22,117 research outputs found
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EEG microstates: Functional significance and short-term test-retest reliability
Appendix A: Supplementary data to this article can be found online at https://doi. org/10.1016/j.ynirp.2022.100089.Copyright /© 2022 The Authors. EEG signal power, may have clinical relevance; however, their functional significance and test-retest reliability remain unclear. To investigate the functional significance of the canonical EEG microstate classes and their pairwise transitions, and to establish their within-session test-retest reliability, we recorded 36-channel EEGs in 20 healthy volunteers during three eyes-closed conditions: mind-wandering, verbalization (silently repeating the word ‘square’ every 2 s), and visualization (visualizing a square every 2 s). Each condition lasted 3 min and the sequence of three conditions was repeated four times (two runs of two sequence repetitions). The participants' alertness and their sense of effort during the experiment were rated using visual-analogue scales. The EEG data were 2–20 Hz bandpass-filtered and analysed into the four canonical microstate classes: A, B, C, and D. EEG microstate classes C and D were persistently more dominant than classes A and B in all conditions. Of the first-order microstate parameters, average microstate duration was most reliable. The duration of class D microstate was longer during mind-wandering (106.8 ms) than verbalization (102.2 ms) or visualization (99.8 ms), with a concomitantly higher coverage (36.4% vs. 34.7% and 35.2%), but otherwise there was no clear association of the four microstate classes to particular mental states. The test-retest reliability was higher at the beginning of each run, together with higher average alpha power and subjective ratings of alertness. Only the transitions between classes C and D (from C to D in particular) were significantly higher than what would be expected from the respective microstates' occurrences. The transition probabilities, however, did not distinguish between conditions, and their test-retest reliability was overall lower than that of the first-order parameters such as duration and coverage. Further studies are needed to establish the functional significance of the canonical EEG microstate classes. This might be more fruitfully achieved by looking at their complex syntax beyond pairwise transitions. To ensure greater test-retest reliability of microstate parameters, study designs should allow for shorter experimental runs with regular breaks, particularly when using EEG microstates as clinical biomarkers.BIAL Foundation (grant number: 183/16)
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European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases.
Women’s Experiences of Accessing Breastfeeding and Perinatal Health Support in the Context of Intimate Partner Violence: An Interpretive Description Study
Background: Women experiencing intimate partner violence are at a heightened risk of negative perinatal and breastfeeding outcomes. This study explored the experiences of accessing breastfeeding support for women who endorse a history of intimate partner violence. A study of five in-depth semi-structured interviews were completed at 12-weeks postpartum with breastfeeding mothers with a history of intimate partner violence. Findings: Women expressed difficulties in accessing a healthcare provider who had specialized skill in breastfeeding support. Trust in their healthcare provider, built through displays of compassion and competence, was important to mitigate obstacles experienced during care access for this population. Trauma-and-violence-informed care principles were beneficial to the development of the therapeutic relationship in perinatal care. Women placed value on breastfeeding support received from both healthcare providers and social supports, which impacted mothers’ perceived breastfeeding support and self-efficacy. Further, mothers described increased levels of breastfeeding self-efficacy after engaging in a trauma-and-violence-informed care program aimed at supporting breastfeeding. Conclusions: Trauma-informed care may aid in the development of trust in the therapeutic relationship, which in turn impacts access to breastfeeding support and breastfeeding self-efficacy. The inclusion of trauma-and-violence informed principles in perinatal care may be effective at mitigating barriers to access for women who endorse a history of intimate partner violence. health care on how to employ trauma-informed breastfeeding care to may lead to better support for this population
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Role of Cerebrovascular Cells in Tau Processing Following Traumatic Brain Injury
Repetitive exposure to mild traumatic brain injuries (r-mTBI) sustained through the participation in contact sports can lead to chronic post-concussive symptoms and the development of neurodegenerative diseases such as Alzheimer’s disease and Chronic Traumatic Encephalopathy (CTE). A primary hallmark of CTE is the accumulation of pathogenic tau in neurons and astrocytes that surround small blood vessels in the brain. Chronic exposure to r-mTBI leads to elevated levels of extracellular tau and pathogenic tau accumulation in neurons, ultimately resulting in neuronal death. While the mechanisms responsible for pathogenic tau elimination from the brain are unclear, our prior work demonstrated that cells associated with the cerebrovasculature can interact with extracellular tau and may contribute to the removal of extracellular tau from the brain.
