Search results for: Kirsty Biggs

Authors: Kirsty Biggs, Peter Larsen-Disney

Abstract:

Background: The UK cervical screening programme significantly reduces cancer mortality through the early detection of abnormal cells. Despite this, over a quarter of eligible women choose not to attend their appointment. Objective: To qualitatively explore patients’ barriers to attending cervical smear appointments and identify key trends of cervical screening behaviour, knowledge, and attitudes in primary and secondary care. Methods: A cross-sectional study was conducted to evaluate smear services in Brighton and Hove using questionnaires in general practice and colposcopy. 226 patients participated in the voluntary questionnaire between 10/11/2017 and 02/02/2018. 118 patients were recruited from general practice surgeries and 108 from the colposcopy department. Women were asked about their smear knowledge, self-perceived risks factors, prior experiences and reasons for non-attendance. Demographic data was also collected. Results: Approximately a third of women did not engage in smear testing services. This was consistent across primary and secondary care groups. Over 90% were aware of the role of the screening process in relation to cervical cancer; however, over two thirds believed the smear was also a tool to screen for other pathologies. The most commonly cited reasons for non-attendance were negative emotions or previous experiences. Inconvenient appointment times were also commonly described. In a comparison of attenders versus non-attenders previous negative experiences (p < 0.01) and number of identified risk factors (p = 0.02) were statistically significant with non-attenders describing more prior negative smears and identifying more risk factors. Smear knowledge, risk perception and perceived importance of screening were not significant. Negative previous experiences were described in relation to poor bedside manner, pain, embarrassment and staff competency. Conclusions: In contrary to the literature, our white Caucasian cohort experienced significant barriers to accessing smear services. Women’s prior negative experiences are overriding their perceived importance to attend the screening programme; therefore, efforts need to focus on improving clinical experiences through auditing tools, training and providing a supportive appointment setting. Positive changes can also be expected by improving appointment availabilities with extended hours and self-booking systems.

Keywords: barriers, cervical, Papanicolaou, screening, smear

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Authors: Ricardo Bragança, Tom Vinaimont

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This paper discusses the introduction of processes of self-determined learning (heutagogy) into a graduate course on financial modeling, using elements of entangled pedagogy and Biggs’ constructive alignment. To encourage learners to take control of their own learning journey and develop critical thinking and problem-solving skills, each session in the course receives tailor-made media-enhanced pedagogical assets. The design of those assets specifically supports entangled pedagogy, which opposes technological or pedagogical determinism in support of the collaborative integration of pedagogy and technology. Media assets for each of the ten sessions in this course consist of three components. The first component in this three-pronged approach is a game-cut-like cinematographic representation that introduces the context of the session. The second component represents a character from an open-source-styled community that encourages self-determined learning. The third component consists of a character, which refers to the in-person instructor and also aligns learning outcomes and assessment tasks, using Biggs’ constructive alignment, to the cinematographic and open-source-styled component. In essence, the course's metamorphosis helps students apply the concepts they've studied to actual financial modeling issues. The audio-visual media assets create a storyline throughout the course based on gamified and real-world applications, thus encouraging student engagement and interaction. The structured entanglement of pedagogy and technology also guides the instructor in the design of the in-class interactions and directs the focus on outcomes and assessments. The transformation process of this graduate course in financial modeling led to an institutional teaching award in 2021. The transformation of this course may be used as a model for other courses and programs in many disciplines to help with intended learning outcomes integration, constructive alignment, and Assurance of Learning.

Keywords: innovative education, active learning, entangled pedagogy, heutagogy, constructive alignment, project based learning, financial modeling, graduate business education

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Authors: Mesias Alfeus, Kirsty Fitzhenry, Alessia Lederer

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The present paper provides empirical studies to estimate defaultable bonds in the South African financial market. The main goal is to estimate the unobservable factors affecting bond yields for South African major banks. The maximum likelihood approach is adopted for the estimation methodology. Extended Kalman filtering techniques are employed in order to tackle the situation that the factors cannot be observed directly. Multi-dimensional Cox-Ingersoll-Ross (CIR)-type factor models are considered. Results show that default risk increased sharply in the South African financial market during COVID-19 and the CIR model with jumps exhibits a better performance.

Keywords: default intensity, unobservable state variables, CIR, α-CIR, extended kalman filtering

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Authors: Zoe Lynch, Kirsty Zieschank

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There are several factors that compromise the utility and wide-spread use of existing emotional and behavioural distress screening instruments. Some of these factors include lengthy administration times, high costs, feasibility issues, and a lack of self-report options for children under 12 years of age. This animation-based resource was developed to overcome as many of these factors as possible. Developed for educators and medical and mental health professionals, this resource offers children a self-guided mechanism for reporting any current emotional and behavioural distress. An avatar assistant, selected by the child, accompanies them through each stage of the screening process, offering further instruction if prompted. Children enter their age and gender before viewing comparative animations conveying common childhood emotional and behavioural difficulties. The child then selects the most relatable animations, along with the frequency with which they experience the depicted emotions. From a perspective of intellectual development, an engaging, animated format means that outcomes will not be constrained by children’s reading, writing, cognitive, or verbal expression abilities. Having been user-tested with children aged 6 to 12, this resource shows promising results as a self-guided screening instrument.

