Tracing the influence of non-narrative film and expanded cinema sound on experimental music

This study surveys and interrogates key conceptual frameworks and artistic practises that flow through the distinct but interconnected traditions of non-narrative film and experimental music, and examines how these are articulated in my own creative sound practise.

Cell migration and proliferation on homogeneous and non-homogeneous domains : modelling on the scale of individuals and populations

Cell migration is a behaviour critical to many key biological effects, including wound healing, cancerous cell invasion and morphogenesis, the development of an organism from an embryo. However, given that each of these situations is distinctly different and cells are extremely complicated biological objects, interest lies in more basic experiments which seek to remove conflating factors and present a less complex environment within which cell migration can be experimentally examined. These include in vitro studies like the scratch assay or circle migration assay, and ex vivo studies like the colonisation of the hindgut by neural crest cells. The reduced complexity of these experiments also makes them much more enticing as problems to mathematically model, like done here. The primary goal of the mathematical models used in this thesis is to shed light on which cellular behaviours work to generate the travelling waves of invasion observed in these experiments, and to explore how variations in these behaviours can potentially predict differences in this invasive pattern which are experimentally observed when cell types or chemical environment are changed. Relevant literature has already identified the difficulty of distinguishing between these behaviours when using traditional mathematical biology techniques operating on a macroscopic scale, and so here a sophisticated individual-cell-level model, an extension of the Cellular Potts Model (CPM), is been constructed and used to model a scratch assay experiment. This model includes a novel mechanism for dealing with cell proliferations that allowed for the differing properties of quiescent and proliferative cells to be implemented into their behaviour. This model is considered both for its predictive power and used to make comparisons with the travelling waves which result in more traditional macroscopic simulations. These comparisons demonstrate a surprising amount of agreement between the two modelling frameworks, and suggest further novel modifications to the CPM that would allow it to better model cell migration. Considerations of the model’s behaviour are used to argue that the dominant effect governing cell migration (random motility or signal-driven taxis) likely depends on the sort of invasion demonstrated by cells, as easily seen by microscopic photography. Additionally, a scratch assay simulated on a non-homogeneous domain consisting of a ’fast’ and ’slow’ region is also used to further differentiate between these different potential cell motility behaviours. A heterogeneous domain is a novel situation which has not been considered mathematically in this context, nor has it been constructed experimentally to the best of the candidate’s knowledge. Thus this problem serves as a thought experiment used to test the conclusions arising from the simulations on homogeneous domains, and to suggest what might be observed should this non-homogeneous assay situation be experimentally realised. Non-intuitive cell invasion patterns are predicted for diffusely-invading cells which respond to a cell-consumed signal or nutrient, contrasted with rather expected behaviour in the case of random-motility-driven invasion. The potential experimental observation of these behaviours is demonstrated by the individual-cell-level model used in this thesis, which does agree with the PDE model in predicting these unexpected invasion patterns. In the interest of examining such a case of a non-homogeneous domain experimentally, some brief suggestion is made as to how this could be achieved.

Ownership, corporate governance and timeliness of price discovery : Australian evidence

This study investigates whether and how a firm’s ownership and corporate governance affect its timeliness of price discovery, which is referred to as the speed of incorporation of value-relevant information into the stock price. Using a panel data of 1,138 Australian firm-year observations from 2001 to 2008, we predict and find a non-linear relationship between ownership concentration and the timeliness of price discovery. We test the identity of the largest shareholder and find that only firms with family as the largest shareholder exhibit faster price discovery. There is no evidence that suggests that the presence of a second largest shareholder affects the timeliness of price discovery materially. Although we find a positive association between corporate governance quality and the timeliness of price discovery, as expected, there is no interaction effect between the largest shareholding and corporate governance in relation to the timeliness of price discovery. Further tests show no evidence of severe endogeneity problems in our study.

