From complexity to category: Responding to diagnostic uncertainties of autistic spectrum disorders

Objective: Recent data from Education Queensland has identified rising numbers of children receiving diagnoses of autistic spectrum disorder (ASD). Faced with funding diagnostic pressures, in clinical situations that are complex and inherently uncertain, it is possible that specialists err on the side of a positive diagnosis. This study examines the extent to which possible overinclusion of ASD diagnosis may exist in the presence of uncertainty and factors potentially related to this practice in Queensland. Methods: Using anonymous self-report, all Queensland child psychiatrists and paediatricians who see paediatric patients with development/behavioural problems were surveyed and asked whether they had ever specified an ASD diagnosis in the presence of diagnostic uncertainty. Using logistic regression, elicited responses to the diagnostic uncertainty questions were related to other clinical- and practice-related characteristics. Results: Overall, 58% of surveyed psychiatrists and paediatricians indicated that, in the face of diagnostic uncertainty, they had erred on the side of providing an ASD diagnosis for educational ascertainment and 36% of clinicians had provided an autism diagnosis for Carer's Allowance when Centrelink diagnostic specifications had not been met. Conclusion: In the absence of definitive biological markers, ASD remains a behavioural diagnosis that is often complex and uncertain. In response to systems that demand a categorical diagnostic response, specialists are providing ASD diagnoses, even when uncertain. The motivation for this practice appears to be a clinical risk/benefit analysis of what will achieve the best outcomes for children. It is likely that these practices will continue unless systems change eligibility to funding based on functional impairment rather than medical diagnostic categories.

The complexity of drinking: Interactions between the cognitive and behavioural determinants of alcohol consumption

This study expanded the earlier work conducted by this laboratory ( Hasking, P.A. and Oei, T.P.S. (2002a) . The differential role of alcohol expectancies, drinking refusal self-efficacy and coping resources in predicting alcohol consumption in community and clinical samples. Addiction Research and Theory , 10 , 465-494), by examining the independent and interactive effects of avoidant coping strategies, positive and negative expectancies and self-efficacy, in predicting volume and frequency of alcohol consumption in a sample of community drinkers. Differential relationships were found between the variables when predicting the two consumption measures. Specifically, while self-efficacy, seeking social support for emotional reasons and using drugs or alcohol to cope were independently related to both volume and frequency of drinking, complex interactions with positive and negative alcohol expectancies were also found. These interactions are discussed in terms of the cognitive and behavioural mechanisms thought to underlie drinking behaviour.

Objective and behavioural assessment of the emergence from post-traumatic amnesia (PTA)

Primary objective: To determine the profile of resolution of typical PTA behaviours and describe new learning and improvements in self-care during PTA. Research design: Prospective longitudinal study monitoring PTA status, functional learning and behaviours on a daily basis. Methods and procedures: Participants were 69 inpatients with traumatic brain injury who were in PTA. PTA was assessed using the Westmead or Oxford PTA assessments. Functional learning capability was assessed using a routine set of daily tasks and behaviour was assessed using an observational checklist. Data was analysed using descriptive statistics. Main outcomes and results: Challenging behaviours that are typically associated with PTA, such as agitation, aggression and wandering resolved in the early stages of PTA and incidence rates of these behaviours were less than 20%. Independence in self-care and bowel and bladder continence emerged later during resolution of PTA. New learning in functional situations was demonstrated by patients in PTA. Conclusions: It is feasible to begin active rehabilitation focused on functional skills-based learning with patients in the later stages of PTA. Formal assessment of typically observed behaviours during PTA may complement memory-based PTA assessments in determining emergence from PTA.

The complexity of p53 stabilization and activation

A number of proteins are activated by stress stimuli but none so spectacularly or with the degree of complexity as the tumour suppressor p53 (human p53 gene or protein). Once stabilized, p53 is responsible for the transcriptional activation of a series of proteins involved in cell cycle control, apoptosis and senescence. This protein is present at low levels in resting cells but after exposure to DNA-damaging agents and other stress stimuli it is stabilized and activated by a series of post-translational modifications that free it from MDM2 (mouse double minute 2 but used interchangeably to denote human also), a ubiquination ligase that ubiquitinates it prior to proteasome degradation. The stability of p53 is also influenced by a series of other interacting proteins. In this review, we discuss the post-translational modifications to p53 in response to different stresses and the consequences of these changes.

