Aggregating Evidence in Climate Science: Consilience, Robustness and the Wisdom of Multiple Models

The goal of this dissertation is to contribute to the epistemology of science by addressing a set of related questions arising from current discussions in the philosophy and science of climate change: (1) Given the imperfection of computer models, how do they provide information about large and complex target systems? (2) What is the relationship between consilient reasoning and robust evidential support in the production of scientific knowledge? (3) Does taking the mean of a set of model outputs provide epistemic advantages over using the output of a single ‘best model’? Synthesizing research in philosophy and science, the thesis analyzes connections among consilient inductions, robustness analysis, and the aggregation of various sources of evidence, including computer simulations, by investigating case studies of climate change that exemplify the strength of consilient reasoning and the security of robust evidential support. It also explains the rationale and epistemic conditions for improving estimates by averaging multiple estimates, comparing a simple case of averaging estimates to practices in multi-model ensemble studies. I argue: (A) the concepts of consilience and robustness account for the strength and security of inferences that rely on imperfect computer modelling methods, (B) consilient reasoning is conducive to attaining robust evidential support, and (C) an analogy can explain why averaging the outputs of multiple models can improve estimates of a target system, given that conditions of model independence, skill and unequal weighting are taken into account

The effects of 3-nitropropionic acid on the behavior and cortical electrical activity of rats in acute administration

In this study, the acute effects of 3-nitropropionic acid was investigated on open field and startle behavior of rats, and on their cortical electrical activity. Spontaneous locomotor activity, acoustic startle response, and pre-pulse inhibition of acoustic startle were measured in male Wistar rats (10 weeks old, 180-200g body weight) after a single dose of 10 or 20 mg/kg i.p. 3-nitropropionic acid. After the behavioral tests, the rats were anaesthetized, and spontaneous cortical electrical activity was recorded. The vertical, horizontal and local open field performance showed dose-dependent deterioration in the rats treated with 3-nitropropionic acid. The number of “noise-positive” startle responses showed non-significant changes, but the inhibition by pre-pulse was significantly reduced in the high dose animals. High dose also increased the proportion of low-frequencies in the cortical activity. Three-nitropropionic acid, known primarily to act in repeated doses (e.g., in animal models of Huntington’s disease) had also some clear-cut acute effects on behavioral and electrophysiological parameters of the treated rats

In vitro mutagenicity evaluation of iron oxide nanoparticles by the bacterial reverse mutation assay

Iron oxide nanoparticles are becoming highly promising tools for a wide spectrum of biomedical applications. The aim of our work was to determine the potential mutagenic effects of Fe2C>3 and FesCU nanoparticles (NPs), using bacterial reverse mutation assay. This is still the most widely used method for evaluating chemicals and environmental samples for mutagenic activity. In the bacterial reverse mutation assay, two genotypic variants of the Salmonella typhimurium strains (TA98 and TA1535) were used. Fe2Ü3 and Fe3Ü4 NPs were incubated with these two strains in four different doses both in presence and in absence of the rat liver metabolic activation system (S9); concurrently, appropriate positive controls were used to validate the test. The assessment of the results was based on the number of reverse mutants. The average number of reverse mutants per plate treated with NPs was less than double compared to negative control. Fe203 and Fe3C>4 NPs proved to have no mutagenic effect in the bacterial cellular systems tested, in that they did not significantly increase the number of revertant colonies. Our findings indicate that Fe203 and Fe304 NPs are non mutagenic in bacterial reverse mutation assay under the present test conditions. These results are useful to expand our knowledge on the safety of iron oxides NPs

Acute effects of lead, mercury and manganese on the central and peripheral nervous system in rats in combination with alcohol exposure

