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  1. Book: Ian McEwan's "Enduring Love"

    Clark, Roger / Gordon, Andy

    a reader's guide

    (Continuum contemporaries)

    2003  

    Author's details Roger Clark and Andy Gordon
    Series title Continuum contemporaries
    Language English
    Size 94 S
    Publisher Continuum
    Publishing place New York, NY
    Document type Book
    ISBN 0826414788 ; 9780826414786
    Database Former special subject collection: coastal and deep sea fishing

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  2. Article ; Online: How diseases caused by parasites allowed a wider understanding of disease in general: my encounters with parasitology in Australia and elsewhere over the last 50 years.

    Clark, Ian A

    International journal for parasitology

    2021  Volume 51, Issue 13-14, Page(s) 1265–1276

    Abstract: This is an account of how it can prove possible to carve a reasonable scientific career by following what brought most scientific thrill rather than pursue a safe, institution-directed, path. The fascination began when I noticed, quite unexpectedly, that ...

    Abstract This is an account of how it can prove possible to carve a reasonable scientific career by following what brought most scientific thrill rather than pursue a safe, institution-directed, path. The fascination began when I noticed, quite unexpectedly, that the normal mouse immune response causes Babesia microti to die, en masse, inside circulating red cells. It eventuated that prior Bacillus Calmette Guerin infection caused the same outcome, even before the protozoal infection became patent. It also rendered mice quite immune, long term. I acquired an obsession about this telling us how little we know. Surrounded by basic immunologists, parasitologists and virologists in London, I had been given, in the days that funding was ample, the opportunity to follow any promising lead with a free hand. Through Bacillus Calmette Guerin, this meant stumbling through a set of phenomena that were in their infancies, and could be explained only through nebulous novel soluble mediators such as TNF, described the following year as causing the in vivo necrosis of tumours in mice. Beginning with malarial disease pathogenesis, I followed TNF wherever it led, into innate immunity, acute and chronic infections, neurophysiology and neurodegenerative diseases, in all of which states awareness of the role of this cytokine is still growing fast. Many of these steps can be illustrated and expanded upon in parasitic diseases. Covering the importance of TNF in the pathogenesis of neurodegenerative disease has proved to be highly illuminating, scientifically and otherwise. But the insights it has given me into understanding the temptations to which patent-owners can succumb when faced with opportunities to put money before people is not for the faint hearted. Clearly, parasitologists inhabit a much more common-good yet science-orientated, civilised, world.
    MeSH term(s) Animals ; Australia ; BCG Vaccine ; Babesia microti ; Humans ; Mice ; Neurodegenerative Diseases ; Parasites
    Chemical Substances BCG Vaccine
    Language English
    Publishing date 2021-10-30
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 120518-3
    ISSN 1879-0135 ; 0020-7519
    ISSN (online) 1879-0135
    ISSN 0020-7519
    DOI 10.1016/j.ijpara.2021.10.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Release of cognitive and multimodal MRI data including real-world tasks and hippocampal subfield segmentations.

    Clark, Ian A / Maguire, Eleanor A

    Scientific data

    2023  Volume 10, Issue 1, Page(s) 540

    Abstract: We share data from N = 217 healthy adults (mean age 29 years, range 20-41; 109 females, 108 males) who underwent extensive cognitive assessment and neuroimaging to examine the neural basis of individual differences, with a particular focus on a brain ... ...

    Abstract We share data from N = 217 healthy adults (mean age 29 years, range 20-41; 109 females, 108 males) who underwent extensive cognitive assessment and neuroimaging to examine the neural basis of individual differences, with a particular focus on a brain structure called the hippocampus. Cognitive data were collected using a wide array of questionnaires, naturalistic tests that examined imagination, autobiographical memory recall and spatial navigation, traditional laboratory-based tests such as recalling word pairs, and comprehensive characterisation of the strategies used to perform the cognitive tests. 3 Tesla MRI data were also acquired and include multi-parameter mapping to examine tissue microstructure, diffusion-weighted MRI, T2-weighted high-resolution partial volume structural MRI scans (with the masks of hippocampal subfields manually segmented from these scans), whole brain resting state functional MRI scans and partial volume high resolution resting state functional MRI scans. This rich dataset will be of value to cognitive and clinical neuroscientists researching individual differences, real-world cognition, brain-behaviour associations, hippocampal subfields and more. All data are freely available on Dryad.
    MeSH term(s) Adult ; Female ; Humans ; Male ; Young Adult ; Cognition ; Diffusion Magnetic Resonance Imaging ; Hippocampus/diagnostic imaging ; Magnetic Resonance Imaging ; Neuroimaging
    Language English
    Publishing date 2023-08-16
    Publishing country England
    Document type Dataset ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2775191-0
    ISSN 2052-4463 ; 2052-4463
    ISSN (online) 2052-4463
    ISSN 2052-4463
    DOI 10.1038/s41597-023-02449-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Autocrine positive feedback of tumor necrosis factor from activated microglia proposed to be of widespread relevance in chronic neurological disease.

