Search results for: Rylands v. Fletcher

Authors: Maria Lubomira Kubica

Abstract:

The paper reveals the birth and evolution of the British precedent Rylands v. Fletcher that, once adopted on the other side of the Ocean (in United States), gave rise to a general clause of liability for abnormally dangerous activities recognized by the §20 of the American Restatements of the Law Third, Liability for Physical and Emotional Harm. The main goal of the paper was to analyze the development of the legal doctrine and of the case law posterior to the precedent together with the intent of the British judicature to leapfrog from the traditional rule contained in Rylands v. Fletcher to a general clause similar to that introduced in the United States and recently also on the European level. As it is well known, within the scope of tort law two different initiatives compete with the aim of harmonizing the European laws: European Group on Tort Law with its Principles of European Tort Law (hereinafter PETL) in which article 5:101 sets forth a general clause for strict liability for abnormally dangerous activities and Study Group on European Civil Code with its Common Frame of Reference (CFR) which promotes rather ad hoc model of listing out determined cases of strict liability. Very narrow application scope of the art. 5:101 PETL, restricted only to abnormally dangerous activities, stays in opposition to very broad spectrum of strict liability cases governed by the CFR. The former is a perfect example of a general clause that offers a minimum and basic standard, possibly acceptable also in those countries in which, like in the United Kingdom, this regime of liability is completely marginalized.

Keywords: Rylands v. Fletcher, strict liability, dangerous activities, general clause

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Authors: Maria Lubomira Kubica

Abstract:

The paper reveals the birth and evolution of the British precedent Rylands v. Fletcher that, once adopted on the other side of the Ocean (in United States), gave rise to a general clause of liability for abnormally dangerous activities recognized by the §20 of the American Restatements of the Law Third, Liability for Physical and Emotional Harm. The main goal of the paper was to analyze the development of the legal doctrine and of the case law posterior to the precedent together with the intent of the British judicature to leapfrog from the traditional rule contained in Rylands v. Fletcher to a general clause similar to that introduced in the United States and recently also on the European level. As it is well known, within the scope of tort law two different initiatives compete with the aim of harmonizing the European laws: European Group on Tort Law with its Principles of European Tort Law (hereinafter PETL) in which article 5:101 sets forth a general clause for strict liability for abnormally dangerous activities and Study Group on European Civil Code with its Common Frame of Reference (CFR) which promotes rather ad hoc model of listing out determined cases of strict liability. Very narrow application scope of the art. 5:101 PETL, restricted only to abnormally dangerous activities, stays in opposition to very broad spectrum of strict liability cases governed by the CFR. The former is a perfect example of a general clause that offers a minimum and basic standard, possibly acceptable also in those countries in which, like in the United Kingdom, this regime of liability is completely marginalized.

Keywords: abnormally dangerous activities, general clause, Rylands v. Fletcher, strict liability

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Authors: Dewi Retno Sari Saputro, Purnami Widyaningsih, Hendrika Handayani

Abstract:

Extreme data on an observation can occur due to unusual circumstances in the observation. The data can provide important information that can’t be provided by other data so that its existence needs to be further investigated. The method for obtaining extreme data is one of them using maxima block method. The distribution of extreme data sets taken with the maxima block method is called the distribution of extreme values. Distribution of extreme values is Gumbel distribution with two parameters. The parameter estimation of Gumbel distribution with maximum likelihood method (ML) is difficult to determine its exact value so that it is necessary to solve the approach. The purpose of this study was to determine the parameter estimation of Gumbel distribution with quasi-Newton BFGS method. The quasi-Newton BFGS method is a numerical method used for nonlinear function optimization without constraint so that the method can be used for parameter estimation from Gumbel distribution whose distribution function is in the form of exponential doubel function. The quasi-New BFGS method is a development of the Newton method. The Newton method uses the second derivative to calculate the parameter value changes on each iteration. Newton's method is then modified with the addition of a step length to provide a guarantee of convergence when the second derivative requires complex calculations. In the quasi-Newton BFGS method, Newton's method is modified by updating both derivatives on each iteration. The parameter estimation of the Gumbel distribution by a numerical approach using the quasi-Newton BFGS method is done by calculating the parameter values that make the distribution function maximum. In this method, we need gradient vector and hessian matrix. This research is a theory research and application by studying several journals and textbooks. The results of this study obtained the quasi-Newton BFGS algorithm and estimation of Gumbel distribution parameters. The estimation method is then applied to daily rainfall data in Purworejo District to estimate the distribution parameters. This indicates that the high rainfall that occurred in Purworejo District decreased its intensity and the range of rainfall that occurred decreased.

Keywords: parameter estimation, Gumbel distribution, maximum likelihood, broyden fletcher goldfarb shanno (BFGS)quasi newton

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Authors: Aaron J. Small, Craig A. Fletcher

Abstract:

This study investigates the effect of closed circuit television (CCTV) image patch layout on performance of a simulated train-platform departure task. The within-subjects experimental design measures target detection rate and response latency during a CCTV visual search task conducted as part of the procedure for safe train dispatch. Three interface designs were developed by manipulating CCTV image patch layout. Eye movements, perceived workload and system usability were measured across experimental conditions. Task performance was compared to identify significant differences between conditions. The results of this study have not been determined.

