Early predictions of a potential drug candidate’s time-course of effect and side-effects, based on models describing drug concentrations, drug effects and disease progression, would be valuable to make drug development more efficient. Pharmacodynamic modeling can incorporate and propagate prior knowledge and be used for simulations of different scenarios. In this thesis three population pharmacodynamic models were developed to describe the antipsychotic effects and the side-effects prolactin elevation and Extra Pyramidal Symptoms (EPS) following administration of D2-receptor antagonists, commonly used in the treatment of schizophrenia. Model parameter estimates of prolactin elevating potencies of six compounds correlated with in vitro values of receptor affinities, and parameters related to diurnal prolactin variation and tolerance were similar for the different compounds. The developed prolactin model can thereby be used to predict the time-course of prolactin elevation in patients for a drug candidate using information on in vitro affinity to the D2-receptor. Furthermore, the clinical antipsychotic effect and the prolactin elevation was found to correlate on the individual level for the three antipsychotic compounds investigated and a quantitative relation between D2-receptor occupancy in the brain and prolactin elevation was established. These results support the use of prolactin concentrations as a biomarker in drug development or for individual dose adjustments in clinical care. The developed model for spontaneously reported EPS adverse events, following treatment with one of five antipsychotics drugs, characterized both the duration and severity of EPS. The model successfully described both the proportions and number of transitions between severity grades and was shown to adequately simulate longitudinal categorical EPS data. Complex pharmacodynamic models are often associated with long estimation times and non-normal distributions of individual parameters. A method for shortening computation times by substituting differential equations for difference equations was evaluated and shown to be valuable for some models. In addition, transformation of distributions allowed for non-normal distributions of between-subject variability to be better characterized and thereby simulation properties were improved. In conclusion, population pharmacodynamic models for a range of D2-receptor antagonists were developed and together with the investigated methods the models can facilitate prediction of effects and side-effects in drug development.

To protect the environment from contaminants, environmental risk assessment (ERA) evaluates the risk of adverse effects to populations, communities and ecosystems. Environmental management decisions rely on ERAs, which commonly are based on a few endpoints at the individual organism level. To bridge the gap between what is measured and what is intended for protection, individual-level effects can be integrated in population models, and translated to the population level. The general aim of this doctoral thesis was to extrapolate individual-level effects of harpacticoid copepods to the population level by developing and using population models. Matrix models and individual based models were developed and applied to life-history data of Nitocra spinipes and Amphiascus tenuiremis, and demographic equations were used to calculate population-level effects in low- and high-density populations. As a basis for the population models, individual-level processes were studied. Development was found to be more sensitive compared to reproduction in standard ecotoxicity tests measuring life-history data. Additional experimental animals would improve statistical power for reproductive endpoints, but at high labor and cost. Therefore, a new test-design was developed in this thesis. Exposing animals in groups included a higher number of animals without increased workload. The number of reproducing females was increased, and the statistical power of reproduction was improved. Individual-level effects were more or equally sensitive compared to population-level effects, and individual-level effects were translated to the population level to various degrees by population models of different complexities. More complex models showed stronger effects at the population level compared to the simpler models. Density dependence affected N. spinipes populations negatively so that toxicant effects were stronger at higher population densities. The tools presented here can be used to assess the toxicity of environmental contaminants at the individual and population level, improve ERA, and thereby the basis for environmental management. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Submitted. Paper 4: Manuscript.</p>

Submitted by Cláudia Bueno (claudiamoura18@gmail.com) on 2016-06-09T17:40:11Z No. of bitstreams: 2 Tese - Claryana Costa Araújo - 2015.pdf: 2174515 bytes, checksum: 2d205f31fba2cbb199ef183432b131d4 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-06-10T11:55:33Z (GMT) No. of bitstreams: 2 Tese - Claryana Costa Araújo - 2015.pdf: 2174515 bytes, checksum: 2d205f31fba2cbb199ef183432b131d4 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2016-06-10T11:55:33Z (GMT). No. of bitstreams: 2 Tese - Claryana Costa Araújo - 2015.pdf: 2174515 bytes, checksum: 2d205f31fba2cbb199ef183432b131d4 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2015-03-20 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The population of humpback dolphins Sousa chinensis that resides in the eastern Taiwan Strait (ETS) is geographically and genetically isolated from populations inhabiting the coastal waters of mainland China and appears to be facing unsustainable levels of human threats. Using VORTEX 9.99b, we modeled the viability of this Critically Endangered population under the present conditions as well as under realistic additional threat scenarios. We examined 6 different levels of bycatch mortality, 3 scenarios of habitat loss/degradation, and scenarios in which these threats were experienced together. Under the baseline (present) scenario, the population exhibited a decreasing growth rate and was predicted to be smaller than the initial population size in more than 76% of all model runs. In all scenarios with additional threats, the proportion of model runs in which population size was smaller than the initial size varied from 77.1 to 92.6%. Over the short term, fisheries-related mortality appears to have a more obvious impact on the population’s trajectory than habitat loss/degradation. Even minimal increases in mortality from the current baseline levels will increase the probability of extinction of this population. Due to the fragile situation of ETS humpback dolphins, mitigation actions to reduce the current threats to this population are needed immediately. / Sem resumo.