    Clark, Ian A / Vissel, Bryce

    Pharmacology research & perspectives

    2023  Volume 11, Issue 5, Page(s) e01136

    Abstract: Over a decade's experience of post-stroke rehabilitation by administering the specific anti-TNF biological, etanercept, by the novel perispinal route, is consistent with a wide range of chronically diminished neurological function having been caused by ... ...

    Abstract Over a decade's experience of post-stroke rehabilitation by administering the specific anti-TNF biological, etanercept, by the novel perispinal route, is consistent with a wide range of chronically diminished neurological function having been caused by persistent excessive cerebral levels of TNF. We propose that this TNF persistence, and cerebral disease chronicity, largely arises from a positive autocrine feedback loop of this cytokine, allowing the persistence of microglial activation caused by the excess TNF that these cells produce. It appears that many of these observations have never been exploited to construct a broad understanding and treatment of certain chronic, yet reversible, neurological illnesses. We propose that this treatment allows these chronically activated microglia to revert to their normal quiescent state, rather than simply neutralizing the direct harmful effects of this cytokine after its release from microglia. Logically, this also applies to the chronic cerebral aspects of various other neurological conditions characterized by activated microglia. These include long COVID, Lyme disease, post-stroke syndromes, traumatic brain injury, chronic traumatic encephalopathy, post-chemotherapy, post-irradiation cerebral dysfunction, cerebral palsy, fetal alcohol syndrome, hepatic encephalopathy, the antinociceptive state of morphine tolerance, and neurogenic pain. In addition, certain psychiatric states, in isolation or as sequelae of infectious diseases such as Lyme disease and long COVID, are candidates for being understood through this approach and treated accordingly. Perispinal etanercept provides the prospect of being able to treat various chronic central nervous system illnesses, whether they are of infectious or non-infectious origin, through reversing excess TNF generation by microglia.
    MeSH term(s) Humans ; Chronic Disease ; Cytokines ; Etanercept/pharmacology ; Etanercept/therapeutic use ; Microglia ; Nervous System Diseases/drug therapy ; Tumor Necrosis Factor Inhibitors ; Tumor Necrosis Factor-alpha/physiology ; Feedback, Physiological
    Chemical Substances Cytokines ; Etanercept (OP401G7OJC) ; Tumor Necrosis Factor Inhibitors ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2023-09-26
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2740389-0
    ISSN 2052-1707 ; 2052-1707
    ISSN (online) 2052-1707
    ISSN 2052-1707
    DOI 10.1002/prp2.1136
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Randomized controlled trial validating the use of perispinal etanercept to reduce post-stroke disability has wide-ranging implications.

    Clark, Ian A

    Expert review of neurotherapeutics

    2020  Volume 20, Issue 3, Page(s) 203–205

    Abstract: Developing effective drug treatments for neurodegenerative disorders has always been hamstrung by the accepted inability of large molecules (roughly those with a molecular weight greater than 600 Daltons) to cross the blood-brain barrier (BBB) in ... ...

    Abstract Developing effective drug treatments for neurodegenerative disorders has always been hamstrung by the accepted inability of large molecules (roughly those with a molecular weight greater than 600 Daltons) to cross the blood-brain barrier (BBB) in therapeutic quantities when administered systemically. The dogma has been that a simple, noninvasive way to accomplish this goal is not possible with many agents, including biologicals, because they are too large. Various novel technologies to breach the BBB have been attempted, but with little success. A randomized double-blind, placebo-controlled clinical trial (RCT) administering a widely used anti-tumor necrosis factor (TNF) biological, etanercept, given via perispinal injection, which bypasses the BBB, turns this dogma on its head. This new trial holds much promise for stroke survivors, as well as having implications for developing treatments based on other large molecules for this and other brain disorders.
    MeSH term(s) Biological Products/administration & dosage ; Double-Blind Method ; Etanercept/administration & dosage ; Humans ; Injections, Spinal ; Randomized Controlled Trials as Topic ; Stroke/complications ; Stroke/drug therapy ; Validation Studies as Topic
    Chemical Substances Biological Products ; Etanercept (OP401G7OJC)
    Language English
    Publishing date 2020-02-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 2112534-X
    ISSN 1744-8360 ; 1473-7175
    ISSN (online) 1744-8360
    ISSN 1473-7175
    DOI 10.1080/14737175.2020.1727742
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Background to new treatments for COVID-19, including its chronicity, through altering elements of the cytokine storm.

