A Gene Signature to Determine Metastatic Behavior in Thymomas

Purpose

Thymoma represents one of the rarest of all malignancies. Stage and completeness of resection have been used to ascertain postoperative therapeutic strategies albeit with limited prognostic accuracy. A molecular classifier would be useful to improve the assessment of metastatic behaviour and optimize patient management.

Methods

qRT-PCR assay for 23 genes (19 test and four reference genes) was performed on multi-institutional archival primary thymomas (n = 36). Gene expression levels were used to compute a signature, classifying tumors into classes 1 and 2, corresponding to low or high likelihood for metastases. The signature was validated in an independent multi-institutional cohort of patients (n = 75).

Results

A nine-gene signature that can predict metastatic behavior of thymomas was developed and validated. Using radial basis machine modeling in the training set, 5-year and 10-year metastasis-free survival rates were 77% and 26% for predicted low (class 1) and high (class 2) risk of metastasis (P = 0.0047, log-rank), respectively. For the validation set, 5-year metastasis-free survival rates were 97% and 30% for predicted low- and high-risk patients (P = 0.0004, log-rank), respectively. The 5-year metastasis-free survival rates for the validation set were 49% and 41% for Masaoka stages I/II and III/IV (P = 0.0537, log-rank), respectively. In univariate and multivariate Cox models evaluating common prognostic factors for thymoma metastasis, the nine-gene signature was the only independent indicator of metastases (P = 0.036).

Conclusion

A nine-gene signature was established and validated which predicts the likelihood of metastasis more accurately than traditional staging. This further underscores the biologic determinants of the clinical course of thymoma and may improve patient management.     

Are Isolated Indigenous Populations Headed toward Extinction?

At least 50 indigenous groups spread across lowland South America remain isolated and have only intermittent and mostly hostile interactions with the outside world. Except in emergency situations, the current policy of governments in Brazil, Colombia, and Peru towards isolated tribes is a “leave them alone” strategy, in which isolated groups are left uncontacted. However, these no-contact policies are based on the assumption that isolated populations are healthy and capable of persisting in the face of mounting external threats, and that they can maintain population viability in the long-term. Here, we test this assumption by tracking the sizes and movements of cleared horticultural areas made by 8 isolated groups over the last 10–14 years. We used deforestation data derived from remote sensing Landsat satellite sensors to identify clearings, and those were then validated and assessed with high-resolution imagery. We found only a single example of a relatively large and growing population (c. 50 cleared ha and 400 people), whereas all of the other 7 groups exhibited much smaller villages and gardens with no sizable growth through time. These results indicated that the smaller groups are critically endangered, and it prompts an urgent re-thinking of policies toward isolated populations, including plans for well-organized contacts that may help save lives and rescue isolated indigenous populations from imminent extinction.     

Phenological mismatch in Arctic‐breeding shorebirds: Impact of snowmelt and unpredictable weather conditions on food availability and chick growth

The ecological consequences of climate change have been recognized in numerous species, with perhaps phenology being the most well‐documented change. Phenological changes may have negative consequences when organisms within different trophic levels respond to environmental changes at different rates, potentially leading to phenological mismatches between predators and their prey. This may be especially apparent in the Arctic, which has been affected more by climate change than other regions, resulting in earlier, warmer, and longer summers. During a 7‐year study near Utqia?vik (formerly Barrow), Alaska, we estimated phenological mismatch in relation to food availability and chick growth in a community of Arctic‐breeding shorebirds experiencing advancement of environmental conditions (i.e., snowmelt). Our results indicate that Arctic‐breeding shorebirds have experienced increased phenological mismatch with earlier snowmelt conditions. However, the degree of phenological mismatch was not a good predictor of food availability, as weather conditions after snowmelt made invertebrate availability highly unpredictable. As a result, the food available to shorebird chicks that were 2–10 days old was highly variable among years (ranging from 6.2 to 28.8 mg trap^?1 day^?1 among years in eight species), and was often inadequate for average growth (only 20%–54% of Dunlin and Pectoral Sandpiper broods on average had adequate food across a 4‐year period). Although weather conditions vary among years, shorebirds that nested earlier in relation to snowmelt generally had more food available during brood rearing, and thus, greater chick growth rates. Despite the strong selective pressure to nest early, advancement of nesting is likely limited by the amount of plasticity in the start and progression of migration. Therefore, long‐term climatic changes resulting in earlier snowmelt have the potential to greatly affect shorebird populations, especially if shorebirds are unable to advance nest initiation sufficiently to keep pace with seasonal advancement of their invertebrate prey.     