Ces dernières décennies, de nouvelles techniques d’anesthésie-analgésie locorégionales ont permis d’améliorer la prise en charge post-opératoire. Cependant, les anesthésiques locaux (AL) exposent les patients à un risque de toxicité systémique potentiellement fatale. La première étude est une étude rétrospective ayant inclus des cas potentiels de toxicité systémique aux AL. Cette étude a montré que, face à l’importante variabilité pharmacocinétique des AL observée, l’interprétation des concentrations est difficile. Sa contribution au diagnostic clinique est limitée aux prélèvements précoces après les signes de toxicité.La deuxième étude porte sur la pharmacocinétique de la lidocaine administrée en anesthésie locale tumescente. Il s’agit de la première description de sa pharmacocinétique dans cette indication. Les concentrations restent faibles pendant la durée de suivi. La modélisation par approche de population a permis de décrire le processus d’absorption systémique de la lidocaine après l’injection d’une solution tumescente. La troisième étude porte sur 10 patientes ayant reçu une infusion cicatricielle de ropivacaine de 40 heures. Il s’agit de la première description pharmacocinétique de l’infusion cicatricielle de ropivacaine dans cette indication. La modélisation a montré que l’absorption systémique de la ropivacaine est retardée et la concentration maximale est atteinte 2 heures après la fin de la perfusion. Les études rapportées dans cette thèse ont exploré les propriétés pharmacocinétiques des AL. L’objectif de ces travaux est de contribuer à une meilleure connaissance des thérapeutiques et de contribuer à une meilleure prise en charge des patients. / New locoregional anaesthetic techniques have permitted an improvement of care. However, local anaesthetics (LA) expose patients to systemic toxicity risks. It is essential to set guidelines for the use of these techniques. A retrospective study includes cases of suspected LA systemic toxicity. Systemic toxicity of LA occur when a large amount of LA reaches the systemic circulation. This thesis shows that the interpretation of plasmatic concentrations remains difficult because of the significant pharmacokinetics variability in the different nervous blocks. The second study deals with the population PK of lidocaine administrated in tumescent local anaesthetic. It is the first description of lidocaine PK is performed in this indication. The lidocaine concentrations remain low during the whole time of the operation. The modelling approach has allowed to highlight the slow systemic absorption process of lidocaine after injection of a tumescent solution. The third study focuses on the PK of ropivacaine administrated via continuous wound infusion in 10 women. It is the first time that the PK of ropivacaine administered using wound infusion is described. The modelling approach shows that systemic absorption of ropivacaine delayed and the maximal serum concentration is reached 2 hours after the end of ropivacaine infusion. These studies explored the PK properties of LA used as an anaesthetic or analgesic drug. The objective of this work is to contribute to a better knowledge of therapeutics and a better handling of patients.

