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Synthesis of Muscleblind-Like Splicing Regulator 1 (MBNL1) protein and CUGexp toxic RNA biomolecules in Myotonic Dystrophy Type 1 disease
Get PDFMyotonic Dystrophy type 1 (dystrophia myotonica type 1 (DM1)) is a debilitating form of Muscular Dystrophy disease, and the most common form of DM affecting ~1 in 8000 individuals. The disease presents an array of multisystemic, typically neuromuscular symptoms, where complications vary considerably between patients, manifesting in an age-onset manner in adult DM1, or earlier in childhood and congenital DM1. Symptomatic relief of DM1 symptoms is the current treatment route under medical consortium guidelines, with no approved available treatments to cure DM1 disease, although promising novel therapeutics are at various stages of clinical trials.
The cause of DM1 is a trinucleotide repeat CTG (n=50 - >3000) sequence located within the 3’-UTR ends of the dystrophia myotonica protein kinase (DMPK) gene, with disease severity directly correlated to repeat length. The transcribed mRNA forms highly structured hairpin conformations, preferentially binding splicing factor Muscleblind-Like Splicing Regulator 1 (MBNL1) protein, and other co-factors, forming large RNA-Protein “foci” located typically in the cell nucleus, or cytoplasm. These complexes sequester MBNL1 from its normal function, leading to DM1 symptoms.
Here, the aim of the study presented is to synthesise DM1 representative mRNA and MBNL1 protein constructs for downstream structural analysis of the RNA-MBNL1 complexes. Current structure data depositions relating to MBNL1 domains with toxic RNA are few, and none on intact DM1 disease complexes. Therefore, the ability to do biophysical investigations into DM1 disease complexes in this detail would allow for future Structure-Based Drug Design (SBDD), an approach widely adopted to increase success of novel treatment compound development
Using human behaviour change interventions to improve the welfare of working equids in Colombia
Get PDFThere are an estimated 116 million working equids that contribute to the daily lives of over 600 million people worldwide. These animals are used for a huge variety of income-generating and non-income generating activities including tourism, agricultural support, mining and transportation. Many of the families these equids support live below the international poverty line. The livelihoods of these individuals as well as the welfare of their equids is often compromised. Health conditions such as equine colic are common within working equid populations, and the consequences of poor welfare can be extremely severe within these populations. There are a number of national and international non-governmental organisations that aim to support the lives of working equids and their owners through a number of methods including provision of free veterinary treatment, advocacy, skills training and community participatory exercises. The lives of working equids are intricately linked with their owners and the wider communities. In order to appropriately support working equids, it is vital to develop a deeper understanding of the communities in which they live and the factors that contribute to their welfare.
The main aims of this thesis were to explore working equid welfare and the external factors that influence this across Colombia. Additionally, this research aimed to develop an evidence-based intervention aimed to improve the welfare of working equids in Colombia through the prevention of equine colic.
The first stage of this project investigated the impact of the Covid-19 pandemic on working equids and their owners across the world in order to identify any changes that may need to be considered. Following the Covid-19 pandemic, working equid owners reported experiencing intensified financial challenges including a reduced income and an increased cost of living. There was some impact on working equid care and welfare; however, these effects were less significant.
The second stage of the project involved 24 focus groups conducted with a range of stakeholders across eight communities in Colombia to explore the welfare of working equids and the factors that influence this. Thematic analysis identified four overarching themes: ‘Testing external environment: “Surviving… is very hard”’, ‘Horse-human relationship: “Some owners have their horses in good condition… but others… tied up on a rope”’, ‘Cross-generational knowledge transfer: “We have to believe the elderly”’, and ‘Traditional management practices: “Fill a rucksack with wet ashes”’. The four overarching themes interact with each other, and all ultimately impact the welfare of working equids within the eight communities across Colombia.
