64623 research outputs found
Sort by
Spatially Resolved Cancer Growth Modelling for Drug Development
Full text linkMathematical models used in preclinical drug discovery tend to be based on empirical growth laws.Such models are well suited to fitting the data available, mostly longitudinal studies of tumourvolume. However, they typically have little connection with the underlying physiological processesand, in general, are not spatially resolved. This lack of a mechanistic underpinning restricts theirflexibility and inhibits their direct translation across studies.In this thesis we build on the well-studied continuum approach of modelling cancerous tumourgrowth. We present a spatially resolved mathematical model describing tumour growth for theevaluation of single agent cytotoxic compounds that is based on nutrient di↵usion. Upon assuminga spherical geometry for the tumour we show that the model can predict spatial distributions ofcell subpopulations, tumour growth fraction, as well as spatial drug distribution within tumours.Importantly, we demonstrate the model can be reduced to a growth law similar in form to thosecurrently implemented in pharmaceutical drug development for preclinical trials so that it can beintegrated into the current workflow. By validating this approach for both Cell-derived xenograft(CDX) and Patient-derived xenograft (PDX) data, we show that our theoretical model fits aswell as the best performing and most widely used models in drug discovery. Our work openscurrent preclinical modelling studies to also incorporating spatially resolved and multi-modal datawithout significant added complexity and creates the opportunity to improve translation and tumourresponse predictions.Utilising the model we explore the Norton-Simon hypothesis of dose scheduling. Alternativedose schedules are also explored to better reduce the tumour burden and control regrowth whilesatisfying current best practice guidelines of the RECIST criteria.Taking another direction we conduct an initial exploration into the e↵ects of delayed proliferationof the quiescent cell subpopulation on cytotoxic treatment. We do so by extending the previousmodel formulation to incorporate this delay. The result is a system of delay di↵erential equationswhich we solve numerically. This additional complexity is considered because cellular quiescence isthought to provide tumours a mechanism of resistance to treatment. This preliminary work opensup numerous avenues to investigate strategies to avoid such resistance
A data-driven approach for characterising revenues of South-Asian long-haul low-cost carriers per equivalent flight capacity per block hour
No full textThis study sets out to investigate the revenue characteristics of long-haul low-cost carriers (LHLCCs) in the Southeast Asian market using a recently established metric that calculates revenue per equivalent flight capacity per block hour (REB). REB allows for the accurate comparison of airlines on different routes with varying cabin configurations, and stage lengths. The majority of the data was sourced from Sabre MIDT and OAG, while supplementary data were from other various sources. In addition to REB, the study investigates: How do LHLCCs yields compare to full-service network carriers (FSNCs)? Are LHLCCs positively impacted by smaller share of connecting passengers? Are LHLCCs positively impacted by ancillary revenues? Do LHLCCs benefit from higher load factors and seat densities? Results show that LHLCCs performed 26.6% less in overall REB compared to their FSNC counterpart despite LHLCCs generating 43.9% less yield. This is a result of less revenue diluting connecting passengers, higher average ancillary revenue per block hour, higher average load factors and higher average seat densities for LHLCCs. On a route-level, some LHLCC operations can equally perform or outperform competition's revenue performance. Furthermore, the findings are mostly consistent with earlier REB research conducted on the North Atlantic market by Soyk et al. (2018). Revenue and operating characteristic showed the same trends in both markets, although to varying degrees. This study exposes, with high detail, the revenue generating inner-workings of the elusive long-haul low-cost model in its second largest market, and compares it on equal grounds to their full-service network competition. We learn that airlines can drive the airfare down while minimising the loss of revenue per flight capacity of the aircraft by adjusting for the numerous variables that directly impact it, such as seat density, cabin configuration, ancillary revenues, load factors, and percentage of connecting passengers
PUMILIO competes with AUF1 to control DICER1 RNA levels and miRNA processing
No full textDICER1 syndrome is a cancer predisposition disorder caused by mutations that disrupt the function of DICER1 in miRNA processing. Studying the molecular, cellular and oncogenic effects of these mutations can reveal novel mechanisms that control cell homeostasis and tumor biology. Here, we conduct the first analysis of pathogenic DICER1 syndrome allele from the DICER1 3 UTR. We find that the DICER1 syndrome allele, rs1252940486, abolishes interaction with the PUMILIO RNA binding protein with the DICER1 3 UTR, resulting in the degradation of the DICER1 mRNA by AUF1. This single mutational event leads to diminished DICER1 mRNA and protein levels, and widespread reprogramming of miRNA networks. The in-depth characterization of the rs1252940486 DICER1 allele, reveals important post-transcriptional regulatory events that control DICER1 levels
Sustainable routes for acetic acid production: Traditional processes vs a low-carbon, biogas-based strategy
