Polyphenols, glucosinolates, dietary fibre and colon cancer: Understanding the potential of specific types of fruit and vegetables to reduce bowel cancer progression

Colorectal cancer is the third most prevalent cancer worldwide and the most common diet-related cancer, influenced by diets rich in red meat, low in plant foods and high in saturated fats. Observational studies have shown that fruit and vegetable intake may reduce colorectal cancer risks, although the precise bioactive components remain unclear. This review will outline the evidence for the role of polyphenols, glucosinolates and fibres against cancer progression in the gastrointestinal tract. Those bioactive compounds are considered protective agents against colon cancer, with evidence taken from epidemiological, human clinical, animal and in vitro studies. Various mechanisms of action have been postulated, such as the potential of polyphenols and glucosinolates to inhibit cancer cell growth and the actions of insoluble fibres as prebiotics and the evidence for these actions are detailed within. In addition, recent evidence suggests that polyphenols also have the potential to shift the gut ecology in a beneficial manner. Such actions of both fibre and polyphenols in the gastrointestinal tract and through interaction with gut epithelial cells may act in an additive manner to help explain why certain fruits and vegetables, but not all, act to differing extents to inhibit cancer incidence and progression. Indeed, a focus on the individual actions of such fruit and vegetable components, in particular polyphenols, glucosinolates and fibres is necessary to help explain which components are active in reducing gastrointestinal cancer risk.

Operational active fire mapping and burnt area identification applicable to Mexican Nature Protection Areas using MODIS and NOAA-AVHRR direct readout data

Since 1999, the National Commission for the Knowledge and Use of the Biodiversity (CONABIO) in Mexico has been developing and managing the “Operational program for the detection of hot-spots using remote sensing techniques”. This program uses images from the MODerate resolution Imaging Spectroradiometer (MODIS) onboard the Terra and Aqua satellites and from the Advanced Very High Resolution Radiometer of the National Oceanic and Atmospheric Administration (NOAA-AVHRR), which are operationally received through the Direct Readout station (DR) at CONABIO. This allows the near-real time monitoring of fire events in Mexico and Central America. In addition to the detection of active fires, the location of hot spots are classified with respect to vegetation types, accessibility, and risk to Nature Protection Areas (NPA). Besides the fast detection of fires, further analysis is necessary due to the considerable effects of forest fires on biodiversity and human life. This fire impact assessment is crucial to support the needs of resource managers and policy makers for adequate fire recovery and restoration actions. CONABIO attempts to meet these requirements, providing post-fire assessment products as part of the management system in particular for satellite-based burnt area mapping. This paper provides an overview of the main components of the operational system and will present an outlook to future activities and system improvements, especially the development of a burnt area product. A special focus will also be placed on the fire occurrence within NPAs of Mexico

Military targeting in the context of self-defence actions

In order to bring conceptual clarity to a particular dimension of the relationship between the jus ad bellum and the jus in bello regimes, this article explores the independent sources of a military targeting rule in both branches of international law. The aim is not to displace the jus in bello as the ‘lead’ regime on how targeting decisions must be made, or to undermine the traditional separation between these regimes. Rather, conceptual light is shed on a sometimes assumed but generally neglected dimension of the jus ad bellum’s necessity and proportionality criteria that may, in limited circumstances, have significance for our understanding of human protection during war, by covering possible gaps in the jus in bello targeting rules.

The Article 51 reporting requirement for self-defense actions

This article examines one legal criterion for the exercise of the right of self-defense that has been significantly overlooked by commentators: the so-called “reporting requirement.” Article 51 of the United Nations (UN) Charter provides, inter alia, that “[m]easures taken by members in the exercise of this right of self-defense shall be immediately reported to the Security Council.” Although the requirement to report all self-defense actions to the Council is clearly set out in Article 51, the Charter offers no further guidance with regard to this obligation. Reference to the practice of states since the UN’s inception in 1945 is therefore essential to understanding the scope and nature of the reporting requirement. As such, this article is underpinned by an extensive original dataset of reporting practice covering the period from January 1, 1998 to December 31, 2013. We know from Article 51 that states “shall” report, but do they, and—if so—in what manner? What are the various implications of reporting, of failing to report, and of the way in which states report? How are reports used, and by whom? Most importantly, this article questions the ultimate value of states reporting their self-defense actions to the Security Council in modern interstate relations.

