Dose-response Function Research Articles

Dose-dependent effects of estrogen on prediction error related neural activity in the nucleus accumbens of healthy young women.

Whereas the effect of the sex steroid 17-beta-estradiol (E2) on dopaminergic (DA) transmission in the nucleus accumbens (NAc) is well evidenced in female rats, studies in humans are inconsistent. Moreover, linear and inverted u-shaped dose response curves have been observed for E2's effects on hippocampal plasticity, but the shape of dose response curves for E2's effects on the NAc is much less characterized. Investigation of dose response curves for E2's effects on DA-related neural activity in the human NAc. Placebo or E2 valerate in doses of 2, 4, 6 or 12 mg was orally administered to 125 naturally cycling young women during the low-hormone menstruation phase on two consecutive days using a randomized, double-blinded design. The E2 treatment regimen induced a wide range of E2 levels, from physiological (2- and 4-mg groups; equivalent to cycle peak) to supraphysiological levels (6- and 12-mg groups; equivalent to early pregnancy). This made it possible to study different dose response functions for E2's effects on NAc activity. During E2 peak, participants performed a well-established reversal learning paradigm. We used trial-wise prediction errors (PE) estimated via a computational reinforcement learning model as a proxy for dopaminergic activity. Linear and quadratic regression analyses predicting PE-related NAc activity from salivary E2 levels were calculated. There was a positive linear relationship between PE-associated NAc activity and salivary E2 increases. The randomized, placebo-controlled elevation of E2 levels stimulates NAc activity in the human brain, likely mediated by dopaminergic processes.

Radiation induced degradation of murexide dye in two media for possible use in dosimetric applications

Purpose The purpose of this paper is to study the effect of gamma-rays on murexide (Mx) dye and its possible use as radiation dosimeters in two different dosimetry systems. The first system depends on the Mx dye as a liquid dosimeter. The second dosimetry system depends also on the same dye but as in a gel form, which is more sensitive to gamma-rays. Design/methodology/approach The prepared Mx (solutions/gels) have a considerable two peaks at 324 and 521 nm that upon irradiation, the intensity of these peaks decreases with the increasing radiation dose. Findings The gamma-ray absorbed dose for these dosimeters was found to be up to 2 kGy for the solution samples and 40 Gy for the gels. Radiation chemical yield, dose response function, radiation sensitivity and before and after-irradiation stability under various conditions were discussed and studied. Practical implications It is expected that the radiolysis of the Mx dye can be used as radiation dosimeters in two different dosimetry systems; liquid and gel dosimeters. This can be applied in a wide range of gamma radiation practical industrial applications in water treatment, food irradiation dosimeters, radiotherapy and fresh food irradiation and seed production. Originality/value Both of the prepared Mx dyes, either as solutions or gel samples, can be facilely prepared from commercially, cheap, safe, available chemicals and suitable for useful applied Mx solutions and gels radiation dosimeters.

Sensitivity Analysis of Zinc Dose-response Function according to Actual Standard Approach

One of the reasons for the decrease in reliability of constructions is the corrosion of carbon steel. Many members are made from carbon steel as embedded reinforcement in reinforced concrete (RC) members, steel structures, steel bearings, barriers, rails, etc. These members from carbon steel can be protected by zinc coating. In these cases, the zinc coating layer provides the passive stage during which the steel does not corrode. Therefore, the first-year corrosion rate, as well as the speed of the corrosion during many years, is a very significant parameter for determination of the decreasing the reliability of structure in time. The determination of the corrosivity of the atmosphere can be either on specimens exposed under outdoor conditions or by calculation, according to so-called dose-response function, based on environmental information observed from the public´s hydrometeorological institutes. The paper is focused on sensitivity analysis of zinc dose-response function rcorr,ZN in the range of input parameter recommended either in the standard STN EN ISO 9223 or in the range of measurement by Slovak Hydrometeorological Institute – SHMI.