Heavy metals, due to their numerous applications in industrial processes, agrochemicals and household articles, have caused a widespread pollution and can be found in different foods. One of their target organs is the central nervous system. The toxic effects of heavy metals can be modified by lifestyle-originated factors such as consumption of alcohol. The aim of this study was to investigate the changes in spontaneous cortical activity (ECoG), cortical sensory evoked potentials (EPs) and peripheral nerve action potentials, recorded in rats pre-treated with alcohol and acutely treated with lead, mercury and manganese by intraperitoneal injection. In the ECoG, Hg2+ caused a massive shift to lower frequencies while the effect of Mn2+ and Pb2+ was slight, and alcohol pre-treatment altered the effect of the metals minimally. The amplitude of EPs increased upon the application of heavy metals, and the peak latency lengthened. The effect of Hg2+ was the strongest and that of Pb2+ the weakest, and these effects were potentiated by alcohol. Exposure to heavy metals, together with alcohol consumption, can aggravate the known neurotoxic effects

Central neurotoxic effects elicited with three organophosphorus compounds: comparison of acute and subchronic effects

The neurotoxic effects of organophosphorous compounds had been amply investigated. There are, however, only a limited number of relevant data concerning neurotoxic effects of these substances exerted on central electrophysiological processes. The aim of the present study was to find out whether the effects of acute and subchronic administration of three organophosphorous compounds (dimethoate, parathion-methyl and dichlorvos) on the spontaneous and evoked cortical activity are comparable. In the acute experiments, male Wistar rats were treated with 1/1 or 1/5 LD50 per os (parathion-methyl: 22.5 and 4.5 mg/kg; dimethoate: 700 and 140 mg/kg; dichlorvos: 98 and 19.6 mg/kg) and the changes of the cortical activity were recorded for at least 2.5 or 4.0 hours. In the subchronic administration, the animals were given 1/25 or 1/100 LD50 (parathion-methyl 0.9 and 0.225 mg/kg; dimethoate 28.0 and 7.0 mg/kg; dichlorvos 3.92 and 0.98 mg/kg) for 4, 8 or 12 weeks after which the animals were prepared and recording was done. In acute experiments, dimethoate was the substance causing the strongest decrease of the ECoG whereas parathion-methyl induced the least changes. The duration of the evoked potentials was the most affected by dimethoate. After 12 weeks of administration, parathion-methyl caused the largest alteration in the spontaneous and stimulus-evoked activity of the somatosensory and auditory focus while in the visual focus dichlorvos was the most effective. The results of the study showed that the changes caused by the subchronic administration of the substances were sometimes equal to or larger than those caused by the acute large doses

Altered open field behavior in rats induced by acute administration of 3-nitropropionic acid: possible glutamatergic and dopaminergic involvement

3-nitropropionic acid (3-NP), a substance used for modelling Huntington’s disease, was given to male Wistar rats once in 20 mg/kg b.w. dose, and the resulting behavioural alterations in spontaneous locomotor activity were measured after 30 minutes. To detect the involvement of neurotransmitter systems in this immediate effect, the NMDA antagonist MK-801 (0.8 mg/kg); as well as an agonist, quinpirole (QP, 5 mg/kg) and an antagonist, sulpiride (SP, 80 mg/kg) of the dopamine D2 receptors, were given before 3-NP to separate groups of rats. Controls were given saline. All substances were injected ip. 3-NP decreased the rats’ locomotor, especially vertical, activity, whereas local activity was increased. Based on the further changes of 3-NP effects in the combination groups it could be concluded that dopaminergic rather than glutamatergic mechanisms were possibly involved in the acute behavioural effect of 3-NP

The acute effects of 3-nitropropionic acid on the behavior and spontaneous cortical electrical activity of rats

