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Pulmonary valve stenosis (PS) is the most common congenital heart defect in dogs. The condition is due to abnormal valve anatomy present at birth that leads to stenosis of the right ventricular outflow tract. The valve stenosis results in pressure overload of the right ventricle. If severe enough, the stenosis leads to right ventricular hypertrophy, arrhythmias, exercise intolerance, and right-sided heart failure. Severity of disease is typically determined based on velocity of blood flow across the lesion via echocardiography. The median survival time for dogs with severe PS is 4-5 years with medical management, while moderately affected cases have a variable prognosis. The prognosis for mild PS is generally good. The Bulldog, which is the fourth most popular breed according to AKC dog rankings, is a breed highly overrepresented in PS cases. Due to this breed predisposition PS is suspected to be inherited. Mildly affected dogs are frequently not diagnosed as traditional auscultation-based tests are insensitive in dogs with profound airway sounds and barrel-shaped chests such as the Bulldog. These subclinical cases make it incredibly difficult to successfully screen and remove affected individuals from the breeding program. Thus, hindering breeding efforts to reduce disease prevalence. Therefore, the development of a genetic screening test represents the most practical approach to identification and reduction of disease frequency in the breed. Additionally, severe and moderately affected PS cases are treated with traditional balloon valvuloplasty, which has good but variable success. The procedure has a significant cost, does not restore normal function, and there is considerable anesthetic risk for the brachycephalic breeds that are predisposed to PS. Additionally, some PS-affected dogs have concurrent coronary anomalies, which are expensive to identify and make balloon valvuloplasty contraindicated, further highlighting the need for genetic screening tests for this condition. There is limited information about the genetic cause of PS in humans with the majority of mutations involving the RAS-MAPK pathway. Although PS is commonly seen in puppies, no mutation to date has been identified, although literature suggests a possible recessive pattern of inheritance. Through the combined efforts of the clinical cardiology service at the University of California Davis, clinical cardiology service at Colorado State University, and the Translational Cardiac Genetics and Pharmacogenomics Laboratory in the University of California Davis School of Veterinary Medicine we aim to elucidate the genetic mechanisms of PS in Bulldogs. The goal of this dissertation is to compile and contribute to what is currently known about the genetics of PS in humans and animals. A retrospective study in a large referral hospital population allowed determination of the prevalence of this disease in dogs and confirmed common breed predisposition. A pedigree analysis was performed in the most affected breed, the Bulldog, to elucidate a common mode of inheritance. A genome-wide association study was performed to refine a region of interest in the canine genome that is associated with PS. Whole genome sequencing followed by variant analysis allowed identification of mutations associated with the disease. The most plausible variants underwent validation in a large population of dogs using MassArray and those that continued to segregate were followed up with immunohistochemistry in cardiac tissue. Finally, the results of this project will contribute to the understanding of heart development and congenital heart disease in dogs overall, thus guiding novel prevention and therapeutic strategies for PS.

Prenatal and early life exposure to cigarette smoke (CS) have repeatedly been shown to induce stable, long-term changes in DNA methylation (DNAm) in offspring. It has been hypothesized that these changes might be functionally related to the known outcomes of prenatal and early life CS exposure, which include impaired lung development, altered lung function and increased risk of asthma and wheeze. However, to date, few studies have examined DNAm changes induced by prenatal CS in tissues of the lung, and even fewer have attempted to examine the specific influences of prenatal versus early postnatal exposures. Here, we have established a mouse model of CS exposure which isolates the effects of prenatal and early postnatal CS exposures in early life. We have used this model to measure the effects of prenatal and/or postnatal CS exposures on lung function and immune cell infiltration as well as DNAm and expression ofCyp1a1, a candidate gene previously observed to demonstrate DNAm differences upon CS exposure in humans. Our study revealed that exposure to CS prenatally and in the early postnatal period cause long-lasting differences in offspring lung function, gene expression and lungCyp1a1DNAm, which wane over time but are reestablished upon re-exposure to CS in adulthood. This study creates a testable mouse model which can be used to investigate the effects of prenatal and early postnatal CS exposures and will contribute to the design of intervention strategies to mediate these detrimental effects.

