Bayesian adaptive designs in early phase clinical trials

There are two practical challenges in the phase I clinical trial conduct: lack of transparency to physicians, and the late onset toxicity. In my dissertation, Bayesian approaches are used to address these two problems in clinical trial designs. The proposed simple optimal designs cast the dose finding problem as a decision making process for dose escalation and deescalation. The proposed designs minimize the incorrect decision error rate to find the maximum tolerated dose (MTD). For the late onset toxicity problem, a Bayesian adaptive dose-finding design for drug combination is proposed. The dose-toxicity relationship is modeled using the Finney model. The unobserved delayed toxicity outcomes are treated as missing data and Bayesian data augment is employed to handle the resulting missing data. Extensive simulation studies have been conducted to examine the operating characteristics of the proposed designs and demonstrated the designs' good performances in various practical scenarios.^

Systematic Approach for the selection of monitoring technologies in CO2 geological storage projects. Application of multicriteria decision making

Geologic storage of carbon dioxide (CO2) has been proposed as a viable means for reducing anthropogenic CO2 emissions. Once injection begins, a program for measurement, monitoring, and verification (MMV) of CO2 distribution is required in order to: a) research key features, effects and processes needed for risk assessment; b) manage the injection process; c) delineate and identify leakage risk and surface escape; d) provide early warnings of failure near the reservoir; and f) verify storage for accounting and crediting. The selection of the methodology of monitoring (characterization of site and control and verification in the post-injection phase) is influenced by economic and technological variables. Multiple Criteria Decision Making (MCDM) refers to a methodology developed for making decisions in the presence of multiple criteria. MCDM as a discipline has only a relatively short history of 40 years, and it has been closely related to advancements on computer technology. Evaluation methods and multicriteria decisions include the selection of a set of feasible alternatives, the simultaneous optimization of several objective functions, and a decision-making process and evaluation procedures that must be rational and consistent. The application of a mathematical model of decision-making will help to find the best solution, establishing the mechanisms to facilitate the management of information generated by number of disciplines of knowledge. Those problems in which decision alternatives are finite are called Discrete Multicriteria Decision problems. Such problems are most common in reality and this case scenario will be applied in solving the problem of site selection for storing CO2. Discrete MCDM is used to assess and decide on issues that by nature or design support a finite number of alternative solutions. Recently, Multicriteria Decision Analysis has been applied to hierarchy policy incentives for CCS, to assess the role of CCS, and to select potential areas which could be suitable to store. For those reasons, MCDM have been considered in the monitoring phase of CO2 storage, in order to select suitable technologies which could be techno-economical viable. In this paper, we identify techniques of gas measurements in subsurface which are currently applying in the phase of characterization (pre-injection); MCDM will help decision-makers to hierarchy the most suitable technique which fit the purpose to monitor the specific physic-chemical parameter.

Control and command systems concepts from early work on a Mars Rover

We recover and develop some robotic systems concepts (on the light of present systems tools) that were originated for an intended Mars Rover in the sixties of the last century at the Instrumentation Laboratory of MIT, where one of the authors was involved. The basic concepts came from the specifications for a type of generalized robot inspired in the structure of the vertebrate nervous systems, where the decision system was based in the structure and function of the Reticular Formation (RF). The vertebrate RF is supposed to commit the whole organism to one among various modes of behavior, so taking the decisions about the present overall task. That is, it is a kind of control and command system. In this concepts updating, the basic idea is that the RF comprises a set of computing units such that each computing module receives information only from a reduced part of the overall, little processed sensory inputs. Each computing unit is capable of both general diagnostics about overall input situations and of specialized diagnostics according to the values of a concrete subset of the input lines. Slave systems to this command and control computer, there are the sensors, the representations of external environment, structures for modeling and planning and finally, the effectors acting in the external world.

