319 research outputs found
The RCS England COVID-19 Surgical Research Group: early findings and lessons to influence surgical practice
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Conditions for safe and effective ADEPT treatment
No full textAntibody directed enzyme prodrug therapy (ADEPT) is a drug delivery system developed for the treatment of cancer. ADEPT uses a systemically administered antibody, tethered to an enzyme, to localize enzyme in tumour deposits. When the antibody-enzyme has cleared from the circulation, a low-toxicity prodrug is given. The prodrug is converted by the tumour-bound enzyme into an active cytotoxic drug. The system has potential to generate a highly potent cytotoxic agent at the tumour site.
A clinical ADEPT system using MFECP1, a recombinant fusion protein consisting of an anti-carcinoembryonic antigen single chain Fv antibody and the bacterial enzyme carboxypeptidase G2, in combination with a bis-iodo phenol mustard prodrug (BIP) has been developed. A previous phase I/II clinical trial established the maximum tolerated dose of a single treatment cycle of this ADEPT system.
In-vivo models with human tumour xenografts indicate that repeated ADEPT treatment with MFECP1/BIP led to greater efficacy without increased toxicity. This thesis aims to establish conditions required for safe and effective ADEPT when using MFECP1/BIP in man. This was achieved by conducting a phase I/II clinical trial of repeat-treatment ADEPT and comparing and combining the results with data from the single-treatment trial. The combined dataset provided mechanistic and clinical information on 43 patients.
Multiple parameters were investigated to examine the likely cause of toxicity and clinical risk factors for its occurrence. Efficacy was evaluated using CT, FDG-PET and serum tumour markers. The nature of the immune response to MFECP1 was investigated and possible strategies to reduce immunogenicity were developed.
Results showed that repeated therapy was feasible in man and did not increase the risk of MFECP1 infusion reactions. At the maximum tolerated total prodrug dose for 2 ADEPT treatments, one of three patients experienced tumour response on FDG-PET imaging. This MD (Res) thesis significantly increases understanding of the conditions required for safe and effective ADEPT
Numerical Investigation of the Influence of Ground Effect on the FV Aircraft: Influence of Ground Effect on the Flying V Aircraft
No full textIn order to meet the growing market demands of quieter, more aerodynamically efficient aircrafts, manufacturers constantly strive to innovate and optimize their designs. Over the years however, the extent of innovation related to the conventional 'tubular fuselage' configurations have somewhat reached a stalemate as the gains obtained have only been marginal. It is for this reason, there has off-late been a surge in research pertaining to unconventional aircraft design and configurations. The Flying V (FV) is one such alternative that was conceptualized by J. Benad at TU Berlin along with the Future Projects Office (FPO) at Airbus Operations GmbH in Hamburg. Results obtained from past studies show a 25% improvement in the lift to drag ratio of the FV as compared to the NASA Common Research Model (CRM), which was set as the basis of comparison for a fixed wing aircraft configuration. So far, aerodynamic studies have only focused on the cruise performance of the FV without any emphasis on its low speed behavior. Conventional aircrafts use high lift devices like flaps and slats to improve stability and increase the amount of lift its wings produce at lower speeds. The FV however, has no such high lift device and solely relies on the lift produced by its wing to achieve a speed that is low enough to land safely. For this reason, this thesis aims to investigate the influence of ground proximity on the lift, drag and pitching moments of the FV which in turn affect its take-off and landing characteristics. Compressible RANS equations were solved with the k-omega SST turbulence model using ANSYS Fluent on a 4.6\% scaled model of the FV. The ground was numerically realized by employing the moving ground boundary condition equal in velocity to the free stream. Results from these simulations have shown a 11% reduction in the drag polar of the FV when closest to the ground as compared to when in unbounded flow. Additionally, the proximity to the ground causes an increase in lift and this allows the FV to touch down