The next stages of the project investigated equine colic within working equid communities in Colombia through a baseline survey and focus groups and workshops. The baseline colic survey highlighted high owner reported mortality and morbidity rates, and low levels of owner knowledge of the signs, causes and appropriate treatment methods of equine colic. The combined analysis from the focus groups and workshop identified three main themes: “The streams dry up in the summer”: Managing accessibility, resources and tradition, “Our faithful friend”: Encouraging desired change, and “Take a wet toad, stick it to its belly and make the mule trot”: Current understanding and perceptions of equine colic. The first two themes explore the presence of barriers and facilitators specific to five working equid owning communities. The third provides an insight into current levels of knowledge and identifies existing community misconceptions. This will provide the starting point for information of colic to be built on. Methods to help improve owner knowledge were discussed throughout the focus groups. Face to face training was identified as the only appropriate methods across all communities.
The final phase of the project developed and evaluated an educational intervention. The development of the educational intervention used finding from prior chapters in this thesis along with existing literature. The educational intervention was evaluated through an owner longitudinal survey, owner focus groups and qualitative questionnaires with the research team. There was an improvement in owner knowledge following the participation in the educational intervention. Analysis of focus groups with owners identified three overarching themes: ‘Awareness and understanding of education content’, ‘Intention and development of ideas for change’, and ‘Evidence of and action towards behaviour change’. There was evidence that the education intervention was successful at improving owner knowledge of equine colic. It was also clear that there had been small changes in the right direction that could help to prevent cases of colic occurring within these working equid populations.
This research highlights the importance of understanding the context in which working equids and their owners exist and to ensure interventions are targeted and appropriate for the specific environment in which they will be delivered
Effect of fermentation on anti-nutritional factors and in vitro protein hydrolysis of Vigna subterranea (L) Verdc. (Bambara groundnut)
No full textVigna subterranea (L) Verdc. (Bambara groundnut) (BG) remains underutilised due to the hard-to-cook (HTC) seed and the presence of anti-nutritional factors (ANF) which negatively affect protein digestibility. Many thermal and physical processing methods have been conventionally used to alleviate the HTC and ANF in legumes. However, these processing methods often involve complex procedures with high cost and energy consumption, while causing unavoidable losses of heat-sensitive and water-soluble nutrients. Fermentation offers an affordable and environmentally friendly method of processing the legumes into nutritious and digestible products. Hence, the current research project aimed to investigate the effect of bacterial and fungal fermentation in reducing the ANF (trypsin inhibitor, phytate and tannin) and enhancing the protein hydrolysis of BG. This project started with a back-slopping method using three Malaysian fermented foods (Tempeh, Tapai ubi and Tapai pulut) as starters for the fermentation of BG. All starters successfully initiated the fermentation process, and a total of seven fungi (Candida akabanensis TEMM-1 to TEMM-5, Diutina mesorugosa TEMS-1, Kodamaea ohmeri TAUM-1) and five bacteria (Leuconostoc mesenteroides TAUM-2, TAUM-3, TAPS-2 and TAPS-3, Pediococcus pentosaceus TAPS-1) were isolated from the fermented foods and identified using 16S rRNA gene sequence analysis. All twelve isolates demonstrated the absence of hemolytic and DNase activity, suggesting that if consumed will not pose a threat to health. To evaluate the effect of fermentation on the ANF and proximate composition of BG, L. mesenteroides TAPS-3 isolated from Tapai pulut was selected as the starter culture. After 24 h of fermentation at 37°C, TAPS-3 successfully reduced the tannin and phytate content (p < 0.05), and improved the protein content by 9.2% with no significant reduction in the remaining nutrients. With this promising finding, a subsequent study was performed using six selected bacterial and fungal isolates for inducing BG fermentation and evaluating their effectiveness in tannin and phytate reduction. Five isolates successfully induced the BG fermentation and reduced the ANF to varying degrees (p < 0.05). Among them, the bacterium P. pentosaceus TAPS-1 produced the highest reductions of tannin (21.2%) and phytate (12.8%). While the fungus C. akabanensis TEMM-1 achieved a maximum phytate reduction of 11.2% at 24 h of fermentation. Both TAPS-1 and TEMM-1 isolates with greater tannin and phytate removal efficiency were subjected to the single- and mixed-starter culture(s) BG fermentations, followed by the INFOGEST in vitro gastrointestinal digestion to determine the extent of protein hydrolysis. Two substrates, non-sterile BG (NsBG) and sterile BG (SBG), were used in this study, and the six fermentation approaches successfully enhanced the protein hydrolysis of these substrates. The fermentation using solely bacterium P. pentosaceus TAPS-1 was most effective in hydrolysing the proteins of NsBG and SBG. When compared to the fungal fermentation, the bacterial fermentation of NsBG (NsBG-B) exhibited the highest degree of protein hydrolysis with more primary amines being liberated (p < 0.05). The NsBG-B also retained most of the amino acids (except serine) at levels comparable to the controls after in vitro digestion. Hence, this study suggests that bacterial fermentation could be a feasible approach for processing the underutilised BG by reducing its undesired ANF and enhancing the protein digestibility. This fermentation approach could potentially be used to process other HTC legumes to improve their protein hydrolysis and promote wider utilisation
Thermophysical and electrochemical properties measurements of novel choline-based ionic liquids
Get PDFThe urgent need for sustainable energy storage propels the search for advanced battery technologies. Traditional lithium-ion batteries with liquid electrolytes pose safety risks like flammability and leakage. Choline-based ionic liquids (ILs) incorporated into gel polymer electrolytes (GPEs) offer a promising solution with the potential to enhance safety, cost-effectiveness, and environmental sustainability. This thesis focuses on the development and optimization of choline-based IL GPEs specifically for lithium battery applications.
