Journal articles on the topic 'Mitigating denominators'
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Kura, Branislav, Ashim K. Bagchi, Pawan K. Singal, Miroslav Barancik, Tyler W. LeBaron, Katarina Valachova, Ladislav Šoltés, and Ján Slezák. "Molecular hydrogen: potential in mitigating oxidative-stress-induced radiation injury." Canadian Journal of Physiology and Pharmacology 97, no. 4 (April 2019): 287–92. http://dx.doi.org/10.1139/cjpp-2018-0604.
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Uncontrolled production of oxygen and nitrogen radicals results in oxidative and nitrosative stresses that impair cellular functions and have been regarded as causative common denominators of many pathological processes. In this review, we report on the beneficial effects of molecular hydrogen in scavenging radicals in an artificial system of•OH formation. As a proof of principle, we also demonstrate that in rat hearts in vivo, administration of molecular hydrogen led to a significant increase in superoxide dismutase as well as pAKT, a cell survival signaling molecule. Irradiation of the rats caused a significant increase in lipid peroxidation, which was mitigated by pre-treatment of the animals with molecular hydrogen. The nuclear factor erythroid 2-related factor 2 is regarded as an important regulator of oxyradical homeostasis, as well as it supports the functional integrity of cells, particularly under conditions of oxidative stress. We suggest that the beneficial effects of molecular hydrogen may be through the activation of nuclear factor erythroid 2-related factor 2 pathway that promotes innate antioxidants and reduction of apoptosis, as well as inflammation.
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Bennett, Julia C., and Maria Deloria Knoll. "1173. Changes in Invasive Pneumococcal Disease Incidence Following Introduction of PCV10 and PCV13 Among Children < 5 Years: The PSERENADE Project." Open Forum Infectious Diseases 8, Supplement_1 (November 1, 2021): S677—S678. http://dx.doi.org/10.1093/ofid/ofab466.1366.
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Abstract Background Higher valency pneumococcal conjugate vaccines (PCV10 and PCV13) replaced PCV7, and an updated global analysis of PCV impact on invasive pneumococcal disease (IPD) incidence is needed. We aimed to estimate the change in vaccine-type (VT), non-VT type and all-serotype (ST) IPD incidence following introduction of PCV10/13 among children < 5 years of age. Methods IPD ST-specific incidence or cases and population denominators were obtained directly from surveillance sites. IPD incidence rate ratios (IRRs) for each site were estimated comparing the pre-any PCV incidence to each post-PCV10/13 year using Bayesian multi-level, mixed effects Poisson regressions. All-site weighted average IRRs were estimated using linear mixed-effects regressions. Results were stratified by product (PCV10 vs. PCV13) and years of prior PCV7 use (none, some [1-3 years or 4-5 years if < 70% PCV uptake], or many [≥ 4 years with ≥ 70% uptake]). Results Analyses included 45 surveillance sites from 31 countries, primarily high-income (80%). Thirty surveillance sites had pre- and post-PCV data (PCV10: no prior PCV7=5 sites, some=2, many=2; PCV13: no prior PCV7=3, some=5, many=13). Five years after PCV10/13 introduction, the all-site IRRs in children < 5 years were generally similar across products and prior PCV7 use strata for all-serotype IPD (range 0.23-0.41), PCV7 STs (0.01-0.13), PCV10non7 STs (1, 5, and 7F; 0.05-0.20), and ST6A (0.01-0.18). IRRs for ST19A were lower for PCV13 sites (range by PCV7 use: 0.09-0.31) than for PCV10 sites (1.1-1.4). ST3 IRRs were dynamic, differing by product at year 5 (range for PCV13 sites=0.86-1.02; PCV10 sites=1.55-1.78), but converging by year 7. NonPCV13 STs increased across all strata (range 1.9-2.6), except one strata with a single African site that declined. Figure 1. All-Site Weighted Average Incidence Rate Ratios, Children <5> * Total sites indicates number of sites with incidence rate data included and pre/post sites indicates number of sites with both pre- and post-PCV data to estimate IRRs for each outcome. ** Year 0 indicates the year of PCV10/13 introduction and year -1 indicates the last year of PCV7 use prior to PCV10/13 introduction. Conclusion All-serotype IPD in children < 5 years declined following both PCV10 and PCV13 use, driven by substantial declines in VT serotypes and offset by increases in nonPCV13 STs. ST19A decreased among PCV13-sites, mitigating replacement disease occurring after PCV7 use, but increased, on average, among PCV10-sites. Changes in ST3 were heterogeneous, increasing in some sites and no change from baseline in others. Data from low-income and high-burden settings were limited. Disclosures Julia C. Bennett, MSPH, Pfizer (Research Grant or Support) Maria Deloria Knoll, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)
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Buraga, Manoj Babu, and Thibault Fournol. "Indo-French Cooperation and Engagement in Holistic Maritime Security: Possibilities and Implications in the Indian Ocean Region." Electronic Journal of Social and Strategic Studies 03, no. 02 (2022): 241–57. http://dx.doi.org/10.47362/ejsss.2022.3209.