Pharmacological actions of nobiletin in the modulation of platelet function

Background and Purpose The discovery that flavonoids are capable of inhibiting platelet function has led to their investigation as potential antithrombotic agents. However, despite the range of studies on the antiplatelet properties of flavonoids, little is known about the mechanisms by which flavonoids inhibit platelet function. In this study, we aimed to explore the pharmacological effects of a polymethoxy flavonoid, nobiletin in the modulation of platelet function. Experimental Approach The ability of nobiletin to modulate platelet function was explored by using a range of in vitro and in vivo experimental approaches. Aggregation, dense granule secretion and spreading assays were performed using washed platelets. The fibrinogen binding, α-granule secretion and calcium mobilisation assays were performed using platelet-rich plasma and whole blood was used in impedance aggregometry and thrombus formation experiments. The effect of nobiletin in vivo was assessed by measuring tail bleeding time using C57BL/6 mice. Key Results Nobiletin was shown to supress a range of well-established activatory mechanisms, including platelet aggregation, granule secretion, integrin modulation, calcium mobilisation and thrombus formation. Nobiletin was shown to extend bleeding time in mice and reduce the phosphorylation of Akt and PLCγ2 within the collagen receptor (GPVI) - stimulated pathway, in addition to increasing the levels of cGMP and phosphorylation of VASP, a protein whose activity is associated with inhibitory cyclic nucleotide signalling. Conclusions and Implications This study provides insight into the underlying molecular mechanisms through which nobiletin modulates haemostasis and thrombus formation. Therefore nobiletin may represent a potential antithrombotic agent of dietary origins.

Using high-frequency water quality data to assess sampling strategies for the EU Water Framework Directive

The EU Water Framework Directive (WFD) requires that the ecological and chemical status of water bodies in Europe should be assessed, and action taken where possible to ensure that at least "good" quality is attained in each case by 2015. This paper is concerned with the accuracy and precision with which chemical status in rivers can be measured given certain sampling strategies, and how this can be improved. High-frequency (hourly) chemical data from four rivers in southern England were subsampled to simulate different sampling strategies for four parameters used for WFD classification: dissolved phosphorus, dissolved oxygen, pH and water temperature. These data sub-sets were then used to calculate the WFD classification for each site. Monthly sampling was less precise than weekly sampling, but the effect on WFD classification depended on the closeness of the range of concentrations to the class boundaries. In some cases, monthly sampling for a year could result in the same water body being assigned to three or four of the WFD classes with 95% confidence, due to random sampling effects, whereas with weekly sampling this was one or two classes for the same cases. In the most extreme case, the same water body could have been assigned to any of the five WFD quality classes. Weekly sampling considerably reduces the uncertainties compared to monthly sampling. The width of the weekly sampled confidence intervals was about 33% that of the monthly for P species and pH, about 50% for dissolved oxygen, and about 67% for water temperature. For water temperature, which is assessed as the 98th percentile in the UK, monthly sampling biases the mean downwards by about 1 °C compared to the true value, due to problems of assessing high percentiles with limited data. Low-frequency measurements will generally be unsuitable for assessing standards expressed as high percentiles. Confining sampling to the working week compared to all 7 days made little difference, but a modest improvement in precision could be obtained by sampling at the same time of day within a 3 h time window, and this is recommended. For parameters with a strong diel variation, such as dissolved oxygen, the value obtained, and thus possibly the WFD classification, can depend markedly on when in the cycle the sample was taken. Specifying this in the sampling regime would be a straightforward way to improve precision, but there needs to be agreement about how best to characterise risk in different types of river. These results suggest that in some cases it will be difficult to assign accurate WFD chemical classes or to detect likely trends using current sampling regimes, even for these largely groundwater-fed rivers. A more critical approach to sampling is needed to ensure that management actions are appropriate and supported by data.

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.

Sticking to the script? The co-production of Neighbourhood Planning in England

Efforts to engage with communities in spatial planning have been criticised as being tokenistic, vehicles for co-option or designed to promote neo-liberal agendas. The introduction of neighbourhood planning (NP) in England under the Localism Act (2011) is claimed by proponents to be a step change in the way that local communities are involved in planning their own areas. However, little empirical evidence has yet emerged to substantiate such claims, or provide details about the practices and experiences of NP. The paper highlights that there are numerous parties involved in the co-production of Neighbourhood Development Plans and there are numerous instances where ideas, policies and priorities that emerge from within neighbourhoods are being ‘rescripted’ to ensure conformity to a bounded form of collaboration.

