Staged surgical palliation and ventricular performance in functionally single ventricle anatomy

This thesis reports a series of laboratory and clinical studies designed to investigate the acute effect of surgical palliation on ventricular function in children with functionally single ventricle anatomy. Ventricular volume and pressure were measured using a combined pressure-conductance catheter. Initial laboratory-based experiments were performed using a physical model of the left ventricle, which allowed examination of the measurement techniques used in the clinical studies but under controlled conditions. These experiments identified a non-linear conductance-absolute volume relationship and demonstrated for the first time that the calibration coefficient, $\alpha_{SV}$ produced a significant, volume-dependent measurement error. These experiments also demonstrated that conductance volume measurements were adversely influenced by other electrical signals. The ventricular electrogram produced clinically important measurement error that has not previously been described. Two clinical studies were then undertaken to investigate the separate effects of the bidirectional cavo-pulmonary anastomosis (BCPA) and the completion total cavo-pulmonary connection (TCPC). These studies represent the core of the thesis. Both procedures were associated with significant changes in the pressure and volume conditions of the dominant ventricle. In addition, the BCPA was associated with a substantial and immediate improvement in ventricular systolic function but this was accompanied by an increase in diastolic chamber stiffness. By contrast, the TCPC was not associated with a significant change ventricular systolic or diastolic function in spite of the changes in ventricular load. Comparable changes were observed in patients with a dominant ventricle of either left or right ventricular morphology. These studies provide a more detailed understanding about the acute events that accompany surgical palliation in children with functionally single ventricle anatomy. These findings confirm the validity of staged surgical palliation in the management of these children

Extra cellular volume imaging of left ventricular walls in children with congenital heart diseases and impaired ventricular function

Background/Hypothesis: In children with congenital heart diseases, myocardial fibrosis is a possible long term complication with impairment of left ventricular function. Extra-Cellular Volume (ECV) imaging of left ventricular (LV) walls using Cardiac Magnetic Resonance Imaging (CMR) offers early detection of fibrosis before late gadolineum enhancement (LGE) changes are seen. Aim of the study was to determine ECV of a cohort of children with congenital heart diseases and any association with their left ventricular function. Materials and Methods: 19 children with congenital cardiac conditions who had undergone CMR from March to December 2016 at Birmingham Children’s Hospital UK were included in the study. All subjects underwent CMR (Siemens Avanto 1.5 T scanner) to assess LV function, measurement of ECV on T1- mapping (MOLLI sequence) and standard late gadolinium enhancement (LGE) imaging. ECV values were determined from 5 different LV wall segments on short axis images (inter-ventricular septum, anterior, antero-lateral, inferio-lateral, inferior segments). Results: 4 children (age 10.9 ±3.9 years old) had impaired LV ejection fraction (44.5±6.0%) and increased LV end diastolic volume indexed (82.2± 14.5 ml.m2). One of the children had LGE changes seen on the inter-ventricular septum. ECV parameters of the inter-ventricular septum were higher in children with impaired LV function (38.6±7.0% vs 30.0±3.5%, p= 0.002). No significant difference were found in the ECV of LV free walls (32.2± 5.2% vs 28.7 ±5.7%, p =0.279). Conclusions: ECV technique has promising possibility in detection of myocardial fibrosis in children with impaired LV function, similar as adult studies. In those with poor LV function, there is a strong possibility that area of fibrosis is in the inter-ventricular septum. However, normal ECV parameters will need to be determined first in children before comparing with those with cardiac illnesses

Post-Pandemic Cities: An Urban Lexicon of Accelerations/Decelerations

COVID-19 has stimulated renewed societal and academic debate about the future of cities and urban life. Future visons have veered from the ‘death of the city’ to visual renderings and limited experiments with 15-minute neighbourhoods. Within this context, we as a diverse group of urban scholars sought to examine the emergent ‘post’-COVID city through the production of an urban lexicon that investigates its socio-material contours. The urban lexicon makes three contributions. First, to explore how the pandemic has accelerated certain processes and agendas while at the same time, other processes, priorities and sites have been decelerated and put on hold. Second, to utilise this framing to examine the impacts of the pandemic on how cities are governed, on how urban geographies are managed and lived, and with how care emerged as a vital urban resource. Third, to tease out what might be temporary intensifications and what may become configurational in a variety of urban domains, including governance, platforming, density, crowds, technosolutionism, dwelling, respatialisation, reconcentration, care, improvisation, and atmosphere. The urban lexicon proposes a vocabulary for delineating, describing, and understanding some of the key aspects of the emergent post-pandemic city

