Programa LIFE Comisión Europea (LIFE NAT 080064 CUBOMED; Ministerio de Agricultura, Alimentación y Medio Ambiente; Fundación Biodiversidad; Dirección General del Agua, Generalitat Valenciana; Fundació Baleària; El Portet de Denia.

<p>Despite 21 years of protection, sideneck river-turtles (<italic>Podocnemis expansa</italic>, <italic>P. unifilis</italic> and <italic>P. vogli</italic>, arrau, terecay and galápago, respectively), an important food resource for riverine communities (<italic>ribereños</italic>) in the Middle Orinoco, have not recovered. To determine the most effective conservation alternative for recovery, we conducted semi-structured interviews of ribereños and determined their attitudes towards turtle conservation; we collected discarded turtle remains in riverine communities to estimate the level of turtle harvest; and constructed a population model to study the effect of reduced survival and future extraction on arrau turtle population growth. We found that ribereños blame continued commercial extraction for the lack of turtle population recovery. Ribereños have a desire to participate actively in conservation and, despite feeling alienated by governmental officials charged with protecting turtles, prefer to be included in conservation efforts. However, ribereños also fear retaliation from turtle poachers. We found widespread turtle harvest along the Middle Orinoco centered on juvenile arrau turtles, and adult female terecay and galápago turtles. In our population model, reducing harvest causes an increase in population growth. A 10% increase in survival causes rapid exponential growth in arrau turtles. The population continues to grow in over 70% of projected scenarios with limited harvest from a recovered stock. Due to the widespread distribution of turtles and their harvest, we recommend increasing ribereño participation in conservation activities, closing outsider (non-ribereño) access to the resource, increasing enforcement against illegal commercial harvest, instating possession limits for subsistence harvest, and promoting localized captive breeding of faster maturing terecay and galápago turtles to satisfy desire for turtle consumption.</p> / Dissertation

Rapid development and urbanization of the Lower Florida Keys in the last 30 years has fragmented the habitat of the Lower Keys marsh rabbit (Sylvilagus palustris hefneri) and threatened it with extinction. Current threats exist at multiple spatiotemporal scales and include threats due to development, invasive species, and global climate change. On Boca Chica Key, the Lower Keys marsh rabbit (LKMR) exists as a metapopulation on Naval Air Station-Key West (NASKW). I conducted a population viability analysis to determine the metapopulation's risk of extinction under multiple management scenarios by developing a spatially-explicit, stage-structured, stochastic matrix model using the programs RAMAS Metapop and ArcGIS. These management scenarios include clearance of airfield vegetation, habitat conversion, and control of feral cats as an invasive species. Model results provided the Navy with relative risk estimates under these different scenarios. Airfield clearance with habitat conversion increased extinction risk, but when coupled with feral cat control, risk was decreased. Because of the potential of sea-level rise due to human-induced global climate change, and its projected impact on the biodiversity of the Florida Keys, I estimated the impacts of rising sea levels on LKMR across its geographic distribution under scenarios of no, low (0.3m), medium (0.6m), and high (0.9m) sea-level rise. I also investigated impacts due to 2 treatments (allowing vegetation to migrate upslope and not allowing migration), and 2 land-use planning decisions (protection and abandonment of humandominated areas). Not surprisingly, under both treatments and both land-use planning decisions, I found a general trend of decreasing total potential LKMR habitat with increasing sea-level rise. Not allowing migration and protecting human-dominated areas both tended to decrease potential LKMR habitat as compared with allowing migration and abandoning human-dominated areas. In conclusion, conservation strategies at multiple scales need to be implemented in order to reduce threats to LKMR, such as development, invasive species, and global climate change.

No description available.

In risk assessment of risk chemicals, variability in susceptibility in the population is an important aspect. The health hazard of a pollutant is related to the internal exposure to the chemical, i.e. the target dose, rather than the external exposure. The target dose may be calculated by physiologically based pharmacokinetic (PBPK) modeling. Furthermore, variability in target dose may be estimated by introducing variability in the physiological, anatomical, and biochemical parameters of the model. Data on these toxicokinetic model parameters may be found in the scientific literature. Since the early seventies, a large number of experimental inhalation studies of the kinetics of several volatiles in human volunteers have been performed at the National Institute for Working Life in Solna. To this day, only very limited analyses of these extensive data have been performed. A Bayesian analysis makes it possible to merge a priori knowledge from the literature with the information in experimental data. If combined with population PBPK modeling, the Bayesian approach may yield posterior estimates of the toxicokinetic parameters for each subject, as well as for the population. One way of producing these estimates is by so-called Markov-chain Monte Carlo (MCMC) simulation. The aim of the thesis was to apply the MCMC technique on previously published experimental data. Another objective was to assess the reliability of PBPK models in general by the combination of the extensive data and Bayesian population techniques. The population kinetics of methyl chloride, dichloromethane, toluene and styrene were assessed. The calibrated model for dichloromethane was used to predict cancer risk in a simulated Swedish population. In some cases, the respiratory uptake of volatiles was found to be lower than predicted from reference values on alveolar ventilation. The perfusion of fat tissue was found to be a complex process that needs special attention in PBPK modeling. These results provide a significant contribution to the field of PBPK modeling of risk chemicals. Appropriate statistical treatment of uncertainty and variability may increase confidence in model results and ultimately contribute to an improved scientific basis for the estimation of occupational health risks.