Invasive species introductions are associated with negative economic and environmental impacts, including reductions in native species populations. Successful invasive species populations often grow rapidly and a new food web equilibrium is established. Invasive, predatory northern pike (Esox lucius; hereafter pike) were detected in 2010 in Utah Lake, UT, a highly-degraded ecosystem home to the endemic, endangered June sucker (Chasmistes liorus). Here we test whether pike predation could hinder the restoration efforts of June sucker using the number of June sucker consumed by pike at various population densities as our metric. More specifically, we considered pike density at which the population could consume all June sucker stocked a critical threshold. Currently the number of naturally recruited June sucker is drastically lower than the number stocked. Thus, the metric we used to determine whether the pike population could hinder the June sucker restoration efforts is the number of pike that could consume the number of June sucker stocked. We combined pike growth and foraging observations with an energy-budget, bioenergetics consumption model to quantify lake-wide pike predation on June sucker. We also used an age-structured density dependent population model to estimate the pike population growth trajectory under various mitigation scenarios. Of 125 pike, we found an average pike consumes 0.8-1.0% June sucker and 40% sport fish. According to our bioenergetics model simulations, a population of adult pike at a very high density (60 pike per hectare) has the potential to consume nearly 6 million age-0 June sucker per year, which is likely more June sucker consumed than exist in the environment. In addition, our model suggests that an adult pike density greater than 1.5 pike per hectare has the potential to consume all June sucker stocked annually. Our age-structured population model suggests the pike population will reach equilibrium around 2026 at between 8 and 12 adult pike per hectare with the potential to consume between 0.8 and 1.2 million age-0 June sucker per year, respectively. The growing pike population could hamper restoration efforts and threaten endangered June sucker, a population with a mere 2,000 adults, in jeopardy of extinction. Our findings not only inform pike management efforts, but also highlight the importance of allocating resources toward habitat restoration to provide refuge for juvenile June sucker from predation, preventing the spread of aquatic invasive species, and the need for aquatic invasive species education.

Η ανάγκη εξατομίκευσης της θεραπείας ασθενών που πάσχουν από καρκίνο κρίνεται επιτακτική, λόγω του στενού θεραπευτικού εύρους των αντινεοπλασματικών φαρμάκων και των παρατηρούμενων δια-ατομικών διαφορών στη φαρμακοκινητική και στην κλινική ανταπόκριση. Ένα πολύ χρήσιμο εργαλείο στην εξατομίκευση της θεραπείας θεωρείται ότι είναι η πληθυσμιακή φαρμακοκινητική-φαρμακοδυναμική μοντελοποίηση, καθώς μπορεί να περιγράψει τις σχέσεις δόσης-ανταπόκρισης, να εξηγήσει την παρατηρούμενη μεταβλητότητα στην έκθεση στο φάρμακο ή στην κλινική ανταπόκριση και να καθοδηγήσει την επιλογή της δόσης βάσει της βέλτιστης αναλογίας οφέλους-κινδύνου για τη δεδομένη θεραπεία. Η παρούσα διδακτορική διατριβή επικεντρώθηκε στην μπεβασιζουμάμπη, ένα σχετικά καινούριο φάρμακο στοχευμένης θεραπείας για το οποίο δεν υπάρχουν αρκετά διαθέσιμα στοιχεία που αφορούν στη φαρμακοκινητική και φαρμακοδυναμική συμπεριφορά του. Σκοπός της συγκεκριμένης μελέτης ήταν ο χαρακτηρισμός της αλληλεπίδρασης της μπεβασιζουμάμπης με τον μοριακό της στόχο, VEGF165, σε ενήλικες ασθενείς με μεταστατικό ορθοκολικό καρκίνο που λαμβάνουν το φάρμακο σε συνδυασμό με χημειοθεραπεία (FOLFIRI, FOLFOX ή CAPIRI). Για αυτόν τον λόγο, προσδιορίστηκαν αρχικά οι συγκεντρώσεις της ολικής μπεβασιζουμάμπης και του ελεύθερου VEGF165 σε διάφορους κύκλους θεραπείας και στη συνέχεια, εφαρμόζοντας τη μη γραμμική μικτών επιδράσεων μοντελοποίηση με το υπολογιστικό πρόγραμμα NONMEM 7.3, αναπτύχθηκε ένα