Flavonoids and cognitive function: a review of human randomized controlled trial studies and recommendations for future studies

Evidence in support of the neuroprotective effects of flavonoids has increased significantly in recent years, although to date much of this evidence has emerged from animal rather than human studies. Nonetheless, with a view to making recommendations for future good practice, we review 15 existing human dietary intervention studies that have examined the effects of particular types of flavonoid on cognitive performance. The studies employed a total of 55 different cognitive tests covering a broad range of cognitive domains. Most studies incorporated at least one measure of executive function/working memory, with nine reporting significant improvements in performance as a function of flavonoid supplementation compared to a control group. However, some domains were overlooked completely (e.g. implicit memory, prospective memory), and for the most part there was little consistency in terms of the particular cognitive tests used making across study comparisons difficult. Furthermore, there was some confusion concerning what aspects of cognitive function particular tests were actually measuring. Overall, while initial results are encouraging, future studies need to pay careful attention when selecting cognitive measures, especially in terms of ensuring that tasks are actually sensitive enough to detect treatment effects.

Cost-effectiveness of a preventive counseling and support package for postnatal depression

Objectives: This study reports the cost-effectiveness of a preventive intervention, consisting of counseling and specific support for the mother-infant relationship, targeted at women at high risk of developing postnatal depression. Methods: A prospective economic evaluation was conducted alongside a pragmatic randomized controlled trial in which women considered at high risk of developing postnatal depression were allocated randomly to the preventive intervention (n = 74) or to routine primary care (n = 77). The primary outcome measure was the duration of postnatal depression experienced during the first 18 months postpartum. Data on health and social care use by women and their infants up to 18 months postpartum were collected, using a combination of prospective diaries and face-to-face interviews, and then were combined with unit costs ( pound, year 2000 prices) to obtain a net cost per mother-infant dyad. The nonparametric bootstrap method was used to present cost-effectiveness acceptability curves and net benefit statistics at alternative willingness to pay thresholds held by decision makers for preventing 1 month of postnatal depression. Results: Women in the preventive intervention group were depressed for an average of 2.21 months (9.57 weeks) during the study period, whereas women in the routine primary care group were depressed for an average of 2.70 months (11.71 weeks). The mean health and social care costs were estimated at 2,396.9 pound per mother-infant dyad in the preventive intervention group and 2,277.5 pound per mother-infant dyad in the routine primary care group, providing a mean cost difference of 119.5 pound (bootstrap 95 percent confidence interval [Cl], -535.4, 784.9). At a willingness to pay threshold of 1,000 pound per month of postnatal depression avoided, the probability that the preventive intervention is cost-effective is .71 and the mean net benefit is 383.4 pound (bootstrap 95 percent Cl, -863.3- pound 1,581.5) pound. Conclusions: The preventive intervention is likely to be cost-effective even at relatively low willingness to pay thresholds for preventing 1 month of postnatal depression during the first 18 months postpartum. Given the negative impact of postnatal depression on later child development, further research is required that investigates the longer-term cost-effectiveness of the preventive intervention in high risk women.

Interest in Medieval accounts: examples from England, 1272-1340

The charging of interest for borrowing money, and the level at which it is charged, is of fundamental importance to the economy. Unfortunately, the study of the interest rates charged in the middle ages has been hampered by the diversity of terms and methods used by historians. This article seeks to establish a standardized methodology to calculate interest rates from historical sources and thereby provide a firmer foundation for comparisons between regions and periods. It should also contribute towards the current historical reassessment of medieval economic and financial development. The article is illustrated with case studies drawn from the credit arrangements of the English kings between 1272 and c.1340, and argues that changes in interest rates reflect, in part, contemporary perceptions of the creditworthiness of the English crown.

