Refinement of the Clinical Scenario Evaluation Framework for Assessment of Competing Development Strategies with an Application to Multiple Sclerosis

When competing strategies for development programs, clinical trial designs, or data analysis methods exist, the alternatives need to be evaluated in a systematic way to facilitate informed decision making. Here we describe a refinement of the recently proposed clinical scenario evaluation framework for the assessment of competing strategies. The refinement is achieved by subdividing key elements previously proposed into new categories, distinguishing between quantities that can be estimated from preexisting data and those that cannot and between aspects under the control of the decision maker from those that are determined by external constraints. The refined framework is illustrated by an application to a design project for an adaptive seamless design for a clinical trial in progressive multiple sclerosis.

Selection of funding schemes by a borrowing decision model: a Hong Kong case study

In financial decision-making, a number of mathematical models have been developed for financial management in construction. However, optimizing both qualitative and quantitative factors and the semi-structured nature of construction finance optimization problems are key challenges in solving construction finance decisions. The selection of funding schemes by a modified construction loan acquisition model is solved by an adaptive genetic algorithm (AGA) approach. The basic objectives of the model are to optimize the loan and to minimize the interest payments for all projects. Multiple projects being undertaken by a medium-size construction firm in Hong Kong were used as a real case study to demonstrate the application of the model to the borrowing decision problems. A compromise monthly borrowing schedule was finally achieved. The results indicate that Small and Medium Enterprise (SME) Loan Guarantee Scheme (SGS) was first identified as the source of external financing. Selection of sources of funding can then be made to avoid the possibility of financial problems in the firm by classifying qualitative factors into external, interactive and internal types and taking additional qualitative factors including sovereignty, credit ability and networking into consideration. Thus a more accurate, objective and reliable borrowing decision can be provided for the decision-maker to analyse the financial options.

Investigation of K14/K5 as a stem cell marker in the limbal region of the bovine cornea

Background: Identification of stem cells from a corneal epithelial cell population by specific molecular markers has been investigated previously. Expressions of P63, ABCG2 and K14/K5 have all been linked to mammalian corneal epithelial stem cells. Here we report on the limitations of K14/K5 as a limbal stem cell marker. Methodology/Principal Findings: K14/K5 expression was measured by immunohistochemistry, Western blotting and Real time PCR and compared between bovine epithelial cells in the limbus and central cornea. A functional study was also included to investigate changes in K5/14 expression within cultured limbal epithelial cells undergoing forced differentiation. K14 expression (or its partner K5) was detected in quiescent epithelial cells from both the limbal area and central cornea. K14 was localized predominantly to basal epithelial cells in the limbus and suprabasal epithelial cells in the central cornea. Western blotting revealed K14 expression in both limbus and central cornea (higher levels in the limbus). Similarly, quantitative real time PCR found K5, partner to K14, to be expressed in both the central cornea and limbus. Following forced differentiation in culture the limbal epithelial cells revealed an increase in K5/14 gene/protein expression levels in concert with a predictable rise in a known differentiation marker. Conclusions/Significance: K14 and its partner K5 are limited not only to the limbus but also to the central bovine cornea epithelial cells suggesting K14/K5 is not limbal specific in situ. Furthermore K14/K5 expression levels were not lowered (in fact they increased) within a limbal epithelial cell culture undergoing forced differentiation suggesting K14/K5 is an unreliable maker for undifferentiated cells ex vivo.

Decision theory and real estate development: a note on uncertainty

Real estate development appraisal is a quantification of future expectations. The appraisal model relies upon the valuer/developer having an understanding of the future in terms of the future marketability of the completed development and the future cost of development. In some cases the developer has some degree of control over the possible variation in the variables, as with the cost of construction through the choice of specification. However, other variables, such as the sale price of the final product, are totally dependent upon the vagaries of the market at the completion date. To try to address the risk of a different outcome to the one expected (modelled) the developer will often carry out a sensitivity analysis on the development. However, traditional sensitivity analysis has generally only looked at the best and worst scenarios and has focused on the anticipated or expected outcomes. This does not take into account uncertainty and the range of outcomes that can happen. A fuller analysis should include examination of the uncertainties in each of the components of the appraisal and account for the appropriate distributions of the variables. Similarly, as many of the variables in the model are not independent, the variables need to be correlated. This requires a standardised approach and we suggest that the use of a generic forecasting software package, in this case Crystal Ball, allows the analyst to work with an existing development appraisal model set up in Excel (or other spreadsheet) and to work with a predetermined set of probability distributions. Without a full knowledge of risk, developers are unable to determine the anticipated level of return that should be sought to compensate for the risk. This model allows the user a better understanding of the possible outcomes for the development. Ultimately the final decision will be made relative to current expectations and current business constraints, but by assessing the upside and downside risks more appropriately, the decision maker should be better placed to make a more informed and “better”.

