The conditional performance of UK property funds

The evaluation of investment fund performance has been one of the main developments of modern portfolio theory. Most studies employ the technique developed by Jensen (1968) that compares a particular fund's returns to a benchmark portfolio of equal risk. However, the standard measures of fund manager performance are known to suffer from a number of problems in practice. In particular previous studies implicitly assume that the risk level of the portfolio is stationary through the evaluation period. That is unconditional measures of performance do not account for the fact that risk and expected returns may vary with the state of the economy. Therefore many of the problems encountered in previous performance studies reflect the inability of traditional measures to handle the dynamic behaviour of returns. As a consequence Ferson and Schadt (1996) suggest an approach to performance evaluation called conditional performance evaluation which is designed to address this problem. This paper utilises such a conditional measure of performance on a sample of 27 UK property funds, over the period 1987-1998. The results of which suggest that once the time varying nature of the funds beta is corrected for, by the addition of the market indicators, the average fund performance show an improvement over that of the traditional methods of analysis.

Evaluating the Survey of Professional Forecasters probability distributions of expected inflation based on derived event probability forecasts

Techniques are proposed for evaluating forecast probabilities of events. The tools are especially useful when, as in the case of the Survey of Professional Forecasters (SPF) expected probability distributions of inflation, recourse cannot be made to the method of construction in the evaluation of the forecasts. The tests of efficiency and conditional efficiency are applied to the forecast probabilities of events of interest derived from the SPF distributions, and supplement a whole-density evaluation of the SPF distributions based on the probability integral transform approach.

Informal sanctions and conditional cooperation: : A natural experiment on voluntary contributions to a public good.

In a natural experiment, this paper studies the impact of an informal sanctioning mechanism on individuals’ voluntary contribution to a public good. Cross-country skiers’ actual cash contributions in two ski resorts, one with and one without an informal sanctioning system, are used. I find the contributing share to be higher in the informal sanctioning system (79 percent) than in the non-sanctioning system (36 percent). Previous studies in one-shot public good situations have found an increasing conditional contribution (CC) function, i.e. the relationship between expected average contributions of other group members and the individual’s own contribution. In contrast, the present results suggest that the CC-function in the non-sanctioning system is non-increasing at high perceived levels of others’ contribution. This relationship deserves further testing in lab.

The assessment of motivation for behaviour change among sex offenders against children: an investigation of the utility of the Stages of Change Questionnaire

A better understanding of motivation for behaviour change among sex offenders against children would improve treatment programmes designed to modify sexual offending behaviour. However, investigation of this issue is limited by lack of theoretically and empirically sound measures of motivation for behaviour change among sex offenders. This paper reports on two studies that were conducted to investigate the psychometric properties (validity, reliability, and social desirability) of the Stages of Change Questionnaire, adapted to measure motivation for behaviour change among sex offenders against children. In Study 1, the psychometric properties of the questionnaire were assessed for sex offenders against children (n=36) who were on a treatment waiting list. In Study 2, the psychometric properties of the questionnaire were assessed for sex offenders against children (n=47) at pre-treatment, mid-treatment, and post-treatment. Both studies supported the validity and reliability of the adapted Stages of Change Questionnaire, and the influence of social desirability upon responding was less than expected. The results of this investigation supported the potential utility of the Stages of Change Questionnaire as a measure of motivation for behaviour change for sex offenders against children.

Generic and diabetes-specific well-being in the AT.LANTUS follow-on study : further psychometric validation of the W-BQ28 indicates its utility in research and clinical practice in type 2 diabetes in the UK

Aims  To undertake further psychometric validation of the W-BQ28 to determine its suitability for use in adults with Type 2 diabetes in the UK using data from the AT.LANTUS follow-on study.

