Willingness to pay for policies to reduce future deaths from climate change: evidence from a British survey.

OBJECTIVES: Without urgent action, climate change will put the health of future populations at risk. Policies to reduce these risks require support from today's populations; however, there are few studies assessing public support for such policies. Willingness to pay (WtP), a measure of the maximum a person is prepared to pay for a defined benefit, is widely used to assess public support for policies. We used WtP to investigate whether there is public support to reduce future health risks from climate change and if individual and contextual factors affect WtP, including perceptions of the seriousness of the impacts of climate change. STUDY DESIGN: A cross-sectional British survey. METHODS: Questions about people's WtP for policies to reduce future climate change-related deaths and their perceptions of the seriousness of climate change impacts were included in a British survey of adults aged 16 years and over (n=1859). We used contingent valuation, a survey-based method for eliciting WtP for outcomes like health which do not have a direct market value. RESULTS: The majority (61%) were willing to pay to reduce future increases in climate change-related deaths in Britain. Those regarding climate change impacts as not at all serious were less willing to pay than those regarding the impacts as extremely serious (OR 0.04, 95% CI 0.02-0.09). Income was also related to WtP; the highest-income group were twice as likely to be willing to pay as the lowest-income group (OR 2.14, 95% CI 1.40-3.29). CONCLUSIONS: There was public support for policies to address future health impacts of climate change; the level of support varied with people's perceptions of the seriousness of these impacts and their financial circumstances. Our study adds to evidence that health, including the health of future populations, is an outcome that people value and suggests that framing climate change around such values may help to accelerate action.

Cigarette smoke modifies neutrophil chemotaxis, neutrophil extracellular trap formation and inflammatory response-related gene expression.

BACKGROUND AND OBJECTIVE: Cigarette smoking is a major risk factor for periodontitis, and smoking perturbs neutrophil reactive oxygen species production. This study tested the hypothesis that cigarette smoke extract (CSE) and its components/metabolites nicotine, cotinine and thiocyanate (SCN-), may influence neutrophil functions. MATERIAL AND METHODS: Chemotaxis was assessed in neutrophils pre-treated with CSE using real-time video microscopy. Neutrophil extracellular trap (NET) release in response to CSE, nicotine, cotinine, SCN- as well as to phorbol 12-myristate-13-acetate and hypochlorous acid following pre-treatment with CSE, nicotine, cotinine or SCN- was assessed using fluorescence-based assays. The impact of CSE and SCN- treatment on neutrophil respiratory burst- and inflammation-related gene expression (NFKBIE, DNAJB1, CXCL8, NCF1, NCF2, CYBB) was determined by real-time polymerase chain reaction. RESULTS: Both CSE and SCN- pre-treatment inhibited phorbol 12-myristate-13-acetate-stimulated NET release. Additionally, SCN- inhibited hypochlorous acid-stimulated NET formation, while SCN- alone stimulated NET release. Overall, neutrophils pre-treated with CSE exhibited reduced speed, velocity and directionality relative to untreated neutrophils. Although CSE and SCN- promoted DNAJB1 expression, increased redox-related gene expression was only detected in response to SCN-. CONCLUSION: These results suggest that CSE can alter ex vivo neutrophil activation by mechanisms independent of SCN- and nicotine, and SCN- may contribute to the perturbed innate immune responses observed in smokers.

Social determinants and lifestyles: integrating environmental and public health perspectives.

OBJECTIVE: Industrialization and urbanization have been associated with an epidemiological transition, from communicable to non-communicable disease, and a geological transition that is moving the planet beyond the stable Holocene epoch in which human societies have prospered. The lifestyles of high-income countries are major drivers of these twin processes. Our objective is to highlight the common causes of chronic disease and environmental change and, thereby, contribute to shared perspectives across public health and the environment. STUDY DESIGN: Integrative reviews focused on social determinants and lifestyles as two 'bridging' concepts between the fields of public health and environmental sustainability. METHODS: We drew on established frameworks to consider the position of the natural environment within social determinants of health (SDH) frameworks and the position of social determinants within environmental frameworks. We drew on evidence on lifestyle factors central to both public health and environmental change (mobility- and diet-related factors). We investigated how public health's focus on individual behaviour can be enriched by environmental perspectives that give attention to household consumption practices. RESULTS: While SDH frameworks can incorporate the biophysical environment, their causal structure positions it as a determinant and one largely separate from the social factors that shape it. Environmental frameworks are more likely to represent the environment and its ecosystems as socially determined. A few frameworks also include human health as an outcome, providing the basis for a combined public health/environmental sustainability framework. Environmental analyses of household impacts broaden public health's concern with individual risk behaviours, pointing to the more damaging lifestyles of high-income households. CONCLUSION: The conditions for health are being undermined by rapid environmental change. There is scope for frameworks reaching across public health and environmental sustainability and a shared evidence base that captures the health- and environmentally damaging impacts of high-consumption lifestyles.