at 19 degrees while the maximum rotation angle during take-off is predicted to be about 13 degrees for a positive climb gradient when also considering the One-Engine-Idle (OEI) scenario. This corresponds to a lift to drag ratio equal to 10 and a lift-off lift coefficient of 0.56 approximately. The effect of ride height on the longitudinal stability of the FV showed that favorable pitching moments were obtained for angles of attack between 0 degrees and 5 degrees and for angles greater than 17.5 degrees. A near wake analysis was also performed for different angles of attack and at different heights from the ground to investigate the flow phenomena over the FV and the evolution of the wake downstream. No significant span wise flow is seen when the angle of attack is 0 degrees and the flow appears to travel parallel to the stream-wise direction. Additionally, in case of very high angles of attack, the flow streamlines confirm the occurrence of a large vortex emanating from the leading edge kink of the wing. When in unbounded flow a secondary vortex located inboard is produced at 17 degrees. The diameter of the tip vortex is seen to be greater than the inboard secondary vortex for an angle of attack equal to 17 degrees. At greater angles of attack, the secondary vortex is seen to grow in diameter as the height reduces.Flying VAerospace Engineerin
FV-MgNet: Fully connected V-cycle MgNet for interpretable time series forecasting
No full textBy investigating iterative methods for a constrained linear model, we propose a new class of fully connected V-cycle MgNet for long-term time series forecasting, which is one of the most difficult tasks in forecasting. MgNet is a CNN model that was proposed for image classification based on the multigrid (MG) methods for solving discretized partial differential equations (PDEs). We replace the convolutional operations with fully connected operations in the existing MgNet and then apply them to forecasting problems. Motivated by the V-cycle structure in MG, we further propose the FV-MgNet, a V-cycle version of the fully connected MgNet, to extract features hierarchically. By evaluating the performance of FV-MgNet on popular datasets and comparing it with state-of-the-art models, we show that the FV-MgNet achieves better results with less memory usage and faster inference speed. In addition, we develop ablation experiments to demonstrate that the structure of FV-MgNet is the best choice among the many variants.The first author is supported in part by Beijing Natural Science Foundation Project (No. Z200002), the second and fourth authors are partially supported by the KAUST Baseline Research Fund, and the third author is supported by Hetao Shenzhen-Hong Kong Science and Technology Innovation Cooperation Zone Project (No. HZOSWS-KCCYB-2022046)
Assessment pedestrian crossing safety using vehicle-pedestrian interaction data through two different approaches: Fixed videography (FV) vs In-Motion Videography (IMV)
No full textA significant portion of pedestrian accidents occurs in the outskirts areas due to the high vehicle speed and lack of safety facilities for pedestrians. Behavioral study on drivers and pedestrians is the key to better understand the causes of pedestrian accidents in order to develop safety models. Despite numerous studies on pedestrian safety based on various roads, outskirt areas have not been considered. Hence, the present study focuses on evaluating the safety of pedestrian crossing in urban and outskirt areas and to determine the differences of drivers and pedestrians’ behaviors between these areas through data based on fixed videography (FV) and in-motion videography (IMV). These approaches may lead to an exact analysis of the behavioral differences of road users behaviors from the perspective of pedestrians (FV data) and drivers (IMV data) in urban and outskirts roads. Accordingly, behavioral studies were conducted at urban and outskirts sites through FV as well as IMV using the behavior of 29 participants in the same roads in Babol city, Iran. The gap acceptance model using linear regression and pedestrian crossing probability model using logistic regression for both approaches showed similarity on results in both urban and outskirts roads. Furthermore, behaviors of pedestrians crossing and drivers’ yielding on urban and outskirts roads were very similar. Vehicle speed, the distance of vehicle to pedestrian at the possible collision point, size of pedestrian groups, and waiting time before crossing were the most important behavioral differences of pedestrian for choosing a gap acceptance and probability of crossing on various sites through two different approaches. The inference of the models obtained in this study will lead to a better understanding of the behavior of road users for studies on advanced driving assistance systems (ADAS).Safety and Security Scienc