Judgments, forecasts and decisions: an analysis of fund managers over time

Decision theory is the study of models of judgement involved in, and leading to, deliberate and (usually) rational choice. In real estate investment there are normative models for the allocation of assets. These asset allocation models suggest an optimum allocation between the respective asset classes based on the investors’ judgements of performance and risk. Real estate is selected, as other assets, on the basis of some criteria, e.g. commonly its marginal contribution to the production of a mean variance efficient multi asset portfolio, subject to the investor’s objectives and capital rationing constraints. However, decisions are made relative to current expectations and current business constraints. Whilst a decision maker may believe in the required optimum exposure levels as dictated by an asset allocation model, the final decision may/will be influenced by factors outside the parameters of the mathematical model. This paper discusses investors' perceptions and attitudes toward real estate and highlights the important difference between theoretical exposure levels and pragmatic business considerations. It develops a model to identify “soft” parameters in decision making which will influence the optimal allocation for that asset class. This “soft” information may relate to behavioural issues such as the tendency to mirror competitors; a desire to meet weight of money objectives; a desire to retain the status quo and many other non-financial considerations. The paper aims to establish the place of property in multi asset portfolios in the UK and examine the asset allocation process in practice, with a view to understanding the decision making process and to look at investors’ perceptions based on an historic analysis of market expectation; a comparison with historic data and an analysis of actual performance.

Uncertainty and feasibility studies: an Italian case study

Uncertainty affects all aspects of the property market but one area where the impact of uncertainty is particularly significant is within feasibility analyses. Any development is impacted by differences between market conditions at the conception of the project and the market realities at the time of completion. The feasibility study needs to address the possible outcomes based on an understanding of the current market. This requires the appraiser to forecast the most likely outcome relating to the sale price of the completed development, the construction costs and the timing of both. It also requires the appraiser to understand the impact of finance on the project. All these issues are time sensitive and analysis needs to be undertaken to show the impact of time to the viability of the project. The future is uncertain and a full feasibility analysis should be able to model the upside and downside risk pertaining to a range of possible outcomes. Feasibility studies are extensively used in Italy to determine land value but they tend to be single point analysis based upon a single set of “likely” inputs. In this paper we look at the practical impact of uncertainty in variables using a simulation model (Crystal Ball ©) with an actual case study of an urban redevelopment plan for an Italian Municipality. This allows the appraiser to address the issues of uncertainty involved and thus provide the decision maker with a better understanding of the risk of development. This technique is then refined using a “two-dimensional technique” to distinguish between “uncertainty” and “variability” and thus create a more robust model.

Trajectory planning of a robot using learning algorithms

The authors consider the problem of a robot manipulator operating in a noisy workspace. The manipulator is required to move from an initial position P(i) to a final position P(f). P(i) is assumed to be completely defined. However, P(f) is obtained by a sensing operation and is assumed to be fixed but unknown. The authors approach to this problem involves the use of three learning algorithms, the discretized linear reward-penalty (DLR-P) automaton, the linear reward-penalty (LR-P) automaton and a nonlinear reinforcement scheme. An automaton is placed at each joint of the robot and by acting as a decision maker, plans the trajectory based on noisy measurements of P(f).

Measuring the discrepancy between fecundity and lifetime reproductive success in a pollinating fig wasp

Lifetime reproductive success in female insects is often egg- or time-limited. For instance in pro-ovigenic species, when oviposition sites are abundant, females may quickly become devoid of eggs. Conversely, in the absence of suitable oviposition sites, females may die before laying all of their eggs. In pollinating fig wasps (Hymenoptera: Agaonidae), each species has an obligate mutualism with its host fig tree species [Ficus spp. (Moraceae)]. These pro-ovigenic wasps oviposit in individual ovaries within the inflorescences of monoecious Ficus (syconia, or ‘figs’), which contain many flowers. Each female flower can thus become a seed or be converted into a wasp gall. The mystery is that the wasps never oviposit in all fig ovaries, even when a fig contains enough wasp females with enough eggs to do so. The failure of all wasps to translate all of their eggs into offspring clearly contributes to mutualism persistence, but the underlying causal mechanisms are unclear. We found in an undescribed Brazilian Pegoscapus wasp population that the lifetime reproductive success of lone foundresses was relatively unaffected by constraints on oviposition. The number of offspring produced by lone foundresses experimentally introduced into receptive figs was generally lower than the numbers of eggs carried, despite the fact that the wasps were able to lay all or most of their eggs. Because we excluded any effects of intraspecific competitors and parasitic non-pollinating wasps, our data suggest that some pollinators produce few offspring because some of their eggs or larvae are unviable or are victims of plant defences.