Choline is a vital water-soluble nutrient that plays a crucial role in numerous physiological processes including neurotransmitter synthesis, cell membrane integrity, and lipid transport. Its versatility extends to diverse fields like aquaculture and beef production, highlighting its potential for large-scale applications. Although the versatility of choline is very broad, research on its usage in lithium-ion batteries is very limited. Choline-based ionic liquids inherit properties like biocompatibility, biodegradability, and cost effectiveness while offering the tunability needed to tailor electrochemical characteristics. These properties make them promising candidates for electrolytes in advanced battery technologies.
A series of novel choline-ester ILs were synthesized using facile methods, including an acid-base reaction to produce choline hydroxide and subsequent esterification with selected carboxylic acids. Their structures were confirmed by NMR and FTIR. These choline ester ILs exhibited high thermal stability (up to 300°C), non-flammability, high ionic conductivities (up to 60.92 mScm-2), high oxidative stability (up to 4.76 V), and impressive lithium-ion transference numbers (up to 0.94). GPEs were fabricated by incorporating these ILs into a PVDF-HFP matrix using a solution casting technique. The fabricated GPEs demonstrated significant safety improvements compared to traditional liquid electrolytes while maintaining electrochemical performance comparable to other ILGPEs systems. The structure-property relationships uncovered, particularly the effect of alkyl chain length on ionic conductivity, offer valuable guidance for further optimization.
This work underscores the potential of choline based ILs as a versatile electrolyte platform. It also highlights the advantages of GPEs for creating safer, high-performance lithium-ion batteries. Further research exploring other choline derivatives, advanced GPE architectures, and detailed battery testing could unlock even greater breakthroughs in energy storage technology. These future research directions could include investigations into bio-derived polymers, the inclusion of fillers for enhanced mechanical and electrochemical properties, and the development of solid-state electrolytes based on choline chemistries
New approaches for the integration of the discrete cosine transform in neural networks for fine-grained image classification
Get PDFA convolutional neural network (CNN) is a popular neural network architecture that excels in its ability to capture patterns in tasks with grid-structured inputs (e.g. visual recognition). Fine-grained visual classification (FGVC) uses CNN to categorise images of high intra-class and low inter-class variance. According to the literature, the 2D Discrete Cosine Transform (DCT) is one of the well-known transformations used in compression for its robustness and high data compaction properties. In compressed domain image classification, many works have focused on extracting features from the low DCT coefficients (L-DCTCs) through a fully pointwise vanilla CNN. Here, the abundant medium to high DCTCs have typically been discarded. Although pointwise convolution is capable of complex transformations, the spatial context and representation are limited. The area of compressed domain FGVC remains a relatively inactive field. It is therefore essential to explore compressed domain FGVC under DCT conditions to investigate the relationship between fine-grained features and the full spectrum of DCTCs. More specifically, this thesis intends to adopt and extend DCT techniques in compressed domain FGVC to address three topics: (1) the usability and inclusive learning of mid-band DCTCs; (2) the adaptive learning of DCT basis functions on composing the pointwise convolutional kernels; (3) the interaction between DCT channel groups in feature representations. The first contribution introduces the ‘Skipped Medium DCT CNN’. The M-DCTCs were processed via a skipping branch with a shallow convolutional block alongside the L-DCTCs which