Modeling is a powerful tool that can be used to identify important relationships between organisms and their habitat (Guisan & Zimmermann, 2000). Understanding the dynamics of how the two relate to one another is important for conserving and managing ecosystems, but the extreme complexity of those ecosystems makes it very difficult to fully diagram. Unlike many other modeling techniques, Multivariate Regression Trees (MRTs) are not limited by a prior assumptions, pre-determined relationships, transformations, or correlations. MRTs have the power to provide both explanation and prediction of ecological data by producing simple models that are easy to interpret. This study proposed to use MRTs to evaluate and model relationships between Lucania parva and the environment and habitat of Florida Bay. Counts were transformed to presence-absence and abundance groupings. Models were first run using a variety of combination of response variables and all explanatory variables. Results of these models were used to select the best combination of response and explanatory variables in an effort to create a best fit model. Models indicated that Lucania parva populations are found in the dense (cover ≥50%), shallow water (<1.8 m) grass beds that occur in the western portion of Florida Bay. A best fit model was able to explain 63.7% of the variance with predictive error of 0.43.

No description available.

Genetic variation was examined in two endangered mussel species, Epioblasma brevidens and E. capsaeformis, and a common species Lampsilis fasciola, in the Clinch River, TN, by screening mitochondrial DNA (mtDNA) sequences and nuclear DNA microsatellites. These species use fish hosts with varying dispersal capabilities, ranging from low, moderate, and high, respectively. Patterns of mtDNA polymorphism exhibited different trends for long-term population sizes for each species during the Holocene (~10,000 ya to present); namely, E. brevidens has declined over time, E. capsaeformis has remained stable, and L. fasciola has expanded. Long-term effective population size (Ne) was smallest in E. brevidens, intermediate in E. capsaeformis, and highest in L. fasciola. Moderately diverged mtDNA lineages, perhaps indicative of secondary contact, were observed in E. brevidens and E. capsaeformis. High levels of gene flow (Nm) were estimated among demes of L. fasciola using traditional F-statistics and likelihood estimates of Nm, whereas such metrics were lower in E. brevidens and E. capsaeformis. Data are consistent with population dynamics and life history traits of each species and their fish hosts. Age, shell growth, and population demography of Epioblasma brevidens, E. capsaeformis, and Lampsilis fasciola were studied from 2004-2007 in a 32-km reach of the Clinch River, TN. Observed maximum age and length of E. brevidens was 28 y and 71.5 mm for males and 11 y and 56.6 mm for females; of E. capsaeformis, 12 y and 54.6 mm for males and 9 y and 48.6 mm for females; and of L. fasciola, 45 y and 91.3 mm for males and 13 y and 62.6 mm for females. For all three species, observed maximum age and length was greater among males than females. Estimated population size in this river reach was approximately 43,000 individuals for E. brevidens, 579,000 individuals for E. capsaeformis, and 30,000 individuals for L. fasciola. Mean recruitment y-1 of 1 y-old E. brevidens ranged from 7.1% to 20%, of E. capsaeformis from 4.0% to 32.4%, and of L. fasciola from 5.8% to 25.6%. Population growth rate y-1 was 24.9% for E. brevidens, 34.6% for E. capsaeformis, and -22.4% for L. fasciola. Mortality rates of females were higher than for males of E. capsaeformis and L. fasciola, but not E. brevidens. Juvenile mussels were collected but temporally and spatially variable in occurrence, and a significant component of the age-class structure of all three species. Recruitment was very high during 2006-2007 for E. capsaeformis and other species, likely due to low river discharges in the spring-summer of 2005-2007. Surplus individuals of E. brevidens and E. capsaeformis are currently available to conduct translocations for restoration purposes. Population modeling of Epioblasma brevidens and E. capsaeformis in the Clinch River was conducted to determine suitable harvest levels for translocation of sub-adults and adults, and to determine quantitative criteria for evaluating performance and recovery of extant and reintroduced populations. For both species, the recommended annual harvest was <1% of local population size to minimize risk of decline. Reintroduction modeling indicated that size of the initial population created during a 5 y build-up phase greatly affected final population size at 25 y, being similar to size at the end of the build-up phase, especially when expected growth rate was low, (e.g., 1-2%). Excluding age-0 individuals, age-1 juveniles or recruits on average comprised approximately 11% and 15% of a stable population of each species, respectively. The age-class distribution of a stable or growing population was characterized by multiple cohorts, to include juvenile recruits, sub-adults, and adults. Molecular genetic and demographic data indicated that the ratio of Ne/Nc was ~5% for both species. Based on this ratio and predicted declines of genetic variation at different population sizes, target sizes for reintroduced or recovered populations of each species should be ≥5,000 individuals (Ne=250) and ≥10,000 individuals (Ne=500), respectively, and should be comprised of multiple smaller demes spread throughout a river. Populations of both species are currently large enough to sustain harvest for translocation and reintroduction purposes, offering an effective species recovery strategy. / Ph. D.