In this thesis, I examined the mechanisms through which the cerebrovascular cells eliminate extracellular tau from the brain and how those processes are impacted by r-mTBI. I demonstrated that brain vascular mural cells (pericytes and smooth muscle cells) progressively degenerate following exposure to r-mTBI consistent with what is observed in individuals with AD. This mural cell dysfunction impairs the ability of the cerebrovessels to interact with tau. Furthermore, I found that the cerebrovasculature can eliminate extracellular tau from the brain through caveolae-mediated endothelial transcytosis, which is impaired following chronic exposure to r-mTBI. The diminished tau transit across the blood-brain barrier following brain injury may be a contributing factor in the pathogenic tau accumulation observed in CTE.
A significant genetic risk factor for neurodegenerative diseases including AD and CTE is possession of the E4 isoform of Apolipoprotein E (ApoE). Astrocytes are the predominant source of ApoE in the brain, though there is very little understanding regarding their interactions with extracellular tau, particularly after exposure to head trauma. While the ApoE4 isoform has been associated with increased tau accumulation and cerebrovascular dysfunction after TBI, investigations into these associations are limited. The current studies found that while astrocytes internalize and release tau back into the extracellular space under normal conditions, these processes become dysfunctional following r-mTBI leading to astrocytic tau accumulation, which is further exacerbated by the ApoE4 isoform.
In summary, I identified the factors responsible for the elimination of extracellular tau across the BBB, which are impaired after head trauma. Therapeutic interventions that restore these processes may ameliorate the chronic accumulation of tau associated with neurodegenerative disease. These findings may be particularly important for individuals with the ApoE4 isoform, who are more susceptible to the pathophysiological sequelae of tau accumulation, particularly after exposure to r-mTBI
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Know Your Bugs: A Collaborative Evaluation of a Community Health Education Module That Aims to be Accessible to Adults with Learning Disabilities
The right to health should be a fundamental right of everyone. However, despite initiatives to improve the health of adults with learning disabilities, concerns about poorer health and health inequalities remain, and have been exacerbated by the COVID-19 pandemic. Accessible health promotion can help to overcome barriers to healthy behaviour but the effectiveness of health education in infection prevention and self-care is unknown. This research aimed to understand the health education experiences of adults with learning disabilities regarding a module designed to improve knowledge about self-care, infection prevention and antibiotic use.
Beginning with a scoping review of ‘what works’, this research involved observation of the learning context in two locations and semi-structured interviews with 18 course participants to explore health knowledge and behaviour change in the short, medium and longer term. Data were analysed iteratively, addressing the realist concept of context/mechanism/outcome configurations.
Participants had a positive learning experience and gained knowledge about microbes, hand hygiene, self-care, and antibiotic use. Some participants reported behaviour change regarding handwashing and self-care. The contexts that influenced learning were personal, social, physical, active, and external. Mechanisms that interacted with these contexts to trigger learning included: accessible teaching methods, interactive resources, relaxed and effective participant interactions, facilitation of independent thinking and planning, appropriate involvement of supporters, and an inclusive and engaging educator style.
Knowledge gain and changed behaviour intentions were achieved through an engaging, interactive, and focused learning environment, underpinned by a complex and changing combination of interactions. However, further research is needed to understand effective ways of communicating health information in an education context, to understand the impact of education on behaviour change, and to identify ways in which the longer-term retention of learning can be achieved. The research proposes a draft model that can guide effective community health education provision
3D printed Microneedles for Transdermal Drug Delivery
3D printing is a revolutionary manufacturing and prototyping technology that has altered the outlooks of numerous industrial and scientific fields since its introduction. Recently, it has attracted attention for its potential as a manufacturing tool for transdermal microneedles for drug delivery. In the present thesis, the 3D printability of solid and hollow microneedles via photopolymerisation-based 3D printing was investigated, aiming at establishing robust manufacturing strategies for reproducible, mechanically strong and versatile microneedles. The developed microneedles were employed as drug delivery systems for the treatment of diabetes via insulin administration.
Solid microneedles featuring different geometries were designed and 3D printed. It was demonstrated that the printing and post-printing parameters affected the printed quality, a finding that was employed to optimise the manufacturing strategy. Microneedle geometry was also found to have an impact on the piercing and fracture behaviour; however all microneedle designs were found to be mechanically safe upon application. The solid microneedles were subsequently coated with insulin-polymer films, using a 2D inkjet printing technology. The coating process achieved spatial control of the drug deposition, with quantitative accuracy. The microneedle geometry was shown to influence the morphology of the coating film, an effect that was pronounced during in the in vitro delivery studies of insulin to porcine skin.
