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  1. Article ; Online: Analysis of protected species observer data: Strengths, weaknesses, and application in the assessment of marine mammal responses to seismic surveys in the northern Gulf of Mexico 2002-2015.

    Barkaszi, Mary Jo / Kelly, Christopher J

    PloS one

    2024  Volume 19, Issue 3, Page(s) e0300658

    Abstract: Visual observation data collected by protected species observers (PSOs) is required per regulations stipulated in Notices to Lessees (NTLs) and geophysical survey Permits (Form BOEM-0328) issued to seismic operators in the Gulf of Mexico (GOM). Here, ... ...

    Abstract Visual observation data collected by protected species observers (PSOs) is required per regulations stipulated in Notices to Lessees (NTLs) and geophysical survey Permits (Form BOEM-0328) issued to seismic operators in the Gulf of Mexico (GOM). Here, data collected by certified and trained PSOs during seismic surveys conducted between 2002-2015 were compiled and analyzed to assess utility in assessing marine mammal responses to seismic noise and effectiveness of required mitigation measures. A total of 3,886 agency-required bi-weekly PSO Effort and Sightings reports were analyzed comprising 598,319 hours of PSO visual effort and 15,117 visual sighting records of marine mammals. The observed closest point of approach (CPA) distance was statistically compared across five species groupings for four airgun activity levels (full, minimum source, ramp up, silent). Whale and dolphin detections were significantly farther from airgun array locations during full power operations versus silence, indicating some avoidance response to full-power operations. Dolphin CPA distances were also significantly farther from airguns operating at minimum source than silence. Blackfish were observed significantly farther from the airgun array during ramp up versus both full and minimum source activities. Blackfish were observed significantly closer to the airgun array during silent activities versus at full, minimum source, and ramp up activities. Beaked whales had the largest mean CPA for detection distance compared to all other species groups. Detection distances for beaked whales were not significantly differences between full and silent operations; however, the sample size was very low. Overall results are consistent with other studies indicating that marine mammals may avoid exposure to airgun sounds based on observed distance from the seismic source during specified source activities. There was geographic variability in sighting rates associated with specific areas of interest within the GOM. This study demonstrates that agency required PSO reports provide a robust and useful data set applicable to impact assessments; management, policy and regulatory decision making; and qualitative input for regional scientific, stock assessment and abundance studies. However, several improvements in content and consistency would facilitate finer-scale analysis of some topics (e.g., effort associated with specific activities, observer biases, sound field estimation) and support statistical comparisons that could provide further insight into marine mammal responses and mitigation efficacy.
    MeSH term(s) Animals ; Gulf of Mexico ; Acoustics ; Sound ; Whales/physiology ; Dolphins
    Language English
    Publishing date 2024-03-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0300658
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Ubiquitin receptors play redundant roles in the proteasomal degradation of the p53 repressor MDM2

    Sparks, Alison / Kelly, Christopher J. / Saville, Mark K.

    FEBS Letters. 2022 Nov., v. 596, no. 21 p.2746-2767

    2022  

    Abstract: Much remains to be determined about the participation of ubiquitin receptors in proteasomal degradation and their potential as therapeutic targets. Suppression of the ubiquitin receptor S5A/PSMD4/hRpn10 alone stabilises p53/TP53 but not the key p53 ... ...

    Abstract Much remains to be determined about the participation of ubiquitin receptors in proteasomal degradation and their potential as therapeutic targets. Suppression of the ubiquitin receptor S5A/PSMD4/hRpn10 alone stabilises p53/TP53 but not the key p53 repressor MDM2. Here, we observed S5A and the ubiquitin receptors ADRM1/PSMD16/hRpn13 and RAD23A and B functionally overlap in MDM2 degradation. We provide further evidence that degradation of only a subset of ubiquitinated proteins is sensitive to S5A knockdown because ubiquitin receptor redundancy is commonplace. p53 can be upregulated by S5A modulation while degradation of substrates with redundant receptors is maintained. Our observations and analysis of Cancer Dependency Map (DepMap) screens show S5A depletion/loss substantially reduces cancer cell line viability. This and selective S5A dependency of proteasomal substrates make S5A a target of interest for cancer therapy.
    Keywords cancer therapy ; cell lines ; neoplasm cells ; ubiquitin ; viability
    Language English
    Dates of publication 2022-11
    Size p. 2746-2767.
    Publishing place John Wiley & Sons, Ltd
    Document type Article ; Online
    Note JOURNAL ARTICLE
    ZDB-ID 212746-5
    ISSN 1873-3468 ; 0014-5793
    ISSN (online) 1873-3468
    ISSN 0014-5793
    DOI 10.1002/1873-3468.14436
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Ubiquitin receptors play redundant roles in the proteasomal degradation of the p53 repressor MDM2.