Improving ultrasound excitation systems using a flexible power supply with adjustable voltage and frequency to drive piezoelectric transducers

The ability of a piezoelectric transducer in energy conversion is rapidly expanding in several applications. Some of the industrial applications for which a high power ultrasound transducer can be used are surface cleaning, water treatment, plastic welding and food sterilization. Also, a high power ultrasound transducer plays a great role in biomedical applications such as diagnostic and therapeutic applications. An ultrasound transducer is usually applied to convert electrical energy to mechanical energy and vice versa. In some high power ultrasound system, ultrasound transducers are applied as a transmitter, as a receiver or both. As a transmitter, it converts electrical energy to mechanical energy while a receiver converts mechanical energy to electrical energy as a sensor for control system. Once a piezoelectric transducer is excited by electrical signal, piezoelectric material starts to vibrate and generates ultrasound waves. A portion of the ultrasound waves which passes through the medium will be sensed by the receiver and converted to electrical energy. To drive an ultrasound transducer, an excitation signal should be properly designed otherwise undesired signal (low quality) can deteriorate the performance of the transducer (energy conversion) and increase power consumption in the system. For instance, some portion of generated power may be delivered in unwanted frequency which is not acceptable for some applications especially for biomedical applications. To achieve better performance of the transducer, along with the quality of the excitation signal, the characteristics of the high power ultrasound transducer should be taken into consideration as well. In this regard, several simulation and experimental tests are carried out in this research to model high power ultrasound transducers and systems. During these experiments, high power ultrasound transducers are excited by several excitation signals with different amplitudes and frequencies, using a network analyser, a signal generator, a high power amplifier and a multilevel converter. Also, to analyse the behaviour of the ultrasound system, the voltage ratio of the system is measured in different tests. The voltage across transmitter is measured as an input voltage then divided by the output voltage which is measured across receiver. The results of the transducer characteristics and the ultrasound system behaviour are discussed in chapter 4 and 5 of this thesis. Each piezoelectric transducer has several resonance frequencies in which its impedance has lower magnitude as compared to non-resonance frequencies. Among these resonance frequencies, just at one of those frequencies, the magnitude of the impedance is minimum. This resonance frequency is known as the main resonance frequency of the transducer. To attain higher efficiency and deliver more power to the ultrasound system, the transducer is usually excited at the main resonance frequency. Therefore, it is important to find out this frequency and other resonance frequencies. Hereof, a frequency detection method is proposed in this research which is discussed in chapter 2. An extended electrical model of the ultrasound transducer with multiple resonance frequencies consists of several RLC legs in parallel with a capacitor. Each RLC leg represents one of the resonance frequencies of the ultrasound transducer. At resonance frequency the inductor reactance and capacitor reactance cancel out each other and the resistor of this leg represents power conversion of the system at that frequency. This concept is shown in simulation and test results presented in chapter 4. To excite a high power ultrasound transducer, a high power signal is required. Multilevel converters are usually applied to generate a high power signal but the drawback of this signal is low quality in comparison with a sinusoidal signal. In some applications like ultrasound, it is extensively important to generate a high quality signal. Several control and modulation techniques are introduced in different papers to control the output voltage of the multilevel converters. One of those techniques is harmonic elimination technique. In this technique, switching angles are chosen in such way to reduce harmonic contents in the output side. It is undeniable that increasing the number of the switching angles results in more harmonic reduction. But to have more switching angles, more output voltage levels are required which increase the number of components and cost of the converter. To improve the quality of the output voltage signal with no more components, a new harmonic elimination technique is proposed in this research. Based on this new technique, more variables (DC voltage levels and switching angles) are chosen to eliminate more low order harmonics compared to conventional harmonic elimination techniques. In conventional harmonic elimination method, DC voltage levels are same and only switching angles are calculated to eliminate harmonics. Therefore, the number of eliminated harmonic is limited by the number of switching cycles. In the proposed modulation technique, the switching angles and the DC voltage levels are calculated off-line to eliminate more harmonics. Therefore, the DC voltage levels are not equal and should be regulated. To achieve this aim, a DC/DC converter is applied to adjust the DC link voltages with several capacitors. The effect of the new harmonic elimination technique on the output quality of several single phase multilevel converters is explained in chapter 3 and 6 of this thesis. According to the electrical model of high power ultrasound transducer, this device can be modelled as parallel combinations of RLC legs with a main capacitor. The impedance diagram of the transducer in frequency domain shows it has capacitive characteristics in almost all frequencies. Therefore, using a voltage source converter to drive a high power ultrasound transducer can create significant leakage current through the transducer. It happens due to significant voltage stress (dv/dt) across the transducer. To remedy this problem, LC filters are applied in some applications. For some applications such as ultrasound, using a LC filter can deteriorate the performance of the transducer by changing its characteristics and displacing the resonance frequency of the transducer. For such a case a current source converter could be a suitable choice to overcome this problem. In this regard, a current source converter is implemented and applied to excite the high power ultrasound transducer. To control the output current and voltage, a hysteresis control and unipolar modulation are used respectively. The results of this test are explained in chapter 7.