In this study, the acute effects of 3-nitropropionic acid was investigated on open field and startle behavior of rats, and on their cortical electrical activity. Spontaneous locomotor activity, acoustic startle response, and pre-pulse inhibition of acoustic startle were measured in male Wistar rats (10 weeks old, 180-200g body weight) after a single dose of 10 or 20 mg/kg i.p. 3-nitropropionic acid. After the behavioral tests, the rats were anaesthetized, and spontaneous cortical electrical activity was recorded. The vertical, horizontal and local open field performance showed dose-dependent deterioration in the rats treated with 3-nitropropionic acid. The number of “noise-positive” startle responses showed non-significant changes, but the inhibition by pre-pulse was significantly reduced in the high dose animals. High dose also increased the proportion of low-frequencies in the cortical activity. Three-nitropropionic acid, known primarily to act in repeated doses (e.g., in animal models of Huntington’s disease) had also some clear-cut acute effects on behavioral and electrophysiological parameters of the treated rats

Különböző kémiai szerkezetű peszticid hatóanyagok - szerves foszfát, piretroid, karbamát, klórozott szénhidrogén, tercier-aromás-triamin - és kombinációik által kiváltott neuro-, magatartás- és immuntoxikológiai hatások vizsgálata állatkísérletes modellekben = Investigation of neuro-, behavioural and immuntoxicological effects caused by single and combined treatment of pesticides of different chemical structure (organophosphate, pyrethroide, carbamate, chlorinated hydrocarbone, tertial-aromatic-triamine)

Inszekticidek (dimetoát, propoxur, cipermetrin, amitraz) önálló ill. kombinált szubkrónikus bevitelével vizsgáltuk felnőtt patkányok immunrendszerének ill. idegrendszerének; valamint akut ill. az intra- és extrauterin egyedfejlődés során való adást követően az idegrendszer működését. Az anyagok jellemzői és alkalmazása valószínűsítik egyidejű jelenlétüket és hatásukat az emberi szervezetben. Neurotoxicitás: Az amitráz esetében igazoltuk a neurotoxicitást. A dimetoát és az amitráz hatásai eltérő hatásmechanizmus mellett hasonlóak, a dimetoát és propoxur hatásai hasonló hatásmechanizmus mellett eltérőek voltak. A dimetoát és az amitráz kombinációs kezelésekben is dominált. A spontán kérgi aktivitás változásai több hatóanyag esetében ellentétesek voltak pre- ill. pre- és posztnatális adagolásnál; a kérgi kiváltott válaszok változásai a pre- és posztnatális expozíció összeadódó hatását jelezték. A kiváltott aktivitás változásai voltak pontosabban értékelhetők. Általános és immuntoxikus hatások: A hatások közül a relatív szervtömegek és egyes hematológiai paraméterek voltak legérzékenyebbek az inszekticidekre. A kezelés időtartamának hatása itt is jelentős volt. Az általános, neuro- ill. immuntoxikológiai eredmények között nem volt minden hatást és kölcsönhatást jól jelző paraméter. Az eredmények hozzájárulhatnak az expozíciós határértékek finomításához. Egyes funkcionális eltérések eléggé érzékenyek és specifikusak ahhoz, hogy a későbbiekben biomarkerré váljanak. | Effects of insecticides (dimethoate, prpopxur, cypermethrin, amitraz) was studied, alone or combined, on the nervous and immune system of adult rats in subchronic exposure, and on the nervous system in acute dosage or in exposure including pre- and postnatal development. The agents' characteristics and usage make their simultaneous presence and effects in humans likely. Neurotoxic effects: Neurotoxicity of amitraz was verified. Effects of dimethoate and amitraz were like, despite different way of action, and those of dimethoate and propoxur were unlike, despite similar way of action. Effects of combinations were dominated by dimethoate or amitraz. Changes of spontaneous cortical activity were with several agents opposite when given only in the prenatal, than when in the pre- and postnatal period. Evoked responses, however, indicated an additive effect of pre- and postnatal exposure. The changes of the evoked activity were to evaluate more accurately. General and immuntoxicological parameters: Of all effects, the changes of relative organ weights and certain haematological parameters were the most sensitive to the insecticides. The length of exposure had a major effect also here. None the general, neuro- and immuntoxicological outcomes indicated all effects and interactions. The results can contribute to refining exposure limit values. Some functional alterations were sensitive and specific enough to be developed to biomarkers