1,020 research outputs found

    Production and characterisation of novel recombinant antibody fragments against sialic acid

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    Sialic acids are a family of acidic monosaccharides that typically reside as terminal moieties on N- and O-linked glycans. These sugars are actively involved in a plethora of biological phenomena, ranging from cell-cell adhesion and recognition, intracellular signalling events, pathogen attack, viral infection and inflammatory disease. In addition, many cancer-related antigens contain terminal sialic acids or altered sialylation patterns. The identification of sialic acid-specific antibodies is important in the fields of basic research and diagnostics. Therefore the primary objective of this thesis was the generation and characterisation of recombinant antisialic acid antibodies.A single-chain antibody fragment (scFv) library was constructed from a chicken that was immunised with a novel synthetic sialic acid protein-conjugate (Neu5Gchumanserum albumin). The scFv library was biopanned using a second novel sialoneoglycoconjugate(Neu5Gc-bovine serum albumin). Anti-sialic scFvs were isolated byphage-display and binding activity, multimeric status, and multivalent properties wereassessed by ELISA, HPLC, FPLC, and SPR. One clone, AE8, displayed the strongest reactivity to a panel of different sialylated structures. In addition, SPR inhibition andkinetic analysis revealed that the AE8 scFv had nanomolar affinity for the Neu5Gc-BSA neoglycoconjugate. The heavy chain gene of the AE8 scFv was assembled with a repertoire of error prone PCR-amplified light chain genes, that originated from the unpanned anti-sialic acid library. The mutant scFv library was biopanned using a depletion protocol and two ovalbumin (OVA) conjugates, Neu5Gc-linker1-OVA and linker1-OVA. ELISA analysis, SPR inhibition and ‘off-rate’ studies identified one mutant clone, E15, which displayed strong affinity for conjugates of sialic acid. A solution-phase SPR-based inhibition study demonstrated that the E15 scFv had an IC50 concentration of 1.6ng/mL for the Neu5Gc-BSA conjugate. When compared to the parental AE8 clone (IC50 of 5.7ng/mL) the mutant E15 scFv exhibited an improvement in sialic acid binding of approximately 3.5-fold. The generation of such highly specific anti-sialic acid antibodies in a recombinant format is exceedingly rare. Most anti-carbohydrate antibodies are not recombinant and display weak carbohydrate-protein interactions. This work shows for the first time, the generation and directed evolution of anti-carbohydrate scFvs that have nanomolar affinity for Neu5Gc-containing structures

    Hydrophilic polymeric coatings for enhanced, serial-siphon based flow control on centrifugal lab-on-disc platforms

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    In this paper, we implement rotational flow control on a polymeric microfluidic “lab-on-a-disc” device by combining serial siphoning and capillary valving for sequential release of on-board stored liquid reagents. The functionality of this integrated, multi-step centrifugal assay platform is tightly linked by the capability to establish reproducible, capillary-driven priming of the innately hydrophobic siphon microchannels. We here demonstrate for the first time that spin-coated hydrophilic polymeric films of poly(vinyl alcohol) and (hydroxylpropyl)methylcellulose provide stable contact angles