Risk management and the corporate real estate portfolio

In a global business economy, firms have a broad range of corporate real estate needs. During the past decade, multiple strategies and tactics have emerged in the corporate real estate community for meeting those needs. We propose here a framework for analysing and prioritising the various types of risk inherent in corporate real estate decisions. From a business strategy perspective, corporate real estate must serve needs beyond the simple one of shelter for the workforce and production process. Certain uses are strategic in that they allow access to externalities, embody the business strategy, or provide entrée to new markets. Other uses may be tactical, in that they arise from business activities of relatively short duration or provide an opportunity to pre-empt competitors. Still other corporate real estate uses can be considered “core” to the existence of the business enterprise. These might be special use properties or may be generic buildings that have become embodiments of the organisation’s culture. We argue that a multi-dimensional matrix approach organised around three broad themes and nine sub-categories allow the decision-maker to organise and evaluate choices with an acceptable degree of rigor and thoroughness. The three broad themes are Use (divided into Core, Cyclical or Casual) – Asset Type (which can be Strategic, Specialty or Generic) and Market Environment (which ranges from Mature Domestic to Emerging Economy). Proper understanding of each of these groupings brings critical variables to the fore and allows for efficient resource allocation and enhanced risk management.

Identification of metabolites in human hepatic bile using 800 MHz 1H NMR spectroscopy, HPLC-NMR/MS and UPLC-MS

The first application of high field NMR spectroscopy (800 MHz for 1H observation) to human hepatic bile (as opposed to gall bladder bile) is reported. The bile sample used for detailed investigation was from a donor liver with mild fat infiltration, collected during organ retrieval prior to transplantation. In addition, to focus on the detection of bile acids in particular, a bile extract was analysed by 800 MHz 1H NMR spectroscopy, HPLC-NMR/MS and UPLC-MS. In the whole bile sample, 40 compounds have been assigned with the aid of two-dimensional 1H–1H TOCSY and 1H–13C HSQC spectra. These include phosphatidylcholine, 14 amino acids, 10 organic acids, 4 carbohydrates and polyols (glucose, glucuronate, glycerol and myo-inositol), choline, phosphocholine, betaine, trimethylamine-N-oxide and other small molecules. An initial NMR-based assessment of the concentration range of some key metabolites has been made. Some observed chemical shifts differ from expected database values, probably due to a difference in bulk diamagnetic susceptibility. The NMR spectra of the whole extract gave identification of the major bile acids (cholic, deoxycholic and chenodeoxycholic), but the glycine and taurine conjugates of a given bile acid could not be distinguished. However, this was achieved by HPLC-NMR/MS, which enabled the separation and identification of ten conjugated bile acids with relative abundances varying from approximately 0.1% (taurolithocholic acid) to 34.0% (glycocholic acid), of which, only the five most abundant acids could be detected by NMR, including the isomers glycodeoxycholic acid and glycochenodeoxycholic acid, which are difficult to distinguish by conventional LC-MS analysis. In a separate experiment, the use of UPLC-MS allowed the detection and identification of 13 bile acids. This work has shown the complementary potential of NMR spectroscopy, MS and hyphenated NMR/MS for elucidating the complex metabolic profile of human hepatic bile. This will be useful baseline information in ongoing studies of liver excretory function and organ transplantation.

Does short termism affect the quality of urban design in the UK?

This paper follows the report on the “Quality of Urban Design: Study of the Influence of Private Property Decision Maker in Urban Design” (RICS 1996). It focuses on one of the findings in the report, namely that decisions made in development, investment and occupation seemed overly influenced by short term considerations. In this paper, the authors review the Report and examine the concept of short termism as it affects urban design decisions. The paper concludes that although it is difficult to establish whether or not short termism exists in many decisions, there are grounds for believing that a priori short termism might particularly influence property orientated decisions. The paper ends with some implications for policy both at the economy and local level.

