scholarly journals COVID-19 vaccines that reduce symptoms but do not block infection need higher coverage and faster rollout to achieve population impact

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
David A. Swan ◽  
Chloe Bracis ◽  
Holly Janes ◽  
Mia Moore ◽  
Laura Matrajt ◽  
...  
Keyword(s):  
Mathematical Model ◽  
No Reduction ◽  
King County ◽  
Symptomatic Disease ◽  
Population Impact ◽  
Susceptibility To Infection ◽  
Infection Susceptibility ◽  
Asymptomatic Infections ◽  
The U.S

AbstractTrial results for two COVID-19 vaccines suggest at least 90% efficacy against symptomatic disease (VEDIS). It remains unknown whether this efficacy is mediated by lowering SARS-CoV-2 infection susceptibility (VESUSC) or development of symptoms after infection (VESYMP). We aim to assess and compare the population impact of vaccines with different efficacy profiles (VESYMP and VESUSC) satisfying licensure criteria. We developed a mathematical model of SARS-CoV-2 transmission, calibrated to data from King County, Washington. Rollout scenarios starting December 2020 were simulated with combinations of VESUSC and VESYMP resulting in up to 100% VEDIS. We assumed no reduction of infectivity upon infection conditional on presence of symptoms. Proportions of cumulative infections, hospitalizations and deaths prevented over 1 year from vaccination start are reported. Rollouts of 1 M vaccinations (5000 daily) using vaccines with 50% VEDIS are projected to prevent 23–46% of infections and 31–46% of deaths over 1 year. In comparison, vaccines with 90% VEDIS are projected to prevent 37–64% of infections and 46–64% of deaths over 1 year. In both cases, there is a greater reduction if VEDIS is mediated mostly by VESUSC. The use of a “symptom reducing” vaccine will require twice as many people vaccinated than a “susceptibility reducing” vaccine with the same 90% VEDIS to prevent 50% of the infections and death over 1 year. Delaying the start of the vaccination by 3 months decreases the expected population impact by more than 50%. Vaccines which prevent COVID-19 disease but not SARS-CoV-2 infection, and thereby shift symptomatic infections to asymptomatic infections, will prevent fewer infections and require larger and faster vaccination rollouts to have population impact, compared to vaccines that reduce susceptibility to infection. If uncontrolled transmission across the U.S. continues, then expected vaccination in Spring 2021 will provide only limited benefit.

scholarly journals COVID-19 vaccines that reduce symptoms but do not block infection need higher coverage and faster rollout to achieve population impact

2020 ◽  
Author(s):  
David A. Swan ◽  
Chloe Bracis ◽  
Holly Janes ◽  
Mia Moore ◽  
Laura Matrajt ◽  
...  
Keyword(s):  
No Reduction ◽  
King County ◽  
Vaccine Candidates ◽  
Symptomatic Disease ◽  
Population Impact ◽  
Susceptibility To Infection ◽  
Infection Susceptibility ◽  
Asymptomatic Infections ◽  
One Year ◽  
The U.S