Furthermore, hollow microneedles were designed and 3D printed, featuring different heights. Two photopolymerisation-based technologies were studied, and their performance was compared. The key influential parameters of the printing outcome and microneedle quality were identified to be the printing angle and the size of the microneedle opening. The hollow microneedles were found to be effective in piercing porcine skin without structural damaging. The hollow microneedles were incorporated into complex patches with internal microfluidic structures for the provision and distribution of drug-containing solutions. The developed complex hollow microneedle patches were coupled with a microelectromechanical system to create a novel platform device for controlled, personalised transdermal drug delivery. Advanced imaging techniques revealed that the device achieved distribution of the liquid within porcine skin tissue without the creation of depots that would delay absorption. The device was evaluated for its efficacy to transdermally deliver a model dye and insulin in vitro. In vivo trials were also conducted using diabetic rodents, with the device achieving faster onset of insulin action and sustained glycemic control, in comparison to subcutaneous injections.
Overall, the findings of the present research are anticipated to elucidate key problematic areas associated with the application of 3D printing for microneedle manufacturing and propose feasible solutions. The outermost goal of this work is to contribute to the advancement of knowledge in the field of 3D printed transdermal drug delivery systems, in order to bring them one step closer to their adoption in the clinical setting
The Role of the GATA Transcription Factor Gaf1 in Nutrient Responses and Cellular Ageing
The discovery of the biological bases of ageing continues to be one of the most fascinating challenges in modern science. Current efforts have narrowed the complexity of such task by focusing on mechanisms used by the cell to couple its physiology with environmental stimuli as they are often involved in the regulation of ageing. The Target of Rapamycin (TOR) have been proved to be a rheostat of nutritional status orchestrating cellular growth and homeostasis mainly through the regulation of transcriptional responses that remain to be understood. Recent studies unveiled novel functions of the evolutionarily conserved GATA transcription factor Gaf1 in nutrient sensing pathways and potentially in cellular ageing by regulating transcription downstream of TOR signalling. To elucidate these questions, the robust model organism Schizosaccharomyces pombe was used in this study due to its relevant similarity with higher eukaryotes and thoroughly described genetics. The experimental settings involved a combination of in silico analyses, fitness assessments, revivability assays, transcriptomics, mutagenesis, chemical-genetics, and interactome to further characterise functions of Gaf1. This study also contributed to the identification of candidate genes that promote longevity and mediate the resistance of mutant cells depleted of gaf1 gene to the TOR-kinase inhibitor torin1. The results indicate that upon TOR complex 1 (TORC1) inhibition, Gaf1 represses genes that induce protein translation (anabolism) and upregulates genes required for survival (catabolism) under adverse nutritional conditions downstream of TORC1
Constructing Cassandra: The social construction of strategic surprise at the Central Intelligence Agency 1947-2001
This dissertation takes a post-positivist approach to strategic surprise, and examines the identity and internal culture of the US Central Intelligence Agency (CIA) through the lens of social constructivism. It identifies numerous social mechanisms that created and maintained four key, persistent attributes of the CIA’s identity and culture between 1947 and 2001. These features are: 1) homogeneity of personnel; 2) scientism and the reification of a narrow form of ‘reason’; 3) an overwhelming preference for ‘secrets’ over openly-available information; and, 4) a relentless drive for consensus. It then documents the influence of these elements of the CIA’s identity and culture in each phase of the intelligence cycle (Tasking, Collection, Analysis, Production and Dissemination), prior to four strategic surprises: the Cuban Missile Crisis, the Iranian Islamic Revolution of 1979, the collapse of the USSR, and al-Qa’ida’s terrorist attacks on September 11th, 2001. It concludes that these key aspects of the CIA’s identity and culture created the antecedent conditions that allowed these four strategic surprises to occur, and thus prevented the CIA from fulfilling its mandate to ‘prevent another Pearl Harbor’. This conclusion is supported by contrasting the majority views at the CIA prior to these events with the views of ‘Cassandras’ (i.e. individuals inside or outside the Agency who anticipated the approximate course of events based on reasoned threat assessments that differed sharply from the Agency’s, but who were ignored or sidelined). In so doing, this work shifts the burden of proof for explaining strategic surprises back to the characteristics and actions of intelligence producers like the CIA, and away from errors by intelligence consumers like politicians and policymakers. This conclusion also allows this work to posit that understanding strategic surprise as a social construction is logically prior to previously proposed, entirely positivist, attempts to explain or to prevent it
Three-dimensional visualisation and quantitative characterisation of fossil fuel flames using tomography and digital imaging techniques
