Operationalising coastal resilience to flood and erosion hazard: A demonstration for England.

Resilience is widely seen as an important attribute of coastal systems and, as a concept, is increasingly prominent in policy documents. However, there are conflicting ideas on what constitutes resilience and its operationalisation as an overarching principle of coastal management remains limited. In this paper, we show how resilience to coastal flood and erosion hazard could be measured and applied within policy processes, using England as a case study. We define resilience pragmatically, integrating what is presently a disparate set of policy objectives for coastal areas. Our definition uses the concepts of resistance, recovery and adaptation, to consider how the economic, social and environmental dimensions of coastal systems respond to change. We develop a set of composite indicators for each dimension, grounded empirically with reference to national geospatial datasets. A prototype Coastal Resilience Model (CRM) has been developed, which combines the dimensions and generates a quantitative resilience index. We apply it to England's coastal hazard zone, capturing a range of different stakeholder perspectives using relative indicator weightings. The illustrative results demonstrate the practicality of formalising and quantifying resilience. To re-focus national policy around the stated desire of enhancing resilience to coastal flooding and erosion would require firm commitment from government to monitor progress towards resilience, requiring extension of the present risk-based approach, and a consensus methodology in which multiple (and sometimes conflicting) stakeholder values are explicitly considered. Such a transition may also challenge existing governance arrangements at national and local levels, requiring incentives for coastal managers to engage with and apply this new approach, more departmental integration and inter-agency cooperation. The proposed Coastal Resilience Model, with the tools to support planning and measure progress, has the potential to help enable this transition.

Hand hygiene practices of veterinary support staff in small animal private practice.

OBJECTIVE: To evaluate the hand hygiene (HH) practices among veterinary technicians (VT) and veterinary support staff (VSS) in small animal private practice. METHODS: This was a prospective questionnaire-based study involving 182 VT and VSS from 18 small animal hospitals in the USA. Questions asked included gender, number of animals handled per work shift, frequency of hand washing, reason for not washing more frequently, most common available hand washing agent, education regarding the importance of HH and frequency of ring wearing. RESULTS: Less than half of the respondents [76 of 182 (41·7%)] reported washing their hands regularly between handling patients and 154 of 182 (85·6%) believed they should have washed more frequently. The most commonly employed HH agent was hand soap [154 of 182 (84·6%)] and the most common reason cited for not washing more frequently was being too busy [132 of 182 (72·5%)]. Only 96 of 182 (52·7%) respondents were educated by doctors at their hospital regarding the importance of HH. CLINICAL SIGNIFICANCE: The HH practices among VT and VSS in small animal private practice is poor. Hand soap was the most commonly employed agent among respondents in this study. Education of VT and VSS regarding the importance of HH requires improvement.

DNA adducts: mass spectrometry methods and future prospects.

Detection of DNA adducts is widely used for the monitoring of exposure to genotoxic carcinogens. Knowledge of the nature and amounts of DNA adducts formed in vivo also gives valuable information regarding the mutational effects that may result from particular exposures. The power of mass spectrometry (MS) to achieve qualitative and quantitative analyses of human DNA adducts has increased greatly in recent years with the development of improved chromatographic interfaces and ionisation sources. Adducts have been detected on nucleic acid bases, 2'-deoxynucleosides or 2'-deoxynucleotides, with LC-MS/MS being the favoured technique for many of these analyses. Our current applications of this technique include the determination of N7-(2-carbamoyl-2-hydroxyethyl)-guanine, which was postulated to be found as a DNA repair product in urine following exposure to acrylamide, and of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8-dihydro-2'-deoxyadenosine, as markers of oxidative damage in human lymphocyte DNA. Higher sensitivity (with a detection limit of 1-10 adducts/10(12) nucleotides) may be achieved by the use of accelerator mass spectrometry (AMS), although this requires the presence of certain isotopes, such as [(14)C], in the material being analysed. In order to make this technique more amenable for studies of human exposure to environmental carcinogens, new postlabelling techniques, incorporating [(14)C] into specific DNA adducts after formation, are being developed. It is expected that combining the use of advanced MS techniques with existing (32)P-postlabelling and immunochemical methodologies will contribute greatly to the understanding of the burden of human exposure to environmental carcinogens.

Oltipraz concentrations in plasma, buccal mucosa cells, and lipids: pharmacological studies.