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The diffusion of the Indo-Pacific concept in India’s strategic vocabulary has accompanied the emergence of a broader strategic reference frame, in which the impacts of climate change on coastal areas and maritime-related environmental issues figure among the lowest common denominators of cooperation at the regional scale. In the Indian Ocean Region (IOR), unregulated fishing, natural disasters relief or marine pollution indeed became major security concerns for littoral States as well as it gave a new role for the armies in mitigating increasing environmental risks. In fact, we are seeing an expansion in India-France maritime security cooperation, with particular focus on the Indian Ocean. With its expanding economic, marine military, and strategic goals in the Indo-Pacific region, India is eager to develop connections with countries throughout the area. France is emphasising its identity as an Indo-Pacific nation and showing interest in bolstering its partnership with India. The Indian Ocean has emerged as a hot topic in recent Indo-French bilateral talks, as both nations seek to broaden their long-standing strategic partnership to the maritime domain. In February 2022, they inked a roadmap to boost their bilateral exchanges on the blue economy and forge a common vision of ocean governance on the basis of the rule of law, and cooperation on sustainable and resilient coastal and waterways infrastructure (MEA, Feb 2022).[i] In this regard, both agreed to explore the potential for collaboration in marine science research for a better understanding of the oceans, including the Indian Ocean. One such partnership is the ‘The Indo-Pacific Oceans Initiative’ (IPOI), wherein France and India have taken the responsibility of being the ‘lead’ for the Marine Resources Pillar, which is one of seven identified pillars (MEA, Mar 2022).[ii] In such a context, this paper aims to explore India’s cooperation opportunities in the field of environmental security in the IOR in the context of Indo-French relations. As a preferred net security provider in the region, India has made of France one of the cornerstones of its SAGAR policy and a first-choice partner on maritime issues, as testified recently by the India-France Roadmap on Blue Economy and Ocean Governance. Based on several years of research on Indo-French relations and environmental security in the Indo-Pacific, the paper will first compare the securitization process of maritime-related environmental issues within the regional security policies of both countries and the adaptation of their navies to emerging environmental risks in the Indian Ocean. Then, it will analyse to what extent this process contributes to reshape military-to-military cooperation between the two navies/coast guard in emerging areas such as disaster relief operations, protection of maritime ecosystems or cyclone early warning. Then, it will consider the multilateral implications of this cooperation and its potential contribution to the security architecture of the Indian Ocean. [i] Ministry of External Affairs of India (February 2022). India-France Roadmap on the Blue Economy and Ocean Governance. [ii] Ministry of External Affairs of India (March 2022). Indo-French Call for an ‘Indo-Pacific Parks Partnership. Joint Declaration, Paris.
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Alihodžić, Sead. "Electoral Violence Early Warning and Infrastructures for Peace." Journal of Peacebuilding & Development 7, no. 3 (December 2012): 54–69. http://dx.doi.org/10.1080/15423166.2013.767592.
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Outbreaks of election-related violence can be devastating, but experience has shown that they can be prevented. The need for improved efficiency of electoral violence early warning and prevention is increasingly argued. Good practices – developed nationally, regionally and globally – offer useful understanding of the phenomenon and of what can be done to improve prevention and mitigation. Although diverse and contingent on mandates and contexts in which organisations operate, early warning and prevention methodologies have common denominators that can be comparatively analysed. The establishment of national infrastructures for peace, which are also mandated to coordinate early warning, prevention and mitigation of electoral violence, helps to ensure that the impact of such efforts is maximised.
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Schaefer, Jame. "Responding to Small Island Nations Imperiled by Human-Forced Climate Change: An Ethical Imperative for Christians." Anglican Theological Review 100, no. 1 (December 2018): 93–111. http://dx.doi.org/10.1177/000332861810000110.
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Small island nations are increasingly imperiled by larger nations that are emitting most of the greenhouse gases, forcing changes in the global climate, and causing catastrophic ecological and social problems. Among the most adversely affected people are islanders who are suffering immense health, economic, and cultural injustices that should be addressed at all levels of governance. Leaders of Anglican, Eastern Orthodox, and Roman Catholic denominations have been responding meaningfully to the plight of the small island nations by drawing motivation from their theological traditions for mitigating the problems and calling all Christians to act individually, collectively within their parishes, and collaboratively in the public square.
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Anklam III, PhD, Charles, Adam Kirby, MS, Filipo Sharevski, MS, and J. Eric Dietz, PhD, PE. "Mitigating active shooter impact: Analysis for policy options based on agent/computer-based modeling." Journal of Emergency Management 13, no. 3 (May 1, 2015): 201. http://dx.doi.org/10.5055/jem.2015.0234.
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Active shooting violence at confined settings, such as educational institutions, poses serious security concerns to public safety. In studying the effects of active shooter scenarios, the common denominator associated with all events, regardless of reason/intent for shooter motives, or type of weapons used, was the location chosen and time expended between the beginning of the event and its culmination. This in turn directly correlates to number of casualties incurred in any given event. The longer the event protracts, the more casualties are incurred until law enforcement or another barrier can react and culminate the situation.Objective: Using AnyLogic technology, devise modeling scenarios to test multiple hypotheses against free-agent modeling simulation to determine the best method to reduce casualties associated with active shooter scenarios.Design, setting, subjects: Test four possible scenarios of responding to active shooter in a public school setting using agent-based computer modeling techniques—scenario 1: basic scenario where no access control or any type of security is used within the school; scenario 2, scenario assumes that concealed carry individual(s) (5-10 percent of the work force) are present in the school; scenario 3, scenario assumes that the school has assigned resource officer; scenario 4, scenario assumes that the school has assigned resource officer and concealed carry individual(s) (5-10 percent) present in the school.Main outcomes measured: Statistical data from modeling scenarios indicating which tested hypothesis resulted in fewer casualties and quicker culmination of event.Results: The use of AnyLogic proved the initial hypothesis that a decrease on response time to an active shooter scenario directly reduced victim casualties.Conclusions: Modeling tests show statistically significant fewer casualties in scenarios where on-scene armed responders such as resource officers and concealed carry personnel were present.
