12508 research outputs found
Sort by
Maleimide-thiol linkages alter the biodistribution of SN38 therapeutic microbubbles compared to biotin-avidin while preserving parity in tumoral drug delivery
Get PDFYesTherapeutic microbubbles (thMBs) contain drug-filled liposomes linked to microbubbles and targeted to vascular proteins. Upon the application of a destructive ultrasound trigger, drug uptake to tumour is improved. However, the structure of thMBs currently uses powerful non-covalent bonding of biotin with avidin-based proteins to link both the liposome to the microbubble (MB) and to bind the targeting antibody to the liposome-MB complex. This linkage is not currently FDA-approved, and therefore, an alternative, maleimide-thiol linkage, that is currently used in antibody-drug conjugates was examined. In a systematic manner, vascular endothelial growth factor receptor 2 (VEGFR2)-targeted MBs and thMBs using both types of linkages were examined for their ability to specifically bind to VEGFR2 in vitro and for their ultrasound imaging properties in vivo. Both showed equivalence in the production of the thMB structure, in vitro specificity of binding and safety profiles. In vivo imaging showed subtle differences for thMBs where biotin thMBs had a faster wash-in rate than thiol thMBs, but thiol thMBs were longer-lived. The drug delivery to tumours was also equivalent, but interestingly, thiol thMBs altered the biodistribution of delivery away from the lungs and towards the liver compared to biotin thMBs, which is an improvement in biosafety.This research was funded by the EPSRC (EP/I000623/1, EP/L504993/1 and EP/P023266/1). S.D.E. is supported by the National Institute for Health Research infrastructure at Leeds
An investigation on hydrate prediction and inhibition: An industrial case study
Get PDFYesThis investigation reports the first study to predict natural gas hydrate formation using both Aspen HYSYS® and HydraFlash software for various gas compositions and thermodynamic inhibitors (monoethylene glycol [MEG] concentrations at 10, 20, 30, and 40 wt.% and methanol concentrations at 10 and 20 wt.%). The simulated predictions are compared with the results of the experimental data in the literature. It has been shown that HydraFlash software can accurately predict hydrate formation conditions for a given industrial case, without having to carry out costly experimental work. This work also evaluated the effect of inhibitors and it appears that inhibitor type and concentration are determined according to condition of gas composition. MEG is consequently selected as the most ideal hydrate inhibitor for the industrial case. This also was confirmed through COSMO-RS studies in which the sigma profile and sigma potential of the considered inhibitors were obtained and presented using density functional (DFT) calculations to verify the hydrogen bonding affinities of the inhibitors to water molecules. HydraFlash was utilized to predict the dissociation conditions of hydrates under the influence of a high concentration of MEG inhibition, reaching up to 40 wt.% at 313 K and a pressure of 311.1 bar. Finally, it is shown that both software packages are quite accurate and useful tools for the prediction of hydrate for simple systems. However, HydraFlash can simulate more complex systems, including different types of salts at higher pressures. Investigation results indicate insightful guidance for accurately predicting hydrate dissociation under simulated conditions.The authors would also like to thank the Turkish National Agency for offering an Erasmus student grant for Mr. Nejmi Söyler under the Erasmus+ Program Action 1 throughout the training period
A qualitative analysis of the role of the diagnostic radiographer in child safeguarding
Get PDFYesBackground: The role of medical imaging in the investigation of suspected child abuse is well documented. However, the role of the radiographer as an instigator of such concerns is less well understood. The fast-paced development of related technology and the evolution of the profession into new areas of work is argued to have impacted upon the traditional interaction between patient and professional; thus requiring a contemporary analysis of current practice.
Objective: As part of a wider multimethod thesis, this qualitative study sought to fill a gap in the literature with regard the role of the radiographer in child safeguarding by exploring their knowledge of, attitude towards and practical experience of the phenomenon.
Participants and setting: Online, semi-structured interviews were conducted with n=12 radiographers from across England between 2020 and 2021. Recruitment occurred via an initial survey and interviews were conducted online.
Methods: Verbatim transcripts were analysed using a framework analysis approach to create initial codes which led to themes for discussion.
Results: The framework analysis approach resulted in the identification of three constituent themes: (1) Patient, (2) Examination and (3) Radiographer. Each constituent themes were built from a comprehensive coding of the data. Analysis of these themes are presented in terms of quotes and diagrammatic depiction.