Neutrophil Extracellular Traps in Periodontitis: A Web of Intrigue.

Neutrophil extracellular traps (NETs) represent a novel paradigm in neutrophil-mediated immunity. NETs are believed to constitute a highly conserved antimicrobial strategy comprising decondensed nuclear DNA and associated histones that are extruded into the extracellular space. Associated with the web-like strands of DNA is an array of antimicrobial peptides (AMPs), which facilitate the extracellular destruction of microorganisms that become entrapped within the NETs. NETs can be released by cells that remain viable or following a unique form of programmed cell death known as NETosis, which is dependent on the production of reactive oxygen species (ROS) and the decondensing of the nuclear DNA catalyzed by peptidyl arginine deiminase-4. NETs are produced in response to a range of pathogens, including bacteria, viruses, fungi, and protozoa, as well as host-derived mediators. NET release is, however, not without cost, as the concomitant release of cytotoxic molecules can also cause host tissue damage. This is evidenced by a number of immune-mediated diseases, in which excess or dysfunctional NET production, bacterial NET evasion, and decreased NET removal are associated with disease pathogenesis. Periodontitis is the most prevalent infectious-inflammatory disease of humans, characterized by a dysregulated neutrophilic response to specific bacterial species within the subgingival plaque biofilm. Neutrophils are the predominant inflammatory cell involved in periodontitis and have previously been found to exhibit hyperactivity and hyperreactivity in terms of ROS production in chronic periodontitis patients. However, the contribution of ROS-dependent NET formation to periodontal health or disease remains unclear. In this focused review, we discuss the mechanisms, stimuli, and requirements for NET production; the ability of NET-DNA and NET-associated AMPs to entrap and kill pathogens; and the potential immunogenicity of NETs in disease. We also speculate on the potential role of NETs in the pathogenesis of periodontitis.

Shared risk factors for multiple livestock diseases: a case study of bovine tuberculosis and brucellosis.

Livestock diseases can result in reduced farm productivity. The bacterial diseases tuberculosis (TB) and brucellosis may share some transmission characteristics which, if managed in common, would result in more cost-effective management. Here, we identify risk factors shared between these diseases using a case-control approach and information theoretic modelling. One-hundred cattle farmers in Atlantic Spain were interviewed about farm characteristics and management practices. The risk factor shared between both diseases was intra- and inter-herd contact between cattle. Disease-specific risk factors were the presence of wildlife for TB, and cattle movement between farms for brucellosis. An integrated approach to disease management needs to consider cattle movement and farm biosecurity, reinforced by an education campaign to increase farmer awareness. This would be likely to bring benefits in reducing both diseases and improve the efficiency of any interventions.

Modelling the impact of vaccination on tuberculosis in badgers.

Tuberculosis (TB) in livestock, caused by Mycobacterium bovis, persists in many countries. In Britain, efforts to control TB through the culling of badgers (Meles meles), the principal wildlife host, have so far been unsuccessful, and there is significant interest in vaccination of badgers as an alternative or complementary strategy [corrected]. Using a simulation model, we show that where TB is self-contained within the badger population and there are no external sources of infection, limited-duration vaccination at a high level of efficacy can reduce or even eradicate TB from the badger population. However, where sources of external infection persist, benefits in TB reduction in badgers can only be achieved by ongoing, annual vaccination. Vaccination is likely to be most effective as part of an integrated disease management strategy incorporating a number of different approaches across the entire host community.

Open Air Laboratories (OPAL): a community-driven research programme.

OPAL is an English national programme that takes scientists into the community to investigate environmental issues. Biological monitoring plays a pivotal role covering topics of: i) soil and earthworms; ii) air, lichens and tar spot on sycamore; iii) water and aquatic invertebrates; iv) biodiversity and hedgerows; v) climate, clouds and thermal comfort. Each survey has been developed by an inter-disciplinary team and tested by voluntary, statutory and community sectors. Data are submitted via the web and instantly mapped. Preliminary results are presented, together with a discussion on data quality and uncertainty. Communities also investigate local pollution issues, ranging from nitrogen deposition on heathlands to traffic emissions on roadside vegetation. Over 200,000 people have participated so far, including over 1000 schools and 1000 voluntary groups. Benefits include a substantial, growing database on biodiversity and habitat condition, much from previously unsampled sites particularly in urban areas, and a more engaged public.

