Biological and Clinical Determinants of Treatment Resistant Schizophrenia

Up to one third of patients with schizophrenia show only limited response todopamine blocking antipsychotic medication. This could be due to distinctneurobiological abnormalities in this subgroup of patients. While there is robustevidence to suggest that the neurobiology of schizophrenia involves increasedpresynaptic striatal dopaminergic elevation, little is known as to whether thisabnormality is present in treatment resistance, and consequently therelationship between this dopamine abnormality and the lack of response totreatment remains unknown. Furthermore, it remains unclear whethertreatment resistance manifests at the outset of illness, and perhaps has aneurodevelopmental origin, or whether it evolves over time, possibly as a resultof a neurodegenerative process.The first study in this thesis investigated striatal presynaptic dopamine synthesisin twelve treatment resistant schizophrenic patients, twelve patients withschizophrenia who had responded to antipsychotics, and twelve healthyvolunteers, using [18F]-DOPA Positron Emission Tomography (PET). Thus, itwas possible to test the hypothesis that the response to treatment is determinedby differences in presynaptic dopamine function. The results demonstrated thatthere were no significant differences in striatal dopamine synthesis capacitybetween treatment resistant patients and healthy volunteers, whilst dopaminesynthesis capacity was significantly increased in responders relative totreatment resistant patients. The difference was most marked in the associativeand the limbic striatal subdivisions.A second, large follow-up study of first episode psychosis (FEP) patients,examined the course of treatment resistance over the 10 year follow up. It wasfound that over 80% of treatment resistant patients were persistently resistantfrom the initiation of antipsychotic treatment. My PET study, due to its crosssectional design, could not determine whether the normal dopamine levelspredate the antipsychotic exposure in treatment resistant patients. However, bydemonstrating that a great majority of treatment resistant patients are resistantto dopamine blocking antipsychotics at first ever initiation of treatment, mysecond study raises the possibility that these patients may have had normaldopamine levels even at the outset of their psychotic illness. In the same FEPcohort it was possible to investigate neurodevelopmental predictors of treatmentresistance. The finding that the negative symptom dimension and younger ageof onset were significant predictors of treatment resistance is compatible withthe view that TRS may be of neurodevelopmental origin.Overall, my observations in this thesis indicate that TRS may be a distinct andenduring subtype of schizophrenic illness of a possible neurodevelopmentalorigin whose pathophysiology is not marked by alterations in dopaminesynthesis capacity. Findings emerging from this thesis provide a platform forfuture studies, which may lead to the discovery of much needed new treatmentsfor this disabling and intractable condition.<br/

Co-design and modelling of security policy for cultural and behavioural aspects of security in organisations

Organisations have historically applied a technology-oriented approach to information security. However, organisations are increasingly acknowledging the importance of human factors in managing secure workplaces. Having an effective security culture is seen as preferable to enforced compliance with policy. Yet, the study of security culture has not been addressed consistently, either in terms of its conceptual meaning or its practical implementation. Consequently, practitioners lack guidance on cultural elements of security provisioning and on engaging employees in identifying security solutions. To address existing problems relating to security policy in respect of organisational culture, this thesis explores behavioural and cultural aspects of organisational security. We address gaps in human-centred research, focusing on the lack of work representing real-world environments and insufficient collaboration between researchers and practitioners in the study of security culture. We address these gaps through analytical work, a novel co-design methodology, and two user studies. We demonstrate that current approaches to security interventions mirror rational-agent economics, even where behavioural economics is embodied in promoting security behaviours. We present two case studies exploring the dynamics between security provisioning and organisational culture in real-world environments, focusing on distinct groups of users — employees, security managers, and IT/security support — whose interactions are understudied. Our co-design methodology surfaces the complex, interconnected nature of supporting workable security practices by engaging modellers and stakeholders in a collaborative process producing mutually understood and beneficial models. We find employees prefer local support and assurances of secure behaviour rather than guidance without local context. Trust-based relationships with support teams improve engagement. Policy is perceived through interactions with support staff and by observing everyday workplace security behaviours. We find value in engaging with decision-makers and understanding their decision-making processes. We encourage researchers and practitioners to engage in a co-design process producing multi-stakeholder views of the complexities of security in organisations

How Genes and Environmental Factors Determine the Different Neurodevelopmental Trajectories of Schizophrenia and Bipolar Disorder

The debate endures as to whether schizophrenia and bipolar disorder are separate entities or different manifestations of a single underlying pathological process. Here, we argue that this sterile argument obscures the fact that the truth lies somewhere in between. Thus, recent studies support a model whereby, on a background of some shared genetic liability for both disorders, patients with schizophrenia have been subject to additional genetic and/or environmental factors that impair neurodevelopment; for example, copy number variants and obstetric complications are associated with schizophrenia but not with bipolar disorder. As a result, children destined to develop schizophrenia show an excess of neuromotor delays and cognitive difficulties while those who later develop bipolar disorder perform at least as well as the general population. In keeping with this model, cognitive impairments and brain structural abnormalities are present at first onset of schizophrenia but not in the early stages of bipolar disorder. However, with repeated episodes of illness, cognitive and brain structural abnormalities accumulate in both schizophrenia and bipolar disorder, thus clouding the picture

The boundedly rational employee: Security economics for behaviour intervention support in organizations

