title: Single nucleotide polymorphisms associated with the human electroencephalogram during desflurane anaesthesia

authors: Mulholland, Claire Vignette

subjects: single nucleotide polymorphism

abstract: General anaesthesia is an induced state that enables a person to endure surgical procedures without pain or recollection. There is substantial individual variability in the response to anaesthesia and in order to avoid adverse effects caused by either under- or over-sedation, anaesthetic drug administration must be tailored to suit the individual patient. This requires a means to monitor the depth of general anaesthesia. The electroencephalogram (EEG) records the electrical activity of the brain and enables effects of anaesthetic drugs on brain functioning to be monitored. Quantitative EEG monitors, such as the Bispectral (BIS) index monitor, process the raw EEG and provide a numerical output that is often used to measure the depth of general anaesthesia during surgery. Due to a number of factors including clinical conditions and genetic variability in the EEG, the BIS value can at times be misleading. 

To identify genetic variations associated with EEG phenotypes relevant to anaesthesia monitoring, an association analysis was performed for 34 single nucleotide polymorphisms (SNPs) in a sample of 125 surgical patients undergoing general, gynaecological or orthopaedic surgery. During surgery, patients were anaesthetised with the volatile anaesthetic agent desflurane, the depth of anaesthesia was measured using BIS monitoring and the raw was also EEG recorded. SNP genotyping was performed for 13 SNPs in five candidate genes; SGIP1, GABRA2, CACNA1G, HCN1 and HCN2, using the polymerase chain reaction and restriction fragment length polymorphism analysis. An additional 21 SNPs in 15 genes involved in various inflammatory and other immune-related pathways were genotyped by Sequenom MassARRAY at the Australian Genome Research Facility.
Six SNPs in five different genes were found to be associated with spindle amplitude (SGIP1, GABRA2, HCN1, IL1B and MYD88), and a further five SNPs were associated with either delta frequency (IL10), or end tidal desflurane concentration (ETDC) (CACNA1G, CRP, MYD88 and TGFB1). The strongest associations were identified for a single SNP located in the 3' UTR of MYD88 (rs6853). The rs6853 A/G genotype was associated with higher median spindle amplitude (p = 0.0040) and spindle amplitude relative to ETDC (p = 0.0006), and lower EDTC (p = 0.0095) than the A/A genotype. No rs6853 G/G homozygotes were identified in the study sample.
MYD88 acts as an adaptor protein in the interleukin-1 receptor and toll-like receptor signalling pathways. Within the brain, cytokines are thought to act as neuronal modulators and influence neurotransmitter signalling and ion channel activity. The association of MYD88 with spindle amplitude, in conjunction with IL1B, suggests that cytokines may influence the EEG during general anaesthesia. Thus cytokine mediated regulation of neuronal activity is speculated to underlie the reported associations. All reported effect sizes were small (0.77- to 1.55-fold) and associated genes had four distinct types of function; ion channels, neurotransmitter signalling, endocytosis, and cytokine signalling. This suggests that numerous genes in different pathways, each with a small, possibly additive effect, are involved in regulating the EEG during general anaesthesia.

text: Single nucleotide polymorphisms associated with the human electroencephalogram during desflurane anaesthesia General anaesthesia is an induced state that enables a person to endure surgical procedures without pain or recollection. There is substantial individual variability in the response to anaesthesia and in order to avoid adverse effects caused by either under- or over-sedation, anaesthetic drug administration must be tailored to suit the individual patient. This requires a means to monitor the depth of general anaesthesia. The electroencephalogram (EEG) records the electrical activity of the brain and enables effects of anaesthetic drugs on brain functioning to be monitored. Quantitative EEG monitors, such as the Bispectral (BIS) index monitor, process the raw EEG and provide a numerical output that is often used to measure the depth of general anaesthesia during surgery. Due to a number of factors including clinical conditions and genetic variability in the EEG, the BIS value can at times be misleading. 

To identify genetic variations associated with EEG phenotypes relevant to anaesthesia monitoring, an association analysis was performed for 34 single nucleotide polymorphisms (SNPs) in a sample of 125 surgical patients undergoing general, gynaecological or orthopaedic surgery. During surgery, patients were anaesthetised with the volatile anaesthetic agent desflurane, the depth of anaesthesia was measured using BIS monitoring and the raw was also EEG recorded. SNP genotyping was performed for 13 SNPs in five candidate genes; SGIP1, GABRA2, CACNA1G, HCN1 and HCN2, using the polymerase chain reaction and restriction fragment length polymorphism analysis. An additional 21 SNPs in 15 genes involved in various inflammatory and other immune-related pathways were genotyped by Sequenom MassARRAY at the Australian Genome Research Facility.
Six SNPs in five different genes were found to be associated with spindle amplitude (SGIP1, GABRA2, HCN1, IL1B and MYD88), and a further five SNPs were associated with either delta frequency (IL10), or end tidal desflurane concentration (ETDC) (CACNA1G, CRP, MYD88 and TGFB1). The strongest associations were identified for a single SNP located in the 3' UTR of MYD88 (rs6853). The rs6853 A/G genotype was associated with higher median spindle amplitude (p = 0.0040) and spindle amplitude relative to ETDC (p = 0.0006), and lower EDTC (p = 0.0095) than the A/A genotype. No rs6853 G/G homozygotes were identified in the study sample.
MYD88 acts as an adaptor protein in the interleukin-1 receptor and toll-like receptor signalling pathways. Within the brain, cytokines are thought to act as neuronal modulators and influence neurotransmitter signalling and ion channel activity. The association of MYD88 with spindle amplitude, in conjunction with IL1B, suggests that cytokines may influence the EEG during general anaesthesia. Thus cytokine mediated regulation of neuronal activity is speculated to underlie the reported associations. All reported effect sizes were small (0.77- to 1.55-fold) and associated genes had four distinct types of function; ion channels, neurotransmitter signalling, endocytosis, and cytokine signalling. This suggests that numerous genes in different pathways, each with a small, possibly additive effect, are involved in regulating the EEG during general anaesthesia.

