Pharmacology and similia principle: indirect secondary counter-regulation. Confirmation from in vitro experiments and classical provings

Homeopathy is universally known as an opponent of allopathic Medicine, namely scientific medicine based on ponderal drugs and recognised mechanisms of receptor agonism and antagonism following the dose-response curve. Over time the difficulty to explain with arguments the action of homeopathic ultra-diluted remedies has led many homeopaths to distance themselves from any pharmacological knowledges. Nevertheless this position fortgets not only the modalities in which homeopathy was born and has grown, but a lot of modern changes of view in body-mind communication, cell communication, neuro-immune-endocrinology and bioelectromagnetism, that could give new reasons to treat as clinical homeopathic practice is teaching and to recognize the principle of similars as a modern pharmacological principle. These arguments, receptorial cell communication, bioelectromagnetism and body-mind unity are the bases of Homeopathy and of the Similia Principle and are all included in embryonic but sufficiently clear considerations in the fundamental book of Hahnemann, the Organon (parr. 11, 13, 15-18, 21, 22, 29-32, 63-70). Two kind of evidences confirm the pharmacological bases of SimiliaPriniciple, in vitro experiments and homeopathic pathogenetic trials on healthy volunteers, best known as provings. Even clinical homeopathic phenomena like initial aggravation and return of old symptoms confirm this pharmacological view of the Simila Principle.

Preclinical Drug Response Metric Based on Cellular Response Phenotype Provides Better Pharmacogenomic Variables with Phenotype Relevance

High-throughput screening of drug response in cultured cell lines is essential for studying therapeutic mechanisms and identifying molecular variants associated with sensitivity to drugs. Assessment of drug response is typically performed by constructing a dose-response curve of viability and summarizing it to a representative, such as IC50. However, this is limited by its dependency on the assay duration and lack of reflections regarding actual cellular response phenotypes. To address these limitations, we consider how each response-phenotype contributes to the overall growth behavior and propose an alternative method of drug response screening that takes into account the cellular response phenotype. In conventional drug response screening methods, the ranking of sensitivity depends on either the metric used to construct the dose-response curve or the representative factor used to summarize the curve. This ambiguity in conventional assessment methods is due to the fact that assessment methods are not consistent with the underlying principles of population dynamics. Instead, the suggested phenotype metrics provide all phenotypic rates of change that shape overall growth behavior at a given dose and better response classification, including the phenotypic mechanism of overall growth inhibition. This alternative high-throughput drug-response screening would improve preclinical pharmacogenomic analysis and the understanding of a therapeutic mechanism of action.

Standardized Dose–Response Curve (sDRC) Construction for OSL Dating of Quartz from Bohai Coast, NE China

The optically stimulated luminescence (OSL) dating method promises to provide reliable ages for various Quaternary archives. Coastal sedimentation in the Bohai Sea (northeastern China) since the Middle Pleistocene has been influenced by paleoenvironmental and sea-level change, of which dating has been restricted using the OSL dating approach in multiple investigations. In this study, to establish a robust OSL chronological framework of the Bohai coastal sediments more effectively, the regional standardized dose–response curve (sDRC) was constructed for quartz OSL dating in the Bohai Coast (NE China) using two existing approaches. The sDRC-determined equivalent doses are broadly in agreement with those using the individual DRC for each sample. Data used for DRC construction of the fine-grained (FG) quartz samples are less scattered than those of the coarse-grained (CG) quartz samples, probably due to the signal-averaging effect for the FG samples, while the OSL signal of the CG quartz samples might document provenance information that yield relatively scattered distribution. The two approaches used in this study yield identical sDRCs, indicating that both the methods are applicable for sDRC construction in the Bohai Sea.

Dynamic Programming for Response-Adaptive Dose-Finding Clinical Trials

Identifying the right dose is one of the most important decisions in drug development. Adaptive designs are promoted to conduct dose-finding clinical trials as they are more efficient and ethical compared with static designs. However, current techniques in response-adaptive designs for dose allocation are complex and need significant computational effort, which is a major impediment for implementation in practice. This study proposes a Bayesian nonparametric framework for estimating the dose-response curve, which uses a piecewise linear approximation to the curve by consecutively connecting the expected mean response at each dose. Our extensive numerical results reveal that a first-order Bayesian nonparametric model with a known correlation structure in prior for the expected mean response performs competitively when compared with the standard approach and other more complex models in terms of several relevant metrics and enjoys computational efficiency. Furthermore, structural properties for the optimal learning problem, which seeks to minimize the variance of the target dose, are established under this simple model. Summary of Contribution: In this work, we propose a methodology to derive efficient patient allocation rules in response-adaptive dose-finding clinical trials, where computational issues are the main concern. We show that our methodologies are competitive with the state-of-the-art methodology in terms of solution quality, are significantly more computationally efficient, and are more robust in terms of the shape of the dose-response curve, among other parameter changes. This research fits in “the intersection of computing and operations research” as it adapts operations research techniques to produce computationally attractive solutions to patient allocation problems in dose-finding clinical trials.

