The Transformative City

The issue of downtown revitalization has been much studied over the past several decades. However, much of the existing knowledge base pertains to our largest urban centres. This leaves a significant information gap with regards to mid-size cities. As a result, past renewal attempts in these cities have often been scaled down versions of what has worked in larger cities. In most cases, this has resulted in detrimental rather than reviving effects. The current trend in cities of all sizes is the implementation of Creative City Theory. This thesis seeks to study this trend and its specific relevance to the mid-size city. The scope of research will then build on the current theory by exploring the effects of well-designed public spaces and their ability to not only unleash the creative spirit but to revitalize the post-industrial mid-size city downtown. This information will then be applied to a design study for Hamilton, Ontario where failed renewal attempts have crippled the city’s downtown. The design will concentrate on Jackson Square (formerly known as Civic Square), a superblock within the very centre of downtown Hamilton. Through a redesign of Jackson Square, the thesis proposes to create a place that not only fosters creativity, but is once again meaningful and significant to Hamilton citizens. While the application of research to Hamilton is specific, the goal is to produce a body of work with principles that can be applied to any number of mid-size cities across the post-industrial world

Investigating students' use of self-assessments in higher education using learning analytics

Background Formative assessments are vital for supporting learning and performance but are also considered to increase the workload of teachers. As self-assessments in higher education are increasingly facilitated via digital learning environments allowing to offer direct feedback and tracking students' digital learning behaviour these constraints might be reduced. Yet, learning analytics do not make sufficient use of data on assessments. Aims This exploratory case study uses learning analytics methods for investigating students' engagement with self-assessments and how this relates to performance in the final exam and self-reported self-testing strategies. Materials & Methods The research study has been conducted at a European university in a twelve-weeks course of a Bachelor's program in Economic and Business Education including nenroll = 159 participants. During the semester, students were offered nine self-assessments each including three to eight tasks plus one mid-term and one exam-preparation self-assessment including all prior self-assessments tasks. The self-assessment interaction data for each student included: the results of the last self-assessment attempt, the number of processed self-assessment tasks, and the time spent on the last self-assessment attempt, the total self-assessment attempts, and the first as well as last access of each self-assessment. Data analytics included unsupervised machine learning and process mining approaches. Results Findings indicate that students use the self-assessments predominantly before summative assessments. Two distinct clusters based on engagement with self-assessments could be identified and engagement was positively related to performance in the final exam. The findings from learning analytics data were also indicated by students' self-reported use of self-testing strategies. Discussion With the help of multiple data from self-reports, formal exams, and a learning analytics system, the findings provided multiple perspectives on the use of self-assessments and their relationships with course performance. These findings call for applying assessment analytics and related frameworks in learning analytics as well as providing learners with related adaptive feedback. Conclusion Future research might investigate different (self-report) variables for clustering, other student cohorts or self-assessment forms.Peer Reviewe

Distinct axo-protective and axo-destructive roles for Schwann cells after injury in a novel compartmentalised mouse myelinating coculture system.

Myelinating Schwann cell (SC)- dorsal root ganglion (DRG) neuron cocultures have been an important technique over the last four decades in understanding cell-cell signalling and interactions during peripheral nervous system (PNS) myelination, injury, and regeneration. While methods using rat SCs and rat DRG neurons are commonplace, there are no established protocols in the field describing the use of mouse SCs with mouse DRG neurons in dissociated myelinating cocultures. There is a great need for such a protocol as this would allow the use of cells from many different transgenic mouse lines. Here we describe a protocol to coculture dissociated mouse SCs and DRG neurons and induce robust myelination. Use of microfluidic chambers permits fluidic isolation for drug treatments, allows cultures to be axotomised to study injury responses, and cells can readily be transfected with lentiviruses to permit live imaging. We used this model to quantify the rate of degeneration after traumatic axotomy in the presence and absence of myelinating SCs and axon aligned SCs that were not induced to myelinate. We find that SCs, irrespective of myelination status, are axoprotective and delay axon degeneration early on. At later time points after injury, we use live imaging of cocultures to show that once axonal degeneration has commenced SCs break up, ingest, and clear axonal debris

Rare germline variants in DNA repair genes and the angiogenesis pathway predispose prostate cancer patients to develop metastatic disease

Background Prostate cancer (PrCa) demonstrates a heterogeneous clinical presentation ranging from largely indolent to lethal. We sought to identify a signature of rare inherited variants that distinguishes between these two extreme phenotypes. Methods We sequenced germline whole exomes from 139 aggressive (metastatic, age of diagnosis < 60) and 141 non-aggressive (low clinical grade, age of diagnosis ≥60) PrCa cases. We conducted rare variant association analyses at gene and gene set levels using SKAT and Bayesian risk index techniques. GO term enrichment analysis was performed for genes with the highest differential burden of rare disruptive variants. Results Protein truncating variants (PTVs) in specific DNA repair genes were significantly overrepresented among patients with the aggressive phenotype, with BRCA2, ATM and NBN the most frequently mutated genes. Differential burden of rare variants was identified between metastatic and non-aggressive cases for several genes implicated in angiogenesis, conferring both deleterious and protective effects. Conclusions Inherited PTVs in several DNA repair genes distinguish aggressive from non-aggressive PrCa cases. Furthermore, inherited variants in genes with roles in angiogenesis may be potential predictors for risk of metastases. If validated in a larger dataset, these findings have potential for future clinical application

