A Permanent-Magnet Linear Generator Wave Energy Converter for Low Power Ocean Sensors

Renewable energy sources are becoming increasingly important due to their low environmental impact and limitless nature. This thesis explores the design of a 250 mW permanent magnet linear generator wave energy converter to power ocean sensors. While many wave energy converters exist, this is a unique application because the wave energy device is neither at the surface nor at the seafloor and is a low power application. The permanent magnet linear generator detailed in this thesis would enable the continuous operation of ocean mixing sensors with minimal maintenance and intervention.Keywords: WEC, Permanent Magnet Linear Generator, Power Ocean Sensors, Wave Energy Converte

SecureMEMS: Selective Deposition of Energetic Materials

There exists a pressing operational need to secure and control access to high-valued electromechanical systems, and in some cases render them inoperable. Developing a reliable method for depositing energetic materials will allow for the near-seamless integration of electromechanical systems and energetic material, and, in turn, provide the pathway for security and selective destruction that is needed. In this work, piezoelectric inkjet printing was used to selectively deposit energetic materials. Nanothermites, comprising of nanoscale aluminum and nanoscale copper oxide suspended in dimethyl-formamide (DMF), were printed onto silicon wafers, which enabled both thermal and thrust measurements of the decomposing energetic material. Various solids loadings were studied in order to optimize printing characteristics. Going forward, further studies will focus on the plausibility of inkjet printing other energetic materials for the purposes of the degradation of electromechanical systems

Timely Considerations of Using the de Jong Gierveld Loneliness Scale with Older Adults Living in Long-Term Care Homes: A Critical Reflection

Context: Despite being widely used with older adults in the community, there is limited literature on using the de Jong Gierveld Loneliness Scale with older adults living in long-term care (LTC). Objective: The purpose of this article is to discuss the considerations of using this scale with older adults in LTC. Method: Our team consisted of older person and family partners, a clinician, and academic researchers working together in all stages of research using the Loneliness scale to conduct individual interviews with 20 older adults in LTC in Vancouver, Canada, as part of a study exploring the experience of loneliness during the COVID-19 pandemic. Team reflection was embedded in the research process, with reflection data consisting of data transcripts, field notes, and regular team meeting notes. Thematic analysis was employed to identify lessons learned and implications. Findings: Participants had various challenges responding to the scale. Our analysis identified five themes: a) diverse meanings of loneliness, b) multi-faceted factors of loneliness, c) technical challenges, d) social desirability, and e) situational experience. We also offer five recommendations to consider when using this scale with older adults in LTC. Limitations: We used this scale with a small sample of older adults in LTC, which is a more time and labour-intensive population. Data on marital status and educational background was not collected but might help in understanding considerations for using the scale with older adults in LTC. Implications: We offer practical recommendations for using the scale with older adults in LTC, especially how qualitative open-ended questions can complement the scale by providing useful insights into context and complex experiences

Implementation of the StandingTall programme to prevent falls in older people:a process evaluation protocol

INTRODUCTION: One in three people aged 65 years and over fall each year. The health, economic and personal impact of falls will grow substantially in the coming years due to population ageing. Developing and implementing cost-effective strategies to prevent falls and mobility problems among older people is therefore an urgent public health challenge. StandingTall is a low-cost, unsupervised, home-based balance exercise programme delivered through a computer or tablet. StandingTall has a simple user-interface that incorporates physical and behavioural elements designed to promote compliance. A large randomised controlled trial in 503 community-dwelling older people has shown that StandingTall is safe, has high adherence rates and is effective in improving balance and reducing falls. The current project targets a major need for older people and will address the final steps needed to scale this innovative technology for widespread use by older people across Australia and internationally. METHODS AND ANALYSIS: This project will endeavour to recruit 300 participants across three sites in Australia and 100 participants in the UK. The aim of the study is to evaluate the implementation of StandingTall into the community and health service settings in Australia and the UK. The nested process evaluation will use both quantitative and qualitative methods to explore uptake and acceptability of the StandingTall programme and associated resources. The primary outcome is participant adherence to the StandingTall programme over 6 months. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the South East Sydney Local Health District Human Research Ethics Committee (HREC reference 18/288) in Australia and the North West- Greater Manchester South Research Ethics Committee (IRAS ID: 268954) in the UK. Dissemination will be via publications, conferences, newsletter articles, social media, talks to clinicians and consumers and meetings with health departments/managers. TRIAL REGISTRATION NUMBER: ACTRN12619001329156