The activity-regulated cytoskeleton-associated protein, Arc/Arg3.1, influences mouse cocaine self-administration

The activity-regulated cytoskeleton-associated protein (Arc, also known as Arg3.1), an immediate early gene and synaptic regulator, is upregulated following a single cocaine exposure. However, there is not much known regarding Arc/Arg3.1's potential contribution to addiction-relevant behaviors. Despite known learning and memory deficits in contextual fear and water-maze reversal learning tasks, we find that mice lacking Arc/Arg3.1 perform conditioned place preference and operant conditioning involving positive reinforcers (food and cocaine) with little-to-no impairment. However, following normal saline-extinction, wild type (WT) mice show a classic inverted-U dose-response function, while Arc/Arg3.1 knockout (KO) mice fail to adjust their intake across multiple doses. Importantly, Arc/Arg3.1 KO and WT mice behave comparably on an increasing cost task (FR1-FR3; acquisition dose), providing evidence that both groups find cocaine reinforcing. Differences in individuals that drive variations in use patterns and particularly, drug intake levels, are critical as they influence the likelihood of developing dependence. Our data suggest that Arc/Arg3.1 may contribute to addiction as a regulator of drug-taking vulnerability under different drug availability conditions.

Evaluation of the anti-conflict, reinforcing, and sedative effects of YT-III-31, a ligand functionally selective for α3 subunit-containing GABAA receptors.

In recent years, pharmacological strategies have implicated α3 subunit-containing GABAA (α3GABAA) receptor subtypes in the anxiety-reducing effects of benzodiazepines, whereas transgenic mouse approaches have implicated α2 or α5 subunit-containing GABAA receptors. We investigated the role of α3GABAA subtypes in benzodiazepine-induced behaviors by evaluating the anti-conflict, reinforcing, and sedative-motor effects of the novel compound YT-III-31, which has functional selectivity for α3GABAA receptors. Female and male rhesus monkeys were trained under a conflict procedure (n = 3), and a progressive-ratio schedule of reinforcement with midazolam as the training drug (n = 4). Sedative-like behavior was assessed using a quantitative behavioral observation procedure (n = 4). A range of doses of YT-III-31 was administered in all tests using the i.v. route of administration. In the conflict procedure, increasing doses of YT-III-31 resulted only in dose-dependent attenuation of non-suppressed responding. In the progressive-ratio model of self-administration, YT-III-31 maintained average injections/session above vehicle levels at 0.1 and 0.18 mg/kg/injection. In quantitative observation procedures, YT-III-31 engendered mild sedative effects ("rest/sleep posture"), and deep sedation at the highest dose tested (5.6 mg/kg, i.v.), along with a suppression of tactile/oral exploration and increased observable ataxia. In contrast to other benzodiazepine-like ligands, YT-III-31 uniquely engendered a biphasic dose-response function for locomotion and suppressed self-groom. The finding that YT-III-31 lacked anti-conflict properties is in accordance with transgenic mouse research indicating no role for α3GABAA subtypes in benzodiazepine-mediated anxiety reduction. Instead, our results raise the possibility of a role for α3GABAA receptors in the abuse potential and sedative effects of benzodiazepine-type drugs.

Shortcomings of International Standard ISO 9223 for the Classification, Determination, and Estimation of Atmosphere Corrosivities in Subtropical Archipelagic Conditions—The Case of the Canary Islands (Spain)

The classification, assessment, and estimation of the atmospheric corrosivity are fixed by the ISO 9223 standard. Its recent second edition introduced a new corrosivity category for extreme environments CX, and defined mathematical models that contain dose–response functions for normative corrosivity estimations. It is shown here that application of the ISO 9223 standard to archipelagic subtropical areas exhibits major shortcomings. Firstly, the corrosion rates of zinc and copper exceed the range employed to define the CX category. Secondly, normative corrosivity estimation would require the mathematical models to be redefined introducing the time of wetness and a new set of operation constants.