    Sparks, Alison / Kelly, Christopher J / Saville, Mark K

    FEBS letters

    2022  Volume 596, Issue 21, Page(s) 2746–2767

    Abstract: Much remains to be determined about the participation of ubiquitin receptors in proteasomal degradation and their potential as therapeutic targets. Suppression of the ubiquitin receptor S5A/PSMD4/hRpn10 alone stabilises p53/TP53 but not the key p53 ... ...

    Abstract Much remains to be determined about the participation of ubiquitin receptors in proteasomal degradation and their potential as therapeutic targets. Suppression of the ubiquitin receptor S5A/PSMD4/hRpn10 alone stabilises p53/TP53 but not the key p53 repressor MDM2. Here, we observed S5A and the ubiquitin receptors ADRM1/PSMD16/hRpn13 and RAD23A and B functionally overlap in MDM2 degradation. We provide further evidence that degradation of only a subset of ubiquitinated proteins is sensitive to S5A knockdown because ubiquitin receptor redundancy is commonplace. p53 can be upregulated by S5A modulation while degradation of substrates with redundant receptors is maintained. Our observations and analysis of Cancer Dependency Map (DepMap) screens show S5A depletion/loss substantially reduces cancer cell line viability. This and selective S5A dependency of proteasomal substrates make S5A a target of interest for cancer therapy.
    MeSH term(s) Ubiquitin/metabolism ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Ubiquitinated Proteins/metabolism ; Carrier Proteins ; Proto-Oncogene Proteins c-mdm2/genetics ; Proto-Oncogene Proteins c-mdm2/metabolism
    Chemical Substances Ubiquitin ; Tumor Suppressor Protein p53 ; Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Ubiquitinated Proteins ; Carrier Proteins ; Proto-Oncogene Proteins c-mdm2 (EC 2.3.2.27)
    Language English
    Publishing date 2022-07-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 212746-5
    ISSN 1873-3468 ; 0014-5793
    ISSN (online) 1873-3468
    ISSN 0014-5793
    DOI 10.1002/1873-3468.14436
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Promoting innovation in healthcare.

    Kelly, Christopher J / Young, Antony J

    Future healthcare journal

    2019  Volume 4, Issue 2, Page(s) 121–125

    Abstract: Innovation can be defined as invention + adoption + diffusion. In healthcare, it may be a novel idea, product, service or care pathway that has clear benefits when compared to what is currently done. Successful innovations often possess two key qualities: ...

    Abstract Innovation can be defined as invention + adoption + diffusion. In healthcare, it may be a novel idea, product, service or care pathway that has clear benefits when compared to what is currently done. Successful innovations often possess two key qualities: they are both usable and desirable. How can proven innovations be quickly and effectively adopted as best practice and taken up across the whole healthcare system? How can the commercial success of our ideas be realised at home rather than abroad, as has too often been the case? This review explores important issues of funding, information governance, interoperability, medical device regulation, procurement, clinical prototyping and the systemic challenge of encouraging and scaling innovation.
    Language English
    Publishing date 2019-05-15
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 3016427-8
    ISSN 2514-6653 ; 2514-6645
    ISSN (online) 2514-6653
    ISSN 2514-6645
    DOI 10.7861/futurehosp.4-2-121
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Development of Good Manufacturing Practice-Compatible Isolation and Culture Methods for Human Olfactory Mucosa-Derived Mesenchymal Stromal Cells.

    Kelly, Christopher J / Lindsay, Susan L / Smith, Rebecca Sherrard / Keh, Siew / Cunningham, Kyle T / Thümmler, Katja / Maizels, Rick M / Campbell, John D M / Barnett, Susan C

    International journal of molecular sciences

    2024  Volume 25, Issue 2

    Abstract: Demyelination in the central nervous system (CNS) resulting from injury or disease can cause loss of nerve function and paralysis. Cell therapies intended to promote remyelination of axons are a promising avenue of treatment, with mesenchymal stromal ... ...