Keywords: rail human factors, workload, closed circuit television, platform departure, attention, information processing, interface design

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Authors: R. Rajabpour, N. Talebbeydokhti, M. H. Ahmadi

Abstract:

In recent years, new techniques for solving complex problems in engineering are proposed. One of these techniques is JPSO algorithm. With innovative changes in the nature of the jump algorithm JPSO, it is possible to construct a graph-based solution with a new algorithm called G-JPSO. In this paper, a new algorithm to solve the optimal control problem Fletcher-Powell and optimal control of pumps in water distribution network was evaluated. Optimal control of pumps comprise of optimum timetable operation (status on and off) for each of the pumps at the desired time interval. Maximum number of status on and off for each pumps imposed to the objective function as another constraint. To determine the optimal operation of pumps, a model-based optimization-simulation algorithm was developed based on G-JPSO and JPSO algorithms. The proposed algorithm results were compared well with the ant colony algorithm, genetic and JPSO results. This shows the robustness of proposed algorithm in finding near optimum solutions with reasonable computational cost.

Keywords: G-JPSO, operation, optimization, pumping station, water distribution networks

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Authors: Rimma Kiseleva

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The hotel business has a long history. The basis of the service of hospitality industry enterprises is the service, attitude, and consciousness of employees as hospitable “hosts of the house”. It is generally accepted that the founder and main expert of quality service is Caesar Ritz, “the king of hoteliers and the hotelier of kings.” However when deeply immersed in the history of the universe, it turns out that the very first book about hospitality, standardization of guest reception processes and the basics of better service is nothing more than the Bible. A unique study on the topic of considering the Church as a hotel, as well as the hotel business itself as the most gracious work of Jesus Christ Himself, which is confirmed by verses from the Gospel, includes the following approaches: analytical, comparative, empirical. The study shows that it was Jesus Christ who became the founder of the rules of the most sacrificial service, real service to people, filled with brotherly love, humility, love for strangers, those qualities that are the foundation, the “three pillars” of the hospitality industry. And also that the hotel is the most charitable cause, which is still relevant today.

Keywords: Augustine Aurelius, Bible, Gospel, guest house, hospitality, hotel, humility, inn, Jesus Christ, Joseph Fletcher, New Testament, Paul Tillich, service, strangeness

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Authors: Strahinja Kovačević, Jelena Vladić, Senka Vidović, Zoran Zeković, Lidija Jevrić, Sanja Podunavac Kuzmanović

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Supercritical extracts of highly valuated medicinal plant Satureja montana were prepared by application of supercritical carbon dioxide extraction in the carbon dioxide pressure range from 125 to 350 bar and temperature range from 40 to 60°C. Using GC/MS method of analysis chemical profiles (aromatic constituents) of S. montana extracts were obtained. Self-training artificial neural networks were applied to predict the retention time of the analyzed terpenes in GC/MS system. The best ANN model obtained was multilayer perceptron (MLP 11-11-1). Hidden activation was tanh and output activation was identity with Broyden–Fletcher–Goldfarb–Shanno training algorithm. Correlation measures of the obtained network were the following: R(training) = 0.9975, R(test) = 0.9971 and R(validation) = 0.9999. The comparison of the experimental and predicted retention times of the analyzed compounds showed very high correlation (R = 0.9913) and significant predictive power of the established neural network.

Keywords: ANN regression, GC/MS, Satureja montana, terpenes

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Authors: Kim Nolte, Ben J. M. Steyn, Pieter E. Krüger, Lizelle Fletcher

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Objective: The primary aim of this research was to determine the attitudes, beliefs and knowledge of talented young South African athletes regarding prohibited performance-enhancing drugs (PEDs) and anti-doping rules and regulations. Methods: This was a survey study and a quantitative research approach was used. South African TuksSport academy athletes at the High Performance Centre, University of Pretoria and competitive high school athletes at four private high schools in Gauteng completed the survey. A self-determined structured questionnaire was used to establish the attitudes, beliefs and knowledge of the athletes. Results: A total of 346 (208 males, 138 females) athletes, age (mean ± SD) 16.9 ±1.41 years participated in the survey. According to this survey, 3.9% of the athletes in this survey admitted to be using a prohibited PED and more than 14% of the athletes said they would consider using a prohibited PED if they knew they would not get caught out. Ambition (46%) and emotional pressure (22.5%) was the primary reasons why the athletes would consider using prohibited PEDs. Even though coaches appear to be the main source of information (PEDs and anti-doping rules), only 42.1% of the athletes felt they were well informed. Conclusion: Controlling doping by means of testing is important. However, it is not sufficient and interventions should include psychosocial programmes planned and developed focusing on changing attitudes towards doping and doping culture, as well as the appropriate education specifically on the health risks of using PEDs.