Methods  A total of 353 people with Type 2 diabetes participated in the AT.LANTUS Follow-on study, completing measures of well-being (W-BQ28), treatment satisfaction (DTSQ) and self-care (SCI-R). Confirmatory factor analyses was used to confirm the W-BQ28 structure and internal consistency reliability was assessed. Additional statistical tests were conducted to explore convergent, divergent and known-groups validity. Minimal important differences were calculated using distribution and anchor-based techniques.

Results  Structure of the W-BQ28 (seven four-item subscales plus 16-item generic and 12-item diabetes-specific scales) was confirmed (comparative fit index = 0.917, root mean square error of approximation (RMSEA) = 0.057). Internal consistency reliability was satisfactory (four-item subscales: alpha = 0.73–0.90; 12/16-item scales: α = 0.84–0.90). Convergent validity was supported by expected moderate to high correlations (rs = 0.35–0.67) between all W-BQ28 subscales (except Energy); divergent validity was supported by expected low to moderate correlations with treatment satisfaction (rs = −0.03–0.52) and self-care (rs = 0.02–0.22). Known-groups validity was supported with statistically significant differences by sex, age and HbA1c for expected subscales. Minimal important differences were established (range 0.14–2.90).

Conclusions  The W-BQ28 is a valid and reliable measure of generic and diabetes-specific well-being in Type 2 diabetes in the UK. Confirmation of the utility of W-BQ28 (including establishment of minimal important differences) means that its use is indicated in research and clinical practice.

A transgenic model for conditional induction and rescue of portal hypertension reveals a role of VEGF-mediated regulation of sinusoidal fenestrations

Portal hypertension (PH) is a common complication and a leading cause of death in patients with chronic liver diseases. PH is underlined by structural and functional derangement of liver sinusoid vessels and its fenestrated endothelium. Because in most clinical settings PH is accompanied by parenchymal injury, it has been difficult to determine the precise role of microvascular perturbations in causing PH. Reasoning that Vascular Endothelial Growth Factor (VEGF) is required to maintain functional integrity of the hepatic microcirculation, we developed a transgenic mouse system for a liver-specific-, reversible VEGF inhibition. The system is based on conditional induction and de-induction of a VEGF decoy receptor that sequesters VEGF and preclude signaling. VEGF blockade results in sinusoidal endothelial cells (SECs) fenestrations closure and in accumulation and transformation of the normally quiescent hepatic stellate cells, i.e. provoking the two processes underlying sinusoidal capillarization. Importantly, sinusoidal capillarization was sufficient to cause PH and its typical sequela, ascites, splenomegaly and venous collateralization without inflicting parenchymal damage or fibrosis. Remarkably, these dramatic phenotypes were fully reversed within few days from lifting-off VEGF blockade and resultant re-opening of SECs' fenestrations. This study not only uncovered an indispensible role for VEGF in maintaining structure and function of mature SECs, but also highlights the vasculo-centric nature of PH pathogenesis. Unprecedented ability to rescue PH and its secondary manifestations via manipulating a single vascular factor may also be harnessed for examining the potential utility of de-capillarization treatment modalities.

Dephosphorylation of p-ERK1/2 in relation to tumor remission after HER-2 and Raf1 blocking therapy in a conditional mouse tumor model