Not all systematic reviews are systematic : a meta-review of the quality of systematic reviews for non-invasive remote monitoring in heart failure

Remote monitoring for heart failure has been evaluated in numerous systematic reviews. The aim of this meta-review was to appraise their quality and synthesise results. We electronically searched online databases, performed a forward citation search and hand-searched bibliographies. Systematic reviews of remote monitoring interventions that were used for surveillance of heart failure patients were included. Seven (41%) systematic reviews pooled results for meta-analysis. Eight (47%) considered all non-invasive remote monitoring strategies. Five (29%) focused on telemonitoring. Four (24%) included both non-invasive and invasive technologies. According to AMSTAR criteria, ten (58%) systematic reviews were of poor methodological quality. In high quality reviews, the relative risk of mortality in patients who received remote monitoring ranged from 0.53 (95% CI=0.29-0.96) to 0.88 (95% CI=0.76-1.01). High quality reviews also reported that remote monitoring reduced the relative risk of all-cause (0.52; 95% CI=0.28-0.96 to 0.96; 95% CI=0.90–1.03) and heart failure-related hospitalizations (0.72; 95% CI=0.64–0.81 to RR 0.79; 95% CI=0.67-0.94) and, as a consequence, healthcare costs. As the high quality reviews reported that remote monitoring reduced hospitalizations, mortality and healthcare costs, research efforts should now be directed towards optimising these interventions in preparation for more widespread implementation.

The effectiveness of non-pharmacologic interventions in improving psychological outcomes for heart transplant recipients : a systematic review

Background The International Society for Heart and Lung Transplantation recommended in 2006 that intervention studies to maximize psychological outcomes after transplantation should be conducted. Potentially, studies reporting on the effectiveness of non-pharmacological interventions in improving psychological outcomes for heart transplant recipients may have been published since the call for this research. Thus, further evidence may currently be available to inform policy and practice decision-making regarding the implementation of such interventions. Accordingly, an evaluation of the evidence is required. Objectives The objective of this review was to identify the effectiveness of non-pharmacological interventions on psychological outcomes for heart transplant recipients.

The development of an effective vaccine against Chlamydia : utilisation of a non-toxic mucosal adjuvant to generate a protective mucosal response