BackgroundAccumulating evidence suggests prenatal air pollution exposure alters DNA methylation (DNAm), which could go on to affect long-term health. However, it remains unclear whether prenatal DNAm alterations persist through early life. Identifying DNAm changes that persist from birth into childhood would provide greater insight into the molecular mechanisms that most likely contribute to the association of prenatal air pollution exposure with health outcomes such as atopic disease.ObjectivesThis study investigated the persistence of DNAm changes associated with prenatal NO2exposure (a surrogate measure of traffic-related air pollution) at age one to begin characterizing which DNAm changes most likely to contribute to atopic disease.MethodsWe used an atopy-enriched subset of CHILD study participants (N=145) to identify individual and regional cord blood DNAm differences associated with prenatal NO2, followed by an investigation of persistence in age one peripheral blood. As we had repeated DNAm measures, we also isolated postnatal-specific DNAm changes and examined their association with NO2exposure in the first year of life. MANOVA tests were used to examine the association between DNAm changes associated with NO2and child wheeze and atopy.ResultsWe identified 24 regions of altered cord blood DNAm, with several annotated toHOXgenes. Two regions annotated toMPDU1andC5orf63were significantly associated with age one wheeze. Further, we found the effect of prenatal NO2exposure across CpGs within all altered regions remained similar at age one. A single region of postnatal-specific DNAm annotated toHOXB6was associated with year one NO2and age one atopy.DiscussionRegional cord blood DNAm changes associated with prenatal NO2exposure persist through at least the first year of life, and some of these changes are associated with age one wheeze. The early-postnatal period remains a sensitive window to DNAm perturbations that may also influence child health.

OBJECTIVES: An association between type-2 diabetes mellitus and cognitive decline is well known. Additionally, type 2 diabetes is known to be more physically burdensome for minorities. However, the combined impact of both ethnicity and diabetes on cognition is still not clear. METHODS: Data from the 2014 Health and Retirement Study (HRS) was used in this study to compare the cognitive functioning of non-Hispanic White (n = 10,658) and White Mexican/Mexican American (n = 847) individuals, age 50+ years, with or without type 2 diabetes. Cognitive functioning was measured by a composite of three constructs (serial 7 s, immediate, delayed recall). Ethnic groups and diabetes status were examined concerning cognitive functioning. RESULTS: A Multivariate Analysis of Covariance (MANCOVA) indicated significant main effects for ethnicity (F(3,11,496) = 11.15, p

The Prevent Alcohol and Risk-related Trauma in Youth (P.A.R.T.Y.) program is an immersive hospital-based education program designed to reduce trauma in adolescents. The efficacy of the program in reducing risk-taking attitudes and preventing traumatic injuries has been proven through various methodologies. However, there is currently no study that has investigated the efficacy of the program using a validated, multi-domain questionnaire. This study outlines the design of the P.A.R.T.Y. Program Questionnaire (PPQ) and validates it through examining its construct and criterion validity as well as its internal consistency. Its capacity to risk-stratify participants was compared against the RT-18, a robust, 18-item risk-profiling instrument. The PPQ and the RT-18 were completed by New South Wales school students (N = 458) aged 15 to 18. The PPQ was designed in consultation with relevant field experts to optimise engagement and sensitivity. Examination of the construct validity of the PPQ was performed through exploratory factor analysis which demonstrated the presence of two underlying factors which aligned with the constructed two-scenario questionnaire format. The PPQ was shown to be internally consistent with a Cronbach's alpha of 0.77. Individual scenarios were shown to be internally consistent as well (α = 0.69, α = 0.66). The PPQ also identified high risk and low risk participants effectively as demonstrated by comparison against the risk stratification performed with the RT-18 (p-value0.001). This suggests the PPQ demonstrates criterion validity. Hence, the PPQ is an effective and valid tool for assessing risk-taking attitudes in adolescent populations.

Rosario, Argentina, a city of more than one million people strategically located on the Parana River in the heart of a fertile agricultural region, is home to a significant industrial corridor where ongoing urbanization for industry, including that associated with the port complex and agroexport industries, vies for real estate space with peri-urban and urban farming production. The city is also the site of thriving municipal programs seeking to change food production and consumption outcomes through urban and peri-urban agriculture projects rooted in agroecology. This paper identifies the socio-natures critical for the formation and endurance of these agroecology assemblages. Based on interviews with 30 stakeholders in government, civil society, and agricultural production, we describe the integrated approach to environmental, social, and economic sustainability embedded in Rosario's institutional agroecology programs. In particular, we discuss the actors and strategies (which seek to preserve land for agricultural uses), discursive renderings of socio-natures (as valuable biodiverse territories and productive diverse bodies), and the marketing of agroecological materialities (through production for public markets) that form and are formed by these assemblages. We also discuss the power dynamics embedded in sustaining urban and peri-urban agroecological projects through institutional means. This research contributes to literature on agroecology, urban agriculture, and the urban metabolism through providing empirical examples of socio-natural entanglements in urban agroecological assemblages.