From point defects to plate tectonic faults

Understanding and explaining emergent constitutive laws in the multi-scale evolution from point defects, dislocations and two-dimensional defects to plate tectonic scales is an arduous challenge in condensed matter physics. The Earth appears to be the only planet known to have developed stable plate tectonics as a means to get rid of its heat. The emergence of plate tectonics out of mantle convection appears to rely intrinsically on the capacity to form extremely weak faults in the top 100 km of the planet. These faults have a memory of at least several hundred millions of years, yet they appear to rely on the effects of water on line defects. This important phenomenon was first discovered in laboratory and dubbed ``hydrolytic weakening''. At the large scale it explains cycles of co-located resurgence of plate generation and consumption (the Wilson cycle), but the exact physics underlying the process itself and the enormous spanning of scales still remains unclear. We present an attempt to use the multi-scale non-equilibrium thermodynamic energy evolution inside the deforming lithosphere to move phenomenological laws to laws derived from basic scaling quantities, develop self-consistent weakening laws at lithospheric scale and give a fully coupled deformation-weakening constitutive framework. At meso- to plate scale we encounter in a stepwise manner three basic domains governed by the diffusion/reaction time scales of grain growth, thermal diffusion and finally water mobility through point defects in the crystalline lattice. The latter process governs the planetary scale and controls the stability of its heat transfer mode.

Trait physiology and crop modelling to link phenotypic complexity to underlying genetic systems

New tools derived from advances in molecular biology have not been widely adopted in plant breeding because of the inability to connect information at gene level to the phenotype in a manner that is useful for selection. We explore whether a crop growth and development modelling framework can link phenotype complexity to underlying genetic systems in a way that strengthens molecular breeding strategies. We use gene-to-phenotype simulation studies on sorghum to consider the value to marker-assisted selection of intrinsically stable QTLs that might be generated by physiological dissection of complex traits. The consequences on grain yield of genetic variation in four key adaptive traits – phenology, osmotic adjustment, transpiration efficiency, and staygreen – were simulated for a diverse set of environments by placing the known extent of genetic variation in the context of the physiological determinants framework of a crop growth and development model. It was assumed that the three to five genes associated with each trait, had two alleles per locus acting in an additive manner. The effects on average simulated yield, generated by differing combinations of positive alleles for the traits incorporated, varied with environment type. The full matrix of simulated phenotypes, which consisted of 547 location-season combinations and 4235 genotypic expression states, was analysed for genetic and environmental effects. The analysis was conducted in stages with gradually increased understanding of gene-to-phenotype relationships, which would arise from physiological dissection and modelling. It was found that environmental characterisation and physiological knowledge helped to explain and unravel gene and environment context dependencies. We simulated a marker-assisted selection (MAS) breeding strategy based on the analyses of gene effects. When marker scores were allocated based on the contribution of gene effects to yield in a single environment, there was a wide divergence in rate of yield gain over all environments with breeding cycle depending on the environment chosen for the QTL analysis. It was suggested that knowledge resulting from trait physiology and modelling would overcome this dependency by identifying stable QTLs. The improved predictive power would increase the utility of the QTLs in MAS. Developing and implementing this gene-to-phenotype capability in crop improvement requires enhanced attention to phenotyping, ecophysiological modelling, and validation studies to test the stability of candidate QTLs.

Distance measurement using the change in junction voltage across a laser diode due to the self-mixing effect

Conventional detection scheme for self-mixing sensors uses an integrated photodiode within the laser package to monitor the self mixing signal. This arrangement can be simplified by directly obtaining the self-mixing signals across the laser diode itself and omitting the photodiode. This work reports on a Vertical-Cavity Surface-Emitting Laser (VCSEL) based selfmixing sensor using the laser junction voltage to obtain the selfmixing signal. We show that the same information can be obtained with only minor changes to the extraction circuitry leading to potential cost saving with reductions in component costs and complexity and significant increase in bandwidth favoring high speed modulation. Experiments using both photo current and voltage detection were carried out and the results obtained show good agreement with the theory.

Developmental stability and leadership effectiveness

Developmental stability is the degree to which we can withstand environmental or genetic stressors during development. Fluctuating asymmetry (FA), concerns the extent to which the right and left side of the body is asymmetrical and is one way to measure developmental stability. Two studies were carried out that examined both the predictive value of leader FA with leadership behaviors and its role in facilitating group performance. The first study examined the hypothesis that a leader's FA is correlated with scores on the Multifactor Leadership Questionnaire (MLQ). The results revealed individuals with a more asymmetrical morphology scored higher on the transformational, but not transactional, dimensions of leadership behavior. A second study examined the hypothesis that asymmetrical morphology and leadership effectiveness would share a positive relationship. In this study participants who led a business game exercise, revealed a positive relationship between FA and self-reported well-being and task satisfaction. Importantly, there was also a positive correlation between the leader's FA score and group performance. The role that developmental stability may play in leadership effectiveness is discussed in the wider context of evolutionary psychology.

