title: Computational Nanobiosensing – Drawing Analogies Between Optimisation and Nanobiosensing for Smart Tumour Targeting

authors: Zhang, Lisa

abstract: Nanotechnology has been rapidly developing for early diagnosis and treatment of cancer, with nanoparticles being a large focus. However, traditional drug delivery mechanisms are passive and inefficient, with only 0.7% of nanoparticles reaching the tumour through blood vasculature. In vivo computation, also known as computational nanobiosensing (CONA), replaces nanoparticles with swarms of externally manipulable nanorobots whose movement is controlled by an external actuating system. The biological problem of smart tumour targeting is viewed from the computational perspective as an optimisation problem: nanorobot swarms (computational agents) explore the blood vasculature of high-risk tissue (search space) to locate the tumour (global optimum). Tumour biological gradient fields (BGF) create a fitness landscape, which can be analysed with fitness landscape analysis (FLA) to select and tune appropriate search algorithms for in vivo computation.

Key limitations of previous work for in vivo computation are a lack of realistic BGFs that reflect the tumour microenvironment to test search algorithms on; and for FLA, no available measures that consider physical constraints of the in vivo environment.

Two realistic tumour BGF models were created using COMSOL Multiphysics software (CFD Module), one highly vascularised, the other less vascularised. The vascular architecture was based on in vivo blood vessel networks in healthy and tumour regions, and blood velocity was used as a BGF. Blood velocity was found to be lowest in the tumour region, not exceeding 100 µm/s, confirming its applicability as a BGF for search algorithm testing.

Three new FLA measures were created and validated with numerical simulations on two possible tumour vascular landscapes. These measures addressed the physical constraints of discrete search space, unidirectional blood flow, and nanorobot steering imperfections when using a uniform magnetic field. The less vascularized landscape was found to be more discrete, more heterogeneous, and contain a smaller countercurrent frequency of search direction. This indicated it would be more challenging to solve for than the highly vascularised landscape.

These advancements of the CONA framework allow the in vivo search environment to be better visualised and understood for algorithmic development, as well as provide realistic BGFs to test these search algorithms on.

text: Computational Nanobiosensing – Drawing Analogies Between Optimisation and Nanobiosensing for Smart Tumour Targeting Nanotechnology has been rapidly developing for early diagnosis and treatment of cancer, with nanoparticles being a large focus. However, traditional drug delivery mechanisms are passive and inefficient, with only 0.7% of nanoparticles reaching the tumour through blood vasculature. In vivo computation, also known as computational nanobiosensing (CONA), replaces nanoparticles with swarms of externally manipulable nanorobots whose movement is controlled by an external actuating system. The biological problem of smart tumour targeting is viewed from the computational perspective as an optimisation problem: nanorobot swarms (computational agents) explore the blood vasculature of high-risk tissue (search space) to locate the tumour (global optimum). Tumour biological gradient fields (BGF) create a fitness landscape, which can be analysed with fitness landscape analysis (FLA) to select and tune appropriate search algorithms for in vivo computation.

Key limitations of previous work for in vivo computation are a lack of realistic BGFs that reflect the tumour microenvironment to test search algorithms on; and for FLA, no available measures that consider physical constraints of the in vivo environment.

Two realistic tumour BGF models were created using COMSOL Multiphysics software (CFD Module), one highly vascularised, the other less vascularised. The vascular architecture was based on in vivo blood vessel networks in healthy and tumour regions, and blood velocity was used as a BGF. Blood velocity was found to be lowest in the tumour region, not exceeding 100 µm/s, confirming its applicability as a BGF for search algorithm testing.

Three new FLA measures were created and validated with numerical simulations on two possible tumour vascular landscapes. These measures addressed the physical constraints of discrete search space, unidirectional blood flow, and nanorobot steering imperfections when using a uniform magnetic field. The less vascularized landscape was found to be more discrete, more heterogeneous, and contain a smaller countercurrent frequency of search direction. This indicated it would be more challenging to solve for than the highly vascularised landscape.

