears to degrade releasing possibly the tetrapeptide and peptide fragment(s). Therefore the results clearly indicate that coupling the tetrapeptide to a short chain LAA enhances its delivery across human epidermis.

Knots in rings - The circular knotted protein momordica cochinchinensis trypsin inhibitor-II folds via a stable two-disulfide intermediate

The aim of this work was to elucidate the oxidative folding mechanism of the macrocyclic cystine knot protein MCoTI-II. We aimed to investigate how the six-cysteine residues distributed on the circular backbone of the reduced unfolded peptide recognize their correct partner and join up to form a complex cystine-knotted topology. To answer this question, we studied the oxidative folding of the naturally occurring peptide using a range of spectroscopic methods. For both oxidative folding and reductive unfolding, the same disulfide intermediate species was prevalent and was characterized to be a native-like two-disulfide intermediate in which the Cys(1)-Cys(18) disulfide bond was absent. Overall, the folding pathway of this head-to-tail cyclized protein was found to be similar to that of linear cystine knot proteins from the squash family of trypsin inhibitors. However, the pathway differs in an important way from that of the cyclotide kalata B1, in that the equivalent two-disulfide intermediate in that case is not a direct precursor of the native protein. The size of the embedded ring within the cystine knot motif appears to play a crucial role in the folding pathway. Larger rings contribute to the independence of disulfides and favor an on-pathway native-like intermediate that has a smaller energy barrier to cross to form the native fold. The fact that macrocyclic proteins are readily able to fold to a complex knotted structure in vitro in the absence of chaperones makes them suitable as protein engineering scaffolds that have remarkable stability.

Mutations within the selectivity filter of the NMDA receptor-channel influence voltage dependent block by 5-hydroxytryptamine

Background and purpose: Voltage-dependent block by Mg2+ is a cardinal feature of NMDA receptors which acts as a coincidence detector to prevent the receptor from over-activation. Inhibition of NMDA receptor currents by 5-hydroxytryptamine (5-HT) indicated that 5-HT, similar to Mg2+, binds within the membrane electric field. In the present study, we assessed whether point mutations of critical asparagine residues located within the selectivity filter of NR1 and NR2A subunits of NMDA receptor-channel affect voltage-dependent block by 5-HT. Experimental approach: The mode of action of 5-HT and Mg2+ on wild-type and mutated NMDA receptor-channels expressed in Xenopus oocytes was investigated using the two-electrode voltage clamp recording technique. Key results: The mutation within the NR1 subunit NR1(N0S or N0Q) strongly reduced the voltage dependent block by 5-HT and increased the IC50. The corresponding mutations within the NR2 subunits NR2A(N0Q or N + 1Q) reduced the block by 5-HT to a lesser extent. This is in contrast to the block produced by external Mg2+ where a substitution at the NR2A(N0) and NR2A(N + 1) sites but not at the NR1(N0) site significantly reduced Mg2+ block. Conclusion and implications: The block of NMDA receptor-channels by 5-HT depends on the NR1-subunit asparagine residue and to a lesser extent on the NR2A-subunit asparagine residues. These data suggest that the interaction of 5-HT with functionally important residues in a narrow constriction of the pore of the NMDA receptor-channel provides a significant barrier to ionic fluxes through the open channel due to energetic factors governed by chemical properties of the binding site and the electric field.

Phosphorus nutrition of Caustis blakei grown with two phosphorus sources of different solubility in two soils of differing phosphorus adsorption capacity

A barrier to the domestication of the phosphorus (P) sensitive Australian species Caustis blakei (Cyperaceae) is the standard production systems used commercially which invariably result in problems associated either with P deficiency or P toxicity. This paper reports on the growth responses of Caustis blakei cv. M63 to applications of fertiliser P as either monocalcium phosphate (MCP) or granulated Guano Gold (R) rock phosphate (RP) in two soils with different capacities to adsorb P. The Caustis M63 plants grown in the two soils did not show P toxicity symptoms when fertilised with RP, but shoot dry weight was 30-60% lower than the control in both soils at the highest rate of MCP-P application (156 kg ha(-1), 184 g m(-3)) and this was associated with visible symptoms of drying of the tips of the ultimate branchlets, in the Mt Cotton soil only. The greatest shoot and root dry weights were achieved by plants grown in the higher P adsorbing Palmwoods soil fertilised with RP at P rates of 30-184 g m(-3). Caustis plants grown in the Palmwoods soil had 2.3 times greater root dry weights than plants grown in the Mt Cotton soil irrespective of the P fertiliser type used. Caustis plants growing in Mt Cotton soil which did not receive P showed significantly lower shoot and root dry weight when compared to plants in the Palmwoods soil, probably due to the low initial bicarbonate-extractable P and the high buffering capacity of the Mt Cotton soil. The P concentration in shoots of Caustis fertilised with MCP at 184 g m(-3) was higher when grown in Mt Cotton soil (0.22%) than in the Palmwoods soil (0.15%). The P concentration was lower in the terminal ultimate branchlets (TUB); 0.15% for the Mt Cotton soil and 0.10% for the Palmwoods soil, suggesting that shoots would provide a more useful indicator of P toxicity than the TUB. It is interesting to speculate as to why plants in the Palmwoods soil showed greater root growth and fewer symptoms of P toxicity. This could be because the Palmwoods soil had the greater P adsorption capacity. These results indicate in ground production of Caustis cut foliage will require careful management of P nutrition and understanding of the complex soil/plant interactions associated with the acquisition of P. (c) 2006 Elsevier B.V. All rights reserved.

