The additional facet of immunoscore: immunoprofiling as a possible predictive tool for cancer treatment

Recent investigations of the tumor microenvironment have shown that many tumors are infiltrated by inflammatory and lymphocytic cells. Increasing evidence suggests that the number, type and location of these tumor-infiltrating lymphocytes in primary tumors has prognostic value, and this has led to the development of an 'immunoscore. As well as providing useful prognostic information, the immunoscore concept also has the potential to help predict response to treatment, thereby improving decision- making with regard to choice of therapy. This predictive aspect of the tumor microenvironment forms the basis for the concept of immunoprofiling, which can be described as 'using an individual's immune system signature (or profile) to predict that patient's response to therapy' The immunoprofile of an individual can be genetically determined or tumor-induced (and therefore dynamic). Ipilimumab is the first in a series of immunomodulating antibodies and has been shown to be associated with improved overall survival in patients with advanced melanoma. Other immunotherapies in development include anti-programmed death 1 protein (nivolumab), anti-PD-ligand 1, anti-CD137 (urelumab), and anti-OX40. Biomarkers that can be used as predictive factors for these treatments have not yet been clinically validated. However, there is already evidence that the tumor microenvironment can have a predictive role, with clinical activity of ipilimumab related to high baseline expression of the immune-related genes FoxP3 and indoleamine 2,3-dioxygenase and an increase in tumor-infiltrating lymphocytes. These biomarkers could represent the first potential proposal for an immunoprofiling panel in patients for whom anti-CTLA-4 therapy is being considered, although prospective data are required. In conclusion, the evaluation of systemic and local immunological biomarkers could offer useful prognostic information and facilitate clinical decision making. The challenge will be to identify the individual immunoprofile of each patient and the consequent choice of optimal therapy or combination of therapies to be used.

Antenna Simulations and Measurements of Focal Plane Array Facet Reflectors

We present a conceptual prototype model of a focal plane array unit for the STEAMR instrument, highlighting the challenges presented by the required high relative beam proximity of the instrument and focus on how edge-diffraction effects contribute to the array's performance. The analysis was carried out as a comparative process using both PO & PTD and MoM techniques. We first highlight general differences between these computational techniques, with the discussion focusing on diffractive edge effects for near-field imaging reflectors with high truncation. We then present the results of in-depth modeling analyses of the STEAMR focal plane array followed by near-field antenna measurements of a breadboard model of the array. The results of these near-field measurements agree well with both simulation techniques although MoM shows slightly higher complex beam coupling to the measurements than PO & PTD.

The cultural facet of suicidal behaviour: Its importance and neglect

Culture is a central but debated concept in many disciplines and its complexity may become an even bigger source of argument in Suicidology. In spite of the intricacy of the study of this construct, the paper illustrates that various scholars have recognised the relevance of culture and ethnicity in the understanding of suicidal behaviour. The author provides evidence of the need to pay more attention to the meaning and interpretation of suicide in cross-cultural research and underlines the necessity to establish cultural-sensitive prevention strategies. The paper closes by providing methodological considerations and suggestions for future research on cultural aspects of suicidal behaviour.

Environmental and nature conservation : a facet study of concern for the quality of the natural environment

A multi-variate descriptive model of environmental and nature conservation attitudes and values is proposed and empirically supported. A mapping sentence is developed out of analysis of data from a series of Repertory Grid interviews addressing conservation employees' attitudes towards their profession's activities. The research is carried out within the meta-theoretical framework of Facet Theory. A mapping sentence is developed consisting of 9 facets. From the mapping sentence 3 questionnaires were constructed viewing the selective orientations towards environmental concern. A mapping sentence and facet model is developed for each study. Once the internal structure of this model had been established using Similarity Structure Analysis, the elements of the facets are subjected to Partial Order Scalogram Analysis with base coordinates. A questionnaire was statistically analysed to assess the relationship between facet elements and 4 measures of attitudes towards, and involvement with, conservation. This enabled the comparison of the relative strengths of attitudes associated with each facet element and each measure of conservation attitude. In general, the relationship between the social value of conservation and involvement pledges to conservation were monotonic; perceived importance of a conservation issue appearing predictive of personal involvement. Furthermore, the elements of the life area and scale facets were differentially related to attitude measures. The multi-variate descriptive model of environmental conservation values and attitudes is discussed in relation to its implications for psychological research into environmental concern and for environmental and nature conservation.

