Assessing the impact of lymphovascular invasion on overall survival in surgically treated renal cell carcinoma patients: A nationwide cohort analysis.

INTRODUCTION: Lymph-vascular invasion (LVI) is recognized as an adverse pathological feature in patients with renal cell carcinoma (RCC). However, its impact on overall survival (OS) is not clear and scarcely addressed in the literature. We aimed to assess the prognostic ability of LVI as a predictor of OS in RCC patients using a large, North American cohort. METHODS: We included 95,783 cM0 RCC patients, diagnosed between 2010 and 2015, who underwent partial or radical nephrectomy within the National Cancer Database. Kaplan-Meier curves and log-rank tests were used to depict and compare survival curves. Cox regression analysis tested the impact of LVI on OS, after adjusting for all available confounders. RESULTS: Mean age (SD) was 59 (12), and most patients had pT1 stage (72.2%). Nodal status was pN0, pN1, and pNx, in 14.5%, 2.3%, and 83.3%, respectively. Overall, 9.0% of patients had LVI. The mean (SD) follow-up of the cohort was 39 months (24). At 5 years, OS was 65% in patients with LVI vs. 86% in patients without LVI (p<.0001). When patients were stratified based on nodal stage, these rates were 64% vs. 78% in pN0 patients, 31% vs. 41% in pN1 patients, and 69% vs. 87% in pNx patients (all P < 0.001). On multivariable analysis, and in comparison to patients without LVI, those with LVI had 1.37- (P < 0.001), 1.18- (P = 0.068), and 1.53-fold (P < 0.001) greater risk of death, when also harboring pN0, pN1, and pNx disease, respectively. CONCLUSIONS: Our findings are the first, to our best knowledge, to illustrate the clear detrimental impact of LVI on OS in surgically treated RCC patients. These findings might be useful in postoperative patient counseling and need to be accounted for when designing future clinical trials.

Late quaternary biotic homogenization of North American mammalian faunas.

Biotic homogenization-increasing similarity of species composition among ecological communities-has been linked to anthropogenic processes operating over the last century. Fossil evidence, however, suggests that humans have had impacts on ecosystems for millennia. We quantify biotic homogenization of North American mammalian assemblages during the late Pleistocene through Holocene (~30,000 ybp to recent), a timespan encompassing increased evidence of humans on the landscape (~20,000-14,000 ybp). From ~10,000 ybp to recent, assemblages became significantly more homogenous (>100% increase in Jaccard similarity), a pattern that cannot be explained by changes in fossil record sampling. Homogenization was most pronounced among mammals larger than 1 kg and occurred in two phases. The first followed the megafaunal extinction at ~10,000 ybp. The second, more rapid phase began during human population growth and early agricultural intensification (~2,000-1,000 ybp). We show that North American ecosystems were homogenizing for millennia, extending human impacts back ~10,000 years.

Reactivation predicts the consolidation of unbiased long-term cognitive maps.

Spatial memories that can last a lifetime are thought to be encoded during 'online' periods of exploration and subsequently consolidated into stable cognitive maps through their 'offline' reactivation. However, the mechanisms and computational principles by which offline reactivation stabilize long-lasting spatial representations remain poorly understood. Here, we employed simultaneous fast calcium imaging and electrophysiology to track hippocampal place cells over 2 weeks of online spatial reward learning behavior and offline resting. We describe that recruitment to persistent network-level offline reactivation of spatial experiences in mice predicts the future representational stability of place cells days in advance of their online reinstatement. Moreover, while representations of reward-adjacent locations are generally more stable across days, offline-reactivation-related stability is, conversely, most prominent for reward-distal locations. Thus, while occurring on the tens of milliseconds timescale, offline reactivation is uniquely associated with the stability of multiday representations that counterbalance the overall reward-adjacency bias, thereby predicting the stabilization of cognitive maps that comprehensively reflect entire underlying spatial contexts. These findings suggest that post-learning offline-related memory consolidation plays a complimentary and computationally distinct role in learning compared to online encoding.

Using Evidence-Based Learning Theories to Guide the Development of Virtual Simulations.

