The Emergence of Rural Artistic Havens: A First Look

Nearly all applied research on arts activity has examined phenomena in metropolitan areas. Findings from this past research confirm an arts specialization in a limited number of cities. This paper finds a similar pattern in nonmetropolitan areas, where a limited number of counties maintain or develop a distinct specialization in the arts. We document the emergence of these "rural artistic havens" and identify county characteristics associated with the attraction of performing, fine, and applied artists. The implications of these findings for rural development strategies focusing on the arts are discussed.arts activity, built amenities, creative class, logistic regression, natural amenities, tourism development, Community/Rural/Urban Development,

SnapShot: Tumor evolution

Understanding how tumors grow and evolve over time is crucial to help shed light on the underlying reasons why treatments fail and tumors metastasize. This SnapShot provides a brief introduction into the main concepts of tumor evolution

Multiple Instance Learning for Heterogeneous Images: Training a CNN for Histopathology

Multiple instance (MI) learning with a convolutional neural network enables end-to-end training in the presence of weak image-level labels. We propose a new method for aggregating predictions from smaller regions of the image into an image-level classification by using the quantile function. The quantile function provides a more complete description of the heterogeneity within each image, improving image-level classification. We also adapt image augmentation to the MI framework by randomly selecting cropped regions on which to apply MI aggregation during each epoch of training. This provides a mechanism to study the importance of MI learning. We validate our method on five different classification tasks for breast tumor histology and provide a visualization method for interpreting local image classifications that could lead to future insights into tumor heterogeneity

Germline ancestry influences the evolutionary disease course in lung adenocarcinomas

Evolutionary Applications published by John Wiley & Sons Ltd Precision medicine relies on targeting specific somatic alterations present in a patient's tumor. However, the extent to which germline ancestry may influence the somatic burden of disease has received little attention. We estimated the genetic ancestry of non-small-cell lung cancer (NSCLC) patients and performed an in-depth analysis of the influence of genetic ancestry on the evolutionary disease course. Compared with European Americans (EA), African Americans (AA) with lung adenocarcinoma (LUAD) were found to be significantly younger and smoke significantly less. However, LUADs from AAs exhibited a significantly higher somatic mutation burden, with a more pronounced tobacco carcinogen footprint and increased frequencies of alterations affecting cancer genes. Conversely, no significant differences were observed between lung squamous cell carcinomas (LUSC) from EAs and AAs. Our results suggest germline ancestry influences the somatic evolution of LUAD but not LUSC

The Marin County Livestock Protection Program: 15 Years in Review

Predation by wild carnivores challenges livestock producers worldwide. To reduce or offset losses due to predation, a variety of predator control methods and compensation schemes have been developed. In 2001, Marin County, California, USA replaced its U.S. Department of Agriculture Wildlife Services (WS) cooperative predator damage management program with a county-run program that emphasized nonlethal methods for preventing and controlling coyote (Canis latrans) predation on domestic sheep (Ovis aries). This new Livestock Protection Program (LPP) cost-shared with livestock producers’ efforts to improve fencing, obtain and maintain guard animals, and other such nonlethal methods, and initially it compensated producers for documented losses to predators. In 2006, 5 years into the program, 17 sheep producers were surveyed to compare the former WS program to the LPP with regard to rancher satisfaction and preferences, lethality to predators, livestock losses, uses of nonlethal predator deterrent techniques, and costs. In 2016, 15 years after the program was replaced by a county-administered nonlethal program, we surveyed sheep producers to determine if their perceptions of the program had changed. Although the lack of standardized data collection complicated our evaluation, the number of sheep and lambs produced in Marin County has continued to decline; 5 producers left the sheep business and others who remain graze less acreage with smaller flocks, predation by coyotes remains a high concern to producers, and producers are generally dissatisfied with the Livestock Protection Program. Recommendations include increased programmatic funding for management practices, payments for losses, and seasonal hiring of wildlife specialists during critical times, especially during lambing seasons

Increasing carbon sequestration of working prairie by reducing invasive species in a fire and grazing system

The investigators looked at one method for curbing invasive species that limit carbon sequestration potential for tallgrass prairie stands. They also learned that grasslands dominated by either warm-season, cool-season, or mixed stands are likely equal in their carbon sequestration potential

Differential binding affinity of mutated peptides for MHC class I is a predictor of survival in advanced lung cancer and melanoma