Keywords: animation-based screening instrument, mental health, primary-aged children, self-guided

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Authors: Laura Gantley, Vanessa M. Conn, Stuart Webb, Kirsty Kirk, Marta Gabryelska, Duncan Holds, Brett W. Stringer, Simon J. Conn

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Trinucleotide repeat disorders comprise ~20 severe, inherited human neuromuscular and neurodegenerative disorders, which are a result of an abnormal expansion of repetitive sequences in the DNA. The most common of these, Huntington’s disease, results from the expansion of the CAG repeat region in exon 1 of the HTT gene via an unknown mechanism. Non-coding RNAs have been implicated in the initiation and progression of many diseases; thus, we focus on one circular RNA (circRNA) molecule arising from non-canonical splicing (back splicing) of HTT pre-mRNA. This circRNA and its mouse orthologue were transgenically overexpressed in human cells (SHSY-5Y and HEK293T) and mouse cells (Mb1), respectively. High-content imaging and flow cytometry demonstrated the overexpression of this circRNA reduces cell proliferation, reduces nuclear size independent of cellular size, and alters cell cycle progression. Analysis of protein by western blot and immunofluorescence demonstrated no change to HTT protein levels but altered nuclear-cytoplasmic distribution without impacting the expansion of the HTT repeat region. As these phenotypic and genotypic changes are found in Huntington’s disease patients, these results may suggest that this circRNA may play a functional role in the progression of Huntington’s disease.

Keywords: cell biology, circular RNAs, Huntington’s disease, molecular biology, neurodegenerative disorders

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Authors: Kirsty Liddiard

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In this paper, we detail the politics and practicalities of co-produced disability research with disabled young people with life-limiting and life-threatening impairments in our ESRC funded project, Life, Death, Disability and the Human: Living Life to the Fullest. We centre our Co-Researcher Collective of disabled young people who, through virtual research methods and social technologies, are co-leading this innovative project exploring the lives, hopes, desires and ambitions of young disabled people living short(er) lives. Co-production is an established approach; however, our co-researchers have led us to develop inclusive and transformative research practices that engage with online social research methods in innovative ways. Through this discussion, we demarcate the Academy and ‘research process’ as potentially deeply ableist spaces that propogate the normative researcher as non-disabled; someone integrated into the Academy and insecure employment; and who enacts normative modes of leadership. We use our experiences of co-production in Living Life to the Fullest, then, to show that research – as a discipline, a set of politics, and scholarly practice – must be transformed in order to enable new inclusive research futures that support meaningful co-production with marginalised young people. In conclusion, as we detail our experiences, we aim to encourage disability studies researchers and others to adopt virtual environments and social technologies when researching with and for the lives of disabled people.

Keywords: co-production, illness, youth, technology

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Authors: James Britton, Vijaya Krishna, Manus Biggs, Abhay Pandit

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Regeneration of the spinal cord after injury remains a great challenge due to the complexity of this organ. Inflammation and gliosis at the injury site hinder the outgrowth of axons and hence prevent synaptic reconnection and reinnervation. Hyaluronic acid (HA) is the main component of the spinal cord extracellular matrix and plays a vital role in cell proliferation and axonal guidance. In this study, we have synthesized and characterized a photo-cross-linkable HA-tyramine (tyr) hydrogel from a chemical, mechanical, electrical, biological and structural perspective. From our experimentation, we have found that HA-tyr can be synthesized with controllable degrees of tyramine substitution using click chemistry. The complex modulus (G*) of HA-tyr can be tuned to mimic the mechanical properties of the native spinal cord via optimization of the photo-initiator concentration and UV exposure. We have examined the degree of tyramine-tyramine covalent bonding (polymerization) as a function of UV exposure and photo-initiator use via Photo and Nuclear magnetic resonance spectroscopy. Both swelling and enzymatic degradation assays were conducted to examine the resilience of our 3D printed hydrogel constructs in-vitro. Using a femtosecond 780nm laser, the two-photon polymerization of HA-tyr hydrogel in the presence of riboflavin photoinitiator was optimized. A laser power of 50mW and scan speed of 30,000 μm/s produced high-resolution spatial patterning within the hydrogel with sustained mechanical integrity. Using dorsal root ganglion explants, the cytocompatibility of photo-crosslinked HA-tyr was assessed. Using potentiometry, the electrical conductivity of photo-crosslinked HA-tyr was assessed and compared to that of native spinal cord tissue as a function of frequency. In conclusion, we have developed a biocompatible hydrogel that can be used for photolithographic 3D printing to fabricate tissue engineered constructs for neural tissue regeneration applications.