Technology-enhanced training such as virtual simulations can be effective only to the extent evidence-based principles of learning are integrated into their training platforms. Assuming skill acquisition is the target of training, programs should include time and space for repeated practice opportunities structured through evidence-based learning theories (Amodeo et al. in Adm Soc Work 33:423-438, 2009). Essential learning attributes derived from Cognitive Load Theory (Sweller in Cognit Sci 12:257-285, 1988) and the Theory of Deliberate Practice (Ericsson et al. in Psychol Rev 100:363-406, 1993) can effectively integrate into virtual simulations intended to build expertise. Virtual Home Simulation (VHS) and Virtual Motivational Interviewing (VMI) are presented in this paper as an approach to develop virtual simulations that provide child welfare workers a means to deliberately practice essential skills toward competence before entering the workforce. This paper reviews the development process, specific design aspects, and lessons learned as a guide on how to integrate effective learning attributes. Implications for using virtual simulations, including cost-benefits, measuring performance over time, and addressing training complications due to Covid-19 or similar obstacles, are also provided.

Functional traits of the world's late Quaternary large-bodied avian and mammalian herbivores.

Prehistoric and recent extinctions of large-bodied terrestrial herbivores had significant and lasting impacts on Earth's ecosystems due to the loss of their distinct trait combinations. The world's surviving large-bodied avian and mammalian herbivores remain among the most threatened taxa. As such, a greater understanding of the ecological impacts of large herbivore losses is increasingly important. However, comprehensive and ecologically-relevant trait datasets for extinct and extant herbivores are lacking. Here, we present HerbiTraits, a comprehensive functional trait dataset for all late Quaternary terrestrial avian and mammalian herbivores ≥10 kg (545 species). HerbiTraits includes key traits that influence how herbivores interact with ecosystems, namely body mass, diet, fermentation type, habitat use, and limb morphology. Trait data were compiled from 557 sources and comprise the best available knowledge on late Quaternary large-bodied herbivores. HerbiTraits provides a tool for the analysis of herbivore functional diversity both past and present and its effects on Earth's ecosystems.

Introduced herbivores restore Late Pleistocene ecological functions.

Large-bodied mammalian herbivores dominated Earth's terrestrial ecosystems for several million years before undergoing substantial extinctions and declines during the Late Pleistocene (LP) due to prehistoric human impacts. The decline of large herbivores led to widespread ecological changes due to the loss of their ecological functions, as driven by their unique combinations of traits. However, recently, humans have significantly increased herbivore species richness through introductions in many parts of the world, potentially counteracting LP losses. Here, we assessed the extent to which introduced herbivore species restore lost-or contribute novel-functions relative to preextinction LP assemblages. We constructed multidimensional trait spaces using a trait database for all extant and extinct mammalian herbivores ≥10 kg known from the earliest LP (∼130,000 ybp) to the present day. Extinction-driven contractions of LP trait space have been offset through introductions by ∼39% globally. Analysis of trait space overlap reveals that assemblages with introduced species are overall more similar to those of the LP than native-only assemblages. This is because 64% of introduced species are more similar to extinct rather than extant species within their respective continents. Many introduced herbivores restore trait combinations that have the capacity to influence ecosystem processes, such as wildfire and shrub expansion in drylands. Although introduced species have long been a source of contention, our findings indicate that they may, in part, restore ecological functions reflective of the past several million years before widespread human-driven extinctions.

The Stockman's Scorecard: quantitative evaluation of beef cattle stockmanship.

An animal's action, or inaction, is the direct result of a stockman's action or inaction. The Stockman's Scorecard is a novel observation instrument that has been proven to be a valid and reliable tool to measure the quality of beef cattle stockmanship. Specific handler actions have been weighted based on their perceived negative relationship to cattle stress from handling. The purpose of this article is to 1) document the initial use of the scorecard in a beef cattle feedlot setting and 2) provide further support to its validity by establishing an association with other quantitative and qualitative means of evaluating stockmanship. The Scorecard was used at 39 beef feedlots in Texas between March 2018 and April 2019. Eighty-four stockman were observed, and the average score received was 84.5 (SD = 14.73, range = 20 to 100). The most frequent mistakes observed were as follows: fills crowd pen/tub over half full (n = 39), slow to remove pressure (n = 29), uses unnecessary noise (n = 25), stands in front and taps rear (n = 24), and fails to regulate animal flow through a pinch point (n = 22). A strong negative association (ρ = -0.51) was found between the points deducted from the Noise and Physical Contact theme of the Scorecard and the number of animals touched with an electric prod from the BQA Feedyard Assessment. Moderate negative associations were found between the Scorecard final score and the number of animals that vocalize in the chute prior to procedures (ρ = -0.31). Those stockmen that scored above average on the Scorecard were qualitatively observed to be calm and quiet while working with the cattle (Kappa = 0.44). The qualitative disposition of cattle had little effect on the final score of stockmen using the Scorecard (Kappa = 0.17). The use of the Scorecard in a feedlot setting has demonstrated that as stockman scores decrease, there is an increase in the number of negative actions toward cattle and a negative behavioral response of the cattle themselves. Establishment of an association between a stockman's score using the Stockman's Scorecard and the animal-based observations from the BQA Feedyard Assessment further strengthens the validity of the Stockman's Scorecard as a tool to measure the quality of beef cattle stockmanship. The Scorecard has application as a tool to identify specific stockmanship deficiencies in order to target stockmanship training.