Impaired balance in developmental dyslexia? A meta-analysis of the contending evidence

Background: Developmental dyslexia is typically defined by deficits in phonological skills, but it is also associated with anomalous performance on measures of balance. Although balance assessments are included in several screening batteries for dyslexia, the association between impairments in literacy and deficits in postural stability could be due to the high co-occurrence of dyslexia with other developmental disorders in which impairments of motor behaviour are also prevalent. Methods: We identified 17 published studies that compared balance function between dyslexia and control samples and obtained effect-sizes for each. Contrast and association analyses were used to quantify the influence of hypothesised moderator variables on differences in effects across studies. Results: The mean effect-size of the balance deficit in dyslexia was .64 (95% CI = .44-.78) with heterogeneous findings across the population of studies. Probable co-occurrence of other developmental disorders and variability in intelligence scores in the dyslexia samples were the strongest moderator variables of effect-size. Conclusions: Balance deficits are associated with dyslexia, but these effects are apparently more strongly related to third variables other than to reading ability. Deficits of balance may indicate increased risk of developmental disorder, but are unlikely to be uniquely associated with dyslexia.

Technological and organisational change in small- to medium-sized manufacturing companies:a learning organisation perspective

This paper examines the extent to which a learning organisation perspective is attainable in small- to medium-sized manufacturing companies. An audit tool is developed from the literature on organisational learning and recognised processes that lead towards becoming a learning organisation. The paper focuses on the application of the audit tool in three UK automotive component suppliers which are all experiencing pressures for change imposed by the major vehicle manufacturers. The main changes are concerned with tiering of the supply chain and substantial delegation of responsibilities to component suppliers including an increasing emphasis on innovation and continuous improvement. The companies presented in the paper are taken from a research project into the impact of changes in supply chain relationships on the operation of small- and medium-sized manufacturing firms in the West Midlands region of the UK. The ways in which the companies are responding to change are presented together with the results of a self-assessment using the developed audit tool. These results suggest that companies of this type tend to focus on change in those areas that involve least challenge to the established power and authority of management.

High stability interleaved fibre Michelson interferometer for on-line precision displacement measurements

A self-reference fiber Michelson interferometer measurement system, which employs fiber Bragg gratings (FBGs) as in-fiber reflective mirrors and interleaves together two fiber Michelson interferometers that share the common-interferometric-optical path, is presented. One of the fiber interferometers is used to stabilise the system by the use of an electronic feedback loop to compensate the influences resulting from the environmental disturbances, while the other one is used to perform the measurement task. The influences resulting from the environmental disturbances have been eliminated by the compensating action of the electronic feedback loop, this makes the system suitable for on-line precision measurement. By means of the homodyne phase-tracking technique, the linearity of the measurement results of displacement measurements has been very high.

Le prix de l'individualité. Maine de Brian, Samuel Taylor Coleridge et la volonté: Deux postétités distinctes

