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  • 1
    Publication Date: 2011-08-10
    Description: During immune responses, neutrophils must integrate survival and death signals from multiple sources to regulate their lifespan. Signals that activate either the Bcl-2- or death receptor-regulated apoptosis pathways can provide powerful stimuli for neutrophils to undergo cell death, but whether they act cooperatively in parallel or directly cross-talk in neutrophils is not known. Previous studies suggested that Bcl-2 family proteins are not required for Fas-induced cell death in neutrophils, but did not examine whether they could modulate its rapid onset. By monitoring the rate of change in neutrophil viability associated with activation of the Fas-triggered death receptor pathway using real-time cell imaging, we show that the Bcl-2-related proteins Bid, Bax, and Bak accelerate neutrophil apoptosis but are not essential for cell death. Increased Bcl-2 or Mcl-1 expression prevents efficient induction of apoptosis by Fas stimulation indicating that the Bcl-2-regulated apoptosis pathway can directly interfere with Fas-triggered apoptosis. Fas has been shown to initiate NFκB activation and gene transcription in cell lines, however gene transcription is not altered in Fas-activated Bid−/− neutrophils, indicating that apoptosis occurs independently of gene transcription in neutrophils. The specification of kinetics of neutrophil apoptosis by Bid impacts on the magnitude of neutrophil IL-1β production, implicating a functional role for the Bcl-2-regulated pathway in controlling neutrophil responses to FasL. These data demonstrate that the intrinsic apoptosis pathway directly controls the kinetics of Fas-triggered apoptosis in neutrophils.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2011-08-20
    Description: Immune clearance and resource limitation (via red blood cell depletion) shape the peaks and troughs of malaria parasitemia, which in turn affect disease severity and transmission. Quantitatively partitioning the relative roles of these effects through time is challenging. Using data from rodent malaria, we estimated the effective propagation number, which reflects the relative importance of contrasting within-host control mechanisms through time and is sensitive to the inoculating parasite dose. Our analysis showed that the capacity of innate responses to restrict initial parasite growth saturates with parasite dose and that experimentally enhanced innate immunity can affect parasite density indirectly via resource depletion. Such a statistical approach offers a tool to improve targeting of drugs or vaccines for human therapy by revealing the dynamics and interactions of within-host regulatory mechanisms.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891600/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891600/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Metcalf, C J E -- Graham, A L -- Huijben, S -- Barclay, V C -- Long, G H -- Grenfell, B T -- Read, A F -- Bjornstad, O N -- R01 GM089932/GM/NIGMS NIH HHS/ -- R01GM089932/GM/NIGMS NIH HHS/ -- R24 HD047879/HD/NICHD NIH HHS/ -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2011 Aug 19;333(6045):984-8. doi: 10.1126/science.1204588.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology, Oxford University, Oxford OX1 3PS, UK. charlotte.metcalf@zoo.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21852493" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptive Immunity ; Animals ; Antibodies/immunology ; CD4-Positive T-Lymphocytes/immunology ; Erythrocyte Aging ; Erythrocyte Count ; Erythrocytes/*parasitology/physiology ; Host-Parasite Interactions ; Humans ; Immunity, Innate ; Interleukin-10/immunology/metabolism ; Malaria/blood/*immunology/*parasitology ; Mice ; Models, Biological ; Models, Statistical ; *Parasitemia/blood/immunology/parasitology ; Plasmodium chabaudi/immunology/*physiology ; Receptors, Interleukin-10/immunology ; Regression Analysis
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2015-03-15
    Description: The Ebola epidemic in West Africa has caused substantial morbidity and mortality. The outbreak has also disrupted health care services, including childhood vaccinations, creating a second public health crisis. We project that after 6 to 18 months of disruptions, a large connected cluster of children unvaccinated for measles will accumulate across Guinea, Liberia, and Sierra Leone. This pool of susceptibility increases the expected size of a regional measles outbreak from 127,000 to 227,000 cases after 18 months, resulting in 2000 to 16,000 additional deaths (comparable to the numbers of Ebola deaths reported thus far). There is a clear path to avoiding outbreaks of childhood vaccine-preventable diseases once the threat of Ebola begins to recede: an aggressive regional vaccination campaign aimed at age groups left unprotected because of health care disruptions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691345/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691345/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takahashi, Saki -- Metcalf, C Jessica E -- Ferrari, Matthew J -- Moss, William J -- Truelove, Shaun A -- Tatem, Andrew J -- Grenfell, Bryan T -- Lessler, Justin -- R01 AI102939/AI/NIAID NIH HHS/ -- U19AI089674/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):1240-2. doi: 10.1126/science.aaa3438.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA. ; Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA. Woodrow Wilson School, Princeton University, Princeton, NJ 08544, USA. ; Centre for Infectious Disease Dynamics, Pennsylvania State University, State College, PA 16801, USA. ; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. ; Department of Geography and Environment, University of Southampton, Southampton SO17 1BJ, UK. Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA. Flowminder Foundation, 17177 Stockholm, Sweden. ; Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA. Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA. ; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. justin@jhu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25766232" target="_blank"〉PubMed〈/a〉
    Keywords: Child, Preschool ; Disease Outbreaks/prevention & control/*statistics & numerical data ; Disease Susceptibility ; Guinea/epidemiology ; Hemorrhagic Fever, Ebola/*epidemiology ; Humans ; Immunization Programs/*statistics & numerical data ; Infant ; Liberia/epidemiology ; Measles/*epidemiology/mortality/*prevention & control ; *Measles Vaccine ; Sierra Leone/epidemiology ; Vaccination/*statistics & numerical data
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2015-05-09
    Description: Immunosuppression after measles is known to predispose people to opportunistic infections for a period of several weeks to months. Using population-level data, we show that measles has a more prolonged effect on host resistance, extending over 2 to 3 years. We find that nonmeasles infectious disease mortality in high-income countries is tightly coupled to measles incidence at this lag, in both the pre- and post-vaccine eras. We conclude that long-term immunologic sequelae of measles drive interannual fluctuations in nonmeasles deaths. This is consistent with recent experimental work that attributes the immunosuppressive effects of measles to depletion of B and T lymphocytes. Our data provide an explanation for the long-term benefits of measles vaccination in preventing all-cause infectious disease. By preventing measles-associated immune memory loss, vaccination protects polymicrobial herd immunity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mina, Michael J -- Metcalf, C Jessica E -- de Swart, Rik L -- Osterhaus, A D M E -- Grenfell, Bryan T -- T32 GM008169/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 May 8;348(6235):694-9. doi: 10.1126/science.aaa3662. Epub 2015 May 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA. Medical Scientist Training Program, School of Medicine, Emory University, Atlanta, GA, USA. michael.j.mina@gmail.com. ; Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA. Fogarty International Center, National Institutes of Health, Bethesda, MD, USA. ; Department of Viroscience, Erasmus University Medical Center, Rotterdam, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25954009" target="_blank"〉PubMed〈/a〉
    Keywords: B-Lymphocytes/immunology ; Child ; *Child Mortality ; Child, Preschool ; England/epidemiology ; Female ; Humans ; Immunologic Memory ; *Immunomodulation ; Incidence ; Lymphocyte Depletion ; Male ; Measles/*epidemiology/*immunology/prevention & control ; Measles Vaccine/administration & dosage/*immunology ; Opportunistic Infections/immunology/*mortality/*prevention & control ; T-Lymphocytes/immunology ; Time Factors ; United States/epidemiology ; Vaccination ; Wales/epidemiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2015-03-15
    Description: Despite some notable successes in the control of infectious diseases, transmissible pathogens still pose an enormous threat to human and animal health. The ecological and evolutionary dynamics of infections play out on a wide range of interconnected temporal, organizational, and spatial scales, which span hours to months, cells to ecosystems, and local to global spread. Moreover, some pathogens are directly transmitted between individuals of a single species, whereas others circulate among multiple hosts, need arthropod vectors, or can survive in environmental reservoirs. Many factors, including increasing antimicrobial resistance, increased human connectivity and changeable human behavior, elevate prevention and control from matters of national policy to international challenge. In the face of this complexity, mathematical models offer valuable tools for synthesizing information to understand epidemiological patterns, and for developing quantitative evidence for decision-making in global health.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445966/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445966/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heesterbeek, Hans -- Anderson, Roy M -- Andreasen, Viggo -- Bansal, Shweta -- De Angelis, Daniela -- Dye, Chris -- Eames, Ken T D -- Edmunds, W John -- Frost, Simon D W -- Funk, Sebastian -- Hollingsworth, T Deirdre -- House, Thomas -- Isham, Valerie -- Klepac, Petra -- Lessler, Justin -- Lloyd-Smith, James O -- Metcalf, C Jessica E -- Mollison, Denis -- Pellis, Lorenzo -- Pulliam, Juliet R C -- Roberts, Mick G -- Viboud, Cecile -- Isaac Newton Institute IDD Collaboration -- U01 GM110721/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):aaa4339. doi: 10.1126/science.aaa4339.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Faculty of Veterinary Medicine, University of Utrecht, Utrecht, Netherlands. j.a.p.heesterbeek@uu.nl. ; School of Public Health, Imperial College, London, UK. ; Roskilde University, Roskilde, Denmark. ; Georgetown University, Washington, DC, USA. ; MRC Biostatistics Unit, Cambridge, UK. ; WHO, Geneva, Switzerland. ; Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene Tropical Medicine, London, UK. ; University of Cambridge, Cambridge, UK. ; School of Life Sciences, University of Warwick, UK. School of Tropical Medicine, University of Liverpool, UK. ; Warwick Mathematics Institute, University of Warwick, Coventry, UK. ; Department of Statistical Science, University College London, London, UK. ; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. ; Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA, USA. ; Department of Zoology, University of Oxford, Oxford, UK, and Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA. ; Heriot-Watt University, Edinburgh, UK. ; Department of Biology-Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA. Division of International Epidemiology and Population Studies, Fogarty International Center, NIH, Bethesda, MD, USA. ; Institute of Natural and Mathematical Sciences, Massey University, Auckland, New Zealand. ; Division of International Epidemiology and Population Studies, Fogarty International Center, NIH, Bethesda, MD, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25766240" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Reproduction Number ; Coinfection ; Communicable Disease Control ; *Communicable Diseases/epidemiology/transmission ; Communicable Diseases, Emerging/epidemiology/transmission ; Disease Outbreaks ; *Global Health ; Health Policy ; Hemorrhagic Fever, Ebola/epidemiology ; Humans ; *Models, Biological ; *Public Health ; Zoonoses/epidemiology/transmission
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
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  • 6
    Publication Date: 2015-08-17
    Description: Changing patterns of human aggregation are thought to drive annual and multiannual outbreaks of infectious diseases, but the paucity of data about travel behavior and population flux over time has made this idea difficult to test quantitatively. Current measures of human mobility, especially in low-income settings, are often static, relying on approximate travel times, road networks, or cross-sectional surveys. Mobile phone data provide a unique source of information about human travel, but the power of these data to describe epidemiologically relevant changes in population density remains unclear. Here we quantify seasonal travel patterns using mobile phone data from nearly 15 million anonymous subscribers in Kenya. Using a rich data source of rubella incidence, we show that patterns of population travel (fluxes) inferred from mobile phone data are predictive of disease transmission and improve significantly on standard school term time and weather covariates. Further, combining seasonal and spatial data on travel from mobile phone data allows us to characterize seasonal fluctuations in risk across Kenya and produce dynamic importation risk maps for rubella. Mobile phone data therefore offer a valuable previously unidentified source of data for measuring key drivers of seasonal epidemics.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 7
    Publication Date: 2020-08-24
    Description: Humans can impact the spatial transmission dynamics of infectious diseases by introducing pathogens into susceptible environments. The rate at which this occurs depends in part on human-mobility patterns. Increasingly, mobile-phone usage data are used to quantify human mobility and investigate the impact on disease dynamics. Although the number of trips between locations and the duration of those trips could both affect infectious-disease dynamics, there has been limited work to quantify and model the duration of travel in the context of disease transmission. Using mobility data inferred from mobile-phone calling records in Namibia, we calculated both the number of trips between districts and the duration of these trips from 2010 to 2014. We fit hierarchical Bayesian models to these data to describe both the mean trip number and duration. Results indicate that trip duration is positively related to trip distance, but negatively related to the destination population density. The highest volume of trips and shortest trip durations were among high-density districts, whereas trips among low-density districts had lower volume with longer duration. We also analyzed the impact of including trip duration in spatial-transmission models for a range of pathogens and introduction locations. We found that inclusion of trip duration generally delays the rate of introduction, regardless of pathogen, and that the variance and uncertainty around spatial spread increases proportionally with pathogen-generation time. These results enhance our understanding of disease-dispersal dynamics driven by human mobility, which has potential to elucidate optimal spatial and temporal scales for epidemic interventions.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 8
    Publication Date: 2008-07-18
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 9
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2019
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2019
    Description: 〈p〉Thakkar and McCarthy suggest that periodicity in measles incidence artifactually drives our estimates of a 2- to 3-year duration of measles "immune-amnesia." We show that periodicity has a negligible effect relative to the immunological signal we detect, and demonstrate that immune-amnesia is largely undetectable in small populations with large fluctuations in mortality of the type they use for illustration.〈/p〉
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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