Rice Intake and Emerging Concerns on Arsenic in Rice: a Review of the Human Evidence and Methodologic Challenges.

PURPOSE OF REVIEW: Rice is a major staple food worldwide and a dietary source of arsenic. We therefore summarized the state of the epidemiologic evidence on whether rice consumption relates to health outcomes associated with arsenic exposure. RECENT FINDINGS: While epidemiologic studies have reported that higher rice consumption may increase the risk of certain chronic conditions, i.e., type 2 diabetes, most did not consider specific constituents of rice or other sources of arsenic exposure. Studies that examined rice intake stratified by water concentrations of arsenic found evidence of increasing trends in cardiovascular disease risk, skin lesions, and squamous cell skin cancers and bladder cancer associated with higher rice consumption. Further studies are needed to understand the health impacts of arsenic exposure from rice consumption taking into account all sources of rice intake and potential confounding by other dietary constituents or contaminants and arsenic exposure from sources such as water.

Reorganization of surviving mammal communities after the end-Pleistocene megafaunal extinction.

Large mammals are at high risk of extinction globally. To understand the consequences of their demise for community assembly, we tracked community structure through the end-Pleistocene megafaunal extinction in North America. We decomposed the effects of biotic and abiotic factors by analyzing co-occurrence within the mutual ranges of species pairs. Although shifting climate drove an increase in niche overlap, co-occurrence decreased, signaling shifts in biotic interactions. Furthermore, the effect of abiotic factors on co-occurrence remained constant over time while the effect of biotic factors decreased. Biotic factors apparently played a key role in continental-scale community assembly before the extinctions. Specifically, large mammals likely promoted co-occurrence in the Pleistocene, and their loss contributed to the modern assembly pattern in which co-occurrence frequently falls below random expectations.

The importance of ecological memory for trophic rewilding as an ecosystem restoration approach.

Increasing human pressure on strongly defaunated ecosystems is characteristic of the Anthropocene and calls for proactive restoration approaches that promote self-sustaining, functioning ecosystems. However, the suitability of novel restoration concepts such as trophic rewilding is still under discussion given fragmentary empirical data and limited theory development. Here, we develop a theoretical framework that integrates the concept of 'ecological memory' into trophic rewilding. The ecological memory of an ecosystem is defined as an ecosystem's accumulated abiotic and biotic material and information legacies from past dynamics. By summarising existing knowledge about the ecological effects of megafauna extinction and rewilding across a large range of spatial and temporal scales, we identify two key drivers of ecosystem responses to trophic rewilding: (i) impact potential of (re)introduced megafauna, and (ii) ecological memory characterising the focal ecosystem. The impact potential of (re)introduced megafauna species can be estimated from species properties such as lifetime per capita engineering capacity, population density, home range size and niche overlap with resident species. The importance of ecological memory characterising the focal ecosystem depends on (i) the absolute time since megafauna loss, (ii) the speed of abiotic and biotic turnover, (iii) the strength of species interactions characterising the focal ecosystem, and (iv) the compensatory capacity of surrounding source ecosystems. These properties related to the focal and surrounding ecosystems mediate material and information legacies (its ecological memory) and modulate the net ecosystem impact of (re)introduced megafauna species. We provide practical advice about how to quantify all these properties while highlighting the strong link between ecological memory and historically contingent ecosystem trajectories. With this newly established ecological memory-rewilding framework, we hope to guide future empirical studies that investigate the ecological effects of trophic rewilding and other ecosystem-restoration approaches. The proposed integrated conceptual framework should also assist managers and decision makers to anticipate the possible trajectories of ecosystem dynamics after restoration actions and to weigh plausible alternatives. This will help practitioners to develop adaptive management strategies for trophic rewilding that could facilitate sustainable management of functioning ecosystems in an increasingly human-dominated world.

