The impact of fruit flavonoids on memory and cognition

There is intense interest in the studies related to the potential of phytochemical-rich foods to prevent age-related neurodegeneration and cognitive decline. Recent evidence has indicated that a group of plant-derived compounds known as flavonoids may exert particularly powerful actions on mammalian cognition and may reverse age-related declines in memory and learning. In particular, evidence suggests that foods rich in three specific flavonoid sub-groups, the flavanols, anthocyanins and/or flavanones, possess the greatest potential to act on the cognitive processes. This review will highlight the evidence for the actions of such flavonoids, found most commonly in fruits, such as apples, berries and citrus, on cognitive behaviour and the underlying cellular architecture. Although the precise mechanisms by which these flavonoids act within the brain remain unresolved, the present review focuses on their ability to protect vulnerable neurons and enhance the function of existing neuronal structures, two processes known to be influenced by flavonoids and also known to underpin neuro-cognitive function. Most notably, we discuss their selective interactions with protein kinase and lipid kinase signalling cascades (i.e. phosphoinositide-3 kinase/Akt and mitogen-activated protein kinase pathways), which regulate transcription factors and gene expression involved in both synaptic plasticity and cerebrovascular blood flow. Overall, the review attempts to provide an initial insight into the potential impact of regular flavonoid-rich fruit consumption on normal or abnormal deteriorations in cognitive performance.

Climate change justice: getting motivated in the last chance saloon

A key reason for pessimism with respect to greenhouse gas emissions reduction relates to the ‘motivation problem’, whereby those who could make the biggest difference prima facie have the least incentive to act because they are most able to adapt: how can we motivate such people (and thereby everyone else) to accept, indeed to initiate, the changes to their lifestyles that are required for effective emissions reductions? This paper offers an account inspired by Rawls of the good of membership of ‘intergenerational cooperative union’ to achieve justice that provides a solution to the motivation problem.

Quantitation of apolipoprotein B-48 in triacylglycerol-rich lipoproteins by a specific enzyme-linked immunosorbent assay

This paper describes the use of an antiserum, specific for apolipoprotein (apo) B-48, in a competitive, enzyme-linked immunosorbent assay (ELISA) for apo B-48 in triacylglycerol-rich lipoprotein (TRL) fractions prepared from fasting and post-prandial plasma samples. Previously we showed the antiserum to act as an effective immunoblotting agent following sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Its use in this ELISA indicates that the antiserum recognises the C-terminal region of the protein on the surface of lipoprotein particles. The ELISA had a sensitivity of less than 37 ng/ml and intra- and inter-assay coefficients of variation of 3.8% and 8.6%, respectively. There was no cross-reaction in the ELISA against serum albumin, ovalbumin, thyroglobulin, or apo B-100 (purified by immunoaffinity chromatography), and high lipid concentrations (as Intralipid) did not interfere. A low density lipoprotein fraction reacted in the ELISA but SDS-PAGE-Western blot analysis confirmed the presence, in the fraction, of a small amount of apo B-48, indicating the existence of low density dietary-derived lipoprotein particles. ELISA and SDS-PAGE-Western blot analysis were used to measure apo B-48 in 12 series of postprandial samples collected from 4 diabetic and 8 normal subjects, following test meals of varying fat content. The mean correlation between the two methods was r = 0.74. The mean fasting concentration of apo B-48 in the TRL fractions from 15 healthy men was 0.46 μg/ml of plasma.

Proposed best practice for statisticians in the reporting and publication of pharmaceutical industry-sponsored clinical trials

In this paper we set out what we consider to be a set of best practices for statisticians in the reporting of pharmaceutical industry-sponsored clinical trials. We make eight recommendations covering: author responsibilities and recognition; publication timing; conflicts of interest; freedom to act; full author access to data; trial registration and independent review. These recommendations are made in the context of the prominent role played by statisticians in the design, conduct, analysis and reporting of pharmaceutical sponsored trials and the perception of the reporting of these trials in the wider community.