AbstractBackgroundSeveral COVID-19 vaccine candidates are in the final stage of testing. Interim trial results for two vaccines suggest at least 90% efficacy against symptomatic disease (VEDIS). It remains unknown whether this efficacy is mediated predominately by lowering SARS-CoV-2 infection susceptibility (VESUSC) or development of symptoms after infection (VESYMP). A vaccine with high VESYMP but low VESUSC has uncertain population impact.MethodsWe developed a mathematical model of SARS-CoV-2 transmission, calibrated to demographic, physical distancing and epidemic data from King County, Washington. Different rollout scenarios starting December 2020 were simulated assuming different combinations of VESUSC and VESYMP resulting in up to 100% VEDIS with constant vaccine effects over 1 year. We assumed no further increase in physical distancing despite expanding case numbers and no reduction of infectivity upon infection conditional on presence of symptoms. Proportions of cumulative infections, hospitalizations and deaths prevented over 1 year from vaccination start are reported.ResultsRollouts of 1M vaccinations (5,000 daily) using vaccines with 50% VEDIS are projected to prevent 30%-58% of infections and 38%-58% of deaths over one year. In comparison, vaccines with 90% VEDIS are projected to prevent 47%-78% of the infections and 58%-77% of deaths over one year. In both cases, there is a greater reduction if VEDIS is mediated mostly by VESUSC. The use of a “symptom reducing” vaccine will require twice as many people vaccinated than a “susceptibility reducing” vaccine with the same 90% VEDIS to prevent 50% of the infections and death over one year. Delaying the start of the vaccination by 3 months decreases the expected population impact by approximately 40%.ConclusionsVaccines which prevent COVID-19 disease but not SARS-CoV-2 infection, and thereby shift symptomatic infections to asymptomatic infections, will prevent fewer infections and require larger and faster vaccination rollouts to have population impact, compared to vaccines that reduce susceptibility to infection. If uncontrolled transmission across the U.S. continues, then expected vaccination in Spring 2021 will provide only limited benefit.

Cadmium and Kidney Function in the U.S. Population: Impact of Sex, Diabetes and Hypertension

2018 ◽  
Vol 2018 (1) ◽  
Author(s):  
Jessica Madrigal ◽  
Ana Ricardo ◽  
Victoria Persky ◽  
Mary Turyk
Keyword(s):  
Kidney Function ◽  
Population Impact ◽  
The U.S

scholarly journals Simulation of a Hydraulic Load Sensing Proportional Valve

2018 ◽  
Author(s):  
Sanjar Mirzaliev ◽  
Kungratbai Sharipov
Keyword(s):  
Mathematical Model ◽  
Energy Consumption ◽  
Control Strategies ◽  
Level Of Detail ◽  
Department Of Energy ◽  
Fluid Power ◽  
Hydraulic Systems ◽  
Proportional Valve ◽  
Load Sensing ◽  
The U.S

Nowadays energy saving is a topical issue due to increasing fuel costs and this aspect is amplified by more stringent emissions regulations that impact on vehicle development. A recent study conducted by the U.S. Department of Energy shows that about five percent of the U.S. energy consumption is transmitted by fluid power equipment. Nevertheless, this study also shows that the efficiency of fluid power averages 21 percent. This offers a huge opportunity to improve the current state-of-the-art of fluid power machines, in particular to improve the energy consumption of current applications. These facts dictate a continuous strive toward improvements and more efficient solutions: to accomplish this objective a strong reduction of hydraulic losses and better control strategies of the hydraulic systems are needed. In fluid power, there exist many techniques to reduce/recover energy losses of the conventional layouts, e.g. load sensing, electrohydraulic flow matching, independent metering, etc. One of the most efficient ways to analyze these different layouts and identify the best hydraulic solution is done through virtual simulations instead of prototyping, since the latter involves higher investment costs to deliver the product into the market. However, to build a fluid power machine virtual model, some problems arise relative to different aspects, for instance: loads on actuators (both linear and rotational) are not constant and pumps are driven by a real engine whose speed depends on required torque. Furthermore, it is important to achieve higher level of detail to simulate each component in the circuit: the greater detail, the better the machine behavior is portrayed, but it obviously entails heavy impact on simulation time and computational resources. Therefore, there is a need to create mathematical model of components and systems with sufficient level of detail to easily acquire all those phenomena necessary to correctly evaluate machine performance and make modifications to the fluid power component design. In this context, a hydraulic proportional valve PVG 32 by Danfoss is taken as an object of study, its performance is analyzed with suitable mathematical model and simulation is done to observe closeness of a model to the laboratory experiment.