Why compatibilist intuitions are not mistaken: a reply to Feltz and Millan

In the past decade, a number of empirical researchers have suggested that laypeople have compatibilist intuitions. In a recent paper, Feltz and Millan (2015) have challenged this conclusion by claiming that most laypeople are only compatibilists in appearance and are in fact willing to attribute free will to people no matter what. As evidence for this claim, they have shown that an important proportion of laypeople still attribute free will to agents in fatalistic universes. In this paper, we first argue that Feltz and Millan’s error-theory rests on a conceptual confusion: it is perfectly acceptable for a certain brand of compatibilist to judge free will and fatalism to be compatible, as long as fatalism does not prevent agents from being the source of their actions. We then present the results of two studies showing that laypeople’s intuitions are best understood as following a certain brand of source compatibilism rather than a “free-will-no-matter-what” strategy.

Predicting how many animals will be where: how to build, calibrate and evaluate individual-based models

Individual-based models (IBMs) can simulate the actions of individual animals as they interact with one another and the landscape in which they live. When used in spatially-explicit landscapes IBMs can show how populations change over time in response to management actions. For instance, IBMs are being used to design strategies of conservation and of the exploitation of fisheries, and for assessing the effects on populations of major construction projects and of novel agricultural chemicals. In such real world contexts, it becomes especially important to build IBMs in a principled fashion, and to approach calibration and evaluation systematically. We argue that insights from physiological and behavioural ecology offer a recipe for building realistic models, and that Approximate Bayesian Computation (ABC) is a promising technique for the calibration and evaluation of IBMs. IBMs are constructed primarily from knowledge about individuals. In ecological applications the relevant knowledge is found in physiological and behavioural ecology, and we approach these from an evolutionary perspective by taking into account how physiological and behavioural processes contribute to life histories, and how those life histories evolve. Evolutionary life history theory shows that, other things being equal, organisms should grow to sexual maturity as fast as possible, and then reproduce as fast as possible, while minimising per capita death rate. Physiological and behavioural ecology are largely built on these principles together with the laws of conservation of matter and energy. To complete construction of an IBM information is also needed on the effects of competitors, conspecifics and food scarcity; the maximum rates of ingestion, growth and reproduction, and life-history parameters. Using this knowledge about physiological and behavioural processes provides a principled way to build IBMs, but model parameters vary between species and are often difficult to measure. A common solution is to manually compare model outputs with observations from real landscapes and so to obtain parameters which produce acceptable fits of model to data. However, this procedure can be convoluted and lead to over-calibrated and thus inflexible models. Many formal statistical techniques are unsuitable for use with IBMs, but we argue that ABC offers a potential way forward. It can be used to calibrate and compare complex stochastic models and to assess the uncertainty in their predictions. We describe methods used to implement ABC in an accessible way and illustrate them with examples and discussion of recent studies. Although much progress has been made, theoretical issues remain, and some of these are outlined and discussed.

Action learning: how learning transfers from entrepreneurs to small firms

The paper presents research with small and medium enterprise (SME) owners who have participated in a leadership development programme. The primary focus of the paper is on learning transfer and factors affecting it, arguing that entrepreneurs must engage in ‘action’ in order to ‘learn’ and that under certain conditions they may transfer learning to their firm. The paper draws on data from 19 focus groups undertaken from 2010 to 2012, involving 51 participants in the LEAD Wales programme. It considers the literatures exploring learning transfer and develops a conceptual framework, outlining four areas of focus for entrepreneurial learning. Utilising thematic analysis, it describes and evaluates what (actual facts and information) and how (techniques, styles of learning) participants transfer and what actions they take to improve the business and develop their people. The paper illustrates the complex mechanisms involved in this process and concludes that action learning is a method of facilitating entrepreneurial learning which is able to help address some of the problems of engagement, relevance and value that have been highlighted previously. The paper concludes that the efficacy of an entrepreneurial learning intervention in SMEs may depend on the effectiveness of learning transfer.

Contribution to collective harms and responsibility

In the present contribution, I discuss the claim, endorsed by a number of authors, that contributing to a collective harm is the ground for special responsibilities to the victims of that harm. Contributors should, between them, cover the costs of the harms they have inflicted, at least if those harms would otherwise be rights-violating. I raise some doubts about the generality of this principle before moving on to sketch a framework for thinking about liability for the costs of harms in general. This framework uses a contractualist framework to build an account of how to think about liability for costs on the basis of the presumably attractive thought that individual agents should have as much control over their liabilities as is compatible with others having like control. I then use that framework to suggest that liability on the basis of contribution should be restricted to cases in which the contributors could have avoided their contribution relatively costlessly, in which meeting the liability is not crippling for them, and in which such a liability would not have chilling effects, either on them or on third parties. This account of the grounds for contributory liability also has the advantage of avoiding a number of awkward questions about what counts as a contribution by shifting the issue away from often unanswerable questions about the precise causal genesis of some harm or other. Instead, control over conduct, which plausibly has some relation to the harm, becomes crucial. On the basis of this account, I then investigate whether a number of uses of the contributory principle are entirely appropriate. I argue that contributory liability is not appropriate for cases of collective harms committed by coordinated groups in the way that, for example, Iris Marion Young and Thomas Pogge have suggested and that further investigation of how members of such groups may be liable will be needed.