The goal of this research work was to understand the clinical-pharmacology based treatment approaches for sorafenib. Treatment with sorafenib is associated with high inter-patient variability in pharmacokinetic exposures, efficacy and toxicity. We explored the demographic, laboratory, clinical and pharmacogenetic factors to elucidate the sources of variability. In addition, we examined the impact of pharmacogenetic variation in VEGFR2, an important mediator of the VEGF pathway, on risk of prostate cancer. To support these investigations, (mainly single-dose) pharmacokinetic, pharmacogenetic, efficacy and toxicity information were collected from patients with solid tumors, enrolled in five phase I / II clinical trials at National Cancer Institute. Non-compartmental analysis-general linear modeling (NCA-GLM), population pharmacokinetic analysis and several correlative studies were performed to characterize the sources of variability in pharmacokinetics and response. The role of prostate specific antigen (PSA) and ex-vivo anti-angiogenic activity as efficacy markers was evaluated, respectively, for patients with prostate cancer treated with sorafenib and patients with solid tumors treated with combination of sorafenib and bevacizumab. Sweat concentrations of sorafenib were measured to study its association with development of hand-foot skin reaction (HFSR). Only body weight was a significant covariate for volume of distribution by population pharmacokinetic analysis, while BSA, albumin and UGT1A9*3 appeared to be significant by NCA-GLM. However, the contribution of these covariates in overall exposure variability was very small; hence, these were considered clinically irrelevant. The association of sorafenib exposure with efficacy in patients with prostate cancer, colorectal cancer and combined solid tumors were not significant; exposure-efficacy relationship for lung cancer patients requires further evaluation. Sorafenib exposures appeared to be associated with incidences of rash in single agent trials and with HFSR in trials involving treatment with sorafenib and bevacizumab combination. In-vitro cell-line experiments determined that prostate specific antigen (PSA) is not a suitable marker of efficacy in patients with prostate cancer treated with sorafenib. The ex-vivo anti-angiogenic activity, measured by rat-aortic ring assay using patient serum samples, appeared to be not associated with clinical response. Sorafenib concentration in sweat, upto ≥5 ng/mL, apparently was not associated with HFSR. The VEGFR2 H472Q polymorphism was associated with progression-free survival (PFS) (with an apparent heterozygous advantage for survival) and toxicities in patients treated with drugs against the VEGF pathway. Patients who developed hypertension and HFSR on bevacizumab and sorafenib therapy, respectively, appeared to have longer PFS. Therefore, these side effects should be effectively managed to avoid/delay the treatment discontinuation. The VEGFR2 H472Q and V297I genotype were not predictive of risk of prostate cancer in Caucasian subjects.

Noteworthy species endemic to the Galapagos Islands off Ecuador are two flightless birds, the Galapagos Penguin (Spheniscus mendiculus) and Flightless Cormorant (Phalacrocrax harrisi). Both adapted increased swimming ability at the cost of flight. This however has limited their ability to find richer feeding grounds in times of low resource availability, or to escape potential predators. Their population numbers, though small, were stable. Stress on this stability has increased since human arrival. Various invasive species from pets, farm animals and rats to even mosquito vectors of avian disease accompanied humans. . El Nino Southern Oscillation or ENSO cycles of warm waters in the Pacific Ocean south of the Equator cause drastic drops in food sources for all Galapagos seabirds. Serious ENSO events in 1983 and 1998 caused some species’ populations to drop by as much as 77%. Periodic less severe cycles may help explain how population recovery has not rebounded to earlier numbers. Reduced chick survival and adult fecundity seem to occur in concert with mild events. With available data and use of a modeling approach, this study focuses and explores their situations. Restoring population stability may include use of models, species monitoring, conservation and limiting invasive species. Usher matrices based on different climate conditions were produced using data combined from current and past census counts and weather. Models are used to compare available census data and test reliable predictors. Climate data from National Oceanic and Atmospheric Administration and the University of Florida provides for testing predictions of current and probable future climate change. Life histories of both species are regarded. Results suggest the current Cormorant population is still stable. The Penguin, however, faces a 20% probability of extinction in 100 years if current conditions remain. Extinction probability rises to 60% if climate change continues to worsen. Interventions such as captive breeding could be suitable for population recovery.