Background Macrolides are recommended as an adjunctive treatment for patients with moderate to severe chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations. The objective of this study was to examine temporal trends in the provision of long-term macrolide therapy, specifically before and after publication of the landmark MACRO trial in August 2011 showing efficacy of macrolides for this indication. Methods We performed an interrupted time series analysis using population-level health administrative data. The study cohort consisted of all Ontario residents who had COPD, were using at least 1 long-acting inhaler, and were aged 65 years and older between Apr. 1, 2004, and Mar. 31, 2018. We compared the baseline characteristics of eligible patients before and after publication of the MACRO trial. Our primary outcome was overall prevalence of long-term macrolide therapy; secondary outcomes were incidence of COPD-related hospitalizations, emergency department visits and outpatient exacerbations requiring high-dose steroids in each quarter. We performed an interrupted time series analysis to assess for changes in the incidence of macrolide prophylaxis by quarter-year over the study period. Results The rate of long-term macrolide use increased from 0.8 per 1000 people in 2004 to 13.8 per 1000 people in 2018 (in the severe COPD group, the rate increased from 1.3 to 32.3 per 1000 people). The interrupted time series analysis showed that, before 2011, the prevalence of macrolide prophylaxis increased at a rate of 0.44 (95% confidence interval [CI] 0.39-0.50) per 1000 people per year; after 2011, the rate of increase grew by 1.18 (95% CI 1.07-1.29) per 1000 people to 1.63 (95% CI 1.56-1.69) per 1000 people per year. The seasonal pattern of COPD-related health care visits remained stable over the study period, and there was no detectable reduction in hospitalizations or emergency department visits at the population level. Interpretation In the past decade, there has been a significant rise in the use of long-term macrolide therapy for patients with COPD. As this practice becomes increasingly common, it will be important to monitor its potential benefits on COPD exacerbations but also its potential effects on adverse events and antimicrobial resistance patterns.

Introduction Melatonin is a widely used pediatric sleep aid. While readily available internationally, regulatory changes in Australia have only recently allowed over-the-counter access for patients aged over 55, triggering renewed public interest in melatonin. However, melatonin access for younger patients with sleep disturbances remains a prescription-only medicine. Furthermore, pharmacist opinions about the use of melatonin in pediatric patients remain unexplored. This study aimed to investigate Australian community pharmacists’ perspectives toward melatonin use in school-aged children and adolescents. Methods A qualitative study was conducted in a convenience sample of community pharmacists/interns practicing in metropolitan Sydney. Participants completed an online questionnaire capturing demographic information and practice context. Participants subsequently indicated their interest in participating in an in-depth semi-structured interview. Interviews were guided by a schedule of questions exploring pharmacists’ knowledge, beliefs, and attitudes toward melatonin use in pediatric patients. The interviews were digitally recorded, transcribed verbatim, and analyzed using the Framework Approach to identify emergent themes. Recruitment continued until thematic saturation was reached. Results Twenty-four interviews were conducted with pharmacists (n=19) and interns (n=5). Participants were mostly female (67%) with a mean age of 29.8 (range: 22-56) years. Pharmacists managed 25.3 (1-300) sleep-related inquiries per day on average and received direct product requests for melatonin 15.9 (2-100) times per week. Preliminary analyses identified three key themes: Conflicting Opinions on Safety, Product Cost and Formulation Availability, and Gaps in Clinical Education. Pharmacists’ involvement in pediatric melatonin use has largely been within the domains of dispensing or compounding prescriptions. While melatonin was perceived as a “better choice over other sedatives” for children, pharmacists expressed uncertainty about the evidence base concerning long-term use in younger age groups, relying heavily on physicians for prescribing discretion and patient supervision. The need for affordable proprietary products with flexible dosing options and targeted education around melatonin and circadian sleep health was also expressed by participants. Conclusion Findings allude to the need for greater availability and accessibility of pediatric-specific melatonin formulations, as well as refinement of clinical education resources that specifically address the use of melatonin among school-aged children and adolescents. Support (if any)