The effect of grazing management on livestock exposure to parasites via the faecal-oral route.

In grazing systems, heterogeneous distributions of forage resources and faeces result in localised accumulations of nutrients and parasites (both macroparasites and microparasites), creating trade-offs between the costs of exposure to infestation or infection and the benefits of nutrient intake. Each contact between livestock and faeces in the environment is a potential parasite/pathogen transmission event. Thus, herbivores must make foraging decisions in complex environments which will affect their intake of both nutrients and parasites. However, the pattern of forage and faecal resources in agricultural environments will also be affected by the grazing management system in place. The aim of this study was to investigate the effect of grazing management on the risk of infection/infestation to livestock. We used a spatially explicit individual based stochastic foraging model to simulate livestock contact (both grazing and investigative) with faeces in the environment. The model was parameterised to simulate cattle grazing under three types of grazing management: set stock (i.e. where sward growth and cattle intake are in equilibrium in a single field); a two pasture rotation grazing system with increasing number of rotations; and a rotational grazing system with two rotations and increasing subdivisions of the pasture. Overall the amount of cattle contact with faecal-contaminated patches was similar in both set stocking and rotational grazing scenarios, suggesting no difference in the risk of infection or infestation between the different systems. However, the timing and absolute amounts of peak contact varied greatly indicating that different grazing management systems expose livestock to risks of different types of parasites at different times of the grazing season. Intensive rotational systems with small pasture blocks (especially the first grazing period) maximised livestock contact with fresh faeces, and thus exposure to microparasites (e.g. bacterial pathogens). Livestock re-entering pasture blocks in rotational systems and set stocked livestock had the highest contact with old faeces and thus have a greater risk of macroparasite transmission (gastrointestinal nematodes). This study highlights how livestock management affects the highly dynamic interaction between livestock and distributions of parasites in the environment and thus the levels of livestock exposure to parasites and pathogens via the faecal-oral route.

Inter- and intra-specific exposure to parasites and pathogens via the faecal-oral route: a consequence of behaviour in a patchy environment.

Livestock herbivores are at risk of inter- and intra-specific exposure to parasites/pathogens via the faecal-oral route during grazing. Each contact between livestock and faeces in the environment is a potential parasite/pathogen transmission event. Cattle grazing contact with faeces varies in relation to the species depositing the faeces and the distribution of the faeces. We used a foraging model to simulate the grazing behaviour of beef cattle in two grazing systems to compare the relative inter-specific and intra-specific exposure risks to parasites/pathogens. Overall, there is a greater level of intra- vs. inter-specific risk via the faecal-oral route. However, under certain conditions, particularly for microparasite infections, e.g. paratuberculosis in rabbits and bovine tuberculosis in badgers, wildlife may pose a significant exposure risk to parasites/pathogens. These risks can be enhanced when cattle are first turned out onto pasture and in situations where intra-specific variations in wildlife behaviour result in more dispersed defecation patterns.

Use of host population reduction to control wildlife infection: rabbits and paratuberculosis.

Reduction in wildlife populations is a common method for the control of livestock infections which have wildlife hosts, but its success is dependent on the characteristics of the infection itself, as well as on the spatial and social structure of the wildlife host. Paratuberculosis (Mycobacterium avium subsp. paratuberculosis; Map) is a widespread and difficult infection to control in livestock populations and also has possible links to Crohn's disease in humans. Rabbits have recently been identified as a key wildlife species in terms of paratuberculosis persistence in the environment and risk to the wider host community, including cattle. Here we use a spatially explicit stochastic simulation model of Map dynamics in rabbit populations to quantify the effects of rabbit population control on infection persistence. The model parameters were estimated from empirical studies of rabbit population dynamics and rabbit-to-rabbit routes of Map transmission. Three rabbit control strategies were compared: single unrepeated population reductions based on removing individual animals; single unrepeated population reductions based on removal of entire social groups; and repeated annual population reductions based on removing individual animals. Unrealistically high rabbit culls (>95% population reduction) are needed if infection is to be eradicated from local rabbit populations with a single one-off population reduction event, either of individuals or social groups. Repeated annual culls are more effective at reducing the prevalence of infection in rabbit populations and eradicating infection. However, annual population reductions of >40% are required over extended periods of time (many years). Thus, using an approach which is both highly conservative and parsimonious with respect to estimating lower bounds on the time to eradicate the infection, we find that Map is extremely persistent in rabbit populations and requires significant and prolonged effort to achieve control.