Evidence that convergence rather than accommodation controls intermittent distance exotropia

Purpose. This study considered whether vergence drives accommodation or accommodation drives vergence during the control of distance exotropia for near fixation. High accommodative convergence to accommodation (AC/A) ratios are often used to explain this control, but the role of convergence to drive accommodation (the CA/C relationship) is rarely considered. Atypical CA/C characteristics could equally, or better, explain common clinical findings. Methods. 19 distance exotropes, aged 4-11 years, were compared while controlling their deviation with 27 non-exotropic controls aged 5-9 years. Simultaneous vergence and accommodation responses were measured to a range of targets incorporating different combinations of blur, disparity and looming cues at four fixation distances between 2m and 33cm. Stimulus and response AC/A and CA/C ratios were calculated. Results. Accommodation responses for near targets (p=0.017) response gains (p=0.026) were greater in the exotropes than the controls. Despite higher clinical stimulus AC/A ratios, the distance exotropes showed lower laboratory response AC/A ratios (p=0.02), but significantly higher CA/C ratios (p=0.02). All the exotropes, whether the angle changed most with lenses (“controlled by accommodation”) or on occlusion (“controlled by fusion”), used binocular disparity not blur as their main cue to target distance. Conclusions. Increased vergence demand to control intermittent distance exotropia for near also drives significantly more accommodation. Minus lens therapy is more likely to act by correcting over-accommodation driven by controlling convergence, rather than by inducing blur-driven vergence. The use of convergence as a major drive to accommodation explains many clinical characteristics of distance exotropia, including apparently high near stimulus AC/A ratios.

Western Chess: Zugzwang data

This data is derived from Eugene Nalimov's Depth-to-Mate Endgame Tables for Western Chess. While having the move is normally advantageous, there are positions where the side-to-move would have a better theoretical result if it were the other side to move. These are (Type A) 'zugzwang' positions where the 'obligation to act' is unwelcome. This data provides lists of all zugzwangs in sub-7-man chess, and summary data about those sets of zugzwangs including exemplar zugzwangs of maximum depth.

Modulation of vaccine response by concomitant probiotic administration

Evidence suggests that probiotic bacteria modulate both innate and adaptive immunity in the host, and in some situations can result in reduced severity of common illnesses, such as acute rotavirus infection and respiratory infections. Responses to vaccination are increasingly being used to provide high quality information on the immunomodulatory effects of dietary components in humans. The present review focuses on the effect of probiotic administration upon vaccination response. The majority of studies investigating the impact of probiotics on responses to vaccination have been conducted in healthy adults, and at best they show modest effects of probiotics on serum or salivary IgA titres. Studies in infants and in elderly subjects are very limited, and it is too early to draw any firm conclusions regarding the potential for probiotics to act as adjuvants in vaccination. Although some studies are comparable in terms of duration of the intervention and age and characteristics of the subjects, most differ in terms of the probiotic selected. Further well designed, randomized, placebo-controlled studies are needed to fully understand the immunomodulatory properties of probiotics, whether the effects exerted are strain-dependent and age-dependent, and their clinical relevance in enhancing immune protection following vaccination.

Protecting recognized Geneva Convention refugees outside their states of asylum

This article highlights the predicament of persons recognized as refugees according to the Convention Relating to the Status of Refugees (CSR1951 refugees) when they travel outside their state of asylum. Their status entails ipso facto that, if they are ill-treated abroad, they cannot turn to representatives of their state of nationality and request its diplomatic protection, nor can they expect to receive its consular assistance. It is submitted that a state of asylum ought to extend the scope of protection that it offers CSR1951 refugees residing in its territory, and provide them diplomatic protection and consular assistance when they travel abroad as if they were its nationals. Four claims are advanced in support of this contention: First: the advent of human rights treaties has not rendered obsolete the protection of nationals abroad nor has the practice fallen into disuse. On the contrary, protection abroad retains its pedigree and significance, as is illustrated by the recently adopted International Law Commission's Draft Articles on Diplomatic Protection and by frequent resort to consular assistance. Second: while states previously enjoyed unfettered discretion concerning whether and when to protect their nationals abroad, recent developments in domestic jurisdictions as well as in European Union (EU) treaties point to the potential emergence of a qualified duty to exercise state protection or to be willing to provide justifications for its refusal. These developments call particular attention to the vulnerability of CSR1951 refugees: the professed aim of the EU treaty regime is that EU citizens should enjoy effective state protection wherever they travel; by contrast, CSR1951 refugees are in need of state protection wherever they travel. Third: according to CSR1951, states of asylum are required to issue Convention Travel Documents (CTDs) to recognized refugees lawfully staying in their territory. While CTDs do not in of themselves authorize states of asylum to provide protection abroad to their CSR1951 refugees, they reflect partial recognition of the instrumental role of these states in facilitating safe refugee travel. Fourth: while the 'nationality of claims' requirement remains pivotal to the institution of diplomatic protection, and efforts to effectuate its general relaxation have thus far failed, the International Law Commission (ILC) has 'carved out' an exception authorizing states of asylum to provide protection abroad to their recognized refugees. The ILC's protection-enhancing agenda, reflecting progressive development of the law, is laudable, even though it has opted for a rather cautious approach.