BackgroundDespite a clear association seen in congenitally infected children, the effect of postnatal cytomegalovirus (CMV) infection during early childhood on cognitive development has not yet been determined.MethodsCMV-infection status was obtained based on serological measurements when children were 7 years old. Using population-based longitudinal data, we employed multivariate Poisson regression with a robust variance estimator to characterize the relationship between childhood CMV infection and adverse neurocognitive outcomes in children. Suboptimal neurocognitive outcomes were compared between CMV-positive and CMV-negative children using various cognitive assessments from 8 to 15 years of age. Children were evaluated on the cognitive domains of language, reading, memory and general intelligence, with a suboptimal score being >2 standard deviations lower than the mean score. Approximate Bayes factor (ABF) analysis was used to determine the level of evidence for the observed associations.ResultsWith adjustment for potential confounders, we observed that early-childhood CMV infection was associated with suboptimal total intelligence quotient (IQ) at 8 years of age [incidence-rate ratio (IRR) = 2.50, 95% confidence interval (CI) 1.35–4.62, ABF = 0.08], but not with suboptimal total IQ at 15 years of age (IRR = 0.97, 95% CI 0.43–2.19, ABF = 1.68). Suboptimal attentional control at 8 years (IRR = 1.74, 95% CI 1.13–2.68, ABF = 0.18) and reading comprehension at 9 years (IRR = 1.93, 95% CI 1.12–3.33, ABF = 0.24) were also associated with CMV infection. ABF analysis provided strong evidence for the association between CMV infection and total IQ at 8 years, and only anecdotal evidence for attentional control at 8 years and reading comprehension at 9 years. All other cognitive measures assessed were not associated with CMV infection.ConclusionIn this large-scale prospective cohort, we observed some evidence for adverse neurocognitive effects of postnatal CMV infection on general intelligence during early childhood, although not with lasting effect. If confirmed, these results could support the implementation of preventative measures to combat postnatal CMV infection.

Aberrant insulin-like growth factor 1 (IGF-1) signaling has been proposed as a contributing factor to the development of neurodegenerative disorders including diabetic neuropathy, and delivery of exogenous IGF-1 has been explored as a treatment for Alzheimer’s disease and amyotrophic lateral sclerosis. However, the role of autocrine/paracrine IGF-1 in neuroprotection has not been well established. We therefore used in vitro cell culture systems and animal models of diabetic neuropathy to characterize endogenous IGF-1 in sensory neurons and determine the factors regulating IGF-1 expression and/or affecting neuronal health. Single-cell RNA sequencing (scRNA-Seq) and in situ hybridization analyses revealed high expression of endogenous IGF-1 in non-peptidergic neurons and satellite glial cells (SGCs) of dorsal root ganglia (DRG). Brain cortex and DRG had higher IGF-1 gene expression than sciatic nerve. Bidirectional transport of IGF-1 along sensory nerves was observed. Despite no difference in IGF-1 receptor levels, IGF-1 gene expression was significantly (P db/db type 2 diabetic mice. Hyperglycemia suppressed IGF-1 gene expression in cultured DRG neurons and this was reversed by exogenous IGF-1 or the aldose reductase inhibitor sorbinil. Transcription factors, such as NFAT1 and CEBPβ, were also less enriched at the IGF-1 promoter in DRG from diabetic rats vs control rats. CEBPβ overexpression promoted neurite outgrowth and mitochondrial respiration, both of which were blunted by knocking down or blocking IGF-1. Suppression of endogenous IGF-1 in diabetes may contribute to neuropathy and its upregulation at the transcriptional level by CEBPβ can be a promising therapeutic approach.

