scholarly journals Dose–response and transmission: the nexus between reservoir hosts, environment and recipient hosts

2019 ◽  
Vol 374 (1782) ◽  
pp. 20190016 ◽  
Author(s):  
Tamika J. Lunn ◽  
Olivier Restif ◽  
Alison J. Peel ◽  
Vincent J. Munster ◽  
Emmie de Wit ◽  
...  
Keyword(s):  
Dose Response ◽  
Nipah Virus ◽  
Underlying Disease ◽  
Host Susceptibility ◽  
Response Models ◽  
Zoonotic Pathogens ◽  
Exposure Experiment ◽  
Reservoir Hosts ◽  
The Relationship ◽  
Dose Dependent

Dose is the nexus between exposure and all upstream processes that determine pathogen pressure, and is thereby an important element underlying disease dynamics. Understanding the relationship between dose and disease is particularly important in the context of spillover, where nonlinearities in the dose–response could determine the likelihood of transmission. There is a need to explore dose–response models for directly transmitted and zoonotic pathogens, and how these interactions integrate within-host factors to consider, for example, heterogeneity in host susceptibility and dose-dependent antagonism. Here, we review the dose–response literature and discuss the unique role dose–response models have to play in understanding and predicting spillover events. We present a re-analysis of dose–response experiments for two important zoonotic pathogens (Middle East respiratory syndrome coronavirus and Nipah virus), to exemplify potential difficulties in differentiating between appropriate models with small exposure experiment datasets. We also discuss the data requirements needed for robust selection between dose–response models. We then suggest how these processes could be modelled to gain more realistic predictions of zoonotic transmission outcomes and highlight the exciting opportunities that could arise with increased collaboration between the virology and epidemiology disciplines. This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’.

Development of Dose-Response Models to Predict the Relationship for HumanToxoplasma gondiiInfection Associated with Meat Consumption

Risk Analysis ◽  
2015 ◽  
Vol 36 (5) ◽  
pp. 926-938 ◽  
Author(s):  
Miao Guo ◽  
Abhinav Mishra ◽  
Robert L. Buchanan ◽  
Jitender P. Dubey ◽  
Dolores E. Hill ◽  
...  
Keyword(s):  
Dose Response ◽  
Meat Consumption ◽  
Response Models ◽  
The Relationship

Ovine corticotrophin-releasing factor in dogs: dose-response relationships and effects of dexamethasone

1986 ◽  
Vol 112 (1) ◽  
pp. 12-19 ◽  
Author(s):  
R.J. Kemppainen ◽  
D. V. Filer ◽  
J. L. Sartin ◽  
R. B. Reed
Keyword(s):  
Dose Response ◽  
Plasma Cortisol ◽  
Peak Plasma ◽  
Cortisol Response ◽  
Corticotrophin Releasing Factor ◽  
Pre Treatment ◽  
The Relationship ◽  
Dose Dependent ◽  
Response Area ◽  
Stimulation Of

Abstract. Dose-response relationships between iv bolus injections (0, 0.1, 1 or 10 μg/kg) of synthetic ovine corticotropin-releasing factor (oCRF) and plasma immunoreactive (i) ACTH and cortisol concentrations were examined in healthy, conscious dogs. All doses of oCRF resulted in elevated plasma iACTH and cortisol levels over those of the controls. Maximum (or Peak) plasma iACTH concentrations were generally observed 20–30 min after oCRF and the magnitude of these peaks was a linear function (P<0.001) of the logarithm of the oCRF dose. The time of peak cortisol concentrations was more variable but the peak cortisol level was also linearly related (P< 0.001) to the logarithm of the oCRF dose. An estimate for the response areas for both hormones demonstrated a quadratic (P < 0.05) relationship with the logarithm of the oCRF dose. The relationship between oCRF and the iACTH response suggested a progressively greater response at increasing oCRF doses while a maximally effective oCRF dose was predicted in the cortisol response area relationship. Graded (0, 0.01, 0.1 or 1 mg/kg) bolus doses of dexamethasone produced a dose-dependent (P < 0.03) decline in baseline plasma iACTH levels and a non-dosedependent suppression in baseline plasma cortisol. Pre-treatment with 0.001 mg dexamethasone/kg 4 or 8 h before injection of 1 μg oCRF/kg did not alter the plasma iACTH or cortisol response; however, 0.1 mg dexarhethasone/kg administered at these times totally abolished the responses to oCRF. An intermediate dose (0.01 mg/kg) of dexamethasone inhibited the plasma iACTH response by an average of 79% (P<0.01) when administered 4 h before oCRF, but did not significantly alter this response when given 8 h prior to oCRF. The plasma cortisol response to oCRF was inhibited (P < 0.01) when 0.01 mg dexamethasone/kg was given as a 4 h, but not as a 8 h, pre-treatment. Iv administration of oCRF produces a profound, dose-dependent stimulation of the pituitary-adrenocortical axis of dogs and should prove useful in studies of this system.