scholarly journals A predictive model for the wettability of chalk

2020 ◽  
Vol 2 (10) ◽  
Author(s):  
Meysam Nourani ◽  
Niels Hemmingsen Schovsbo ◽  
Ashkan Jahanbani Ghahfarokhi ◽  
Carsten Møller Nielsen ◽  
Lykourgos Sigalas ◽  
...  
Keyword(s):  
Mathematical Model ◽  
North Sea ◽  
Analytical Method ◽  
Oil Fields ◽  
Laboratory Measurements ◽  
The North ◽  
Water Wettability ◽  
The North Sea ◽  
Capillary Pressure Curves ◽  
The U.S

Abstract Wettability is usually measured in special core analyses of limited plug samples according to typically costly and time-consuming procedures. For comparative purposes, wettability is considered an index. The two most frequently used wettability indices are the Amott–Harvey wettability index and the U.S. Bureau of Mines (USBM) index. The Amott–Harvey wettability index is linked to imbibition characteristics and the USBM index is associated with the area under capillary pressure curves. To provide a fast analytical method, a mathematical model for predicting the wettability of chalk is presented. The model is calibrated using experimental wettability data and subsequently applied to two wells in Danish chalk oil fields in the North Sea and to outcrop chalk samples. The model supplements traditional labor-intensive laboratory measurements and predicts water wettability variations with depth by modeling both depth and porosity dependencies; in addition, it provides estimates of the effects of the aging time and displacement temperature of chalk wettability measurements in the laboratory.

scholarly journals Mathematical Model of the Role of Asymptomatic Infection in Outbreaks of Some Emerging Pathogens

2020 ◽  
Vol 5 (4) ◽  
pp. 184
Author(s):  
Nourridine Siewe ◽  
Bradford Greening ◽  
Nina H. Fefferman
Keyword(s):  
Mathematical Model ◽  
Emerging Infectious Diseases ◽  
Asymptomatic Infection ◽  
Emerging Diseases ◽  
Accurate Estimation ◽  
Disease Dynamics ◽  
Emerging Pathogens ◽  
Hypothetical Scenario ◽  
Asymptomatic Infections

Preparation for outbreaks of emerging infectious diseases is often predicated on beliefs that we will be able to understand the epidemiological nature of an outbreak early into its inception. However, since many rare emerging diseases exhibit different epidemiological behaviors from outbreak to outbreak, early and accurate estimation of the epidemiological situation may not be straightforward in all cases. Previous studies have proposed considering the role of active asymptomatic infections co-emerging and co-circulating as part of the process of emergence of a novel pathogen. Thus far, consideration of the role of asymptomatic infections in emerging disease dynamics have usually avoided considering some important sets of influences. In this paper, we present and analyze a mathematical model to explore the hypothetical scenario that some (re)emerging diseases may actually be able to maintain stable, endemic circulation successfully in an entirely asymptomatic state. We argue that an understanding of this potential mechanism for diversity in observed epidemiological dynamics may be of considerable importance in understanding and preparing for outbreaks of novel and/or emerging diseases.

scholarly journals PD-L1+ neutrophils contribute to injury-induced infection susceptibility

2021 ◽  
Vol 7 (10) ◽  
pp. eabd9436
Author(s):  
Ajitha Thanabalasuriar ◽  
Abby J. Chiang ◽  
Christopher Morehouse ◽  
Margarita Camara ◽  
Shonda Hawkins ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Neutrophil Accumulation ◽  
Susceptibility To Infection ◽  
Infection Susceptibility ◽  
Epidermal Growth ◽  
Lung Endothelial Cells ◽  
Altered Gene ◽  
Underlying Mechanisms ◽  
Skin Healing

