971 research outputs found

    Effective risk governance for environmental policy making: a knowledge management perspective

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    Effective risk management within environmental policy making requires knowledge on natural, economic and social systems to be integrated; knowledge characterised by complexity, uncertainty and ambiguity. We describe a case study in a (UK) central government department exploring how risk governance supports and hinders this challenging integration of knowledge. Forty-five semi-structured interviews were completed over a two year period. We found that lateral knowledge transfer between teams working on different policy areas was widely viewed as a key source of knowledge. However, the process of lateral knowledge transfer was predominantly informal and unsupported by risk governance structures. We argue this made decision quality vulnerable to a loss of knowledge through staff turnover, and time and resource pressures. Our conclusion is that the predominant form of risk governance framework, with its focus on centralised decision-making and vertical knowledge transfer is insufficient to support risk-based, environmental policy making. We discuss how risk governance can better support environmental policy makers through systematic knowledge management practices

    City of clones: Facsimiles and governance in Sao Paulo, Brazil

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    SĆ£o Paulo is a megacity defined by formal and informal patterns of urbanization. Informally urbanized spaces are not absent of state intent, despite appearances. Grassroots-led social and spatial practices for survival, agency and self-governance contribute to the reproduction of urban political order in surprisingly unoriginal and routinely recognizable ways. This article argues that these unexceptional informal practices can be understood as ā€˜facsimilesā€™ of their formal institutional originals. Using the example of cloned cars the article shows that the facsimile and the original are the same in form and function. Facsimiles do not exist outside of political authority, but are a byproduct and a component of it. They are indistinguishable in their bureaucratic deployment, recognition and acceptance as part of social and spatial order. This is the author accepted manuscript. The final version is available from Sage via https://doi.org/10.1177/001139211665729

    Potentiated virucidal activity of pomegranate rind extract (PRE) and punicalagin against Herpes simplex virus (HSV) when co-administered with zinc (II) ions, and antiviral activity of PRE against HSV and aciclovir-resistant HSV

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    Background There is a clinical need for new therapeutic products against Herpes simplex virus (HSV). The pomegranate, fruit of the tree Punica granatum L, has since ancient times been linked to activity against infection. This work probed the activity of pomegranate rind extract (PRE) and co-administered zinc (II) ions. Materials and methods PRE was used in conjunction with zinc (II) salts to challenge HSV-1 and aciclovir-resistant HSV in terms of virucidal plaque assay reduction and antiviral activities in epithelial Vero host cells. Cytotoxicity was determined by the MTS assay using a commercial kit. Results Zinc sulphate, zinc citrate, zinc stearate and zinc gluconate demonstrated similar potentiated virucidal activity with PRE against HSV-1 by up to 4-fold. A generally parabolic relationship was observed when HSV-1 was challenged with PRE and varying concentrations of ZnSO4, with a maximum potentiation factor of 5.5. Punicalagin had 8-fold greater virucidal activity than an equivalent mass of PRE. However, antiviral data showed that punicalagin had significantly lower antiviral activity compared to the activity of PRE (EC50 = 0.56 Ī¼g mL-1) a value comparable to aciclovir (EC50 = 0.18 Ī¼g mL-1); however, PRE also demonstrated potency against aciclovir-resistant HSV (EC50 = 0.02 Ī¼g mL-1), whereas aciclovir showed no activity. Antiviral action of PRE was not influenced by ZnSO4. No cytotoxicity was detected with any test solution. Conclusions The potentiated virucidal activity of PRE by coadministered zinc (II) has potential as a multi-action novel topical therapeutic agent against HSV infections, such as coldsores

    Bacillus subtilis vegetative isolate surviving chlorine dioxide exposure: an elusive mechanism of resistance

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    Aims Oxidizing agents such as chlorine dioxide are widely used microbicides, including for disinfection of medical equipment. We isolated a Bacillus subtilis isolate from a washer-disinfector whose vegetative form demonstrated unique resistance to chlorine dioxide (0Ā·03%) and hydrogen peroxide (7Ā·5%). The aim of this study was to understand the mechanisms of resistance expressed by this isolate. Methods and Results A range of resistance mechanisms were investigated in the B. subtilis isolate and a reference B. subtilis strain (ATCC 6051) to include bacterial cell aggregation, the presence of profuse exopolysaccharide (EPS), and the expression of detoxification enzymes. The basis of resistance of the isolate to high concentrations of oxidizing agents was not linked to the presence of endospores. Although, the presence of EPS, aggregation and expression of detoxification enzymes may play a role in bacterial survival to low concentrations of chlorine dioxide, it is unlikely that the mechanisms helped tested to survive the bactericidal effect of higher oxidizer concentrations. Conclusions Overall, the mechanisms conferring resistance to chlorine dioxide and hydrogen peroxide remains elusive. Based on recent advances in the mode of action of oxidizing agents and notably hydrogen peroxide, we postulate that additional efficient intracellular mechanisms may be involved to explain significant resistance to in-use concentrations of commonly used high-level disinfectants

    New approaches to social skills training: Blended group interventions for girls with social communication difficulties

