The Impact of Vein Mechanical Compliance on Arteriovenous Fistula Outcomes

© 2016 Elsevier Inc. Background Arteriovenous fistulae (AVFs) are the preferred access for hemodialysis but suffer a high early failure rate. The aim of this study was to determine how venous distensibility, as measured in vitro, relates to early outcomes of AVF formed with the sampled vein. Methods Ethical approval was obtained for all aspects of this study. During AVF formation a circumferential segment of the target vein was sampled. Mechanical stress testing of the venous segments was undertaken using a dynamic mechanical analyzer, with progressive stress loading at 2 N/min to a maximum of 10 N or until sample disruption. Stress-strain curves were obtained for vein samples and Young's modulus (YM) calculated. Duplex assessment of the fistulae was undertaken at 30 days. Results Thirty patients consented to participate with 29 samples obtained for analysis. Statistical comparison of YM demonstrated no relationship with common cardiovascular risk factors or dialysis status. Subject age greater than 65 was the only patient factor which showed a significant difference in YM (P = 0.05). Furthermore, a negative correlation was confirmed between age and YM (Pearson's r = -0.465, P < 0.05). Nine of the 29 subjects suffered an early AVF failure. Mann-Whitney U testing for differences in distribution reported that YM was significantly higher in those fistulas which failed (P < 0.005). Conclusions Reduced venous compliance appears to result in higher failure rates of AVFs. With the advancement of clinical tools such as speckle tracing ultrasound identification of vessel compliance in vivo may produce valuable additional information for clinicians planning AVF surgery

Investigating the use of Deep Learning Algorithms to Automatically Score Micronuclei in Human Cell Lines

The in vitro micronucleus (MN) assay is a globally used test to quantify DNA damage induced by test chemicals from various industries such as pharmaceuticals, cosmetics and agriculture. Currently, manual scoring is used which is extremely time-consuming and scorer subjective so causes a significant bottleneck in the use of the MN assay. This project shows that imaging flow cytometry coupled with deep learning neural networks can be reliably and accurately used with inter-laboratory function, to automatically score micronucleus events in chemically exposed human B lymphoblastoid cells called TK6 cells. Images were taken from both the cytokinesis-block micronucleus (CBMN) assay and the mononucleate MN assay at Newcastle University. Six different chemicals were tested in this study which are known genotoxic agents and known non-genotoxic agents: aroclor, carbendazim, methyl methanosulphate (MMS), vinblastine, benzo(a)pyrene, D-mannitol. These images were then inputted into a “Deep Flow” neural network, coded in the MATLAB platform which was previously trained on human-scored images assembled from the CBMN assay conducted by Cardiff and Cambridge universities, using MMS and carbendazim treated TK6 cells. Using image data from multiple laboratories in this study provides evidence that the neural network can be used to score unseen data from any laboratory. The neural network correctly scores micronucleus events for both the CBMN and mononucleate MN assays at a percentage confidence of 70% and above. Dose response data for each chemical is parallel to ECVAM guidelines. The aneugen, carbendazim, was shown by the deep learning algorithm to increase the mean dose response by 3.4-fold which shows that as the dose of carbendazim increases, the abundance of micronuclei increases. Further optimisation of the ground truth will prevent underscoring of micronuclei in binucleated cells. It can be concluded that with further optimisation and development of the neural network, this automated platform offers a great potential for the use of the in vitro MN assay to be widened. This method has a higher throughput and has the capability to test greater numbers of compounds and chemicals, therefore, this method will be able to keep up with the increasing demand for genotoxicity testing in industrial and pharmaceutical settings

The role of peroneal nerve electrical neuromuscular stimulation in the augmentation of lower limb circulatory physiology in lower limb arterial and venous disease