were passed through the main branch of the CNN. This architecture achieved a classification error drop of up to 7% over the standard model without the skipping branch. It highlights the importance of combining higher-frequency DCTCs with lower ones for improved robustness. The second contribution enhances the prior network by adaptively weighting the DCT basis functions to form a pointwise convolutional kernel. The spatial details were considered when constructing the pointwise convolutional kernel apart from the frequency contents. The adaptive weights are referred to as the ‘Adaptive DCT (Adapt-DCT)’ kernel. This network achieved up to 8% classification error drop on small-scale FGVC datasets and a top-5 testing accuracy of 73.93% on mini-ImageNet. The third contribution investigates the significance of DCT feature groups in the compressed domain FGVC. The modified attention mechanism that prioritises the channel interactions within the DCT group is referred to as the ‘Hybrid Modified Efficient Channel Attention’ (HyMod-ECA). It reduces the classification error by up to 3.5% over the original ECA. The optimised Adapt-DCT CNN with HyMod-ECA achieves a substantial parameter reduction of up to 73%. It is shown that the interactions among the DCT feature groups are one of the promising mechanisms to ease compressed domain FGVC. To conclude, this thesis discusses novel contributions in the context of combining the higher frequency DCTCs via a DCT-oriented convolutional kernel with an attention mechanism to address compressed domain FGVC
The impact of Trichoderma spp. treatment on physical and biochemical properties of oil palm (Elaeis guineensis Jacq.), and associated soil fungal biodiversity under challenge with Ganoderma boninense
No full textOil palm (Elaeis guineensis Jacq.) is a crucial crop in Malaysia, significantly contributing to the economy and global food supply. However, it is threatened by basal stem rot (BSR) disease caused by Ganoderma boninense without early infection symptoms, leading to reduced yields and premature palm death. This study aimed to evaluate the efficacy of Trichoderma spp. formulations in supporting plant growth and suppressing BSR disease under semi-controlled conditions. Additionally, it explored fungal biodiversity in the oil palm rhizospheric soil and identified potential early detection approaches for BSR through changes in fungal community composition.
The experiment was conducted with two categories of oil palm ramets: T1-T4 (non-inoculated) and T5-T8 (BSR-inoculated). The treatments were as follows: T1, T5 (no treatment/control); T2, T6 (Trichoderma spp. and biochar mixture, Tmix); T3, T7 (living organic fertilizer, LOF); T4, T8 (Tmix- and LOF-treated). LOF is nutrient-rich, containing high organic matter that enhances soil fertility and supports plant growth. Tmix promotes plant growth and suppresses BSR disease, with biochar serving as a carrier for Trichoderma spp. The ramets were inoculated with Ganoderma boninense using rubber wood blocks (RWBs) pre-colonized by the fungus while Trichoderma spp. were lab-cultured and mixed with biochar.
Post-infection analyses were only conducted at two time points, first and fourth months after planting, due to COVID-19 movement control order from March 2020 to November 2021. The analyses included the plant's physical properties (plant height, weight, stem diameter, leaf length, chlorophyll content/SPAD value, root length and weight), plants' disease severity index (DSI), soil chemical properties (pH and electrical conductivity, EC) and microbial counts. T1 ramets demonstrated the best growth and lowest DSI, likely due to minimal treatment stress, enabling better acclimatization and high survival rates. Among other treatments, T2 (non-inoculated, Tmix-treated) also had low DSI and the highest survival rate, highlighting the potential of Trichoderma spp. as a growth promoter. Conversely, T5 performed the worst in growth parameters and highest DSI (79.8%), emphasizing the severity of BSR disease in non-Tmix diseased plants.