Geographic Distribution of Isolated Indigenous Societies in Amazonia and the Efficacy of Indigenous Territories

The headwaters of the Amazon Basin harbor most of the world’s last indigenous peoples who have limited contact with encroaching colonists. Knowledge of the geographic distribution of these isolated groups is essential to assist with the development of immediate protections for vulnerable indigenous settlements. We used remote sensing to document the locations of 28 isolated villages within the four Brazilian states of Acre, Amazonas, Roraima, and Rondônia. The sites were confirmed during previous over-flights and by image evidence of thatched-roof houses; they are estimated to host over 1,700 individuals. Locational data were used to train maximum entropy models that identified landscape and anthropogenic features associated with the occurrence of isolated indigenous villages, including elevation, proximity to streams of five different orders, proximity to roads and settlements, proximity to recent deforestation, and vegetation cover type. Isolated villages were identified at mid elevations, within 20 km of the tops of watersheds and at greater distances from existing roads and trails. We further used model results, combined with boundaries of the existing indigenous territory system that is designed to protect indigenous lands, to assess the efficacy of the existing protected area network for isolated peoples. Results indicate that existing indigenous territories encompass all of the villages we identified, and 50% of the areas with high predicted probabilities of isolated village occurrence. Our results are intended to help inform policies that can mitigate against future external threats to isolated peoples.     

Quantifying an overlooked aspect of partial migration using otolith microchemistry

For the first time, an overlooked aspect of partial migration was quantified using otolith microchemistry and brown trout, Salmo trutta, as a model species. Relative contributions of freshwater resident and anadromous female brown trout to mixed-stock sea trout populations in the Baltic Sea were estimated. Out of 236 confirmed wild sea trout sampled around the coast of Estonia 88% were of anadromous maternal origin and 12% were of resident maternal origin. This novel finding underscores the importance of the resident contingent in maintaining the persistence and resilience of the migratory contingent.     

Quantitative and Qualitative Approaches to Identifying Migration Chronology in a Continental Migrant

The degree to which extrinsic factors influence migration chronology in North American waterfowl has not been quantified, particularly for dabbling ducks. Previous studies have examined waterfowl migration using various methods, however, quantitative approaches to define avian migration chronology over broad spatio-temporal scales are limited, and the implications for using different approaches have not been assessed. We used movement data from 19 female adult mallards (Anas platyrhynchos) equipped with solar-powered global positioning system satellite transmitters to evaluate two individual level approaches for quantifying migration chronology. The first approach defined migration based on individual movements among geopolitical boundaries (state, provincial, international), whereas the second method modeled net displacement as a function of time using nonlinear models. Differences in migration chronologies identified by each of the approaches were examined with analysis of variance. The geopolitical method identified mean autumn migration midpoints at 15 November 2010 and 13 November 2011, whereas the net displacement method identified midpoints at 15 November 2010 and 14 November 2011. The mean midpoints for spring migration were 3 April 2011 and 20 March 2012 using the geopolitical method and 31 March 2011 and 22 March 2012 using the net displacement method. The duration, initiation date, midpoint, and termination date for both autumn and spring migration did not differ between the two individual level approaches. Although we did not detect differences in migration parameters between the different approaches, the net displacement metric offers broad potential to address questions in movement ecology for migrating species. Ultimately, an objective definition of migration chronology will allow researchers to obtain a comprehensive understanding of the extrinsic factors that drive migration at the individual and population levels. As a result, targeted conservation plans can be developed to support planning for habitat management and evaluation of long-term climate effects.