Relying on repeated biospecimens to reduce the effects of exposure measurement error in studies linking the exposome to health

OPS 19: Chemicals: exposure assessment challenges, Room 110, Floor 1, August 28, 2019, 1:30 PM - 3:00 PM Background/Aim: The exposome concept encompasses all environmental exposures a human is exposed to from the prenatal period onwards, and calls for assessing numerous exposures, typically using biomarkers. The amount of measurement error may differ between exposures, possibly influencing the performance of variable selection models in exposome-health studies. We evaluated this impact, and the efficiency in this context of two measurement error correction methods relying on the collection of repeated biospecimens. Methods: In a simulation study, we generated 237 exposures with different amounts of measurement error, assuming that 1 to 10 exposures linearly influenced a continuous health outcome and that up to 10 biospecimens were available per subject. We applied within-subject biospecimens pooling or regression calibration (RC), both followed by the deletion/substitution/addition algorithm to estimate the exposure-health associations, and compared their performances. Results: In the absence of measurement error, the average sensitivity to identify exposures influencing health was 75% and false detection proportion (FDP) was 26%. Measurement error decreased sensitivity to 46%, increased FDP to 49% and caused 52% attenuation bias in dose-response functions. When repeated biospecimens were available, within-subject pooling and RC improved sensitivity (average, 63%), FDP (average, 37%) and attenuation bias (average, 48%), and performance increased with the number of available biospecimens. Conclusions: Exposome studies relying on spot exposure biospecimens suffer from decreased sensitivity and increased bias and FDP, with greater amplitude for the exposures with the largest amount of measurement error. Study performances can be improved by collecting repeated biospecimens per subject.

Poly(vinyl alcohol) and liposomes as a synthetic biodegradable model membrane for probing radiation interactions

This work aims to investigate the effect of X-rays on poly(vinyl alcohol) (PVA) films and studying the ability to be a model of a synthetic cell membrane when compared to liposomes as biological models. The influence of X-ray irradiation on thin films of PVA doped with safranin (SAF) dye and liposomes encapsulated by SAF dye is studied using UV–visible spectrophotometry. These films are exposed to X-ray radiation with accumulated doses range of 10–50 Gy of 140 kVp at a constant dose rate of 2002 μGy/s. The absorption spectra of the PVA/SAF and the liposomes/SAF are measured. The absorption spectra of the PVA/SAF showed a decrease in the absorbance band peak with the increase of the dose with values are similar to those observed with the liposomes/SAF. The dose response function indicates the same radiation sensitivity of both samples. The results indicated that full width at half maximum of SAF/PVA and SAF/liposomes show linear decrease with an increase of dose. The variation in dose response is relatively small and found to be within 3.5% and the variations in a decrease of the absorbance peak are found to be with maximum 5%. These values can indicate that both of SAF/PVA and SAF/liposomes have the same behavior under the applied X-ray dose range. The results viewed that the PVA doped with SAF dye behave similarly as the liposomes doped with SAF dye. PVA may be used as a synthetic model for a cell membrane for probing X-ray-membrane interactions.

14 COMPARATIVE FUNCTIONAL GENOMICS ANALYSES OF THE 16P11.2 DELETION AND DUPLICATION CNVS IN A HUMAN IPSC-TO-INDUCED NEURON MODEL

Chronic stress leads to a dysregulated inhibitory tone that could impact hippocampal-dependent spatial learning and memory. The present study examined whether spatial memory deficits resulting from chronic stress could be overcome by antagonizing the GABAA receptor, a prominent inhibitory receptor of GABA in the hippocampus. Young adult male Sprague-Dawley rats were chronically stressed (STR, wire mesh restraint, 6 h/d/21 d) or placed in a no-stress control group (CON). When chronic restraint ended, rats were tested on a 2-trial object placement (OP) task at a delay (3 h) that would result in chance performance without intervention and then on novel object recognition (NOR) and the elevated plus maze (EPM) to assess non-spatial memory and anxiety profile. In CON rats, Bicuculline (BIC, 0, 0.25, 0.5 mg/kg), a GABAA antagonist, injected 30 min prior to training led to facilitated OP performance with 0.25 and 0.5 mg/kg doses. In contrast, STR rats required BIC at the highest dose (0.5 mg/kg) to improve OP performance. While overall object exploration was decreased by chronic stress, motivation or anxiety profile were unlikely to explain these results. These findings reveal two different dose response functions for BIC in control and chronically stressed rats, with the dose response function of BIC being shifted to the right for chronically stressed rats compared to controls in order to improve spatial memory. While the literature demonstrates that chronic stress disrupts hippocampal inhibitory tone, the current study reveals that a single injection to antagonize the GABAA receptor can restore hippocampal-dependent spatial memory in chronically stressed subjects.

