Sequence diversity in the A domain of Staphylococcus aureus fibronectin-binding protein A

<p>Abstract</p> <p>Background</p> <p>Fibronectin-binding protein A (FnBPA) mediates adhesion of <it>Staphylococcus aureus </it>to fibronectin, fibrinogen and elastin. We previously reported that <it>S. aureus </it>strain P1 encodes an FnBPA protein where the fibrinogen/elastin-binding domain (A domain) is substantially divergent in amino acid sequence from the archetypal FnBPA of <it>S. aureus </it>NCTC8325, and that these variations created differences in antigenicity. In this study strains from multilocus sequence types (MLST) that spanned the genetic diversity of <it>S.aureus </it>were examined to determine the extent of FnBPA A domain variation within the <it>S. aureus </it>population and its effect on ligand binding and immuno-crossreactivity.</p> <p>Results</p> <p>Seven different isotype forms (I – VII) of the FnBPA A domain were identified which were between 66 to 76% identical in amino acid sequence in any pair-wise alignment. The <it>fnbA </it>allelic variants in strains of different multilocus sequence type were identified by DNA hybridization using probes specific for sequences encoding the highly divergent N3 sub-domain of different isotypes. Several isotypes were not restricted to specific clones or clonal complexes but were more widely distributed. It is highly likely that certain <it>fnbA </it>genes have been transferred horizontally. Residues lining the putative ligand-binding trench were conserved, which is consistent with the ability of each A domain isotype to bind immobilized fibrinogen and elastin by the dock-latch-lock mechanism. Variant amino acid residues were mapped on a three-dimensional model of the FnBPA A domain and were predicted to be surface-exposed. Polyclonal antibodies raised against the recombinant isotype I A domain bound that protein with a 4 – 7 fold higher apparent affinity compared to the A domains of isotypes II – VII, while some monoclonal antibodies generated against the isotype I A domain showed reduced or no binding to the other isotypes.</p> <p>Conclusion</p> <p>The FnBPA A domain occurs in at least 7 different isotypes which differ antigenically and exhibit limited immuno-crossreactivity, yet retain their ligand-binding functions. Antigenic variation of the FnBPA A domain may aid <it>S. aureus </it>to evade the host's immune responses. These findings have implications for the development of vaccines or immunotherapeutics that target FnBPA.</p

Gut microbiome patterns depending on children's psychosocial stress : reports versus biomarkers

Aim: Chronic stress increases disease vulnerability factors including inflammation, a pathological characteristic potentially regulated by the gut microbiota. We checked the association between the gut microbiome and psychosocial stress in children/adolescents and investigated which stress parameter (negative versus positive emotion, self-report versus parental report, events versus emotions, biomarker cortisol versus parasympathetic activity) is the most relevant indicator herein. Methods: Gut microbiome sequencing was completed in fecal samples from 93 Belgian 8-16y olds. Stress measures included negative events, negative emotions, emotional problems reported by parents, happiness, hair cortisol and heart rate variability (pnn50 parameter reflecting parasympathetic activity). Alpha diversity, beta diversity and linear discriminant analysis were the unadjusted analyses. Age, sex, socio-economic status, diet, physical activity, sleep and weight status were adjusted for via a redundancy analysis and differential abundance via zero-inflated negative binomial regression. Results: High stress as reflected by low pnn50 and more negative events were associated with a lower alpha diversity as indicated by the Simpson index. Happiness and pnn50 showed significant differences between high and low stress groups based on weighted UniFrac distance, and this remained significant after confounder adjustment. Adjusted and unadjusted taxonomic differences were also most pronounced for happiness and pnn50 being associated respectively with 24 OTU (=11.8% of bacterial counts) and 31 OTU (=13.0%). As a general pattern, high stress was associated with lower Firmicutes at the phylum level and higher Bacteroides, Parabacteroides, Rhodococcus, Methanobrevibacter and Roseburia but lower Phascolarctobacterium at genus level. Several genera gave conflicting results between different stress measures e.g. Ruminococcaceae UCG014, Tenericutes, Eubacterium coprostanoligenes, Prevotella 9 and Christensenellaceae R7. Differential results in preadolescents versus adolescents were also evident. Conclusion: Even in this young healthy population, stress parameters were cross-sectionally associated with gut microbial composition but this relationship was instrument specific. Positive emotions and parasympathetic activity appeared the strongest parameters and should be integrated in future microbiota projects amongst other stress measures