scholarly journals Unveiling Time in Dose-Response Models to Infer Host Susceptibility to Pathogens

2014 ◽  
Vol 10 (8) ◽  
pp. e1003773 ◽  
Author(s):  
Delphine Pessoa ◽  
Caetano Souto-Maior ◽  
Erida Gjini ◽  
Joao S. Lopes ◽  
Bruno Ceña ◽  
...  
Keyword(s):  
Dose Response ◽  
Host Susceptibility ◽  
Response Models

scholarly journals Dose–Response Effects of 3-Nitrooxypropanol Combined with Low- and High-Concentrate Feed Proportions in the Dairy Cow Ration on Fermentation Parameters in a Rumen Simulation Technique

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1784
Author(s):  
Matthias Schilde ◽  
Dirk von Soosten ◽  
Liane Hüther ◽  
Susanne Kersten ◽  
Ulrich Meyer ◽  
...  
Keyword(s):  
Dose Response ◽  
Gas Production ◽  
Hydrogen Gas ◽  
Simulation Technique ◽  
Mitigation Strategies ◽  
Feed Additive ◽  
Future Research ◽  
Dependent Manner ◽  
Dose Dependent

Methane (CH4) from ruminal feed degradation is a major pollutant from ruminant livestock, which calls for mitigation strategies. The purpose of the present 4 × 2 factorial arrangement was to investigate the dose–response relationships between four doses of the CH4 inhibitor 3-nitrooxypropanol (3-NOP) and potential synergistic effects with low (LC) or high (HC) concentrate feed proportions (CFP) on CH4 reduction as both mitigation approaches differ in their mode of action (direct 3-NOP vs. indirect CFP effects). Diet substrates and 3-NOP were incubated in a rumen simulation technique to measure the concentration and production of volatile fatty acids (VFA), fermentation gases as well as substrate disappearance. Negative side effects on fermentation regarding total VFA and gas production as well as nutrient degradability were observed for neither CFP nor 3-NOP. CH4 production decreased from 10% up to 97% in a dose-dependent manner with increasing 3-NOP inclusion rate (dose: p < 0.001) but irrespective of CFP (CFP × dose: p = 0.094). Hydrogen gas accumulated correspondingly with increased 3-NOP dose (dose: p < 0.001). In vitro pH (p = 0.019) and redox potential (p = 0.066) varied by CFP, whereas the latter fluctuated with 3-NOP dose (p = 0.01). Acetate and iso-butyrate (mol %) decreased with 3-NOP dose, whereas iso-valerate increased (dose: p < 0.001). Propionate and valerate varied inconsistently due to 3-NOP supplementation. The feed additive 3-NOP was proven to be a dose-dependent yet effective CH4 inhibitor under conditions in vitro. The observed lack of additivity of increased CFP on the CH4 inhibition potential of 3-NOP needs to be verified in future research testing further diet types both in vitro and in vivo.

scholarly journals Weighted mixed-effects dose–response models for tables of correlated contrasts

2021 ◽  
Vol 21 (2) ◽  
pp. 320-347
Author(s):  
Nicola Orsini
Keyword(s):  
Dose Response ◽  
Response Pattern ◽  
Mixed Effects ◽  
Data Generation ◽  
Measures Of Association ◽  
Response Models ◽  
Response Data ◽  
Hazard Ratios ◽  
Health Related ◽  
Generation Mechanisms

Recognizing a dose–response pattern based on heterogeneous tables of contrasts is hard. Specification of a statistical model that can consider the possible dose–response data-generating mechanism, including its variation across studies, is crucial for statistical inference. The aim of this article is to increase the understanding of mixed-effects dose–response models suitable for tables of correlated estimates. One can use the command drmeta with additive (mean difference) and multiplicative (odds ratios, hazard ratios) measures of association. The postestimation command drmeta_graph greatly facilitates the visualization of predicted average and study-specific dose–response relationships. I illustrate applications of the drmeta command with regression splines in experimental and observational data based on nonlinear and random-effects data-generation mechanisms that can be encountered in health-related sciences.