    Abstract Demyelination in the central nervous system (CNS) resulting from injury or disease can cause loss of nerve function and paralysis. Cell therapies intended to promote remyelination of axons are a promising avenue of treatment, with mesenchymal stromal cells (MSCs) a prominent candidate. We have previously demonstrated that MSCs derived from human olfactory mucosa (hOM-MSCs) promote myelination to a greater extent than bone marrow-derived MSCs (hBM-MSCs). However, hOM-MSCs were developed using methods and materials that were not good manufacturing practice (GMP)-compliant. Before considering these cells for clinical use, it is necessary to develop a method for their isolation and expansion that is readily adaptable to a GMP-compliant environment. We demonstrate here that hOM-MSCs can be derived without enzymatic tissue digestion or cell sorting and without culture antibiotics. They grow readily in GMP-compliant media and express typical MSC surface markers. They robustly produce CXCL12 (a key secretory factor in promoting myelination) and are pro-myelinating in in vitro rodent CNS cultures. GMP-compliant hOM-MSCs are comparable in this respect to those grown in non-GMP conditions. However, when assessed in an in vivo model of demyelinating disease (experimental autoimmune encephalitis, EAE), they do not significantly improve disease scores compared with controls, indicating further pre-clinical evaluation is necessary before their advancement to clinical trials.
    MeSH term(s) Humans ; Culture Techniques ; Anti-Bacterial Agents ; Axons ; Biological Transport ; Mesenchymal Stem Cells
    Chemical Substances Anti-Bacterial Agents
    Language English
    Publishing date 2024-01-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25020743
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: MRI studies of brain size and growth in individuals with congenital heart disease.

    Bonthrone, Alexandra F / Kelly, Christopher J / Ng, Isabel H X / Counsell, Serena J

    Translational pediatrics

    2021  Volume 10, Issue 8, Page(s) 2171–2181

    Abstract: Congenital heart disease (CHD) is the most frequent congenital abnormality. Most infants born with CHD now survive. However, survivors of CHD are at increased risk of neurodevelopmental impairment, which may be due to impaired brain development in the ... ...

    Abstract Congenital heart disease (CHD) is the most frequent congenital abnormality. Most infants born with CHD now survive. However, survivors of CHD are at increased risk of neurodevelopmental impairment, which may be due to impaired brain development in the fetal and neonatal period. Magnetic resonance imaging (MRI) provides objective measures of brain volume and growth. Here, we review MRI studies assessing brain volume and growth in individuals with CHD from the fetus to adolescence. Smaller brain volumes compared to healthy controls are evident from around 30 weeks gestation in fetuses with CHD and are accompanied by increased extracerebral cerebrospinal fluid. This impaired brain growth persists after birth and throughout childhood to adolescence. Risk factors for impaired brain growth include reduced cerebral oxygen delivery in utero, longer time to surgery and increased hospital stay. There is increasing evidence that smaller total and regional brain volumes in this group are associated with adverse neurodevelopmental outcome. However, to date, few studies have assessed the association between early measures of cerebral volume and neurodevelopmental outcome in later childhood. Large prospective multicentre studies are required to better characterise the relationship between brain volume and growth, clinical risk factors and subsequent cognitive, motor, and behavioural impairments in this at-risk population.
    Language English
    Publishing date 2021-09-28
    Publishing country China
    Document type Journal Article ; Review
    ZDB-ID 2901309-4
    ISSN 2224-4344 ; 2224-4344 ; 2224-4336
    ISSN (online) 2224-4344
    ISSN 2224-4344 ; 2224-4336
    DOI 10.21037/tp-20-282
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Inflammatory Chemokine Receptors Support Inflammatory Macrophage and Dendritic Cell Maturation.

    Bartolini, Robin / Medina-Ruiz, Laura / Hayes, Alan J / Kelly, Christopher J / Halawa, Heba A / Graham, Gerard J

    ImmunoHorizons

    2022  Volume 6, Issue 11, Page(s) 743–759

    Abstract: Dendritic cells form clusters in vivo, but the mechanism behind this has not been determined. In this article, we demonstrate that monocytes from mice deficient in the chemokine receptors CCR1, CCR2, CCR3, and CCR5 display reduced clustering in vitro, ... ...

