A polymorphism in the dysbindin gene (DTNBP1) associated with multiple psychiatric disorders including schizophrenia

Background A number of studies have found associations between dysbindin (DTNBP1) polymorphisms and schizophrenia. Recently we identified a DTNBP1 SNP (rs9370822) that is strongly associated with schizophrenia. Individuals diagnosed with schizophrenia were nearly three times as likely to carry the CC genotype compared to the AA genotype. Methods To investigate the importance of this SNP in the function of DTNBP1, a number of psychiatric conditions including addictive behaviours and anxiety disorders were analysed for association with rs9370822. Results The DTNBP1 polymorphism was significantly associated with post-traumatic stress disorder (PTSD) as well as nicotine and opiate dependence but not alcohol dependence. Individuals suffering PTSD were more than three times as likely to carry the CC genotype compared to the AA genotype. Individuals with nicotine or opiate dependence were more than twice as likely to carry the CC genotype compared to the AA genotype. Conclusions This study provides further support for the importance of DTNBP1 in psychiatric conditions and suggests that there is a common underlying molecular defect involving DTNBP1 that contributes to the development of several anxiety and addictive disorders that are generally recognised as separate clinical conditions. These disorders may actually be different expressions of a single metabolic pathway perturbation. As our participant numbers are limited our observations should be viewed with caution until they are independently replicated.

Eigengaze : covert behavioral biometric exploiting visual attention characteristics

It is possible for the visual attention characteristics of a person to be exploited as a biometric for authentication or identification of individual viewers. The visual attention characteristics of a person can be easily monitored by tracking the gaze of a viewer during the presentation of a known or unknown visual scene. The positions and sequences of gaze locations during viewing may be determined by overt (conscious) or covert (sub-conscious) viewing behaviour. This paper presents a method to authenticate individuals using their covert viewing behaviour, thus yielding a unique behavioural biometric. A method to quantify the spatial and temporal patterns established by the viewer for their covert behaviour is proposed utilsing a principal component analysis technique called `eigenGaze'. Experimental results suggest that it is possible to capture the unique visual attention characteristics of a person to provide a simple behavioural biometric.

Bayesian methodology for genetics of complex diseases

Genetic research of complex diseases is a challenging, but exciting, area of research. The early development of the research was limited, however, until the completion of the Human Genome and HapMap projects, along with the reduction in the cost of genotyping, which paves the way for understanding the genetic composition of complex diseases. In this thesis, we focus on the statistical methods for two aspects of genetic research: phenotype definition for diseases with complex etiology and methods for identifying potentially associated Single Nucleotide Polymorphisms (SNPs) and SNP-SNP interactions. With regard to phenotype definition for diseases with complex etiology, we firstly investigated the effects of different statistical phenotyping approaches on the subsequent analysis. In light of the findings, and the difficulties in validating the estimated phenotype, we proposed two different methods for reconciling phenotypes of different models using Bayesian model averaging as a coherent mechanism for accounting for model uncertainty. In the second part of the thesis, the focus is turned to the methods for identifying associated SNPs and SNP interactions. We review the use of Bayesian logistic regression with variable selection for SNP identification and extended the model for detecting the interaction effects for population based case-control studies. In this part of study, we also develop a machine learning algorithm to cope with the large scale data analysis, namely modified Logic Regression with Genetic Program (MLR-GEP), which is then compared with the Bayesian model, Random Forests and other variants of logic regression.

The genetics of cutaneous melanoma

Although germline mutations in CDKN2A are present in approximately 25% of large multicase melanoma families, germline mutations are much rarer in the smaller melanoma families that make up most individuals reporting a family history of this disease. In addition, only three families worldwide have been reported with germline mutations in a gene other than CDKN2A (i.e., CDK4). Accordingly, current genomewide scans underway at the National Human Genome Research Institute hope to reveal linkage to one or more chromosomal regions, and ultimately lead to the identification of novel genes involved in melanoma predisposition. Both CDKN2A and PTEN have been identified as genes involved in sporadic melanoma development; however, mutations are more common in cell lines than uncultured tumors. A combination of cytogenetic, molecular, and functional studies suggests that additional genes involved in melanoma development are located to chromosomal regions 1p, 6q, 7p, 11q, and possibly also 9p and 10q. With the near completion of the human genome sequencing effort, combined with the advent of high throughput mutation analyses and new techniques including cDNA and tissue microarrays, the identification and characterization of additional genes involved in melanoma pathogenesis seem likely in the near future.