Background: Cancer mutations generate novel (neo-)peptides recognised by T cells, but the determinants of recognition are not well characterised. The difference in predicted class I major histocompatibility complex (MHC-I) binding affinity between wild-type and corresponding mutant peptides (differential agretopicity index; DAI) may reflect clinically relevant cancer peptide immunogenicity. Our aim was to explore the relationship between DAI, measures of immune infiltration and patient outcomes in advanced cancer. Patients and methods: Cohorts of patients with advanced non-small-cell lung cancer (NSCLC; LUAD, n = 66) and melanoma (SKCM, n = 72) were obtained from The Cancer Genome Atlas. Three additional cohorts of immunotherapy treated patients with advanced melanoma (total n = 131) and NSCLC (n = 31) were analysed. Neopeptides and their clonal status were defined using genomic data. MHC-I binding affinity was predicted for each neopeptide and DAI values summarised as the sample mean DAI. Correlations between mean DAI and markers of immune activity were evaluated using measures of lymphocyte infiltration and immune gene expression. Results: In univariate and multivariate analyses, mean DAI significantly correlated with overall survival in 3/5 cohorts, with evidence of superiority over nonsynonymous mutational and neoantigen burden. In these cohorts, the effect was seen for mean DAI of clonal but not subclonal peptides. In SKCM, the association between mean DAI and survival bordered significance (P = 0.068), reaching significance in an immunotherapy-treated melanoma cohort (P = 0.003). Mean DAI but not mutational nor neoantigen burden was positively correlated with independently derived markers of immune infiltration in both SKCM (P = 0.027) and LUAD (P = 0.024). Conclusions: The association between mean DAI, survival and measures of immune activity support the hypothesis that DAI is a determinant of cancer peptide immunogenicity. Investigation of DAI as a marker of immunologically relevant peptides in further datasets and future clinical studies of neoantigen based immunotherapies is warranted

Tracking Cancer Evolution through the Disease Course.

During cancer evolution, constituent tumor cells compete under dynamic selection pressures. Phenotypic variation can be observed as intratumor heterogeneity, which is propagated by genome instability leading to mutations, somatic copy-number alterations, and epigenomic changes. TRACERx was set up in 2014 to observe the relationship between intratumor heterogeneity and patient outcome. By integrating multiregion sequencing of primary tumors with longitudinal sampling of a prospectively recruited patient cohort, cancer evolution can be tracked from early- to late-stage disease and through therapy. Here we review some of the key features of the studies and look to the future of the field. SIGNIFICANCE: Cancers evolve and adapt to environmental challenges such as immune surveillance and treatment pressures. The TRACERx studies track cancer evolution in a clinical setting, through primary disease to recurrence. Through multiregion and longitudinal sampling, evolutionary processes have been detailed in the tumor and the immune microenvironment in non-small cell lung cancer and clear-cell renal cell carcinoma. TRACERx has revealed the potential therapeutic utility of targeting clonal neoantigens and ctDNA detection in the adjuvant setting as a minimal residual disease detection tool primed for translation into clinical trials

The effect of age on the acquisition and selection of cancer driver mutations in sun-exposed normal skin

BACKGROUND: The accumulation of somatic mutations contributes to ageing and cancer. Sunlight is the principal aetiological factor associated with skin cancer development. However, genetic and phenotypic factors also contribute to skin cancer risk. This study aimed at exploring the role of photoaging, as well as other well-known epidemiological risk factors, in the accumulation of somatic mutations in cancer-free human epidermis. MATERIAL AND METHODS: We deeply sequenced 46 genes in normal skin biopsies from 127 healthy donors, from which phenotypic data (including age, pigmentation-related genotype and phenotype) and sun exposure habits were collected. We determined the somatic mutational burden, mutational signatures, clonal selection and frequency of driver mutations in all samples. RESULTS: Our results reveal an exponential accumulation of UV-related somatic mutations with age, matching skin cancer incidence. The increase of mutational burden is in turn modified by an individual's skin phototype. Somatic mutations preferentially accumulated in cutaneous squamous cell carcinoma (cSCC) cancer genes and clonally expanded with age, with distinct mutational processes underpinning different age groups. Our results suggest loss of fidelity in transcription-coupled repair later in life. CONCLUSION: Our findings reveal that aging is not only associated with an exponential increase in the number of somatic mutations accumulated in normal epidermis, but also with selection and expansion of cancer-associated mutations. Aged, sun-exposed normal skin is thus an extended mosaic of multiple clones with driver mutations, poised for the acquisition of transforming events