φαρμακοκινητικό μοντέλο σύνδεσης της μπεβασιζουμάμπης με τον VEGF165. Επιπλέον, διερευνήθηκε η επίδραση των δημογραφικών δεδομένων και των VEGF μονονουκλεοτιδικών πολυμορφισμών στην αλληλεπίδραση μεταξύ της φαρμακοκινητικής της μπεβασιζουμάμπης και των συγκεντρώσεων του VEGF165. Είναι η πρώτη φορά που χρησιμοποιήθηκε η TMDD προσέγγιση για τον χαρακτηρισμό της in vivo αλληλεπίδρασης μπεβασιζουμάμπης-VEGF165. Σύμφωνα με αυτή την προσέγγιση, η φαρμακοκινητική ενός φαρμάκου επηρεάζεται από την υψηλής συγγένειας δέσμευση με τον μοριακό του στόχο και την επακόλουθη αποικοδόμηση του σχηματιζόμενου συμπλόκου μέσω ενδοκυττάρωσης. Το αναπτυχθέν μοντέλο επέτρεψε την ικανοποιητική περιγραφή της φαρμακοκινητικής της μπεβασιζουμάμπης και των ιδιοτήτων σύνδεσής της με τον VEGF165. Η κάθαρση της μπεβασιζουμάμπης βρέθηκε να είναι 0.18 L/day, η τιμή αναφοράς της συγκέντρωσης του ελεύθερου VEGF165 ήταν 212 ng/L, η σταθερά του ρυθμού απομάκρυνσης του ελεύθερου VEGF165 ήταν 0.401 day-1 και η Kss ήταν 267 nM. Η επίδραση του πραγματικού σωματικού βάρους συνυπολογίστηκε στην εκτίμηση όλων των φαρμακοκινητικών παραμέτρων του μοντέλου. Κάποιες στατιστικά μη σημαντικές συσχετίσεις παρατηρήθηκαν μεταξύ της συγγένειας δέσμευσης του φαρμάκου και των VEGF-2578C/A και VEGF-634G/C πολυμορφισμών. Το αναπτυχθέν μοντέλο θα μπορούσε να αποτελέσει ένα χρήσιμο εργαλείο στην εξατομίκευση της θεραπείας και στην αξιολόγηση της κλινικής ανταπόκρισης ασθενών που λαμβάνουν μπεβασιζουμάμπη σε συνδυασμό με χημειοθεραπεία. / The need for individualized treatment in cancer patients is considered crucial due to the narrow therapeutic range of antineoplastic drugs and the observed inter-individual differences in pharmacokinetics and clinical response. Population pharmacokinetic-pharmacodynamic modeling has been recognized as a beneficial tool for personalizing treatment, as it can describe the dose-response relationships, explain the observed variability in drug exposure or response and guide dose selection based on the optimal benefit-risk ratio for a given treatment. The current doctoral thesis was focused on bevacizumab, a relatively new targeted therapy drug for which no sufficient data are available regarding its pharmacokinetic and pharmacodynamic behavior. The aim of the present study was to characterize the interaction of bevacizumab with its molecular target, VEGF165, in adult patients with metastatic colorectal cancer who receive the drug in combination with chemotherapy (FOLFIRI, FOLFOX or CAPIRI). For this reason, the concentrations of total bevacizumab and free VEGF165 were first determined in different cycles of treatment and then, a pharmacokinetic model for bevacizumab binding to VEGF165 was developed by using nonlinear mixed-effects modeling implemented in NONMEM 7.3 software. Moreover, the effect of demographic data and VEGF single nucleotide polymorphisms on the interplay between bevacizumab pharmacokinetics and VEGF165 concen-trations was investigated. This is the first time the TMDD approach was applied to characterize the in vivo bevacizumab-VEGF165 interaction. According to this approach, the pharmacokinetics of a drug is affected by its high affinity binding to its molecular target and subsequent degradation of the formed complex via endocytosis. The developed model allowed an adequate description of bevacizumab pharmacokinetics and its binding properties to VEGF165. Bevacizumab clearance was found to be 0.18 L/day, the free VEGF165 concentration at baseline was 212 ng/L, the elimination rate constant of free VEGF165 was 0.401 day-1, and Kss was 267 nM. The effect of actual body weight was taken into account in the estimation of all pharmacokinetic model parameters. Correlations, which were not statistically significant, were noticed between the binding affinity of the drug and the VEGF-2578C/A and VEGF-634G/C polymorphisms. The developed model could become a useful tool for individualizing treatment and evaluating clinical response of patients receiving bevacizumab in combination with chemotherapy.