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De Leonardis, Federico, Gaia Colalillo, Enrico Finazzi Agrò, Roberto Miano, Andrea Fuschi, and Anastasios D. Asimakopoulos. "Endothelial Dysfunction, Erectile Deficit and Cardiovascular Disease: An Overview of the Pathogenetic Links." Biomedicines 10, no. 8 (August 1, 2022): 1848. http://dx.doi.org/10.3390/biomedicines10081848.
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Erectile dysfunction (ED) is a condition with multifactorial pathogenesis, quite common among men, especially those above 60 years old. A vascular etiology is the most common cause. The interaction between chronic inflammation, androgens, and cardiovascular risk factors determines macroscopically invisible alterations such as endothelial dysfunction and subsequent atherosclerosis and flow-limiting stenosis that affects both penile and coronary arteries. Thus, ED and cardiovascular disease (CVD) should be considered two different manifestations of the same systemic disorder, with a shared aetiological factor being endothelial dysfunction. Moreover, the penile arteries have a smaller size compared with coronary arteries; thus, for the same level of arteriopathy, a more significant blood flow reduction will occur in erectile tissue compared with coronary circulation. As a result, ED often precedes CVD by 2–5 years, and its diagnosis offers a time window for cardiovascular risk mitigation. Growing evidence suggests, in fact, that patients presenting with ED should be investigated for CVD even if they have no symptoms. Early detection could facilitate prompt intervention and a reduction in long-term complications. In this review, we provide an overview of the pathogenetic mechanisms behind arteriogenic ED and CVD, focusing on the role of endothelial dysfunction as the common denominator of the two disorders. Developed algorithms that may help identify those patients complaining of ED who should undergo detailed cardiologic assessment and receive intensive treatment for risk factors are also analyzed.
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Stocker, B. D., and F. Joos. "Quantifying differences in land use emission estimates implied by definition discrepancies." Earth System Dynamics 6, no. 2 (November 27, 2015): 731–44. http://dx.doi.org/10.5194/esd-6-731-2015.
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Abstract. The quantification of CO2 emissions from anthropogenic land use and land use change (eLUC) is essential to understand the drivers of the atmospheric CO2 increase and to inform climate change mitigation policy. Reported values in synthesis reports are commonly derived from different approaches (observation-driven bookkeeping and process-modelling) but recent work has emphasized that inconsistencies between methods may imply substantial differences in eLUC estimates. However, a consistent quantification is lacking and no concise modelling protocol for the separation of primary and secondary components of eLUC has been established. Here, we review differences of eLUC quantification methods and apply an Earth System Model (ESM) of Intermediate Complexity to quantify them. We find that the magnitude of effects due to merely conceptual differences between ESM and offline vegetation model-based quantifications is ~ 20 % for today. Under a future business-as-usual scenario, differences tend to increase further due to slowing land conversion rates and an increasing impact of altered environmental conditions on land-atmosphere fluxes. We establish how coupled Earth System Models may be applied to separate secondary component fluxes of eLUC arising from the replacement of potential C sinks/sources and the land use feedback and show that secondary fluxes derived from offline vegetation models are conceptually and quantitatively not identical to either, nor their sum. Therefore, we argue that synthesis studies should resort to the "least common denominator" of different methods, following the bookkeeping approach where only primary land use emissions are quantified under the assumption of constant environmental boundary conditions.
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Stocker, B. D., and F. Joos. "Large differences in land use emission quantifications implied by definition discrepancies." Earth System Dynamics Discussions 6, no. 1 (March 19, 2015): 547–77. http://dx.doi.org/10.5194/esdd-6-547-2015.
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Abstract. The quantification of CO2 emissions from anthropogenic land use and land use change (eLUC) is essential to understand the drivers of the atmospheric CO2 increase and to inform climate change mitigation policy. Reported values in synthesis reports are commonly derived from different approaches (observation-driven bookkeeping and process-modelling) but recent work has emphasized that inconsistencies between methods may imply substantial differences in eLUC estimates. However, a consistent quantification is lacking and no concise modelling protocol for the separation of primary and secondary components of eLUC has been established. Here, we review the conceptual differences of eLUC quantification methods and apply an Earth System Model to demonstrate that what is claimed to represent total eLUC differs by up to ~20% when quantified from ESM vs. offline vegetation models. Under a future business-as-usual scenario, differences tend to increase further due to slowing land conversion rates and an increasing impact of altered environmental conditions on land–atmosphere fluxes. We establish how coupled Earth System Models may be applied to separate component fluxes of eLUC arising from the replacement of potential C sinks/sources and the land use feedback and show that secondary fluxes derived from offline vegetation models are conceptually and quantitatively not identical to either, nor their sum. Therefore, we argue that synthesis studies and global carbon budget accountings should resort to the "least common denominator" of different methods, following the bookkeeping approach where only primary land use emissions are quantified under the assumption of constant environmental boundary conditions.