Can company-fund manager meetings convey informational benefits? Exploring the rationalisation of equity investment decision making by UK fund managers

Conventional economic theory, applied to information released by listed companies, equates ‘useful’ with ‘price-sensitive’. Stock exchange rules accordingly prohibit the selec- tive, private communication of price-sensitive information. Yet, even in the absence of such communication, UK equity fund managers routinely meet privately with the senior execu- tives of the companies in which they invest. Moreover, they consider these brief, formal and formulaic meetings to be their most important sources of investment information. In this paper we ask how that can be. Drawing on interview and observation data with fund managers and CFOs, we find evidence for three, non-mutually exclusive explanations: that the characterisation of information in conventional economic theory is too restricted, that fund managers fail to act with the rationality that conventional economic theory assumes, and/or that the primary value of the meetings for fund managers is not related to their investment decision making but to the claims of superior knowledge made to clients in marketing their active fund management expertise. Our findings suggest a disconnect between economic theory and economic policy based on that theory, as well as a corre- sponding limitation in research studies that test information-usefulness by assuming it to be synonymous with price-sensitivity. We draw implications for further research into the role of tacit knowledge in equity investment decision-making, and also into the effects of the principal–agent relationship between fund managers and their clients.

Peroxidative bromination and oxygenation of organic compounds: synthesis, X-ray crystal structure and catalytic implications of mononuclear and binuclear oxovanadium(V) complexes containing Schiffbase ligands

Treatment of of (R,R)-N,N-salicylidene cyclohexane 1,2-diamine(H(2)L(1)) in methanol with aqueous NH(4)VO(3) solution in perchloric acid medium affords the mononuclear oxovanadium(V) complex [VOL(1)(MeOH)]-ClO(4) (1) as deep blue solid while the treatment of same solution of (R,R)-N,N-salicylidene cyclohexane 1,2-diamine(H(2)L(1)) with aqueous solution of VOSO(4) leads to the formation of di-(mu-oxo) bridged vanadium(V) complex [VO(2)L(2)](2) (2) as green solid where HL(2) = (R,R)-N-salicylidene cyclohexane 1,2-diamine. The ligand HL(2) is generated in situ by the hydrolysis of one of the imine bonds of HL(1) ligand during the course of formation of complex [VO(2)L(2)](2) (2). Both the compounds have been characterized by single crystal X-ray diffraction as well as spectroscopic methods. Compounds 1 and 2 are to act as catalyst for the catalytic bromide oxidation and C-H bond oxidation in presence of hydrogen peroxide. The representative substrates 2,4-dimethoxy benzoic acid and para-hydroxy benzoic acids are brominated in presence of H(2)O(2) and KBr in acid medium using the above compounds as catalyst. The complexes are also used as catalyst for C-H bond activation of the representative hydrocarbons toluene, ethylbenzene and cyclohexane where hydrogen peroxide acts as terminal oxidant. The yield percentage and turnover number are also quite good for the above catalytic reaction. The oxidized products of hydrocarbons have been characterized by GC Analysis while the brominated products have been characterized by (1)H NMR spectroscopic studies.

