Efficacy of memantine for agitation in Alzheimer's dementia:a randomised double-blind placebo controlled trial

Background - Agitation in Alzheimer’s disease (AD) is common and associated with poor patient life-quality and carer distress. The best evidence-based pharmacological treatments are antipsychotics which have limited benefits with increased morbidity and mortality. There are no memantine trials in clinically significant agitation but post-hoc analyses in other populations found reduced agitation. We tested the primary hypothesis, memantine is superior to placebo for clinically significant agitation, in patients with moderate-to-severe AD. Methods and Findings - We recruited 153 participants with AD and clinically significant agitation from care-homes or hospitals for a double-blind randomised-controlled trial and 149 people started the trial of memantine versus placebo. The primary outcome was 6 weeks mixed model autoregressive analysis of Cohen-Mansfield Agitation Inventory (CMAI). Secondary outcomes were: 12 weeks CMAI; 6 and 12 weeks Neuropsychiatric symptoms (NPI), Clinical Global Impression Change (CGI-C), Standardised Mini Mental State Examination, Severe Impairment Battery. Using a mixed effects model we found no significant differences in the primary outcome, 6 weeks CMAI, between memantine and placebo (memantine lower -3.0; -8.3 to 2.2, p = 0.26); or 12 weeks CMAI; or CGI-C or adverse events at 6 or 12 weeks. NPI mean difference favoured memantine at weeks 6 (-6.9; -12.2 to -1.6; p = 0.012) and 12 (-9.6; -15.0 to -4.3 p = 0.0005). Memantine was significantly better than placebo for cognition. The main study limitation is that it still remains to be determined whether memantine has a role in milder agitation in AD. Conclusions - Memantine did not improve significant agitation in people with in moderate-to-severe AD. Future studies are urgently needed to test other pharmacological candidates in this group and memantine for neuropsychiatric symptoms.

The impact of portfolio diversification on trading rule profits:some evidence for UK share portfolios

This paper demonstrates how the autocorrelation structure of UK portfolio returns is linked to dynamic interrelationships among the component securities of that portfolio. Moreover, portfolio return autocorrelation is shown to be an increasing function of the number of securities in the portfolio. Since the security interrelationships seemed to be more a product of their history of non-synchronous trading than of systematic industry-related phenomena, it should not be possible to exploit the high levels of return persistence using trading rules. We show that rules designed to exploit this portfolio autocorrelation structure do not produce economic profits.

Testing the assertion that 'local food is best':the challenges of an evidence-based approach

Advocates of ‘local food’ claim it serves to reduce food miles and greenhouse gas emissions, improve food safety and quality, strengthen local economies and enhance social capital. We critically review the philosophical and scientific rationale for this assertion, and consider whether conventional scientific approaches can help resolve the debate. We conclude that food miles are a poor indicator of the environmental and ethical impacts of food production. Only through combining spatially explicit life cycle assessment with analysis of social issues can the benefits of local food be assessed. This type of analysis is currently lacking for nearly all food chains.

The sociolinguistic stratification of a connected speech process - The case of the T to R rule in the Black Country

This paper examines the connected speech process described by Wells (1982b) as the T to R rule in the West Midlands speech variety associated with the Black Country. The T to R rule is well known as a linguistic marker of local varieties of the middle and far north of England. Less well understood is its position in the phonological systems of Midlands varieties. Varieties of the Midlands of England are underresearched in comparison with varieties of the north, and what is known about the application of the T to R rule in this transitional dialect area is correspondingly nebulous. This paper focuses on the Black Country area, and examines the possible outputs in the contexts which give rise to /t/ becoming [?] in local varieties of the north. I examine the written and spoken evidence which suggests that the T to R rule does indeed operate in the Black Country variety. My analysis focuses on possible phonetic outcomes of the T to R rule across time. In my conclusion, I discuss briefly the possibility that, lying on a bundle of isoglosses separating north from south, the variety of the Black Country reflects this in that a T to [?] rule, rather than a T to R rule, is the dominant output of this connected speech process in the Black Country.