Chlamydia is responsible for a wide range of diseases with enormous global economic and health burden. As the majority of chlamydial infections are asymptomatic, a vaccine has greatest potential to reduce infection and disease prevalence. Protective immunity against Chlamydia requires the induction of a mucosal immune response, ideally, at the multiple sites in the body where an infection can be established. Mucosal immunity is most effectively stimulated by targeting vaccination to the epithelium, which is best accomplished by direct vaccine application to mucosal surfaces rather than by injection. The efficacy of needle-free vaccines however is reliant on a powerful adjuvant to overcome mucosal tolerance. As very few adjuvants have proven able to elicit mucosal immunity without harmful side effects, there is a need to develop non-toxic adjuvants or safer ways to administered pre-existing toxic adjuvants. In the present study we investigated the novel non-toxic mucosal adjuvant CTA1-DD. The immunogenicity of CTA1-DD was compared to our "gold-standard" mucosal adjuvant combination of cholera toxin (CT) and cytosine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN). We also utilised different needle-free immunisation routes, intranasal (IN), sublingual (SL) and transcutaneous (TC), to stimulate the induction of immunity at multiple mucosal surfaces in the body where Chlamydia are known to infect. Moreover, administering each adjuvant by different routes may also limit the toxicity of the CT/CpG adjuvant, currently restricted from use in humans. Mice were immunised with either adjuvant together with the chlamydial major outer membrane protein (MOMP) to evaluate vaccine safety and quantify the induction of antigen-specific mucosal immune responses. The level of protection against infection and disease was also assessed in vaccinated animals following a live genital or respiratory tract infectious challenge. The non-toxic CTA1-DD was found to be safe and immunogenic when delivered via the IN route in mice, inducing a comparable mucosal response and level of protective immunity against chlamydial challenge to its toxic CT/CpG counterpart administered by the same route. The utilisation of different routes of immunisation strongly influenced the distribution of antigen-specific responses to distant mucosal surfaces and also abrogated the toxicity of CT/CpG. The CT/CpG-adjuvanted vaccine was safe when administered by the SL and TC routes and conferred partial immunity against infection and pathology in both challenge models. This protection was attributed to the induction of antigen-specific pro-inflammatory cellular responses in the lymph nodes regional to the site of infection and rather than in the spleen. Development of non-toxic adjuvants and effective ways to reduce the side effects of toxic adjuvants has profound implications for vaccine development, particularly against mucosal pathogens like Chlamydia. Interestingly, we also identified two contrasting vaccines in both infection models capable of preventing infection or pathology exclusively. This indicated that the development of pathology following an infection of vaccinated animals was independent of bacterial load and was instead the result of immunopathology, potentially driven by the adaptive immune response generated following immunisation. While both vaccines expressed high levels of interleukin (IL)-17 cytokines, the pathology protected group displayed significantly reduced expression of corresponding IL-17 receptors and hence an inhibition of signalling. This indicated that the balance of IL-17-mediated responses defines the degree of protection against infection and tissue damage generated following vaccination. This study has enabled us to better understand the immune basis of pathology and protection, necessary to design more effective vaccines.

A discourse on the non-method

In spite of the activism of professional bodies and researchers, empirical evidence shows that project management still does not deliver the expected benefits and promises. Hence, many have questioned the validity of the hegemonic rationalist paradigm anchored in the Enlightenment and Natural Sciences tradition supporting project management research and practice for the last 60 years and the lack of relevance to practice of the current conceptual base of project management. In order to address these limitations many authors, taking a post-modernist stance in social sciences, build on ‘pre-modern’ philosophies such as the Aristotelian one, specially emphasizing the role of praxis (activity), and phronesis (practical wisdom, prudence). Indeed, ‘Praxis … is the central category of the philosophy which is not merely an interpretation of the world, but is also a guide to its transformation …’ (Vazquez, 1977:. 149). Therefore, praxis offers an important focus for practitioners and researchers in social sciences, one in which theory is integrated with practice at the point of intervention. Simply stated, praxis can serve as a common ground for those interested in basic and applied research by providing knowledge of the reality in which action, informed by theory, takes place. Consequently, I suggest a ‘praxeological’ style of reasoning (praxeology being defined as study or science of human actions and conduct, including praxis, practices and phronesis) and to go beyond the ‘Theory-Practice’ divide. Moreover, I argue that we need to move away from the current dichotomy between the two classes ‘scholars experts-researchers’ and ‘managers/workers-practitioners-participants’. Considering one single class of ‘PraXitioner’, becoming a phronimos, may contribute to create new perspectives and open up new ways of thinking and acting in project situations. Thus, I call for a Perestroika in researching and acting in project management situations. My intent is to suggest a balanced praxeological view of the apparent opposition between social and natural science approaches. I explore, in this chapter, three key questions, covering the ontological, epistemological and praxeological dimensions of project management in action. 1. Are the research approaches being currently used appropriate for generating contributions that matter to both theory and practice with regards to what a ‘project’ is or to what we do when we call a specific situation ‘a project’? 2. On the basis of which intellectual virtues is the knowledge generated and what is the impact for theory and practice? 3. Are the modes of action of the practitioners ‘prudent’ and are they differentiating or reconciling formal and abstract rationality from substantive rationality and situated reasoning with regards to the mode of action they adopt in particular project situations? The investigation of the above questions leads me to debate about ‘Project Management-as-Praxis’, and to suggest ‘A’ (not ‘THE’) ‘praxeological’ style of reasoning and mode of inquiry – acknowledging a non-paradigmatic, subjective and kaleidoscopic perspective – for ‘Knowing-as-Practicing’ in project management. In short, this is about making a ‘Projects Science’ that matters.