Several studies have shown that HER-2/neu (erbB-2) blocking therapy strategies can cause tumor remission. However, the responsible molecular mechanisms are not yet known. Both ERK1/2 and Akt/PKB are critical for HER-2-mediated signal transduction. Therefore, we used a mouse tumor model that allows downregulation of HER-2 in tumor tissue by administration of anhydrotetracycline (ATc). Switching-off HER-2 caused a rapid tumor remission by more than 95% within 7 d of ATc administration compared to the volume before switching-off HER-2. Interestingly, HER-2 downregulation caused a dephosphorylation of p-ERK1/2 by more than 80% already before tumor remission occurred. Levels of total ERK protein were not influenced. In contrast, dephosphorylation of p-Akt occurred later, when the tumor was already in remission. These data suggest that in our HER-2 tumor model dephosphorylation of p-ERK1/2 may be more critical for tumor remission than dephosphorylation of p-Akt. To test this hypothesis we used a second mouse tumor model that allows ATc controlled expression of BXB-Raf1 because the latter constitutively signals to ERK1/2, but cannot activate Akt/PKB. As expected, downregulation of BXB-Raf1 in tumor tissue caused a strong dephosphorylation of p-ERK1/2, but did not decrease levels of p-Akt. Interestingly, tumor remission after switching-off BXB-Raf1 was similarly efficient as the effect of HER-2 downregulation, despite the lack of p-Akt dephosphorylation. In conclusion, two lines of evidence strongly suggest that dephosphorylation of p-ERK1/2 and not that of p-Akt is critical for the rapid tumor remission after downregulation of HER-2 or BXB-Raf1 in our tumor model: (i) dephosphorylation of p-ERK1/2 but not that of p-Akt precedes tumor remission after switching-off HER-2 and (ii) downregulation of BXB-Raf1 leads to a similarly efficient tumor remission as downregulation of HER-2, although no p-Akt dephosphorylation was observed after switching-off BXB-Raf1.

Establishment of murine cell lines by constitutive and conditional immortalization

Mouse cell lines were immortalized by introduction of specific immortalizing genes. Embryonic and adult animals and an embryonal stem cell line were used as a source of primary cells. The immortalizing genes were either introduced by DNA transfection or by ecotropic retrovirus transduction. Fibroblasts were obtained by expression of SV40 virus large T antigen (TAg). The properties of the resulting fibroblast cell lines were reproducible, independent of the donor mouse strains employed and the cells showed no transformed properties in vitro and did not form tumors in vivo. Endothelial cell lines were generated by Polyoma virus middle T antigen expression in primary embryonal cells. These cell lines consistently expressed relevant endothelial cell surface markers. Since the expression of the immortalizing genes was expected to strongly influence the cellular characteristics fibroblastoid cells were reversibly immortalized by using a vector that allows conditional expression of the TAg. Under inducing conditions, these cells exhibited properties that were highly similar to the properties of constitutively immortalized cells. In the absence of TAg expression, cell proliferation stops. Cell growth is resumed when TAg expression is restored. Gene expression profiling indicates that TAg influences the expression levels of more than 1000 genes that are involved in diverse cellular processes. The data show that conditionally immortalized cell lines have several advantageous properties over constitutively immortalized cells.

Transgenic system for conditional induction and rescue of chronic myocardial hibernation provides insights into genomic programs of hibernation

A key energy-saving adaptation to chronic hypoxia that enables cardiomyocytes to withstand severe ischemic insults is hibernation, i.e., a reversible arrest of contractile function. Whereas hibernating cardiomyocytes represent the critical reserve of dysfunctional cells that can be potentially rescued, a lack of a suitable animal model has hampered insights on this medically important condition. We developed a transgenic mouse system for conditional induction of long-term hibernation and a system to rescue hibernating cardiomyocytes at will. Via myocardium-specific induction (and, in turn, deinduction) of a VEGF-sequestering soluble receptor, we show that VEGF is indispensable for adjusting the coronary vasculature to match increased oxygen consumption and exploit this finding to generate a hypoperfused heart. Importantly, ensuing ischemia is tunable to a level at which large cohorts of cardiomyocytes are driven to enter a hibernation mode, without cardiac cell death. Relieving the VEGF blockade even months later resulted in rapid revascularization and full recovery of contractile function. Furthermore, we show that left ventricular remodeling associated with hibernation is also fully reversible. The unique opportunity to uncouple hibernation from other ischemic heart phenotypes (e.g., infarction) was used to determine the genetic program of hibernation; uncovering hypoxia-inducible factor target genes associated with metabolic adjustments and induced expression of several cardioprotective genes. Autophagy, specifically self-digestion of mitochondria, was identified as a key prosurvival mechanism in hibernating cardiomyocytes. This system may lend itself for examining the potential utility of treatments to rescue dysfunctional cardiomyocytes and reverse maladaptive remodeling.