year: 2012

title: µ-Charts and Z: hows, whys and wherefores

authors: Reeve, Greg

subjects: computer science

abstract: In this paper we show, by a series of examples, how the µ-chart formalism can be translated into Z. We give reasons for why this is an interesting and sensible thing to do and what it might be used for.

text: µ-Charts and Z: hows, whys and wherefores In this paper we show, by a series of examples, how the µ-chart formalism can be translated into Z. We give reasons for why this is an interesting and sensible thing to do and what it might be used for.

year: 2000-03

title: Site-specific performance rituals in the Anthropocene

authors: Claus, Johanna

abstract: In this creative practice PhD, I investigated site-specific performance rituals in the Anthropocene. Driven by the urge to respond to the challenges of the current time, I examined how different seasonal rituals might be expressed in specific sites in Aotearoa, New Zealand. Furthermore, including participants from diverse cultural backgrounds, and carrying an awareness of the complexities of colonialism, I analysed insights from key ritual experts to enhance my understanding of ritual practices within the specific socio-cultural and environmental context of Aotearoa. Inspired by critical posthumanist philosophies, I viewed ritual practices through a lens that considered the interconnectedness of technology, culture, and nature, moving beyond essentialist and dualistic tendencies. Inspired by (Haraway, 2007) and Braidotti (2019), I embraced a perspective of ‘staying with the trouble’ and ‘radical hope’ as a strategy to inspire commitments to safeguarding life on Earth amid increasing societal divisions, and environmental disasters.
Working at the intersection of various disciplines, I crafted a qualitative research design that embraced multiple ways of knowing through creative practice research. I gathered insights from four ritual experts grounded in mātauranga Māori or neo-Paganism through in-depth interviews, to comprehend multifaceted and culturally sensitive approaches to ritual practices in Aotearoa. Moreover, the creative investigation of four seasonal performance rituals served as the primary mode of inquiry (Niedderer & Roworth-Stokes, 2007; Skains, 2018). The methods used for these rituals included contemporary performance practices, eco-somatic movement, improvisation, site-specific dance, audience participation, and others.
The rich knowledge gained throughout these investigations is conveyed through the documentation of four seasonal rituals, presented in video works alongside this thesis. The findings are articulated in two empirical chapters, one focusing on the findings and analysis of the expert interviews and the other on the findings and analysis of four performance rituals, revealing nuanced and complex insights into the creation of site-specific performance rituals in the Anthropocene. Navigating site-specific performance practices as an immigrant necessitated continuous critical self-reflection on biases and assumptions, leading to intricate explorations of embodiment, identity, culture, nature, and the more-than-human world within a posthuman context. Operating in the liminal space of this tension alongside performer participants, ritual experts, and audience members yielded the articulation of my findings: a ritual score capable of accommodating the complexities of the Anthropocene.

text: Site-specific performance rituals in the Anthropocene In this creative practice PhD, I investigated site-specific performance rituals in the Anthropocene. Driven by the urge to respond to the challenges of the current time, I examined how different seasonal rituals might be expressed in specific sites in Aotearoa, New Zealand. Furthermore, including participants from diverse cultural backgrounds, and carrying an awareness of the complexities of colonialism, I analysed insights from key ritual experts to enhance my understanding of ritual practices within the specific socio-cultural and environmental context of Aotearoa. Inspired by critical posthumanist philosophies, I viewed ritual practices through a lens that considered the interconnectedness of technology, culture, and nature, moving beyond essentialist and dualistic tendencies. Inspired by (Haraway, 2007) and Braidotti (2019), I embraced a perspective of ‘staying with the trouble’ and ‘radical hope’ as a strategy to inspire commitments to safeguarding life on Earth amid increasing societal divisions, and environmental disasters.
Working at the intersection of various disciplines, I crafted a qualitative research design that embraced multiple ways of knowing through creative practice research. I gathered insights from four ritual experts grounded in mātauranga Māori or neo-Paganism through in-depth interviews, to comprehend multifaceted and culturally sensitive approaches to ritual practices in Aotearoa. Moreover, the creative investigation of four seasonal performance rituals served as the primary mode of inquiry (Niedderer & Roworth-Stokes, 2007; Skains, 2018). The methods used for these rituals included contemporary performance practices, eco-somatic movement, improvisation, site-specific dance, audience participation, and others.
The rich knowledge gained throughout these investigations is conveyed through the documentation of four seasonal rituals, presented in video works alongside this thesis. The findings are articulated in two empirical chapters, one focusing on the findings and analysis of the expert interviews and the other on the findings and analysis of four performance rituals, revealing nuanced and complex insights into the creation of site-specific performance rituals in the Anthropocene. Navigating site-specific performance practices as an immigrant necessitated continuous critical self-reflection on biases and assumptions, leading to intricate explorations of embodiment, identity, culture, nature, and the more-than-human world within a posthuman context. Operating in the liminal space of this tension alongside performer participants, ritual experts, and audience members yielded the articulation of my findings: a ritual score capable of accommodating the complexities of the Anthropocene.

year: 2024-05-27