Poor Uncorrected Visual Acuity and Association With Sleep Duration and Screen Time: A Dose–Response Relationship Study

Background We aimed to investigate the prevalence of poor uncorrected visual acuity and the difference among students with different ages and residential areas in the Northeast of China. The relationships between screen time, nighttime sleep duration, and poor uncorrected visual acuity would be explored. Methods It was a cross-sectional study using multi-stage stratified random sampling method to recruit participants. 2149 students have completed questionnaires and underwent visual acuity examinations. The dose–response curve method was applied to examine the non-linear associations between sleep duration and poor uncorrected visual acuity under different screen time subgroups. Results The overall prevalence of poor uncorrected visual acuity and severe poor uncorrected visual acuity was 84.7% and 63.3%, respectively. The dose–response curve showed the odds ratios (ORs) of sleep duration for the poor uncorrected visual increased relatively slowly when screen time <1 hour, then increased dramatically in screen time ≥1 hours. The ORs of sleep time and poor uncorrected visual acuity showed a U-shaped change trend among students with 2 or more hours of screen time every day. Conclusion We found associations between nighttime sleep duration and poor uncorrected visual acuity in adolescents. However, these associations were not consistent across all screen time categories.

Productivity Responses of Buckwheat IPR 91 Baili to Different Doses of NPK in Brazil

Buckwheat (Fagopyrum esculentum Moench) is a prominent crop in today&rsquo;s agriculture. However, information about its behavior at different doses of NPK fertilization is scarce. The aim of this work was to determine the ideal fertilizer dose for the buckwheat cultivar IPR 91 Baili by establishing the dose-response curve. Two experiments were carried out (greenhouse and in the field). The treatments consisted of different doses of NPK (0, 100, 200, 300, 400 and 500 kg ha-1). After the crop cycle, productivity was obtained. There was a statistical difference between the treatments and the control, in both experiments. The lowest yields were obtained in the controls, 2,301.156 and 2,262.500 kg ha-1, and the highest 4,052.023 and 4,027.778 kg ha-1 at the dose of 500 kg ha-1, in the greenhouse and in the field, respectively. There was no statistical difference between the NPK doses for the yield obtained. The rural producer must use the lowest dose (100 kg ha-1). Future experiments are needed to evaluate the culture response to doses below 100 kg ha-1.

When does contacting more people lessen the transmission of infectious diseases?

A primary concern in epidemics is to minimize the probability of contagion, often resorting to reducing the number of contacted people. However, the success of that strategy depends on the shape of the dose-response curve, which relates the response of the exposed person to the pathogen dose received from surrounding infected people. If the reduction is achieved by spending more time with each contacted person, the pathogen charge received from each infected individual will be larger. The extended time spent close to each person may worsen the expected response if the dose-response curve is concave for small doses. This is the case when the expected response is negligible below a certain dose threshold and rises sharply above it. This paper proposes a mathematical model to calculate the expected response and uses it to identify the conditions when it would be advisable to reduce the contact time with each individual even at the cost of increasing the number of contacted people.

US Federal Aviation Administration Neighborhood Environmental Survey: Study Design and Survey Methodology

As part of the agency's broader noise research program, the Federal Aviation Administration (FAA) has undertaken a multi-year research effort to quantify the impacts of aircraft noise exposure on communities around commercial service airports in the United States (U.S.). The overall goal of the study was to produce an updated and nationally representative civil aircraft dose-response curve; providing the relationship between annoyance and aircraft noise exposure around U.S. airport communities. To meet this goal, the FAA sponsored a research team to help design and conduct a national survey, known as the Neighborhood Environmental Survey (NES). Residents from households around 20 airports were selected for participation in the survey; the detailed sampling process is covered in another paper. Two survey instruments were administered to adult residents within the NES: a mail questionnaire and a follow-up telephone interview for the mail respondents. The mail survey was administered to samples of individuals in the selected airport communities in six separate "waves" over a 12-month period starting in October 2015. All mail survey respondents were invited to complete a follow-up telephone interview, which asked detailed questions on several areas including respondents' opinions on noise, exposure to aircraft noise, relationship to the airport, concerns about aircraft operations, views on airport community relations, among others. Analysis of the survey responses on annoyance levels and the associated DNL was used to estimate dose-response curves for each individual airport and a national dose-response curve. The national dose-response curve created from the mail questionnaire shows considerably more people are highly annoyed by aircraft noise at a given noise exposure level compared to historical FICON data. This paper provides a detailed discussion of the survey design and methodology. Additional information describing the motivation to conduct the NES and how its findings will help inform ongoing work to address aircraft noise concerns; and the noise methodology are provided in companion papers.