Spectrophotometric enzyme assay for plant lignin biosynthesis enzymes (LBE: cinnamate 4-hydroxylase [C4H] and cinnamyl alcohol dehydrogenase [CAD]) and plant cell wall degrading enzymes (CWDE: chitinase and glucanase), along with lignothioglycolic acid (LTGA) assay, were conducted to evaluate enzyme activities and lignin content. Across treatments except T7, LBE activities increased from first month to the fourth month, especially in Tmix-treated plants. T4 showed the largest increment in CAD activity, while T2 recorded the highest CAD activity, 6.43 ODmin⁻¹mg⁻¹ and second-highest C4H activity, 5.80 ODmin⁻¹mg⁻¹, correlating with increased LTGA content. CWDE activities rose significantly in disease-inoculated plants (T5 to T8), with T6 and T8 (both Tmix-treated) showing the greatest increases. By the fourth month, chitinase activity in all diseased treatments exceeded 2.5 ODmin-1mg-1, with T6 and T8 reaching 2.78 and 2.71 ODmin-1mg-1 respectively. Glucanase activity followed a similar trend, with T8 having the highest activity, 6.14 ODmin-1mg-1 and followed by T6, 4.59 ODmin-1mg-1, while T5 and T7 exhibited smaller increases. Real-time polymerase chain reaction (qPCR) analysis revealed high Ganoderma spp. DNA in untreated diseased plants (T5, T7), but significantly reduced in Tmix-treated diseased plants (T6, T8), where Trichoderma spp. DNA remained high. These findings suggested Trichoderma spp. enhance LBE and CWDE enzyme activites as part of plant defences while suppressing Ganoderma spp. through direct antagonism and plant-mediated responses.
Subsequently, the fungal biodiversity of oil palm ramets' rhizospheric soil was analysed using next-generation sequencing and Microbiome Analyst tool. Four treatments were selected for analysis and relabelled for clarity: T1 (healthy control, HC); T2 (healthy treated, HT); T5 (diseased, D); T6 (diseased treated/recovering, R). HT exhibited the highest number of amplicon sequence variants (284 ASVs) and genus count (113 genera), whereas D had only 112 ASVs and 46 genera. Besides, the beta diversity plot showed the fungal cluster of D group distinctly located from the other groups, indicating high dissimilarity in fungal genera compared to others. Relative abundance comparisons of Trichoderma spp. and Ganoderma spp. revealed that naturally occurring Trichoderma spp. exhibited high relative abundance in HC without Tmix-treated but decreased in D, which was found lower than the relative abundance of Ganoderma spp. In R samples, the relative abundance of Trichoderma spp. increased following Tmix treatment, suppressing Ganoderma spp. These findings suggested that high relative abundance of naturally occurring Trichoderma spp. correlates with reduced disease incidence, while lower relative abundance increases risk of disease outbreaks. This insight offers a potential early detection strategy for BSR disease by monitoring fungal biodiversity, similar to a "health check" for plants and soil.
In conclusion, although assessing plant physical properties and biochemical interactions among ramets, BSR disease, and biocontrol agents is not novel, this study provided valuable insights into these interactions under semi-controlled conditions. It explored biochemical interactions by examining activities of LBE and CWDE. Moreover, it highlighted the soil fungal biodiversity associated with different plant health statuses, paving the way for identifying beneficial fungal clusters that promote plant growth, improve soil health, and suppress pathogens. This study could be the first to explore soil fungal biodiversity in oil palm rhizospheric soil concerning BSR disease under semi-controlled conditions. The findings suggested that Trichoderma spp. could potentially serve as a disease bioindicator for early BSR detection, as a decline in the relative abundance of naturally occurring Trichoderma spp. signals the onset of BSR disease. Future research could optimise Tmix application in infected plants to minimise the impact on microbial diversity. Additionally, validating the fungal community composition associated with different plant health statuses using field samples would enhance the applicability of these findings
Generative sustainability: a human resource framework to navigate the future of work
Get PDFThe Future of Work (FoW) has raised concerns about sustainability, leading to significant changes in the workplace. Key megatrends such automation displacing routine tasks, gig work transforming employer-employee contracts, remote and hybrid work impacting employee management, and environmental, social and governance (ESG) concerns driving various diversity, equity and inclusion (DEI), corporate social responsibility (CSR) and sustainability initiatives, are all impacting organisational and workforce resilience. As such, implementing future-proofed human resource management (HRM) practices can help navigate FoW challenges. Adopting an interpretivist-constructivist thinking, this research utilised a qualitative approach in the form of semi-structured interviews with 39 senior managers and human resource professionals from organisations implementing ESG, CSR and FOW practices. Data collected was then analysed through a qualitative analysis software.