Enhancement of Opioid Antinociception by Nicotine.

Nicotine can produce antinociception in preclinical pain models; however, the ability of nicotine to augment the antinociceptive effects of opioid agonists has not been investigated. The present experiments were conducted to determine how nicotine modifies the effects of opioid agonists differing in efficacy. Male squirrel monkeys responded for the delivery of milk under a fixed ratio 10 schedule of reinforcement. During the 30-second timeout period following each milk delivery, the subject's tail was immersed in 35, 50, 52, or 55°C water, and the latency to remove the tail was recorded. Dose-response functions for tail-withdrawal latency and operant performance were determined for fentanyl, oxycodone, buprenorphine, and nalbuphine alone and after treatment with nicotine. Excepting nalbuphine, all opioids produced dose-related disruptions in food-maintained responding and increases in tail-withdrawal latency at each water temperature. Nicotine did not exacerbate the behaviorally disruptive effects of the μ-opioids on operant performance but produced a significant mecamylamine-sensitive enhancement of the antinociceptive potency of each opioid. Failure of arecoline to augment the antinociceptive effects of oxycodone and antagonism by mecamylamine suggests this nicotine-induced augmentation of prescription opioid antinociception was nicotinic acetylcholine receptor (nAChR) mediated. This was reflected in leftward shifts in the antinociceptive dose-response curve of each opioid, ranging from 2- to 7-fold increases in the potency of oxycodone across all water temperatures to an approximately 70-fold leftward shift in the antinociceptive dose-response curve of nalbuphine at the lower and intermediate water temperatures. These results suggest that nicotine may enhance μ-opioid antinociceptive effects without concomitantly exacerbating their behaviorally disruptive effects. SIGNIFICANCE STATEMENT: Prescription opioids remain the most effective pain-management pharmacotherapeutics but are limited by their adverse effects. The present results indicate that nicotine enhances antinociceptive effects of various opioid agonists in nonhuman primates without increasing their disruptive effects on operant performance. These results suggest that nicotine might function as an opioid adjuvant for pain management by enabling decreased clinically effective analgesic doses of prescription opioids without exacerbating their adverse behavioral effects.

Using dose–response functions to improve calculations of the impact of anthropogenic noise

Abstract Estimating the number of animals impacted by a stressor typically involves combining a dose–response function with information about the distribution of animals and of the stressor. Regulators often prefer a single threshold to a full dose–response function, but much of the variability observed in the threshold at which different individuals respond to a stressor is an inherent characteristic of populations that needs to be taken into account to predict the effects of stressors. When selecting an exposure threshold, regulators need information on the proportion of the population that will be protected. Regulatory processes that calculate the number of animals impacted must draw from the dose–response function, the actual distribution of the animals, and a model mapping how the stressor intensity declines with distance from the source. Ignoring any of these factors can lead to significant errors in estimates of the area and numbers of animals affected. This paper focuses on behavioural responses of marine mammals to anthropogenic sound and demonstrates that a common approach of selecting the threshold at which half of the animals respond (RLp50) grossly underestimates the number of animals affected. We present an example, using a published dose–response function, where the number affected is underestimated by a factor of 280. Results would be similar for any stressor whose strength decreases following an inverse‐square function as it dilutes into the environment. This paper presents a method to use a dose–response function to derive a more accurate estimate of animals affected and to set a threshold (the Effective Response Level) that corrects the problem with the RLp50 estimate. Estimates of effects of stressors should include estimates of uncertainty, which can be used to adapt thresholds to different policy contexts and conservation problems.

An Empirical Validation of the Within-subject Biospecimens Pooling Approach to Minimize Exposure Misclassification in Biomarker-based Studies.