Mammal diversity will take millions of years to recover from the current biodiversity crisis.

The incipient sixth mass extinction that started in the Late Pleistocene has already erased over 300 mammal species and, with them, more than 2.5 billion y of unique evolutionary history. At the global scale, this lost phylogenetic diversity (PD) can only be restored with time as lineages evolve and create new evolutionary history. Given the increasing rate of extinctions however, can mammals evolve fast enough to recover their lost PD on a human time scale? We use a birth-death tree framework to show that even if extinction rates slow to preanthropogenic background levels, recovery of lost PD will likely take millions of years. These findings emphasize the severity of the potential sixth mass extinction and the need to avoid the loss of unique evolutionary history now.

PHYLACINE 1.2: The Phylogenetic Atlas of Mammal Macroecology.

Data needed for macroecological analyses are difficult to compile and often hidden away in supplementary material under non-standardized formats. Phylogenies, range data, and trait data often use conflicting taxonomies and require ad hoc decisions to synonymize species or fill in large amounts of missing data. Furthermore, most available data sets ignore the large impact that humans have had on species ranges and diversity. Ignoring these impacts can lead to drastic differences in diversity patterns and estimates of the strength of biological rules. To help overcome these issues, we assembled PHYLACINE, The Phylogenetic Atlas of Mammal Macroecology. This taxonomically integrated platform contains phylogenies, range maps, trait data, and threat status for all 5,831 known mammal species that lived since the last interglacial (~130,000 years ago until present). PHYLACINE is ready to use directly, as all taxonomy and metadata are consistent across the different types of data, and files are provided in easy-to-use formats. The atlas includes both maps of current species ranges and present natural ranges, which represent estimates of where species would live without anthropogenic pressures. Trait data include body mass and coarse measures of life habit and diet. Data gaps have been minimized through extensive literature searches and clearly labelled imputation of missing values. The PHYLACINE database will be archived here as well as hosted online so that users may easily contribute updates and corrections to continually improve the data. This database will be useful to any researcher who wishes to investigate large-scale ecological patterns. Previous versions of the database have already provided valuable information and have, for instance, shown that megafauna extinctions caused substantial changes in vegetation structure and nutrient transfer patterns across the globe.

What North America's skeleton crew of megafauna tells us about community disassembly.

Functional trait diversity is increasingly used to model future changes in community structure despite a poor understanding of community disassembly's effects on functional diversity. By tracking the functional diversity of the North American large mammal fauna through the End-Pleistocene megafaunal extinction and up to the present, I show that contrary to expectations, functionally unique species are no more likely to go extinct than functionally redundant species. This makes total functional richness loss no worse than expected given similar taxonomic richness declines. However, where current species sit in functional space relative to pre-anthropogenic baselines is not random and likely explains ecosystem functional changes better than total functional richness declines. Prehistoric extinctions have left many extant species functionally isolated and future extinctions will cause even more rapid drops in functional richness.

Impact of a western diet on the ovarian and serum metabolome.