Many Facet, Common Latent Trait Polytomous IRT Model and EM Algorithm

2000 Mathematics Subject Classification: 91E45.

A Sense of Wonder: Enhancing Access to Folktales through Task and Facet Analysis

Discusses the approach taken in Phase 1 of a three-phase project Folktales, Facets and FRBR [funded by a grant from OCLC/ALISE]. This project works with the special collection of folktales at the Center for Children’s Books (CCB) at the University of Illinois at Urbana-Champaign, and the scholars who use this collection. The project aims to enhance the effectiveness and efficiency of folktale access through deep understanding of user needs. Phase 1 included facet analysis of the bibliographic records for a sample of 100 folktale books in the CCB, and task analysis of interviews with four CCB-affiliated faculty. Describes the information tasks, information seeking obstacles, and desired features for a discovery and access tool related to folktales for this initial group of scholarly users of folktales.

The role of decision-maker preferences in tenancy selection of CBD office accommodation – preliminary literature review

The literature and anecdotal evidence suggests that that there is more to tenancy selection (firm location) than the profit maximisation drive that traditional neo-classical economic location theory suggests. In the first instance these models assume property markets are rational and perfectly competitive; the CBD office market is clearly neither rational nor perfectly competitive. This fact alone relegates such models to the margins of usefulness for an industry that seeks to satisfy tenant demand in order to optimise returns on capital invested. Acknowledgment of property market imperfections are universally accepted to the extent that all contemporary texts discuss the lack of a coherent centralised market place and incomplete and poorly disseminated information processes as fundamental inadequacies which characterise the property market inefficiencies. Less well researched are the facets of the market which allow the observer to determine market activity to be significantly irrational. One such facet is that of ‘decision maker preferences’. The decision to locate a business operation at one location as opposed to another seems ostensibly a routine choice based on short, medium and long term business objectives. These objectives are derived from a process of strategic planning by one or more individuals whose goal is held to be to optimise outcomes which benefit the business (and presumably those employed within it). However the decision making processes appear bounded by how firms function, the institutional context in which they operate, as well as by opportunistic behaviour by individual decision makers who allow personal preferences to infiltrate and ‘corrupt’ the process. In this way, history, culture, geography, as well as institutions all become significant to the extent that these influence and shape individual behaviour which in turn determine the morphology of individual preferences, as well as providing a conduit for them to take effect. This paper exams historical and current literature on the impact of individual behaviour in the decision making process within organisations as a precursor to an investigation of the tenancy decision making process within the CBD office market. Literature on the topic falls within a number of research disciplines, philosophy, psychology and economics to name a few.

Governance and negotiation : context revisited

Context is acknowledged as a significant feature of a negotiation. Background information about the relationship between the parties, available resources and organisational data are readily identifiable as key components of the contextual make-up of negotiations. However, information deriving from the broader setting of the negotiation may be less well-utilised or simply taken-for-granted in a negotiation. This paper suggests that this broader setting, discussed under the rubric of governance, is a critical facet of the context of negotiations. The paper explores the notion of governance and traces its relationship with negotiation. It then offers a framework that sets out the different governance approaches and allows for identifying and assessing potential negotiation strategies according to the dominant governance mode. It concludes that while a mix of governance approaches may be present in negotiations, identifying ‘ideal types’ or dominant governance modes assists in choosing appropriate strategies for successfully undertaking negotiations.