Bloodstream infections (BSIs) represent a substantial mortality risk, yet most studies are limited to select pathogens or populations. The aim of this study was to describe the population-wide prevalence of BSIs and examine the associated mortality risk for the responsible microorganisms. We conducted a population-wide retrospective cohort study of BSIs in Ontario in 2017. Blood culture data was collected from almost all microbiology laboratories in Ontario and linked to data sets of patient characteristics. For each organism, we determined the prevalence and crude mortality risk, and using logistic regression models, the adjusted odds of 30-day mortality was calculated relative to patients with negative blood cultures and matched patients without blood culture testing. From 531,065 blood cultures, we identified 22,935 positive BSI episodes in 19,326 patients, for an incidence of 150 per 100,000 population. The most frequently isolated organisms were Escherichia coli, Staphylococcus aureus, coagulase-negative staphylococci, Klebsiella species, and Enterococcus species with 40.2, 22.4, 12.1, 11.1, and 7.1 episodes per 100,000 population respectively. BSI episodes were associated with 17.0% mortality at 30 days. Compared to patients with negative cultures, the adjusted 30-day mortality risk for positive BSIs was 1.47 (95% confidence interval (CI), 1.41 to 1.54) and compared to matched patients without blood culture testing was 2.62 (95% CI, 2.52 to 2.73). Clostridium species were associated with the highest adjusted odds of mortality compared to that of negative cultures (adjusted odds ratio, 5.81; 95% CI, 4.00 to 8.44). Among high incidence pathogens, Staphylococcus aureus had the highest odds ratio of mortality (adjusted odds ratio, 2.14; 95% CI, 1.94 to 2.36). BSIs are associated with increased mortality risk, varying across organisms.

Background Peer comparison audit and feedback has demonstrated effectiveness in improving antibiotic prescribing practices, but only a minority of prescribers view their reports. We rigorously tested 3 behavioral nudging techniques delivered by email to improve report opening. Methods We conducted a pragmatic randomized controlled trial among Ontario long-term care prescribers enrolled in an ongoing peer comparison audit and feedback program which includes data on their antibiotic prescribing patterns. Physicians were randomized to 1 of 8 possible sequences of intervention/control allocation to 3 different behavioral email nudges: a social peer comparison nudge (January 2020), a maintenance of professional certification incentive nudge (October 2020), and a prior participation nudge (January 2021). The primary outcome was feedback report opening; the primary analysis pooled the effects of all 3 nudging interventions. Results The trial included 421 physicians caring for >28 000 residents at 450 facilities. In the pooled analysis, physicians opened only 29.6% of intervention and 23.9% of control reports (odds ratio [OR], 1.51 [95% confidence interval {CI}, 1.10–2.07], P = .011); this difference remained significant after accounting for physician characteristics and clustering (adjusted OR [aOR], 1.74 [95% CI, 1.24–2.45], P = .0014). Of individual nudging techniques, the prior participation nudge was associated with a significant increase in report opening (OR, 1.62 [95% CI, 1.06–2.47], P = .026; aOR, 2.16 [95% CI, 1.33–3.50], P = .0018). In the pooled analysis, nudges were also associated with accessing more report pages (aOR, 1.28 [95% CI, 1.14–1.43], P Conclusions Enhanced nudging strategies modestly improved report opening, but more work is needed to optimize physician engagement with audit and feedback. Clinical Trials Registration NCT04187742.

Background With the challenges that aging populations pose to health care, interventions that facilitate alleviation of age-related morbidities are imperative. A prominent risk factor for developing age-related morbidities is immunosenescence, characterized by increased chronic low-grade inflammation, resulting in T-cell exhaustion and senescence. Contact with nature and associated physical activities have been shown to boost immunity in older adults and may be promoted in the form of horticultural therapy (HT). We aimed to examine the effects of HT on immunosenescence. Method We conducted a randomized controlled trial with 59 older adults assigned to either the HT intervention or waitlist control group. Older adults in the HT intervention group underwent HT intervention program over 6 months. Venous blood was drawn at baseline and at the third and sixth month from the commencement of this study. For participants who attended all 3 blood collection time points (HT: n = 22; waitlist: n = 24), flow cytometry analysis was performed on whole blood samples to evaluate the kinetics of lymphocyte subsets over the intervention period, revealing the composition of CD4+ and CD8+ subsets expressing exhaustion markers—CD57, CTLA4, and KLRG1. Enzyme-linked immunosorbent assays were employed to measure changes in plasma IL-6 levels. Results HT is associated with increased numbers of naive CD8+ T cells and fewer CTLA4-expressing terminally differentiated effector CD4+ and CD8+ memory T cells re-expressing CD45RA (TEMRA). Furthermore, IL-6 levels were reduced during HT, and the frequencies of naive and TEMRA CD8+ T cells were found to be associated with IL-6 levels. Conclusion HT is associated with a reduction in the levels of biomarkers that measure the extent of T-cell exhaustion and inflammaging in older adults. The positive effects of HT on T-cell exhaustion were associated with the reduction of IL-6 levels.