Quality of life and genetics in men with prostate cancer

As family history has been established as a risk factor for prostate cancer, attempts have been made to isolate predisposing genetic variants that are related to hereditary prostate cancer. With many genetic variants still to be identified and investigated, it is not yet possible to fully understand the impact of genetic variants on prostate cancer development. The high survival rates among men with prostate cancer have meant that other issues, such as quality of life (QoL), have also become important. Through their effect on a person’s health, a range of inherited genetic variants may potentially influence QoL in men with prostate cancer, even prior to treatment. Until now, limited research has been conducted on the relationship between genetics and QoL. Thus, this study contributes to an emerging field by aiming to identify certain genetic variants related to the QoL found in men with prostate cancer. It is hoped that this study may lead to future research that will identify men who have an increased risk of a poor QoL following prostate cancer treatment, which will aid in developing treatments that are individually tailored to support them. Previous studies have established that genetic variants of Vascular Endothelial Growth Factor (VEGF) and Insulin-like Growth Factor 1 (IGF-1) may play a role in prostate cancer development. VEGF and IGF-1 have also been reported to be associated with QoL in people with ovarian cancer and colorectal cancer, respectively. This study completed a series of secondary analyses using two major data-sets (from 850 men newly diagnosed with prostate cancer, and approximately 550 men from the general Queensland population), in which genetic variants of VEGF and IGF-1 were investigated for associations with prostate cancer susceptibility and QoL. The first aim of this research was to investigate genetic variants in the VEGF and IGF-I gene for an association with the risk of prostate cancer. It was found that one IGF-1 genetic variant (rs35765) had a statistically significant association with prostate cancer (p = 0.04), and one VEGF genetic variant (rs2146323) had a statistically significant association with advanced prostate cancer (p = 0.02). The estimates suggest that carriers of the CA and AA genotype for rs35765 may have a reduced risk of developing prostate cancer (Odds Ratio (OR) = 0.72, 95% Confidence Interval (CI) = 0.55, 0.95, OR = 0.60, 95% CI = 0.26, 1.39, respectively). Meanwhile, carriers of the CA and AA genotype for rs2146323 may be at increased risk of advanced prostate cancer, which was determined by a Gleason score of above 7 (OR = 1.72, 95% CI = 1.12, 2.63, OR = 1.90, 95% CI = 1.08, 3.34, respectively). Utilising the widely used short-form health survey, the SF-36v2, the second aim of this study was to investigate the relationship between prostate cancer and QoL prior to treatment. Assessing QoL at this time-point was important as little research has been conducted to evaluate if prostate cancer affects QoL regardless of treatment. The analyses found that mean SF-36v2 scale scores related to physical health were higher by at least 0.3 Standard Deviations (SD) among men with prostate cancer than the general population comparison group. This difference was considered clinically significant (defined by group differences in mean SF-36v2 scores by at least 0.3 SD). These differences were also statistically significant (p<0.05). Mean QoL scale scores related to mental health were similar between men with prostate cancer and those from the general population comparison group. The third aim of this study was to investigate genetic variants in the VEGF and IGF-1 gene for an association with QoL in prostate cancer patients prior to their treatment. It was essential to evaluate these relationships prior to treatment, before the involvement of these genes was potentially interrupted by treatment. The analyses found that some genetic variants had a small clinically significant association (0.3 SD) to some QoL domains experienced by these men. However, most relationships were not statistically significant (p>0.05). Most of the associations found identified that a small sub-group of men with prostate cancer (approximately 2%) reported, on average, a slightly better QoL than the majority of the prostate cancer patients. The fourth aim of this research was to investigate whether associations between genetic variants in VEGF and IGF-1 and QoL were specific to men with prostate cancer, or were also applicable to the general male population. It was found that twenty out of one-hundred relationships between the genetic variants of VEGF and IGF-1 and QoL health-measures and scales examined differed between these groups. In the majority of the relationships involving VEGF SNPs that differed, a clinically significant difference (0.3 or more SD) between mean scores among the genotype groups in prostate cancer patients was found, while mean scores among men from the general-population comparison group were similar. For example, prostate cancer participants who carried at least one T allele (CT or TT genotype) for rs3024994 had a clinically significant higher (0.3 SD) mean QoL score in terms of the role-physical scale, than participants who carried the CC genotype. This was not seen among men from the general population sample, as the mean score was similar between genotype groups. The opposite was seen in regards to the IGF-1 SNPs examined. Overall, these relationships were not considered to directly impact on the clinical options for men with prostate cancer. As this study utilised secondary data from two separate studies, there are a number of important limitations that should be acknowledged including issues of multiple comparisons, power, and missing or unavailable data. It is recommended that this study be replicated as a better-designed study that takes greater consideration of the many factors involved in prostate cancer and QoL. Investigation into other genetic variants of VEGF or IGF-1 is also warranted, as is consideration of other genes and their relationship with QoL. Through identifying certain genetic variants that have a modest association to prostate cancer, this project adds to the knowledge surrounding VEGF and IGF-1 and their role in prostate cancer susceptibility. Importantly, this project has also introduced the potential role genetics plays in QoL, through investigating the relationships between genetic variants of VEGF and IGF-1 and QoL.

