Rock art and social life - Revisiting the Neolithic transition in Mediterranean Iberia

This article revisits the Neolithic transition in Mediterranean Iberia taking into account an aspect usually neglected in the archaeological discourse: the rock art styles that emerged in this context. These distinct styles have been generally attributed to different populations, according to a historicist point of view that equates stylistic variability and ethnic identity. However, the recent recognition that they were developed by the same social group requires the formulation of an alternative explanation. My proposal is based on the exploration of the social context of production and consumption of the rock art, through the analysis of the patterns of location of the sites within the landscape and the definition of their archaeological context.

The social impacts of heat waves

The effects of the 2003 European heat wave have highlighted the need for society to prepare itself for and cope more effectively with heat waves. This is particularly important in the context of predicted climate change and the likelihood of more frequent extreme climate events; to date, heat as a natural hazard has been largely ignored. In order to develop better coping strategies, this report explores the factors that shape the social impacts of heat waves, and sets out a programme of research to address the considerable knowledge gaps in this area. Heat waves, or periods of anomalous warmth, do not affect everyone; it is the vulnerable individuals or sectors of society who will most experience their effects. The main factors of vulnerability are being elderly, living alone, having a pre-existing disease, being immobile or suffering from mental illness and being economically disadvantaged. The synergistic effects of such factors may prove fatal for some. Heat waves have discernible impacts on society including a rise in mortality, an increased strain on infrastructure (power, water and transport) and a possible rise in social disturbance. Wider impacts may include effects on the retail industry, ecosystem services and tourism. Adapting to more frequent heat waves should include soft engineering options and, where possible, avoid the widespread use of air conditioning which could prove unsustainable in energy terms. Strategies for coping with heat include changing the way in which urban areas are developed or re-developed, and setting up heat watch warning systems based around weather and seasonal climate forecasting and intervention strategies. Although heat waves have discernible effects on society, much remains unknown about their wider social impacts, diffuse health issues and how to manage them.

British Nutrition Foundation annual lecture: chips with everything? Nutritional genomics and the application of diet in disease prevention

The development of high throughput techniques ('chip' technology) for measurement of gene expression and gene polymorphisms (genomics), and techniques for measuring global protein expression (proteomics) and metabolite profile (metabolomics) are revolutionising life science research, including research in human nutrition. In particular, the ability to undertake large-scale genotyping and to identify gene polymorphisms that determine risk of chronic disease (candidate genes) could enable definition of an individual's risk at an early age. However, the search for candidate genes has proven to be more complex, and their identification more elusive, than previously thought. This is largely due to the fact that much of the variability in risk results from interactions between the genome and environmental exposures. Whilst the former is now very well defined via the Human Genome Project, the latter (e.g. diet, toxins, physical activity) are poorly characterised, resulting in inability to account for their confounding effects in most large-scale candidate gene studies. The polygenic nature of most chronic diseases offers further complexity, requiring very large studies to disentangle relatively weak impacts of large numbers of potential 'risk' genes. The efficacy of diet as a preventative strategy could also be considerably increased by better information concerning gene polymorphisms that determine variability in responsiveness to specific diet and nutrient changes. Much of the limited available data are based on retrospective genotyping using stored samples from previously conducted intervention trials. Prospective studies are now needed to provide data that can be used as the basis for provision of individualised dietary advice and development of food products that optimise disease prevention. Application of the new technologies in nutrition research offers considerable potential for development of new knowledge and could greatly advance the role of diet as a preventative disease strategy in the 21st century. Given the potential economic and social benefits offered, funding for research in this area needs greater recognition, and a stronger strategic focus, than is presently the case. Application of genomics in human health offers considerable ethical and societal as well as scientific challenges. Economic determinants of health care provision are more likely to resolve such issues than scientific developments or altruistic concerns for human health.

Omega-3 fatty acids, cardiovascular disease and stability of atherosclerotic plaques