OBJECTIVE: The objective of this investigation was to determine differences in the profiles of endogenous metabolites (metabolomics) among ovaries and serum derived from Old World nonhuman primates fed prudent or Western diets. DESIGN: A retrospective, observational study was done using archived ovarian tissue and serum from midlife cynomolgus monkeys (Macaca fasicularis). Targeted and broad spectrum metabolomics analysis was used to compare ovarian tissue and serum from monkeys that had been exposed to a prudent diet or a Western diet. Monkeys in the prudent diet group (n=13) were research naïve and had been exposed only to a commercial monkey chow diet (low in cholesterol and saturated fats, high in complex carbohydrates). Western diet monkeys (n=8) had consumed a diet that was high in cholesterol, saturated animal fats and soluble carbohydrates for 2 years prior to ovarian tissue and serum collection. OUTCOME MEASURES: Metabolomic analyses were done on extracts of homogenized ovary tissue samples, and extracts of serum. Targeted analysis was conducted using the Biocrates p180 kit and broad spectrum analysis was conducted using UPLC-TOF-MS, resulting in the detection of 3500 compound ions. RESULTS: Using metabolomics methods, which capture thousands of signals for metabolites, 64 metabolites were identified in serum and 47 metabolites were identified in ovarian tissue that differed by diet. Quantitative targeted analysis revealed 13 amino acids, 6 acrylcarnitines, and 2 biogenic amines that were significantly (p<0.05) different between the two diet groups for serum extracts, and similar results were observed for the ovary extracts. CONCLUSIONS: These data demonstrate that dietary exposure had a significant impact on the serum and ovarian metabolome, and demonstrated perturbation in carnitine, lipids/fatty acid, and amino acid metabolic pathways.

The temporal scale of diet and dietary proxies.

Diets estimated from different proxies such as stable isotopes, stomach contents, and dental microwear often disagree, leading to nominally well-supported but greatly differing estimates of diet for both extinct and extant species that complicate our understanding of ecology. We show that these perceived incongruences can be caused by proxies recording diet over vastly different timescales. Field observations reveal a diet averaged over minutes or hours, whereas dental morphology may reflect the diet of a lineage over millions of years of evolution. Failing to explicitly consider the scale of proxies and the potentially large temporal variability in diet can cause erroneous predictions in any downstream analyses such as conservation planning or paleohabitat reconstructions. We propose a cross-scale framework for conceptualizing diet suitable for both modern ecologists and paleontologists and provide recommendations for any studies involving dietary data. Treating diet in this temporally explicit framework and matching the scale of our questions with the scale of our data will lead to a much richer and clearer understanding of ecological and evolutionary processes.

Was Frozen Mammoth or Giant Ground Sloth Served for Dinner at The Explorers Club?

Accounts of woolly mammoths (Mammuthus primigenius) preserved so well in ice that their meat is still edible have a long history of intriguing the public and influencing paleontological thought on Quaternary extinctions and climate, with some scientists resorting to catastrophism to explain the instantaneous freezing necessary to preserve edible meat. Famously, members of The Explorers Club purportedly dined on frozen mammoth from Alaska, USA, in 1951. This event, well received by the press and general public, became an enduring legend for the Club and popularized the notorious annual tradition of serving rare and exotic food at Club dinners that continues to this day. The Yale Peabody Museum holds a sample of meat preserved from the 1951 meal, interestingly labeled as a South American giant ground sloth (Megatherium), not mammoth. We sequenced a fragment of the mitochondrial cytochrome-b gene and studied archival material to verify its identity, which if genuine, would extend the range of Megatherium over 600% and alter our views on ground sloth evolution. Our results indicate that the meat was not mammoth or Megatherium but green sea turtle (Chelonia mydas). The prehistoric dinner was likely an elaborate publicity stunt. Our study emphasizes the value of museums collecting and curating voucher specimens, particularly those used for evidence of extraordinary claims.

Holocene shifts in the assembly of plant and animal communities implicate human impacts.

Understanding how ecological communities are organized and how they change through time is critical to predicting the effects of climate change. Recent work documenting the co-occurrence structure of modern communities found that most significant species pairs co-occur less frequently than would be expected by chance. However, little is known about how co-occurrence structure changes through time. Here we evaluate changes in plant and animal community organization over geological time by quantifying the co-occurrence structure of 359,896 unique taxon pairs in 80 assemblages spanning the past 300 million years. Co-occurrences of most taxon pairs were statistically random, but a significant fraction were spatially aggregated or segregated. Aggregated pairs dominated from the Carboniferous period (307 million years ago) to the early Holocene epoch (11,700 years before present), when there was a pronounced shift to more segregated pairs, a trend that continues in modern assemblages. The shift began during the Holocene and coincided with increasing human population size and the spread of agriculture in North America. Before the shift, an average of 64% of significant pairs were aggregated; after the shift, the average dropped to 37%. The organization of modern and late Holocene plant and animal assemblages differs fundamentally from that of assemblages over the past 300 million years that predate the large-scale impacts of humans. Our results suggest that the rules governing the assembly of communities have recently been changed by human activity.