    The Effects of Psychosis Risk Variants on Brain Connectivity: A Review

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    In light of observed changes in connectivity in schizophrenia and the highly heritable nature of the disease, neural connectivity may serve as an important intermediate phenotype for schizophrenia. However, how individual variants confer altered connectivity and which measure of brain connectivity is more proximal to the underlying genetic architecture (i.e., functional or structural) has not been well delineated. In this review we consider these issues and the relative sensitivity of imaging methodologies to schizophrenia-related changes in connectivity. We searched PubMed for studies considering schizophrenia risk genes AND functional or structural connectivity. Where data was available, summary statistics were used to determine an estimate of effect size (i.e., Cohen’s d). A random-effects meta-analysis was used to consider (1) the largest effect and (2) all significant effects between functional and structural studies. Schizophrenia risk variants involved in neurotransmission, neurodevelopment and myelin function were found to be associated with altered neural connectivity. On average, schizophrenia risk genes had a large effect on functional (mean d = 0.76) and structural connectivity (mean d = 1.04). The examination of the largest effect size indicated that the outcomes of functional and structural studies were comparable (Q = 2.17, p > 0.05). Conversely, consideration of effect size estimates for all significant effects suggest that reported effect sizes in structural connectivity studies were more variable than in functional connectivity studies, and that there was a significant lack of homogeneity across the modalities (Q = 6.928, p = 0.008). Given the more variable profile of effect sizes associated with structural connectivity, these data may suggest that structural imaging methods are more sensitive to a wider range of effects, as opposed to functional studies which may only be able to determine large effects. These conclusions are limited by methodological considerations, and require further investigation involving larger samples, multiple genes, and novel analysis techniques for confirmation

    Requirements engineering in software product line engineering

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    The final publication is available at Springer via http://dx.doi.org/10.1007/s00766-013-0189-0Many attempts have been made to increase the productivity and quality of software products based on software reuse. Software product line practice is one such approach, one that focuses on developing a family of products which have a majority of features in common. Hence, there are numerous requirements that are common across the family, but others are unique to individual products. Traditional requirements engineering methods were conceived to deal with single product requirements and are usually not flexible enough to address the needs arising from reusing requirements for a family of products. There is also the additional burden of correctly identifying and engineering both product-line-wide requirements and product-specific requirements as well as evolving them. Therefore, in this special issue, we want to highlight the importance and the role of requirements engineering for product line development as well as to provide insights into the state of the art in the field.Insfrán Pelozo, CE.; Chastek, G.; Donohoe, P.; Sampaio Do Prado Leite, JC. (2014). Requirements engineering in software product line engineering. Requirements Engineering. 19(4):331-332. doi:10.1007/s00766-013-0189-0S331332194Clements P, Northrop LM (2001) Software product lines: practices and patterns. Addison-Wesley, BostonDerakhshanmanesh M, Fox J, Ebert J (2012) Adopting feature-centric reuse of requirements assets: an industrial experience report. First international workshop on requirements engineering practices on software product line engineering, Salvador, BrazilKuloor C, Eberlein A (2002) Requirements engineering for software product lines, proceedings of the 15th international conference on software and systems engineering and their applications (ICSSEA’02), Paris, FranceNorthrop LM, Clements P (2013) A framework for software product line practice. Software engineering institute. http://www.sei.cmu.edu/productlines/tools/framework/index.cfm . Accessed 22 July 2013Yu Y, Lapouchnian A, Liaskos S, Mylopoulos J, Leite JCSP (2008) From Goals to High-Variability Software Design. Foundations of Intelligent Systems, 17th International Symposium Proceedings. ISMIS 2008. Springer Lecture Notes in Computer Science, 4994: 1–1

    Exploring co-production of accessible digital mental health tools in collaboration with young people from marginalised backgrounds:A Scoping Review