Keywords: doping, anti-doping, attitudes, athletes and sport

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Authors: Gautam Kumar Saharia, Sagardeep Talukdar, Riki Dutta, Sudipta Nandy

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The physics informed neural network (PINN) method opens up an approach for numerically solving nonlinear partial differential equations leveraging fast calculating speed and high precession of modern computing systems. We construct the PINN based on strong universal approximation theorem and apply the initial-boundary value data and residual collocation points to weekly impose initial and boundary condition to the neural network and choose the optimization algorithms adaptive moment estimation (ADAM) and Limited-memory Broyden-Fletcher-Golfard-Shanno (L-BFGS) algorithm to optimize learnable parameter of the neural network. Next, we improve the PINN with a weighted loss function to obtain both the bright and dark soliton solutions of Fokas-Lenells equation (FLE). We find the proposed scheme of adjustable weight coefficients into PINN has a better convergence rate and generalizability than the basic PINN algorithm. We believe that the PINN approach to solve the partial differential equation appearing in nonlinear optics would be useful to study various optical phenomena.

Keywords: deep learning, optical Soliton, neural network, partial differential equation

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Authors: Gautam Kumar Saharia, Sagardeep Talukdar, Riki Dutta, Sudipta Nandy

Abstract:

The physics-informed neural network (PINN) method opens up an approach for numerically solving nonlinear partial differential equations leveraging fast calculating speed and high precession of modern computing systems. We construct the PINN based on a strong universal approximation theorem and apply the initial-boundary value data and residual collocation points to weekly impose initial and boundary conditions to the neural network and choose the optimization algorithms adaptive moment estimation (ADAM) and Limited-memory Broyden-Fletcher-Golfard-Shanno (L-BFGS) algorithm to optimize learnable parameter of the neural network. Next, we improve the PINN with a weighted loss function to obtain both the bright and dark soliton solutions of the Fokas-Lenells equation (FLE). We find the proposed scheme of adjustable weight coefficients into PINN has a better convergence rate and generalizability than the basic PINN algorithm. We believe that the PINN approach to solve the partial differential equation appearing in nonlinear optics would be useful in studying various optical phenomena.

Keywords: deep learning, optical soliton, physics informed neural network, partial differential equation

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Authors: Bhaskar Chakravorti, Christopher Tunnard, Ravi Shankar Chaturvedi

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This report introduces the Digital Evolution Index (DEI) as a way to gauge the transformation of economies in the advanced and developing world from traditional brick-and-mortar to digitally enabled. The DEI measures the digital trajectories of 50 countries to provide actionable, data-informed insights for businesses, investors and policymakers. Created by The Fletcher School, in collaboration with MasterCard Worldwide and DataCash, the DEI analyzes the key underlying drivers and barriers that govern a country’s evolution into a digital economy: Demand, Supply, Institutional Environment and Innovation. A longitudinal analysis of these four drivers during the years 2008 to 2013 reveals both the current state of a country’s digital economy, as well as changes over time. Combining these two measures allows us to assign each country to one of four Trajectory Zones: • Stand Out countries have shown high levels of digital development in the past and continue to remain on an upward trajectory. • Stall Out countries have achieved a high level of evolution in the past but are losing momentum and risk falling behind. • Break Out countries have the potential to develop strong digital economies. Though their overall score is still low, they are moving upward and are poised to become Stand Out countries in the future. • Watch Out countries face significant opportunities and challenges, with low scores on both current level and upward motion of their DEI. Some may be able to overcome limitations with clever innovations and stopgap measures, while others seem to be stuck.

Keywords: e-commerce, digital evolution, digital commerce ecosystems, e-consumer

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Authors: Onyedikachi Ulelu, Andrew P. Longstaff, Simon Fletcher, Simon Parkinson

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The widespread interest in 'Industry 4.0' or 'digital manufacturing' has led to significant research requiring the acquisition of data from sensors, instruments, and machine signals. In-depth research then identifies methods of analysis of the massive amounts of data generated before and during manufacture to solve a particular problem. The ultimate goal is for industrial Internet of Things (IIoT) data to be processed automatically to assist with either visualisation or autonomous system decision-making. However, the collection and processing of data in an industrial environment come with a cost. Little research has been undertaken on how to specify optimally what data to capture, transmit, process, and store at various levels of an edge-cloud network. The first step in this specification is to categorise IIoT data for efficient and effective use. This paper proposes the required attributes and classification to take manufacturing digital data from various sources to determine the most suitable location for data processing on the edge-cloud network. The proposed classification framework will minimise overhead in terms of network bandwidth/cost and processing time of machine tool data via efficient decision making on which dataset should be processed at the ‘edge’ and what to send to a remote server (cloud). A fast-and-frugal heuristic method is implemented for this decision-making. The framework is tested using case studies from industrial machine tools for machine productivity and maintenance.