    Abstract Dendritic cells form clusters in vivo, but the mechanism behind this has not been determined. In this article, we demonstrate that monocytes from mice deficient in the chemokine receptors CCR1, CCR2, CCR3, and CCR5 display reduced clustering in vitro, which is associated with impaired dendritic cell and macrophage differentiation. We further show that the differentiating cells themselves produce ligands for these receptors that function, in a redundant manner, to regulate cell clustering. Deletion of, or pharmacological blockade of, more than one of these receptors is required to impair clustering and differentiation. Our data show that chemokines and their receptors support clustering by increasing expression of, and activating, cell-surface integrins, which are associated with cell-cell interactions and, in the context of monocyte differentiation, with reduced expression of Foxp1, a known transcriptional suppressor of monocyte differentiation. Our data therefore provide a mechanism whereby chemokines and their receptors typically found in inflammatory environments can interact to promote murine monocyte differentiation to macrophages and dendritic cells.
    MeSH term(s) Mice ; Animals ; Receptors, Chemokine/metabolism ; Macrophages/metabolism ; Monocytes/metabolism ; Chemokines/metabolism ; Dendritic Cells/metabolism
    Chemical Substances Receptors, Chemokine ; Chemokines
    Language English
    Publishing date 2022-11-25
    Publishing country United States
    Document type Journal Article
    ISSN 2573-7732
    ISSN (online) 2573-7732
    DOI 10.4049/immunohorizons.2200069
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Book ; Conference proceedings ; Online: Cassian's Conferences

    Kelly, Christopher J

    scriptual interpretation and the monastic ideal

    (Ashgate new critical thinking in religion, theology, and biblical studies)

    2012  

    Abstract: This book explores Cassian's use of scripture in the 'Conferences', especially its biblical models to convey his understanding of the desert ideal to the monastic communities of Gaul. This book demonstrates how the scriptures functioned as a dynamic ... ...

    Author's details Christopher J. Kelly
    Series title Ashgate new critical thinking in religion, theology, and biblical studies
    Abstract This book explores Cassian's use of scripture in the 'Conferences', especially its biblical models to convey his understanding of the desert ideal to the monastic communities of Gaul. This book demonstrates how the scriptures functioned as a dynamic force in the lives of Christian, emphasizes the importance of Cassian in the development of the western monastic tradition, and offers an alternative to the sometimes problematic descriptions of patristic exegesis as "allegory" or "typology."
    Keywords Monastic and religious life/History of doctrines
    Language English
    Size Online-Ressource (xi, 134 p.)
    Publisher Ashgate
    Publishing place Farnham, Surrey, England ;Burlington, VT
    Document type Book ; Conference proceedings ; Online
    Note Includes bibliographical references (p. [127]-132) and index
    ISBN 1283382385 ; 1283382687 ; 1409405591 ; 1409405605 ; 9781283382687 ; 9781409405597 ; 9781409405603 ; 9781283382380
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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  9. Article ; Online: Stakeholder Perspectives of Clinical Artificial Intelligence Implementation: Systematic Review of Qualitative Evidence.

    Hogg, Henry David Jeffry / Al-Zubaidy, Mohaimen / Talks, James / Denniston, Alastair K / Kelly, Christopher J / Malawana, Johann / Papoutsi, Chrysanthi / Teare, Marion Dawn / Keane, Pearse A / Beyer, Fiona R / Maniatopoulos, Gregory

    Journal of medical Internet research

    2023  Volume 25, Page(s) e39742

    Abstract: 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 ... ...

    Abstract 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=256005.
    International registered report identifier (irrid): RR2-10.2196/33145.
    MeSH term(s) Humans ; Artificial Intelligence ; Health Personnel ; Machine Learning ; Qualitative Research
    Language English
    Publishing date 2023-01-10
    Publishing country Canada
    Document type Journal Article ; Review ; Systematic Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2028830-X
    ISSN 1438-8871 ; 1438-8871
    ISSN (online) 1438-8871
    ISSN 1438-8871
    DOI 10.2196/39742
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Advances in neonatal MRI of the brain: from research to practice.

    Kelly, Christopher J / Hughes, Emer J / Rutherford, Mary A / Counsell, Serena J

    Archives of disease in childhood. Education and practice edition

    2018  Volume 104, Issue 2, Page(s) 106–110

    MeSH term(s) Brain/diagnostic imaging ; Brain Diseases/diagnostic imaging ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases/diagnostic imaging ; Magnetic Resonance Imaging ; Neonatology
    Language English
    Publishing date 2018-03-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2148818-6
    ISSN 1743-0593 ; 1743-0585
    ISSN (online) 1743-0593
    ISSN 1743-0585
    DOI 10.1136/archdischild-2018-314778
    Database MEDical Literature Analysis and Retrieval System OnLINE

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