Biophysical characterization and single-chain Fv construction of a neutralizing antibody to measles virus
Get PDFThe measles virus (MV) is a major cause of childhood morbidity and mortality worldwide. We previously established a mouse monoclonal antibody, 2F4, which shows high neutralizing titers against eight different genotypes of MV. However, the molecular basis for the neutralizing activity of the 2F4 antibody remains incompletely understood. Here, we have evaluated the binding characteristics of a Fab fragment of the 2F4 antibody. Using the MV infectious assay, we demonstrated that 2F4 Fab inhibits viral entry via either of two cellular receptors, SLAM and Nectin4. Surface plasmon resonance (SPR) analysis of recombinant proteins indicated that 2F4 Fab interacts with MV hemagglutinin (MV-H) with a K-D value at the nm level. Furthermore, we designed a single-chain Fv fragment of 2F4 antibody as another potential biopharmaceutical to target measles. The stable 2F4 scFv was successfully prepared by the refolding method and shown to interact with MV-H at the mu m level. Like 2F4 Fab, scFv inhibited receptor binding and viral entry. This indicates that 2F4 mAb uses the receptor-binding site and/or a neighboring region as an epitope with high affinity. These results provide insight into the neutralizing activity and potential therapeutic use of antibody fragments for MV infection
Time to rethink medical disinfection from a planetary health perspective
Get PDFDisinfection products can have substantial environmental impacts which include associated manufacturing emissions, toxicity to marine life and potential adverse health outcomes. Despite this, disinfection is under-represented in sustainability approaches. Disinfection is a key part of healthcare provision and as such should be reflected in healthcare sustainability strategies. The adverse environmental effects of several common disinfectants are highlighted here. Sustainable alternatives should be considered. Hypochlorous acid (HOCl) is a potential alternative disinfectant that could be used in sustainability strategies, carrying a minimal toxicity profile compared to hypochlorite (bleach) and the unique ability to be made on site. Better clarity is needed regarding the environmental impact of disinfectants used in the healthcare setting and healthcare providers should move to seek sustainable alternatives such as hypochlorous acid
Measuring children’s self-efficacy and proxy efficacy related to fruit and vegetable consumption
Get PDFBACKGROUND: Social cognitive theory describes self-efficacy and proxy efficacy as influences on fruit and vegetable consumption (FVC). Proxy efficacy was defined as a child’s confidence in his or her skills and abilities to get others to act in one’s interests to provide fruit and vegetable (FV) opportunities. The purpose of this study was to develop a scale assessing children’s self-efficacy and proxy efficacy for FVC at after-school programs and at home.
METHODS: Elementary-aged children (n = 184) attending 7 after-school programs completed a self-efficacy questionnaire relevant to FVC. Questionnaire validity was investigated with exploratory factor analysis and mixed-model analysis of covariance. Internal consistency reliability and readability were also assessed.
RESULTS: The questionnaire assessed 4 constructs: self-efficacy expectations for fruit consumption, self-efficacy expectations for vegetable consumption, proxy efficacy to influence parents to make FV available, and proxy efficacy to influence after-school staff to make FV available. Children perceiving FV opportunities in after-school had greater self-efficacy expectations for FVC and greater proxy efficacy to influence after-school staff compared to students who did not perceive FV opportunities. Children attending schools of higher socioeconomic status (SES) and less diversity were more confident they could influence their parents to make FV available than students attending lower SES and less diverse schools. Adequate internal consistency and test-retest reliabilities were established.