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Wortham, Jonathan M., Seth A. Meador, James L. Hadler, Kimberly Yousey-Hindes, Isaac See, Michael Whitaker, Alissa O’Halloran, et al. "Census tract socioeconomic indicators and COVID-19-associated hospitalization rates—COVID-NET surveillance areas in 14 states, March 1–April 30, 2020." PLOS ONE 16, no. 9 (September 24, 2021): e0257622. http://dx.doi.org/10.1371/journal.pone.0257622.
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Objectives Some studies suggested more COVID-19-associated hospitalizations among racial and ethnic minorities. To inform public health practice, the COVID-19-associated Hospitalization Surveillance Network (COVID-NET) quantified associations between race/ethnicity, census tract socioeconomic indicators, and COVID-19-associated hospitalization rates. Methods Using data from COVID-NET population-based surveillance reported during March 1–April 30, 2020 along with socioeconomic and denominator data from the US Census Bureau, we calculated COVID-19-associated hospitalization rates by racial/ethnic and census tract-level socioeconomic strata. Results Among 16,000 COVID-19-associated hospitalizations, 34.8% occurred among non-Hispanic White (White) persons, 36.3% among non-Hispanic Black (Black) persons, and 18.2% among Hispanic or Latino (Hispanic) persons. Age-adjusted COVID-19-associated hospitalization rate were 151.6 (95% Confidence Interval (CI): 147.1–156.1) in census tracts with >15.2%–83.2% of persons living below the federal poverty level (high-poverty census tracts) and 75.5 (95% CI: 72.9–78.1) in census tracts with 0%–4.9% of persons living below the federal poverty level (low-poverty census tracts). Among White, Black, and Hispanic persons living in high-poverty census tracts, age-adjusted hospitalization rates were 120.3 (95% CI: 112.3–128.2), 252.2 (95% CI: 241.4–263.0), and 341.1 (95% CI: 317.3–365.0), respectively, compared with 58.2 (95% CI: 55.4–61.1), 304.0 (95%: 282.4–325.6), and 540.3 (95% CI: 477.0–603.6), respectively, in low-poverty census tracts. Conclusions Overall, COVID-19-associated hospitalization rates were highest in high-poverty census tracts, but rates among Black and Hispanic persons were high regardless of poverty level. Public health practitioners must ensure mitigation measures and vaccination campaigns address needs of racial/ethnic minority groups and people living in high-poverty census tracts.
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Kirshner, Jeffrey J., Kelly Cohn, Steven Dunder, Karri Donahue, Madeline Richey, Peter Larson, Lauren Sutton, et al. "An automated EHR-based tool for identification of patients (pts) with metastatic disease to facilitate clinical trial pt ascertainment." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 2051. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.2051.
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2051 Background: Efforts to facilitate patient identification for clinical trials in routine practice, such as automating electronic health record (EHR) data reviews, are hindered by the lack of information on metastatic status in structured format. We developed a machine learning tool that infers metastatic status from unstructured EHR data, and we describe its real-world implementation. Methods: This machine learning model scans EHR documents, extracting features from text snippets surrounding key words (ie, ‘Metastatic’ ‘Progression’ ‘Local’). A regularized logistic regression model was trained, and used to classify patients across 5 metastatic status inference categories: highly-likely and likely positive, highly-likely and likely negative, and unknown. The model accuracy was characterized using the Flatiron Health EHR-derived de-identified database of patients with solid tumors, where manually abstracted information served as standard accurate reference. We assessed model accuracy using sensitivity and specificity (patients in the ‘unknown’ category omitted from numerator), negative and positive predictive values (NPV, PPV; patients ‘unknown’ included in denominator), and its performance in a real-world dataset. In a separate validation, we evaluated the accuracy gained upon additional user review of the model outputs after integration of this tool into workflows. Results: This metastatic status inference model was characterized using a sample of 66,532 patients. The model sensitivity and specificity (95%CI) were 82.% (82, 83) and 95% (95, 96), respectively; PPV was 89% (89, 90) and NPV was 94% (94, 94). In the validation sample (N = 200 originated from 5 distinct care sites), and after user review of model outputs, values increased to 97% (85, 100) for sensitivity, 98% (95, 100) for specificity, 92 (78, 98) for PPV and 99% (97, 100) for NPV. The model assigned 163/200 patients to the highly-likely categories, which were deemed not to require further EHR review by users. The prevalence of errors was 4% without user review, and 2% after user review. Conclusions: This machine learning model infers metastatic status from unstructured EHR data with high accuracy. The tool assigns metastatic status with high confidence in more than 75% of cases without requiring additional manual review, allowing more efficient identification of clinical trial candidates and clinical trial matching, thus mitigating a key barrier for clinical trial participation in community clinics.
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Aylmer, G. E. "Presidential Address: Collective Mentalities in mid Seventeenth-Century England: I. The Puritan Outlook." Transactions of the Royal Historical Society 36 (December 1986): 1–25. http://dx.doi.org/10.2307/3679057.
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IT may seem unwise, if not downright foolish, and hubristic too, for someone who is not a historian of religion or the Church to choose such a topic as mine today. In mitigation of my offence, religion in the seventeenth century is in truth not only too important to be left to the theologians, but likewise too protean in its ramifications to re-main the exclusive preserve of ecclesiastical historians. Not that I wish in any way to slight the achievements of those scholars (some of them present this afternoon), without whose work I should not have had the temerity to attempt such a study as this at all. The problem which I wish to address is as follows: there are several interpretations of the different factions, parties and tendencies within the Church of England before 1640. There are disagreements con-cerning both the nature and extent of the differences between these groups, and the causes and significance of such divisions. There are many studies of the ecclesiastical parties and denominations which emerged on the anti-Catholic and then the anti-episcopalian side in 1641 and after, and of their part in the general history of the Civil War and Interregnum. Moving forward in time, there are studies of the restored Church and of the Dissenters or Nonconformists after 1660–2. In spite of all that has been written about Puritans from that day to this, especially about their theology, ecclesiology, liturgical practices, their moral, social and political tenets, less attention has been paid to the question of what constituted a Puritan in the first place.