Background Intra-hepatocyte triglyceride accumulation is the hallmark of non-alcoholic fatty liver disease (NAFLD). Little is known of the role of lipid droplets in the pathogenesis of this increasingly common condition. Eicosapentaenoic acid (EPA), an omega-3 fatty acid, has been suggested as a potential treatment for NAFLD. Within this study we explore different energy substrates with and without EPA and evaluate biochemical markers alongside lipid droplet characteristics. Methods EPA was added to C3A cells incubated in standard media, oleate (which mimics simple steatosis) or lactate, pyruvate, octanoate and ammonia (LPON), mimicking pathophysiology of NAFLD. At 72 hours, glucose, ketone bodies and various markers of liver function were assessed and triglyceride content was determined using confocal images of cells stained with BODIPY 493/503 and DAPI. Z stacks of confocal images were analysed using Volocity 3D image analysis and Visual Basic software to estimate the physical characteristics of lipid droplets. Liver function was assessed by measuring AST, albumin and LDH. Results Albumin levels increased in control and oleate and LDH showed EPA did not affect viability in concentrations up to 250µm. There was no effect to AST with addition of EPA. Glucose and ketone bodies were reduced in LPON treated cells in a dose dependent manner. EPA reduced triglyceride concentrations and lipid droplets per nucleus in untreated cells compared with control, however, there was no significant difference to total triglyceride concentration of cells treated with oleate + EPA or LPON + EPA. Lipid droplet volume increased in both fat loaded models with the addition of EPA, but untreated control remained the same. Surface area of lipid droplets was higher in oleate model compared to LPON. Conclusion The LPON + EPA model shows reduction of glucose and ketone bodies in a dose dependent manner indicating EPA may be useful as an adjunct to treatment of type 2 diabetes. Accumulation of lipid droplets at different rates and physical characteristics compared to oleate may reflect differences in FFA metabolism or their incorporation into the cell and lipid droplet membrane.

MEd (Educational Psychology), North-West University, Potchefstroom Campus This dissertation aimed to explore how collaboration between parents and teachers could support the emotional well-being of learners with ADHD. The emotional difficulties that go along with ADHD are often overlooked, all the while influencing many other aspects of the learner’s life. The participants in this study together addressed a gap in the available literature with respect to sustainable support for the learner’s emotional well-being by means of collaboration, ultimately benefitting the learners, parents, and teachers. The emotional challenges learners with ADHD face first prompted my interest in undertaking this study. My interest in this topic grew once I started working as an educator at an underprivileged school. Here I encountered learners with ADHD who had severe difficulties with the control of and understanding of their own emotions. The study examined whether parent-teacher collaboration could offer an avenue to support learners with these difficulties. Parents and teachers seldom actively collaborate to provide support to these learners. In this dissertation, I point out how sustained collaborative efforts could improve the emotional well-being of these learners and how this is beneficial to all parties involved. This study used a Participatory Action Learning and Action Research (PALAR) design with nine participants. The participants and I formed an action learning set where we collaborated to gain an understanding of the challenges learners with ADHD face. We developed strategies and guidelines to support these challenges from an early age, with the hope that it will positively affect the learners’ emotional well-being into adulthood. Visual artefacts and transcripts from the action learning set meetings were analysed to generate data, supported by relevant literature. The collaborative and participatory approach to this study gave each participant an opportunity to have their voices be heard. The primary research question was: How can teachers and parents collaborate to support the emotional well-being of FP learners with ADHD? The study was conducted in three cycles to answer the primary research question. In Cycle One, data were generated in action learning set discussions to answer the following sub-question: What challenges do teachers and parents face in providing support to ensure the emotional well-being of FP learners with ADHD? After the data analysis, the following themes emerged: cognitive challenges, behavioural challenges, emotional challenges, and physical challenges. The findings from this cycle revealed multiple challenges that were faced by the parents and teachers when supporting the learner with ADHD. From here, we continued to Cycle Two of the research, during which we used asset-mapping to generate data and address the second research sub-question: What collaboratively developed strategies are effective to support the emotional well-being of FP learners with ADHD? The findings from this cycle revealed the strategies that were necessary to support these learners and led us to the final sub-question in Cycle Three: What guidelines for collaborative parent/teacher support can be derived from the findings to enhance the emotional well-being of FP learners with ADHD? The findings from the final cycle revealed the guidelines that could be useful to support the emotional well-being of FP learners with ADHD. The research process and findings from this study, this being the identification of challenges, and the development of strategies and guidelines, added to parents’ knowledge and brought changes to their attitudes. This had a positive effect on the learners and led to improvements in their emotional well-being. This study contributes valuable information towards the theoretical body of knowledge on ADHD and the emotional difficulties learners and the parents and teachers who support them, experience. Masters

