The Will Rogers phenomenon, breast cancer and race.

BACKGROUND: The Will Rogers phenomenon [WRP] describes an apparent improvement in outcome for patients' group due to tumor grade reclassification. Staging of cancers is important to select appropriate treatment and to estimate prognosis. The WRP has been described as one of the most important biases limiting the use of historical cohorts when comparing survival or treatment. The main purpose of this study is to assess whether the WRP exists with the move from the AJCC 7th to AJCC 8th edition in breast cancer [BC] staging, and if racial differences are manifested in the expression of the WRP. METHODS: This is a retrospective analysis of 300 BC women (2007-2017) at an academic medical center. Overall survival [OS] and disease-free survival [DFS] was estimated by Kaplan-Meier analysis. Bi and multi-variate Cox regression analyses was used to identify racial factors associated with outcomes. RESULTS: Our patient cohort included 30.3% Caucasians [Whites] and 69.7% African-Americans [Blacks]. Stages I, II, III, and IV were 46.2, 26.3, 23.1, and 4.4% of Whites; 28.7, 43.1, 24.4, and 3.8% of Blacks respectively, in anatomic staging (p = 0.043). In prognostic staging, 52.8, 18.7, 23, and 5.5% were Whites while 35, 17.2, 43.5, and 4.3% were Blacks, respectively (p = 0.011). A total of Whites (45.05% vs. 47.85%) Blacks, upstaged. Whites (16.49% vs. 14.35%) Blacks, downstaged. The remaining, 38.46 and 37.79% patients had their stages unchanged. With a median follow-up of 54 months, the Black patients showed better stage-by-stage 5-year OS rates using 8th edition compared to the 7th edition (p = 0.000). Among the Whites, those who were stage IIIA in the 7th but became stage IB in the 8th had a better prognosis than stages IIA and IIB in the 8th (p = 0.000). The 8th showed complex results (p = 0.176) compared to DFS estimated using the 7th edition (p = 0.004). CONCLUSION: The WRP exists with significant variability in the move from the AJCC 7th to the 8th edition in BC staging (both White and Black patients). We suggest that caution needs to be exercised when results are compared across staging systems to account for the WRP in the interpretation of the data.

Making Breast Screening Convenient: a Community-Based Breast Screening Event During a Historically Black University's Homecoming Festivities.

A breast screening event was conducted during the homecoming festivities of a historically Black university located in a rural county in Mississippi. Two healthcare providers performed clinical breast exams for 26 African American women during the event. This was a prime opportunity to make breast screening accessible for non-elderly African American women.

Pairing field methods to improve inference in wildlife surveys while accommodating detection covariance.

It is common to use multiple field sampling methods when implementing wildlife surveys to compare method efficacy or cost efficiency, integrate distinct pieces of information provided by separate methods, or evaluate method-specific biases and misclassification error. Existing models that combine information from multiple field methods or sampling devices permit rigorous comparison of method-specific detection parameters, enable estimation of additional parameters such as false-positive detection probability, and improve occurrence or abundance estimates, but with the assumption that the separate sampling methods produce detections independently of one another. This assumption is tenuous if methods are paired or deployed in close proximity simultaneously, a common practice that reduces the additional effort required to implement multiple methods and reduces the risk that differences between method-specific detection parameters are confounded by other environmental factors. We develop occupancy and spatial capture-recapture models that permit covariance between the detections produced by different methods, use simulation to compare estimator performance of the new models to models assuming independence, and provide an empirical application based on American marten (Martes americana) surveys using paired remote cameras, hair catches, and snow tracking. Simulation results indicate existing models that assume that methods independently detect organisms produce biased parameter estimates and substantially understate estimate uncertainty when this assumption is violated, while our reformulated models are robust to either methodological independence or covariance. Empirical results suggested that remote cameras and snow tracking had comparable probability of detecting present martens, but that snow tracking also produced false-positive marten detections that could potentially substantially bias distribution estimates if not corrected for. Remote cameras detected marten individuals more readily than passive hair catches. Inability to photographically distinguish individual sex did not appear to induce negative bias in camera density estimates; instead, hair catches appeared to produce detection competition between individuals that may have been a source of negative bias. Our model reformulations broaden the range of circumstances in which analyses incorporating multiple sources of information can be robustly used, and our empirical results demonstrate that using multiple field-methods can enhance inferences regarding ecological parameters of interest and improve understanding of how reliably survey methods sample these parameters.

Intraspecific functional diversity of common species enhances community stability.