Long-chain n-3 polyunsaturated fatty acids are found in oily fish and in fish oils and similar preparations. Substantial evidence from epidemiological and case-control studies indicates that consumption of fish, oily fish and long-chain n-3 fatty acids reduces risk of cardiovascular mortality. Secondary prevention studies using long-chain n-3 fatty acids in patients post-myocardial infarction have shown a reduction in total and cardiovascular mortality with an especially potent effect on sudden death. Long-chain n-3 fatty acids have been shown to beneficially modify a range of cardiovascular risk factors, which may result in primary cardiovascular prevention. However, reduced non-fatal and fatal events and a reduction in sudden death probably involve other mechanisms. Reduced thrombosis following long-chain n-3 fatty acids may play a role. A decrease in arrhythmias is a favoured mechanism of action of long-chain n-3 fatty acids and is supported by cell culture and animal studies. However human trials using implantable cardiac defibrillators have produced inconsistent findings and a recent meta-analysis does not support this mechanism of action. An alternative mechanism of action may be stabilisation of atherosclerotic plaques by long-chain n-3 fatty acids. This is suggested by one published human study which showed that incorporation of long-chain n-3 fatty acids into plaques collected at carotid endarterectomy resulted in fewer macrophages in the plaque and a morphology indicative of increased stability. These findings are supported from observations in an animal model and suggest that the primary effect of long-chain n-3 fatty acids might be on macrophages within the plaque.

Use and abuse of mathematical models: an illustration from the 2001 foot and mouth disease epidemic in the United Kingdom

Foot and mouth disease (FMD) is a major threat, not only to countries whose economies rely on agricultural exports, but also to industrialised countries that maintain a healthy domestic livestock industry by eliminating major infectious diseases from their livestock populations. Traditional methods of controlling diseases such as FMD require the rapid detection and slaughter of infected animals, and any susceptible animals with which they may have been in contact, either directly or indirectly. During the 2001 epidemic of FMD in the United Kingdom (UK), this approach was supplemented by a culling policy driven by unvalidated predictive models. The epidemic and its control resulted in the death of approximately ten million animals, public disgust with the magnitude of the slaughter, and political resolve to adopt alternative options, notably including vaccination, to control any future epidemics. The UK experience provides a salutary warning of how models can be abused in the interests of scientific opportunism.

Investment in preventing and preparing for biological emergencies and disasters: social and economic costs of disasters versus costs of surveillance and response preparedness

Biological emergencies such as the appearance of an exotic transboundary or emerging disease can become disasters. The question that faces Veterinary Services in developing countries is how to balance resources dedicated to active insurance measures, such as border control, surveillance, working with the governments of developing countries, and investing in improving veterinary knowledge and tools, with passive measures, such as contingency funds and vaccine banks. There is strong evidence that the animal health situation in developed countries has improved and is relatively stable. In addition, through trade with other countries, developing countries are becoming part of the international animal health system, the status of which is improving, though with occasional setbacks. However, despite these improvements, the risk of a possible biological disaster still remains, and has increased in recent times because of the threat of bioterrorism. This paper suggests that a model that combines decision tree analysis with epidemiology is required to identify critical points in food chains that should be strengthened to reduce the risk of emergencies and prevent emergencies from becoming disasters.

Modelling disease spread and control in networks: implications for plant sciences

Networks are ubiquitous in natural, technological and social systems. They are of increasing relevance for improved understanding and control of infectious diseases of plants, animals and humans, given the interconnectedness of today's world. Recent modelling work on disease development in complex networks shows: the relative rapidity of pathogen spread in scale-free compared with random networks, unless there is high local clustering; the theoretical absence of an epidemic threshold in scale-free networks of infinite size, which implies that diseases with low infection rates can spread in them, but the emergence of a threshold when realistic features are added to networks (e.g. finite size, household structure or deactivation of links); and the influence on epidemic dynamics of asymmetrical interactions. Models suggest that control of pathogens spreading in scale-free networks should focus on highly connected individuals rather than on mass random immunization. A growing number of empirical applications of network theory in human medicine and animal disease ecology confirm the potential of the approach, and suggest that network thinking could also benefit plant epidemiology and forest pathology, particularly in human-modified pathosystems linked by commercial transport of plant and disease propagules. Potential consequences for the study and management of plant and tree diseases are discussed.

Targeting the cell cycle machinery for the treatment of cardiovascular disease

Cardiovascular disease represents a major clinical problem affecting a significant proportion of the world's population and remains the main cause of death in the UK. The majority of therapies currently available for the treatment of cardiovascular disease do not cure the problem but merely treat the symptoms. Furthermore, many cardioactive drugs have serious side effects and have narrow therapeutic windows that can limit their usefulness in the clinic. Thus, the development of more selective and highly effective therapeutic strategies that could cure specific cardiovascular diseases would be of enormous benefit both to the patient and to those countries where healthcare systems are responsible for an increasing number of patients. In this review, we discuss the evidence that suggests that targeting the cell cycle machinery in cardiovascular cells provides a novel strategy for the treatment of certain cardiovascular diseases. Those cell cycle molecules that are important for regulating terminal differentiation of cardiac myocytes and whether they can be targeted to reinitiate cell division and myocardial repair will be discussed as will the molecules that control vascular smooth muscle cell (VSMC) and endothelial cell proliferation in disorders such as atherosclerosis and restenosis. The main approaches currently used to target the cell cycle machinery in cardiovascular disease have employed gene therapy techniques. We will overview the different methods and routes of gene delivery to the cardiovascular system and describe possible future drug therapies for these disorders. Although the majority of the published data comes from animal studies, there are several instances where potential therapies have moved into the clinical setting with promising results.