We report the first case series of 14 children with intracranial germ cell tumour (iGCT) and concomitant central diabetes insipidus (DI), who developed hyponatremia secondary to renal salt wasting syndrome (RSWS) following the administration of carboplatin. Clinicians prescribing platinum-based chemotherapy for this group of patients should be alert to the risk of RSWS. Regular monitoring should be performed as hyponatraemia can be asymptomatic until it is severe.

Idiopathic pulmonary fibrosis (IPF) is a common interstitial lung disease (ILD) caused by environmental exposures, infections, or traumatic injuries and subsequent epithelial damage. Since IPF is a progressively fatal disease without remission, treatment is both urgent and necessary. The two medications indicated solely for treatment include the tyrosine kinase inhibitor nintedanib (Ofev®) and the anti-fibrotic agent pirfenidone (Esbriet®). This chapter discusses in detail the current treatment options for clinical management of IPF, specifically the mentioned two pharmacotherapeutic agents that decrease physiological progression and likely improve progression-free survival. The chapter also discusses the evolution of drug therapy in IPF management and the drawbacks and limitations learned throughout historical trials and observational studies.

Coral reefs are currently threatened by both natural and human-driven disturbances, and climate change scenarios suggest that the health of future reefs is uncertain. To better inform management and preservation of coral reef ecosystems, it is critical that we understand the mechanisms that support recovery of coral habitat after coral mortality events. Macroalgae can inhibit coral recovery by preventing recruitment and growth of corals after a disturbance, leading to a shift in the dominant benthic community from coral to macroalgae. These macroalgal habitats do not support the same diversity of fish and other species as healthy coral reefs, and are thus undesirable on large scales. This dissertation addresses some processes that are important in the establishment and persistence of these macroalgal phase shifts. Through an enhanced understanding of macroalgal persistence, we may be able to identify (and protect) key species and processes that are critical to promoting coral reef recovery.I used the macroalga Turbinaria ornata as a model species to examine the potential for herbivore-algal feedbacks that can promote persistent macroalgal phase shifts. This species is perennial and patches appear to persist inter-annually once established. In areas where macroalgae is present, Turbinaria largely dominates the benthic community. Results of observational studies of tagged Turbinaria patches suggest that Turbinaria populations exhibit positive population growth (both number of adult thalli and patch area increased over a 2 year period). Several factors including high turnover rates of thalli, year-round reproduction, and a buffer of immature individuals that may act as a “seed bank” following a disturbance may contribute to the expansion of this species in the lagoons of Moorea.In addition, I used field experiments to assess the potential for associational refuge to provide a mechanism for Turbinaria persistence in the lagoons of Moorea. Results from these experiments suggest that an associational refuge may facilitate persistence of Turbinaria, as predation on small vulnerable individuals (< 2 cm in length) is reduced when associated with larger, less palatable adults. However, the significance of this refuge depends on the local abundance of browsing herbivores that can consume macroalgae. An associational refuge that results in higher recruit survival in the presence of herbivory could represent a self-reinforcement mechanism that could facilitate the establishment and multi-generational persistence of Turbinaria patches on coral reefs.To determine the effects of herbivore pressure on the development and persistence of a macroalgal community, I examined the effects of herbivores on mature (dominated by the late stage macroalga Turbinaria ornata) and early stage (dominated by turf algae) algal communities. Results suggest that the effects of herbivores depend upon the initial conditions of the benthic community, and this may have implications for management practices for disturbed, degraded and healthy reefs. Herbivores, particularly browsing fish that can consume mature macroalgae, appear to be limited in their capacity to remove established macroalgae. These critical species appear to be present in low abundance in some habitats, and are targeted as part of a local fishery. In contrast, other herbivores (grazers that consume turf algae and immature macroalgae) appear to readily limit the development of macroalgal communities. I also found that herbivores differentially influence the richness of macroalgal communities depending on the initial macroalgal community. Specifically, an initial presence of the mature macroalga, Turbinaria ornata, enhanced richness of macroalgal assemblage even as herbivore pressure increased. At the same level of herbivore pressure, communities with Turbinaria present had greater richness than communities that initially were dominated by turf algae, even after two years. Results from this experiment provide some of the first empirical tests of hysteresis (path-dependency) in reef recovery, and reinforce the importance of different herbivore functional groups at different points along the recovery trajectory.Overall, this research highlights characteristics of macroalgae and interactions between macroalgal and herbivore communities that can drive persistent macroalgal phase shifts in coral reef ecosystems. This information may be used to develop sustainable management and conservation strategies to preserve these valuable ecosystems and the services that they provide for local communities.