A supervised cooperative learning system for early detection of language disorders

The Quality of Life of a person may depend on early attention to his neurodevel-opment disorders in childhood. Identification of language disorders under the age of six years old can speed up required diagnosis and/or treatment processes. This paper details the enhancement of a Clinical Decision Support System (CDSS) aimed to assist pediatricians and language therapists at early identification and re-ferral of language disorders. The system helps to fine tune the Knowledge Base of Language Delays (KBLD) that was already developed and validated in clinical routine with 146 children. Medical experts supported the construction of Gades CDSS by getting scientific consensus from literature and fifteen years of regis-tered use cases of children with language disorders. The current research focuses on an innovative cooperative model that allows the evolution of the KBLD of Gades through the supervised evaluation of the CDSS learnings with experts¿ feedback. The deployment of the resulting system is being assessed under a mul-tidisciplinary team of seven experts from the fields of speech therapist, neonatol-ogy, pediatrics, and neurology.

Evaluating a web-based clinical decision support system for language disorders screening in a nursery school

Background: Early and effective identification of developmental disorders during childhood remains a critical task for the international community. The second highest prevalence of common developmental disorders in children are language delays, which are frequently the first symptoms of a possible disorder. Objective: This paper evaluates a Web-based Clinical Decision Support System (CDSS) whose aim is to enhance the screening of language disorders at a nursery school. The common lack of early diagnosis of language disorders led us to deploy an easy-to-use CDSS in order to evaluate its accuracy in early detection of language pathologies. This CDSS can be used by pediatricians to support the screening of language disorders in primary care. Methods: This paper details the evaluation results of the ?Gades? CDSS at a nursery school with 146 children, 12 educators, and 1 language therapist. The methodology embraces two consecutive phases. The first stage involves the observation of each child?s language abilities, carried out by the educators, to facilitate the evaluation of language acquisition level performed by a language therapist. Next, the same language therapist evaluates the reliability of the observed results. Results: The Gades CDSS was integrated to provide the language therapist with the required clinical information. The validation process showed a global 83.6% (122/146) success rate in language evaluation and a 7% (7/94) rate of non-accepted system decisions within the range of children from 0 to 3 years old. The system helped language therapists to identify new children with potential disorders who required further evaluation. This process will revalidate the CDSS output and allow the enhancement of early detection of language disorders in children. The system does need minor refinement, since the therapists disagreed with some questions from the CDSS knowledge base (KB) and suggested adding a few questions about speech production and pragmatic abilities. The refinement of the KB will address these issues and include the requested improvements, with the support of the experts who took part in the original KB development. Conclusions: This research demonstrated the benefit of a Web-based CDSS to monitor children?s neurodevelopment via the early detection of language delays at a nursery school. Current next steps focus on the design of a model that includes pseudo auto-learning capacity, supervised by experts.

EEAS 2.0. A legal commentary on Council Decision 2010/427/EU establishing the organisation and functioning of the European External Action Service. EIPA Working Paper, 2013

From the Preface. Pursuant to Article 13(3) of Council Decision 2010/427/EU of 26 July 2010 establishing the organisation and functioning of the European External Action Service, the High Representative is held to provide a review of the organisation and functioning of the EEAS by mid-­‐2013. This review will cover, inter alia, the implementation of Article 6(6), (8) and (11), so as to ensure an adequate geographical and gender balance and a meaningful presence of nationals from all member states in the EEAS. If necessary, the review will be accompanied by appropriate proposals for the revision of the 2010 Council Decision (e.g., suggestions for additional specific measures to correct possible imbalances of staffing). In that case, the Council will, in accordance with Article 27(3) TEU, revise the Decision in light of the review by the beginning of 2014. This short and user-­‐friendly legal commentary on the 2010 Council Decision is the first of its kind and is intended to inform those involved in the review process and to serve as a reference document for practitioners and analysts dealing with the EEAS. This commentary is not an elaborate doctrinal piece, but rather a textual and contextual analysis of each article, that takes account of i) other relevant legal provisions (primary, secondary, international), ii) the process leading to the adoption of the 2010 Council Decision (i.e. travauxpréparatoires), iii) the preamble of the Council Decision, and iv) insofar as it is possible at this stage, early implementation. Wherever relevant, cross-­‐references to other provisions of the EEAS Council Decision have been made so as to tie in the different commentaries and ensure overall consistency.