Soft branes in supersymmetry-breaking backgrounds

We revisit the analysis of effective field theories resulting from non-supersymmetric perturbations to supersymmetric flux compactifications of the type-IIB superstring with an eye towards those resulting from the backreaction of a small number of anti-D3-branes. Independently of the background, we show that the low-energy Lagrangian describing the fluctuations of a stack of probe D3-branes exhibits soft supersymmetry breaking, despite perturbations to marginal operators that were not fully considered in some previous treatments. We take this as an indication that the breaking of supersymmetry by anti-D3-branes or other sources may be spontaneous rather than explicit. In support of this, we consider the action of an anti-D3-brane probing an otherwise supersymmetric configuration and identify a candidate for the corresponding goldstino.Comment: 36+5 pages. References added, minor typos correcte

Why does urban Artificial Intelligence (AI) matter for urban studies? Developing research directions in urban AI research

New digital technologies and systems are being extensively applied in urban contexts. These technologies and systems include algorithms, robotics, drones, Autonomous Vehicles (AVs) and autonomous systems that can collectively be labelled as Artificial Intelligence (AI). Critical debates have recognized that these various forms of AI do not merely layer onto existing urban infrastructures, forms of management and practices of everyday life. Instead, they have social and material power: they perform work, anticipate and assess risks and opportunities, are aberrant or glitchy, cause accidents, and make new demands on humans as well as the design of cities. And yet, urban scholars have only recently started to engage with research on urban AI and to begin articulating research directions for urban development beyond the current focus on smart cities. To enhance this engagement, this intervention explores three sets of questions: what is distinctive about this novel way of thinking about and doing cities; what are the emerging mutual interdependencies and interrelations between AI and their urban contexts; and what are the consequent challenges and opportunities for urban governance. In closing, we outline research directions shaped around new research questions raised by the emergence of urban AI

IMPLEmenting a clinical practice guideline for acute low back pain evidence-based manageMENT in general practice (IMPLEMENT) : cluster randomised controlled trial study protocol

Background: Evidence generated from reliable research is not frequently implemented into clinical practice. Evidence-based clinical practice guidelines are a potential vehicle to achieve this. A recent systematic review of implementation strategies of guideline dissemination concluded that there was a lack of evidence regarding effective strategies to promote the uptake of guidelines. Recommendations from this review, and other studies, have suggested the use of interventions that are theoretically based because these may be more effective than those that are not. An evidencebased clinical practice guideline for the management of acute low back pain was recently developed in Australia. This provides an opportunity to develop and test a theory-based implementation intervention for a condition which is common, has a high burden, and for which there is an evidence-practice gap in the primary care setting. Aim: This study aims to test the effectiveness of a theory-based intervention for implementing a clinical practice guideline for acute low back pain in general practice in Victoria, Australia. Specifically, our primary objectives are to establish if the intervention is effective in reducing the percentage of patients who are referred for a plain x-ray, and improving mean level of disability for patients three months post-consultation. Methods/Design: This study protocol describes the details of a cluster randomised controlled trial. Ninety-two general practices (clusters), which include at least one consenting general practitioner, will be randomised to an intervention or control arm using restricted randomisation. Patients aged 18 years or older who visit a participating practitioner for acute non-specific low back pain of less than three months duration will be eligible for inclusion. An average of twenty-five patients per general practice will be recruited, providing a total of 2,300 patient participants. General practitioners in the control arm will receive access to the guideline using the existing dissemination strategy. Practitioners in the intervention arm will be invited to participate in facilitated face-to-face workshops that have been underpinned by behavioural theory. Investigators (not involved in the delivery of the intervention), patients, outcome assessors and the study statistician will be blinded to group allocation. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN012606000098538 (date registered 14/03/2006).The trial is funded by the NHMRC by way of a Primary Health Care Project Grant (334060). JF has 50% of her time funded by the Chief Scientist Office3/2006). of the Scottish Government Health Directorate and 50% by the University of Aberdeen. PK is supported by a NHMRC Health Professional Fellowship (384366) and RB by a NHMRC Practitioner Fellowship (334010). JG holds a Canada Research Chair in Health Knowledge Transfer and Uptake. All other authors are funded by their own institutions