No full textThe conversion of biogas, mainly formed of CO2 and CH4, into high-value platform chemicals is increasing attention in a context of low-carbon societies. In this new paradigm, acetic acid (AA) is deemed as an interesting product for the chemical industry. Herein we present a fresh overview of the current manufacturing approaches, compared to potential low-carbon alternatives. The use of biogas as primary feedstock to produce acetic acid is an auspicious alternative, representing a step-ahead on carbon-neutral industrial processes. Within the spirit of a circular economy, we propose and analyse a new BIO-strategy with two noteworthy pathways to potentially lower the environmental impact. The generation of syngas via dry reforming (DRM) combined with CO2 utilisation offers a way to produce acetic acid in a two-step approach (BIO-Indirect route), replacing the conventional, petroleum-derived steam reforming process. The most recent advances on catalyst design and technology are discussed. On the other hand, the BIO-Direct route offers a ground-breaking, atom-efficient way to directly generate acetic acid from biogas. Nevertheless, due to thermodynamic restrictions, the use of plasma technology is needed to directly produce acetic acid. This very promising approach is still in an early stage. Particularly, progress in catalyst design is mandatory to enable low-carbon routes for acetic acid production.[Display omitted]•Biogas conversion to acetic acid represents a circular economy route for chemicals manufacturing.•Two new BIO-strategies are proposed to obtain acetic acid from CO2 and CH4.•The implementation of plasma technology in dry reforming represents a step-ahead on carbon-neutral processes.•The state-of-the-art of lab-scale non-thermal plasma dry reforming to value-added products has been reviewed
Successful negotiation of goal conflict between romantic partners predicts better goal outcomes during COVID-19: A mixed methods study
No full textWhen romantic partners' personal goals conflict, this can negatively affect personal goal outcomes, such as progress. In a concurrent mixed methods study, we investigated whether goal conflict and negation of goal conflict were associated with goal outcomes (progress, confidence, motivation) and what strategies partners used during the COVID-19 pandemic to negotiate goal conflict. Survey participants (n = 200) completed a daily diary for a week and weekly longitudinal reports for a month and interview participants (n = 48) attended a semi-structured interview. Results showed that higher goal conflict was associated with lower goal outcomes, and successful negotiation of goal conflict was associated with better goal outcomes. Qualitative analyses identified three goal conflict negotiation strategies (compromise, integration, concession). Conversations focused on both practical and emotional needs and included respectful communication and space from conflict (timeout or avoidance). The mixed methods results suggest that goal conflict was low during the pandemic and participants were often able to negotiate goal conflict resulting in better goal outcomes
Multi‐family therapy for eating disorders across the lifespan: A systematic review and meta‐analysis
No full textEating disorders (EDs) have an estimated prevalence rate of 1%–5% across Europe. Effective adjunct interventions are needed to support the 20%–40% of families whose recovery requires additional support to first line approaches. This systematic review and meta‐analysis aimed to establish whether multi‐ family therapy (MFT) improves the physical and psychological health of patients and family members. Searches were conducted in PsycINFO, MED-LINE, PubMed, EMBASE, CINAHL, and the Cochrane Library in March 2021. 15 studies (850 patients) met the inclusion criteria. Meta‐analysis demonstrated MFT resulted in significant benefits in weight gain, ED symptoms, patients' and parents' depression symptoms, and parents' negative experiences of caregiving. However, significant improvements were only evident when comparisons were drawn before and after the intervention; these dissipated when MFT was compared to another intervention. There was no evidence MFT improves family functioning, positive aspects of caregiving, nor patient and parental anxiety. Intervention completion rates ranged from 86% to 100% indicating a high level of acceptability. Studies varied with regard to intervention length and structure, follow‐up period, and outcome measures uti-lised; most were rated as moderate or weak in methodological quality. More rigorous and large scale randomised controlled trials are needed to fully assess the effectiveness of MFT. </p
A Review on Recent Progress in the Integrated Green Hydrogen Production Processes
Full text linkThe thermochemical water-splitting method is a promising technology for efficiently converting renewable thermal energy sources into green hydrogen. This technique is primarily based on recirculating an active material, capable of experiencing multiple reduction-oxidation (redox) steps through an integrated cycle to convert water into separate streams of hydrogen and oxygen. The thermochemical cycles are divided into two main categories according to their operating temperatures, namely low-temperature cycles (<1100 °C) and high-temperature cycles (<1100 °C). The copper chlorine cycle offers relatively higher efficiency and lower costs for hydrogen production among the low-temperature processes. In contrast, the zinc oxide and ferrite cycles show great potential for developing large-scale high-temperature cycles. Although, several challenges, such as energy storage capacity, durability, cost-effectiveness, etc., should be addressed before scaling up these technologies into commercial plants for hydrogen production. This review critically examines various aspects of the most promising thermochemical water-splitting cycles, with a particular focus on their capabilities to produce green hydrogen with high performance, redox pairs stability, and the technology maturity and readiness for commercial use
The Professional Qualifications Directive. An, as yet, incomplete attempt to fully operationalize the principle of mutual recognition.
