Effects of Plant Phenology and Vertical Height on Accuracy of Radio-telemetry Locations

The use of very high frequency (VHF) radio-telemetry remains wide-spread in studies of wildlife ecology andmanagement. However, few studies have evaluated the influence of vegetative obstruction on accuracy in differing habitats with varying transmitter types and heights. Using adult and fawn collars at varying heights above the ground (0, 33, 66 and 100 cm) to simulate activities (bedded, feeding and standing) and ages (neonate, juvenile and adult) of deer Odocoileus spp., we collected 5,767 bearings and estimated 1,424 locations (28-30 for each of 48 subsamples) in three habitat types (pasture, grassland and forest), during two stages of vegetative growth (spring and late summer). Bearing error was approximately twice as large at a distance of 900mfor fawn (9.98) than for adult deer collars (4.98). Of 12 models developed to explain the variation in location error, the analysis of covariance model (HT*D + C*D + HT*TBA + C*TBA) containing interactions of height of collar above ground (HT), collar type (C), vertical height of understory vegetation (D) and tree basal area (TBA) was the best model (wi¼0.92) and explained ; 71% of the variation in location error. Location error was greater for both collar types at 0 and 33 cmabove the ground compared to 66 and 100 cm above the ground; however, location error was less for adult than fawn collars. Vegetation metrics influenced location error, which increased with greater vertical height of understory vegetation and tree basal area. Further, interaction of vegetation metrics and categorical variables indicated significant effects on location error. Our results indicate that researchers need to consider study objectives, life history of the study animal, signal strength of collar (collar type), distance from transmitter to receiver, topographical changes in elevation, habitat composition and season when designing telemetry protocols. Bearing distances in forested habitat should be decreased (approximately 23% in our study) compared to bearing distances in open habitat to maintain a consistent bearing error across habitats. Additionally, we believe that field biologists monitoring neonate ungulates for habitat selection should rely on visual locations rather than using VHF-collars and triangulation

National Performance Benchmarks for Modern Screening Digital Mammography: Update from the Breast Cancer Surveillance Consortium

Purpose To establish performance benchmarks for modern screening digital mammography and assess performance trends over time in U.S. community practice. Materials and Methods This HIPAA-compliant, institutional review board-approved study measured the performance of digital screening mammography interpreted by 359 radiologists across 95 facilities in six Breast Cancer Surveillance Consortium (BCSC) registries. The study included 1 682 504 digital screening mammograms performed between 2007 and 2013 in 792 808 women. Performance measures were calculated according to the American College of Radiology Breast Imaging Reporting and Data System, 5th edition, and were compared with published benchmarks by the BCSC, the National Mammography Database, and performance recommendations by expert opinion. Benchmarks were derived from the distribution of performance metrics across radiologists and were presented as 50th (median), 10th, 25th, 75th, and 90th percentiles, with graphic presentations using smoothed curves. Results Mean screening performance measures were as follows: abnormal interpretation rate (AIR), 11.6 (95% confidence interval [CI]: 11.5, 11.6); cancers detected per 1000 screens, or cancer detection rate (CDR), 5.1 (95% CI: 5.0, 5.2); sensitivity, 86.9% (95% CI: 86.3%, 87.6%); specificity, 88.9% (95% CI: 88.8%, 88.9%); false-negative rate per 1000 screens, 0.8 (95% CI: 0.7, 0.8); positive predictive value (PPV) 1, 4.4% (95% CI: 4.3%, 4.5%); PPV2, 25.6% (95% CI: 25.1%, 26.1%); PPV3, 28.6% (95% CI: 28.0%, 29.3%); cancers stage 0 or 1, 76.9%; minimal cancers, 57.7%; and node-negative invasive cancers, 79.4%. Recommended CDRs were achieved by 92.1% of radiologists in community practice, and 97.1% achieved recommended ranges for sensitivity. Only 59.0% of radiologists achieved recommended AIRs, and only 63.0% achieved recommended levels of specificity. Conclusion The majority of radiologists in the BCSC surpass cancer detection recommendations for screening mammography; however, AIRs continue to be higher than the recommended rate for almost half of radiologists interpreting screening mammograms. © RSNA, 2016 Online supplemental material is available for this article

Evidence that dopamine acts via Kisspeptin to Hold GnRH pulse frequency in check in Anestrous Ewes

Recent work has implicated stimulatory kisspeptin neurons in the arcuate nucleus (ARC) as important for seasonal changes in reproductive function in sheep, but earlier studies support a role for inhibitory A15 dopaminergic (DA) neurons in the suppression of GnRH (and LH) pulse frequency in the nonbreeding (anestrous) season. Because A15 neurons project to the ARC, we performed three experiments to test the hypothesis that A15 neurons act via ARC kisspeptin neurons to inhibit LH in anestrus: 1) we used dual immunocytochemistry to determine whether these ARC neurons contain D2 dopamine receptor (D2-R), the receptor responsible for inhibition of LH in anestrus; 2) wetested the ability of local administration of sulpiride, a D2-R antagonist, into theARCto increase LH secretion in anestrus; and 3) we determined whether an antagonist to the kisspeptin receptor could block the increase in LH secretion induced by sulpiride in anestrus. In experiment 1, 40% of this ARC neuronal subpopulation contained D2-R in breeding season ewes, but this increased to approximately 80% in anestrus. In experiment 2, local microinjection of the two highest doses (10 and 50 nmol) of sulpiride into the ARC significantly increased LH pulse frequency to levels 3 times that seen with vehicle injections. Finally, intracerebroventricular infusion of a kisspeptin receptor antagonist completely blocked the increase in LH pulse frequency induced by systemic administration of sulpiride to anestrous ewes. These results support the hypothesis that DA acts to inhibit GnRH (and LH) secretion in anestrus by suppressing the activity of ARC kisspeptin neurons.We thank Heather Bungard and Jennifer Lydon (West Virginia University Food Animal Research Facility) for the care of animals and Paul Harton for his technical assistance in sectioning tissue. We also thank Dr. Al Parlow and the National Hormone and Peptide Program (Torrance, CA) for the reagents used to measure LH and prolactin.http://endo.endojournals.org/am201