The European Flood Alert System and the communication, perception, and use of ensemble predictions for operational flood risk management

Although ensemble prediction systems (EPS) are increasingly promoted as the scientific state-of-the-art for operational flood forecasting, the communication, perception, and use of the resulting alerts have received much less attention. Using a variety of qualitative research methods, including direct user feedback at training workshops, participant observation during site visits to 25 forecasting centres across Europe, and in-depth interviews with 69 forecasters, civil protection officials, and policy makers involved in operational flood risk management in 17 European countries, this article discusses the perception, communication, and use of European Flood Alert System (EFAS) alerts in operational flood management. In particular, this article describes how the design of EFAS alerts has evolved in response to user feedback and desires for a hydrographic-like way of visualizing EFAS outputs. It also documents a variety of forecaster perceptions about the value and skill of EFAS forecasts and the best way of using them to inform operational decision making. EFAS flood alerts were generally welcomed by flood forecasters as a sort of ‘pre-alert’ to spur greater internal vigilance. In most cases, however, they did not lead, by themselves, to further preparatory action or to earlier warnings to the public or emergency services. Their hesitancy to act in response to medium-term, probabilistic alerts highlights some wider institutional obstacles to the hopes in the research community that EPS will be readily embraced by operational forecasters and lead to immediate improvements in flood incident management. The EFAS experience offers lessons for other hydrological services seeking to implement EPS operationally for flood forecasting and warning. Copyright © 2012 John Wiley & Sons, Ltd.

Sharing power? Prospects for a U.S. concert-balance strategy

The Pax Americana and the grand strategy of hegemony (or “Primacy”) that underpins it may be becoming unsustainable. Particularly in the wake of exhausting wars, the Global Financial Crisis, and the shift of wealth from West to East, it may no longer be possible or prudent for the United States to act as the unipolar sheriff or guardian of a world order. But how viable are the alternatives, and what difficulties will these alternatives entail in their design and execution? This analysis offers a sympathetic but critical analysis of alternative U.S. National Security Strategies of “retrenchment” that critics of American diplomacy offer. In these strategies, the United States would anticipate the coming of a more multipolar world and organize its behavior around the dual principles of “concert” and “balance,” seeking a collaborative relationship with other great powers, while being prepared to counterbalance any hostile aggressor that threatens world order. The proponents of such strategies argue that by scaling back its global military presence and its commitments, the United States can trade prestige for security, shift burdens, and attain a more free hand. To support this theory, they often look to the 19th-century concert of Europe as a model of a successful security regime and to general theories about the natural balancing behavior of states. This monograph examines this precedent and measures its usefulness for contemporary statecraft to identify how great power concerts are sustained and how they break down. The project also applies competing theories to how states might behave if world politics are in transition: Will they balance, bandwagon, or hedge? This demonstrates the multiple possible futures that could shape and be shaped by a new strategy. viii A new strategy based on an acceptance of multipolarity and the limits of power is prudent. There is scope for such a shift. The convergence of several trends—including transnational problems needing collaborative efforts, the military advantages of defenders, the reluctance of states to engage in unbridled competition, and hegemony fatigue among the American people—means that an opportunity exists internationally and at home for a shift to a new strategy. But a Concert-Balance strategy will still need to deal with several potential dilemmas. These include the difficulty of reconciling competitive balancing with cooperative concerts, the limits of balancing without a forward-reaching onshore military capability, possible unanticipated consequences such as a rise in regional power competition or the emergence of blocs (such as a Chinese East Asia or an Iranian Gulf), and the challenge of sustaining domestic political support for a strategy that voluntarily abdicates world leadership. These difficulties can be mitigated, but they must be met with pragmatic and gradual implementation as well as elegant theorizing and the need to avoid swapping one ironclad, doctrinaire grand strategy for another.

Participation in Higher Education: aspirations, attainment and social background

The recent report of the Milburn Review into Social Mobility highlights the under-representation of young people from lower socio-economic groups in higher education and encourages universities and others to act to remedy this situation as a contribution to greater social mobility. The paper uses data from the Longitudinal Study of Young People in England to examine the relationship between social background, attainment and university participation. The results show that differences in school-level attainment associated with social background are by far the most important explanation for social background differences in university attendance. However, there remains a small proportion of the participation gap that is not accounted for by attainment. It is also the case that early intentions for higher education participation are highly predictive of actual participation. The results suggest that although there may be some scope for universities to act to improve participation by people from less advantaged backgrounds, a much more important focus of action is on improving the school-level achievement of these students.