Cognitive tests used in chronic adult human randomised controlled trial micronutrient and phytochemical intervention studies

In recent years there has been a rapid growth of interest in exploring the relationship between nutritional therapies and the maintenance of cognitive function in adulthood. Emerging evidence reveals an increasingly complex picture with respect to the benefits of various food constituents on learning, memory and psychomotor function in adults. However, to date, there has been little consensus in human studies on the range of cognitive domains to be tested or the particular tests to be employed. To illustrate the potential difficulties that this poses, we conducted a systematic review of existing human adult randomised controlled trial (RCT) studies that have investigated the effects of 24 d to 36 months of supplementation with flavonoids and micronutrients on cognitive performance. There were thirty-nine studies employing a total of 121 different cognitive tasks that met the criteria for inclusion. Results showed that less than half of these studies reported positive effects of treatment, with some important cognitive domains either under-represented or not explored at all. Although there was some evidence of sensitivity to nutritional supplementation in a number of domains (for example, executive function, spatial working memory), interpretation is currently difficult given the prevailing 'scattergun approach' for selecting cognitive tests. Specifically, the practice means that it is often difficult to distinguish between a boundary condition for a particular nutrient and a lack of task sensitivity. We argue that for significant future progress to be made, researchers need to pay much closer attention to existing human RCT and animal data, as well as to more basic issues surrounding task sensitivity, statistical power and type I error.

PINCER trial: a cluster randomised trial comparing the effectiveness and cost-effectiveness of a pharmacist-led IT-based intervention with simple feedback in reducing rates of clinically important errors in medicines management in general practices

Background: Medication errors in general practice are an important source of potentially preventable morbidity and mortality. Building on previous descriptive, qualitative and pilot work, we sought to investigate the effectiveness, cost-effectiveness and likely generalisability of a complex pharm acist-led IT-based intervention aiming to improve prescribing safety in general practice. Objectives: We sought to: • Test the hypothesis that a pharmacist-led IT-based complex intervention using educational outreach and practical support is more effective than simple feedback in reducing the proportion of patients at risk from errors in prescribing and medicines management in general practice. • Conduct an economic evaluation of the cost per error avoided, from the perspective of the National Health Service (NHS). • Analyse data recorded by pharmacists, summarising the proportions of patients judged to be at clinical risk, the actions recommended by pharmacists, and actions completed in the practices. • Explore the views and experiences of healthcare professionals and NHS managers concerning the intervention; investigate potential explanations for the observed effects, and inform decisions on the future roll-out of the pharmacist-led intervention • Examine secular trends in the outcome measures of interest allowing for informal comparison between trial practices and practices that did not participate in the trial contributing to the QRESEARCH database. Methods Two-arm cluster randomised controlled trial of 72 English general practices with embedded economic analysis and longitudinal descriptive and qualitative analysis. Informal comparison of the trial findings with a national descriptive study investigating secular trends undertaken using data from practices contributing to the QRESEARCH database. The main outcomes of interest were prescribing errors and medication monitoring errors at six- and 12-months following the intervention. Results: Participants in the pharmacist intervention arm practices were significantly less likely to have been prescribed a non-selective NSAID without a proton pump inhibitor (PPI) if they had a history of peptic ulcer (OR 0.58, 95%CI 0.38, 0.89), to have been prescribed a beta-blocker if they had asthma (OR 0.73, 95% CI 0.58, 0.91) or (in those aged 75 years and older) to have been prescribed an ACE inhibitor or diuretic without a measurement of urea and electrolytes in the last 15 months (OR 0.51, 95% CI 0.34, 0.78). The economic analysis suggests that the PINCER pharmacist intervention has 95% probability of being cost effective if the decision-maker’s ceiling willingness to pay reaches £75 (6 months) or £85 (12 months) per error avoided. The intervention addressed an issue that was important to professionals and their teams and was delivered in a way that was acceptable to practices with minimum disruption of normal work processes. Comparison of the trial findings with changes seen in QRESEARCH practices indicated that any reductions achieved in the simple feedback arm were likely, in the main, to have been related to secular trends rather than the intervention. Conclusions Compared with simple feedback, the pharmacist-led intervention resulted in reductions in proportions of patients at risk of prescribing and monitoring errors for the primary outcome measures and the composite secondary outcome measures at six-months and (with the exception of the NSAID/peptic ulcer outcome measure) 12-months post-intervention. The intervention is acceptable to pharmacists and practices, and is likely to be seen as costeffective by decision makers.