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Kurtz, Steven M., Edmund Lau, Kevin L. Ong, Leah Carreon, Heather Watson, Todd Albert, and Steven Glassman. "Infection risk for primary and revision instrumented lumbar spine fusion in the Medicare population." Journal of Neurosurgery: Spine 17, no. 4 (October 2012): 342–47. http://dx.doi.org/10.3171/2012.7.spine12203.
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Object This retrospective analysis of Medicare administrative data was performed to evaluate the risk of infection following instrumented lumbar fusion over a 10-year follow-up period in the Medicare population. Although infection can be a devastating complication, due to its rarity it is difficult to characterize infection risk except in large patient populations. Methods Using ICD-9-CM and CPT4 procedure codes, the Medicare 5% analytical research files for inpatient, outpatient, and physician carrier claims were checked to identify patients who were treated between 1997 and 2009 with lumbar spine fusion in which cages or posterior instrumentation were used. Patients younger than 65 years old were excluded. Patients were followed continuously by using the matching denominator file until they withdrew from Medicare or died. The authors identified 15,069 patients with primary fusion procedures and 605 with revision of instrumented lumbar fusion. Infections were identified by the related ICD-9 codes (998.59 or 996.67) after fusion. Kaplan-Meier survival analysis and Cox regression were performed to determine adjusted infection risk for each type of spine procedure (primary vs revision) and surgical approach (anterior, posterior, combined anteroposterior), accounting for patient (for example, age, sex, comorbidities/Charlson Comorbidity Index [CCI], and state buy-in) and hospital (census region) characteristics. Results At 10 years, the overall infection incidence, including superficial and deep infections, was 8.5% in primary procedures and 12.2% in revisions. Among the factors considered, infection risk within 10 years was most influenced by comorbidities: for a CCI of 5 versus 0, the adjusted hazard ratio (AHR) was 2.48 (95% CI 1.93–3.19, p < 0.001); for ≥ 9 versus 2–3 fused vertebrae, the AHR was 2.39 (95% CI 1.20–4.76, p < 0.001); for revision versus primary fusion procedures, the AHR was 1.66 (95% CI 1.28–2.15, p < 0.001). Other significant predictors of 10-year infection risk included diagnosis of obesity (p < 0.001); state buy-in—a proxy for socioeconomic status (p = 0.02); age (p = 0.003); surgical approach (p = 0.03); census region (p = 0.02); and the year of the index procedure (p = 0.03). Conclusions Patient comorbidities were the greatest predictor of infection risk for the Medicare population. The high incidence of infection following instrumented fusion warrants increased focus on infection risk mitigation, especially for patients with comorbid conditions.
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Spivak, Jerry L., Donna Marie Williams, Zhizhuang Joe Zhao, Ophelia Rogers, Amy S. Duffield, W. David Hankins, and Alison R. Moliterno. "MPL SV, a Unique MPN MPL Splice Variant, Provokes a Fulminant Myeloid Leukemia in a JAK2 V617F Transgenic Mouse Model of Polycythemia Vera." Blood 126, no. 23 (December 3, 2015): 484. http://dx.doi.org/10.1182/blood.v126.23.484.484.
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Abstract Introduction: The MPN, polycythemia vera (PV), essential thrombocytosis (ET) and primary myelofibrosis (PMF) are clonal stem cell disorders, which share mutations constitutively activating the physiologic signal transduction pathways for hematopoiesis. Although the MPN have different natural histories, they share in common transformation to myelofibrosis and acute leukemia at differing frequencies and not explainable by a specific mutation. Impaired MPL expression, due to incomplete glycosylation is another common denominator amongst the MPN. Significantly, MPL is the only hematopoietic growth factor receptor expressed in MPN HSC, and we have demonstrated that the PV phenotype in a JAK2 V617F transgenic (V617tg) mouse could be abrogated by elimination of MPL or its ligand, TPO. Impaired MPL expression in the MPN cannot be completely explained by receptor-activated down regulation because not all MPN driver mutations directly activate MPL. However, we have discovered another common denominator in the MPN, variant MPL splicing, eliminating 7 amino acids in the MPL N-terminal domain, a common hotspot for both MPL driver and inactivating mutations, which impairs MPL glycosylation and expression. Methods: To determine the role of the MPL splice variant (MPL SV) in MPN pathophysiology, we cloned the full length MPLSV cDNA and created a transgenic mouse (MPLSV tg) using the same VAV promoter as the V617Ftg mouse to ensure hematopoietic cell-specific transcription. The MPLSV tg mice were produced by pronuclear injection of purified MPLSV cDNA into B6SJLF1 mice. Founders were crossed into a C57Bl/6 background, and then were crossed with V617Ftg mice in either an MPL knockout or wild type background. Mice were phenotyped by blood counts and necropsy with morphologic and immunophenotyping of bone marrow and tumor masses. Results: Amongst 19 founder B6SJLF1 mice, 6 expressed the MPLSV transgene with copy numbers ranging from one to 30; single copy number mice had no hematopoietic phenotype but all mice with higher MPLSV tg copy numbers had thrombocytopenia (median platelet count 500,000/µL; range 200- 600,000; wild type, 750,000/µL; 550-950,000). MPLSV tg mice from several different founders bred into a C57Bl/6 background for 6 generations maintained consistent copy numbers, Mendelian ratios and hematopoietic phenotypes with 100% penetrance and an inverse correlation