Quantifying uncertainty on Pareto fronts with Gaussian process conditional simulations

Multi-objective optimization algorithms aim at finding Pareto-optimal solutions. Recovering Pareto fronts or Pareto sets from a limited number of function evaluations are challenging problems. A popular approach in the case of expensive-to-evaluate functions is to appeal to metamodels. Kriging has been shown efficient as a base for sequential multi-objective optimization, notably through infill sampling criteria balancing exploitation and exploration such as the Expected Hypervolume Improvement. Here we consider Kriging metamodels not only for selecting new points, but as a tool for estimating the whole Pareto front and quantifying how much uncertainty remains on it at any stage of Kriging-based multi-objective optimization algorithms. Our approach relies on the Gaussian process interpretation of Kriging, and bases upon conditional simulations. Using concepts from random set theory, we propose to adapt the Vorob’ev expectation and deviation to capture the variability of the set of non-dominated points. Numerical experiments illustrate the potential of the proposed workflow, and it is shown on examples how Gaussian process simulations and the estimated Vorob’ev deviation can be used to monitor the ability of Kriging-based multi-objective optimization algorithms to accurately learn the Pareto front.

Binary recombinase systems for high-resolution conditional mutagenesis.

Conditional mutagenesis using Cre recombinase expressed from tissue specific promoters facilitates analyses of gene function and cell lineage tracing. Here, we describe two novel dual-promoter-driven conditional mutagenesis systems designed for greater accuracy and optimal efficiency of recombination. Co-Driver employs a recombinase cascade of Dre and Dre-respondent Cre, which processes loxP-flanked alleles only when both recombinases are expressed in a predetermined temporal sequence. This unique property makes Co-Driver ideal for sequential lineage tracing studies aimed at unraveling the relationships between cellular precursors and mature cell types. Co-InCre was designed for highly efficient intersectional conditional transgenesis. It relies on highly active trans-splicing inteins and promoters with simultaneous transcriptional activity to reconstitute Cre recombinase from two inactive precursor fragments. By generating native Cre, Co-InCre attains recombination rates that exceed all other binary SSR systems evaluated in this study. Both Co-Driver and Co-InCre significantly extend the utility of existing Cre-responsive alleles.

Employment rate impacts of charging the Heavy Good Vehicle corridor (Madrid-Sevilla) across Spanish regions: a Random Utility Based Multiregional Input-Output approach

The implementation of a charging policy for heavy goods vehicles in European Union (EU) member countries has been imposed to reflect costs of construction and maintenance of infrastructure as well as externalities such as congestion, accidents and environmental impact. In this context, EU countries approved the Eurovignette directive (1999/62/EC) and its amending directive (2006 /38/EC) which established a legal framework to regulate the system of tolls. Even if that regulation seek s to increase the efficien cy of freight, it will trigger direct and indirect effects on Spain’s regional economies by increasing transport costs. This paper presents the development of a multiregional Input-Output methodology (MRIO) with elastic trade coefficients to predict in terregional trade, using transport attributes integrated in multinomial logit models. This method is highly useful to carry out an ex-ante evaluation of transport policies because it involves road freight transport cost sensitivity, and determine regional distributive and substitution economic effect s of countries like Spain, characterized by socio-demographic and economic attributes, differentiated region by region. It will thus be possible to determine cost-effective strategies, given different policy scenarios. MRIO mode l would then be used to determine the impact on the employment rate of imposing a charge in the Madrid-Sevilla corridor in Spain. This methodology is important for measuring the impact on the employment rate since it is one of the main macroeconomic indicators of Spain’s regional and national economic situation. A previous research developed (DESTINO) using a MRIO method estimated employment impacts of road pricing policy across Spanish regions considering a fuel tax charge (€/liter) in the entire shortest cost path network for freight transport. Actually, it found that the variation in employment is expected to be substantial for some regions, and negligible for others. For example, in this Spanish case study of regional employment has showed reductions between 16.1% (Rioja) and 1.4% (Madrid region). This variation range seems to be related to either the intensity of freight transport in each region or dependency of regions to transport intensive economic sect ors. In fact, regions with freight transport intensive sectors will lose more jobs while regions with a predominantly service economy undergo a fairly insignificant loss of employment. This paper is focused on evaluating a freight transport vehicle-kilometer charge (€/km) in a non-tolled motorway corridor (A-4) between Madrid-Sevilla (517 Km.). The consequences of the road pricing policy implementation show s that the employment reductions are not as high as the diminution stated in the previous research because this corridor does not affect the whole freight transport system of Spain.