Quantifying the value of ecosystem services: a case study of honeybee pollination in the UK

There is concern that insect pollinators, such as honey bees, are currently declining in abundance, and are under serious threat from environmental changes such as habitat loss and climate change; the use of pesticides in intensive agriculture, and emerging diseases. This paper aims to evaluate how much public support there would be in preventing further decline to maintain the current number of bee colonies in the UK. The contingent valuation method (CVM) was used to obtain the willingness to pay (WTP) for a theoretical pollinator protection policy. Respondents were asked whether they would be WTP to support such a policy and how much would they pay? Results show that the mean WTP to support the bee protection policy was £1.37/week/household. Based on there being 24.9 million households in the UK, this is equivalent to £1.77 billion per year. This total value can show the importance of maintaining the overall pollination service to policy makers. We compare this total with estimates obtained using a simple market valuation of pollination for the UK.

A method for the economic valuation of animal welfare benefits using a single welfare score

Unless the benefits to society of measures to protect and improve the welfare of animals are made transparent by means of their valuation they are likely to go unrecognised and cannot easily be weighed against the costs of such measures as required, for example, by policy-makers. A simple single measure scoring system, based on the Welfare Quality® index, is used, together with a choice experiment economic valuation method, to estimate the value that people place on improvements to the welfare of different farm animal species measured on a continuous (0-100) scale. Results from using the method on a survey sample of some 300 people show that it is able to elicit apparently credible values. The survey found that 96% of respondents thought that we have a moral obligation to safeguard the welfare of animals and that over 72% were concerned about the way farm animals are treated. Estimated mean annual willingness to pay for meat from animals with improved welfare of just one point on the scale was £5.24 for beef cattle, £4.57 for pigs and £5.10 for meat chickens. Further development of the method is required to capture the total economic value of animal welfare benefits. Despite this, the method is considered a practical means for obtaining economic values that can be used in the cost-benefit appraisal of policy measures intended to improve the welfare of animals.

Office sustainability: occupier perceptions and implementation of policy

Purpose – The purpose of this research was twofold. First, to investigate the views of occupiers in a typical UK city on the importance of various sustainability issues, their perceived impact of different sustainability drivers and willingness to pay. Second, the environmental and social performance of existing buildings in that city was examined. Design/methodology/approach – The research focuses on buildings of 10,000 feet2 or more that have been constructed in the Bristol city-region in the UK over the past 50 years. The buildings in the sample are located in the city centre and in out-of-town business parks. A questionnaire survey investigated the views of occupiers and follow-up interviews looked more closely at the sustainability performance of the existing stock. Findings – The findings indicate that, as far as occupiers are concerned, the strongest drivers are consumer demand and staff demand. Green features of a building appear to rank low in the overall building selection preference structure and a willingness to pay a premium for green features was indicated. The interviews uncovered barriers to progress as well as initiatives to reduce both energy consumption and the environmental impact of office space. Practical implications – The paper identifies progress and issues which could form obstacles to improving the environmental performance of office buildings. It is argued that there is a need to focus on energy efficiency. Originality/value – This paper explores the linkage between the perception and use of office space by occupants and how this affects the environmental performance of this space.

A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis

Background: Medication errors are common in primary care and are associated with considerable risk of patient harm. We tested whether a pharmacist-led, information technology-based intervention was more effective than simple feedback in reducing the number of patients at risk of measures related to hazardous prescribing and inadequate blood-test monitoring of medicines 6 months after the intervention. Methods: In this pragmatic, cluster randomised trial general practices in the UK were stratified by research site and list size, and randomly assigned by a web-based randomisation service in block sizes of two or four to one of two groups. The practices were allocated to either computer-generated simple feedback for at-risk patients (control) or a pharmacist-led information technology intervention (PINCER), composed of feedback, educational outreach, and dedicated support. The allocation was masked to general practices, patients, pharmacists, researchers, and statisticians. Primary outcomes were the proportions of patients at 6 months after the intervention who had had any of three clinically important errors: non-selective non-steroidal anti-inflammatory drugs (NSAIDs) prescribed to those with a history of peptic ulcer without co-prescription of a proton-pump inhibitor; β blockers prescribed to those with a history of asthma; long-term prescription of angiotensin converting enzyme (ACE) inhibitor or loop diuretics to those 75 years or older without assessment of urea and electrolytes in the preceding 15 months. The cost per error avoided was estimated by incremental cost-eff ectiveness analysis. This study is registered with Controlled-Trials.com, number ISRCTN21785299. Findings: 72 general practices with a combined list size of 480 942 patients were randomised. At 6 months’ follow-up, patients in the PINCER group were significantly less likely to have been prescribed a non-selective NSAID if they had a history of peptic ulcer without gastroprotection (OR 0∙58, 95% CI 0∙38–0∙89); a β blocker if they had asthma (0∙73, 0∙58–0∙91); or an ACE inhibitor or loop diuretic without appropriate monitoring (0∙51, 0∙34–0∙78). PINCER has a 95% probability of being cost eff ective if the decision-maker’s ceiling willingness to pay reaches £75 per error avoided at 6 months. Interpretation: The PINCER intervention is an effective method for reducing a range of medication errors in general practices with computerised clinical records. Funding: Patient Safety Research Portfolio, Department of Health, England.