Knowledge, perceptions and expectations of nurses in e-health: results of a survey in a children's hospital

We surveyed all nurses working at a tertiary paediatric hospital (except casual staff and those who were on leave) from 27 hospital departments. A total of 365 questionnaires were distributed. There were 40 questions in six sections: demographic details, knowledge of e-health, relevance of e-health to nursing profession, computing skills, Internet use and access to e-health education. A total of 253 surveys were completed (69%). Most respondents reported that that they had never had e-health education of any sort (87%) and their e-health knowledge and skills were low (71%). However, 11% of nurses reported some exposure to e-health through their work. Over half (56%) of respondents indicated that e-health was important, very important or critical for health professions while 26% were not sure. The lack of education and training was considered by most respondents (71%) to be the main barrier to adopting e-health. While nurses seemed to have moderate awareness of the potential benefits of e-health, their practical skills and knowledge of the topic were very limited.

Local skirmishes in the contruction of (global) digital business communication technologies

This paper applies Latour’s 1992 translation map as a device to explore the development of and recent conflict between two data standards for the exchange of business information – EDIFACT and XBRL. Our research is focussed in France, where EDIFACT is well established and XBRL is just emerging. The alliances supporting both standards are local and global. The French/European EDIFACT is promulgated through the United Nations while a consortium of national jurisdictions and companies has coalesced around the US initiated XBRL International (XII). We suggest cultural differences pose a barrier to co-operation between the two networks. Competing data standards create the risk of switching costs. The different technical characteristics of the standards are identified as raising implications for regulators and users. A key concern is the lack of co-ordination of data standard production and the mechanisms regulatory agencies use to choose platforms for electronic data submission.

The influence of excipients on the diffusion of ibuprofen and paracetamol in gastric mucus

The aim of this study was to examine the diffusion of commonly administered analgesics, ibuprofen and paracetamol, through gastric mucus. As ibuprofen and paracetamol are often formulated with alkalising excipients, or are commonly co-administered with antacids that have been demonstrated to alter their absorption, diffusion was also studied in the presence of a range of soluble and insoluble antacids or buffering agents. The effect of pH, which has been demonstrated to modify the properties of mucus, was also studied. Mucus was a significant barrier to diffusion for both drugs, compared to an unstirred aqueous layer with diffusion rates significantly lower in the presence of a mucus barrier for both drugs; ibuprofen diffusion also demonstrated a significant increase in the lag time. Paracetamol diffusion was not significantly affected by addition of any antacid, whereas ibuprofen rates were affected and the diffusion lag time for ibuprofen was significantly reduced in all cases. Isolated increases in pH increased the rate and reduced the lag time for ibuprofen diffusion. It was shown that mucus acts as a passive barrier in the case of paracetamol diffusion, and an interactive barrier to ibuprofen diffusion. Changes in mucus viscosity at different pH values may be responsible for the observed changes in ibuprofen diffusion rate. © 2004 Elsevier B.V. All rights reserved.

The training experience of primary care pharmacists

Objectives — To map the tasks, activities and training provision for primary care pharmacists (PCPs) and to identify perceived future training needs. Methods — Survey undertaken in 1998/1999 using a pre-piloted, postal, self-completion questionnaire to two samples of PCPs. Setting — PCPs in (a) the West Midlands and (b) England (outside West Midlands). Key findings — The response rate was 66 per cent. A majority (68 per cent) had worked in the role for less than two years. Eighty per cent had some form of continuing education or training for the role although only 50 per cent had a formal qualification. Over two-thirds had contributed to the funding of their training, with one-third providing all funding. Seventy-four per cent of PCPs agreed that pharmacists should go through a procedure to ensure competence (accreditation) before being allowed to work for a general medical practice or primary care group. Views on the need for formal education/training prior to work differed: 82 per cent of those with formal qualifications, but only 46 per cent of those without, considered that this should be a requirement. There was general agreement that training/education had met training needs. Views on future training closely reflected previous training experiences, with a focus upon pharmaceutical roles rather than upon generic skill development and the acquisition of management skills. Conclusions — The study provides a snapshot in time of the experience of pioneer PCPs and the training available to them. PCPs will need further training or updating if they are to provide the wider roles required by the developing needs of the National Health Service. Consideration should be given to formal recognition of the training of PCPs in order to assure competence. The expectation that pharmacists should fund their own training is likely to be a barrier to uptake of training and uncertainties over funding will militate against consistency of training.

XBRL:an (open) source of enlightenment or disillusion?

Extensible Business Reporting Language (XBRL) is being adopted by European regulators as a data standard for the exchange of business information. This paper examines the approach of XBRL International (XII) to the meta-data standard's development and diffusion. We theorise the development of XBRL using concepts drawn from a model of successful open source projects. Comparison of the open source model to XBRL enables us to identify a number of interesting similarities and differences. In common with open source projects, the benefits and progress of XBRL have been overstated and 'hyped' by enthusiastic participants. While XBRL is an open data standard in terms of access to the equivalent of its 'source code' we find that the governance structure of the XBRL consortium is significantly different to a model open source approach. The barrier to participation that is created by requiring paid membership and a focus on transacting business at physical conferences and meetings is identified as particularly critical. Decisions about the technical structure of XBRL, the regulator-led pattern of adoption and the organisation of XII are discussed. Finally areas for future research are identified.