Keywords: data classification, decision making, edge computing, industrial IoT, industry 4.0

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Authors: Pegah Ebrahimi, Farshad Oveissi, Iman Manavi-Tehrani, Sina Naficy, David F. Fletcher, Fariba Dehghani, David S. Winlaw

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Despite advances in modern surgery, congenital heart disease remains a medical challenge and a major cause of infant mortality. Cardiovascular prostheses are routinely used in surgical procedures to address congenital malformations, for example establishing a pathway from the right ventricle to the pulmonary arteries in pulmonary valvar atresia. Current off-the-shelf options including human and adult products have limited biocompatibility and durability, and their fixed size necessitates multiple subsequent operations to upsize the conduit to match with patients’ growth over their lifetime. Non-physiological blood flow is another major problem, reducing the longevity of these prostheses. These limitations call for better designs that take into account the hemodynamical and anatomical characteristics of different patients. We have integrated tissue engineering techniques with modern medical imaging and image processing tools along with mathematical modeling to optimize the design of cardiovascular grafts in a patient-specific manner. Computational Fluid Dynamics (CFD) analysis is done according to models constructed from each individual patient’s data. This allows for improved geometrical design and achieving better hemodynamic performance. Tissue engineering strives to provide a material that grows with the patient and mimic the durability and elasticity of the native tissue. Simulations also give insight on the performance of the tissues produced in our lab and reduce the need for costly and time-consuming methods of evaluation of the grafts. We are also developing a methodology for the fabrication of the optimized designs.

Keywords: computational fluid dynamics, cardiovascular grafts, design optimization, tissue engineering

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Authors: Iveta Eimontaite, Sarah R. Fletcher, Michele Surico, Alfio Minissale, Fabio F. Abba

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Industry 4.0 offers possibilities for increased production volumes and greater efficiency whilst at the same time presenting new opportunities and challenges for the human workforce. Exoskeletons have been used in healthcare and are now starting to be adopted in manufacturing. The potential benefits of reducing fatigue and physical strain are attractive prospects of the technology for industry; however, the novelty of exoskeletons and surrounding ethical issues raise concerns amongst the stakeholders. The current case study investigated the introduction of an upper body exoskeleton designed to support posture but not increase physical strength in a factory over three time points: before the exoskeleton was introduced, and one and two months post-introduction once operators had experienced working with it. The main focus was to evaluate changes in operators' workload, situation awareness, technology self-efficacy, and physical discomfort following the introduction of the exoskeleton. After using the exoskeleton over two months, operators reported a decrease in temporal demand and an increase in performance of the NASA TLX instrument. Furthermore, over the second month, operators' self-reported technology self-efficacy scores increased, but at the same time, their situation awareness decreased. Interestingly, operators' physical discomfort after using the exoskeleton for two months increased from not uncomfortable to quite uncomfortable in the shoulder, arm, and middle back regions. The results suggest that self-perceived task efficiency improved; however, increased discomfort and decreased situation awareness scores indicate that two months might not be long enough for the exoskeleton to be integrated into operators’ mental body schema. The paper will discuss further implications and suggestions for exoskeleton introduction to manufacturing environments.

Keywords: exoskeleton, manufacturing, mental workload, physical discomfort, situation awareness, technology self-efficacy

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Authors: Manal Elgallal, Louise Fletcher, Barbara Evans

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Water scarcity is a growing concern in many arid and semi-arid countries. The increase of water scarcity threatens economic development and sustainability of human livelihoods as well as environment especially in developing countries. Globally, agriculture is the largest water consumption sector, accounting for approximately 70% of all freshwater extraction. Growing competition between the agricultural and higher economic value in urban and industrial uses of high-quality freshwater supplies, especially in regions where water scarcity major problems, will increase the pressure on this precious resource. In this circumstance, wastewater may provide reliable source of water for agriculture and enable freshwater to be exchanged for more economically valuable purposes. Concern regarding the risks from microbial and toxic components to human health and environment quality is a serious obstacle for wastewater reuse particularly in agriculture. Although powerful approaches and tools for microbial risk assessment and management for safe use of wastewater are now available, few studies have attempted to provide any mechanism to quantitatively assess and manage the environmental risks resulting from reusing wastewater. In seeking pragmatic solutions to sustainable wastewater reuse, there remains a lack of research incorporating both health and environmental risk assessment and management with economic analysis in order to quantitatively combine cost, benefits and risks to rank alternative reuse options. This study seeks to enhance effective reuse of wastewater for irrigation in arid and semi-arid areas, the outcome of the study is an evaluation approach that can be used to assess different reuse strategies and to determine the suitable scale at which treatment alternatives and interventions are possible, feasible and cost effective in order to optimise the trade-offs between risks to protect public health and the environment and preserving the substantial benefits.

Keywords: environmental risks, management, life cycle costs, waste water irrigation

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Authors: Nchanji Yvonne Kiki, Mala William Armand, Nchanji Eileen Bogweh, Ramcilovik-Suominen Sabaheta, Kotilainen Juha

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The Campo Ma'an National Park was created as part of an environmental and biodiversity compensation for the Chad-Cameroon Oil Pipeline Project, which was meant to help alleviate poverty and boost the livelihood of rural communities around the area. This paper examines different strategies and coping mechanisms employed by the indigenous people and local communities to deal with the national and internationally driven conservation policies and initiatives in the case of the Campo Ma'an National Park. While most literature on park management/co-management/nature conservation has focused on the negative implications for local peoples’ livelihoods, fewer studies have investigated the strategies of local people to respond to these policies and renegotiate their position in a way that enables them to continue their traditional livelihoods using the existing local knowledge systems. This study contributes to the current literature by zooming into not only the impacts of nature conservation policies but also the local individual and collective strategies and responses to such policies and initiatives. We employ a qualitative research approach using ethnomethodology and a convivial lens to analyze data collected from October to November 2018. We find that conservation policies have worsened some existing livelihoods on the one hand and constrained livelihood improvement of indigenous people and local communities (IPLC) on the other hand. Nonetheless, the IPLC has devised individual and collective coping mechanisms to deal with these conservation interventions and the negative effects they have caused. Upon exploring these mechanisms and their effectiveness, this study proposes a management approach to conservation centered on both people and nature, based on indigenous and local people's knowledge and practices, promoting nature for and by humans and strengthening both livelihood and conservation. We take inspiration from the convivial conservation approach and thinking by Bucher and Fletcher.