ETHNOVETERINARY APPLICATION OF MORINDA CITRIFOLIA FRUIT PUREE ON A COMMERCIAL HEIFER REARING FACILITY WITH ENDEMIC SALMONELLOSIS

Abstract We have previously reported that Morinda citrifolia (noni) puree modulates neonatal calves developmental maturation of the innate and adaptive immune system. In this study, the effect of noni puree on respiratory and gastrointestinal (GI), health in preweaned dairy calves on a farm with endemic salmonellosis was examined. Two clinical trials were conducted whereby each trial evaluated one processing technique of noni puree. Trials 1 and 2 tested noni versions A and B, respectively. Puree analysis and trial methods were identical to each other, with the calf as the experimental unit. Calves were designated to 1 of 3 treatment groups in each trial and received either: 0, 15 or 30 mL every 12 hr of noni supplement for the first 3 weeks of life. Health scores, weaning age, weight gain from admission to weaning, and weaned by 6 weeks, were used as clinical endpoints for statistical analysis. In trial 1, calves supplemented with 15 mL noni puree of version A every 12 hr had a higher probability of being weaned by 6 weeks of age than control calves (P = 0.04). In trial 2, calves receiving 30 mL of version B every 12 hr had a 54.5% reduction in total medical treatments by 42 days of age when compared to controls (P = 0.02). There was a trend in reduced respiratory (61%), and GI (52%) medical treatments per calf when compared to controls (P = 0.06 and 0.08, respectively). There were no differences in weight gain or mortality for any treatment group in either trial

The impact of digital start-up founders’ higher education on reaching equity investment milestones

This paper builds on human capital theory to assess the importance of formal education among graduate entrepreneurs. Using a sample of 4.953 digital start-ups the paper evaluates the impact of start-up founding teams’ higher education on the probability of securing equity investment and subsequent exit for investors. The main findings are: (1), teams with a founder that has a technical education are less likely to remain self-financed and are more likely to secure equity investment and to exit, but the impact of technical education declines with higher level degrees, (2) teams with a founder that has doctoral level business education are less likely to remain self-financed and have a higher probability of securing equity investment, while undergraduate and postgraduate business education have no significant effect, and (3) teams with a founder that has an undergraduate general education (arts and humanities) are less likely to remain self-financed and are more likely to secure equity investment and exit while postgraduate and doctoral general education have no significant effect on securing equity investment and exit. The findings enhance our understanding of factors that influence digital start-ups achieving equity milestones by showing the heterogeneous influence of different types of higher education, and therefore human capital, on new ventures achieving equity milestones. The results suggest that researchers and policy-makers should extend their consideration of universities entrepreneurial activity to include the development of human capital

Vaccine antigens modulate the innate response of monocytes to Al(OH)3.

Aluminum-based adjuvants have widely been used in human vaccines since 1926. In the absence of antigens, aluminum-based adjuvants can initiate the inflammatory preparedness of innate cells, yet the impact of antigens on this response has not been investigated so far. In this study, we address the modulating effect of vaccine antigens on the monocyte-derived innate response by comparing processes initiated by Al(OH)3 and by Infanrix, an Al(OH)3-adjuvanted trivalent combination vaccine (DTaP), containing diphtheria toxoid (D), tetanus toxoid (T) and acellular pertussis (aP) vaccine antigens. A systems-wide analysis of stimulated monocytes was performed in which full proteome analysis was combined with targeted transcriptome analysis and cytokine analysis. This comprehensive study revealed four major differences in the monocyte response, between plain Al(OH)3 and DTaP stimulation conditions: (I) DTaP increased the anti-inflammatory cytokine IL-10, whereas Al(OH)3 did not; (II) Al(OH)3 increased the gene expression of IFNγ, IL-2 and IL-17a in contrast to the limited induction or even downregulation by DTaP; (III) increased expression of type I interferons-induced proteins was not observed upon DTaP stimulation, but was observed upon Al(OH)3 stimulation; (IV) opposing regulation of protein localization pathways was observed for Al(OH)3 and DTaP stimulation, related to the induction of exocytosis by Al(OH)3 alone. This study highlights that vaccine antigens can antagonize Al(OH)3-induced programming of the innate immune responses at the monocyte level