Security policy-makers (influencers) in an organization set security policies that embody intended behaviours for employees (as decision-makers) to follow. Decision-makers then face choices, where this is not simply a binary decision of whether to comply or not, but also how to approach compliance and secure working alongside other workplace pressures, and limited resources for identifying optimal security-related choices. Conflict arises because of information asymmetries present in the relationship, where influencers and decision-makers both consider costs, gains, and losses in ways which are not necessarily aligned. With the need to promote ‘good enough’ decisions about security-related behaviours under such constraints, we hypothesize that actions to resolve this misalignment can benefit from constructs from both traditional economics and behavioural economics. Here we demonstrate how current approaches to security behaviour provisioning in organizations mirror rational-agent economics, even where behavioural economics is embodied in the promotion of individual security behaviours. We develop and present a framework to accommodate bounded security decision-making, within an ongoing programme of behaviours which must be provisioned for and supported. Our four stage plan to Capture, Adapt, Realign, and Enable behaviour choices provides guidance for security managers, focusing on a more effective response to the uncertainty associated with security behaviour in organizations

Philosophical afterthought and Hegel's account of the Fall in the Encyclopaedia logic

The purpose of the essay is to offer a close reading of Hegel's account of the Fall along theologically orthodox lines. To this extent I am more in agreement with traditional readers of Hegel like Peter Hodgson, and more recently theologians like Graham Ward and Nicholas Adams who wish to bring Hegel closer to a 'generous orthodoxy' (Ward, p. 290) in order to open up the possibility of appropriating elements of the Hegelian project for the purposes of Christian theology and philosophy. In so far as I will argue for an orthodox reading of the Fall in the Encyclopaedia Logic, I will nevertheless try to show how this more or less theologically traditional reading of a religious account in Hegel engenders a sophisticated and in many ways novel meta-philosophical argument for the foundations of philosophy grounded in the features of human thought which participates in divine thought

Auditory hallucinations in non-psychotic disorders – an analytical psychological perspective

Although hallucinations are a feature of psychosis, they can present in non-psychotic disorders and may occur in non-pathological states. Jung argues that unconscious complexes underpin hallucinations and further observes that some of the symptoms of ‘hysteric' patients – including hallucinations – were also common amongst patients with schizophrenia. However, the outward presentation of symptoms was markedly different for each patient group. Jung mobilises his complex theory to explain this difference. We argue that Jung’s understanding of hallucinations applies to contemporary healthcare; it frames how hallucinations may manifest in multiple conditions, not just psychosis. This brief report discusses Jung’s theories and their continued veracity in contemporary contexts

Level of Work Related Stress among Teachers in Elementary Schools

BACKGROUND: Teaching is considered a highly stressful occupation, with work-related stress levels among teachers being among the highest compared to other professions. Unfortunately there are very few studies regarding the levels of work-related stress among teachers in the Republic of Macedonia.AIM: To identify the level of self-perceived work-related stress among teachers in elementary schools and its relationship to gender, age, position in the workplace, the level of education and working experience.MATERIAL AND METHODS: We performed a descriptive-analytical model of a cross-sectional study that involved 300 teachers employed in nine elementary schools.  Evaluation of examined subjects included completion of a specially designed questionnaire.RESULTS: We found that the majority of interviewed teachers perceive their work-related stress as moderate. The level of work-related stress was significantly high related to the gender, age, position in workplace, as well as working experience (p &lt; 0.01), while it was significant related to level of education (p &lt; 0.05). Significantly greater number of lower-grade teachers perceives the workplace as extremely stressful as compared to the upper-grade teachers (18.5% vs. 5.45%), while the same is true for female respondents as compared to the male ones (15.38% vs. 3.8%). In addition, our results show that teachers with university education significantly more often associate their workplace with stronger stress than their colleagues with high education (13.48% vs. 9.4%). We also found that there is no significant difference of stress levels between new and more experienced teachers.CONCLUSION: Our findings confirm that the majority of interviewed teachers perceived their work-related stress as high or very high. In terms of the relationship between the level of teachers’ stress and certain demographic and job characteristics, according to our results, the level of work-related stress has shown significantly high relation to gender, age, levels of grades taught as well as working experience, and significant relation to the level of education

Future Opportunities for Spatial Development of the University in Line with Contemporary City Concepts

The university as a knowledge-intense space-also referred to as the brain of the city-is one of the key urban factors whose role is gradually being repositioned in the city and society during its social and urban transformation. New concepts of cities have entered professional discourses, and six categories were found to be conceptually distinct enough to be seen as supported by a specific body of theories. The research goal for this study is to define three of these-the sustainable city, smart city and resilient city—and the evolving university-city co-influencing relationship. The main methods used for this study are the analytical and descriptive methods, and the research materials are drawn from wide-ranging literature, such as books, research articles, published analyses, reports, urban plans, and other documents

Bruxism Unconscious Oral Habit in Everyday Life

BACKGROUND: Bruxism is defined as an unconscious oral habit of rhythmical, unfunctional clenching, grinding and making chewy sounds with the teeth while making movements that are not part of the masticatory function and that lead to occlusal trauma. AIM: The purpose of this article is to show the habit bruxism, in everyday life, reviewing literature data. METHODS: Data was researched by using information on the internet on Researchgate, Pubmed, ScienceDirect, by analysing written articles and books and student books. From 200 articles that were analysed, 45 articles and two textbooks were involved in writing of this review article. RESULTS: Results derived from the analyzed literature, classify the main consequences of bruxism, from fatigue, pain, wasting of the incisal edges and occlusal surfaces of the teeth to loss of teeth, dental implants, headaches, periodontal lesions and TMD (dysfunctions of the masticatory muscles and temporomandibular joint (TMJ)) in severe cases. All these problems negatively affect the quality of everyday life of the patient. CONCLUSION: Bruxism as a parafunctional habit is present in everyday life needing a multidisciplinary approach for prevention of the teeth, bone and prosthetic restorations. The prevalence of bruxism is growing related to stress, drugs, changes in lifestyle, bad nutrition and sleep problems. The therapist should follow signs and symptoms to ensure the best treatment plan of the patient