Keywords: conservation policies, national park management, indigenous and local people’s experiences, livelihoods, local knowledge, coping strategies, conviviality

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Authors: Lubaina Soni, Claire Farrell, Christopher Szota, Tim D. Fletcher

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Green roofs are a promising engineered ecosystem for reducing stormwater runoff and restoring vegetation cover in cities. Plants can contribute to rainfall retention by rapidly depleting water in the substrate; however, this increases the risk of plant drought stress. Green roof configurations, therefore, need to provide plants the opportunity to efficiently deplete the substrate but also avoid severe drought stress. This study used green roof modules placed in a rainout shelter during a six-month rainfall regime simulated in Melbourne, Australia. Rainfall was applied equally with an overhead irrigation system on each module. Aside from rainfall, modules were under natural climatic conditions, including temperature, wind, and radiation. A single species, Ficinia nodosa, was planted with five different treatments and three replicates of each treatment. In this experiment, we tested the impact of three plant cover treatments (0%, 50% and 100%) on rainfall retention and plant drought stress. We also installed two runoff zone treatments covering 50% of the substrate surface for additional modules with 0% and 50% plant cover to determine whether directing rainfall resources towards plant roots would reduce drought stress without impacting rainfall retention. The retention performance for the simulated rainfall events was measured, quantifying all components for hydrological performance and survival on green roofs. We found that evapotranspiration and rainfall retention were similar for modules with 50% and 100% plant cover. However, modules with 100% plant cover showed significantly higher plant drought stress. Therefore, planting at a lower cover/density reduced plant drought stress without jeopardizing rainfall retention performance. Installing runoff zones marginally reduced evapotranspiration and rainfall retention, but by approximately the same amount for modules with 0% and 50% plant cover. This indicates that reduced evaporation due to the installation of the runoff zones likely contributed to reduced evapotranspiration and rainfall retention. Further, runoff occurred from modules with runoff zones faster than those without, indicating that we created a faster pathway for water to enter and leave the substrate, which also likely contributed to lower overall evapotranspiration and retention. However, despite some loss in retention performance, modules with 50% plant cover installed with runoff zones showed significantly lower drought stress in plants compared to those without runoff zones. Overall, we suggest that reducing plant cover represents a simple means of optimizing green roof performance but creating runoff zones may reduce plant drought stress at the cost of reduced rainfall retention.

Keywords: green roof, plant cover, plant drought stress, rainfall retention

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Authors: Abraham Castellanos, Christophe Durville, Sophie Echenim

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In this article, a portfolio optimization problem is performed in a Solvency II context: it illustrates how advanced optimization techniques can help to tackle complex operational pain points around the monitoring, control, and stability of Solvency Capital Requirement (SCR). The market SCR of a portfolio is calculated as a combination of SCR sub-modules. These sub-modules are the results of stress-tests on interest rate, equity, property, credit and FX factors, as well as concentration on counter-parties. The market SCR is non convex and non differentiable, which does not make it a natural optimization criteria candidate. In the SCR formulation, correlations between sub-modules are fixed, whereas risk-driven portfolio allocation is usually driven by the dynamics of the actual correlations. Implementing a portfolio construction approach that is efficient on both a regulatory and economic standpoint is not straightforward. Moreover, the challenge for insurance portfolio managers is not only to achieve a minimal SCR to reduce non-invested capital but also to ensure stability of the SCR. Some optimizations have already been performed in the literature, simplifying the standard formula into a quadratic function. But to our knowledge, it is the first time that the standard formula of the market SCR is used in an optimization problem. Two solvers are combined: a bundle algorithm for convex non- differentiable problems, and a BFGS (Broyden-Fletcher-Goldfarb- Shanno)-SQP (Sequential Quadratic Programming) algorithm, to cope with non-convex cases. A market SCR minimization is then performed with historical data. This approach results in significant reduction of the capital requirement, compared to a classical Markowitz approach based on the historical volatility. A comparative analysis of different optimization models (equi-risk-contribution portfolio, minimizing volatility portfolio and minimizing value-at-risk portfolio) is performed and the impact of these strategies on risk measures including market SCR and its sub-modules is evaluated. A lack of diversification of market SCR is observed, specially for equities. This was expected since the market SCR strongly penalizes this type of financial instrument. It was shown that this direct effect of the regulation can be attenuated by implementing constraints in the optimization process or minimizing the market SCR together with the historical volatility, proving the interest of having a portfolio construction approach that can incorporate such features. The present results are further explained by the Market SCR modelling.