Common species are fundamental to the structure and function of their communities and may enhance community stability through intraspecific functional diversity (iFD). We measured among-habitat and within-habitat iFD (i.e., among- and within-plant community types) of two common small mammal species using stable isotopes and functional trait dendrograms, determined whether iFD was related to short-term population stability and small mammal community stability, and tested whether spatially explicit trait filters helped explain observed patterns of iFD. Southern red-backed voles (Myodes gapperi) had greater iFD than deer mice (Peromyscus maniculatus), both among habitats, and within the plant community in which they were most abundant (their "primary habitat"). Peromyscus maniculatus populations across habitats differed significantly between years and declined 78% in deciduous forests, their primary habitat, as did the overall deciduous forest small mammal community. Myodes gapperi populations were stable across habitats and within coniferous forest, their primary habitat, as was the coniferous forest small mammal community. Generalized linear models representing internal trait filters (e.g., competition), which increase within-habitat type iFD, best explained variation in M. gapperi diet, while models representing internal filters and external filters (e.g., climate), which suppress within-habitat iFD, best explained P. maniculatus diet. This supports the finding that M. gapperi had higher iFD than P. maniculatus and is consistent with the theory that internal trait filters are associated with higher iFD than external filters. Common species with high iFD can impart a stabilizing influence on their communities, information that can be important for conserving biodiversity under environmental change.

Geminin overexpression promotes imatinib sensitive breast cancer: a novel treatment approach for aggressive breast cancers, including a subset of triple negative.

Breast cancer is the second leading cause of cancer-related deaths in women. Triple negative breast cancer (TNBC) is an aggressive subtype that affects 10-25% mostly African American women. TNBC has the poorest prognosis of all subtypes with rapid progression leading to mortality in younger patients. So far, there is no targeted treatment for TNBC. To that end, here we show that c-Abl is one of several tyrosine kinases that phosphorylate and activate geminin's ability to promote TNBC. Analysis of >800 breast tumor samples showed that geminin is overexpressed in ∼50% of all tumors. Although c-Abl is overexpressed in ∼90% of all tumors, it is only nuclear in geminin overexpressing tumors. In geminin-negative tumors, c-Abl is only cytoplasmic. Inhibiting c-Abl expression or activity (using imatinib or nilotinib) prevented geminin Y150 phosphorylation, inactivated the protein, and most importantly converted overexpressed geminin from an oncogene to an apoptosis inducer. In pre-clinical orthotopic breast tumor models, geminin-overexpressing cells developed aneuploid and invasive tumors, which were suppressed when c-Abl expression was blocked. Moreover, established geminin overexpressing orthotopic tumors regressed when treated with imatinib or nilotinib. Our studies support imatinib/nilotonib as a novel treatment option for patients with aggressive breast cancer (including a subset of TNBCs)-overexpressing geminin and nuclear c-Abl.

Whitebark pine stand condition, tree abundance, and cone production as predictors of visitation by Clark's nutcracker.

BACKGROUND: Accurately quantifying key interactions between species is important for developing effective recovery strategies for threatened and endangered species. Whitebark pine (Pinus albicaulis), a candidate species for listing under the Endangered Species Act, depends on Clark's nutcracker (Nucifraga columbiana) for seed dispersal. As whitebark pine succumbs to exotic disease and mountain pine beetles (Dendroctonus ponderosae), cone production declines, and nutcrackers visit stands less frequently, reducing the probability of seed dispersal. METHODOLOGY/PRINCIPAL FINDINGS: We quantified whitebark pine forest structure, health metrics, and the frequency of nutcracker occurrence in national parks within the Northern and Central Rocky Mountains in 2008 and 2009. Forest health characteristics varied between the two regions, with the northern region in overall poorer health. Using these data, we show that a previously published model consistently under-predicts the proportion of survey hours resulting in nutcracker observations at all cone density levels. We present a new statistical model of the relationship between whitebark pine cone production and the probability of Clark's nutcracker occurrence based on combining data from this study and the previous study. CONCLUSIONS/SIGNIFICANCE: Our model clarified earlier findings and suggested a lower cone production threshold value for predicting likely visitation by nutcrackers: Although nutcrackers do visit whitebark pine stands with few cones, the probability of visitation increases with increased cone production. We use information theoretics to show that beta regression is a more appropriate statistical framework for modeling the relationship between cone density and proportion of survey time resulting in nutcracker observations. We illustrate how resource managers may apply this model in the process of prioritizing areas for whitebark pine restoration.

Tree squirrel habitat selection and predispersal seed predation in a declining subalpine conifer.