Assessing urban mobility through participatory scenario building and combined utility-regret assessment

La planificación de la movilidad sostenible urbana es una tarea compleja que implica un alto grado de incertidumbre debido al horizonte de planificación a largo plazo, la amplia gama de paquetes de políticas posibles, la necesidad de una aplicación efectiva y eficiente, la gran escala geográfica, la necesidad de considerar objetivos económicos, sociales y ambientales, y la respuesta del viajero a los diferentes cursos de acción y su aceptabilidad política (Shiftan et al., 2003). Además, con las tendencias inevitables en motorización y urbanización, la demanda de terrenos y recursos de movilidad en las ciudades está aumentando dramáticamente. Como consecuencia de ello, los problemas de congestión de tráfico, deterioro ambiental, contaminación del aire, consumo de energía, desigualdades en la comunidad, etc. se hacen más y más críticos para la sociedad. Esta situación no es estable a largo plazo. Para enfrentarse a estos desafíos y conseguir un desarrollo sostenible, es necesario considerar una estrategia de planificación urbana a largo plazo, que aborde las necesarias implicaciones potencialmente importantes. Esta tesis contribuye a las herramientas de evaluación a largo plazo de la movilidad urbana estableciendo una metodología innovadora para el análisis y optimización de dos tipos de medidas de gestión de la demanda del transporte (TDM). La metodología nueva realizado se basa en la flexibilización de la toma de decisiones basadas en utilidad, integrando diversos mecanismos de decisión contrariedad‐anticipada y combinados utilidad‐contrariedad en un marco integral de planificación del transporte. La metodología propuesta incluye dos aspectos principales: 1) La construcción de escenarios con una o varias medidas TDM usando el método de encuesta que incorpora la teoría “regret”. La construcción de escenarios para este trabajo se hace para considerar específicamente la implementación de cada medida TDM en el marco temporal y marco espacial. Al final, se construyen 13 escenarios TDM en términos del más deseable, el más posible y el de menor grado de “regret” como resultado de una encuesta en dos rondas a expertos en el tema. 2) A continuación se procede al desarrollo de un marco de evaluación estratégica, basado en un Análisis Multicriterio de Toma de Decisiones (Multicriteria Decision Analysis, MCDA) y en un modelo “regret”. Este marco de evaluación se utiliza para comparar la contribución de los distintos escenarios TDM a la movilidad sostenible y para determinar el mejor escenario utilizando no sólo el valor objetivo de utilidad objetivo obtenido en el análisis orientado a utilidad MCDA, sino también el valor de “regret” que se calcula por medio del modelo “regret” MCDA. La función objetivo del MCDA se integra en un modelo de interacción de uso del suelo y transporte que se usa para optimizar y evaluar los impactos a largo plazo de los escenarios TDM previamente construidos. Un modelo de “regret”, llamado “referencedependent regret model (RDRM)” (modelo de contrariedad dependiente de referencias), se ha adaptado para analizar la contribución de cada escenario TDM desde un punto de vista subjetivo. La validación de la metodología se realiza mediante su aplicación a un caso de estudio en la provincia de Madrid. La metodología propuesta define pues un procedimiento técnico detallado para la evaluación de los impactos estratégicos de la aplicación de medidas de gestión de la demanda en el transporte, que se considera que constituye una herramienta de planificación útil, transparente y flexible, tanto para los planificadores como para los responsables de la gestión del transporte. Planning sustainable urban mobility is a complex task involving a high degree of uncertainty due to the long‐term planning horizon, the wide spectrum of potential policy packages, the need for effective and efficient implementation, the large geographical scale, the necessity to consider economic, social, and environmental goals, and the traveller’s response to the various action courses and their political acceptability (Shiftan et al., 2003). Moreover, with the inevitable trends on motorisation and urbanisation, the demand for land and mobility in cities is growing dramatically. Consequently, the problems of traffic congestion, environmental deterioration, air pollution, energy consumption, and community inequity etc., are becoming more and more critical for the society (EU, 2011). Certainly, this course is not sustainable in the long term. To address this challenge and achieve sustainable development, a long‐term perspective strategic urban plan, with its potentially important implications, should be established. This thesis contributes on assessing long‐term urban mobility by establishing an innovative methodology for optimizing and evaluating two types of transport demand management measures (TDM). The new methodology aims at relaxing the utility‐based decision‐making assumption by embedding anticipated‐regret and combined utilityregret decision mechanisms in an integrated transport planning framework. The proposed methodology includes two major aspects: 1) Construction of policy scenarios within a single measure or combined TDM policy‐packages using the survey method incorporating the regret theory. The purpose of building the TDM scenarios in this work is to address the specific implementation in terms of time frame and geographic scale for each TDM measure. Finally, 13 TDM scenarios are built in terms of the most desirable, the most expected and the least regret choice by means of the two‐round Delphi based survey. 2) Development of the combined utility‐regret analysis framework based on multicriteria decision analysis (MCDA). This assessment framework is used to compare the contribution of the TDM scenario towards sustainable mobility and to determine the best scenario considering not only the objective utility value obtained from the utilitybased MCDA, but also a regret value that is calculated via a regret‐based MCDA. The objective function of the utility‐based MCDA is integrated in a land use and transport interaction model and is used for optimizing and assessing the long term impacts of the constructed TDM scenarios. A regret based model, called referente dependent regret model (RDRM) is adapted to analyse the contribution of each TDM scenario in terms of a subjective point of view. The suggested methodology is implemented and validated in the case of Madrid. It defines a comprehensive technical procedure for assessing strategic effects of transport demand management measures, which can be useful, transparent and flexible planning tool both for planners and decision‐makers.