Integrating nitrogen fluxes at the European scale

Executive summary Nature of the problem • Environmental problems related to nitrogen concern all economic sectors and impact all media: atmosphere, pedosphere, hydrosphere and anthroposphere. • Therefore, the integration of fluxes allows an overall coverage of problems related to reactive nitrogen (Nr) in the environment, which is not accessible from sectoral approaches or by focusing on specific media. Approaches • This chapter presents a set of high resolution maps showing key elements of the N flux budget across Europe, including N2 and Nr fluxes. • Comparative nitrogen budgets are also presented for a range of European countries, highlighting the most efficient strategies for mitigating Nr problems at a national scale. A new European Nitrogen Budget (EU-27) is presented on the basis of state-of-the-art Europe-wide models and databases focusing on different segments of Europe’s society. Key findings • From c. 18 Tg Nr yr −1 input to agriculture in the EU-27, only about 7 Tg Nr yr− 1 find their way to the consumer or are further processed by industry. • Some 3.7 Tg Nr yr−1 is released by the burning of fossil fuels in the EU-27, whereby the contribution of the industry and energy sectors is equal to that of the transport sector. More than 8 Tg Nr yr−1 are disposed of to the hydrosphere, while the EU-27 is a net exporter of reactive nitrogen through atmospheric transport of c. 2.3 Tg Nr yr−1. • The largest single sink for Nr appears to be denitrifi cation to N2 in European coastal shelf regions (potentially as large as the input of mineral fertilizer, about 11 Tg N yr–1 for the EU-27); however, this sink is also the most uncertain, because of the uncertainty of Nr import from the open ocean. Major uncertainties • National nitrogen budgets are diffi cult to compile using a large range of data sources and are currently available only for a limited number of countries. • Modelling approaches have been used to fill in the data gaps in some of these budgets, but it became obvious during this study that further research is needed in order to collect necessary data and make national nitrogen budgets inter-comparable across Europe. • In some countries, due to inconsistent or contradictory information coming from different data sources, closure of the nitrogen budget was not possible. Recommendations • The large variety of problems associated with the excess of Nr in the European environment,including adverse impacts, requires an integrated nitrogen management approach that would allow for creation and closure of N budgets within European environments. • Development of nitrogen budgets nationwide, their assessment and management could become an effective tool to prioritize measures and prevent unwanted side effects.

Skilloscopy: Bayesian modeling of decision makers' skill

This paper proposes and demonstrates an approach, Skilloscopy, to the assessment of decision makers. In an increasingly sophisticated, connected and information-rich world, decision making is becoming both more important and more difficult. At the same time, modelling decision-making on computers is becoming more feasible and of interest, partly because the information-input to those decisions is increasingly on record. The aims of Skilloscopy are to rate and rank decision makers in a domain relative to each other: the aims do not include an analysis of why a decision is wrong or suboptimal, nor the modelling of the underlying cognitive process of making the decisions. In the proposed method a decision-maker is characterised by a probability distribution of their competence in choosing among quantifiable alternatives. This probability distribution is derived by classic Bayesian inference from a combination of prior belief and the evidence of the decisions. Thus, decision-makers’ skills may be better compared, rated and ranked. The proposed method is applied and evaluated in the gamedomain of Chess. A large set of games by players across a broad range of the World Chess Federation (FIDE) Elo ratings has been used to infer the distribution of players’ rating directly from the moves they play rather than from game outcomes. Demonstration applications address questions frequently asked by the Chess community regarding the stability of the Elo rating scale, the comparison of players of different eras and/or leagues, and controversial incidents possibly involving fraud. The method of Skilloscopy may be applied in any decision domain where the value of the decision-options can be quantified.

Parallel editing, multi-positionality and maximalism: cosmopolitan effects as explored in some art works by Melanie Jackson and Vivienne Dick

Garfield produces a critique of neo-minimalist art practice by demonstrating how the artist Melanie Jackson’s Some things you are not allowed to send around the world (2003 and 2006) and the experimental film-maker Vivienne Dick’s Liberty’s booty (1980) – neither of which can be said to be about feeling ‘at home’ in the world, be it as a resident or as a nomad – examine global humanity through multi-positionality, excess and contingency, and thereby begin to articulate a new cosmopolitan relationship with the local – or, rather, with many different localities – in one and the same maximalist sweep of the work. ‘Maximalism’ in Garfield’s coinage signifies an excessive overloading (through editing, collage, and the sheer density of the range of the material) that enables the viewer to insert themselves into the narrative of the work. In the art of both Jackson and Dick Garfield detects a refusal to know or to judge the world; instead, there is an attempt to incorporate the complexities of its full range into the singular vision of the work, challenging the viewer to identify what is at stake.