Variations in plant forage quality in the range of the Porcupine caribou herd

Understanding potential impacts of vegetation change on caribou energetics requires information on variations in forage quality among different plant types and over time. We synthesized data on forage quality (nitrogen, neutral detergent fiber and dry matter digestibility) for 10 plant growth forms from existing scientific literature and from field research in the Arctic National Wildlife Refuge, Alaska. These data describe forage quality of plant species in habitats found within the summer and winter range of the Porcupine caribou herd in northwestern Canada and northern Alaska, U.S.A. We compared mean levels of summer forage quality among growth forms and, where possible, estimated seasonal changes in forage quality. Preferred forage groups (deciduous shrubs, forbs, and cottongrass flowers) had higher nitrogen and digestibility, and lower fiber content, than other growth forms. Nitrogen concentration in green biomass peaked at the onset of the growing season in forbs and deciduous shrubs, whereas graminoids reached peak nitrogen concentrations approximately 15-30 days after growth initiation. In vitro dry matter digestibility (IVDMD) and concentration of neutral detergent fiber (NDF) of green biomass differed among growth forms, but did not show strong seasonal changes. IVDMD and NDF concentrations were correlated with nitrogen concentrations in studies that had paired sampling

Central Arctic Caribou and Petroleum Development: Distributional, Nutritional, and Reproductive Implications

We synthesize findings from cooperative research on effects of petroleum development on caribou (Rangifer tarandus granti) of the Central Arctic Herd (CAH). The CAH increased from about 6000 animals in 1978 to 23000 in 1992, declined to 18 000 by 1995, and again increased to 27 000 by 2000. Net calf production was consistent with changes in herd size. In the Kuparuk Development Area (KDA), west of Prudhoe Bay, abundance of calving caribou was less than expected within 4 km of roads and declined exponentially with road density. With increasing infrastructure, high-density calving shifted from the KDA to inland areas with lower forage biomass. During July and early August, caribou were relatively unsuccessful in crossing road/pipeline corridors in the KDA, particularly when in large, insect-harassed aggregations; and both abundance and movements of females were lower in the oil field complex at Prudhoe Bay than in other areas along the Arctic coast. Female caribou exposed to petroleum development west of the Sagavanirktok River may have consumed less forage during the calving period and experienced lower energy balance during the midsummer insect season than those under disturbance-free conditions east of the river. The probable consequences were poorer body condition at breeding and lower parturition rates for western females than for eastern females (e.g., 1988–94: 64% vs. 83% parturient, respectively; p = 0.003), which depressed the productivity of the herd. Assessments of cumulative effects of petroleum development on caribou must incorporate the complex interactions with a variable natural environment.On a procédé à une synthèse des résultats de travaux de recherche coopérative concernant les effets de l’exploitation pétrolière sur le caribou (Rangifer tarandus granti) formant la harde du centre de l’Arctique (HCA). La population de celle-ci est passée de 6000 têtes en 1978 à 23 000 en 1992, puis a diminué à 18 000 en 1995 pour augmenter de nouveau à 27 000 en 2000. La production nette des veaux allait de pair avec les changements dans la taille de la harde. Dans la zone de développement de Kuparuk (KDA), située à l’ouest de Prudhoe Bay, l’abondance des caribous qui mettaient bas était inférieure à celle prévue dans une bande de 4 km de part et d’autre des routes, et elle déclinait de façon exponentielle avec la densité routière. Avec une augmentation des infrastructures, on assistait à un déplacement du vêlage à forte densité de la KDA vers des zones de l’intérieur ayant une biomasse de fourrage moins importante. Durant juillet et au début d’août, il était assez rare que les caribous réussissent à traverser les corridors routiers/pipeliniers dans la KDA, surtout lorsqu’ils formaient de vastes agrégations harcelées par les insectes; l’abondance de même que les déplacements des femelles étaient en outre moindres au sein du complexe pétrolier de Prudhoe Bay qu’à d’autres endroits situés le long du rivage arctique. Il est possible que les femelles qui étaient exposées à l’exploitation pétrolière à l’ouest de la rivière Sagavanirktok aient consommé moins de fourrage au cours de la période de vêlage et que, durant la saison des insectes au milieu de l’été, elles aient connu une balance énergétique inférieure à celle des femelles vivant sans perturbations à l’est de la rivière. Les conséquences probables étaient un état corporel de qualité inférieure au moment de l’accouplement, et des taux de parturition plus faibles pour les femelles situées à l’ouest que pour celles situées à l’est (p. ex., de 1988 à 1994: 64 % c. 83 % de parturientes respectivement: p = 0,003), faisant ainsi baisser la productivité de la harde. Les évaluations des effets cumulatifs de l’exploitation pétrolière sur le caribou doivent intégrer les interactions complexes avec un environnement naturel variable