between MPLSV copy number and the platelet count. The number of double transgenic (V617Ftg/MPLSV tg) offspring observed in the MPLSV tg to V617Ftg crosses were slightly lower than expected (20% vs 25%), indicating reduced embryo viability. Four week old V617Ftg/MPLSV tg mice displayed tumorous abnormalities of the head and hips as well as small size and failure to thrive (median weight 8.5 gms; range 8-9; wild type, 13 gms; 10-14), and enlarged spleens (median weight 0.29 gms; range 0.15-0.64; wild type 0.086 gms; 0.05-0.10). Histologically, the V617Ftg/MPLSV tg-associated head and hip abnormalities represented monomorphic myeloid sarcomas extending through the calvarium both extra and intracranially and from the femur into surrounding muscle. Both the marrow and spleen were diffusely infiltrated by large blasts with abundant basophilic cytoplasm, expressing CD34, CD61 and CD117 but lacking CD127, consistent with a myeloid origin. All V617Ftg/MPLSV tg mice either died or required humane sacrifice by 6 weeks. The extramedullary tumor was transplantable in secondary recipients, and flow cytometry-based phenotyping showed that the tumors (both primary and secondary) were CD34, CD117, CD61 and CD71- positive. Penetrance of the leukemia phenotype was 100% in V617Ftg/MPLSV tg from all founder lines with multiple copies of the MPLSV tg, whether in an MPL knockout or wild type background. The leukemia phenotype was never observed with the MPLSV tg alone or with V617Ftg alone despite observation of over 300 V617Ftg mice up to 50 weeks of age. Conclusion: We identified an MPL SV in human MPN that was functional in mice with a dominant-negative effect with respect to platelet production and at the same time synergized with JAK2 V617F to create a fulminant myeloid malignancy. We have recently shown that knockout of MPL or TPO alone abrogates the PV phenotype in the V617Ftg mouse, whereas the MPLSV uniquely drives a highly penetrant and fulminant leukemia, establishing MPL and TPO as targets for mitigation of malignant transformation in the MPN. Disclosures Spivak: Incyte: Membership on an entity's Board of Directors or advisory committees. Moliterno:incyte: Membership on an entity's Board of Directors or advisory committees.
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Petrescu, Ana Maria Roxana, Chunjing Qiu, Philippe Ciais, Rona L. Thompson, Philippe Peylin, Matthew J. McGrath, Efisio Solazzo, et al. "The consolidated European synthesis of CH<sub>4</sub> and N<sub>2</sub>O emissions for the European Union and United Kingdom: 1990–2017." Earth System Science Data 13, no. 5 (May 28, 2021): 2307–62. http://dx.doi.org/10.5194/essd-13-2307-2021.
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Abstract. Reliable quantification of the sources and sinks of greenhouse gases, together with trends and uncertainties, is essential to monitoring the progress in mitigating anthropogenic emissions under the Paris Agreement. This study provides a consolidated synthesis of CH4 and N2O emissions with consistently derived state-of-the-art bottom-up (BU) and top-down (TD) data sources for the European Union and UK (EU27 + UK). We integrate recent emission inventory data, ecosystem process-based model results and inverse modeling estimates over the period 1990–2017. BU and TD products are compared with European national greenhouse gas inventories (NGHGIs) reported to the UN climate convention UNFCCC secretariat in 2019. For uncertainties, we used for NGHGIs the standard deviation obtained by varying parameters of inventory calculations, reported by the member states (MSs) following the recommendations of the IPCC Guidelines. For atmospheric inversion models (TD) or other inventory datasets (BU), we defined uncertainties from the spread between different model estimates or model-specific uncertainties when reported. In comparing NGHGIs with other approaches, a key source of bias is the activities included, e.g., anthropogenic versus anthropogenic plus natural fluxes. In inversions, the separation between anthropogenic and natural emissions is sensitive to the geospatial prior distribution of emissions. Over the 2011–2015 period, which is the common denominator of data availability between all sources, the anthropogenic BU approaches are directly comparable, reporting mean emissions of 20.8 Tg CH4 yr−1 (EDGAR v5.0) and 19.0 Tg CH4 yr−1 (GAINS), consistent with the NGHGI estimates of 18.9 ± 1.7 Tg CH4 yr−1. The estimates of TD total inversions give higher emission estimates, as they also include natural emissions. Over the same period regional TD inversions with higher-resolution atmospheric transport models give a mean emission of 28.8 Tg CH4 yr−1. Coarser-resolution global TD inversions are consistent with regional TD inversions, for global inversions with GOSAT satellite data (23.3 Tg CH4 yr−1) and surface network (24.4 Tg CH4 yr−1). The magnitude of natural peatland emissions from the JSBACH–HIMMELI model, natural rivers and lakes emissions, and geological sources together account for the gap between NGHGIs and inversions and account for 5.2 Tg CH4 yr−1. For N2O emissions, over the 2011–2015 period, both BU approaches (EDGAR v5.0 and GAINS) give a mean value of anthropogenic emissions of 0.8 and 0.9 Tg N2O yr−1, respectively, agreeing with the NGHGI data (0.9 ± 0.6 Tg N2O yr−1). Over the same period, the average of the three total TD global and regional inversions was 1.3 ± 0.4 and 1.3 ± 0.1 Tg N2O yr−1, respectively. The TD and BU comparison method defined in this study can be operationalized for future yearly updates for the calculation of CH4 and N2O budgets both at the EU+UK scale and at the national scale. The referenced datasets related to figures are visualized at https://doi.org/10.5281/zenodo.4590875 (Petrescu et al., 2020b).