The effect of a game-based mobile app “MyHeartMate” to promote lifestyle change in coronary disease patients: a randomised controlled trial

AimsSecondary prevention reduces coronary heart disease (CHD) progression. Traditional prevention programs including cardiac rehabilitation are under-accessed, which smartphone apps may overcome. To evaluate the effect of a game-based mobile app intervention (MyHeartMate) to improve cardiovascular risk factors and lifestyle behaviours.Methods and resultsSingle-blind randomized trial of CHD patients in Sydney, 2017–2021. Intervention group were provided the MyHeartMate app for 6 months. Co-designed features included an avatar of the patient’s heart and tokens earned by risk factor work (tracking, challenges, and quizzes). The control group received usual care. Primary outcome was self-reported physical activity [metabolic equivalents (METs), Global Physical Activity Questionnaire] and secondary outcomes included lipid levels, blood pressure (BP), body mass index, and smoking. Pre-specified sample size was achieved (n = 390), age 61.2 ± 11.5 years; 82.5% men and 9.2% current smokers. At 6 months, adjusted for baseline levels, the intervention group achieved more physical activity than control (median difference 329 MET mins/wk), which was not statistically significant (95% CI −37.4, 696; P = 0.064). No differences occurred between groups on secondary outcomes except for lower triglyceride levels in the intervention [mean difference −0.3 (95% CI −0.5, −0.1 mmoL/L, P = 0.004)]. Acceptability was high: 94.8% of intervention participants engaged by tracking exercise or BP and completing missions; 26.8% continued to engage for ≥30 days. Participants (n = 14) reported the app supported tracking behaviours and risk factors, reinforcing and improving self-care confidence, and decreasing anxiety.ConclusionA game-based app proved highly acceptable for patients with CHD but did not improve risk factors or lifestyle behaviours other than triglyceride levels

Design and rationale of the MyHeartMate study: a randomised controlled trial of a game-based app to promote behaviour change in patients with cardiovascular disease

Introduction: Recurrence of cardiac events is common after a first event, leading to hospitalisations and increased health burden. Patients have difficulties achieving the lifestyle changes required for secondary prevention and access to secondary prevention programs is limited. This study aims to evaluate the impact of a game-based mobile app, MyHeartMate, which is designed to motivate engagement in secondary prevention behaviours for cardiovascular risk factors.Methods and analysis: The MyHeartMate study is a randomised controlled trial with 6-month follow-up and blinded assessment of the primary outcome. Participants (n=394) with coronary heart disease will be recruited from hospitals in metropolitan Sydney and randomly allocated to standard care or the MyHeartMate app intervention. The intervention group will receive the app, which uses game techniques to promote engagement and lifestyle behaviour change for secondary prevention. The primary outcome is difference between the groups in physical activity (metabolic equivalent of task minutes/week) at 6 months. Secondary outcomes include change in low-density lipoprotein cholesterol, systolic blood pressure, medication adherence, body mass index, waist circumference, mood and dietary changes at 6 months. Data on app engagement, and patient perspectives of usability and acceptability, will also be analysed.Ethics and dissemination: The study has received ethics approval from Northern Sydney Local Health District Human Research Ethics Committee. The study findings will be disseminated via peer-reviewed publications and presentation at international scientific meetings/conferences.Trial registration number: ACTRN12617000869370; Pre-results

Designed Ankyrin Repeat Proteins provide insights into the structure and function of CagI and are potent inhibitors of CagA translocation by the Helicobacter pylori type IV secretion system

The bacterial human pathogen Helicobacter pylori produces a type IV secretion system ( cag T4SS) to inject the oncoprotein CagA into gastric cells. The cag T4SS external pilus mediates attachment of the apparatus to the target cell and the delivery of CagA. While the composition of the pilus is unclear, CagI is present at the surface of the bacterium and required for pilus formation. Here, we have investigated the properties of CagI by an integrative structural biology approach. Using Alpha Fold 2 and Small Angle X-ray scattering, it was found that CagI forms elongated dimers mediated by rod-shape N-terminal domains (CagI N ) prolonged by globular C-terminal domains (CagI C ). Three Designed Ankyrin Repeat Proteins (DARPins) K2, K5 and K8 selected against CagI interacted with CagI C with subnanomolar affinities. The crystal structures of the CagI:K2 and CagI:K5 complexes were solved and identified the interfaces between the molecules, thereby providing a structural explanation for the difference in affinity between the two binders. Purified CagI and CagI C were found to interact with adenocarcinoma gastric (AGS) cells, induced cell spreading and the interaction was inhibited by K2. The same DARPin inhibited CagA translocation by up to 65% in AGS cells while inhibition levels were 40% and 30% with K8 and K5, respectively. Our study suggests that CagI C plays a key role in cag T4SS-mediated CagA translocation and that DARPins targeting CagI represent potent inhibitors of the cag T4SS, a crucial risk factor for gastric cancer development.Bases structurale du système de secretion de type IV d'Helicobacter pyloriBases structurales et moléculaires de l'exploitation de l'integrin a5ß1 par le système de sécrétion de type IV d'Helicobacter pylor