Differential responses by species to modern perturbations in forest ecosystems may have undesirable impacts on plant-animal interactions. If such disruptions cause declines in a plant species without corresponding declines in a primary seed predator, the effects on the plant could be exacerbated. We examined one such interaction between Pinus albicaulis (whitebark pine), a bird-dispersed, subalpine forest species experiencing severe population declines in the northern part of its range, and Tamiasciurus hudsonicus (red squirrel), an efficient conifer seed predator, at 20 sites in two distinct ecosystems. Hypotheses about squirrel habitat preferences were tested to determine how changes in forest conditions influence habitat use and subsequent levels of predispersal cone predation. We performed habitat selection modeling and variable ranking based on Akaike's information criterion; compared the level and variance of habitat use between two forest types (P. albicaulis dominant and mixed conifer); and modeled the relationship between P. albicaulis relative abundance and predispersal cone predation. T. hudsonicus did not demonstrate strong habitat preference for P. albicaulis, and thus, declines in the pine were not met with proportional declines in squirrel habitat use. P. albicaulis habitat variables were the least important in squirrel habitat selection. Squirrel habitat use was lower and varied more in P. albicaulis-dominant forests, and predispersal cone predation decreased linearly with increasing P. albicaulis relative abundance. In Northern Rocky Mountain sites, where P. albicaulis mortality was higher and abundance lower, squirrel predation was greater than in Central Rocky Mountain sites. In ecosystems with reduced P. albicaulis abundance, altered interactions between the squirrel and pine may lead to a lower proportion of P. albicaulis contributing to population recruitment because of reduced seed availability. Reducing the abundance of competing conifers will create suboptimal squirrel habitat, thus lowering cone predation in P. albicaulis and ensuring more seeds are available for avian dispersal.

Invasive pathogen threatens bird-pine mutualism: implications for sustaining a high-elevation ecosystem.

Human-caused disruptions to seed-dispersal mutualisms increase the extinction risk for both plant and animal species. Large-seeded plants can be particularly vulnerable due to highly specialized dispersal systems and no compensatory regeneration mechanisms. Whitebark pine (Pinus albicaulis), a keystone subalpine species, obligately depends upon the Clark's Nutcracker (Nucifraga columbiana) for dispersal of its large, wingless seeds. Clark's Nutcracker, a facultative mutualist with whitebark pine, is sensitive to rates of energy gain, and emigrates from subalpine forests during periods of cone shortages. The invasive fungal pathogen Cronartium ribicola, which causes white pine blister rust, reduces whitebark pine cone production by killing cone-bearing branches and trees. Mortality from blister rust reaches 90% or higher in some whitebark pine forests in the Northern Rocky Mountains, USA, and the rust now occurs nearly rangewide in whitebark pine. Our objectives were to identify the minimum level of cone production necessary to elicit seed dispersal by nutcrackers and to determine how cone production is influenced by forest structure and health. We quantified forest conditions and ecological interactions between nutcrackers and whitebark pine in three Rocky Mountain ecosystems that differ in levels of rust infection and mortality. Both the frequency of nutcracker occurrence and probability of seed dispersal were strongly related to annual whitebark pine cone production, which had a positive linear association with live whitebark pine basal area, and negative linear association with whitebark pine tree mortality and rust infection. From our data, we estimated that a threshold level of approximately 1000 cones/ha is needed for a high likelihood of seed dispersal by nutcrackers (probability > or = 0.7), and that this level of cone production can be met by forests with live whitebark pine basal area > 5.0 m2/ha. The risk of mutualism disruption is greatest in northern most Montana (USA), where three-year mean cone production and live basal area fell below predicted threshold levels. There, nutcracker occurrence, seed dispersal, and whitebark pine regeneration were the lowest of the three ecosystems. Managers can use these threshold values to differentiate between restoration sites requiring planting of rust-resistant seedlings and sites where nutcracker seed dispersal can be expected.

Squamous cell carcinoma at herniorrhaphy and unilateral renal agenesis.

Unilateral renal agenesis occurs infrequently. However, it has been associated with malignancies at multiple primary sites, anomalies of the genitourinary system, and supernumerary limbs. We present the case of a 60-year-old man with an incarcerated left inguinal hernia and renal insufficiency. At herniorrhaphy, he had squamous cell carcinoma in the hernia sac. A postoperative evaluation revealed unilateral renal agenesis, stage IV squamous cell carcinoma of the urinary bladder, and urolithiasis. The clinician should consider the genitourinary system as a primary site when patients present with the unusual finding of squamous cell carcinoma in the abdominal cavity and unilateral renal agenesis.