Conclusion: For radiographers to be able to identify child safeguarding concerns, alignment of these constituent themes is necessary with the radiographer being the theme that can be greater controlled in terms of knowledge and attitude. Conceptually, this analysis could be extended to other professionals.
Contemporary practice within medical imaging has made it more challenging to assess some physical and social signs of child safeguarding concern, and thus for the alignment to occur, as compared with previous generations.
To maximise the contribution, education needs to account for wider paediatric practice and the imaging modality utilised by the radiographer. A case study approach demonstrating the potential that exists for the profession to contribute would be beneficial. Interprofessionally, greater involvement of radiographers in the assessment and escalation of any concerns could provide benefit to the patient.This research was undertaken as part of internally funded PhD at University of Bradford, UK
Analytical modelling and electrochemical impedance spectroscopy (EIS) to evaluate influence of corrosion product on solution resistance
Get PDFYesElectrochemical impedance spectroscopy (EIS) is a technique used to evaluate the electrochemical behavior of
metallic materials in different environments. In this study, a mathematical model has been developed to analyse
the relationship between solution resistance and concentration conductive-corrosion products (Fe2O3) of metallic
corroded materials. This model has been designed as a part of an experimental series to use EIS as a tool for
mapping the spatial distribution of corrosion by-product from bridge, in order to evaluate the impact of
conductive-corrosion on the properties of the solution. The influence of Fe2O3 on the solution resistance at
varying concentrations, has been modelled. Repetitive electrochemical tests were conducted to investigate the
relationship between the impedance and concentration in three different concentrations of corrosion by-product.
Nyquist and Bode's graphs have been used to quantitatively analyse the EIS data. The implementation of the
proposed mathematical model can quantify the solution resistace based on the mass of presented particles, and
provide significant efficiency and methodological advancement over EIS technique. The experimental outcomes
show a clear link between solution resistance and iron oxide concentration within the solution which is
consistent with the model's finding
Interaction of Acinetobacter sp. RIT 592 induces the production of broad-spectrum antibiotics in Exiguobacterium sp. RIT 594
Get PDFYesAntimicrobial resistance (AMR) is one of the most alarming global public health
challenges of the 21st century. Over 3 million antimicrobial-resistant infections
occur in the United States annually, with nearly 50,000 cases being fatal.
Innovations in drug discovery methods and platforms are crucial to identify
novel antibiotics to combat AMR. We present the isolation and
characterization of potentially novel antibiotic lead compounds produced by
the cross-feeding of two rhizosphere bacteria, Acinetobacter sp. RIT 592 and
Exiguobacterium sp. RIT 594. We used solid-phase extraction (SPE) followed by
liquid chromatography (LC) to enrich antibiotic extracts and subsequently mass
spectrometry (MS) analysis of collected fractions for compound structure
identification and characterization. The MS data were processed through the
Global Natural Product Social Molecular Networking (GNPS) database. The
supernatant from RIT 592 induced RIT 594 to produce a cocktail of
antimicrobial compounds active against Gram-positive and negative bacteria.
The GNPS analysis indicated compounds with known antimicrobial activity in the
bioactive samples, including oligopeptides and their derivatives. This work
emphasizes the utility of microbial community-based platforms to discover
novel clinically relevant secondary metabolites. Future work includes further
structural characterization and antibiotic activity evaluation of the individual
compounds against pathogenic multidrug-resistant (MDR) bacteria.This work was supported by a National Institutes of Health (NIH) award (R15GM144862) to AH
Bio-energy programs in Europe
No full textNoBio-energy availability, its potential and production, challenges, and opportunities in Europe are addressed in this chapter. In addition, a comprehensive comparison of different generations of biofuels, types of bioenergy resource availability for various EU countries, and the prediction of the supply rate has been explained. This book chapter helps us understand the progress of consumable bioenergy resources and expected future trends, which is highly important to know. The basis of this chapter is on the agreements in the European energy institutes and related policies. Furthermore, the potential resources of bio-energy in Europe, environmental impacts, and the challenges and barriers that may be faced in the present and future have been investigated
Establishing the size and configuration of the imaging support workforce: a census of national workforce data in England
Get PDFYesObjectives: The imaging support workforce is a key enabler in unlocking imaging capacity and capability, yet no evidence exists of the workforce size and configuration. This research provides the first comprehensive analysis of workforce data to explore the deployment of the support workforce within National Health Service (NHS) imaging services in England.