Kisspeptin, neurokinin B, and dynorphin cct in the arcuate nucleus to control activity of the GnRH pulse generator in Ewes

Recent work has led to the hypothesis that kisspeptin/neurokinin B/dynorphin (KNDy) neurons in the arcuate nucleus play a key role in GnRH pulse generation, with kisspeptin driving GnRH release and neurokinin B (NKB) and dynorphin acting as start and stop signals, respectively. In this study, we tested this hypothesis by determining the actions, if any, of four neurotransmitters found in KNDy neurons (kisspeptin, NKB, dynorphin, and glutamate) on episodic LH secretion using local administration of agonists and antagonists to receptors for these transmitters in ovariectomized ewes. We also obtained evidence that GnRH-containing afferents contact KNDy neurons, so we tested the role of two components of these afferents: GnRH and orphanin-FQ. Microimplants of a Kiss1r antagonist briefly inhibited LH pulses and microinjections of 2 nmol of this antagonist produced a modest transitory decrease in LH pulse frequency. An antagonist to the NKB receptor also decreased LH pulse frequency, whereas NKB and an antagonist to the receptor for dynorphin both increased pulse frequency. In contrast, antagonists toGnRHreceptors, orphanin-FQ receptors, and the N-methyl-D-aspartate glutamate receptor had no effect on episodic LH secretion.Wethus conclude that the KNDy neuropeptides act in the arcuate nucleus to control episodic GnRH secretion in the ewe, but afferent input from GnRH neurons to this area does not. These data support the proposed roles forNKBand dynorphin within theKNDyneural network and raise the possibility that kisspeptin contributes to the control ofGnRHpulse frequency in addition to its established role as an output signal from KNDy neurons that drives GnRH pulses.National Institutes of Health Grants R01-HD039916 and RO1-HD017864.http://press.endocrine.org/journal/endoam201

Hunting and mountain sheep: Do current harvest practices affect horn growth?

The influence of human harvest on evolution of secondary sexual characteristics has implications for sustainable management of wildlife populations. The phenotypic consequences of selectively removing males with large horns or antlers from ungulate populations have been a topic of heightened concern in recent years. Harvest can affect size of horn-like structures in two ways: (a) shifting age structure toward younger age classes, which can reduce the mean size of horn-like structures, or (b) selecting against genes that produce large, fast-growing males. We evaluated effects of age, climatic and forage conditions, and metrics of harvest on horn size and growth of mountain sheep (Ovis canadensis ssp.) in 72 hunt areas across North America from 1981 to 2016. In 50% of hunt areas, changes in mean horn size during the study period were related to changes in age structure of harvested sheep. Environmental conditions explained directional changes in horn growth in 28% of hunt areas, 7% of which did not exhibit change before accounting for effects of the environment. After accounting for age and environment, horn size of mountain sheep was stable or increasing in the majority (similar to 78%) of hunt areas. Age-specific horn size declined in 44% of hunt areas where harvest was regulated solely by morphological criteria, which supports the notion that harvest practices that are simultaneously selective and intensive might lead to changes in horn growth. Nevertheless, phenotypic consequences are not a foregone conclusion in the face of selective harvest; over half of the hunt areas with highly selective and intensive harvest did not exhibit age-specific declines in horn size. Our results demonstrate that while harvest regimes are an important consideration, horn growth of harvested male mountain sheep has remained largely stable, indicating that changes in horn growth patterns are an unlikely consequence of harvest across most of North America.Utah Division of Wildlife Resources; National Wild Sheep Foundation (WSF); Wyoming Wild Sheep Foundation; Alberta Wild Sheep Foundation; California Wild Sheep Foundation; Arizona Desert Bighorn Sheep Society; Wyoming Governor's Big Game License Coalition; Iowa Foundation for North American Wild Sheep; Utah Foundation for North American Wild Sheep; Pope and Young ClubOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group.

Cancer immunotherapy has transformed the treatment of cancer. However, increasing use of immune-based therapies, including the widely used class of agents known as immune checkpoint inhibitors, has exposed a discrete group of immune-related adverse events (irAEs). Many of these are driven by the same immunologic mechanisms responsible for the drugs\u27 therapeutic effects, namely blockade of inhibitory mechanisms that suppress the immune system and protect body tissues from an unconstrained acute or chronic immune response. Skin, gut, endocrine, lung and musculoskeletal irAEs are relatively common, whereas cardiovascular, hematologic, renal, neurologic and ophthalmologic irAEs occur much less frequently. The majority of irAEs are mild to moderate in severity; however, serious and occasionally life-threatening irAEs are reported in the literature, and treatment-related deaths occur in up to 2% of patients, varying by ICI. Immunotherapy-related irAEs typically have a delayed onset and prolonged duration compared to adverse events from chemotherapy, and effective management depends on early recognition and prompt intervention with immune suppression and/or immunomodulatory strategies. There is an urgent need for multidisciplinary guidance reflecting broad-based perspectives on how to recognize, report and manage organ-specific toxicities until evidence-based data are available to inform clinical decision-making. The Society for Immunotherapy of Cancer (SITC) established a multidisciplinary Toxicity Management Working Group, which met for a full-day workshop to develop recommendations to standardize management of irAEs. Here we present their consensus recommendations on managing toxicities associated with immune checkpoint inhibitor therapy

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin