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"Bolton, Christopher"
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Review of evidence linking exposure to environmental stressors and associated alterations in the dynamics of immunosenescence (ISC) with the global increase in multiple sclerosis (MS)
Historical survey confirms that, over the latter part of the 20
th
century, autoimmune-based diseases, including multiple sclerosis (MS), have shown a worldwide increase in incidence and prevalence. Analytical population studies have established that the exponential rise in MS is not solely due to improvements in diagnosis and healthcare but relates to an increase in autoimmune risk factors. Harmful environmental exposures, including non-communicable social determinants of health, anthropogens and indigenous or transmissible microbes, constitute a group of causal determinants that have been closely linked with the global rise in MS cases. Exposure to environmental stressors has profound effects on the adaptive arm of the immune system and, in particular, the associated intrinsic process of immune ageing or immunosenescence (ISC). Stressor-related disturbances to the dynamics of ISC include immune cell-linked untimely or premature (p) alterations and an accelerated replicative (ar) change. A recognised immune-associated feature of MS is pISC and current evidence supports the presence of an arISC during the disease. Moreover, collated data illustrates the immune-associated alterations that characterise pISC and arISC are inducible by environmental stressors strongly implicated in causing duplicate changes in adaptive immune cells during MS. The close relationship between exposure to environmental risk factors and the induction of pISC and arISC during MS offers a valid mechanism through which pro-immunosenescent stressors may act and contribute to the recorded increase in the global rate and number of new cases of the disease. Confirmation of alterations to the dynamics of ISC during MS provides a rational and valuable therapeutic target for the use of senolytic drugs to either prevent accumulation and enhance ablation of less efficient untimely senescent adaptive immune cells or decelerate the dysregulated process of replicative proliferation. A range of senotherapeutics are available including kinase and transcriptase inhibitors, rapalogs, flavanols and genetically-engineered T cells and the use of selective treatments to control emerging and unspecified aspects of pISC and arISC are discussed.
Journal Article
Interpreting anime
\"Well-known through hit movies like Spirited Away, Akira, and Ghost in the Shell, anime has a long history spanning a wide range of directors, genres, and styles. Christopher Bolton's Interpreting Anime is a thoughtful, carefully organized introduction to Japanese animation for anyone eager to see why this genre has remained a vital, adaptable art form for decades. Interpreting Anime is easily accessible and structured around individual films and a broad array of critical approaches. Each chapter centers on a different feature-length anime film, juxtaposing it with a particular medium--like literary fiction, classical Japanese theater, and contemporary stage drama--in order to reveal what is unique about anime's way of representing the world. This analysis is abetted by a suite of questions provoked by each film, along with Bolton's incisive responses. Throughout, Interpreting Anime applies multiple frames, such as queer theory, psychoanalysis, and theories of postmodernism, giving readers a thorough understanding of both the cultural underpinnings and critical significance of each film. What emerges from the sweep of Interpreting Anime is Bolton's original, articulate case for what makes anime unique as a medium: how it at once engages profound social and political realities while also drawing attention to the very challenges of representing reality in animation's imaginative and compelling visual forms\"-- Provided by publisher.
Book
An evaluation of the recognised systemic inflammatory biomarkers of chronic sub-optimal inflammation provides evidence for inflammageing (IFA) during multiple sclerosis (MS)
The pathogenesis of the human demyelinating disorder multiple sclerosis (MS) involves the loss of immune tolerance to self-neuroantigens. A deterioration in immune tolerance is linked to inherent immune ageing, or immunosenescence (ISC). Previous work by the author has confirmed the presence of ISC during MS. Moreover, evidence verified a prematurely aged immune system that may change the frequency and profile of MS through an altered decline in immune tolerance. Immune ageing is closely linked to a chronic systemic sub-optimal inflammation, termed inflammageing (IFA), which disrupts the efficiency of immune tolerance by varying the dynamics of ISC that includes accelerated changes to the immune system over time. Therefore, a shifting deterioration in immunological tolerance may evolve during MS through adversely-scheduled effects of IFA on ISC. However, there is, to date, no collective proof of ongoing IFA during MS. The Review addresses the constraint and provides a systematic critique of compelling evidence, through appraisal of IFA-related biomarker studies, to support the occurrence of a sub-optimal inflammation during MS. The findings justify further work to unequivocally demonstrate IFA in MS and provide additional insight into the complex pathology and developing epidemiology of the disease.
Journal Article
X-Men. Colossus : God's country
Presents the backstory of the steel-skinned mutant, from his youth in Russia to his education during the early days of Charles Xavier's school.
BOOK
Consensus clinical management guidelines for acid sphingomyelinase deficiency (Niemann–Pick disease types A, B and A/B)
Background
Acid Sphingomyelinase Deficiency (ASMD) is a rare autosomal recessive disorder caused by mutations in the
SMPD1
gene. This rarity contributes to misdiagnosis, delayed diagnosis and barriers to good care. There are no published national or international consensus guidelines for the diagnosis and management of patients with ASMD. For these reasons, we have developed clinical guidelines that defines standard of care for ASMD patients.