Where the wild things are: Seasonal variation in caribou distribution in relation to climate change

In this study, we develop a method to analyse the relationships between seasonal caribou distribution and climate, to estimate how climatic conditions affect interactions between humans and caribou, and ultimately to predict patterns of distribution relative to climate change. Satellite locations for the Porcupine (Rangifer tarandus granti) and Bathurst (R. t. groenlandicus) caribou herds were analysed for eight ecologically-defined seasons. For each season, two levels of a key environmental factor influencing caribou distribution were identified, as well as the best climate data available to indicate the factor's annual state. Satellite locations were grouped according to the relevant combination of season and environmental factor. Caribou distributions were compared for opposing environmental factors; this comparison was undertaken relative to hunting access for the Porcupine Herd and relative to exposure to mining activity for the Bathurst Herd. Expected climate trends suggest an overall increase in access to Porcupine caribou for Aklavik (NWT) hunters during the winter and rut seasons, for Venetie (Alaska) hunters during midsummer and fall migration and for Arctic Village (Alaska) during midsummer. Arctic Village may experience reduced availability with early snowfalls in the fall, but we expect there to be little directional shift in the spring migration patterns. For the Bathurst Herd, we expect that fewer caribou would be exposed to the mines during the winter, while more caribou would be exposed to the combined Ekati and Diavik mining zone in the early summer and to the Lupin-Jericho mining zone during the fall migration. If changes in climate cause an increased presence of caribou in the mining sites, monitoring and mitigation measures may need to be intensified

Extending Construal Level Theory to Distributed Teams: Perception and Evaluation of Distant Others

Building on prior research on distributed teams that has identified physical and temporal distance as impediments to collaboration and relationship development, this paper explores how and why we treat geographically distant others differently from those who are proximal. According to construal level theory, physically- or temporally-distant events or objects are more psychologically distant and are more likely to be described in terms of their more general characteristics, while views of more proximal events or objects will be more detailed and nuanced. We extend construal level theory to the distributed team context by advancing propositions about how group members perceive and evaluate distant others in contrast to proximal others. By comparing to alternative computer-mediated communication and social psychological theories that have been applied to this phenomenon, we show that construal level theory offers parsimonious explanations as well as novel predictions about how and why we perceive and evaluate distant others differently. The paper then considers theoretical, methodological, and practical implications of construal level theory for distributed teams and other virtual settings

Mutations associated with progression in follicular lymphoma predict inferior outcomes at diagnosis: Alliance A151303

Follicular lymphoma (FL) is clinically heterogeneous, with select patients tolerating extended watch-and-wait, whereas others require prompt treatment, suffer progression of disease within 24 months of treatment (POD24), and/or experience aggressive histologic transformation (t-FL). Because our understanding of the relationship between genetic alterations in FL and patient outcomes remains limited, we conducted a clinicogenomic analysis of 370 patients with FL or t-FL (from Cancer and Leukemia Group B/Alliance trials 50402/50701/50803, or real-world cohorts from Washington University School of Medicine, Cleveland Clinic, or University of Miami). FL subsets by grade, stage, watch-and-wait, or POD24 status did not differ by mutation burden, whereas mutation burden was significantly higher in relapsed/refractory (rel/ref) FL and t-FL than in newly diagnosed (dx) FL. Nonetheless, mutation burden in dx FL was not associated with frontline progression-free survival (PFS). CREBBP was the only gene more commonly mutated in FL than in t-FL yet mutated CREBBP was associated with shorter frontline PFS in FL. Mutations in 20 genes were more common in rel/ref FL or t-FL than in dx FL, including 6 significantly mutated genes (SMGs): STAT6, TP53, IGLL5, B2M, SOCS1, and MYD88. We defined a mutations associated with progression (MAP) signature as ≥2 mutations in these 7 genes (6 rel/ref FL or t-FL SMGs plus CREBBP). Patients with dx FL possessing a MAP signature had shorter frontline PFS, revealing a 7-gene set offering insight into FL progression risk potentially more generalizable than the m7-Follicular Lymphoma International Prognostic Index (m7-FLIPI), which had modest prognostic value in our cohort. Future studies are warranted to validate the poor prognosis associated with a MAP signature in dx FL, potentially facilitating novel trials specifically in this high-risk subset of patients