    Clark, Ian A

    Reviews in medical virology

    2020  Volume 31, Issue 5, Page(s) 1–13

    Abstract: Anti-tumour necrosis factor (TNF) biologicals, Dexamethasone and rIL-7 are of considerable interest in treating COVID-19 patients who are in danger of, or have become, seriously ill. Yet reducing sepsis mortality by lowering circulating levels of TNF ... ...

    Abstract Anti-tumour necrosis factor (TNF) biologicals, Dexamethasone and rIL-7 are of considerable interest in treating COVID-19 patients who are in danger of, or have become, seriously ill. Yet reducing sepsis mortality by lowering circulating levels of TNF lost favour when positive endpoints in earlier simplistic models could not be reproduced in well-conducted human trials. Newer information with anti-TNF biologicals has encouraged reintroducing this concept for treating COVID-19. Viral models have had encouraging outcomes, as have the effects of anti-TNF biologicals on community-acquired COVID-19 during their long-term use to treat chronic inflammatory states. The positive outcome of a large scale trial of dexamethasone, and its higher potency late in the disease, harmonises well with its capacity to enhance levels of IL-7Rα, the receptor for IL-7, a cytokine that enhances lymphocyte development and is increased during the cytokine storm. Lymphoid germinal centres required for antibody-based immunity can be harmed by TNF, and restored by reducing TNF. Thus the IL-7- enhancing activity of dexamethasone may explain its higher potency when lymphocytes are depleted later in the infection, while employing anti-TNF, for several reasons, is much more logical earlier in the infection. This implies dexamethasone could prove to be synergistic with rIL-7, currently being trialed as a COVID-19 therapeutic. The principles behind these COVID-19 therapies are consistent with the observed chronic hypoxia through reduced mitochondrial function, and also the increased severity of this disease in ApoE4-positive individuals. Many of the debilitating persistent aspects of this disease are predictably susceptible to treatment with perispinal etanercept, since they have cerebral origins.
    MeSH term(s) Animals ; COVID-19/drug therapy ; COVID-19/genetics ; COVID-19/immunology ; Cytokine Release Syndrome/drug therapy ; Cytokine Release Syndrome/genetics ; Cytokine Release Syndrome/immunology ; Dexamethasone/administration & dosage ; Humans ; Interleukin-17/administration & dosage ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Tumor Necrosis Factor-alpha/genetics ; Tumor Necrosis Factor-alpha/immunology
    Chemical Substances Interleukin-17 ; Tumor Necrosis Factor-alpha ; Dexamethasone (7S5I7G3JQL)
    Language English
    Publishing date 2020-12-24
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1086043-5
    ISSN 1099-1654 ; 1052-9276
    ISSN (online) 1099-1654
    ISSN 1052-9276
    DOI 10.1002/rmv.2210
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Automated protocols for delineating human hippocampal subfields from 3 Tesla and 7 Tesla magnetic resonance imaging data.

    Hickling, Alice L / Clark, Ian A / Wu, Yan I / Maguire, Eleanor A

    Hippocampus

    2024  

    Abstract: Researchers who study the human hippocampus are naturally interested in how its subfields function. However, many researchers are precluded from examining subfields because their manual delineation from magnetic resonance imaging (MRI) scans (still the ... ...

    Abstract Researchers who study the human hippocampus are naturally interested in how its subfields function. However, many researchers are precluded from examining subfields because their manual delineation from magnetic resonance imaging (MRI) scans (still the gold standard approach) is time consuming and requires significant expertise. To help ameliorate this issue, we present here two protocols, one for 3T MRI and the other for 7T MRI, that permit automated hippocampus segmentation into six subregions, namely dentate gyrus/cornu ammonis (CA)4, CA2/3, CA1, subiculum, pre/parasubiculum, and uncus along the entire length of the hippocampus. These protocols are particularly notable relative to existing resources in that they were trained and tested using large numbers of healthy young adults (n = 140 at 3T, n = 40 at 7T) whose hippocampi were manually segmented by experts from MRI scans. Using inter-rater reliability analyses, we showed that the quality of automated segmentations produced by these protocols was high and comparable to expert manual segmenters. We provide full open access to the automated protocols, and anticipate they will save hippocampus researchers a significant amount of time. They could also help to catalyze subfield research, which is essential for gaining a full understanding of how the hippocampus functions.
    Language English
    Publishing date 2024-04-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1074352-2
    ISSN 1098-1063 ; 1050-9631
    ISSN (online) 1098-1063
    ISSN 1050-9631
    DOI 10.1002/hipo.23606
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Posterior hippocampal CA2/3 volume is associated with autobiographical memory recall ability in lower performing individuals.