Stakeholder Perspectives on Clinical Decision Support Tools to Inform Clinical Artificial Intelligence Implementation: Protocol for a Framework Synthesis for Qualitative Evidence

BACKGROUND: Quantitative systematic reviews have identified clinical artificial intelligence (AI)-enabled tools with adequate performance for real-world implementation. To our knowledge, no published report or protocol synthesizes the full breadth of stakeholder perspectives. The absence of such a rigorous foundation perpetuates the "AI chasm," which continues to delay patient benefit. OBJECTIVE: The aim of this research is to synthesize stakeholder perspectives of computerized clinical decision support tools in any health care setting. Synthesized findings will inform future research and the implementation of AI into health care services. METHODS: The search strategy will use MEDLINE (Ovid), Scopus, CINAHL (EBSCO), ACM Digital Library, and Science Citation Index (Web of Science). Following deduplication, title, abstract, and full text screening will be performed by 2 independent reviewers with a third topic expert arbitrating. The quality of included studies will be appraised to support interpretation. Best-fit framework synthesis will be performed, with line-by-line coding completed by 2 independent reviewers. Where appropriate, these findings will be assigned to 1 of 22 a priori themes defined by the Nonadoption, Abandonment, Scale-up, Spread, and Sustainability framework. New domains will be inductively generated for outlying findings. The placement of findings within themes will be reviewed iteratively by a study advisory group including patient and lay representatives. RESULTS: Study registration was obtained from PROSPERO (CRD42021256005) in May 2021. Final searches were executed in April, and screening is ongoing at the time of writing. Full text data analysis is due to be completed in October 2021. We anticipate that the study will be submitted for open-access publication in late 2021. CONCLUSIONS: This paper describes the protocol for a qualitative evidence synthesis aiming to define barriers and facilitators to the implementation of computerized clinical decision support tools from all relevant stakeholders. The results of this study are intended to expedite the delivery of patient benefit from AI-enabled clinical tools. TRIAL REGISTRATION: PROSPERO CRD42021256005; https://tinyurl.com/r4x3thvp. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/33145

Stakeholder Perspectives on Clinical Decision Support Tools to Inform Clinical Artificial Intelligence Implementation: Protocol for a Framework Synthesis for Qualitative Evidence

Quantitative systematic reviews have identified clinical artificial intelligence (AI)-enabled tools with adequate performance for real-world implementation. To our knowledge, no published report or protocol synthesizes the full breadth of stakeholder perspectives. The absence of such a rigorous foundation perpetuates the "AI chasm," which continues to delay patient benefit. The aim of this research is to synthesize stakeholder perspectives of computerized clinical decision support tools in any health care setting. Synthesized findings will inform future research and the implementation of AI into health care services. The search strategy will use MEDLINE (Ovid), Scopus, CINAHL (EBSCO), ACM Digital Library, and Science Citation Index (Web of Science). Following deduplication, title, abstract, and full text screening will be performed by 2 independent reviewers with a third topic expert arbitrating. The quality of included studies will be appraised to support interpretation. Best-fit framework synthesis will be performed, with line-by-line coding completed by 2 independent reviewers. Where appropriate, these findings will be assigned to 1 of 22 a priori themes defined by the Nonadoption, Abandonment, Scale-up, Spread, and Sustainability framework. New domains will be inductively generated for outlying findings. The placement of findings within themes will be reviewed iteratively by a study advisory group including patient and lay representatives. Study registration was obtained from PROSPERO (CRD42021256005) in May 2021. Final searches were executed in April, and screening is ongoing at the time of writing. Full text data analysis is due to be completed in October 2021. We anticipate that the study will be submitted for open-access publication in late 2021. This paper describes the protocol for a qualitative evidence synthesis aiming to define barriers and facilitators to the implementation of computerized clinical decision support tools from all relevant stakeholders. The results of this study are intended to expedite the delivery of patient benefit from AI-enabled clinical tools. PROSPERO CRD42021256005; https://tinyurl.com/r4x3thvp. DERR1-10.2196/33145. [Abstract copyright: ©Mohaimen Al-Zubaidy, HD Jeffry Hogg, Gregory Maniatopoulos, James Talks, Marion Dawn Teare, Pearse A Keane, Fiona R Beyer. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 01.04.2022.