Tissue distribution and elimination of C-14 apixaban in rats

Abbreviations used: AUC, area under the plasma concentration-time curve; BCRP, breast cancer resistance protein; BLQ, below limit of quantitation; LSC, liquid scintillation counting; LC/MS, liquid chromatography/mass spectrometry; MS/MS, tandem mass spectrometry; Mrp, multidrug resistance protein; LLOQ, low limit of quantitation; P-gp, Pglycoprotein; PK, pharmacokinetics; QWBA, Whole-body autoradiography; SD, SpragueDawley rats. ABSTRACT Apixaban, a potent and highly selective factor Xa inhibitor, is currently under development for treatment of arterial and venous thrombotic diseases. The distribution, metabolism, and elimination of C-14 apixaban were investigated in male, female, pregnant and lactating rats following single oral doses. Tissue distribution of radioactivity in rats was measured using quantitative whole-body autoradiography. Following single oral administration, radioactivity distributed quickly in rats with C max at 1 h for most tissues. The elimination t 1/2 of radioactivity in blood was 1.7 to 4.2 h. The blood AUC of radioactivity was similar between male and female rats and was slightly higher in pregnant and lower in lactating rats. The radioactivity concentration in tissues involved in elimination was greater than blood with the highest concentration in gastrointestinal tracts, liver, urinary bladder/contents, and lowest level in brains. In pregnant rats, the whole-body autoradiogram showed that low levels of radioactivity were present in fetal blood, liver, and kidney, and were much lower than the radioactivity in respective maternal organs. Fecal route was the major (74% of dose) and urinary was minor pathway (14%) for apixaban elimination. Following single oral doses of C-14 apixaban to lactating rats, apixaban exhibited extensive lacteal excretion with apixaban as the major component. In summary, tissue distribution of apixaban in rats was extensive, but with limited transfer to fetal and brain tissues and extensive secretion into rat milk with parent drug as the major component. Milk excretion could account for 10% of apixaban dose, which was comparable to urinary elimination in rats. Tissue distribution and drug excretion of apixaban are consistent with a moderately permeable drug that is a substrate for P-gp and BCRP efflux transporters

Ultra-deep sequencing reveals the mutational landscape of classical Hodgkin lymphoma

UNLABELLED: The malignant Hodgkin and Reed Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) are scarce in affected lymph nodes, creating a challenge to detect driver somatic mutations. As an alternative to cell purification techniques, we hypothesized that ultra-deep exome sequencing would allow genomic study of HRS cells, thereby streamlining analysis and avoiding technical pitfalls. To test this, 31 cHL tumor/normal pairs were exome sequenced to approximately 1,000× median depth of coverage. An orthogonal error-corrected sequencing approach verified \u3e95% of the discovered mutations. We identified mutations in genes novel to cHL including: CDH5 and PCDH7, novel stop gain mutations in IL4R, and a novel pattern of recurrent mutations in pathways regulating Hippo signaling. As a further application of our exome sequencing, we attempted to identify expressed somatic single-nucleotide variants (SNV) in single-nuclei RNA sequencing (snRNA-seq) data generated from a patient in our cohort. Our snRNA analysis identified a clear cluster of cells containing a somatic SNV identified in our deep exome data. This cluster has differentially expressed genes that are consistent with genes known to be dysregulated in HRS cells (e.g., PIM1 and PIM3). The cluster also contains cells with an expanded B-cell clonotype further supporting a malignant phenotype. This study provides proof-of-principle that ultra-deep exome sequencing can be utilized to identify recurrent mutations in HRS cells and demonstrates the feasibility of snRNA-seq in the context of cHL. These studies provide the foundation for the further analysis of genomic variants in large cohorts of patients with cHL. SIGNIFICANCE: Our data demonstrate the utility of ultra-deep exome sequencing in uncovering somatic variants in Hodgkin lymphoma, creating new opportunities to define the genes that are recurrently mutated in this disease. We also show for the first time the successful application of snRNA-seq in Hodgkin lymphoma and describe the expression profile of a putative cluster of HRS cells in a single patient