EEAS 2.0: A legal commentary on Council Decision 2010/427/EU establishing the organisation and functioning of the European External Action Service. CEPS Paperbacks. February 2013

This short and user-friendly legal commentary on the 2010 Council Decision establishing the organisation and functioning of the EEAS is the first of its kind. It is intended to inform those involved in the review process and to serve as a reference document for practitioners and analysts dealing with the EEAS. Rather than an elaborate doctrinal piece, this legal commentary is a textual and contextual analysis of each article that takes account of i) other relevant legal provisions (primary, secondary, international); ii) the process leading to the adoption of the 2010 Council Decision; iii) the preamble of the Council Decision and iv) insofar as it is possible at this stage, early implementation. Wherever relevant, cross-references to other provisions of the Council Decision have been made so as to tie in the different commentaries and ensure overall consistency.

Dealing with the Fallout: West Germany's Response to the Solange Decision (1974). ACES Working Papers, 2011

The European Union's powerful legal system has proven to be the vanguard moment in the process of European integration. As early as the 1960s, the European Court of Justice established an effective and powerful supranational legal order, beyond the original wording of the Treaties of Rome through the doctrines of direct effect and supremacy. Whereas scholars have analyzed the evolution of EU case law and its implications, only very recent historical scholarship has examined how the Member States received this process in the context of a number of difficult political and economic crises for the integration process. This paper investigates how the national level dealt with these fundamental transformations in the European legal system. Specifically, it examines one of the Union's most important member states, the Federal Republic of Germany. Faced with a huge number of cases dealing with European law, German judges dealt with the supremacy of European law very cautiously, negotiating between increasingly polarized academic, public and ministerial debates on the question throughout the 1960s. By the mid 1970s, the German Constitutional Court famously limited the power of the ECJ in its Solange decision (1974). This was an expression of a broader discourse in Germany from 1968 onwards about the qualitative nature of democracy and participation in public life and was in some aspects a marker, at which the German elites felt comfortable expressing the value of their national constitutional system on the European stage. This paper examines the political, media and academic build up and response to the Constitutional Court's decision in the 1970s, arguing that the national "reception" is central to understanding the dynamics and evolution of European Union legal history.

'Going Public': The Mediatization of Decision-Making Processes

In most Western countries, the media are said to exert an increasing influence on the political game. This development, which has been described variably as a shift towards an 'audience democracy' (Manin 1995) or the 'mediatization of politics' (Mazzoleni and Schulz 1999), emphasizes the increasing importance of the media for political actors and political decision-making. In such a context, political actors need to communicate with both the media and the public in order to gain support for their policy plans and to influence decision-making. The media were noticeably absent from Kriesi's (1980) in-depth analysis of political decision-making in Switzerland. This suggests that in the early 1970s, the media did not matter or mattered far less than they do today.

Political Decision-Making in Switzerland. The Consensus Model under Pressure

This in-depth study of the decision-making processes of the early 2000s shows that the Swiss consensus democracy has changed considerably. Power relations have transformed, conflict has increased, coalitions have become more unstable and outputs less predictable. Yet these challenges to consensus politics provide opportunities for innovation.

Debates, resolutions and other proceedings of the convention of the commonwealth of Massachusetts : Convened at Boston, on the 9th of January, 1788, and continued until the 7th of February following, for the purpose of assenting to and ratifying the Constitution recommended by the grand federal convention. : Together with the yeas and nays on the decision of the grand question. : To which the federal Constitution is prefixed; and to which are added, the amendments which have been made therein.

Shaw & Shoemaker

Information giving and decision-making in patients with advanced cancer: A systematic review

Patients with advanced, non-curable cancer face difficult decisions on further treatment, where a small increase in survival time must be balanced against: the toxicity of the treatment. If patients want to be involved in these decisions, in keeping with current notions of autonomy and empowerment, they also require to be adequately informed both on the treatments proposed and on their own disease status and prognosis. A systematic review was performed on decision-making and information provision in patients with advanced cancer. Studies of interventions to improve information giving and encourage participation in decision-making were reviewed, including both randomised controlled trials and uncontrolled studies. Almost all patients expressed a desire for full information, but only about two-thirds wished to participate actively in decision-making. Higher educational level, younger age and female sex were predictive of a desire to participate in decision-making. Active decision-making was more common in patients with certain cancers (e.g. breast) than others (e.g. prostate). A number of simple interventions including question prompt sheets, audio-taping of consultations and patient decision aids have been shown to facilitate such involvement. (c) 2005 Elsevier Ltd. All rights reserved.