Within-subject biospecimens pooling can theoretically reduce bias in dose-response functions from biomarker-based studies when exposure assessment suffers from classical-type error. However, collecting many urine voids each day is cumbersome. We evaluated the empirical validity of a within-subject pooling approach and compared several options to avoid sampling each void. In 16 pregnant women who collected a spot of each urine void over several nonconsecutive weeks, we compared concentrations of 10 phenols in daily, weekly, and pregnancy within-subject pools. We pooled either three or all daily samples. In a simulation study using these data, we quantified bias in dose-response functions when using one to 20 urine samples per subject to assess methylparaben (a compound with moderate within-subject variability) and bisphenol A (high variability) exposures. Correlations between exposure estimates from pools of all and of only three voids per day were above 0.80 for all time windows and compounds, except for benzophenone-3 and triclosan in the daily time window (correlations, 0.57-0.68). With one spot sample to assess pregnancy exposure, correlations were all below 0.74. Using only one biospecimen led to attenuation bias in the dose-response functions of 29% (methylparaben) and 69% (bisphenol A); four samples for methylparaben and 18 for bisphenol A decreased bias to 10%. For nonpersistent chemicals, collecting and pooling three samples per day instead of all daily samples efficiently estimates exposures over a week or more. Collecting around 20 biospecimens can strongly limit attenuation bias for nonpersistent chemicals such as bisphenol A.

The Impact of R&D Tax Reduction and Exemption on Financial Constraints of Enterprises and Its Functional Mechanisms: An Empirical Research Based on Micro-data of Chinese Enterprises

Under the background of innovation-driven in China, in view of the fact that there are few studies on the impact of R&D tax reduction and exemption on financial constraints of enterprises, this paper absorbs the frontier perspectives of the financial constraint theory, and uses the endogenous treatment effect model including the triple difference method and the cubic Dose-Response function method to empirically study the impact of R&D tax reduction and exemption on financial constraints. This paper uses the asset size, which is the strong endogenous variable”, as the proxy variable of financial constraints and the explanatory variable for investment to research the asset size effect of R&D tax reduction and exemption. We find that R&D tax reduction and exemption has a significant investment accelerator effect, and the cubic Dose-Response function between the reduction rate and the scale of assets also confirm the non-monotonic quadratic function effect through tax reduction for enterprises to invest. R&D tax reduction and exemption has a positive impact on the asset size and financial constraints, but also restricts the expansion of enterprise assets through labor factor compensation and the current period of profitability. At the same time, R&D tax reduction and exemption worsens the financial constraints of enterprises through labor factor rewards and current profitability. This paper provides beneficial enlightenment for the implementation of innovation-driven development strategy and industrial transformation and upgrading, and giving full play to the tax relief policy to support innovation-driven development.

Fish disease dynamics in changing rivers: Salmonid Ceratomyxosis in the Klamath River

The myxozoan parasite Ceratomyxa shasta has been identified as the main contributor of mortality in salmon in the Klamath River, California. The life cycle of the parasite is complex, involving a polychaete and a salmonid host. Infection dynamics are greatly influenced by environmental factors, such as temperature and water velocity. If we are to control the disease it is important to predict the impact of environmental scenarios on spore concentration and infection prevalence. Here, we introduce a model based on partial differential equations to study the spore concentration in the river and the infection prevalence of returning salmon. The analysis of the model shows that for current climate conditions, additional dam release can reduce the actinospore concentration up to 48% and the prevalence up to 40% thus providing a potential disease management option. However, the infection risk is likely to increase for future climate conditions by 10–54% and this will lead to an infection level comparable to that of a recent high-disease year. Our simulations show that dam removal cannot be assumed to mitigate the effect of climate change or to have influence on infection prevalence. We show that our detailed model system can be reduced to a simpler exponential dose-response function, which predicts infection levels based on transmission rates, travel time and mean spore concentration, quantities that can be measured in-situ or given empirically. The dose-response function may therefore be a useful tool in disease management.

Evaluation of Sweetener Synergy in Humans by Isobole Analyses.

