Exome array analysis of pulmonary function in smokers with and without chronic obstructive pulmonary disease (COPD)

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease characterized by airflow restriction and decreased lung function. It is the 3rd leading cause of death worldwide, accounting for approximately 3 million deaths in 2010. It is diagnosed using spirometric measurements, including the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC). These measures reflect the severity of airway obstruction and predict population morbidity and mortality. The primary environmental cause of COPD is cigarette smoking, but genetics also play a role in individual susceptibility and disease progression. Genome-wide association studies (GWAS) have identified over 30 loci associated with lung, but together the identified variants can only explain a small proportion of the variation in spirometric measures and a small proportion of the estimated heritability. We hypothesized: 1) rare functional variation also affects lung function; and 2) genetic variation (both common and rare) affects longitudinal changes in lung function. This dissertation tests these hypotheses using data from the COPDgene study, a large multicenter study of current and former smokers

Lessons Learned During Turbulent Times to Weather and Thrive in the Storm of COVID-19

This article describes the lessons learned by our university during the global healthcare crisis of COVID-19. It highlights the agile solutions employed to continue learning under extraordinary circumstances. While we have captured the stories that allowed our students to power through this tumultuous period if they so desired, these lessons may also provide guidance to other higher education institutions not only for the current turbulent times, but also enhance their ability to pause and pivot by utilizing agile management to weather this and future storms

Strategies for Writing a Self-Study and Conducting a Site Review

This presentation will include a discussion of the principle components of a department self-study and provide examples from two departments (English and Fine and Performing Arts). The specific self-study structure we developed is especially beneficial for small university campuses that may need to justify programs or budgetary expenditures

Identification of novel small molecule inhibitors of adenovirus gene transfer using a high throughput screening approach

Due to many favourable attributes adenoviruses (Ads) are the most extensively used vectors for clinical gene therapy applications. However, following intravascular administration, the safety and efficacy of Ad vectors are hampered by the strong hepatic tropism and induction of a potent immune response. Such effects are determined by a range of complex interactions including those with neutralising antibodies, blood cells and factors, as well as binding to native cellular receptors (coxsackie adenovirus receptor (CAR), integrins). Once in the bloodstream, coagulation factor X (FX) has a pivotal role in determining Ad liver transduction and viral immune recognition. Due to difficulties in generating a vector devoid of multiple receptor binding motifs, we hypothesised that a small molecule inhibitor would be of value. Here, a pharmacological approach was implemented to block adenovirus transduction pathways. We developed a high throughput screening (HTS) platform to identify the small molecule inhibitors of FX-mediated Ad5 gene transfer. Using an in vitro fluorescence and cell-based HTS, we evaluated 10,240 small molecules. Following sequential rounds of screening, three compounds, T5424837, T5550585 and T5660138 were identified that ablated FX-mediated Ad5 transduction with low micromolar potency. The candidate molecules possessed common structural features and formed part of the one pharmacophore model. Focused, mini-libraries were generated with structurally related molecules and in vitro screening revealed novel hits with similar or improved efficacy. The compounds did not interfere with Ad5:FX engagement but acted at a subsequent step by blocking efficient intracellular transport of the virus. In vivo, T5660138 and its closely related analogue T5660136 significantly reduced Ad5 liver transgene expression at 48 h post-intravenous administration of a high viral dose (1 × 10<sup>11</sup> vp/mouse). Therefore, this study identifies novel and potent small molecule inhibitors of the Ad5 transduction which may have applications in the Ad gene therapy setting

Hybrid approaches to teaching: Re-imagining the teaching of a foundational science course during a global pandemic

Access to scientific knowledge, and teaching in the sciences, is believed to be about training because scientific knowledge is, generally, specialised. However, for students to gain full epistemological access in the sciences, they also need to be inducted as scientists and learners of science. We use Bernstein’s regulative and instructional discourse to engage with the notion of epistemological access and effectiveness of a foundational science course. We examine how the course can cultivate scientific identities amongst first year students at a recently established South African university. Our analysis assesses the impact of the forced shift from contact teaching to Emergency Remote Teaching due to the COVID-19 pandemic. We demonstrate that the course was able to begin to facilitate the cultivation of different kinds of knowers in science. However, several gaps remain. Thus, we argue that foundational science lecturers should focus on hybrid teaching approaches to promote enhanced learning amongst students

The OPERA trial : a protocol for the process evaluation of a randomised trial of an exercise intervention for older people in residential and nursing accommodation

Background: The OPERA trial is large cluster randomised trial testing a physical activity intervention to address depression amongst people living in nursing and residential homes for older people. A process evaluation was commissioned alongside the trial and we report the protocol for this process evaluation. Challenges included the cognitive and physical ability of the participants, the need to respect the privacy of all home residents, including study non-participants, and the physical structure of the homes. Evaluation activity had to be organised around the structured timetable of homes, leaving limited opportunities for data collection. The aims of this process evaluation are to provide findings that will assist in the interpretation of the clinical trial results, and to inform potential implementation of the physical activity intervention on a wider scale. Methods/design: Quantitative data on recruitment of homes and individuals is being collected. For homes in the intervention arm, data on dose and fidelity of the intervention delivered; including individual rates of participation in exercise classes are collected. In the control homes, uptake and delivery of depression awareness training is monitored. These data will be combined with qualitative data from an in-depth study of a purposive sample of eight homes (six intervention and two control). Discussion: Although process evaluations are increasingly funded alongside trials, it is still rare to see the findings published, and even rarer to see the protocol for such an evaluation published. Process evaluations have the potential to assist in interpreting and understanding trial results as well as informing future roll-outs of interventions. If such evaluations are funded they should also be reported and reviewed in a similar way to the trial outcome evaluation

Smooth and sharp creation of a pointlike source for a (3+1)-dimensional quantum field

We analyze the smooth and sharp creation of a pointlike source for a quantized massless scalar field in (3+1)-dimensional Minkowski spacetime, as a model for the breakdown of correlations that has been proposed to occur at the horizon of an evaporating black hole. The creation is implemented by a time-dependent self-adjointness parameter at the excised spatial origin. In a smooth creation, the renormalized energy density is well defined away from the source, but it is unbounded both above and below: the outgoing pulse contains an infinite negative energy, while a cloud of infinite positive energy lingers near the fully-formed source. In the sharp creation limit, diverges everywhere in the timelike future of the creation event, and so does the response of an Unruh-DeWitt detector that operates in the timelike future of the creation event. The source creation is significantly more singular than the corresponding process in 1 + 1 dimensions, analyzed previously, and it may be sufficiently singular to break quantum correlations as proposed in a black hole spacetime