Non-tuberculous mycobacterial pulmonary disease (NTM-PD): Epidemiology, diagnosis and multidisciplinary management

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause significant disease in both immunocompromised and immunocompetent individuals. The incidence of NTM pulmonary disease (NTM-PD) is rising globally. Diagnostic challenges persist and treatment efficacy is variable. This article provides an overview of NTM-PD for clinicians. We discuss how common it is, who is at risk, how it is diagnosed and the multidisciplinary approach to its clinical management. [Abstract copyright: Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.

Dissecting the illegal ivory trade: an analysis of ivory seizures data

Reliable evidence of trends in the illegal ivory trade is important for informing decision making for elephants but it is difficult to obtain due to the covert nature of the trade. The Elephant Trade Information System, a global database of reported seizures of illegal ivory, holds the only extensive information on illicit trade available. However inherent biases in seizure data make it difficult to infer trends; countries differ in their ability to make and report seizures and these differences cannot be directly measured. We developed a new modelling framework to provide quantitative evidence on trends in the illegal ivory trade from seizures data. The framework used Bayesian hierarchical latent variable models to reduce bias in seizures data by identifying proxy variables that describe the variability in seizure and reporting rates between countries and over time. Models produced bias-adjusted smoothed estimates of relative trends in illegal ivory activity for raw and worked ivory in three weight classes. Activity is represented by two indicators describing the number of illegal ivory transactions--Transactions Index--and the total weight of illegal ivory transactions--Weights Index--at global, regional or national levels. Globally, activity was found to be rapidly increasing and at its highest level for 16 years, more than doubling from 2007 to 2011 and tripling from 1998 to 2011. Over 70% of the Transactions Index is from shipments of worked ivory weighing less than 10 kg and the rapid increase since 2007 is mainly due to increased consumption in China. Over 70% of the Weights Index is from shipments of raw ivory weighing at least 100 kg mainly moving from Central and East Africa to Southeast and East Asia. The results tie together recent findings on trends in poaching rates, declining populations and consumption and provide detailed evidence to inform international decision making on elephants

Stakeholder Perspectives of Clinical Artificial Intelligence Implementation: Systematic Review of Qualitative Evidence

Background: The rhetoric surrounding clinical artificial intelligence (AI) often exaggerates its effect on real-world care. Limited understanding of the factors that influence its implementation can perpetuate this. Objective: In this qualitative systematic review, we aimed to identify key stakeholders, consolidate their perspectives on clinical AI implementation, and characterize the evidence gaps that future qualitative research should target. Methods: Ovid-MEDLINE, EBSCO-CINAHL, ACM Digital Library, Science Citation Index-Web of Science, and Scopus were searched for primary qualitative studies on individuals’ perspectives on any application of clinical AI worldwide (January 2014-April 2021). The definition of clinical AI includes both rule-based and machine learning–enabled or non–rule-based decision support tools. The language of the reports was not an exclusion criterion. Two independent reviewers performed title, abstract, and full-text screening with a third arbiter of disagreement. Two reviewers assigned the Joanna Briggs Institute 10-point checklist for qualitative research scores for each study. A single reviewer extracted free-text data relevant to clinical AI implementation, noting the stakeholders contributing to each excerpt. The best-fit framework synthesis used the Nonadoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework. To validate the data and improve accessibility, coauthors representing each emergent stakeholder group codeveloped summaries of the factors most relevant to their respective groups. Results: The initial search yielded 4437 deduplicated articles, with 111 (2.5%) eligible for inclusion (median Joanna Briggs Institute 10-point checklist for qualitative research score, 8/10). Five distinct stakeholder groups emerged from the data: health care professionals (HCPs), patients, carers and other members of the public, developers, health care managers and leaders, and regulators or policy makers, contributing 1204 (70%), 196 (11.4%), 133 (7.7%), 129 (7.5%), and 59 (3.4%) of 1721 eligible excerpts, respectively. All stakeholder groups independently identified a breadth of implementation factors, with each producing data that were mapped between 17 and 24 of the 27 adapted Nonadoption, Abandonment, Scale-up, Spread, and Sustainability subdomains. Most of the factors that stakeholders found influential in the implementation of rule-based clinical AI also applied to non–rule-based clinical AI, with the exception of intellectual property, regulation, and sociocultural attitudes. Conclusions: Clinical AI implementation is influenced by many interdependent factors, which are in turn influenced by at least 5 distinct stakeholder groups. This implies that effective research and practice of clinical AI implementation should consider multiple stakeholder perspectives. The current underrepresentation of perspectives from stakeholders other than HCPs in the literature may limit the anticipation and management of the factors that influence successful clinical AI implementation. Future research should not only widen the representation of tools and contexts in qualitative research but also specifically investigate the perspectives of all stakeholder HCPs and emerging aspects of non–rule-based clinical AI implementation. Trial Registration: PROSPERO (International Prospective Register of Systematic Reviews) CRD42021256005; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=25600