The chemical senses and pharmaceuticals fundamentally depend on similar biological processes, but novel molecule discovery has classically been approached from vastly different vantage points. From the perspective of ingredient and flavor companies, there are countless ingredients that act via largely unknown mechanisms, whereas the pharmaceutical industry has numerous mechanisms in search of novel compounds. Mixtures of agonists can result in synergistic (superadditive) responses, which can be quantified via isobole analysis, a well-proven clinical approach in pharmacology. For the food and beverage industries, bulk (caloric) sweeteners like sugars are a key ingredient in sweetened foods and beverages, but consumers also desire products with fewer calories, which has led to the development of sweet enhancers and sweetener blends intended to achieve synergy or superadditivity. Synergistic mixtures are highly attractive targets commercially as they enable lower usage levels and enhanced efficacy. Although the psychophysical literature contains numerous prior reports of sweetener synergy, others have also noted that classical additive models fail to account for nonlinear dose-response functions. To address this shortcoming, here we systematically apply the isobole method from pharmacology to quantify the presence or absence of psychophysical synergy for binary pairs of sweeteners in a series of 15 separate experiments, each with ~100 adult volunteers (total n = 1576). Generally, these data support the hypothesis that structurally similar sweeteners acting as agonists will not synergize, whereas structurally dissimilar sweeteners binding to overlapping or distal sites can act as allosteric agonists or agonist-antagonists, respectively.

Oral intake exposure to phthalates in vegetables produced in plastic greenhouses and its health burden in Shaanxi province, China

Phthalate exposure from Vegetables grown in Plastic Greenhouses (VPGs) represents an important source of total daily phthalate exposure in China. However, quantified health risks of phthalates attributable to VPG intake have not been documented. To fill this gap, this study estimates phthalate exposure from VPG intake in western China and calculates the first assessment of the disease burden associated with phthalate exposure from VPG intake in China based on a simple steady-state exposure model and a linear dose-response function between human bio-monitoring phthalates and Type 2 Diabetes (T2D) prevalence. What we present in this paper is a problem identification and screening level risk assessment. We chose Shaanxi province as the research field site due to its large contribution to the total vegetable yield and consumption in western China. Phthalate concentration in VPG samples, phthalate exposure levels from VPG intake, and the T2D burden caused by phthalate attributable to VPG intake for adults were measured or calculated. Di-2-ethylhexyl phthalate (DEHP) was found to represent over 55% of the total phthalate concentration in VPGs, followed by di-n-butyl phthalate (DnBP) and di-isobutyl phthalate (DiBP). Phthalate exposure from VPG intake for urban adults was higher than the level for rural adults. The share of DEHP exposure from VPG intake to urinary total DEHP metabolites were nearly 8% and 15%, and the share of DnBP exposure caused by VPG intake to total daily DnBP metabolites were nearly 4% and 7%, for rural and urban adult populations in Shaanxi, respectively. The adult population with T2D attributable to phthalate exposure from VPG intake was 2561, nearly 6.4% to the T2D burden attributable to total phthalate exposure, and 0.4% to the total adult population with T2D in Shaanxi. The authors recommend policy interventions to protect populations from future risk of phthalate exposure.

Development of dose-response functions for historic paper degradation using exposure to natural conditions and multivariate regression

Many collections of documents, manuscripts, and works of art on paper are prone to degradation due to a complex interplay of extrinsic and intrinsic factors. The aim of this study was to examine the simultaneous effect of multiple degradation agents on selected non-model types of paper in natural environments, and the relative effect of environmental parameters (heat, humidity, light and pollution) compared to material parameters (pH, fibre composition and presence of additives). An exposure experiment was set up to investigate visual and chemical changes of 12 different types of paper in real time in different environmental conditions over a 1.5-year period at 11 sites across Europe and North Africa, sheltered from UV light and precipitation. Suitable environmental monitoring equipment, such as data loggers and gas samplers, and analytical methods to characterise sample degradation, specifically spectrocolorimetry and capillary viscometry, were used to estimate alterations in visual appearance and degree of cellulose polymerisation, which are the most important properties of paper in the heritage context. Multiple linear regression and principal component regression were used to interpret the large volume of data and calculate a set of dose-response functions. The results of this study not only suggested that most of the considered variables are of significance in relation to changes in colour and in average molecular weight, but also revealed a number of meaningful interactions between these variables. Based on the assessment of the relative contributions of environmental and material-related variables to the natural ageing processes of paper, the dose-response functions proposed in this study enable prioritisation of degradation factors in environmental management of paper-based collections and in historic paper degradation studies; however, further work is required to increase accuracy and understanding of the chemistry of degradation.