An Integrated Transport Planning Framework Involving a Combined Utility-Regret Approach

Sustainable transport planning requires an integrated approach involving strategic planning, impact analysis and multi-criteria evaluation. This study aims at relaxing the utility-based decision-making assumption by newly embedding anticipated-regret and combined utility-regret decision mechanisms in an integrated transport planning framework. The framework consists of a two-round Delphi survey, an integrated land-use and transport model for Madrid, and multi-criteria analysis. Results show that (i) regret-based ranking has similar mean but larger variance than utility-based ranking; (ii) the least-regret scenario forms a compromise between the desired and the expected scenarios; (iii) the least-regret scenario can lead to higher user benefits in the short-term and lower user benefits in the long-term; (iv) utility-based, regret-based and combined utility-regret-based multi-criteria analysis result in different rankings of policy packages; and (v) the combined utility-regret ranking is more informative compared with utility-based or regret-based ranking.

Patched 1 conditional null allele in mice

The patched gene (Ptc) is a member of the hedgehog signaling pathway which plays a central role in the development of many invertebrate and vertebrate tissues. In addition, Ptc and a number of other pathway members are mutated in some common human cancers. Patched is the receptor for the hedgehog ligand and in the mouse ablation of the Ptc gene leads to developmental defects and an embryonic lethal phenotype. Here we describe a conditional Ptc allele in mice which will have utility for the temporospatial ablation of Ptc function. genesis 36:158-161, 2003. (C) 2003 Wiley-Liss, Inc.