Accounting for Location Uncertainty in Azimuthal Telemetry Data Improves Ecological Inference

Background: Characterizing animal space use is critical for understanding ecological relationships. Animal telemetry technology has revolutionized the fields of ecology and conservation biology by providing high quality spatial data on animal movement. Radio-telemetry with very high frequency (VHF) radio signals continues to be a useful technology because of its low cost, miniaturization, and low battery requirements. Despite a number of statistical developments synthetically integrating animal location estimation and uncertainty with spatial process models using satellite telemetry data, we are unaware of similar developments for azimuthal telemetry data. As such, there are few statistical options to handle these unique data and no synthetic framework for modeling animal location uncertainty and accounting for it in ecological models. We developed a hierarchical modeling framework to provide robust animal location estimates from one or more intersecting or non-intersecting azimuths. We used our azimuthal telemetry model (ATM) to account for azimuthal uncertainty with covariates and propagate location uncertainty into spatial ecological models. We evaluate the ATM with commonly used estimators (Lenth (1981) maximum likelihood and M-Estimators) using simulation. We also provide illustrative empirical examples, demonstrating the impact of ignoring location uncertainty within home range and resource selection analyses. We further use simulation to better understand the relationship among location uncertainty, spatial covariate autocorrelation, and resource selection inference. Results: We found the ATM to have good performance in estimating locations and the only model that has appropriate measures of coverage. Ignoring animal location uncertainty when estimating resource selection or home ranges can have pernicious effects on ecological inference. Home range estimates can be overly confident and conservative when ignoring location uncertainty and resource selection coefficients can lead to incorrect inference and over confidence in the magnitude of selection. Furthermore, our simulation study clarified that incorporating location uncertainty helps reduce bias in resource selection coefficients across all levels of covariate spatial autocorrelation. Conclusion: The ATM can accommodate one or more azimuths when estimating animal locations, regardless of how they intersect; this ensures that all data collected are used for ecological inference. Our findings and model development have important implications for interpreting historical analyses using this type of data and the future design of radio-telemetry studies

DNA Methylation Analysis Reveals Distinct Methylation Signatures in Pediatric Germ Cell Tumors

Background: Aberrant DNA methylation is a prominent feature of many cancers, and may be especially relevant in germ cell tumors (GCTs) due to the extensive epigenetic reprogramming that occurs in the germ line during normal development. Methods: We used the Illumina GoldenGate Cancer Methylation Panel to compare DNA methylation in the three main histologic subtypes of pediatric GCTs (germinoma, teratoma and yolk sac tumor (YST); N = 51) and used recursively partitioned mixture models (RPMM) to test associations between methylation pattern and tumor and demographic characteristics. We identified genes and pathways that were differentially methylated using generalized linear models and Ingenuity Pathway Analysis. We also measured global DNA methylation at LINE1 elements and evaluated methylation at selected imprinted loci using pyrosequencing. Results: Methylation patterns differed by tumor histology, with 18/19 YSTs forming a distinct methylation class. Four pathways showed significant enrichment for YSTs, including a human embryonic stem cell pluripotency pathway. We identified 190 CpG loci with significant methylation differences in mature and immature teratomas (q \u3c 0.05), including a number of CpGs in stem cell and pluripotency-related pathways. Both YST and germinoma showed significantly lower methylation at LINE1 elements compared with normal adjacent tissue while there was no difference between teratoma (mature and immature) and normal tissue. DNA methylation at imprinted loci differed significantly by tumor histology and location. Conclusion: Understanding methylation patterns may identify the developmental stage at which the GCT arose and the at-risk period when environmental exposures could be most harmful. Further, identification of relevant genetic pathways could lead to the development of new targets for therapy

An exploratory analysis of mitochondrial haplotypes and allogeneic hematopoietic cell transplantation (HCT) outcomes

AbstractCertain mitochondrial haplotypes (mthaps) are associated with disease, possibly through differences in oxidative phosphorylation and/or immunosurveillance. We explored whether mthaps are associated with allogeneic hematopoietic cell transplantation (HCT) outcomes. Recipient (n = 437) and donor (n = 327) DNA were genotyped for common European mthaps (H, J, U, T, Z, K, V, X, I, W, and K2). HCT outcomes for mthap matched siblings (n = 198), all recipients, and all donors were modeled using relative risks (RR) and 95% confidence intervals and compared with mthap H, the most common mitochondrial haplotypes. Siblings with I and V were significantly more likely to die within 5 years (RR = 3.0; 95% confidence interval [CI], 1.2 to 7.9; and RR = 4.6; 95% CI, 1.8 to 12.3, respectively). W siblings experienced higher acute graft-versus-host disease (GVHD) grades II to IV events (RR = 2.1; 95% CI, 1.1 to 2.4) with no events for those with K or K2. Similar results were observed for all recipients combined, although J recipients experienced lower GVHD and higher relapse. Patients with I donors had a 2.7-fold (1.2 to 6.2) increased risk of death in 5 years, whereas few patients with K2 or W donors died. No patients with K2 donors and few patients with U donors relapsed. Mthap may be an important consideration in HCT outcomes, although validation and functional studies are needed. If confirmed, it may be feasible to select donors based on mthap to increase positive or decrease negative outcomes