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    ContextDespite evidence that digital mental health supports can improve young people’s access to mental health care, guidance on the most appropriate co-production processes for engaging youth in designing and evaluating these technologies is lacking. User input is critical in digital mental health solutions, particularly for marginalised young people who are often excluded from co-production processes.AimsTo explore the extant literature on co-production processes with marginalised youth in digital mental health supports, ranging from mental health promotion to targeted interventions. A scoping review was chosen to map and summarise the evidence and identify knowledge gaps.MethodThe search spanned 12 databases, including studies from 2021 onwards, focused on co-production with young people aged 16-25 in different stages of designing and assessing digital mental health technologies, especially those who are marginalised.ResultsAfter the screening process, 20 studies were included in the review. Design (n=8) and overall evaluation of the co-design process (n=5) were the primary study foci, with qualitative (n=10) and mixed methods (n=7) dominating the study designs. Most studies utilised human support with a digital component (n=15), while a small number (n=5) used a digital only approach. Promotion/ primary prevention was the dominant study focus (n=16), while four studies addressed targeted interventions. Common study areas included mental wellbeing (n=8), coping/resilience and help-seeking (n=3), followed by interventions addressing stress (n=2), depression (n=2) and anxiety (n=2), but also substance abuse, trauma, and suicide. 8 studies recruited participants through social media, while 6 recruited through health care settings, schools/universities (n=5) or community partners (n=3). In terms of marginalised youth, studies mostly comprised LGBTQ+ (n=12) and ethnic minorities (n=10), and sample sizes averaged 745 in quantitative studies to 22 for qualitative studies.ConclusionThis review covers the co-production processes of design, implementation, evaluation and overall evaluation of co- producing digital mental health supports with marginalised youth. The review highlights youth involvement primarily in design and overall evaluations, with apps being the type of digital mental health support in 6 of those studies and surveys and workshops the most common approaches to involving youth. Overall evaluation studies predominantly focus on promotion/primary prevention and the LGBTQ+ community. There is a need for more consistent user input from marginalised youth such as those with disability, rurally isolated, unemployed/ out of education and immigrants in not only the design stage, but also during implementation, and assessment of digital mental health supports.ImplicationThe findings have clear implications for advancing the inclusion of marginalised youth in the co-production of digital mental health supports and ensuring more effective use of digital technologies in youth mental health services.<br/

    Preliminary findings from a scoping review on co-producing accessible digital mental health tools in partnership with marginalized young people

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    Despite evidence that digital mental health supports can improve young people's access to mental health care, guidance on the most appropriate co-production processes for engaging youth in designing and evaluating these technologies is lacking. User input is critical in digital mental health solutions, particularly for marginalised young people who are often excluded from co-production processes.The aim was to explore the extant literature on co-production processes with marginalised youth in digital mental health supports, ranging from mental health promotion to targeted interventions to serve as the basis for our wider, youth-led project, including a qualitative exploration of digital mental health challenges facing young people across the island of Ireland; identifying, with young people, appropriate digital mental health apps and interventions; validating, in partnership with young people, what digital mental health interventions work; and using these findings to inform policy and practice recommendations for health providers across the island of Ireland and beyond.The scoping review was guided by Arksey and O’Malley’s framework and PRISMA-ScR. The search spanned 12 databases, including studies from 2021 onwards, focused on co-production with young people aged 16-25 in different stages of designing and assessing digital mental health technologies, especially those who are marginalised. Twenty-two studies were identified as meeting the inclusion criteria. Preliminary findings suggest that young people are mainly involved in the initial design phase (n=8) or overall evaluations (n=5) of digital mental health supports and that studies use primarily qualitative (e.g. focus groups and interviews; n=10) or mixed methods (=7) rather than participatory design for co- production.Implications of these findings will be discussed in light of feedback received from the wider project’s youth panel and service provider advisory board to showcase a) the multifaceted concept of co- production and b) how to best translate it into practice to achieve truly youth-led results

    Preliminary findings from a scoping review on co-production of accessible digital mental health tools in collaboration with young people from marginalised backgrounds

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    Despite evidence that digital mental health supports can improve young people's access to mental health care, guidance on the most appropriate co-production processes for engaging youth in designing and evaluating these technologies is lacking. User input is critical in digital mental health solutions, particularly for marginalised young people who are often excluded from co-production processes. The aim was to explore the extant literature on co-production processes with marginalised youth in digital mental health supports, ranging from mental health promotion to targeted interventions.The search spanned 12 databases, including studies from 2021 onwards, focused on co-production with young people aged 16-25 in different stages of designing and assessing digital mental health technologies, especially those who are marginalised.22 studies identified with young people mainly involved in initial design (n=8) or overall evaluation (n=5). 16 studies focused on mental health promotion and apps (n=8) and web-based (n=4) were the most popular digital means.<br/