Introduction: Studies in healthy volunteers have demonstrated that peroneal nerve stimulation augments blood flow. The studies described within this thesis aimed to establish whether use of the geko™ neuromuscular stimulation device was effective and augments arterial venous and microcirculatory flow in patients with lower limb arterial and venous disease. The fibrinolytic and angiogenic activity of electrical stimulation within this cohort was also examined. Methods:Ethical approval was obtained for all aspects of the described studies. Participants with claudication, varicose veins or post- operative infrainguinal bypass grafts were assigned to receive either unilateral active stimulation or sham. Duplex assessments of arterial and venous volume flow were performed at baseline and following stimulation. Laser Doppler flowmetry measurements of microcirculatory flow were made continuously throughout the study period. ELISA analysis was undertaken of plasma samples drawn at baseline and following stimulation to determine the effect on vascular endothelial growth factor(VEGF), tissue plasminogen activator(t-PA) and plasminogen activator inhibitor 1(PAI-1). Results:The geko™ device was effective at producing visible muscle contraction in only 59% patients tested due to a combination of oedema and neuropathy. 77 participants were recruited in total to either a proof of concept study or the initial phase of a randomised trial: 30 claudicants (25 active, 5 control), 25 post infrainguinal bypass (19 active, 6 control) and 22 varicose veins (17 active, 5 control). Arterial volume flow increased significantly in all patient groups receiving active stimulation: claudicants 60 ml/ min(P<0.001); infra-inguinal bypass grafts 70ml/min(P<0.001) and varicose veins 80 ml/min(P<0.001). Venous volume flow significantly increased in all patient groups: claudicants 30 ml/min(P=0.001); infra-inguinal bypass grafts 30 ml/min(P=0.004) and varicose veins 80 ml/min(P<0.001).Microcirculatory flow increased in all patient groups: claudicants 22.2 flux units(P<0.001); infra-inguinal bypass grafts 21.8 flux units(P<0.001) and varicose veins 28.4 flux units(P<0.001). ELISA analysis demonstrated no statistically significant change in VEGF or t-PA antigen levels when comparing the active with the passive and control limbs. Peroneal nerve stimulation in the active limbs resulted in a significant decrease in PAI-1 of 34 ng/ml(P<0.001). Conclusion: Transcutaneous peroneal nerve stimulation with the geko™ device is potentially beneficial in patients with lower limb arterial and venous disease. This is primarily due to its ability to augment venous, arterial and microcirculatory flow. The results of this study were influential in the NICE guidance approving its use in vascular patients as a means of DVT prophylaxis.The enhanced fibrinolytic effect, by decreasing levels of PAI-1, warrants further investigation.[Thesis also includes articles published in the following journals:Blood coagulation & fibrinolysis: http://journals.lww.com/bloodcoagulation/Abstract/2016/04000/Fibrinolytic_effects_of_peroneal_nerve_stimulation.8.aspxdoi: 10.1097/MBC.0000000000000409European journal of clinical investigation:http://onlinelibrary.wiley.com/doi/10.1111/eci.12244/fulldoi: 10.1111/eci.12244Hypertension research:http://www.nature.com/hr/journal/v36/n3/full/hr2012144a.htmldoi:10.1038/hr.2012.144

Decision Making Towards Maternal Health Services in Central Java, Indonesia

Background: Indonesia has always been struggling with maternal health issue even after the Millennium Development Goals (MDGs) programs were done. Prior research findings identified many factors which influenced maternal health status in developing countries such Indonesia and even though various efforts had been made, the impact of the transformation of maternal health behavior was minimal.Purpose: This study aimed to seek an understanding of the factors influencing decisions towards maternal health services.Methods: A case study with a single case embedded design was employed. Interviews and Focus Group Discussions (FGDs) were held to collect data from 3 health workers and 40 maternal women in a sub-district in Central Java, Indonesia.Results: Interviews with the village midwives as the main health providers in the Getasan sub-district concluded that there were several factors influencing the women\u27s decisions towards maternal services. The factors were options to have services with other health workers outside the area, and shaman services as alternative care and family influencing maternal health behaviors. The analysis of the FGDs also supported the village midwives\u27 statements that in spite of their awareness towards the available maternal health services, the existence of shamans and traditional beliefs strongly affected their decision.Conclusion: The findings in this study showed that cultural issues prevented the maximum maternal health status in Getasan sub-district. This study recommends Puskesmas (Primary Health Care) as the first level of health institutions in Indonesia to support the village midwives\u27 roles within their target area