Oltipraz is considered one of the most potent cancer chemoprevention agents, as shown in preclinical studies. Its pharmacological effects in humans have been associated with unusual toxicity affecting the fingers and toes. This study was designed to test intermittent dosing schedules using two dosage levels: 500 mg as a single weekly dose and 200 mg as a biweekly dose, each for 30 days. Fifteen men and women were studied in each dosing group. All were heavy smokers considered to be at high risk for developing lung cancer. Plasma, buccal mucosa cell, and lipoprotein concentrations were measured at different intervals corresponding to the time period when most of the adverse effects occur. No serious toxicities were observed using these doses and schedules. The plasma and buccal mucosa cell concentrations of Oltipraz showed substantial interindividual variations at each sampling. Some subjects had no detectable plasma or buccal mucosal cell Oltipraz concentrations. The distribution of Oltipraz incorporation into the lipid fractions and albumin was changed by the administration of different schedules of Oltipraz. The results of this study suggest that the intermittent dosing is well tolerated and does not result in steady state in plasma or buccal mucosa cells. The variation and lack of detectable Oltipraz concentration in plasma, buccal mucosa cells, and lipids may affect both the toxicity and the pharmacological effects when these doses and schedules are used.

Coping with clinical site shortages.

The shrinking number of nursing clinical sites and the backlog of nursing students in generic programs waiting for clinical placement present major problems in nursing education. Positioning the clinical practicum of generic nursing programs in the final year of the curriculum is suggested. Advantages and disadvantages are discussed.

Site-directed mutagenesis--molecular biology and rational drug design.

Using site-directed mutagenesis, we have determined the location and composition of the binding sites in human IL-1 alpha and IL-1 beta for the Type I IL-1 receptor (IL-1R). The binding site in each ligand is a discontinuous epitope made up of at least seven amino acids whose side chains are exposed on a contiguous region of the protein surface. Although human IL-1 alpha and IL-1 beta have similar affinities and cross-compete for binding to the human Type I IL-1R, the binding site residues are not identical in the two ligands. In addition, the residues in the binding site of each ligand contribute differently to binding of the human versus the mouse IL-1R. The structure of the IL-1 binding site has implications for the rational design of IL-1 antagonists.

Structure-function analysis of human IL-1 alpha: identification of residues required for binding to the human type I IL-1 receptor.

Using oligonucleotide-directed mutagenesis, the binding site on human interleukin-1 alpha (IL-1 alpha) for the human type I IL-1 receptor (IL-1R) has been analyzed. Substitution of seven amino acids (Arg12, Ile14, Asp60, Asp61, Ile64, Lys96 and Trp109) resulted in a significant loss of binding to the receptor. Based on crystallographic information, the side chains of these residues are clustered in one region of IL-1 alpha and exposed on the surface of the protein. Five of the residues in the IL-1 alpha binding site align with the binding residues previously determined in human IL-1 beta, demonstrating that the type I IL-1R recognizes homologous regions in both ligands. Unexpectedly, only three of the aligned residues are identical between IL-1 alpha and IL-1 beta. These observations suggest that the composition of contact residues in the binding site is unique for each ligand-receptor complex in the IL-1 system.

Identification of the discontinuous binding site in human interleukin 1 beta for the type I interleukin 1 receptor.

Human interleukin 1 beta (IL-1 beta) exerts its diverse biological effects by binding to specific receptors on target cells. Two types of IL-1 receptor (IL-1R) have been identified: the type I IL-1R (p80) and the type II IL-1R (p68). Using site-specific mutagenesis, we have identified the binding site on IL-1 beta for the murine type I IL-1R. Analogs of the IL-1 beta protein containing defined amino acid substitutions were produced and tested for competitive binding to the two IL-1Rs. Substitutions of the amino acids at seven positions resulted in analogs that had greater than or equal to 100-fold reductions in competitive binding to the type I IL-1R, while maintaining substantial binding to the type II IL-1R. These seven amino acids (Arg-4, Leu-6, Phe-46, Ile-56, Lys-93, Lys-103, and Glu-105) are clustered in the IL-1 beta molecule, forming a discontinuous binding site. The side chains of all seven residues are exposed on the surface of IL-1 beta. The cumulative binding energies contributed by each of the residues predict a binding affinity that is consistent with the observed Kd of the wild-type protein for the type I IL-1R.

Conversion of the interleukin 1 receptor antagonist into an agonist by site-specific mutagenesis.