Periodically-harvested fisheries closures (PHCs) are a widespread form of community-based marine spatial management used throughout the Indo-Pacific that also is currently being intensively advocated by conservation organizations for supporting productive fisheries and healthy marine ecosystems. However, local implementation of PHCs has historically been designed to support occasional and efficient exploitation of fish stocks, and not necessarily sustainable fisheries yields and stock conservation. The efficacy of PHCs for achieving their historical cultural objectives of periodicity and efficiency of harvest, simultaneously with achieving contemporary fisheries objectives of fisheries productivity and conservation is undetermined. As a result, the utility of PHCs for supporting contemporary ecosystem-based fisheries management is uncertain given environmental, social and climate change. We developed a biological-economic fisheries model of PHCs to test the value of this form of marine resource management for achieving cultural, fisheries and conservation objectives under sustainable and overfishing scenarios. Our results reveal PHCs to be more effective at achieving the multiple objectives than either non-spatial or fully-protected area management when fisher impact on fish behavior is considered. These results describe the performance of PHCs in general when fish behavior is considered, but does not provide detailed guidance for a particular PHC. Thus, we modified and calibrated our biological-economic fisheries model with empirical data from Nakodu Village on Koro Island in Fiji. The calibrated model allowed us to estimate the effectiveness of Nakodu Village’s current PHC management and predict consequences of future management actions. Results suggest that 5-year PHC closures are optimal for simultaneously achieving fisheries productivity and conservation goals in Nakodu Village. These findings challenge the dogma that PHCs are simply a cultural legacy and warrant further investigation of the utility of PHCs for supporting ecosystem-based management beyond the Indo-Pacific.

Monitoring population trend and estimating vital demographic parameters are essential for effective management of a mule deer (Odocoileus hemionus) population. Because of financial constraints, many wildlife agencies use computer models to obtain indirect indices of population size and trend as an alternative to annual field-based estimates of population size. These models are based primarily on herd composition counts and harvest rates from hunter-harvest surveys, and are rarely field validated. I developed an alternative method for monitoring population dynamics of wintering populations of mule deer. I designed a hybrid monitoring program that combined annual vital rate monitoring to track changes in population growth rate with a field-based approach for estimating population abundance. The program allocated resources optimally towards the most critical components of mule deer population dynamics, and consisted of 4 field surveys: annual monitoring of age ratios, overwinter fawn survival, and annual doe survival, with field-based estimates of population size only once every 4 years. Surveys were conducted from 2006 to 2008 in Wildlife Management Unit (WMU) 2, Utah, and cost $29,298 per year, prorated over 4 years. Unfortunately, financial constraints prohibit the implementation of this monitoring program in every WMU in Utah. Instead, the program can be implemented in select WMUs throughout the state, with survival data collected in these core units, providing estimates for nearby satellite units. To establish core-satellite unit pairs, I developed a proxy method for determining correlation in survival rates between core and satellite units using model-simulated estimates. I demonstrated this core-satellite method using WMU 2 as a core and WMU 3, an adjacent unit, as a satellite. Finally, I compared a multiple data sources (MDS) model with a herd composition-based population model, POP-II. The MDS model better approximated observed data, and provided statistical rigor. Overall, the hybrid program was less costly and provided more precise estimates of population trend than could be achieved with a monitoring program focused on abundance alone, and was more defensible than herd composition monitoring. After establishing correlations in doe and fawn survival between core and satellite units, data collected in core units via the hybrid program could then be used to model the mule deer population dynamics of other units using MDS modeling procedures. This combined approach could be an effective statewide program for monitoring mule deer populations.

Understanding factors limiting population growth is crucial to evaluating species persistence in changing environments. I used Integral Projection Models (IPMs) to elucidate the role of biotic interactions and disturbance on population growth rate in two plants: Helianthemum squamatum, a perennial endemic to gypsum habitats in central Spain, and Liatris ohlingerae, a long-lived perennial endemic to the Lake Wales Ridge of central Florida. In H. squamatum, there was a strong positive effect of trampling in the site with the highest plant density and moderate positive effects of seed addition in the site with the lowest plant density. Differences in treatment effectiveness between sites may represent a shift from seed to microsite limitation at increasing densities. Additionally, a distinct drop in population growth rate occurred in the hottest and driest year (2009-10). In Liatris ohlingerae, roadside populations had consistently higher population growth rates than scrub populations. A modest negative effect of time-since-fire was observed in plants that did not experience herbivory. Both habitat and time-since-fire showed distinct interactions with vertebrate herbivory, with herbivory increasing the difference in growth rate between habitats and decreasing the difference between time-since-fire classes. The direct effect of herbivory was negative in all environmental combinations except in long unburned populations. These results demonstrate the importance of considering environmental interactions when constructing population models, as well as the validity of using IPMs to assess interactions in species with differing life histories.