Analysis of distrubances in large interconnected power systems

World economies increasingly demand reliable and economical power supply and distribution. To achieve this aim the majority of power systems are becoming interconnected, with several power utilities supplying the one large network. One problem that occurs in a large interconnected power system is the regular occurrence of system disturbances which can result in the creation of intra-area oscillating modes. These modes can be regarded as the transient responses of the power system to excitation, which are generally characterised as decaying sinusoids. For a power system operating ideally these transient responses would ideally would have a “ring-down” time of 10-15 seconds. Sometimes equipment failures disturb the ideal operation of power systems and oscillating modes with ring-down times greater than 15 seconds arise. The larger settling times associated with such “poorly damped” modes cause substantial power flows between generation nodes, resulting in significant physical stresses on the power distribution system. If these modes are not just poorly damped but “negatively damped”, catastrophic failures of the system can occur. To ensure system stability and security of large power systems, the potentially dangerous oscillating modes generated from disturbances (such as equipment failure) must be quickly identified. The power utility must then apply appropriate damping control strategies. In power system monitoring there exist two facets of critical interest. The first is the estimation of modal parameters for a power system in normal, stable, operation. The second is the rapid detection of any substantial changes to this normal, stable operation (because of equipment breakdown for example). Most work to date has concentrated on the first of these two facets, i.e. on modal parameter estimation. Numerous modal parameter estimation techniques have been proposed and implemented, but all have limitations [1-13]. One of the key limitations of all existing parameter estimation methods is the fact that they require very long data records to provide accurate parameter estimates. This is a particularly significant problem after a sudden detrimental change in damping. One simply cannot afford to wait long enough to collect the large amounts of data required for existing parameter estimators. Motivated by this gap in the current body of knowledge and practice, the research reported in this thesis focuses heavily on rapid detection of changes (i.e. on the second facet mentioned above). This thesis reports on a number of new algorithms which can rapidly flag whether or not there has been a detrimental change to a stable operating system. It will be seen that the new algorithms enable sudden modal changes to be detected within quite short time frames (typically about 1 minute), using data from power systems in normal operation. The new methods reported in this thesis are summarised below. The Energy Based Detector (EBD): The rationale for this method is that the modal disturbance energy is greater for lightly damped modes than it is for heavily damped modes (because the latter decay more rapidly). Sudden changes in modal energy, then, imply sudden changes in modal damping. Because the method relies on data from power systems in normal operation, the modal disturbances are random. Accordingly, the disturbance energy is modelled as a random process (with the parameters of the model being determined from the power system under consideration). A threshold is then set based on the statistical model. The energy method is very simple to implement and is computationally efficient. It is, however, only able to determine whether or not a sudden modal deterioration has occurred; it cannot identify which mode has deteriorated. For this reason the method is particularly well suited to smaller interconnected power systems that involve only a single mode. Optimal Individual Mode Detector (OIMD): As discussed in the previous paragraph, the energy detector can only determine whether or not a change has occurred; it cannot flag which mode is responsible for the deterioration. The OIMD seeks to address this shortcoming. It uses optimal detection theory to test for sudden changes in individual modes. In practice, one can have an OIMD operating for all modes within a system, so that changes in any of the modes can be detected. Like the energy detector, the OIMD is based on a statistical model and a subsequently derived threshold test. The Kalman Innovation Detector (KID): This detector is an alternative to the OIMD. Unlike the OIMD, however, it does not explicitly monitor individual modes. Rather it relies on a key property of a Kalman filter, namely that the Kalman innovation (the difference between the estimated and observed outputs) is white as long as the Kalman filter model is valid. A Kalman filter model is set to represent a particular power system. If some event in the power system (such as equipment failure) causes a sudden change to the power system, the Kalman model will no longer be valid and the innovation will no longer be white. Furthermore, if there is a detrimental system change, the innovation spectrum will display strong peaks in the spectrum at frequency locations associated with changes. Hence the innovation spectrum can be monitored to both set-off an “alarm” when a change occurs and to identify which modal frequency has given rise to the change. The threshold for alarming is based on the simple Chi-Squared PDF for a normalised white noise spectrum [14, 15]. While the method can identify the mode which has deteriorated, it does not necessarily indicate whether there has been a frequency or damping change. The PPM discussed next can monitor frequency changes and so can provide some discrimination in this regard. The Polynomial Phase Method (PPM): In [16] the cubic phase (CP) function was introduced as a tool for revealing frequency related spectral changes. This thesis extends the cubic phase function to a generalised class of polynomial phase functions which can reveal frequency related spectral changes in power systems. A statistical analysis of the technique is performed. When applied to power system analysis, the PPM can provide knowledge of sudden shifts in frequency through both the new frequency estimate and the polynomial phase coefficient information. This knowledge can be then cross-referenced with other detection methods to provide improved detection benchmarks.

Multicultural education, global studies and studies of Asia

Like other nations, Australia has experienced significant change in the past few decades as its society has become increasingly diverse. The new cultures and traditions that result from ethnic and religious diversity have both enriched Australian society and presented it with some challenges. Other challenges have resulted from increased globalisation. For example, the economic fallout from the recent global financial crisis indicates that global issues can impact across a range of levels, from multinational corporations and nation-states to local sites and individual livelihoods. Some suggest that Australia fared better than other nations during this economic crisis because of its export trade with China. Although this is disputed by economists, it highlights another facet of change that is impacting on Australian society and this relates to Australia’s growing engagement with the nations of Asia. There is increasing awareness in education systems that if young people are to achieve their potential as future citizens they need to be able to negotiate the cultural, social, political and economic ties that connect them to the global and regional community through work, leisure and citizenship. Multicultural education, global studies and studies of Asia play a particular part in helping young people to: • appreciate cultural diversity within and beyond their own nation • imagine with some accuracy how others view their world • participate in shaping a better future. This chapter explores the origins, distinctions and common features of each approach.