Refined plastic hinge analysis of steel frame structures comprising non-compact sections : II : verification

Application of "advanced analysis" methods suitable for non-linear analysis and design of steel frame structures permits direct and accurate determination of ultimate system strengths, without resort to simplified elastic methods of analysis and semi-empirical specification equations. However, the application of advanced analysis methods has previously been restricted to steel frames comprising only compact sections that are not influenced by the effects of local buckling. A refined plastic hinge method suitable for practical advanced analysis of steel frame structures comprising non-compact sections is presented in a companion paper. The method implicitly accounts for the effects of gradual cross-sectional yielding, longitudinal spread of plasticity, initial geometric imperfections, residual stresses, and local buckling. The accuracy and precision of the method for the analysis of steel frames comprising non-compact sections is established in this paper by comparison with a comprehensive range of analytical benchmark frame solutions. The refined plastic hinge method is shown to be more accurate and precise than the conventional individual member design methods based on elastic analysis and specification equations.

Bridging the gap: Wellness differences between high and low SES Australian adolescents

Aims Wellness assessments can determine adolescent lifestyle behaviors. A better understanding of wellness differences between high and low SES adolescents could assist policy makers to develop improved strategies to bridge the gap between these two groups. The aim of this investigation was to explore wellness differences between high and low SES adolescents. Methods In total, 241 (125 high and 116 low SES) adolescents completed the 5-Factor Wellness Inventory (5F-Wel). The 5F-Wel comprises 97 items contributing to 17 subscales, 5 dimensions, 4 contexts, total wellness, and a life satisfaction index, with scores ranging from 0-100. Independent sample t-tests were performed with Levene’s test of equality for variances, which checked the assumption of homogeneity of variances. Results Overall, 117 (94%) and 112 (97 %) high and low SES participants had complete data and were included in the analysis. The high SES group scored higher for total wellness (M = 81.09, SE = .61) than the low SES group (M = 75.73, SE = .99). This difference was significant t (186) = 4.635, p < .05, with a medium effect size r = .32. The high SES group scored higher on 23 of 27 scales (21 scales, p < .05), while the low SES group scored higher on the remaining 3 scales (all non-significant). Conclusion These results contribute empirical data to the body of literature, indicating a large wellness discrepancy between high and low SES youth. Deficient areas can be targeted by policymakers to assist in bridging the gap between these groups.

Study protocol : establishing good relationships between patients and health care providers while providing cardiac care. Exploring how patient-clinician engagement contributes to health disparities between indigenous and non-indigenous Australians in South Australia