Keywords: financial risk, numerical optimization, portfolio management, solvency capital requirement

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Authors: Nicholas Fletcher, Zachary Houston, Yongmei Zhao, Christopher Howard, Kristofer Thurecht

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One promising approach to enhance nanomedicine therapeutic efficacy is to include a targeting agent, such as an antibody, to increase accumulation at the tumor site. However, the application of such targeted nanomedicines remains limited, in part due to difficulties involved with biomolecule conjugation to synthetic nanomaterials. One approach recently developed to overcome this has been to engineer bispecific antibodies (BsAbs) with dual specificity, whereby one portion binds to methoxy polyethyleneglycol (mPEG) epitopes present on synthetic nanomedicines, while the other binds to molecular disease markers of interest. In this way, noncovalent complexes of nanomedicine core, comprising a hyperbranched polymer (HBP) of primarily mPEG, decorated with targeting ligands are able to be produced by simple mixing. Further work in this area has now demonstrated such complexes targeting the breast cancer marker epidermal growth factor receptor (EGFR) to show enhanced binding to tumor cells both in vitro and in vivo. Indeed the enhanced accumulation at the tumor site resulted in improved therapeutic outcomes compared to untargeted nanomedicines and free chemotherapeutics. The current work on these BsAb-HBP conjugates focuses on further probing antibody-nanomaterial interactions and demonstrating broad applicability to a range of cancer types. Herein are reported BsAb-HBP materials targeted towards prostate-specific membrane antigen (PSMA) and study of their behavior in vivo using ⁸⁹Zr positron emission tomography (PET) in a dual-tumor prostate cancer xenograft model. In this model mice bearing both PSMA+ and PSMA- tumors allow for PET imaging to discriminate between nonspecific and targeted uptake in tumors, and better quantify the increased accumulation following BsAb conjugation. Also examined is the potential for formation of these targeted complexes in situ following injection of individual components? The aim of this approach being to avoid undesirable clearance of proteinaceous complexes upon injection limiting available therapeutic. Ultimately these results demonstrate BsAb functionalized nanomaterials as a powerful and versatile approach for producing targeted nanomedicines for a variety of cancers.

Keywords: bioengineering, cancer, nanomedicine, polymer chemistry

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Authors: Philippa Saunders, Claire Fletcher

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INTRODUCTION: Prostate cancer is the most prevalent malignancy affecting Western males. It is initially an androgen-dependent disease: androgens bind to the androgen receptor and drive the expression of genes that promote proliferation and evasion of apoptosis. Despite reduced androgen dependence in advanced prostate cancer, androgen receptor signaling remains a key driver of growth. Androgen deprivation therapy (ADT) is, therefore, a first-line treatment approach and works well initially, but resistance inevitably develops. Abiraterone and Enzalutamide are drugs widely used in ADT and are androgen synthesis and androgen receptor signaling inhibitors, respectively. The shortage of other treatment options means acquired resistance to these drugs is a major clinical problem. MicroRNAs (miRs) are important mediators of post-transcriptional gene regulation and show altered expression in cancer. Several have been linked to the development of resistance to ADT. Manipulation of such miRs may be a pathway to breakthrough treatments for advanced prostate cancer. This study aimed to validate ADT resistance-implicated miRs and their clinically relevant targets. MATERIAL AND METHOD: Small RNA-sequencing of Abiraterone- and Enzalutamide-resistant C42 prostate cancer cells identified subsets of miRs dysregulated as compared to parental cells. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to validate altered expression of candidate ADT resistance-implicated miRs 195-5p, 497-5p and 29a-5p in ADT-resistant and -responsive prostate cancer cell lines, patient-derived xenografts (PDXs) and primary prostate cancer explants. RESULTS AND DISCUSSION: This study suggests a possible role for miR-497-5p in the development of ADT resistance in prostate cancer. MiR-497-5p expression was increased in ADT-resistant versus ADT-responsive prostate cancer cells. Importantly, miR-497-5p expression was also increased in Enzalutamide-treated, castrated (ADT-mimicking) PDXs versus intact PDXs. MiR-195-5p was also elevated in ADT-resistant versus -responsive prostate cancer cells, while there was a drop in miR-29a-5p expression. Candidate clinically relevant targets of miR-497-5p in prostate cancer were identified by mining AGO-PAR-CLIP-seq data sets and may include AVL9 and FZD6. CONCLUSION: In summary, this study identified microRNAs that are implicated in prostate cancer resistance to androgen deprivation therapy and could represent novel therapeutic targets for advanced disease.

Keywords: microRNA, androgen deprivation therapy, Enzalutamide, abiraterone, patient-derived xenograft

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Authors: Lisa Robins, Jill Newby, Kay Wilhelm, Therese Fletcher, Jessica Smith, Trevor Ma, Adam Finch, Lesley Campbell, Jerry Greenfield, Gavin Andrews