Testing term structure estimation methods:evidence from the UK STRIPs market

Prices and yields of UK government zero-coupon bonds are used to test alternative yield curve estimation models. Zero-coupon bonds permit a more pure comparison, as the models are providing only the interpolation service and also not making estimation feasible. It is found that better yield curves estimates are obtained by fitting to the yield curve directly rather than fitting first to the discount function. A simple procedure to set the smoothness of the fitted curves is developed, and a positive relationship between oversmoothness and the fitting error is identified. A cubic spline function fitted directly to the yield curve provides the best overall balance of fitting error and smoothness, both along the yield curve and within local maturity regions.

Institutions and firm ownership structure:evidence from Central and Eastern Europe

FDI plays a key role in development, particularly in resource-constrained transition economies of Central and Eastern Europe with relatively low savings rates. Gains from technology transfer play a critical role in motivating FDI, yet potential for it may be hampered by a large technology gap between the source and host country. While the extent of this gap has traditionally been attributed to education, skills and capital intensity, recent literature has also emphasized the possible role of institutional environment in this respect. Despite tremendous interest among policy-makers and academics to understand the factors attracting FDI (Bevan and Estrin, 2000; Globerman and Shapiro, 2003) our knowledge about the effects of institutions on the location choice and ownership structure of foreign firms remains limited. This paper attempts to fill this gap in the literature by examining the link between institutions and foreign ownership structures. To the best of our knowledge, Javorcik (2004) is the only papers, which use firm-level data to analyse the role of institutional quality on an outward investor’s entry mode in transition countries. Our paper extends Javorcik (2004) in a number of ways: (a) rather than a cross-section, we use panel data for the period 1997-2006; (b) rather than a binary variable, we use the percentage foreign ownership as continuous variable; (c) we consider multi-dimensional institutional variables, such as corruption, intellectual property rights protection and government stability. We also use factor analysis to generate a composite index of institutional quality and see how stronger institutional environment could affect foreign ownership; (d) we explore how the distance between institutional environment in source and host countries affect foreign ownership in a host country. The firm-level data used includes both domestic and foreign firms for the period 1997-2006 and is drawn from ORBIS, a commercially available dataset provided by Bureau van Dijk. In order to examine the link between institutions and foreign ownership structures, we estimate four log-linear ownership equations/specifications augmented by institutional and other control variables. We find evidence that the decision of a foreign firm to either locate its subsidiary or acquire an existing domestic firm depends not only on factor cost differences but also on differences in institutional environment between the host and source countries.

Portfolio diversification and filter rule profits

Previously, it has been shown that the profits from a simple market timing trading rule applied to a portfolio of shares can be affected by the inter-relationships between the returns of the component securities. In this short letter, the results from applying a more sophisticated 'filter' rule to the same data are reported. Unlike the simple trading rule, the filter rule does produce some evidence of economic profits.

To challenge, or not to challenge? Best practice when interviewing vulnerable suspects

This paper examines to what extent police investigators can reliably question a vulnerable suspect’s account when the evidence base for appropriate questioning styles for this particular vulnerable group is limited. We examine a simulated interview to demonstrate how difficult it is to challenge discrepancies in a vulnerable suspect’s account. It is argued from both linguistic and psychological perspectives that certain question formats may lead to acquiescence, cognitive overload and confusion for the suspect. It is suggested that one way of trying to manage these issues is through the provision of alternative narratives (i.e. ‘only one of those stories can be true’) but these too are found to be problematic.