Isotactics as a foundation for alignment and abstraction of behavioral models

There are many use cases in business process management that require the comparison of behavioral models. For instance, verifying equivalence is the basis for assessing whether a technical workflow correctly implements a business process, or whether a process realization conforms to a reference process. This paper proposes an equivalence relation for models that describe behaviors based on the concurrency semantics of net theory and for which an alignment relation has been defined. This equivalence, called isotactics, preserves the level of concurrency of aligned operations. Furthermore, we elaborate on the conditions under which an alignment relation can be classified as an abstraction. Finally, we show that alignment relations induced by structural refinements of behavioral models are indeed behavioral abstractions.

Microscopic traffic hysteresis in traffic oscillations : a behavioral perspective

This paper studies traffic hysteresis arising in traffic oscillations from a behavioral perspective. It is found that the occurrence and type of traffic hysteresis is closely correlated with driver behavior when experiencing traffic oscillations and with the time driver reaction begins relative to the starting deceleration wave. Statistical results suggest that driver behavior is different depending on its position along the oscillation. This suggests that different car-following models should be used inside the different stages of an oscillation in order to replicate realistic congestion features.

Benefit cost analysis applied to behavioral and engineering safety countermeasures in San Francisco, California

The state of the practice in safety has advanced rapidly in recent years with the emergence of new tools and processes for improving selection of the most cost-effective safety countermeasures. However, many challenges prevent fair and objective comparisons of countermeasures applied across safety disciplines (e.g. engineering, emergency services, and behavioral measures). These countermeasures operate at different spatial scales, are funded often by different financial sources and agencies, and have associated costs and benefits that are difficult to estimate. This research proposes a methodology by which both behavioral and engineering safety investments are considered and compared in a specific local context. The methodology involves a multi-stage process that enables the analyst to select countermeasures that yield high benefits to costs, are targeted for a particular project, and that may involve costs and benefits that accrue over varying spatial and temporal scales. The methodology is illustrated using a case study from the Geary Boulevard Corridor in San Francisco, California. The case study illustrates that: 1) The methodology enables the identification and assessment of a wide range of safety investment types at the project level; 2) The nature of crash histories lend themselves to the selection of both behavioral and engineering investments, requiring cooperation across agencies; and 3) The results of the cost-benefit analysis are highly sensitive to cost and benefit assumptions, and thus listing and justification of all assumptions is required. It is recommended that a sensitivity analyses be conducted when there is large uncertainty surrounding cost and benefit assumptions.

Identity theft, computers and behavioral biometrics

The increase of online services, such as eBanks, WebMails, in which users are verified by a username and password, is increasingly exploited by Identity Theft procedures. Identity Theft is a fraud, in which someone pretends to be someone else is order to steal money or get other benefits. To overcome the problem of Identity Theft an additional security layer is required. Within the last decades the option of verifying users based on their keystroke dynamics was proposed during login verification. Thus, the imposter has to be able to type in a similar way to the real user in addition to having the username and password. However, verifying users upon login is not enough, since a logged station/mobile is vulnerable for imposters when the user leaves her machine. Thus, verifying users continuously based on their activities is required. Within the last decade there is a growing interest and use of biometrics tools, however, these are often costly and require additional hardware. Behavioral biometrics, in which users are verified, based on their keyboard and mouse activities, present potentially a good solution. In this paper we discuss the problem of Identity Theft and propose behavioral biometrics as a solution. We survey existing studies and list the challenges and propose solutions.

A generic framework and runtime environment for development and evaluation of behavioral biometrics solutions

Increasing use of computerized systems in our daily lives creates new adversarial opportunities for which complex mechanisms are exploited to mend the rapid development of new attacks. Behavioral Biometrics appear as one of the promising response to these attacks. But it is a relatively new research area, specific frameworks for evaluation and development of behavioral biometrics solutions could not be found yet. In this paper we present a conception of a generic framework and runtime environment which will enable researchers to develop, evaluate and compare their behavioral biometrics solutions with repeatable experiments under the same conditions with the same data.

Behavioral biometrics for persistent single sign-on

Driven by the rapid development of ubiquitous and pervasive computing, personalized services and applications are deployed to support our lives. Accordingly, the number of interfaces and devices (smartphone, tablet computer, etc.) provided to access and consume these services is growing continuously. To simplify the complexity of managing many accounts with different credentials, Single Sign-On (SSO) solutions have been introduced. However, a single password for many accounts represents a single-point-of-failure. Furthermore, once initiated SSO session is a high potential risk when the working station is left unlocked and unattended. In this paper, we present a conception of a Persistent Single Sign-On (PSSO) for ubiquitous home environments by involving the capabilities of Behavioral Biometrics to check the identity of the user continuously in an unobtrusive manner.