This thesis describes the design, implementation and experimental evaluation of a prototype instrumentation system for the three-dimensional (3-D) visualisation and quantitative characterisation of fossil fuel flames. A review of methodologies and technologies for the 3-D visualisation and characterisation of combustion flames is given, together with a discussion of main difficulties and technical requirements in their applications. A strategy incorporating optical sensing, digital image processing and tomographic reconstruction techniques is proposed. The strategy was directed towards the reconstruction of 3-D models of a flame and the subsequent quantification of its 3-D geometric, luminous and fluid dynamic parameters. Based on this strategy, a flame imaging system employing three identical synchronised RG B cameras has been developed. The three cameras, placed equidistantly and equiangular on a semicircle around the flame, captured six simultaneous images of the flame from six different directions. Dedicated computing algorithms, based on image processing and tomographic reconstruction techniques have been developed to reconstruct the 3-D models of a flame. A set of geometric, luminous and fluid dynamic parameters, including surface area, volume, length, circularity, luminosity and temperature are determined from the 3-D models generated. Systematic design and experimental evaluation of the system on a gas-fired combustion rig are reported. The accuracy, resolution and validation of the system were also evaluated using purpose-designed templates including a high precision laboratory ruler, a colour flat panel and a tungsten lamp. The results obtained from the experimental evaluation are presented and the relationship between the measured parameters and the corresponding operational conditions are quantified. Preliminary investigations were conducted on a coal-fired industry-scale combustion test facility. The multi-camera system was reconfigured to use only one camera due to the restrictions at the site facility. Therefore the property of rotational symmetry of the flame had to be assumed. Under such limited conditions, the imaging system proved to provide a good reconstruction of the internal structures and luminosity variations inside the This thesis describes the design, implementation and experimental evaluation of a prototype instrumentation system for the three-dimensional (3-D) visualisation and quantitative characterisation of fossil fuel flames. A review of methodologies and technologies for the 3-D visualisation and characterisation of combustion flames is given, together with a discussion of main difficulties and technical requirements in their applications. A strategy incorporating optical sensing, digital image processing and tomographic reconstruction techniques is proposed. The strategy was directed towards the reconstruction of 3-D models of a flame and the subsequent quantification of its 3-D geometric, luminous and fluid dynamic parameters. Based on this strategy, a flame imaging system employing three identical synchronised RG B cameras has been developed. The three cameras, placed equidistantly and equiangular on a semicircle around the flame, captured six simultaneous images of the flame from six different directions. Dedicated computing algorithms, based on image processing and tomographic reconstruction techniques have been developed to reconstruct the 3-D models of a flame. A set of geometric, luminous and fluid dynamic parameters, including surface area, volume, length, circularity, luminosity and temperature are determined from the 3-D models generated. Systematic design and experimental evaluation of the system on a gas-fired combustion rig are reported. The accuracy, resolution and validation of the system were also evaluated using purpose-designed templates including a high precision laboratory ruler, a colour flat panel and a tungsten lamp. The results obtained from the experimental evaluation are presented and the relationship between the measured parameters and the corresponding operational conditions are quantified. Preliminary investigations were conducted on a coal-fired industry-scale combustion test facility. The multi-camera system was reconfigured to use only one camera due to the restrictions at the site facility. Therefore the property of rotational symmetry of the flame had to be assumed. Under such limited conditions, the imaging system proved to provide a good reconstruction of the internal structures and luminosity variations inside the This thesis describes the design, implementation and experimental evaluation of a prototype instrumentation system for the three-dimensional (3-D) visualisation and quantitative characterisation of fossil fuel flames. A review of methodologies and technologies for the 3-D visualisation and characterisation of combustion flames is given, together with a discussion of main difficulties and technical requirements in their applications. A strategy incorporating optical sensing, digital image processing and tomographic reconstruction techniques is proposed. The strategy was directed towards the reconstruction of 3-D models of a flame and the subsequent quantification of its 3-D geometric, luminous and fluid dynamic parameters. Based on this strategy, a flame imaging system employing three identical synchronised RG B cameras has been developed. The three cameras, placed equidistantly and equiangular on a semicircle around the flame, captured six simultaneous images of the flame from six different directions. Dedicated computing algorithms, based on image processing and tomographic reconstruction techniques have been developed to reconstruct the 3-D models of a flame. A set of geometric, luminous and fluid dynamic parameters, including surface area, volume, length, circularity, luminosity and temperature are determined from the 3-D models generated. Systematic design and experimental evaluation of the system on a gas-fired combustion rig are reported. The accuracy, resolution and validation of the system were also evaluated using purpose-designed templates including a high precision laboratory ruler, a colour flat panel and a tungsten lamp. The results obtained from the experimental evaluation are presented and the relationship between the measured parameters and the corresponding operational conditions are quantified. Preliminary investigations were conducted on a coal-fired industry-scale combustion test facility. The multi-camera system was reconfigured to use only one camera due to the restrictions at the site facility. Therefore the property of rotational symmetry of the flame had to be assumed. Under such limited conditions, the imaging system proved to provide a good reconstruction of the internal structures and luminosity variations inside the flame. Suggestions for future development of the technology are also reported
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