Evidence of a transition from perceptual to category induction in 3- to 9-year-old children

We examined whether inductive reasoning development is better characterized by accounts assuming an early category bias versus an early perceptual bias. We trained 264 children aged 3 to 9 years to categorize novel insects using a rule that directly pitted category membership against appearance. This was followed by an induction task with perceptual distractors at different levels of featural similarity. An additional 52 children were given the same training followed by an induction task with alternative stimuli. Categorization performance was consistently high, however we found a gradual transition from a perceptual bias in our youngest children to a category bias around age 6-7. In addition, children of all ages were equally distracted by higher levels of featural similarity. The transition is unlikely to be due to an increased ability to inhibit perceptual distractors. Instead, we argue that the transition is driven by a fundamental change in children’s understanding of category membership.

Blobs versus bars:psychophysical evidence supports two types of orientation response in human color vision

The classic hypothesis of Livingstone and Hubel (1984, 1987) proposed two types of color pathways in primate visual cortex based on recordings from single cells: a segregated, modularpathway that signals color but provides little information about shape or form and a second pathway that signals color differences and so defines forms without the need to specify their colors. A major problem has been to reconcile this neurophysiological hypothesis with the behavioral data. A wealth of psychophysical studies has demonstrated that color vision has orientation-tuned responses and little impairment on form related tasks, but these have not revealed any direct evidence for nonoriented mechanisms. Here we use a psychophysical method of subthreshold summation across orthogonal orientations for isoluminant red-green gratings in monocular and dichoptic viewing conditions to differentiate between nonoriented and orientation-tuned responses to color contrast. We reveal nonoriented color responses at low spatial frequencies (0.25-0.375 c/deg) under monocular conditions changing to orientation-tuned responses at higher spatial frequencies (1.5 c/deg) and under binocular conditions. We suggest that two distinct pathways coexist in color vision at the behavioral level, revealed at different spatial scales: one is isotropic, monocular, and best equipped for the representation of surface color, and the other is orientation-tuned, binocular, and selective for shape and form. This advances our understanding of the organization of the neural pathways involved in human color vision and provides a strong link between neurophysiological and behavioral data. © 2013 ARVO.

Privatisation, corporate control and employment growth:evidence from a panel of large Polish firms, 1996-2002

Using panel data on large Polish firms this paper examines the relationship between corporate control structures, sales growth and the determinants of employment change during the period 1996-2002. We find that privatised and de novo firms are the main drivers of employment growth and that, in the case of de novo firms, it is foreign ownership which underpins the result. Interestingly, we find that being privatised has a positive impact on employment growth but that this impact is concentrated within a range of three to six years after privatisation. In contrast with the findings of earlier literature, we find evidence that there are no systematic differences in employment response to negative sales growth across the ownership categories. On the other hand, employment in state firms is less responsive to positive sales growth. From these combined results we infer that the behaviour of state firms is constrained by both insider rent sharing and binding budget constraints. Consistent with this, we find that privatised companies, three to six years post-privatisation, are the firms for whom employment is most responsive to positive sales growth and as such, offer the best hope for rapid labour market expansion.

Productivity change using growth accounting and frontier-based approaches:evidence from a Monte Carlo analysis

This study presents some quantitative evidence from a number of simulation experiments on the accuracy of the productivitygrowth estimates derived from growthaccounting (GA) and frontier-based methods (namely data envelopment analysis-, corrected ordinary least squares-, and stochastic frontier analysis-based malmquist indices) under various conditions. These include the presence of technical inefficiency, measurement error, misspecification of the production function (for the GA and parametric approaches) and increased input and price volatility from one period to the next. The study finds that the frontier-based methods usually outperform GA, but the overall performance varies by experiment. Parametric approaches generally perform best when there is no functional form misspecification, but their accuracy greatly diminishes otherwise. The results also show that the deterministic approaches perform adequately even under conditions of (modest) measurement error and when measurement error becomes larger, the accuracy of all approaches (including stochastic approaches) deteriorates rapidly, to the point that their estimates could be considered unreliable for policy purposes.