Public sector investment appraisal:the place of flexibility in the decision making process

This thesis reviews the main methodological developments in public sector investment appraisal and finds growing evidence that appraisal techniques are not fulfilling their earlier promise. It is suggested that an important reason for this failure lies in the inability of these techniques to handle uncertainty except in a highly circumscribed fashion. It is argued that a more fruitful approach is to strive for flexibility. Investment projects should be formulated with a view to making them responsive to a wide range of possible future events, rather than embodying a solution which is optimal for one configuration of circumstances only. The distinction drawn in economics between the short and the long run is used to examine the nature of flexibility. The concept of long run flexibility is applied to the pre-investment range of choice open to the decisionmaker. It is demonstrated that flexibility is reduced at a very early stage of decisionmaking by the conventional system of appraisal which evaluates only a small number of options. The pre-appraisal filtering process is considered further in relation to decisionmaking models. It is argued that for public sector projects the narrowing down of options is best understood in relation to an amended mixed scanning model which places importance on the process by which the 'national interest ' is determined. Short run flexibility deals with operational characteristics, the degree to which particular projects may respond to changing demands when the basic investment is already in place. The tension between flexibility and cost is noted. A short case study on the choice of electricity generating plant is presented. The thesis concludes with a brief examination of the approaches used by successive British governments to public sector investment, particularly in relation to the nationalised industries

A reevaluation of achromatic spatio-temporal vision: nonoriented filters are monocular, they adapt, and can be used for decision making at high flicker speeds

Masking, adaptation, and summation paradigms have been used to investigate the characteristics of early spatio-temporal vision. Each has been taken to provide evidence for (i) oriented and (ii) nonoriented spatial-filtering mechanisms. However, subsequent findings suggest that the evidence for nonoriented mechanisms has been misinterpreted: those experiments might have revealed the characteristics of suppression (eg, gain control), not excitation, or merely the isotropic subunits of the oriented detecting mechanisms. To shed light on this, we used all three paradigms to focus on the ‘high-speed’ corner of spatio-temporal vision (low spatial frequency, high temporal frequency), where cross-oriented achromatic effects are greatest. We used flickering Gabor patches as targets and a 2IFC procedure for monocular, binocular, and dichoptic stimulus presentations. To account for our results, we devised a simple model involving an isotropic monocular filter-stage feeding orientation-tuned binocular filters. Both filter stages are adaptable, and their outputs are available to the decision stage following nonlinear contrast transduction. However, the monocular isotropic filters (i) adapt only to high-speed stimuli—consistent with a magnocellular subcortical substrate—and (ii) benefit decision making only for high-speed stimuli (ie, isotropic monocular outputs are available only for high-speed stimuli). According to this model, the visual processes revealed by masking, adaptation, and summation are related but not identical.

Supporting decision-making for self-adaptive systems:from goal models to dynamic decision networks

Context/Motivation - Different modeling techniques have been used to model requirements and decision-making of self-adaptive systems (SASs). Specifically, goal models have been prolific in supporting decision-making depending on partial and total fulfilment of functional (goals) and non-functional requirements (softgoals). Different goalrealization strategies can have different effects on softgoals which are specified with weighted contribution-links. The final decision about what strategy to use is based, among other reasons, on a utility function that takes into account the weighted sum of the different effects on softgoals. Questions/Problems - One of the main challenges about decisionmaking in self-adaptive systems is to deal with uncertainty during runtime. New techniques are needed to systematically revise the current model when empirical evidence becomes available from the deployment. Principal ideas/results - In this paper we enrich the decision-making supported by goal models by using Dynamic Decision Networks (DDNs). Goal realization strategies and their impact on softgoals have a correspondence with decision alternatives and conditional probabilities and expected utilities in the DDNs respectively. Our novel approach allows the specification of preferences over the softgoals and supports reasoning about partial satisfaction of softgoals using probabilities. We report results of the application of the approach on two different cases. Our early results suggest the decision-making process of SASs can be improved by using DDNs. © 2013 Springer-Verlag.