Sector and regional factors in real estate returns

This paper presents a simple method to measure the effect of sector and regional factors in real estate returns, and thus provides a quantitative framework for analysing the relative impact of these two diversification categories to real estate portfolio selection. Using data on Retail, Office and Industrial properties spread across 326 real estate locations in the UK, over the period 1981 to 1995, the results show that the performance of real estate is largely sector-driven. A result in line with previous work. Which implies that the sector composition of the real estate fund should be the first level of analysis in constructing and managing the real estate portfolio. As a consequence real estate fund managers need to pay more attention to the sector allocation of their portfolios than the regional spread.

Marriage value and scarcity in agricultural rents: a discussion of the findings in Childers v Ankers

Formal statutory guidance to arbitrators involved in settling disputes over rents for agricultural holdings is contained in the Agricultural Holdings Act 1986. The particular features of the agricultural letting market raise valuation problems which the Act itself has failed to satisfactorily address, most notably the degree to which marriage value and scarcity should be taken into account. The 1995 Court of Appeal case of Childers v Anker addresses several of the key issues. This paper seeks to explore the findings and practical implications of the case for rental valuers and arbitrators. It argues that sitting tenants may be seriously disadvantaged by the court's judgements, not least by having to pay rents on review which reflect elements of marriage value and possibly scarcity value.

On an alleged truth/falsity asymmetry in context shifting experiments

Keith DeRose has argued that context shifting experiments should be designed in a specific way in order to accommodate what he calls a ‘truth/falsity asymmetry’. I explain and critique DeRose's reasons for proposing this modification to contextualist methodology, drawing on recent experimental studies of DeRose's bank cases as well as experimental findings about the verification of affirmative and negative statements. While DeRose's arguments for his particular modification to contextualist methodology fail, the lesson of his proposal is that there is good reason to pay close attention to several subtle aspects of the design of context shifting experiments.

Deal size, acquisition premia and shareholder gains

This study examines the contradictory predictions regarding the association between the premium paid in acquisitions and deal size. We document a robust negative relation between offer premia and target size, indicating that acquirers tend to pay less for large firms, not more. We also find that the overpayment potential is lower in acquisitions of large targets. Yet, they still destroy more value for acquirers around deal announcements, implying that target size may proxy, among others, for the unobserved complexity inherent in large deals. We provide evidence in favor of this interpretation.

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.

Contested institutions? Traditional leaders and land access and control in communal areas of Eastern Cape Province, South Africa

The South African government has endeavoured to strengthen property rights in communal areas and develop civil society institutions for community-led development and natural resource management. However, the effectiveness of this remains unclear as the emergence and operation of civil society institutions in these areas is potentially constrained by the persistence of traditional authorities. Focusing on the former Transkei region of Eastern Cape Province, three case study communities are used examine the extent to which local institutions overlap in issues of land access and control. Within these communities, traditional leaders (chiefs and headmen) continue to exercise complete and sole authority over land allocation and use this to entrench their own positions. However, in the absence of effective state support, traditional authorities have only limited power over how land is used and in enforcing land rights, particularly over communal resources such as rangeland. This diminishes their local legitimacy and encourages some groups to contest their authority by cutting fences, ignoring collective grazing decisions and refusing to pay ‘fees’ levied on them. They are encouraged in such activities by the presence of democratically elected local civil society institutions such as ward councillors and farmers’ organisations, which have broad appeal and are increasingly responsible for much of the agrarian development that takes place, despite having no direct mandate over land. Where it occurs at all, interaction between these different institutions is generally restricted to approval being required from traditional leaders for land allocated to development projects. On this basis it is argued that a more radical approach to land reform in communal areas is required, which transfers all powers over land to elected and accountable local institutions and integrates land allocation, land management and agrarian development more effectively.