How do people perceive, understand, and anticipate responding to flash flood risks and warnings? Results from a public survey in Boulder, Colorado, USA

This study investigates flash flood forecast and warning communication, interpretation, and decision making, using data from a survey of 418 members of the public in Boulder, Colorado, USA. Respondents to the public survey varied in their perceptions and understandings of flash flood risks in Boulder, and some had misconceptions about flash flood risks, such as the safety of crossing fast-flowing water. About 6% of respondents indicated consistent reversals of US watch-warning alert terminology. However, more in-depth analysis illustrates the multi-dimensional, situationally dependent meanings of flash flood alerts, as well as the importance of evaluating interpretation and use of warning information along with alert terminology. Some public respondents estimated low likelihoods of flash flooding given a flash flood warning; these were associated with lower anticipated likelihood of taking protective action given a warning. Protective action intentions were also lower among respondents who had less trust in flash flood warnings, those who had not made prior preparations for flash flooding, and those who believed themselves to be safer from flash flooding. Additional analysis, using open-ended survey questions about responses to warnings, elucidates the complex, contextual nature of protective decision making during flash flood threats. These findings suggest that warnings can play an important role not only by notifying people that there is a threat and helping motivate people to take protective action, but also by helping people evaluate what actions to take given their situation.

Using Africa’s protected area network to estimate the global population of a threatened and declining species: a case study of the critically endangered White-headed Vulture Trigonoceps occipitalis

The White-headed Vulture Trigonoceps occipitalis (WhV) is uncommon and largely restricted to protected areas across its range in sub-Saharan Africa. We used the World Database on Protected Areas to identify protected areas (PAs) likely to contain White-headed Vultures. Vulture occurrence on road transects in Southern, East, and West Africa was adjusted to nests per km2 using data from areas with known numbers of nests and corresponding road transect data. Nest density was used to calculate the number of WhV nests within identified PAs and from there extrapolated to estimate the global population. Across a fragmented range, 400 PAs are estimated to contain 1893 WhV nests. Eastern Africa is estimated to contain 721 nests, Central Africa 548 nests, Southern Africa 468 nests, and West Africa 156 nests. Including immature and nonbreeding birds, and accounting for data deficient PAs, the estimated global population is 5475 - 5493 birds. The identified distribution highlights are alarming: over 78% (n = 313) of identified PAs contain fewer than five nests. A further 17% (n = 68) of PAs contain 5 - 20 nests and 4% (n = 14) of identified PAs are estimated to contain >20 nests. Just 1% (n = 5) of PAs are estimated to contain >40 nests; none is located in West Africa. Whilst ranging behavior of WhVs is currently unknown, 35% of PAs large enough to hold >20 nests are isolated by more than 100 km from other PAs. Spatially discrete and unpredictable mortality events such as poisoning pose major threats to small localized vulture populations and will accelerate ongoing local extinctions. Apart from reducing the threat of poisoning events, conservation actions promoting linkages between protected areas should be pursued. Identifying potential areas for assisted re-establishment via translocation offers the potential to expand the range of this species and alleviate risk.

'You show me yours, I'll show you mine': the negotiation of shifts from textual to visual modes in computer-mediated interaction among gay men

This article explores the way users of an online gay chat room negotiate the exchange of photographs and the conduct of video conferencing sessions and how this negotiation changes the way participants manage their interactions and claim and impute social identities. Different modes of communication provide users with different resources for the control of information, affecting not just what users are able to reveal, but also what they are able to conceal. Thus, the shift from a purely textual mode for interacting to one involving visual images fundamentally changes the kinds of identities and relationships available to users. At the same time, the strategies users employ to negotiate these shifts of mode can alter the resources available in different modes. The kinds of social actions made possible through different modes, it is argued, are not just a matter of the modes themselves but also of how modes are introduced into the ongoing flow of interaction.