Abstract Background: Studies that compare Indigenous Australian and non-Indigenous patients who experience a cardiac event or chest pain are inconclusive about the reasons for the differences in-hospital and survival rates. The advances in diagnostic accuracy, medication and specialised workforce has contributed to a lower case fatality and lengthen survival rates however this is not evident in the Indigenous Australian population. A possible driver contributing to this disparity may be the impact of patient-clinician interface during key interactions during the health care process. Methods/Design: This study will apply an Indigenous framework to describe the interaction between Indigenous patients and clinicians during the continuum of cardiac health care, i.e. from acute admission, secondary and rehabilitative care. Adopting an Indigenous framework is more aligned with Indigenous realities, knowledge, intellects, histories and experiences. A triple layered designed focus group will be employed to discuss patient-clinician engagement. Focus groups will be arranged by geographic clusters i.e. metropolitan and a regional centre. Patient informants will be identified by Indigenous status (i.e. Indigenous and non-Indigenous) and the focus groups will be convened separately. The health care provider focus groups will be convened on an organisational basis i.e. state health providers and Aboriginal Community Controlled Health Services. Yarning will be used as a research method to facilitate discussion. Yarning is in congruence with the oral traditions that are still a reality in day-to-day Indigenous lives. Discussion: This study is nestled in a larger research program that explores the drivers to the disparity of care and health outcomes for Indigenous and non-Indigenous Australians who experience an acute cardiac admission. A focus on health status, risk factors and clinical interventions may camouflage critical issues within a patient-clinician exchange. This approach may provide a way forward to reduce the appalling health disadvantage experienced within the Indigenous Australian communities. Keywords: Patient-clinician engagement, Qualitative, Cardiovascular disease, Focus groups, Indigenous

Postpartum care for Aboriginal and non-Aboriginal women with Gestational Diabetes Mellitus across urban, rural and remote locations : a protocol for a cohort linkage study

Background: Gestational diabetes mellitus (GDM) is increasing, along with obesity and type 2 diabetes (T2DM), with Aboriginal and Torres Strait Islander people* in Australia particularly affected. GDM causes serious complications in pregnancy, birth, and the longer term, for both women and their infants. Women diagnosed with GDM have an eightfold risk of developing T2DM after pregnancy, compared with women who have not had GDM. Indigenous women have an even higher risk, at a younger age, and progress more quickly from GDM to T2DM, compared to non-Indigenous women. If left undetected and untreated, T2DM can lead to heart disease, stroke, renal disease, kidney failure, amputations and blindness. A GDM diagnosis offers a ‘window of opportunity’ for diabetes health interventions and it is vital that acceptable and effective prevention, treatment, and post-pregnancy care are provided. Low rates of post-pregnancy screening for T2DM are reported among non-Aboriginal women in Australia and among Indigenous women in other countries, however data for Aboriginal women are scarce. Breastfeeding, a healthy diet, and exercise can also help to prevent T2DM, and together with T2DM screening are recommended elements of ‘post-pregnancy care’ for women with GDM, This paper describes methods for a data linkage study to investigate rates of post-pregnancy care among women with GDM. Methods/Design: This retrospective cohort includes all women who gave birth at Cairns Base Hospital in Far North Queensland, Australia, from 2004 to 2010, coded as having GDM in the Cairns Base Hospital Clinical Coding system. Data linkage is being conducted with the Queensland Perinatal Data Collection, and three laboratories. Hospital medical records are being reviewed to validate the accuracy of GDM case ascertainment, and gather information on breastfeeding and provision of dietary advice. Multiple logistic regression is being used to compare post-pregnancy care between Aboriginal and non-Aboriginal women, while adjusting for other factors may impact on post-pregnancy care. Survival analysis is being used to estimate the rates of progression from GDM to T2DM. Discussion: There are challenges to collecting post-pregnancy data for women with GDM. However, research is urgently needed to ensure adequate post-pregnancy care is provided for women with GDM in Australia.