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Background:Depression treatment for people living with depression comorbid with diabetes is of critical importance for improving quality of life and diabetes self-management, however depression remains under-recognised and under-treated in this population. Cost—effective and accessible forms of depression treatment that can enhance the delivery of mental health services in routine diabetes care are needed. Provision of internet-delivered Cognitive Behaviour Therapy (iCBT) provides a promising way to deliver effective depression treatment to people with diabetes. Aims:To explore the outcomes of the clinician assisted iCBT program for people with comorbid Major Depressive Disorder (MDD) and diabetes compared to those who remain under usual care. The main hypotheses are that: (1) Participants in the treatment group would show a significant improvement on disorder specific measures (Patient Health Questionnaire; PHQ-9) relative to those in the control group; (2) Participants in the treatment group will show a decrease in diabetes-related distress relative to those in the control group. This study will also examine: (1) the effect of iCBT for MDD on disability (as measured by the SF-12 and SDS), general distress (as measured by the K10), (2) the feasibility of these treatments in terms of acceptability to diabetes patients and practicality for clinicians (as measured by the Credibility/Expectancy Questionnaire; CEQ). We hypothesise that associated disability, and general distress will reduce, and that patients with comorbid MDD and diabetes will rate the program as acceptable. Method:Recruit 100 people with MDD comorbid with diabetes (either Type 1 or Type 2), and randomly allocate to: iCBT (over 10 weeks) or treatment as usual (TAU) for 10 weeks, then iCBT. Measure pre- and post-intervention MDD severity, anxiety, diabetes-related distress, distress, disability, HbA1c, lifestyle, adherence, satisfaction with clinicians input and the treatment. Results:Preliminary results comparing MDD symptom levels, anxiety, diabetes-specific distress, distress, disability, HbA1c levels, and lifestyle factors from baseline to conclusion of treatment will be presented, as well as data on adherence to the lessons, homework downloads, satisfaction with the clinician's input and satisfaction with the mode of treatment generally.

Keywords: cognitive behaviour therapy, depression, diabetes, internet

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Authors: B. M. Y. I. Basnayake, G. G. T. Nisansala, P. I. J. B. Wijewickrama, U. S. Weerathunga, K. W. M. Y. D. Gunasekara, N. K. Jayasekera, A. W. Kalupahana, R. S. Kalupahana, A. Silva- Fletcher, K. S. A. Kottawatta

Abstract:

Antimicrobial resistance (AMR) has attracted significant attention worldwide as an emerging threat to public health. Understanding the role of livestock and wildlife with the shared environment in the maintenance and transmission of AMR is of utmost importance due to its interactions with humans for combating the issue in one health approach. This study aims to investigate the extent of AMR distribution among wild animals, livestock, and environment cohabiting in a rural ecosystem in Sri Lanka: Hambegamuwa. One square km area at Hambegamuwa was mapped using GPS as the sampling area. The study was conducted for a period of five months from November 2020. Voided fecal samples were collected from 130 wild animals, 123 livestock: buffalo, cattle, chicken, and turkey, with 36 soil and 30 water samples associated with livestock and wildlife. From the samples, Escherichia coli (E. coli) was isolated, and their AMR profiles were investigated for 12 antimicrobials using the disk diffusion method following the CLSI standard. Seventy percent (91/130) of wild animals, 93% (115/123) of livestock, 89% (32/36) of soil, and 63% (19/30) of water samples were positive for E. coli. Maximum of two E. coli from each sample to a total of 467 were tested for the sensitivity of which 157, 208, 62, and 40 were from wild animals, livestock, soil, and water, respectively. The highest resistance in E. coli from livestock (13.9%) and wild animals (13.3%) was for ampicillin, followed by streptomycin. Apart from that, E. coli from livestock and wild animals revealed resistance mainly against tetracycline, cefotaxime, trimethoprim/ sulfamethoxazole, and nalidixic acid at levels less than 10%. Ten cefotaxime resistant E. coli were reported from wild animals, including four elephants, two land monitors, a pigeon, a spotted dove, and a monkey which was a significant finding. E. coli from soil samples reflected resistance primarily against ampicillin, streptomycin, and tetracycline at levels less than in livestock/wildlife. Two water samples had cefotaxime resistant E. coli as the only resistant isolates out of 30 water samples tested. Of the total E. coli isolates, 6.4% (30/467) was multi-drug resistant (MDR) which included 18, 9, and 3 isolates from livestock, wild animals, and soil, respectively. Among 18 livestock MDRs, the highest (13/ 18) was from poultry. Nine wild animal MDRs were from spotted dove, pigeon, land monitor, and elephant. Based on CLSI standard criteria, 60 E. coli isolates, of which 40, 16, and 4 from livestock, wild animal, and environment, respectively, were screened for Extended Spectrum β-Lactamase (ESBL) producers. Despite being a rural ecosystem, AMR and MDR are prevalent even at low levels. E. coli from livestock, wild animals, and the environment reflected a similar spectrum of AMR where ampicillin, streptomycin, tetracycline, and cefotaxime being the predominant antimicrobials of resistance. Wild animals may have acquired AMR via direct contact with livestock or via the environment, as antimicrobials are rarely used in wild animals. A source attribution study including the effects of the natural environment to study AMR can be proposed as this less contaminated rural ecosystem alarms the presence of AMR.