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Jamieson, Lisa, Joanne Hedges, Marco A. Peres, Carol C. Guarnizo-Herreño, and João L. Bastos. "Challenges in identifying indigenous peoples in population oral health surveys: a commentary." BMC Oral Health 21, no. 1 (April 28, 2021). http://dx.doi.org/10.1186/s12903-021-01455-w.
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AbstractThere are currently 370 million persons identifying as indigenous across 90 countries globally. Indigenous peoples generally face substantial exclusion/marginalization and poorer health status compared with non-indigenous majority populations; this includes poorer oral health status and reduced access to dental services. Population-level oral health surveys provide data to set priorities, inform policies, and monitor progress in dental disease experience/dental service utilisation over time. Rigorously and comprehensively measuring the oral health burden of indigenous populations is an ethical issue, though, given that survey instruments and sampling procedures are usually not sufficiently inclusive. This results in substantial underestimation or even biased estimation of dental disease rates and severity among indigenous peoples, making it difficult for policy makers to prioritise resources in this area. The methodological challenges identified include: (1) suboptimal identification of indigenous populations; (2) numerator-denominator bias and; (3) statistical analytic considerations. We suggest solutions that can be implemented to strengthen the visibility of indigenous peoples around the world in an oral health context. These include acknowledgment of the need to engage indigenous peoples with all data-related processes, encouraging the use of indigenous identifiers in national and regional data sets, and mitigating and/or carefully assessing biases inherent in population oral health methodologies for indigenous peoples.
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Pray, Ian W., Barbara Grajewski, Collin Morris, Komi Modji, Peter DeJonge, Katherine McCoy, Carrie Tomasallo, Traci DeSalvo, Ryan P. Westergaard, and Jonathan Meiman. "Measuring work-related risk of COVID-19: comparison of COVID-19 incidence by occupation and industry – Wisconsin, September 2020-May 2021." Clinical Infectious Diseases, August 4, 2022. http://dx.doi.org/10.1093/cid/ciac586.
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Abstract Background Work-related exposures play an important role in SARS-CoV-2 transmission, yet few studies have measured the risk of COVID-19 across occupations and industries. Methods During September 2020 – May 2021, the Wisconsin Department of Health Services collected occupation and industry data as part of routine COVID-19 case investigations. Adults aged 18-64 years with confirmed or probable COVID-19 in Wisconsin were assigned standardized occupation and industry codes. Cumulative incidence rates were weighted for non-response and calculated using full-time equivalent (FTE) workforce denominators from the 2020 American Community Survey. Results An estimated 11.6% of workers (347,013 of 2.98 million) in Wisconsin, ages 18-64 years, had COVID-19 from September 2020 to May 2021. The highest incidence by occupation (per 100 full-time equivalents) occurred among personal care and services workers (22.4), healthcare practitioners and support staff (20.7), and protective services workers (20.7). High risk sub-groups included nursing assistants and personal care aides (28.8), childcare workers (25.8), food and beverage service workers (25.3), personal appearance workers (24.4), and law enforcement workers (24.1). By industry, incidence was highest in healthcare (18.6); the highest risk sub-sectors were nursing care facilities (30.5) and warehousing (28.5). Conclusions This analysis represents one of the most complete examinations to date of COVID-19 incidence by occupation and industry. Our approach demonstrates the value of standardized occupational data collection by public health, and may be a model for improved occupational surveillance elsewhere. Workers at higher risk of SARS-CoV-2 exposure may benefit from targeted workplace COVID-19 vaccination and mitigation efforts.
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Elliot, Alex J., Sally E. Harcourt, Helen E. Hughes, Paul Loveridge, Roger A. Morbey, Sue Smith, Ana Soriano, et al. "The COVID-19 pandemic: a new challenge for syndromic surveillance." Epidemiology and Infection 148 (2020). http://dx.doi.org/10.1017/s0950268820001314.
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Abstract The COVID-19 pandemic is exerting major pressures on society, health and social care services and science. Understanding the progression and current impact of the pandemic is fundamental to planning, management and mitigation of future impact on the population. Surveillance is the core function of any public health system, and a multi-component surveillance system for COVID-19 is essential to understand the burden across the different strata of any health system and the population. Many countries and public health bodies utilise ‘syndromic surveillance’ (using real-time, often non-specific symptom/preliminary diagnosis information collected during routine healthcare provision) to supplement public health surveillance programmes. The current COVID-19 pandemic has revealed a series of unprecedented challenges to syndromic surveillance including: the impact of media reporting during early stages of the pandemic; changes in healthcare-seeking behaviour resulting from government guidance on social distancing and accessing healthcare services; and changes in clinical coding and patient management systems. These have impacted on the presentation of syndromic outputs, with changes in denominators creating challenges for the interpretation of surveillance data. Monitoring changes in healthcare utilisation is key to interpreting COVID-19 surveillance data, which can then be used to better understand the impact of the pandemic on the population. Syndromic surveillance systems have had to adapt to encompass these changes, whilst also innovating by taking opportunities to work with data providers to establish new data feeds and develop new COVID-19 indicators. These developments are supporting the current public health response to COVID-19, and will also be instrumental in the continued and future fight against the disease.