The southeastern United States is a global biodiversity hotspot but has experienced severe declines of natural ecosystems. The southeast is currently facing widespread change, particularly from an increasing human population and climate change, that is likely to impact all remaining natural areas to some degree. In this work, I examine some of the challenges currently facing imperiled species of reptiles and amphibians in this region. The work is focused on two species, the Reticulated Flatwoods Salamander (Ambystoma bishopi) and the Eastern Indigo Snake (Drymarchon couperi) both of which are listed on the U.S. Endangered Species List. Chapter 1 used Light Detection and Ranging (LiDAR) data to measure wetland bathymetry (basin shape) in flatwoods salamander breeding wetlands. Bathymetry data were used to construct stage–area relationships for each wetland, and a history of water level monitoring data were applied to these relationships to build multi-year time series of flooded area metrics. These metrics were then combined with an assessment of vegetation characteristics to map potentially suitable habitat for flatwoods salamander breeding within each wetland. Chapter 2 focused on flatwoods salamander phenology (the timing of life history events) in response to climate change. I quantified flatwoods salamander movements into and out of breeding wetlands over a 10-year period (2010–2020), identifying temperature and precipitation patterns that were conducive to salamander movements. I then used future climate projections to forecast movement opportunities for flatwoods salamander from 2030–2099 and used an existing hydrologic model built on the same climate data to understand how phenology may interact with hydrology. Overall, only a small number of years are likely to have an ideal intersection of phenology and hydrology as has been observed during recent breeding seasons. Chapter 3 described the construction of a stochastic Integral Projection Model for flatwoods salamanders. I integrated the projections from Chapter 2 with the population model to estimate the viability of two flatwoods salamander populations from 2030–2099 under multiple climate change scenarios. The results indicated that approximately half of the examined scenarios resulted in a high probability (>0.5) of extinction when considering both wetland hydrology and salamander phenology. In Chapter 4, I described the creation of a stochastic Integral Projection Model for indigo snakes. I then demonstrated the utility of this model by examining the effects of initial population size, road density, and removal of individuals to support a captive colony on indigo snake populations. I found that high road densities and high collection rates would likely lead to population declines, although the rate of declines and extinction risk varied across scenarios. Taken together, these projects highlight some of the challenges currently facing herpetofauna in the southeastern United States, demonstrate the difficulty in conserving these often-overlooked species, and provide useful tools for ongoing conservation efforts focusing on these two imperiled species. / Doctor of Philosophy / We are in the midst of a global biodiversity crisis, with rates of species extinction far exceeding normal levels. Species loss is largely driven by global change attributable to human activities. A rapidly changing world can make it challenging to effectively conserve and manage imperiled species. In this work, I studied two species found only in the southeastern United States that are listed on the U.S. Endangered Species List. Chapters 1–3 focused on the Reticulated Flatwoods Salamander (Ambystoma bishopi), while Chapter 4 focused on the Eastern Indigo Snake (Drymarchon couperi). In Chapter 1, I used high resolution elevation data to map the shape of flatwoods salamander breeding wetlands. These data were then used to estimate flooded areas across multiple years. Flooded area metrics were combined with vegetation measurements to map potential flatwoods salamander breeding habitat. In Chapter 2, I examined how flatwoods salamander movements may respond to climate change. I identified time periods and weather conditions that coincided with flatwoods salamander movements into and out of breeding wetlands. I then projected potential movement opportunities based on multiple future climate scenarios for each breeding season from 2030–2099. My results showed that few years are likely to be ideal for flatwoods salamander reproduction, which is similar to trends observed in recent years. In Chapter 3, I built a population model for flatwoods salamanders. I then combined the model with predictions made in Chapter 2 to estimate the probability that populations would go extinct by the end of the century. The results indicated that the two flatwoods salamander populations examined had a high probability (>0.5) of extinction in about 50% of the climate scenarios. In Chapter 4, I constructed a population model for indigo snakes using a variety of available data. I used this model to examine the effects of road density, initial population size, and removal of individuals to support a captive colony on indigo snake populations. The results suggested that populations experiencing high road densities or high collection rates were likely to decline over time. These projects highlight some of the difficulties in conserving often-overlooked reptiles and amphibians in the southeastern United States and provide important tools for ongoing conservation projects working with these two imperiled species.