The safe release of a patient from hospital care after bariatric surgery depends upon the achievement of satisfactory health status. Here, we describe a new objective scale (the Readiness for Discharge, RFD Scale) to measure the patient’s suitability for hospital discharge after bariatric surgery. We conducted a retrospective, observational analysis of data collected in a randomized clinical trial of an enhanced recovery after surgery protocol for laparoscopic sleeve gastrectomy from 3/15/2018 to 1/12/2019. Nursing staff assessed 122 patients every 4–8 h after surgery using a checklist to document 5 components: ambulation, vital signs, pain, nausea, and oral intake of clear fluid. Satisfaction of each component was scored as “1” (satisfactory) or “0” (not satisfactory). Scores were summed and analyzed for patterns. RFD = 5 marked the patient as ready for discharge. Sufficient intake of clear liquid was the last RFD component satisfied in 87% of patients. Two overall response patterns emerged: “Steady Progressors” (n = 51) whose RFD score rose steadily from 0 to 5 without reversion to a lower score; and “Oscillators” (n = 71) who had at least one temporary decrease in RFD score on the way to attaining 5, or showed a simultaneous oscillation of components without change in RFD. The RFD checklist allows objective scoring of medical readiness for discharge after LSG and has the potential to improve clinical communication.

Anaerobic fungi and methanogenic archaea are two classes of microorganisms found in the rumen microbiome that metabolically interact during lignocellulose breakdown. Here, stable synthetic co-cultures of the anaerobic fungusCaecomyces churrovisand the methanogenMethanobacterium bryantii(not native to the rumen) were formed, demonstrating that microbes from different environments can be paired based on metabolic ties. Transcriptional and metabolic changes induced by methanogen co-culture were evaluated inC. churrovisacross a variety of substrates to identify mechanisms that impact biomass breakdown and sugar uptake. A high-quality genome ofC. churroviswas obtained and annotated, which is the first sequenced genome of a non-rhizoid forming anaerobic fungus.C. churrovispossess an abundance of CAZymes and carbohydrate binding modules and, in agreement with previous studies of early-diverging fungal lineages, N6-methyldeoxyadenine (6mA) was associated with transcriptionally active genes. Co-culture with the methanogen increased overall transcription of CAZymes, carbohydrate binding modules, and dockerin domains in co-cultures grown on both lignocellulose and cellulose and caused upregulation of genes coding associated enzymatic machinery including carbohydrate binding modules in family 18 and dockerin domains across multiple growth substrates relative toC. churrovismonoculture. Two other fungal strains grown on a reed canary grass substrate in co-culture with the same methanogen also exhibited high log2fold change values for upregulation of genes encoding carbohydrate binding modules in families 1 and 18. Transcriptional upregulation indicated that co-culture of theC. churrovisstrain with a methanogen may enhance pyruvate formate lyase (PFL) function for growth on xylan and fructose and production of bottleneck enzymes in sugar utilization pathways, further supporting the hypothesis that co-culture with a methanogen may enhance certain fungal metabolic functions. Upregulation of CBM18 may play a role in fungal-methanogen physical associations and fungal cell wall development and remodeling.