Methods: Using a census methodology, an anonymized electronic staff record (ESR) data set extracted in December 2022 was analysed to identify support workers and their employment bandings at NHS Trust, regional and national (England) level. Support workforce proportions, median values, and Spearman’s rank correlations were calculated.
Results: Analysis of 137 NHS Trusts, comprising 100% of acute trusts (n = 124) and specialist trusts with imaging services (n = 13), identified that the support workforce (pay bands 2-4) constitutes 23.6% of the imaging staff base. Ranking trusts into 3 categories based on the proportion of support workers in their imaging establishment, median values ranged from 30.7% (high) to 22.2% (medium) and 10.5% (low). Two opposing deployment models of band 2 and band 3 support workers were identified.
Conclusions: Comprising almost one-quarter of the imaging establishment, models of deployment at bands 2 and 3 are highly variable. Assistant practitioners (band 4) are under-utilised, providing an opportunity to introduce innovations to address workforce demands.
Advances in knowledge: This census is the first to provide evidence of the size and structure of the support workforce, the first step in enabling effective workforce transformation. Further research is required to explain the two opposing deployment models.This study is funded by the NIHR Health Services and Delivery Research programme (I.D. NIHR133813)
Genetic networks suggest Asperger’s syndrome as a distinct subtype of autism spectrum disorders
Get PDFYesBackground: The Diagnostic and Statistical Manual of Mental Disorders (DSM-V) issued new diagnostic criteria for autism spectrum disorders (ASD) which resulted in missing the diagnosis of some cases of Asperger’s syndrome (AS). This negatively affected the support received by those affected. In this study, we explored if AS could be biologically stratified from the broader spectrum through a gene co-expression network preservation analysis.
Methods: We analysed the GEO microarray data of 24 individuals with Asperger’s syndrome and 72 individuals with autism. Then, we used a weighted gene co-expression network (WGCNA) pipeline to construct gene co-expression networks. We explored whether these modules share the same co-expression patterns between autism and Asperger’s syndrome using network preservation analysis.
Results: Our results showed that all co-expression modules of autism are preserved into the Asperger’s syndrome. However, three modules of Asperger’s syndrome out of 30 modules were not preserved in autism.
Gene enrichment analysis revealed that these modules were involved in chromatin remodelling, immune and neuroinflammatory response, synaptic and neuronal development. Brain enrichment analysis showed significant downregulation of neurodevelopment genes in different brain regions associated with impaired social recognition in Asperger’s syndrome.
Conclusions: The identified genetic and molecular profiles suggest that Asperger’s syndrome, despite sharing numerous similarities with autism, possesses a distinct genetic profile that makes it a distinct subtype of autism. This distinction could have significant implications for the management and treatment strategies tailored to individuals with Asperger’s syndrome
Seismic performance of ultra-high performance concrete-filled FRP tube composite columns reinforced with SFCBs: Test and modeling
No full textYesTo reduce residual deformation and address corrosion issues, this paper introduces a novel type of composite columns, utilizing ultra-high-performance concrete (UHPC)-filled fiber reinforced polymer (FRP) tubes (UHPC-FFT) and reinforced with steel-FRP composite bars (SFCBs). The seismic performance of the proposed SFCB-reinforced UHPC-FFT composite columns was evaluated through pseudo-static experiments and numerical analysis in comparison with those of traditional composite columns. Results indicated that the UHPC-FFT composite columns reinforced with SFCB exhibited larger energy dissipation compared with those reinforced with either steel or FRP bars. Increasing the axial compression ratio from 0.15 to 0.25 enhance load-bearing capacity but reduces ductility and energy dissipation. Increasing the yield strength of internal steel bar of SFCBs can improve the load-bearing capacity and deformation of the columns without affecting the ductility, initial stiffness, and stiffness degradation rate. Increasing the elastic modulus of out-wrapped FRP of SFCBs enhanced the seismic performance of UHPC-FFT composite columns but could lead to premature failure due to FRP rupture. It is recommended to set an elastic modulus for the outer FRP wrap at 55 GPa for optimal seismic performance in UHPC-FFT composite columns.High-End Foreign Experts Project of Ministry of Science and Technology, China (G2022014054L), the Natural Science Foundation of Jiangsu Province, China (BK20201436), the Science and Technology Cooperation Fund Project of Yangzhou City and Yangzhou University (YZ2022194), the Science and Technology Project of Jiangsu Construction System (2023ZD104 and 2023ZD105) and the Science and Technology Project of Yangzhou Constructio