Keywords: AMR, Escherichia coli, livestock, wildlife

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Authors: Chevonne Reynolds, Robert J. Fletcher, Jr, Celine M. Carneiro, Nicole Jennings, Alison Ke, Michael C. LaScaleia, Mbhekeni B. Lukhele, Mnqobi L. Mamba, Muzi D. Sibiya, James D. Austin, Cebisile N. Magagula, Themba’alilahlwa Mahlaba, Ara Monadjem, Samantha M. Wisely, Robert A. McCleery

Abstract:

A key challenge for the developing world is reconciling biodiversity conservation with the growing demand for food. In these regions, agriculture is typically interspersed among other land-uses creating heterogeneous landscapes. A primary hypothesis for promoting biodiversity in agricultural landscapes is the habitat heterogeneity hypothesis. While there is evidence that landscape heterogeneity positively influences biodiversity, the application of this hypothesis is hindered by a need to determine which components of landscape heterogeneity drive these effects and at what spatial scale(s). Additionally, whether diverse taxonomic groups are similarly affected is central for determining the applicability of this hypothesis as a general conservation strategy in agricultural mosaics. Two major components of landscape heterogeneity are compositional and configurational heterogeneity. Disentangling the roles of each component is important for biodiversity conservation because each represents different mechanisms underpinning variation in biodiversity. We identified a priori independent gradients of compositional and configurational landscape heterogeneity within an extensive agricultural mosaic in north-eastern Swaziland. We then tested how bird, dung beetle, ant and meso-carnivore diversity responded to compositional and configurational heterogeneity across six different spatial scales. To determine if a general trend could be observed across multiple taxa, we also tested which component and spatial scale was most influential across all taxonomic groups combined, Compositional, not configurational, heterogeneity explained diversity in each taxonomic group, with the exception of meso-carnivores. Bird and ant diversity was positively correlated with compositional heterogeneity at fine spatial scales < 1000 m, whilst dung beetle diversity was negatively correlated to compositional heterogeneity at broader spatial scales > 1500 m. Importantly, because of these contrasting effects across taxa, there was no effect of either component of heterogeneity on the combined taxonomic diversity at any spatial scale. The contrasting responses across taxonomic groups exemplify the difficulty in implementing effective conservation strategies that meet the requirements of diverse taxa. To promote diverse communities across a range of taxa, conservation strategies must be multi-scaled and may involve different strategies at varying scales to offset the contrasting influences of compositional heterogeneity. A diversity of strategies are likely key to conserving biodiversity in agricultural mosaics, and we have demonstrated that a landscape management strategy that only manages for heterogeneity at one particular scale will likely fall short of management objectives.

Keywords: agriculture, biodiversity, composition, configuration, heterogeneity

Procedia PDF Downloads 264

Authors: Monica Jong, Antonios Banos, Tom Scott, Chris Webster, David Fletcher

Abstract:

Hydrogen, as a clean alternative to methane, is relatively easy to make, either from water using electrolysis or from methane using steam reformation. However, hydrogen is much trickier to store than methane, and without effective storage, it simply won’t pass muster as a suitable methane substitute. Physical storage of hydrogen is quite inefficient. Storing hydrogen as a compressed gas at pressures up to 900 times atmospheric is volumetrically inefficient and carries safety implications, whilst storing it as a liquid requires costly and constant cryogenic cooling to minus 253°C. This is where DU steps in as a possible solution. Across the periodic table, there are many different metallic elements that will react with hydrogen to form a chemical compound known as a hydride (or metal hydride). From a chemical perspective, the ‘king’ of the hydride forming metals is palladium because it offers the highest hydrogen storage volumetric capacity. However, this material is simply too expensive and scarce to be used in a scaled-up bulk hydrogen storage solution. Depleted Uranium is the second most volumetrically efficient hydride-forming metal after palladium. The UK has accrued a significant amount of DU because of manufacturing nuclear fuel for many decades, and that is currently without real commercial use. Uranium trihydride (UH3) contains three hydrogen atoms for every uranium atom and can chemically store hydrogen at ambient pressure and temperature at more than twice the density of pure liquid hydrogen for the same volume. To release the hydrogen from the hydride, all you do is heat it up. At temperatures above 250°C, the hydride starts to thermally decompose, releasing hydrogen as a gas and leaving the Uranium as a metal again. The reversible nature of this reaction allows the hydride to be formed and unformed again and again, enabling its use as a high-density hydrogen storage material which is already available in large quantities because of its stockpiling as a ‘waste’ by-product. Whilst the tritium storage credentials of Uranium have been rigorously proven at the laboratory scale and at the fusion demonstrator JET for over 30 years, there is a need to prove the concept for depleted uranium hydrogen storage (HyDUS) at scales towards that which is needed to flexibly supply our national power grid with energy. This is exactly the purpose of the HyDUS project, a collaborative venture involving EDF as the interested energy vendor, Urenco as the owner of the waste DU, and the University of Bristol with the UKAEA as the architects of the technology. The team will embark on building and proving the world’s first pilot scale demonstrator of bulk chemical hydrogen storage using depleted Uranium. Within 24 months, the team will attempt to prove both the technical and commercial viability of this technology as a longer duration energy storage solution for the UK. The HyDUS project seeks to enable a true by-product to wonder material story for depleted Uranium, demonstrating that we can think sustainably about unlocking the potential value trapped inside nuclear waste materials.

Keywords: hydrogen, long duration storage, storage, depleted uranium, HyDUS

Procedia PDF Downloads 160