Debt specialization and performance of European firms

Abstract Relying on a cross-country comparable sample of European manufacturing firms, this paper investigates the relationship between the level of debt specialization (i.e. composition of the various types of debt) and firm turnover reduction in a time of crisis. The analysis is conducted applying the generalized propensity score matching methodology for continuous variables recently developed by Hirano and Imbens (2004) and Imai and Van Dyk (2004). This quasi-experimental setting allows estimating the (average) firm turnover reduction at each level of debt concentration (i.e. the dose–response function). Consistent with the theoretical analysis of De Fiore and Uhlig (2015) on the flexibility of the financial system, results from the empirical analysis suggest that firms having a diversified debt structure are less likely to experience a severe turnover reduction.

A general model of hormesis in biological systems and its application to pest management.

Hormesis, a phenomenon whereby exposure to high levels of stressors is inhibitory but low (mild, sublethal and subtoxic) doses are stimulatory, challenges decision-making in the management of cancer, neurodegenerative diseases, nutrition and ecotoxicology. In the latter, increasing amounts of a pesticide may lead to upsurges rather than declines of pests, ecological paradoxes that are difficult to predict. Using a novel re-formulation of the Ricker population equation, we show how interactions between intervention strengths and dose timings, dose–response functions and intrinsic factors can model such paradoxes and hormesis. A model with three critical parameters revealed hormetic biphasic dose and dose timing responses, either in a J-shape or an inverted U-shape, yielding a homeostatic change or a catastrophic shift and hormetic effects in many parameter regions. Such effects were enhanced by repeated pulses of low-level stimulations within one generation at different dose timings, thereby reducing threshold levels, maximum responses and inhibition. The model provides insights into the complex dynamics of such systems and a methodology for improved experimental design and analysis, with wide-reaching implications for understanding hormetic effects in ecology and in medical and veterinary treatment decision-making. We hypothesized that the dynamics of a discrete generation pest control system can be determined by various three-parameter spaces, some of which reveal the conditions for occurrence of hormesis, and confirmed this by fitting our model to both hormetic data from the literature and to a non-hormetic dataset on pesticidal control of mirid bugs in cotton.

Technical Note: Characterization of the new microSilicon diode detector.

PurposeDosimetric properties of the new microSilicon diode detector (60023) have been studied with focus on application in small‐field dosimetry. The influences of the dimensions of the sensitive volume and the density of the epoxy layer surrounding the silicon chip of microSilicon have been quantified and compared to its predecessor (Diode E 60017) and the microDiamond (60019, all PTW‐Freiburg, Germany).MethodsDose linearity has been studied in the range from 0.01 to 8.55 Gy and dose‐per‐pulse dependence from 0.13 to 0.86 mGy/pulse. The effective point of measurement (EPOM) was determined by comparing measured percentage depth dose curves with a reference curve (Roos chamber). Output ratios were measured for nominal field sizes from 0.5 × 0.5 cm2 to 4 × 4 cm2. The corresponding small‐field output correction factors, k, were derived with a plastic scintillation detector as reference. The lateral dose–response function, K(x), was determined using a slit beam geometry.ResultsMicroSilicon shows linear dose response (R 2 = 1.000) in both low and high dose range up to 8.55 Gy with deviations of only up to 1% within the dose‐per‐pulse values investigated. The EPOM was found to lie (0.7 ± 0.2) mm below the front detector’s surface. The derived k for microSilicon (0.960 at s eff = 0.55 cm) is similar to that of microDiamond (0.956), while Diode E requires larger corrections (0.929). This improved behavior of microSilicon in small‐fields is reflected in the slightly wider K(x) compared to Diode E. Furthermore, the amplitude of the negative values in K(x) at the borders of the sensitive volume has been reduced.ConclusionsCompared to its predecessor, microSilicon shows improved dosimetric behavior with higher sensitivity and smaller dose‐per‐pulse dependence. Profile measurements demonstrated that microSilicon causes less perturbation in off‐axis measurements. It is especially suitable for the applications in small‐field output factors and profile measurements.