This thesis is concerned with Maine de Biran’s and Samuel Taylor Coleridge’s conceptions of will, and the way in which both thinkers’ posterities have been affected by the central role of these very conceptions in their respective bodies of thought. The research question that animates this work can therefore be divided into two main parts, one of which deals with will, while the other deals with its effects on posterity. In the first pages of the Introduction, I make the case for a comparison between two philosophers, and show how this comparison can bring one closer to truth, understood not in objective, but in subjective terms. I then justify my choice by underlining that, in spite of their many differences, Maine de Biran and Samuel Taylor Coleridge followed comparable paths, intellectually and spiritually, and came to similar conclusions concerning the essential activity of the human mind. Finally, I ask whether it is possible that this very focus on the human will may have contributed to the state of both thinkers’ works and of the reception of those works. This prologue is followed by five parts. In the first part, the similarities and differences between the two thinkers are explored further. In the second part, the connections between philosophy and singularity are examined, in order to show the ambivalence of the will as a foundation for truth. The third part is dedicated to the traditional division between subject and object in psychology, and its relevance in history and in moral philosophy. The fourth part tackles the complexity of the question of influence, with respect to both Maine de Biran’s and Coleridge’s cases, both thinkers being indebted to many philosophers of all times and places, and having to rely heavily on others for the publication, or the interpretation of their own works. The fifth part is concerned with the different aspects of the faculty of will, and primarily its relationship with interiority, as incommensurability, and actual, conditioned existence in a certain historical and spatial context. It ends with a return to the question of will and posterity and an announcement of what will be covered in the main body of the thesis. The main body is divided into three parts:‘L’émancipation’, ‘L’affirmation, and ‘La projection’. The first part is devoted to the way Maine de Biran and Samuel Taylor Coleridge extricated themselves from one epistemological paradigm to contribute to the foundation of another. It is divided in four chapters. The first chapter deals with the aforementioned change of paradigm, as corresponding to the emergence of two separate but associated movements, Romanticism and what the French philosopher refers to as ‘The Age of History’. The second chapter concerns the movement that preceded them, i.e. the Enlightenment, its main features according to both of our thinkers, and the two epistemological models that prevailed under it and influenced them heavily in their early years: Sensationism (Maine de Biran) and Associationism (Coleridge). The third chapter is about the probable influence of Immanuel Kant and his followers on Maine de Biran and Coleridge, and the various facts that allow us to claim originality for both thinkers’ works. In the fourth chapter, I contrast Maine de Biran and Coleridge with other movements and thinkers of their time, showing that, contrary to their respective thoughts, Maine de Biran and Coleridge could not but break free from the then prevailing systematic approach to truth. The second part of the thesis is concerned with the first part of its research question, namely, Maine de Biran’s and Coleridge’s conceptions of the will. It is divided into four chapters. The first chapter is a reflection on the will as a paradox: on the one hand, the will cannot be caused by any other phenomenon, or it is no longer a will; but it cannot be left purely undetermined, as if it is, it is then not different from chance. It thus needs, in order to be, to be contradictorily already moral. The second chapter is a comparison between Maine de Biran’s and Coleridge’s accounts of the origin of the will, where it is found that the French philosopher only observes that he has a will, whereas the English philosopher postulates the existence of this will. The comparison between Maine de Biran’s and Coleridge’s conceptions of the will is pursued in the third chapter, which tackles the question of the coincidence between the will and the self, in both thinkers’ works. It ends with the fourth chapter, which deals with the question of the relationship between the will and what is other to it, i.e. bodily sensations, passions and desires. The third part of the thesis focuses on the second part of its research question, namely the posterity of Maine de Biran’s and Coleridge’s works. It is divided into four chapters. The first chapter constitutes a continuation of the last chapter of the preceding part, in that that it deals with Maine de Biran’s and Coleridge’s relations to the ‘other’, and particularly their potential and actual audience, and with the way these relations may have affected their writing and publishing practices. The second chapter is a survey of both thinkers’ general reception, where it is found that, while Maine de Biran has been claimed by two important movements of thoughts as their initiator, Coleridge has been neglected by the only real movement he could have, or may indeed have pioneered. The third chapter is more directly concerned with the posterities of Maine de Biran’s and Coleridge’s conceptions of will, and attempts to show that the approach to, and the meaning of the will have evolved throughout the nineteenth century, and in the French Spiritualist and the British Idealist movements, from an essentially personal one to a more impersonal one. The fourth chapter is a partial conclusion, whose aim is to give a precise idea of where Maine de Biran and Coleridge stand, in relation to their century and to the philosophical movements and matters we are concerned with. The conclusion is a recapitulation of what has been found, with a particular emphasis on the dialogue initiated between Maine de Biran and Coleridge on the will, and the relation between will and posterity. It suggests that both thinkers have to pay the price of a problematic reception for the individuality that pervades their respective works, and goes further in suggesting that s/he who chooses to found his individuality on the will is bound to feel this incompleteness in his/her own personal life more acutely than s/he who does not. It ends with a reflection on fixedness and movement, as the two antagonistic states that the theoretician of the will paradoxically aspires to.

Increased potential of a cationic liposome-based delivery system:enhancing stability and sustained immunological activity in pre-clinical development

The combination of dimethyl dioctadecyl ammonium bromide (DDA) and the synthetic cord factor trehalose dibehenate (TDB) with Ag85B-ESAT-6 (H1 fusion protein) has been found to promote strong protective immune responses against Mycobacterium tuberculosis. The development of a vaccine formulation that is able to facilitate the requirements of sterility, stability and generation of a vaccine product with acceptable composition, shelf-life and safety profile may necessitate selected alterations in vaccine formulation. This study describes the implementation of a sterilisation protocol and the use of selected lyoprotective agents in order to fulfil these requirements. Concomitantly, close analysis of any alteration in physico-chemical characteristics and parameters of immunogenicity have been examined for this promising DDA liposome-based tuberculosis vaccine. The study addresses the extensive guidelines on parameters for non-clinical assessment, suitable for liposomal vaccines and other vaccine delivery systems issued by the World Health Organisation (WHO) and the European Medicines Agency (EMEA). Physical and chemical stability was observed following alteration in formulations to include novel cryoprotectants and radiation sterilisation. Immunogenicity was maintained following these alterations and even improved by modification with lysine as the cryoprotective agent for sterilised formulations. Taken together, these results outline the successful alteration to a liposomal vaccine, representing improved formulations by rational modification, whilst maintaining biological activity.