On the discourse of construction competitiveness

It is contended that competitiveness is better understood as a discourse rather than as a characteristic that is supposedly possessed. The discourse of competitiveness derives its legitimacy from the enterprise culture that came to dominance during the 1980s. Current popularized theories of competitiveness are constituent parts of this broader discourse, which has had significant material implications for the UK construction sector. The dominant discourse of competitiveness amongst contracting firms is shaped by the need to achieve structural flexibility to cope with fluctuations in demand. Fashionable espoused improvement recipes such as total quality management, business process re-engineering, and lean construction legitimize and reinforce the material manifestations of the enterprise culture. In consequence, the UK industry is characterized by a plethora of hollowed-out firms that have failed to invest in their human capital. While the adopted model may be rational for individual firms, the systemic effect across the sector as a whole equates to a form of anorexia. However, the discourse of competitiveness is by no means monolithic and continues to be contested locally. There have also been numerous counter-discourses that have been mobilized in response to the undesirable externalities of unbridled enterprise. Currently, important counter-discourses promote the ideas of sustainability and corporate social responsibility.

Targeting C-reactive protein for the treatment of cardiovascular disease

Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new cardioprotective and neuroprotective treatments. We have previously shown that human C-reactive protein (CRP), the classical acute-phase protein that binds to ligands exposed in damaged tissue and then activates complement(1), increases myocardial and cerebral infarct size in rats subjected to coronary or cerebral artery ligation, respectively(2,3). Rat CRP does not activate rat complement, whereas human CRP activates both rat and human complement(4). Administration of human CRP to rats is thus an excellent model for the actions of endogenous human CRP2,3. Here we report the design, synthesis and efficacy of 1,6-bis(phosphocholine)-hexane as a specific small-molecule inhibitor of CRP. Five molecules of this palindromic compound are bound by two pentameric CRP molecules, crosslinking and occluding the ligand-binding B-face of CRP and blocking its functions. Administration of 1,6-bis(phosphocholine)-hexane to rats undergoing acute myocardial infarction abrogated the increase in infarct size and cardiac dysfunction produced by injection of human CRP. Therapeutic inhibition of CRP is thus a promising new approach to cardioprotection in acute myocardial infarction, and may also provide neuroprotection in stroke. Potential wider applications include other inflammatory, infective and tissue-damaging conditions characterized by increased CRP production, in which binding of CRP to exposed ligands in damaged cells may lead to complement-mediated exacerbation of tissue injury.

Microglial activation correlates with severity in Huntington disease: a clinical and PET study

Background: Huntington disease ( HD) is characterized by the progressive death of medium spiny dopamine receptor bearing striatal GABAergic neurons. In addition, microglial activation in the areas of neuronal loss has recently been described in postmortem studies. Activated microglia are known to release neurotoxic cytokines, and these may contribute to the pathologic process. Methods: To evaluate in vivo the involvement of microglia activation in HD, the authors studied patients at different stages of the disease using [ C-11]( R)-PK11195 PET, a marker of microglia activation, and [ C-11] raclopride PET, a marker of dopamine D2 receptor binding and hence striatal GABAergic cell function. Results: In HD patients, a significant increase in striatal [ C-11]( R)-PK11195 binding was observed, which significantly correlated with disease severity as reflected by the striatal reduction in [ C-11] raclopride binding, the Unified Huntington's Disease Rating Scale score, and the patients' CAG index. Also detected were significant increases in microglia activation in cortical regions including prefrontal cortex and anterior cingulate. Conclusions: These [ C-11]( R)-PK11195 PET findings show that the level of microglial activation correlates with Huntington disease ( HD) severity. They lend support to the view that microglia contribute to the ongoing neuronal degeneration in HD and indicate that [ C-11]( R)-PK11195 PET provides a valuable marker when monitoring the efficacy of putative neuroprotecting agents in this relentlessly progressive genetic disorder.