Seasonal cycles and variability of O3 and H2O in the UT/LMS during SPURT

Airborne high resolution in situ measurements of a large set of trace gases including ozone (O3) and total water (H2O) in the upper troposphere and the lowermost stratosphere (UT/LMS) have been performed above Europe within the SPURT project. SPURT provides an extensive data coverage of the UT/LMS in each season within the time period between November 2001 and July 2003. In the LMS a distinct spring maximum and autumn minimum is observed in O3, whereas its annual cycle in the UT is shifted by 2–3 months later towards the end of the year. The more variable H2O measurements reveal a maximum during summer and a minimum during autumn/winter with no phase shift between the two atmospheric compartments. For a comprehensive insight into trace gas composition and variability in the UT/LMS several statistical methods are applied using chemical, thermal and dynamical vertical coordinates. In particular, 2-dimensional probability distribution functions serve as a tool to transform localised aircraft data to a more comprehensive view of the probed atmospheric region. It appears that both trace gases, O3 and H2O, reveal the most compact arrangement and are best correlated in the view of potential vorticity (PV) and distance to the local tropopause, indicating an advanced mixing state on these surfaces. Thus, strong gradients of PV seem to act as a transport barrier both in the vertical and the horizontal direction. The alignment of trace gas isopleths reflects the existence of a year-round extra-tropical tropopause transition layer. The SPURT measurements reveal that this layer is mainly affected by stratospheric air during winter/spring and by tropospheric air during autumn/summer. Normalised mixing entropy values for O3 and H2O in the LMS appear to be maximal during spring and summer, respectively, indicating highest variability of these trace gases during the respective seasons.