Proposing a unified framework for organisations to navigate FoW, it began by identifying the impact of the megatrends into the 4Ds namely Disruption, Disconnect, Discontent and Degradation and proposing the 4Ps of Profit, People, Purpose and Planet as a way forward in navigating the 4Ds. A Generative Growth approach was identified to manage the tensions between the Ps by leveraging on growth theory to move beyond a focus on economic expansion to one that incorporates sustainable and adaptive growth. This research has also proposed for the need of Generative Organisations that are able to develop generative capability, that of absorptive, adaptive and generative capacity, to navigate FOW. A Generative Organisation matrix is also identified to identify the traits of organisations that are able to drive holistic and sustainable outcomes and future-proof in the face of FOW. This leads to the development of the Generative HRM Framework covering key themes such as strategy and foresight, organisational design, policies and processes, leadership and culture, change management, and organisational learning and growth and extends the role of Generative Leadership in supporting Generative HRM
initiatives for overall organisational success. Together, these theories form a unified framework
that promotes sustainable development, adaptability, and long-term resilience and brings us to the final model, that of Generative Sustainability.
Limitations to the study include the limited scope of comparison due to FoW’s lack of clear definition on FoW, the diverse theoretical framework variations of StHRM and SuHRM, the cultural and contextual impact of the study which is only limited to the Malaysian context, the inability to measure the longitudinal impact of megatrends and the generalisability of the study. Future research could include conducting more empirical studies to identify generative HRM solutions in practice as well to examine the impact of different country and sector-based influences on developing generative solutions. It would also be useful to conduct quantitative studies to development measurement scales to identify the maturity levels of different organisations and HR departments that would fall into the various grids proposed in the Generative Organisation and Generative HRM frameworks. Finally, expanding the participant base in future studies to include a broader range of organisational roles and types, particularly from SMEs, is crucial to obtain a fuller picture of organisational dynamics and HRM effectiveness
Characterising Fish Collagen for Expression in Bacterial Systems
Get PDFIsinglass, a collagen-based fining agent commonly used in the brewing industry for centuries, is traditionally produced from the swim bladder of tropical and sub-tropical fishes. However, the production of isinglass raises sustainability concerns, such as overfishing and environmental impact.
Arius maculatus, the species widely used in commercial isinglass production, there is limited data available on the specific protein characteristics of the collagen derived from this source. This study aimed to optimise the extraction and preliminary characterisation of collagen from isinglass from Arius maculatus swim bladders in a laboratory setting, addressing the gap in existing knowledge.
The collagen extraction process was refined using acid extraction techniques. The resultants were analysed through SDS-PAGE, revealing the presence of two α-chains and a β-chain with molecular weights slightly over 115kDa and 190kDa, respectively. The study provided essential preliminary data on the molecular structure of this collagen for the future work on the full confirmation of the protein structure. The functionality of these crude extracts as a fining agent was compared against commercial products. The findings reveal that laboratory-extracted protein crude shared structural characteristics with collagen type I and potential in maintaining functionality in finings.
The study also pursued the goal of expressing this collagen in a bacterial host; however, achieving suitable DNA templates for PCR was challenging. Repeated failures with commercial DNA extraction kits led to the development of an optimized protocol using conventional methods, yielding high-molecular-weight genomic DNA (>10 kb) for potential future applications. While time constraints prevented the completion of gene expression efforts, this research successfully refined both collagen and DNA extraction techniques, providing a critical foundation for future work on sustainable isinglass production and related collagen-based applications
Optimal Parameter Estimation for Quantum Markov Chains and IID Pure State Models
Get PDFThis thesis presents several optimal estimation strategies for quantum parameter estimation, mostly applied to quantum Markov chains (QMCs) - discrete-time quantum open systems. Chapter 4, based on [78], solves the problem of optimal estimation of a QMC using adaptive measurements. This culminates in an algorithm that determines the optimal measurement basis for the next step of the QMC by tracking an object known as the measurement filter. Crucially, this involves only local measurements on the environment of the QMC; a considerable simplification in comparison to other optimal strategies. Additionally, this estimation scheme utilizes a coherent absorber. This is a secondary system that we use to post-process the quantum Markov chain before measurement, which we include to purify the stationary state of the QMC.