Underestimation of Dose - Response Relationship with Particular Reference to the Relationship between the Dietary Intake of Mercury and its Concentration in Blood

1988 ◽  
Vol 7 (2) ◽  
pp. 129-132 ◽  
Author(s):  
J.C. Sherlock ◽  
M.J. Quinn
Keyword(s):  
Linear Regression ◽  
Dietary Intake ◽  
Dose Response ◽  
Mercury Concentration ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Blood Mercury ◽  
Relationship Of ◽  
The Relationship ◽  
Blood Mercury Concentration

Wide discrepancies have been observed between controlled and uncontrolled intake studies of the relationship of blood mercury concentration to intake of mercury. The probable reason for the apparent discrepancies is that the within-subject variation of mercury intake in the uncontrolled studies was almost certainly considerably larger than the within-subject variation in blood mercury concentration; in these circumstances, the apparent slope obtained from a linear regression of blood mercury on intake will invariably be much smaller than the true slope. Studies of the exposure or intake of any substance should therefore include a consideration of the likely within-subject variation in the exposure or intake relative to that in the effect.

Retropharyngeal abscess. A rare presentation of nasopharyngeal carcinoma

1999 ◽  
Vol 113 (1) ◽  
pp. 70-72 ◽  
Author(s):  
Martin Wai Pak ◽  
Ka Lai Chan ◽  
Charles Andrew van Hasselt
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Underlying Disease ◽  
Retropharyngeal Abscess ◽  
Advanced Stage ◽  
Rare Presentation ◽  
Adequate Treatment ◽  
Neck Abscess ◽  
Early Symptoms ◽  
Deep Neck Abscess ◽  
The Relationship

AbstractEarly symptoms of nasopharyngeal carcinoma (NPC) can often be deceptive and confusing. Most patients with nasopharyngeal carcinoma present at an advanced stage with metastatic cervical nodes present at the time of diagnosis. A deep neck abscess as the presenting feature has not been reported. We report two cases of nasopharyngeal carcinoma which presented with retropharyngeal abscesses and persistent lymphadenopathy. These two patients illustrate that refractory lymphadenopathy, despite adequate treatment of the associated infection, should prompt a search for underlying disease. The relationship between nasopharyngeal carcinoma and retropharyngeal abscess is discussed.

scholarly journals Association of psychiatric comorbidities with the risk of transport accidents in ADHD and MPH

2021 ◽  
Vol 30 ◽  
Author(s):  
Yi-Chun Liu ◽  
Vincent Chin-Hung Chen ◽  
Yao-Hsu Yang ◽  
Yi-Lung Chen ◽  
Michael Gossop
Keyword(s):  
Dose Response ◽  
Case Series ◽  
Autism Spectrum ◽  
Research Database ◽  
Accident Risk ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Series Analysis ◽  
The Relationship ◽  
Transport Accidents

Abstract Aims Although the relationship between attention-deficit/hyperactivity disorder (ADHD) and transport accidents has been shown, there is limited information on the relationship between medication and dose–response effects and transport accident risk. This study aims to determine whether young people with ADHD, including adolescents, are more prone to transport accidents than those without, and the extent to which methylphenidate (MPH) prescription in these patients reduces the risk. Methods We identified 114 486 patients diagnosed with ADHD from Taiwan's National Health Insurance Research Database from 1997 to 2013. Using a Cox regression model, we compared the risk of transport accidents between ADHD and non-ADHD groups and estimated the effect of MPH on accidents. Furthermore, we applied a self-control case-series analysis to compare the risk of accidents during the medication periods with the same patients' non-medication periods. Results Male ADHD patients had a higher risk of transport accidents than non-ADHD individuals (adjusted hazard ratio [aHR] = 1.24, [95% confidence interval (CI) 1.10–1.39]), especially for those comorbid with epilepsy, oppositional defiant disorder/conduct disorder (ODD/CD), and intellectual disabilities (ID). Female ADHD patients showed no relationship, except for comorbid with autism spectrum disorder (ASD) or ID. We found a reduced risk of transport accidents in patients with ADHD with MPH medication than those without MPH, with a plausible dose–response relationship (aHR of 0.23 to 0.07). A similar pattern was found in self-controlled case-series analysis. Conclusions Male patients with ADHD, especially those comorbid with epilepsy, ODD/CD, or ID, were at high risk of transport accidents. Female patients, when comorbid with ASD or ID, also exhibited a higher risk of accidents. MPH treatment lowered the accident risk with a dose–response relationship.

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