Keywords: 3D printing, hyaluronic acid, photolithography, spinal cord injury

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Authors: Patrick C. H. Morel, Ian W. Barugh, Kirsty L. Chidgey

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The aim of this study was to quantify the level of piglet deaths in outdoor farrowing systems in New Zealand. A total of 14 farms were visited, the farmers interviewed, and data collected. A total of 10,154 sows were kept on those farms representing an estimated 33% of the NZ sow herd or 80% of the outdoor sow herd in 2016. Data from 25,911 litters was available for the different analyses. The characteristics and reproductive performance for the years 2015-2016 from the 14 farms surveyed in this study were analysed, and the following results were obtained. The average percentage of stillbirths was 7.1% ranging between 3.5 and 10.7%, and the average pre-weaning live-born mortality was 16.7% ranging between 3.7% and 23.6%. The majority of piglet deaths (89%) occurred during the first week after birth, with 81% of deaths occurring up to day three. The number of piglets born alive was 12.3 (8.0 to 14.0), and average number of piglets weaned per sow per year was 22.4, range 10.5-27.3. The average stocking rate per ha (number of sows and mated gilts) was 15.3 and ranged from 2.8 to 28.6. The sow to boar ratio average was 20.9:1 and the range was 7.1: 1 to 63:1. The sow replacement rate ranged between 37% and 78%. There was a large variation in the piglet live-born mortality both between months within a farm and between farms within a given month. The monthly recorded piglet mortality ranged between 7.7% and 31.5%, and there was no statistically significant difference between months on the number of piglets born, born alive, weaned or on pre-weaning piglet mortality. Twelve different types of hut/farrowing systems were used on the 14 farms. No difference in piglet mortality was observed between A-Frame, A-Frame Modified and for Box-shape huts. There was a positive relationship between the average number of piglets born per litter and the number of piglets born alive (r=0.975) or the number weaned per litter (r=0.845). Moreover, as the average number of piglets born-alive increases, both pre-weaning live-born mortality rate and the number of piglets weaned increased. An increase of 1 piglet in the number born alive corresponds to an increase of 2.9% in live-born mortality and an increase of 0.56 piglets weaned. Farmers reported that staff are the key to success with the key attributes being: good and reliable with attention to detail and skills with the stock.

Keywords: mortality, piglets, outdoor, pig farm

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Authors: Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Lucinda Kurzava, Hannah Buvala, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M. Flanagan, Barbara Stefanska

Abstract:

Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, is the second leading cause of cancer death worldwide. Late onset of clinical symptoms in HCC results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable early detection biomarkers that can distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed and could increase the cure rate from 5% to 80%. We used Illumina-450K microarray to test whether blood DNA, an easily accessible source of DNA, bear site-specific changes in DNA methylation in response to HCC before diagnosis with conventional tools (pre-diagnostic). Top 11 differentially methylated sites were selected for validation by pyrosequencing. The diagnostic potential of the 11 pyrosequenced probes was tested in blood samples from a prospective cohort of cirrhotic patients. We identified 971 differentially methylated CpG sites in pre-diagnostic HCC cases as compared with healthy controls (P < 0.05, paired Wilcoxon test, ICC ≥ 0.5). Nearly 76% of differentially methylated CpG sites showed lower levels of methylation in cases vs. controls (P = 2.973E-11, Wilcoxon test). Classification of the CpG sites according to their location relative to CpG islands and transcription start site revealed that those hypomethylated loci are located in regulatory regions important for gene transcription such as CpG island shores, promoters, and 5’UTR at higher frequency than hypermethylated sites. Among 735 CpG sites hypomethylated in cases vs. controls, 482 sites were assigned to gene coding regions whereas 236 hypermethylated sites corresponded to 160 genes. Bioinformatics analysis using GO, KEGG and DAVID knowledgebase indicate that differentially methylated CpG sites are located in genes associated with functions that are essential for gene transcription, cell adhesion, cell migration, and regulation of signal transduction pathways. Taking into account the magnitude of the difference, statistical significance, location, and consistency across the majority of matched pairs case-control, we selected 11 CpG loci corresponding to 10 genes for further validation by pyrosequencing. We established that methylation of CpG sites within 5 out of those 10 genes distinguish cirrhotic patients who subsequently developed HCC from those who stayed cancer free (cirrhotic controls), demonstrating potential as biomarkers of early detection in populations at risk. The best predictive value was detected for CpGs located within BARD1 (AUC=0.70, asymptotic significance ˂0.01). Using an additive logistic regression model, we further showed that 9 CpG loci within those 5 genes, that were covered in pyrosequenced probes, constitute a panel with high diagnostic accuracy (AUC=0.887; 95% CI:0.80-0.98). The panel was able to distinguish pre-diagnostic cases from cirrhotic controls free of cancer with 88% sensitivity at 70% specificity. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established biomarker panel has high potential to be developed into a routine clinical test after validation in larger cohorts. This study was supported by Showalter Trust, American Cancer Society (IRG#14-190-56), and Purdue Center for Cancer Research (P30 CA023168) granted to BS.

Keywords: biomarker, DNA methylation, early detection, hepatocellular carcinoma

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