Alzheimer\u27s Therapeutics Targeting Amyloid Beta 1-42 Oligomers I: Abeta 42 Oligomer Binding to Specific Neuronal Receptors is Displaced by Drug Candidates That Improve Cognitive Deficits

Synaptic dysfunction and loss caused by age-dependent accumulation of synaptotoxic beta amyloid (Abeta) 1-42 oligomers is proposed to underlie cognitive decline in Alzheimer\u27s disease (AD). Alterations in membrane trafficking induced by Abeta oligomers mediates reduction in neuronal surface receptor expression that is the basis for inhibition of electrophysiological measures of synaptic plasticity and thus learning and memory. We have utilized phenotypic screens in mature, in vitro cultures of rat brain cells to identify small molecules which block or prevent the binding and effects of Abeta oligomers. Synthetic Abeta oligomers bind saturably to a single site on neuronal synapses and induce deficits in membrane trafficking in neuronal cultures with an EC50 that corresponds to its binding affinity. The therapeutic lead compounds we have found are pharmacological antagonists of Abeta oligomers, reducing the binding of Abeta oligomers to neurons in vitro, preventing spine loss in neurons and preventing and treating oligomer-induced deficits in membrane trafficking. These molecules are highly brain penetrant and prevent and restore cognitive deficits in mouse models of Alzheimer\u27s disease. Counter-screening these compounds against a broad panel of potential CNS targets revealed they are highly potent and specific ligands of the sigma-2/PGRMC1 receptor. Brain concentrations of the compounds corresponding to greater than 80% receptor occupancy at the sigma-2/PGRMC1 receptor restore cognitive function in transgenic hAPP Swe/Ldn mice. These studies demonstrate that synthetic and human-derived Abeta oligomers act as pharmacologically-behaved ligands at neuronal receptors--i.e. they exhibit saturable binding to a target, they exert a functional effect related to their binding and their displacement by small molecule antagonists blocks their functional effect. The first-in-class small molecule receptor antagonists described here restore memory to normal in multiple AD models and sustain improvement long-term, representing a novel mechanism of action for disease-modifying Alzheimer\u27s therapeutics

Street-connectedness and education in Kenya: Experiences of formal schooling as rationale for inclusive pedagogies of practice

This paper contributes to the literature on street-connectedness and inclusive education, presenting original research findings from two Kenyan studies aiming to understand street-connected young people’s experiences of education. The first focused on transitioning from the street into education or training to explore the challenges of making that transition. The second, on young people who had lived on the street for extended periods of time and were still there at the time of data generation. From these studies, significant understandings emerged concerning: a) education as motivating initial migrations to the street; b) the role of fear, embarrassment and shame in preventing young people going (back) into formal education; and c) how acceptance and support are key to overcoming feelings of not belonging and challenges faced when transitioning from the street into schools. The paper provides empirical evidence that should be considered when planning inclusive education provision for street-connected young people globally

The P323L substitution in the SARS-CoV-2 polymerase (NSP12) confers a selective advantage during infection

Background The mutational landscape of SARS-CoV-2 varies at the dominant viral genome sequence and minor genomic variant population. During the COVID-19 pandemic, an early substitution in the genome was the D614G change in the spike protein, associated with an increase in transmissibility. Genomes with D614G are accompanied by a P323L substitution in the viral polymerase (NSP12). However, P323L is not thought to be under strong selective pressure. Results Investigation of P323L/D614G substitutions in the population shows rapid emergence during the containment phase and early surge phase during the first wave. These substitutions emerge from minor genomic variants which become dominant viral genome sequence. This is investigated in vivo and in vitro using SARS-CoV-2 with P323 and D614 in the dominant genome sequence and L323 and G614 in the minor variant population. During infection, there is rapid selection of L323 into the dominant viral genome sequence but not G614. Reverse genetics is used to create two viruses (either P323 or L323) with the same genetic background. L323 shows greater abundance of viral RNA and proteins and a smaller plaque morphology than P323. Conclusions These data suggest that P323L is an important contribution in the emergence of variants with transmission advantages. Sequence analysis of viral populations suggests it may be possible to predict the emergence of a new variant based on tracking the frequency of minor variant genomes. The ability to predict an emerging variant of SARS-CoV-2 in the global landscape may aid in the evaluation of medical countermeasures and non-pharmaceutical interventions

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570