Storying student belonging in UK higher education

This paper explores how storying can be used to uncover experiences of student belonging throughout their time in Higher Education. It adopts a framing of belonging that is fluid and which recognises shifting notions of belonging over time. A focus on storying is particularly useful for understanding belonging as it enables university staff to listen carefully and with empathy to what matters to students, what shapes their experiences, and how to communicate these in a way which invites positive action. Through storying with undergraduate student articulations gathered through a survey, interviews and focus groups at a university in the UK, the paper identifies the multifaceted and connected spaces of belonging, temporalities and relationships that come to affect student belonging. Ultimately the paper argues for the collective responsibility of staff and students to create a space of belonging for all, rather than the prevalent discourse which often puts the onus on an individual to “fit in”

Exploring the Impact of COVID-19 on the Postnatal Period for First-time Mothers Experiencing Postnatal Depression: a Thematic Analysis

Research has identified the negative impact that postnatal depression has on new mothers' wellbeing and that of their family. With mothers in the postnatal period facing unique challenges during the COVID-19 pandemic, there is an increased need to explore the effects of the pandemic on mothers experiencing postnatal depression to understand where support may be needed. A systematic literature review highlighted a gap in this area of inquiry. This study employed a qualitative approach to explore the impact of COVID-19 on the postnatal period for first-time mothers experiencing postnatal depression. Using semi-structured interviews, this research sought to understand the experiences of 12 first-time mothers who experienced postnatal depression during the pandemic. Five main themes were identified through analysis: 'fear of COVID-19', 'being alone', 'relationship with services', 'impact on partner relationships' and 'coping strategies'. Nine respective subthemes were constructed, which identified that COVID-19 had a predominantly negative impact on the wellbeing of new mothers experiencing postnatal depression, however, there were some advantages to their partner being home for several participants. Findings are discussed in relation to the wider literature and the implications are presented, alongside a critical appraisal of the research. Recommendations for future research will also be outlined

Furthering a Synergetic Sustainability Curriculum at The Ohio State University

Course Code: AEDECON 4567This project contributes to a larger initiative by the Ohio State University (OSU) to further transdisciplinary environmental and sustainability education. The goal of our project was to assist OSU in developing a comprehensive framework for delivering sustainability education. We provided benchmark information from 8 peer institutions, survey results, and set of recommendations with which these groups could begin the development process.Academic Major: Environment, Economy, Development, and Sustainabilit

Anti-schistosomal activities of quinoxaline-containing compounds: From hit identification to lead optimisation

Schistosomiasis is a neglected disease of poverty that is caused by infection with blood fluke species contained within the genus Schistosoma. For the last 40 years, control of schistosomiasis in endemic regions has predominantly been facilitated by administration of a single drug, praziquantel. Due to limitations in this mono-chemotherapeutic approach for sustaining schistosomiasis control into the future, alternative anti-schistosomal compounds are increasingly being sought by the drug discovery community. Herein, we describe a multi-pronged, integrated strategy that led to the identification and further exploration of the quinoxaline core as a promising anti-schistosomal scaffold.Firstly, phenotypic screening of commercially available small molecules resulted in the identification of a moderately active hit compound against Schistosoma mansoni (1, EC50 = 4.59 μM on schistosomula). Secondary exploration of the chemical space around compound 1 led to the identification of a quinoxaline-core containing, non-genotoxic lead (compound 22). Compound 22 demonstrated substantially improved activities on both intra-mammalian (EC50 = 0.44 μM, 0.20 μM and 84.7 nM, on schistosomula, juvenile and adult worms, respectively) and intra-molluscan (sporocyst) S. mansoni lifecycle stages. Further medicinal chemistry optimisation of compound 22, resulting in the generation of 20 additional analogues, improved our understanding of the structure-activity relationship and resulted in considerable improvements in both anti-schistosome potency and selectivity (e.g. compound 30; EC50 = 2.59 nM on adult worms; selectivity index compared to the HepG2 cell line = 348). Some derivatives of compound 22 (e.g. 31 and 33) also demonstrated significant activity against the two other medically important species, Schistosoma haematobium and Schistosoma japonicum. Further optimisation of this class of anti-schistosomal is ongoing and could lead to the development of an urgently needed alternative to praziquantel for assisting in schistosomiasis elimination strategies