These advancements of the CONA framework allow the in vivo search environment to be better visualised and understood for algorithmic development, as well as provide realistic BGFs to test these search algorithms on.

year: 2024

title: Female suicidal behaviour: Initiation, cessation and prevention

authors: Curtis, Cate

abstract: This thesis explores non-fatal suicidal behaviour in young women. The approach taken is qualitative in orientation. The central form of data collection was the semi-structured interview. Interviews were conducted with key informants, including counsellors, clinicians and social workers and with women who had engaged in suicidal behaviour. The primary focus of the research was to explore the narratives of women who had engaged in suicidal behaviour, to contextualise their insights, understand their experiences and to examine the meanings of events leading to, and implicated in the recovery from, suicidal behaviour. This material demonstrates the importance of gender in suicidal behaviour and cessation as well as highlighting the limitations of many available therapeutic settings. A key finding of the research is the confirmation of sexual abuse as a common precursor to suicidal behaviour, especially when in conjunction with other, mainly familial, risk factors and an absence of protective factors. More significantly, the women noted that the effects of sexual abuse were exacerbated by problems with disclosure. Issues of control emerged as key to both suicidal behaviour and cessation, relating to family circumstance, abuse, disclosure of abuse and efficacy of forms of intervention. In contrast to the literature which suggests that any movement of self-harming behaviours is along a continuum from the less to more severe, the data gathered in this research suggests an episodic, or punctuated, pattern of behaviour, in which the protagonist moves between self-mutilation and suicidal behaviour. These findings problematise the notion of self-mutilation and suicidal behaviour as somewhat distinct behaviours. More generally, the material gathered from the women emphasizes the multi-causal and complex aspects of suicidal behaviour. The complexity of lived experience has implications for effective intervention and prevention strategies. Many of the women stressed the problematic nature of the forms of intervention they were able to access. Indeed, some regarded their experiences of intervention as reinforcing their feelings of lack of control This was largely confirmed by analysis of the interviews with key informants.

text: Female suicidal behaviour: Initiation, cessation and prevention This thesis explores non-fatal suicidal behaviour in young women. The approach taken is qualitative in orientation. The central form of data collection was the semi-structured interview. Interviews were conducted with key informants, including counsellors, clinicians and social workers and with women who had engaged in suicidal behaviour. The primary focus of the research was to explore the narratives of women who had engaged in suicidal behaviour, to contextualise their insights, understand their experiences and to examine the meanings of events leading to, and implicated in the recovery from, suicidal behaviour. This material demonstrates the importance of gender in suicidal behaviour and cessation as well as highlighting the limitations of many available therapeutic settings. A key finding of the research is the confirmation of sexual abuse as a common precursor to suicidal behaviour, especially when in conjunction with other, mainly familial, risk factors and an absence of protective factors. More significantly, the women noted that the effects of sexual abuse were exacerbated by problems with disclosure. Issues of control emerged as key to both suicidal behaviour and cessation, relating to family circumstance, abuse, disclosure of abuse and efficacy of forms of intervention. In contrast to the literature which suggests that any movement of self-harming behaviours is along a continuum from the less to more severe, the data gathered in this research suggests an episodic, or punctuated, pattern of behaviour, in which the protagonist moves between self-mutilation and suicidal behaviour. These findings problematise the notion of self-mutilation and suicidal behaviour as somewhat distinct behaviours. More generally, the material gathered from the women emphasizes the multi-causal and complex aspects of suicidal behaviour. The complexity of lived experience has implications for effective intervention and prevention strategies. Many of the women stressed the problematic nature of the forms of intervention they were able to access. Indeed, some regarded their experiences of intervention as reinforcing their feelings of lack of control This was largely confirmed by analysis of the interviews with key informants.

year: 2003

title: Early French views of the Waikato and its inhabitants (1840-54)

authors: Jennings, William

abstract: This paper will investigate how the cultural background of these Frenchmen informed their descriptions of Waikato Maori and the Waikato environment. It will use the newly-published ten-volume collected correspondence of the pioneer Marists in the Pacific,the Lettres refues d'Odanie, as its principal source.

text: Early French views of the Waikato and its inhabitants (1840-54) This paper will investigate how the cultural background of these Frenchmen informed their descriptions of Waikato Maori and the Waikato environment. It will use the newly-published ten-volume collected correspondence of the pioneer Marists in the Pacific,the Lettres refues d'Odanie, as its principal source.

year: 2011