Methods
The information contained in these guidelines was obtained through a systematic literature review and the experiences of the authors in their care of patients with ASMD. We adopted the Appraisal of Guidelines for Research and Evaluation (AGREE II) system as method of choice for the guideline development process.
Results
The clinical spectrum of ASMD, although a continuum, varies substantially with subtypes ranging from a fatal infantile neurovisceral disorder to an adult-onset chronic visceral disease. We produced 39 conclusive statements and scored them according to level of evidence, strengths of recommendations and expert opinions. In addition, these guidelines have identified knowledge gaps that must be filled by future research.
Conclusion
These guidelines can inform care providers, care funders, patients and their carers about best clinical practice and leads to a step change in the quality of care for patients with ASMD with or without enzyme replacement therapy (ERT).
Journal Article
Review of evidence linking exposure to environmental stressors and associated alterations in the dynamics of immunosenescence
Historical survey confirms that, over the latter part of the 20.sup.th century, autoimmune-based diseases, including multiple sclerosis (MS), have shown a worldwide increase in incidence and prevalence. Analytical population studies have established that the exponential rise in MS is not solely due to improvements in diagnosis and healthcare but relates to an increase in autoimmune risk factors. Harmful environmental exposures, including non-communicable social determinants of health, anthropogens and indigenous or transmissible microbes, constitute a group of causal determinants that have been closely linked with the global rise in MS cases. Exposure to environmental stressors has profound effects on the adaptive arm of the immune system and, in particular, the associated intrinsic process of immune ageing or immunosenescence (ISC). Stressor-related disturbances to the dynamics of ISC include immune cell-linked untimely or premature (p) alterations and an accelerated replicative (ar) change. A recognised immune-associated feature of MS is pISC and current evidence supports the presence of an arISC during the disease. Moreover, collated data illustrates the immune-associated alterations that characterise pISC and arISC are inducible by environmental stressors strongly implicated in causing duplicate changes in adaptive immune cells during MS. The close relationship between exposure to environmental risk factors and the induction of pISC and arISC during MS offers a valid mechanism through which pro-immunosenescent stressors may act and contribute to the recorded increase in the global rate and number of new cases of the disease. Confirmation of alterations to the dynamics of ISC during MS provides a rational and valuable therapeutic target for the use of senolytic drugs to either prevent accumulation and enhance ablation of less efficient untimely senescent adaptive immune cells or decelerate the dysregulated process of replicative proliferation. A range of senotherapeutics are available including kinase and transcriptase inhibitors, rapalogs, flavanols and genetically-engineered T cells and the use of selective treatments to control emerging and unspecified aspects of pISC and arISC are discussed. Keywords: Multiple sclerosis, Immunosenescence, Replicative immunosenescence, Premature immunosenescence, Environmental stressors, Senotherapy
Journal Article
An evaluation of the recognised systemic inflammatory biomarkers of chronic sub-optimal inflammation provides evidence for inflammageing
The pathogenesis of the human demyelinating disorder multiple sclerosis (MS) involves the loss of immune tolerance to self-neuroantigens. A deterioration in immune tolerance is linked to inherent immune ageing, or immunosenescence (ISC). Previous work by the author has confirmed the presence of ISC during MS. Moreover, evidence verified a prematurely aged immune system that may change the frequency and profile of MS through an altered decline in immune tolerance. Immune ageing is closely linked to a chronic systemic sub-optimal inflammation, termed inflammageing (IFA), which disrupts the efficiency of immune tolerance by varying the dynamics of ISC that includes accelerated changes to the immune system over time. Therefore, a shifting deterioration in immunological tolerance may evolve during MS through adversely-scheduled effects of IFA on ISC. However, there is, to date, no collective proof of ongoing IFA during MS. The Review addresses the constraint and provides a systematic critique of compelling evidence, through appraisal of IFA-related biomarker studies, to support the occurrence of a sub-optimal inflammation during MS. The findings justify further work to unequivocally demonstrate IFA in MS and provide additional insight into the complex pathology and developing epidemiology of the disease. Keywords: Biomarker, multiple sclerosis, immune tolerance, immunosenescence, inflammageing, premature immune ageing
Journal Article
Commander's Critical Information Requirements: Crucial for Decisionmaking and Joint Synchronization
Across the competition continuum, speed of action requires timely decisions and adjustments to a joint task force operation plan. As mission command systems improve and information-gathering tools increase in sophistication, a consistent challenge for a headquarters staff is determining the relevant information to analyze for decisionmaking. The commander's critical information requirements are designed specifically to combat these challenges and enable the commander's decisionmaking process. Here, Bolton and Prescott describe the importance of CCIRs, offer techniques to develop CCIRs to ensure they are tied to decision points, and relate CCIRs development and use across all three planning horizons. Furthermore, they recommend how headquarters should use CCIRs and decision support tools across an operation and describes several recommendations joint doctrine should incorporate to improve CCIR understanding across the joint force.
Journal Article