Chapter 5, based on [77], then examines another measurement scheme - null measurements. A null measurement involves measuring the quantum system in a basis that contains the system’s state. It has been claimed that this is an optimal measurement for parameter estimation, but we demonstrate that this is not the case through an independent identically distributed pure state model. This is due to an identifiability issue that occurs when one attempts the naive implementation the null measurement. We then present a solution to this problem, where we introduce some displacement into the null measurement. This removes the identification issue and provides a proper statistical foundation to the estimation scheme.
In chapter 6, based on [75], we apply this displaced null measurement to a QMC; this provides a second optimal estimation scheme for QMCs. In particular, the displaced null measurement is implemented through the coherent absorber and a simple fixed measurement basis on the environment of the QMC. Therefore, this estimation scheme can be implemented with considerably reduced measurement complexity. The coherent absorber plays an essential, but very different, role in this estimation scheme; it effectively reverses the evolution in each step of the QMC when an initial estimate θ_0 is equal to the true value of the parameters θ. The environment of the QMC can then be modelled as a vacuum state, but introducing some displacement results in ’excitation’ patterns in this vacuum state. The chapter develops the mathematical theory of these patterns and the culminates in an optimal estimator that utilizes the observed pattern counts
Acceptance and commitment therapy for older adults who hear voices: a hermeneutic single case efficacy design (HSCED) series
Get PDFBackground
The ageing population is growing (United Nations, 2022), with 20% of this cohort anticipated to experience mental health and/or neurological difficulties (World Health Organisation, 2017). Hearing voices (HV) is a common and transdiagnostic symptom within the older adult (OA) population (Cort et al., 2021) that can be associated with increased psychological distress (van der Gaag et al., 2003) and significant morbidity and mortality (Tampi et al., 2019). The dominant treatment for these symptoms for OAs are antipsychotic medications, however, given the increased risks of complications for OAs who use these medications, there are recommendations that such interventions should be avoided if possible (Badcock et al., 2020). Therefore, calls have been made for alternative treatments to be explored.
Acceptance and Commitment Therapy (ACT) has been shown to be an effective intervention for psychotic symptoms such as HV amongst the working-age adult population (Morris et al, 2024). ACT aims to reduce psychological distress through enhancing psychological flexibility (Hayes et al., 2005). ACT is well suited to facilitate more helpful and effective ways of responding to voices that can reduce voice-related distress (Stephanie et al., 2018) and is believed to be an approach that is well-suited to OAs (Petkus & Wetherell, 2013). However, there is not currently any research that explores this. Therefore, this study explores the efficacy of ACT for OAs whose experience of HV is psychologically distressing, using an adjudicated Hermeneutic Single Case Efficacy Design (HSCED) series.
Methods
Two participants aged 65 and above who experienced voice-related distress completed a 12-session ACT intervention. HSCED methodology was used to examine the presence and mechanisms of meaningful change. A range of quantitative and qualitative data was collated and critically analysed by a panel of three independent expert judges. Conclusions were drawn about the outcome for each client.
Results
Meaningful changes were indicated for both participants, including in measures of psychological flexibility, anxiety, and depression. These changes were attributed to therapy processes, with ACT-specific processes appearing the most dominant mechanisms of change, however generic therapy-factors were still concluded as influential in therapeutic change. The therapeutic relationship was identified as a mediating factor, whilst client motivation, openness, and familial support were identified as moderating factors.
Discussion/Conclusion
This study is the first of its kind in exploring the effectiveness and acceptability of ACT for OAs who HV. HSCED methodology allowed a nuanced approach to examining change mechanisms. Findings offer support for the use of ACT for OAs who HV, aligning with literature for the working-age population. However, given the small sample size and lack of research within this area, these claims remain tentative and require more extensive research.
This study contributes to the limited evidence base supporting the use of psychological interventions for OAs whose experience of HV is psychologically distressing
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