Bovine tuberculosis in southern African wildlife: a multi-species host-pathogen system.

This review examines the current situation of bovine tuberculosis (bTB) in southern African savannah systems, and uses theory on multi-species host-pathogen systems to suggest possible options for future research and management. In southern Africa, the buffalo (Syncerus caffer) and the Kafue lechwe [Marsh antelope] (Kobus leche) have been found to be maintenance hosts for this disease, but the importance of other host species is becoming apparent. The role of other host species in the maintenance and spread of the disease varies, depending on the spatial distribution and resource utilization patterns of the species, disease susceptibility, transmission modes and the ecology of both host(s) and vector(s). Future research needs to identify the pathogenicity of bTB in each of the host species, and the mechanisms and rates of inter- and intra-specific transmission among different species, in order to develop multi-host models to understand the development and spread of the disease.

Regulation of cyclin D2 and the cyclin D2 promoter by protein kinase A and CREB in lymphocytes.

Lymphocyte proliferation is key to the regulation of the immune system. Cyclin D2 is the first cell cycle protein induced following stimulation through the T-cell receptor, the B-cell receptor or cytokines. The promoter of this cyclin integrates a diverse range of signals. Through investigating the regulation of this promoter by interleukin-2 and phosphatidylinositol 3-kinase, we have identified a role for the transcription factor CREB, cAMP response element-binding protein. Mutation of the CREB-binding site reduced cyclin D2 promoter activity 5-10-fold. CREB-1 is phosphorylated at serine 133, a critical site for activity, in both T cells and Epstein-Barr virus immortalized B cells. The introduction of an S133A mutant of CREB-1 reduces IL-2 induction of cyclin D2 promoter activity, demonstrating a role for this phosphorylation site in promoter activity. Two inhibitors of protein kinase A reduce lymphocyte proliferation and CREB-1 phosphorylation. This study demonstrates that the cyclin D2 promoter is capable of being regulated by PI3K and CREB and identifies CREB-1 and protein kinase A as potential targets for altering lymphocyte proliferation.

Mortality due to fox predation in free-range poultry flocks in Britain.

Information derived from questionnaires sent to producers of free-range eggs, chickens, turkeys and geese was used to assess the extent of fox predation in terms of the density of the fox population and farm management factors. The mean reported bird mortality was less than 2 per cent for all the producers, but there were marked differences between them. Egg producers reported losing many more birds to foxes than other types of producer (up to 1000 birds in a laying cycle). On average, egg and goose producers lost the highest proportions of their total flocks (0.5 per cent). The extent of predation was not associated either with large-scale estimations of the density of the fox population or with variations in the farms' habitat. Chicken predation was not linked to differences in types of housing or fencing. However, there was a positive association between losses due to other causes and chicken predation. The results suggest that changes in farm management would be the most cost-effective means of reducing fox predation, rather than greater fox control.

In situ surface enhanced resonance Raman scattering (SERRS) spectroscopy of biro inks--long-term stability of colloid treated samples.

The script produced by two black biro inks in 1998 in a document that was not subjected to any special storage conditions or further treatment was re-analysed by SERRS spectroscopy. The results presented show that the analyses of the areas of the ink strokes previously treated with an aggregating agent. poly-(L-lysine), and then silver colloid still produce strong SERRS spectra. No major changes are observed in the spectra thus still providing a method for discriminating between the two inks used in the document and illustrating the long-term stability of the colloid treatment. This ability to re-analyse the ink samples without any further treatment is attributed to the use of very fine pen nibs to apply the reagents.

Differential regulation of aldosterone synthase and 11beta-hydroxylase transcription by steroidogenic factor-1.