    Clark, Ian A / Dalton, Marshall A / Maguire, Eleanor A

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 7924

    Abstract: People vary substantially in their capacity to recall past experiences, known as autobiographical memories. Here we investigated whether the volumes of specific hippocampal subfields were associated with autobiographical memory retrieval ability. We ... ...

    Abstract People vary substantially in their capacity to recall past experiences, known as autobiographical memories. Here we investigated whether the volumes of specific hippocampal subfields were associated with autobiographical memory retrieval ability. We manually segmented the full length of the two hippocampi in 201 healthy young adults into DG/CA4, CA2/3, CA1, subiculum, pre/parasubiculum and uncus, in the largest such manually segmented subfield sample yet reported. Across the group we found no evidence for an association between any subfield volume and autobiographical memory recall ability. However, when participants were assigned to lower and higher performing groups based on their memory recall scores, we found that bilateral CA2/3 volume was significantly and positively associated with autobiographical memory recall performance specifically in the lower performing group. We further observed that this effect was attributable to posterior CA2/3. By contrast, semantic details from autobiographical memories, and performance on a range of laboratory-based memory tests, did not correlate with CA2/3 volume. Overall, our findings highlight that posterior CA2/3 may be particularly pertinent for autobiographical memory recall. They also reveal that there may not be direct one-to-one mapping of posterior CA2/3 volume with autobiographical memory ability, with size mattering perhaps only in those with poorer memory recall.
    MeSH term(s) Young Adult ; Humans ; Memory, Episodic ; CA3 Region, Hippocampal ; Hippocampus ; Mental Recall ; Memory Disorders ; Magnetic Resonance Imaging
    Language English
    Publishing date 2023-05-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-35127-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Book: Practical obstetric hematology

    Clark, Peter / Greer, Ian A.

    2006  

    Author's details Peter Clark ; Ian A. Greer
    Language English
    Size XII, 196 S. : Ill., graph. Darst.
    Publisher Taylor & Francis
    Publishing place London u.a.
    Publishing country Great Britain
    Document type Book
    HBZ-ID HT014404714
    ISBN 978-1-84214-262-2 ; 1-84214-262-3
    Database Catalogue ZB MED Medicine, Health

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  10. Article: How diseases caused by parasites allowed a wider understanding of disease in general: my encounters with parasitology in Australia and elsewhere over the last 50 years

    Clark, Ian A.

    International journal for parasitology. 2021 Dec., v. 51, no. 13-14

    2021  

    Abstract: This is an account of how it can prove possible to carve a reasonable scientific career by following what brought most scientific thrill rather than pursue a safe, institution-directed, path. The fascination began when I noticed, quite unexpectedly, that ...

    Abstract This is an account of how it can prove possible to carve a reasonable scientific career by following what brought most scientific thrill rather than pursue a safe, institution-directed, path. The fascination began when I noticed, quite unexpectedly, that the normal mouse immune response causes Babesia microti to die, en masse, inside circulating red cells. It eventuated that prior Bacillus Calmette Guerin infection caused the same outcome, even before the protozoal infection became patent. It also rendered mice quite immune, long term. I acquired an obsession about this telling us how little we know. Surrounded by basic immunologists, parasitologists and virologists in London, I had been given, in the days that funding was ample, the opportunity to follow any promising lead with a free hand. Through Bacillus Calmette Guerin, this meant stumbling through a set of phenomena that were in their infancies, and could be explained only through nebulous novel soluble mediators such as TNF, described the following year as causing the in vivo necrosis of tumours in mice. Beginning with malarial disease pathogenesis, I followed TNF wherever it led, into innate immunity, acute and chronic infections, neurophysiology and neurodegenerative diseases, in all of which states awareness of the role of this cytokine is still growing fast. Many of these steps can be illustrated and expanded upon in parasitic diseases. Covering the importance of TNF in the pathogenesis of neurodegenerative disease has proved to be highly illuminating, scientifically and otherwise. But the insights it has given me into understanding the temptations to which patent-owners can succumb when faced with opportunities to put money before people is not for the faint hearted. Clearly, parasitologists inhabit a much more common-good yet science-orientated, civilised, world.
    Keywords Babesia microti ; immune response ; innate immunity ; mice ; necrosis ; neurodegenerative diseases ; neurophysiology ; parasitology ; pathogenesis ; people ; protozoal infections ; Australia
    Language English
    Dates of publication 2021-12
    Size p. 1265-1276.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 120518-3
    ISSN 1879-0135 ; 0020-7519
    ISSN (online) 1879-0135
    ISSN 0020-7519
    DOI 10.1016/j.ijpara.2021.10.002
    Database NAL-Catalogue (AGRICOLA)

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