    Landscape of Digital Mental Health Interventions for Youth Aged 12-25

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    Young people’s mental health is a growing global public concern. Digital mental health interventions offer a cost-effective and accessible solution to complement traditional care, reaching those facing difficulties accessing in-person support. These interventions show promise in enhancing mental health outcomes and can be a valuable component to a comprehensive strategy for young people's well-being.A scoping review was conducted to explore the range of digital solutions to support young people’s mental health. The review included studies that focus on mental wellbeing, mental health, and mental illness, including all types of digital interventions. All types of studies, published from 2017 onwards with a population of young people between ages of 12-25 and validated pre and post mental health or wellbeing primary outcome measure, were included. The search was conducted in 6 databases, initially returning 8,227 records. After screening, 146 studies were included in the final review.Half of the studies recruited participants from the general population who weren’t experiencing mental ill health (n=72, 49%), around a third recruited participants experiencing mental ill health symptoms (n=44, 30%), and 14% (n=21) studies included participants with a mental health diagnosis. Most studies utilised a digital only approach, where the entire intervention was delivered though a digital tool (n=80, 55%) while 45% used a blended approach, where participants used a digital intervention with some degree of human support. However, these figures differed depending on the study population (Figure 1). The most common type of digital tool used was websites (n=79, 54%), followed by apps (n=50, 34%), apps or websites with another tool such as wearables or telehealth (n=7, 5%), chatbots (n=6, 4%), virtual reality (n=2, 1%), text messaging (n=1, &lt;1%) and emails (n=1, &lt;1%). Studies predominately recruited females making up an overage of 70% population, while males accounted for 30% on average. Only 31 out of 146 studies included participants of other genders. Retention rates ranged from 2-100%, with an average of 66% of participants completing the studies. This review highlights the range of digital approaches used with young people, but also the lack of diversity in youth digital mental health study populations. Future work should seek to include more representative populations and overcome barriers to engagement with digital mental health supports. <br/

    Patient-reported outcome measures (PROMs) after laparoscopic cholecystectomy: systematic review

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    BACKGROUND: Healthcare requires patient feedback to improve outcomes and experience. This study undertook a systematic review of the depth, variability, and digital suitability of current patient-reported outcome measures (PROMs) in patients undergoing laparoscopic cholecystectomy. METHODS: A PROSPERO-registered (registration number CRD42021261707) systematic review was undertaken for all relevant English language articles using PubMed version of MEDLINE, Scopus, and Web of Science electronic databases in June 2021. The search used Boolean operators and wildcards and included the keywords: laparoscopic cholecystectomy AND patient outcome OR patient-reported outcome OR patient-reported outcome measure OR PRO OR PROM. Medical Subjects Heading terms were used to search PubMed and Scopus. Articles published from 1 January 2011 to 2 June 2021 were included. RESULTS: A total of 4960 individual articles were reviewed in this study, of which 44 were found to evaluate PROMs in patients undergoing laparoscopic cholecystectomy and underwent methodological index for non-randomized studies (MINORS) grading. Twenty-one articles spanning 19 countries and four continents met all inclusion criteria and were included in the qualitative data synthesis. There was significant heterogeneity in PROMs identified with eight different comprehensive PROM tools used in the 21 studies. There was wide variation in the time points at which PROMs were recorded. Fourteen of 21 studies recorded PROMs before and after surgery, and 7 of 21 recorded PROMs only after surgery. Follow-up intervals ranged from 3 days to 2 years after surgery. CONCLUSIONS: This study identified that while post-laparoscopic cholecystectomy PROMs are infrequently measured currently, tools are widely available to achieve this in clinical practice. PROMs may not capture all the outcomes but should be incorporated into future cholecystectomy outcome research. The EQ-5D™ (EuroQoL Group, Rotterdam, the Netherlands) provides a simple platform for the modern digital era
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