High-resolution loss of heterozygosity screening implicates PTPRJ as a potential tumor suppressor gene that affects susceptibility to non-Hodgkin's Lymphoma

We employed a Hidden-Markov-Model (HMM) algorithm in loss of heterozygosity (LOH) analysis of high-density single nucleotide polymorphism (SNP) array data from Non-Hodgkin’s lymphoma (NHL) entities, follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). This revealed a high frequency of LOH over the chromosomal region 11p11.2, containing the gene encoding the protein tyrosine phosphatase receptor type J (PTPRJ). Although PTPRJ regulates components of key survival pathways in B-cells (i.e., BCR, MAPK, and PI3K signaling), its role in B-cell development is poorly understood. LOH of PTPRJ has been described in several types of cancer but not in any hematological malignancy. Interestingly, FL cases with LOH exhibited down-regulation of PTPRJ, in contrast no significant variation of expression was shown in DLBCLs. In addition, sequence screening in Exons 5 and 13 of PTPRJ identified the G973A (rs2270993), T1054C (rs2270992), A1182C (rs1566734), and G2971C (rs4752904) coding SNPs (cSNPs). The A1182 allele was significantly more frequent in FLs and in NHLs with LOH. Significant over-representation of the C1054 (rs2270992) and the C2971 (rs4752904) alleles were also observed in LOH cases. A haplotype analysis also revealed a significant lower frequency of haplotype GTCG in NHL cases, but it was only detected in cases with retention. Conversely, haplotype GCAC was over-representated in cases with LOH. Altogether, these results indicate that the inactivation of PTPRJ may be a common lymphomagenic mechanism in these NHL subtypes and that haplotypes in PTPRJ gene may play a role in susceptibility to NHL, by affecting activation of PTPRJ in these B-cell lymphomas.

Role of the apolipoprotein E and catechol-O-methyltransferase genes in prospective and retrospective memory traits

Human memory is a complex neurocognitive process. By combining psychological and molecular genetics expertise, we examined the APOE ε4 allele, a known risk factor for Alzheimer's disease, and the COMT Val 158 polymorphism, previously implicated in schizophrenia, for association with lowered memory functioning in healthy adults. To assess memory type we used a range of memory tests of both retrospective and prospective memory. Genotypes were determined using RFLP analysis and compared with mean memory scores using univariate ANOVAs. Despite a modest sample size (n=197), our study found a significant effect of the APOE ε4 polymorphism in prospective memory. Supporting our hypothesis, a significant difference was demonstrated between genotype groups for means of the Comprehensive Assessment of Prospective Memory total score (p=0.036; ε4 alleles=1.99; all other alleles=1.86). In addition, we demonstrate a significant interactive effect between the APOE ε4 and COMT polymorphisms in semantic memory. This is the first study to investigate both APOE and COMT genotypes in relation to memory in non-pathological adults and provides important information regarding the effect of genetic determinants on human memory.

Integrative genomic profiling reveals conserved genetic mechanisms for tumorigenesis in common entities of non-Hodgkin's lymphoma

Recent developments in genomic technologies have resulted in increased understanding of pathogenic mechanisms and emphasized the importance of central survival pathways. Here, we use a novel bioinformatic based integrative genomic profiling approach to elucidate conserved mechanisms of lymphomagenesis in the three commonest non-Hodgkin's lymphoma (NHL) entities: diffuse large B-cell lymphoma, follicular lymphoma, and B-cell chronic lymphocytic leukemia. By integrating genome-wide DNA copy number analysis and transcriptome profiling of tumor cohorts, we identified genetic lesions present in each entity and highlighted their likely target genes. This revealed a significant enrichment of components of both the apoptosis pathway and the mitogen activated protein kinase pathway, including amplification of the MAP3K12 locus in all three entities, within the set of genes targeted by genetic alterations in these diseases. Furthermore, amplification of 12p13.33 was identified in all three entities and found to target the FOXM1 oncogene. Amplification of FOXM1 was subsequently found to be associated with an increased MYC oncogenic signaling signature, and siRNA-mediated knock-down of FOXM1 resulted in decreased MYC expression and induced G2 arrest. Together, these findings underscore genetic alteration of the MAPK and apoptosis pathways, and genetic amplification of FOXM1 as conserved mechanisms of lymphomagenesis in common NHL entities. Integrative genomic profiling identifies common central survival mechanisms and highlights them as attractive targets for directed therapy.