Full text link"Mutual recognition constitutes a principle of the EU legal order whose purpose is to alleviate Member State beneficiaries from having to comply to a dual regulatory burden during cross border transactions. It relies on the premise that a destination EU state recognizes the given regulations of an origin member state.The arguments put forward in this thesis are that in the context of the secondary legislation regarding professional qualifications recognition, this premise has not been adhered to; that an alternative paradigm of mutual recognition has been employed instead, such that excludes certain beneficiaries from the recognition equation; and such as to render the operationalization of mutual recognition in this domain incomplete.These arguments raise concerns on several levels. Does the emergence of this new paradigm completely undermine the customary application of the mutual recognition principle? Is there scope for the old traditional paradigm to also be applied to the area related to the recognition of professional qualifications? Is there room for the mutual recognition exercise within the context of the Professional Qualifications Directive to be completed?To address the concerns raised, methodologically, the thesis employs a doctrinal legal research approach calling on primary and secondary EU legislation and associated materials relevant to the mutual recognition principle inclusive of those decisions of the CJEU that relate to the Professional Qualifications Directive. The development and functioning of the principle are examined in detail through the prism of the evolution of the directive.The findings of the thesis suggest that mutual recognition in the area of the free movement of workers remains not fully operationalized. The conclusion of the thesis is that for the mutual recognition exercise, within the context of the Professional Qualifications Directive, to be completed the traditional mode of operation of the principle must be firmly embedded in it.
Stigma management in grief after suicide: A grounded theory study of parental experience
Full text link"Aim: This study aimed to understand the impact of stigma on how parents cope with grief after the suicide of an adult child.Background: Globally, 703,000 suicides occur every year; each one affects between 10-135 people. Studies have suggested that those who are bereaved by suicide are more likely to experience stigma that leads to complications during mourning Few studies have explored the influence of stigma in how parents cope with grief after the suicide of their adult child.Methods: A systematic literature review informed the design of a longitudinal study that used a constructivist grounded theory approach. In total, 12 parents of adult children who had died by suicide were recruited. Semi-structured interviews were conducted at two time points between 2015 and 2016.Findings: Three stigma-related processes emerged from the data: gaining awareness of stigma, hiding stigma and concealment of death, and surviving stigma to cope with grief. The following novel findings were observed; blame is averted from the deceased, acts of remembrance held specific significance and parents become involved in therapeutic activism in order to cope with grief and stigma and prevent further suicides.Conclusion: Building on existing theories of grief and stigma this qualitative work informed the development of a new triple process model of stigma management in coping with grief after suicide.
European Union How Does It Work?
No full textAs the most concise, accessible guide to the EU, The European Union: How does it work? is an ideal introduction for those coming to the subject for the first time. A team of expert scholars cut through the complexity to explain how the EU works, both in theory and in practice, helping students gain the knowledge they need to succeed.A perfect introduction to the EU for those with little or no prior knowledge of the subject: concise and readable, with coverage of the key actors, policies, and developments in the EUAn expert line-up combines leading scholars and practitioners with first-hand experience of the EU's institutions'How it really works' boxes help students connect theory with clear explanations illustrated by real-world examples'Key concepts and terms' boxes, discussion questions and further reading features further support students in broadening their knowledge of the EUA range of boxes throughout the text explore specific cases that highlight how the EU works, what it does, or how it has evolvedAlso available as an e-book with functionality, navigation features, and links that offer extra learning support</p
Data sources:
Access Repository Dashboard
Do you manage University of Surrey? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!