Human microbiota in health and disease

Each human body plays host to a microbial population which is both numerically vast (at around 1014 microbial cells) and phenomenally diverse (over 1,000 species). The majority of the microbial species in the gut have not been cultured but the application of culture-independent approaches for high throughput diversity and functionality analysis has allowed characterisation of the diverse microbial phylotypes present in health and disease. Studies in monozygotic twins, showing that these retain highly similar microbiota decades after birth and initial colonisation, are strongly indicative that diversity of the microbiome is host-specific and affected by the genotype. Microbial diversity in the human body is reflected in both richness and evenness. Diversity increases steeply from birth reaching its highest point in early adulthood, before declining in older age. However, in healthy subjects there appears to be a core of microbial phylotypes which remains relatively stable over time. Studies of individuals from diverse geopraphies suggest that clusters of intestinal bacterial groups tend to occur together, constituting ‘enterotypes’. So variation in intestinal microbiota is stratified rather than continuous and there may be a limited number of host/microbial states which respond differently to environmental influences. Exploration of enterotypes and functional groups may provide biomarkers for disease and insights into the potential for new treatments based on manipulation of the microbiome. In health, the microbiota interact with host defences and exist in harmonious homeostasis which can then be disturbed by invading organisms or when ‘carpet bombing’ by antibiotics occurs. In a portion of individuals with infections, the disease will resolve itself without the need for antibiotics and microbial homeostasis with the host’s defences is restored. The administration of probiotics (live microorganisms which when administered in adequate amounts confer a health benefit on the host) represents an artificial way to enhance or stimulate these natural processes. The study of innate mechanisms of antimicrobial defence on the skin, including the production of numerous antimicrobial peptides (AMPs), has shown an important role for skin commensal organisms. These organisms may produce AMPs, and also amplify the innate immune responses to pathogens by activating signalling pathways and processing host produced AMPs. Research continues into how to enhance and manipulate the role of commensal organisms on the skin. The challenges of skin infection (including diseases caused by multiply resistant organisms) and infestations remain considerable. The potential to re-colonise the skin to replace or reduce pathogens, and exploring the relationship between microbiota elsewhere and skin diseases are among a growing list of research targets. Lactobacillus species are among the best known ‘beneficial’ bacterial members of the human microbiota. Of the approximately 120 species known, about 15 are known to occur in the human vagina. These organisms have multiple properties, including the production of lactic acid, hydrogen peroxide and bacteriocins, which render the vagina inhospitable to potential pathogens. Depletion of the of the normal Lactobacillus population and overgrowth of vaginal anaerobes, accompanied by the loss of normal vaginal acidity can lead to bacterial vaginosis – the commonest cause of abnormal vaginal discharge in women. Some vaginal anaerobes are associated with the formation of vaginal biofilms which serve to act as a reservoir of organisms which persists after standard antibiotic therapy of bacterial vaginosis and may help to account for the characteristically high relapse rate in the condition. Administration of Lactobacillus species both vaginally and orally have shown beneficial effects in the treatment of bacterial vaginosis and such treatments have an excellent overall safety record. Candida albicans is a frequent coloniser of human skin and mucosal membranes, and is a normal part of the microbiota in the mouth, gut and vagina. Nevertheless Candida albicans is the most common fungal pathogen worldwide and is a leading cause of serious and often fatal nosocomial infections. What turns this organism from a commensal to a pathogen is a combination of increasing virulence in the organism and predisposing host factors that compromise immunity. There has been considerable research into the use of probiotic Lactobacillus spp. in vaginal candidiasis. Studies in reconstituted human epithelium and monolayer cell cultures have shown that L. rhamnosus GG can protect mucosa from damage caused by Candida albicans, and enhance the immune responses of mucosal surfaces. Such findings offer the promise that the use of such probiotic bacteria could provide new options for antifungal therapy. Studies of changes of the human intestinal microbiota in health and disease are complicated by its size and diversity. The Alimentary Pharmabiotic Centre in Cork (Republic of Ireland) has the mission to ‘mine microbes for mankind’ and its work illustrates the potential benefits of understanding the gut microbiota. Work undertaken at the centre includes: mapping changes in the microbiota with age; studies of the interaction between the microbiota and the gut; potential interactions between the gut microbiota and the central nervous system; the potential for probiotics to act as anti-infectives including through the production of bacteriocins; and the characterisation of interactions between gut microbiota and bile acids which have important roles as signalling molecules and in immunity. The important disease entity where the role of the gut microbiota appears to be central is the Irritable Bowel Syndrome (IBS). IBS patients show evidence of immune activation, impaired gut barrier function and abnormal gut microbiota. Studies with probiotics have shown that these organisms can exert anti-inflammatory effects in inflammatory bowel disease and may strengthen the gut barrier in IBS of the diarrhoea-predominant type. Formal randomised trials of probiotics in IBS show mixed results with limited benefit for some but not all. Studies confirm that administered probiotics can survive and temporarily colonise the gut. They can also stimulate the numbers of other lactic acid bacilli in the gut, and reduce the numbers of pathogens. However consuming live organisms is not the only way to influence gut microbiota. Dietary prebiotics are selectively fermented ingredients that can change the composition and/or activity of the gastrointestinal microbiota in beneficial ways. Dietary components that reach the colon, and are available to influence the microbiota include poorly digestible carbohydrates, such as non-starch polysaccharides, resistant starch, non-digestible oligosaccharides (NDOs) and polyphenols. Mixtures of probiotic and prebiotic ingredients that can selectively stimulate growth or activity of health promoting bacteria have been termed ‘synbiotics’. All of these approaches can influence gut microbial ecology, mainly to increase bifidobacteria and lactobacilli, but metagenomic approaches may reveal wider effects. Characterising how these changes produce physiological benefits may enable broader use of these tactics in health and disease in the future. The current status of probiotic products commercially available worldwide is less than ideal. Prevalent problems include misidentification of ingredient organisms and poor viability of probiotic microorganisms leading to inadequate shelf life. On occasions these problems mean that some commercially available products cannot be considered to meet the definition of a probiotic product. Given the potential benefits of manipulating the human microbiota for beneficial effects, there is a clear need for improved regulation of probiotics. The potential importance of the human microbiota cannot be overstated. ‘We feed our microbes, they talk to us and we benefit. We just have to understand and then exploit this.’ (Willem de Vos).