Interleukin 1 (IL-1) receptor antagonist (IL-1ra) is a naturally occurring protein that binds to the IL-1 receptor present on T cells, fibroblasts, and other cell types and acts to block IL-1-induced responses. IL-1ra is a pure antagonist and has no agonist activity in in vitro or in vivo systems. By site-specific mutagenesis, an analog of IL-1ra was created that contained a substitution of a single amino acid, Lys-145----Asp. This analog, IL-1ra K145D, exhibited partial agonist activity in the D10.G4.1 cell proliferation assay. The newly acquired agonist activity could not be neutralized by antisera to IL-1 alpha or IL-1 beta, but it could be blocked by a monoclonal antibody to the T-cell IL-1 receptor. The analog also showed agonist activity as assayed by increased prostaglandin E2 synthesis from CHO cells expressing recombinant mouse IL-1 receptor. These results with IL-1ra K145D demonstrate the importance of the region surrounding the corresponding Asp-145 residue in IL-1 beta for triggering the biological response to IL-1.

A comparative model of the psychological effects on the victims of state and anti-state terrorism.

This paper has examined and compared the psychological impact of both state and anti-state terrorism on the victim. In this regard, three dimensions to this issue were discussed: (a) the effects that are common to anti-state terror and state-terror; (b) the effects that are unique to anti-state terror; and (c) the psychological effects and sequelae specifically associated with state-terror. Given the paucity of empirical research together with the complexity of the subject matter, definitive statements are difficult to advance. Despite this, however, a number of tentative conclusions can be made. With respect to psychological reactions during the incident, many similarities seem to hold for victims of a hostage-taking, concentration camps, and torture. That is, the incident begins with a period of initial shock accompanied by extreme fear and anxiety. This is followed by a phase characterized by outward acceptance of the perpetrator's control while inside the victim is experiencing extreme fright. Gradually, a period of adaptation sets in, whereby the victim may resort to a number of coping strategies. Although similarities continue after the incident--the post-traumatic stress syndrome, for example--the intensity and duration of psychological sequelae appear to be much greater in victims of state-terror. Given the extreme brutality that invariably accompanies state-terror, this is not surprising. While the methods of anti-state terrorists may take a number of different forms, usually their resources and techniques are limited in comparison to state-terror. It is only more recently in the Middle East that anti-state terrorists more routinely are engaging in long-term detention and torture of victims. On the other hand, regimes that employ state-terror have a wide range of violent techniques at their disposal, most importantly concentration camps. It appears that prolonged physical and emotional violence combined with little hope of relief or escape is critical to understanding why victims of state terrorism are more likely to suffer more serious mental disorders than victims of anti-state terrorism.

In support of the discipline of nursing: a nursing assessment.

The format of the nursing assessment frequently tends to be unit specific and secondary to the goals of other disciplines. This defeats the purpose of the holistic assessment that nurses consider essential. The framework of the eleven functional health patterns proposed by Gordon provides a strong focus for assessment of functional ability as the purpose for collection of assessment data. Data collected systematically in this way in any setting provide a definitive position from which nursing can contribute well-focused and well-documented input for more effective participation in institutional decision making.

Effect of restricted mobility and dominance on perceived duration.

Perceived duration has been found to decrease with decreased cadence and with increased muscular effort. In this study, 64 volunteer college-student subjects who walked a circular track at a preferred tempo produced temporal judgments significantly longer when either the right knee and ankle or the left knee and ankle were restricted, compared to their production estimates when they walked without restriction. No difference in production estimates was found when the effect of restriction of one leg was compared with that of the other. Decreased perceived duration, thought to result from a combination of decreased cadence and increased muscular effort necessitated by the restriction of mobility, may be a mechanism for preserving system integrity in those whose mobility is restricted.

A long-term mortality study of workers occupationally exposed to metallic nickel at the Oak Ridge Gaseous Diffusion Plant.

This study was undertaken to determine whether mortality from respiratory cancer among workers occupationally exposed to metallic nickel at the Oak Ridge Gaseous Diffusion Plant (ORGDP) differed from that of workers at the same plant with no record of occupational exposure to metallic nickel or any nickel compound. A cohort of ,14 nickel-exposed workers and one of 1600' controls were identified. The members of both cohorts had a minimum follow-up period of 19 years. Mortality from respiratory cancer and from other causes was examined in both groups. The data showed no evidence of an increased risk of mortality due to respiratory cancer among the nickel-exposed workers. The exposed cohort experienced lower mortality than the controls, both in deaths due to respiratory cancer and in deaths due to all causes, although neither of these differences was statistically significant.