11beta-Hydroxylase (hCYP11B1) and aldosterone synthase (hCYP11B2) are closely related isozymes with distinct roles in cortisol and aldosterone production respectively. Aldosterone synthase catalyzes the final step in aldosterone biosynthesis and is expressed only in the zona glomerulosa of the normal adrenal. 11beta-Hydroxylase catalyzes the final reaction in the production of cortisol and is expressed at higher levels in the zona fasciculata. The mechanisms causing differential expression of these genes are not well defined. Herein, we demonstrate contrasting roles for the orphan receptor steroidogenic factor-1 (SF-1) in the regulation of human (h) CYP11B1 and hCYP11B2. Human NCI-H295R (H295R) or mouse Y-1 cells were transiently transfected with luciferase reporter constructs containing 5'-flanking regions of hCYP11B1, hCYP11B2, human 17alpha-hydroxylase (hCYP17), human cholesterol side-chain cleavage (hCYP11A1) or mouse (m) cyp11b2 (mcyp11b2). Co-transfection of vectors encoding SF-1 increased expression of hCYP11B1, hCYP11A1 and hCYP17 constructs, but inhibited hCYP11B2 reporter activity. Murine, bovine and human SF-1 were unable to increase transcription of hCYP11B2 in H295R cells. Both hCYP11B2 and mcyp11b2 promoter constructs were inhibited similarly by human SF-1. In mouse Y-1 cells, reporter expression of hCYP11B2 and mcyp11b2 was very low compared with hCYP11B1 constructs, suggesting that this adrenal cell model may not be appropriate for studies of CYP11B2. Electrophoretic mobility shift assay demonstrated that SF-1 interacted with an element from both hCYP11B1 and hCYP11B2. However, mutation of this element, termed Ad4, did not prevent agonist stimulation of hCYP11B2 by angiotensin II or forskolin but blocked activity of hCYP11B1. In some, but not all, reports of genetic linkage analysis, a naturally occurring single nucleotide polymorphism within the Ad4 element of hCYP11B2 (-344C/T) has been associated with cardiovascular disease. Herein, we have demonstrated that this polymorphism influenced binding of SF-1 in electrophoretic mobility shift assays, with the C allele binding SF-1 more strongly than the T allele. However, when hCYP11B2 constructs containing these alleles were transfected into H295R cells, there was no difference in agonist-stimulated expression or the response of either reporter construct to co-expression with human SF-1. Taken together, these data suggest that SF-1 and the Ad4 element are not major regulators of adrenal hCYP11B2 gene expression. Thus far, hCYP11B2 is the first steroid hydroxylase gene which is not positively regulated by SF-1.

Congenital hyperreninemic hypoaldosteronism unlinked to the aldosterone synthase (CYP11B2) gene.

Isolated hyperreninemic hypoaldosteronism presenting in infancy is usually caused by mutations in the CYP11B2 gene encoding aldosterone synthase. We studied five patients in four unrelated kindreds with hyperreninemic hypoaldosteronism, in whom we were unable to find such mutations. All presented in infancy with failure to thrive, hyponatremia, hyperkalemia, markedly elevated plasma renin activity, and low or inappropriately normal aldosterone levels. All had normal cortisol levels and no signs or symptoms of congenital adrenal hyperplasia. All responded to fludrocortisone treatment. There were no mutations detected in exons or splice junctions of CYP11B2. Linkage of the disorder to CYP11B2 was studied in two unrelated consanguineous patients and in an affected sib pair. The consanguineous patients were each heterozygous for at least one of three polymorphic microsatellite markers near CYP11B2, excluding linkage to CYP11B2. However, linkage of the disease to CYP11B2 could not be excluded in the affected sib pair. Genes involved in the regulation of aldosterone biosynthesis, including those encoding angiotensinogen, angiotensin-converting enzyme, and the AT1 angiotensin II receptor were similarly excluded from linkage. These results demonstrate the existence of an inherited form of hyperreninemic hypoaldosteronism distinct from aldosterone synthase deficiency. The affected gene(s) remain to be determined.

Possible association but no linkage of the HSD11B2 gene encoding the kidney isozyme of 11beta-hydroxysteroid dehydrogenase to hypertension in Black people.

OBJECTIVE: The HSD11B2 (HSD11K) gene encoding the kidney isozyme of 11beta-hydroxysteroid dehydrogenase is mutated in the syndrome of apparent mineralocorticoid excess, an autosomal recessive form of salt-sensitive hypertension. This gene is thus a logical candidate locus for risk of essential hypertension. DESIGN AND METHODS: Because hypertension in Black people tends to be of the low-renin, salt sensitive type, we genotyped independent sets of hypertensives of Afro-American (59 kindreds) and Afro-Caribbean (66 kindreds) origin using a highly polymorphic (heterozygosity index 0.84) CA repeat polymorphism in the first intron of HSD11B2. Linkage was assessed by the affected pedigree member method. RESULTS: No linkage of hypertension to this locus could be demonstrated, but statistically significant allelic associations were noted. CONCLUSIONS: HSD11B2 does not have a strong influence on the development of essential hypertension in Black people, but weaker effects on blood pressure cannot be ruled out.