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Boutzoukas, Angelique E., Kanecia O. Zimmerman, Daniel K. Benjamin, Gregory P. DeMuri, Ibukunoluwa C. Kalu, Michael J. Smith, Kathleen A. McGann, Shawn Koval, M. Alan Brookhart, and Sabrina M. Butteris. "Secondary Transmission of COVID-19 in K–12 Schools: Findings From 2 States." Pediatrics 149, Supplement_2 (February 1, 2022). http://dx.doi.org/10.1542/peds.2021-054268k.
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OBJECTIVES We evaluated the impact of distancing practices on secondary transmission of severe acute respiratory syndrome coronavirus 2 and the degree of sports-associated secondary transmission across a large diverse cohort of schools during spring 2021. METHODS Participating districts in North Carolina and Wisconsin and North Carolina charter schools offering in-person instruction between March 15, 2021 and June 25, 2021 reported on distancing policies, community- and school-acquired infections, quarantines, and infections associated with school-sponsored sports. We calculated the ratio of school-acquired to community-acquired infection, secondary attack rates, and the proportion of secondary transmission events associated with sports. To estimate the effect of distancing and bus practices on student secondary transmission, we used a quasi–Poisson regression model with the number of primary student cases as the denominator. RESULTS During the study period, 1 102 039 students and staff attended in-person instruction in 100 North Carolina school districts, 13 Wisconsin school districts, and 14 North Carolina charter schools. Students and staff had 7865 primary infections, 386 secondary infections, and 48 313 quarantines. For every 20 community-acquired infections, there was 1 within-school transmission event. Secondary transmissions associated with school sports composed 46% of secondary transmission events in middle and high schools. Relaxed distancing practices (<3 ft, 3 ft) and increased children per bus seat were not associated with increased relative risk of secondary transmission. CONCLUSIONS With universal masking, in-person education was associated with low rates of secondary transmission, even with less stringent distancing and bus practices. Given the rates of sports-associated secondary transmission, additional mitigation may be warranted.
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DeGroot, David W., Catherine A. Rappole, Paige McHenry, and Robyn M. Englert. "Seasonal Trends for Environmental Illness Incidence in the U.S. Army." Military Medicine, February 19, 2021. http://dx.doi.org/10.1093/milmed/usab072.
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ABSTRACT Introduction The incidence of and risk factors for exertional heat illness (EHI) and cold weather injury (CWI) in the U.S. Army have been well documented. The “heat season”, when the risk of EHI is highest and application of risk mitigation procedures is mandatory, has been arbitrarily defined as May 1 through September 30, while the “cold season” is understood to occur from October 1 to April 30 each year. The proportions of EHI and CWI that occur outside of the traditional heat and cold seasons are unknown. Additionally, it is unknown if either of the seasonal definitions are appropriate. The primary purpose of this study was to determine the proportion of EHI and of CWI that occur within the commonly accepted seasonal definitions. We also report the location-specific variability, seasonal definitions, and the demographic characteristics of the populations. Methods The U.S. Army installations with the highest frequency of EHI and of CWI from 2008 to 2013 were identified and used for analysis. In total there were 15 installations included in the study, with five installations used for analysis in both the EHI and CWI projects. In- and out-patient EHI and CWI data (ICD-9-CM codes 992.0 to 992.9 and ICD codes 991.0 to 991.9, respectively) were obtained from the Defense Medical Surveillance System. Installation-specific denominator data were obtained from the Defense Manpower Data Center, and incidence rates were calculated by week, for each installation. Segmental (piecewise) regression analysis was used to determine the start and end of the heat and cold seasons. Results Our analysis indicates that the heat season starts around April 22 and ends around September 9. The cold season starts on October 3 and ends on March 24. The majority (n = 6,445, 82.3%) of EHIs were diagnosed during the “heat season” of May 1 to September 30, while 10.3% occurred before the heat season started (January1 to April 30) and 7.3% occurred after the heat season ended (October 1 to December 31). Similar to EHI, 90.5% of all CWIs occurred within the traditionally defined cold season, while 5.7% occurred before and 3.8% occurred after the cold season. The locations with the greatest EHI frequency were Ft Bragg (n = 2,129), Ft Benning (n = 1,560), and Ft Jackson (n = 1,538). The bases with the largest proportion of CWI in this sample were Ft Bragg (17.8%), Ft Wainwright (17.2%), and Ft Jackson (12.7%). There were considerable inter-installation differences for the start and end dates of the respective seasons. Conclusions The present study indicates that the traditional heat season definition should be revised to begin ∼3 weeks earlier than the current date of May 1; our data indicate that the current cold season definition is appropriate. Inter-installation variability in the start of the cold season was much larger than that for the heat season. Exertional heat illnesses are a year-round problem, with ∼17% of all cases occurring during non-summer months, when environmental heat strain and vigilance are lower. This suggests that EHI mitigation policies and procedures require greater year-round emphasis, particularly at certain locations.