CONCLUSIONS: Self-efficacy is a multicomponent construct that can be assessed in children using the reliable and valid instrument evaluated by the current study
Can anonymisation become disempowering? Rethinking ethics for low-risk global health research
Get PDFAnonymisation is intended to confer protection in research, yet in research where disclosure poses minimal threat, blanket anonymisation may disempower participants who explicitly seek recognition. Drawing on fieldwork examining task shifting and sharing in India, we present an example where the leadership of a non-profit questioned why they must stay anonymous, viewing research participation as a rare chance to share learnings, document impact, and build credibility; opportunities otherwise constrained by funding and capacity limitations. Looking through an epistemic injustice lens, we argue that mandatory anonymisation policies reflect global north institutional assumptions about protection rather than the preferences of participants, potentially perpetuating patterns where researchers advance their goals whilst organisations whose knowledge forms their evidence remain invisible. While anonymisation is critical for sensitive research where disclosure could do harm, we call for flexible ethical guidelines that empower participants to make informed choices regarding recognition if risks are minimal. We recommend tiered consent processes which allow participants to select their levels of identification, differentiate between organisational and individual visibility, and use context-dependent frameworks like the Global Ethical Research toolkit to move towards proportionate, context-dependent decisions that truly protect those we study
Flying-V Family Design
No full textThe Flying-V is a novel aircraft configuration that promises a large improvement in fuel burn performance compared to conventional aircraft, integrating the passenger cabin and cargo volume into the lifting surface. The Flying-V is a V-shaped flying wing with an oval cabin and engines over the trailing edge. The aircraft does not have high-lift devices, and fins and elevons provide stability and control. The Flying-V has been studied on several aspects such as aerodynamics and structures, confirming its large potential fuel burn reduction. This study focuses on the feasibility of developing a family of Flying-V aircraft, which is a crucial step in passenger aircraft development offering multiple aircraft variants at limited development and production cost. The ability to design a family of Flying-V aircraft can be a large advantage with respect to blended wing body designs, of which earlier research suggests that developing a family is difficult due to its lack of a constant cross-section. On a higher level, this research is one of the few focusing on family design of an unconventional aircraft configuration in the conceptual design phase. The Flying-V family is optimised for minimal fuel burn, ensuring commonality in terms of common variables and common components between family members. Fuel burn is calculated using fuel fractions and the Breguet range equation. A vortex-lattice method is employed to study the aerodynamic characteristics of the aircraft, enhanced with a viscous module to estimate its lift-to-drag ratio. The weight of the aircraft is estimated using empirical relations, a semi-analytical oval fuselage weight estimation method and a quasi-analytical conventional aircraft wing weight estimation method. The fuel burn model is validated using the reference aircraft family, resulting in a fuel burn within 0.9% of the data provided by the aircraft manufacturer. Feasibility of the Flying-V family design is ensured by including a range of top-level aircraft requirements on payload, range, cruise speed and altitude, low-speed performance, stability and control and airport regulations. The complete model is built within a ParaPy framework, which is a Knowledge-Based Engineering environment programmed in Python. Optimisation of the Flying-V aircraft family is performed using an iterative procedure, optimising variables that describe the planform and cross-section of the aircraft. The only unique variable for each aircraft variant is the length of the untapered part of the cabin, maximising commonality in the aircraft family. The optimised Flying-V (FV) family consists of three aircraft with a passenger capacity of 293, 328 and 361 for the FV-800, FV-900 and FV-1000 respectively. The design ranges of the Flying-V family members at maximum passenger capacity are 11.2x103 km, 14.8x103 km and 15.4x103 km. The range of the FV-800 is smaller than the other two aircraft family members because no requirement was imposed on this range, determining the range implicitly from the available fuel volume resulting from optimisation of a two-member aircraft family. The optimised design suggests a 20% and 22% lower fuel burn than the modelled reference aircraft family for the FV-900 and FV-1000 on the design mission, proving the feasibility in terms of fuel burn of a Flying-V aircraft family. The penalty in fuel burn compared to individually optimised aircraft is 8.9%, 7.1% and 4.2% for the FV-800, FV-900 and FV-1000 respectively. The takeoff mass of the Flying-V family members is 185x103 kg, 234x103 kg and 266x103 kg respectively. With respect to the modelled A350 family, this is a reduction of 17% and 15% for the -900 and -1000 variant. The approach speed of the FV-900 and FV-1000 is estimated at 136 and 137 kts, much lower than the specified approach speed of the reference aircraft of 140 and 147 kts. Besides constraints on payload and commonality, driving requirements in Flying-V family design are the shift in centre of gravity during flight, the wingspan and the fuel tank volume. Feasibility of the design is ensured by drawing a floor plan of the aircraft fitting its payload and furnishing. Additionally, a sensitivity analysis on the obtained design vector confirms its optimality.Flying VAerospace Engineerin
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