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    Social skills group interventions are increasing popular for children with social communication disorders but there is little evidence of their acceptability or effectiveness when delivered online. We report a feasibility study that adapted the Program for Education and Enrichment of Relational Skills (PEERS) to provide an intensive 8 week online delivery to female adolescents, blended with some faceā€toā€face group meetings. A systematic multipleā€case series design with case tracking was developed, comprising a 3ā€month baseline, a 2ā€month intervention and a 3ā€month followā€up period. Seven adolescents with Turner Syndrome and social communication difficulties (17ā€“20ā€‰years) took part, together with their parents. Acceptability and feasibility were assessed by means of qualitative feedback and attendance rates. Changes in social adaptation were tracked using measures of social knowledge, social behaviour and autistic symptoms, plus anxiety and selfā€esteem. Attendance rates were consistently high and there were no dropouts. Qualitative feedback indicated the online format was acceptable to both the participants and their families. Objective outcome measures showed significant gains in social knowledge and improved social initiations from measures made during the preā€intervention baseline. This proofā€ofā€principle pilot study demonstrated blended social skills interventions are both feasible and acceptable to adolescent females with social communication difficulties

    In vitro permeation and biological activity of punicalagin and zinc (II) across skin and mucous membranes prone to Herpes simplex virus infection

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    Coadministration of pomegranate rind extract (PRE) and zinc (II) ions has recently been reported as a potential new topical treatment for Herpes simplex virus (HSV) infections. In the current work we examined the in vitro topical delivery of punicalagin (major phytochemical of PRE) and zinc from hydrogels across epithelial membranes that can become infected with HSV. Porcine epidermal, buccal and vaginal mucous membranes were excised and mounted in Franz diffusion cells and dosed with a simple hydrogel containing PRE and zinc sulphate (ZnSO4). The permeation of punicalagin and zinc were determined by HPLC and ICPMS respectively; punicalagin was also determined in the basal layers by reverse tape stripping. Receptor phases from the epidermal membrane experiment were also used to challenge HSV-1 in Vero host cells, and ex vivo porcine skin was used to probe COX-2 modulation. Punicalagin and zinc permeated each of the three test membranes, with significantly greater amounts of both delivered across the epidermal membrane. The amounts of punicalagin permeating the buccal and vaginal membranes were similar, although the amount of zinc permeating the vaginal membrane was comparatively very large ā€“ it is known that zinc interacts with vaginal mucosa. The punicalagin recovered by reverse tape stripping of the epidermal, buccal and vaginal membranes gave 0.47 Ā± 0.016, 0.45 Ā± 0.052 and 0.51 Ā± 0.048 nM cmāˆ’ 2 respectively, and were statistically the same (p < 0.05). A 2.5 log reduction was achieved against HSV-1 using diffusion cell receptor phase, and COX-2 expression was reduced by 64% in ex vivo skin after 6 h. Overall, a hydrogel containing 1.25 mg mLāˆ’ 1 PRE and 0.25 M ZnSO4 was able to topically deliver both the major bioactive compound within PRE and Zn (II) across all membranes and into the site specific region of Herpes simplex vesicular clusters, while maintaining potentiated virucidal and anti-inflammatory properties. This novel therapeutic system therefore has potential for the topical treatment of HSV infections

    The role of framing mechanisms in explaining system wide change: the case of the Northern Ireland conflict and peace process

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    System-wide change is often challenging to achieve due to complex and fragmented institutions, dispersed and diffused power structures, confidence sapping histories of failure and the influence of multiple and over-lapping fields. This study examines how a large complex system wide problem such as the Northern Ireland Conflict and Peace Process was paradoxically opened up and made more receptive to change by widening of the way the problem was framed. We demonstrate how and why the framing enables the mobilisation of cooperation and the delivery of contextually appropriate collective action critical to the achievement of outcomes in system wide change processes. More specifically, we examine how and why such complex and precarious processes emerge over extended timescales through four mechanisms: frame contesting, reframing, frame reproduction and frame defending. Each of these mechanisms is agentic, dynamic, purposive and politically charged. The time series analysis of these interlinked mechanisms is a crucial and innovative feature of the study. We encourage management and organizational scholars to elevate their gaze to system-wide changes so emblematic of contemporary society and offer an outline agenda for research

    Pharmacological characterization of the Ī±vĪ²6 integrin binding and internalization kinetics of the foot-and-mouth disease virus derived peptide A20FMDV2

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    A20FMDV2 is a peptide derived from the foot-and-mouth disease virus with a high affinity and selectivity for the alphav beta-6 (Ī±vĪ²6) arginyl-glycinyl-aspartic acid (RGD)-binding integrin. It has been shown to be an informative tool ligand in pre-clinical imaging studies for selective labelling of the Ī±vĪ²6 integrin in a number of disease models. In a radioligand- binding assay using a radiolabelled form of the peptide ([3H]A20FMDV2), its high affinity (KD:0.22nmol/l) and selectivity (at least 85-fold) for Ī±vĪ²6 over the other members of the RGD integrin family was confirmed. [3H]A20FMDV2 Ī±vĪ²6 binding could be fully reversed only in the presence of EDTA, whereas a partial reversal was observed in the presence of excess concentrations of an RGD-mimetic small molecule (SC-68448) or unlabelled A20FMDV2. Using flow cytometry on bronchial epithelial cells, the ligand-induced internalization of Ī±vĪ²6 by A20FMDV2 and LAP1 was shown to be fast (t1/2:1.5and 3.1 min, respectively), concentration-dependent (EC50:values 1.1 and 3.6nmol/l, respectively) and was followed by a moderately slow return of integrin to the surface. The results of the radioligand-binding studies suggest that the binding of A20FMDV2 to the RGD-binding site on Ī±vĪ²6 is required to maintain its engagement with the hypothesised A20FMDV2 synergy site on the integrin. In addition, there is evidence from flow cytometric studies that the RGD-ligand engagement of Ī±vĪ²6 post-internalization plays a role in delaying recycling of the integrin to the cell surface. This mechanism may act as a homeostatic control of membrane Ī±vĪ²6 following RGD ligand engagement
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