A review of innovation strategies and processes to improve access to AT: Looking ahead to open innovation ecosystems.

It is essential to understand the strategies and processes which are deployed currently across the Assistive Technology (AT) space toward measuring innovation. The main aim of this paper is to identify functional innovation strategies and processes which are being or can be deployed in the AT space to increase access to AT globally. We conducted a scoping review of innovation strategies and processes in peer-reviewed literature databases and complemented this by identifying case studies demonstrating innovation strategies. The review includes WHO world region, publication year, AT type and a sector analysis against the Systems-Market for Assistive and Related Technologies Framework. We analyzed the case studies and interviews using thematic analysis. We included 91 papers out of 3,127 after review along with 72 case studies. Our results showed that product innovations were more prevalent than provision or supply innovations across papers and case studies. Case studies yielded two themes: open innovation (OI); radical and disruptive innovation. Financial instruments which encourage OI are needed and we recommend pursuing OI for AT innovation. Embedding AT within larger societal missions will be key to success governments and investors need to understand what AT is and their translational socioeconomic value

Primary Care and Youth Mental Health in Ireland: Qualitative Study in Deprived Urban Areas

BACKGROUND: Mental disorders account for six of the 20 leading causes of disability worldwide with a very high prevalence of psychiatric morbidity in youth aged 15-24 years. However, healthcare professionals are faced with many challenges in the identification and treatment of mental and substance use disorders in young people (e.g. young people\u27s unwillingness to seek help from healthcare professionals, lack of training, limited resources etc.) The challenge of youth mental health for primary care is especially evident in urban deprived areas, where rates of and risk factors for mental health problems are especially common. There is an emerging consensus that primary care is well placed to address mental and substance use disorders in young people especially in deprived urban areas. This study aims to describe healthcare professionals\u27 experience and attitudes towards screening and early intervention for mental and substance use disorders among young people (16-25 years) in primary care in deprived urban settings in Ireland. METHODS: The chosen method for this qualitative study was inductive thematic analysis which involved semi-structured interviews with 37 healthcare professionals from primary care, secondary care and community agencies at two deprived urban centres. RESULTS: We identified three themes in respect of interventions to increase screening and treatment: (1) Identification is optimised by a range of strategies, including raising awareness, training, more systematic and formalised assessment, and youth-friendly practices (e.g. communication skills, ensuring confidentiality); (2) Treatment is enhanced by closer inter-agency collaboration and training for all healthcare professionals working in primary care; (3) Ongoing engagement is enhanced by motivational work with young people, setting achievable treatment goals, supporting transition between child and adult mental health services and recognising primary care\u27s longitudinal nature as a key asset in promoting treatment engagement. CONCLUSIONS: Especially in deprived areas, primary care is central to early intervention for youth mental health. Identification, treatment and continuing engagement are likely to be enhanced by a range of strategies with young people, healthcare professionals and systems. Further research on youth mental health and primary care, including qualitative accounts of young people\u27s experience and developing complex interventions that promote early intervention are priorities