Reduced attentional capacity, but normal processing speed and shifting of attention in developmental dyslexia: evidence from a serial task

We report the performance of a group of adult dyslexics and matched controls in an array-matching task where two strings of either consonants or symbols are presented side by side and have to be judged to be the same or different. The arrays may differ either in the order or identity of two adjacent characters. This task does not require naming – which has been argued to be the cause of dyslexics’ difficulty in processing visual arrays – but, instead, has a strong serial component as demonstrated by the fact that, in both groups, Reaction times (RTs) increase monotonically with position of a mismatch. The dyslexics are clearly impaired in all conditions and performance in the identity conditions predicts performance across orthographic tasks even after age, performance IQ and phonology are partialled out. Moreover, the shapes of serial position curves are revealing of the underlying impairment. In the dyslexics, RTs increase with position at the same rate as in the controls (lines are parallel) ruling out reduced processing speed or difficulties in shifting attention. Instead, error rates show a catastrophic increase for positions which are either searched later or more subject to interference. These results are consistent with a reduction in the attentional capacity needed in a serial task to bind together identity and positional information. This capacity is best seen as a reduction in the number of spotlights into which attention can be split to process information at different locations rather than as a more generic reduction of resources which would also affect processing the details of single objects.

An improved conflicting evidence combination approach based on a new supporting probability distance

To avoid counter-intuitive result of classical Dempster's combination rule when dealing with highly conflict information, many improved combination methods have been developed through modifying the basic probability assignments (BPAs) of bodies of evidence (BOEs) by using a certain measure of the degree of conflict or uncertain information, such as Jousselme's distance, the pignistic probability distance and the ambiguity measure. However, if BOEs contain some non-singleton elements and the differences among their BPAs are larger than 0.5, the current conflict measure methods have limitations in describing the interrelationship among the conflict BOEs and may even lead to wrong combination results. In order to solve this problem, a new distance function, which is called supporting probability distance, is proposed to characterize the differences among BOEs. With the new distance, the information of how much a focal element is supported by the other focal elements in BOEs can be given. Also, a new combination rule based on the supporting probability distance is proposed for the combination of the conflicting evidences. The credibility and the discounting factor of each BOE are generated by the supporting probability distance and the weighted BOEs are combined directly using Dempster's rules. Analytical results of numerical examples show that the new distance has a better capability of describing the interrelationships among BOEs, especially for the highly conflicting BOEs containing non-singleton elements and the proposed new combination method has better applicability and effectiveness compared with the existing methods.

Corporate governance and compliance with International Financial Reporting Standards (IFRSs):evidence from two MENA stock exchanges

This study examines the influence of corporate governance structures on the levels of compliance with IFRSs disclosure requirements by companies listed on the stock exchanges of two leading MENA (Middle East and North Africa) countries, Egypt and Jordan. This study employs a cross-sectional analysis of a sample of non-financial companies listed on the two stock exchanges for the fiscal year 2007. Using an unweighted disclosure index, the study measures the levels of compliance by companies listed on the two stock exchanges investigated.Univariate and multivariate regression analyses are used to estimate the relationships proposed in the hypotheses. In addition, the study uses semi-structured interviews in order to supplement the interpretation of the findings of the quantitative analyses. An innovative theoretical foundation is deployed, in which compliance is interpretable through three lenses - institutional isomorphism theory, secrecy versus transparency (one of Gray’s accounting sub-cultural values), and financial economics theories. The study extends the financial reporting literature, cross-national comparative financial disclosure literature, and the emerging markets disclosure literature by carrying out one of the first comparative studies of the above mentioned stock exchanges. Results provide evidence of a lack of de facto compliance (i.e., actual compliance) with IFRSs disclosure requirements in the scrutinised MENA countries. The impact of corporate governance mechanisms for best practice on enhancing the extent of compliance with mandatory IFRSs is absent in the stock exchanges in question. The limited impact of corporate governance best practice is mainly attributed to the novelty of corporate governance in the region, a finding which lends support to the applicability of the proposed theoretical foundation to the MENA context. Finally, the study provides recommendations for improving de facto compliance with IFRSs disclosure requirements and corporate governance best practice in the MENA region and suggests areas for future research.