scholarly journals A model-based approach to designing developmental toxicology experiments using sea urchin embryos

Author(s):  
Michael D. Collins ◽  
Elvis Han Cui ◽  
Seung Won Hyun ◽  
Weng Kee Wong

AbstractThe key aim of this paper is to suggest a more quantitative approach to designing a dose–response experiment, and more specifically, a concentration–response experiment. The work proposes a departure from the traditional experimental design to determine a dose–response relationship in a developmental toxicology study. It is proposed that a model-based approach to determine a dose–response relationship can provide the most accurate statistical inference for the underlying parameters of interest, which may be estimating one or more model parameters or pre-specified functions of the model parameters, such as lethal dose, at maximal efficiency. When the design criterion or criteria can be determined at the onset, there are demonstrated efficiency gains using a more carefully selected model-based optimal design as opposed to an ad-hoc empirical design. As an illustration, a model-based approach was theoretically used to construct efficient designs for inference in a developmental toxicity study of sea urchin embryos exposed to trimethoprim. This study compares and contrasts the results obtained using model-based optimal designs versus an ad-hoc empirical design.

2021 ◽  
Vol 41 (2) ◽  
pp. 194-208
Author(s):  
Hugo Pedder ◽  
Sofia Dias ◽  
Meg Bennetts ◽  
Martin Boucher ◽  
Nicky J. Welton

Background Network meta-analysis (NMA) synthesizes direct and indirect evidence on multiple treatments to estimate their relative effectiveness. However, comparisons between disconnected treatments are not possible without making strong assumptions. When studies including multiple doses of the same drug are available, model-based NMA (MBNMA) presents a novel solution to this problem by modeling a parametric dose-response relationship within an NMA framework. In this article, we illustrate several scenarios in which dose-response MBNMA can connect and strengthen evidence networks. Methods We created illustrative data sets by removing studies or treatments from an NMA of triptans for migraine relief. We fitted MBNMA models with different dose-response relationships. For connected networks, we compared MBNMA estimates with NMA estimates. For disconnected networks, we compared MBNMA estimates with NMA estimates from an “augmented” network connected by adding studies or treatments back into the data set. Results In connected networks, relative effect estimates from MBNMA were more precise than those from NMA models (ratio of posterior SDs NMA v. MBNMA: median = 1.13; range = 1.04–1.68). In disconnected networks, MBNMA provided estimates for all treatments where NMA could not and were consistent with NMA estimates from augmented networks for 15 of 18 data sets. In the remaining 3 of 18 data sets, a more complex dose-response relationship was required than could be fitted with the available evidence. Conclusions Where information on multiple doses is available, MBNMA can connect disconnected networks and increase precision while making less strong assumptions than alternative approaches. MBNMA relies on correct specification of the dose-response relationship, which requires sufficient data at different doses to allow reliable estimation. We recommend that systematic reviews for NMA search for and include evidence (including phase II trials) on multiple doses of agents where available.


1962 ◽  
Vol 41 (2) ◽  
pp. 268-273 ◽  
Author(s):  
Ralph I. Dorfman

ABSTRACT The stimulating action of testosterone on the chick's comb can be inhibited by the subcutaneous injection of 0.1 mg of norethisterone or Ro 2-7239 (2-acetyl-7-oxo-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene), 0.5 mg of cortisol or progesterone, and by 4.5 mg of Mer-25 (1-(p-2-diethylaminoethoxyphenyl)-1-phenyl-2-p-methoxyphenyl ethanol). No dose response relationship could be established. Norethisterone was the most active anti-androgen by this test.


2021 ◽  
Vol 34 (01) ◽  
pp. 003-016
Author(s):  
John Michel Warner

AbstractAccording to Hahnemann, homoeopathic medicines must be great immune responses inducers. In crude states, these medicines pose severe threats to the immune system. So, the immune-system of an organism backfires against the molecules of the medicinal substances. The complex immune response mechanism activated by the medicinal molecules can handle any threats which are similar to the threats posed by the medicinal molecules. The intersectional operation of the two sets, medicine-induced immune responses and immune responses necessary to cure diseases, shows that any effective homoeopathic medicine, which is effective against any disease, can induce immune responses which are necessary to cure the specific disease. In this article, this mechanism has been exemplified by the action of Silicea in human body. Also, a neuroimmunological assessment of the route of medicine administration shows that the oral cavity and the nasal cavity are two administration-routes where the smallest doses (sometimes even few molecules) of a particular homoeopathic medicine induce the most effective and sufficient (in amount) purgatory immune responses. Administering the smallest unitary doses of Silicea in the oral route can make significant changes in the vital force line on the dose–response relationship graph. The dose–response relationship graph further implicates that the most effective dose of a medicine must be below the lethality threshold. If multiple doses of any medicine are administered at same intervals, the immune-system primarily engages with the medicinal molecules; but along the passage of time, the engagement line splits into two: one engages with the medicinal molecules and another engages with diseases. The immune system's engagement with the diseases increases along the passage of time, though the engagement with the medicinal molecules gradually falls with the administration of descending doses. Necessarily, I have shown through mathematical logic that the descending doses, though they seem to be funny, can effectively induce the most effective immune responses.


Author(s):  
Satoru Kodama ◽  
Chika Horikawa ◽  
Kazuya Fujihara ◽  
Mariko Hatta ◽  
Yasunaga Takeda ◽  
...  

Atmosphere ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 371
Author(s):  
Yan Zhang ◽  
Weihua Yang ◽  
Günther Schauberger ◽  
Jianzhuang Wang ◽  
Jing Geng ◽  
...  

Municipal wastewater treatment plants (WWTPs) inside cities have been the major complained sources of odor pollution in China, whereas there is little knowledge about the dose–response relationship to describe the resident complaints caused by odor exposure. This study explored a dose–response relationship between the modelled exposure and the annoyance surveyed by questionnaires. Firstly, the time series of odor concentrations were preliminarily simulated by a dispersion model. Secondly, the perception-related odor exposures were further calculated by combining with the peak to mean factors (constant value 4 (Germany) and 2.3 (Italy)), different time periods of “a whole year”, “summer”, and “nighttime of summer”, and two approaches of odor impact criterion (OIC) (“odor-hour” and “odor concentration”). Thirdly, binomial logistic regression models were used to compare kinds of perception-related odor exposures and odor annoyance by odds ratio, goodness of fit and predictive ability. All perception-related odor exposures were positively associated with odor annoyance. The best goodness of fit was found when using “nighttime of summer” in predicting odor-annoyance responses, which highlights the importance of the time of the day and the time of the year weighting. The best predictive performance for odor perception was determined when the OIC was 4 ou/m3 at the 99th percentile for the odor exposure over time periods of nighttime of summer. The study of dose–response relationship could be useful for the odor management and control of WWTP to maximize the satisfaction of air quality for the residents inside city.


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