The underlying mechanisms contributing to injury-induced infection susceptibility remain poorly understood. Here, we describe a rapid increase in neutrophil cell numbers in the lungs following induction of thermal injury. These neutrophils expressed elevated levels of programmed death ligand 1 (PD-L1) and exhibited altered gene expression profiles indicative of a reparative population. Upon injury, neutrophils migrate from the bone marrow to the skin but transiently arrest in the lung vasculature. Arrested neutrophils interact with programmed cell death protein 1 (PD-1) on lung endothelial cells. A period of susceptibility to infection is linked to PD-L1+ neutrophil accumulation in the lung. Systemic treatment of injured animals with an anti–PD-L1 antibody prevented neutrophil accumulation in the lung and reduced susceptibility to infection but augmented skin healing, resulting in increased epidermal growth. This work provides evidence that injury promotes changes to neutrophils that are important for wound healing but contribute to infection susceptibility.

scholarly journals Adrenergic-mediated loss of splenic marginal zone B cells contributes to infection susceptibility after stroke

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Laura McCulloch ◽  
Craig J. Smith ◽  
Barry W. McColl
Keyword(s):  
B Cells ◽  
Marginal Zone ◽  
Major Complication ◽  
Experimental Stroke ◽  
Stroke Patients ◽  
Marginal Zone B Cells ◽  
Mortality And Morbidity ◽  
Susceptibility To Infection ◽  
Infection Susceptibility ◽  
Improve Clinical Outcome

Abstract Infection is a major complication of acute stroke and causes increased mortality and morbidity; however, current interventions do not prevent infection and improve clinical outcome in stroke patients. The mechanisms that underlie susceptibility to infection in these patients are unclear. Splenic marginal zone (MZ) B cells are innate-like lymphocytes that provide early defence against bacterial infection. Here we show experimental stroke in mice induces a marked loss of MZ B cells, deficiencies in capturing blood-borne antigen and suppression of circulating IgM. These deficits are accompanied by spontaneous bacterial lung infection. IgM levels are similarly suppressed in stroke patients. β-adrenergic receptor antagonism after experimental stroke prevents loss of splenic MZ B cells, preserves IgM levels, and reduces bacterial burden. These findings suggest that adrenergic-mediated loss of MZ B cells contributes to the infection-prone state after stroke and identify systemic B-cell disruption as a target for therapeutic manipulation.

scholarly journals PO 8567 ASSOCIATION OF POLYMORPHISM RS 73885319 OF THE APOL1 GENE AND RESISTANCE/SUSCEPTIBILITY TO TRYPANOSOMA BRUCEI GAMBIENSE

2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. A54.3-A54
Author(s):  
Mwamba Miaka Erick ◽  
Veerle Lejon ◽  
Hamidou Ilboudou ◽  
Philippe Solano
Keyword(s):  
Trypanosoma Brucei ◽  
Neurological Disorders ◽  
Human African Trypanosomiasis ◽  
Democratic Republic ◽  
Central Africa ◽  
Susceptibility To Infection ◽  
Trypanosoma Brucei Gambiense ◽  
Republic Of The Congo ◽  
Asymptomatic Infections ◽  
Stage 1

BackgroundIn Central Africa, human African trypanosomiasis (HAT) or sleeping sickness is caused by Trypanosoma brucei gambiense (T.b gambiense). Classically, the disease is characterised by an early haemolymphatic phase (stage 1) followed by a meningo-encephalitic phase (stage 2) leading to neurological disorders and death if left untreated. However, field observations suggest that infection by T.b gambiense may result in a great diversity of clinical outcomes ranging from rapid progressions into stage 2, to asymptomatic infections that can last for years or even spontaneous cure in the absence of treatment.The determinants of this clinical diversity are not known but might have their origin both in the parasite (genetic variability) and in the host (individual susceptibility to disease). This study in the Democratic Republic of the Congo aimed at examining the association between the rs73885319 polymorphism of the APOL1 gene and resistance/susceptibility to T. b gambiense. We genotyped the APOL1 gene polymorphism in a total of 257 people comprised of 90 patients, 119 endemic controls and 48 seropositives. The analysis of the results has not shown any significant differences between HAT patients, controls and seropositives. Our results seem to suggest that the G allele of the rs 73885319 polymorphism of the APOL1 gene is not associated to resistance or susceptibility to infection.

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