Keeping Data Science Broad: Negotiating the Digital and Data Divide Among Higher Education Institutions

The goal of the “Keeping Data Science Broad” series of webinars and workshops was to garner community input into pathways for keeping data science education broadly inclusive across sectors, institutions, and populations. Input was collected from data science programs across the nation, either traditional or alternative, and from a range of institution types including community colleges, minority-led and minority-serving institutions, liberal arts colleges, tribal colleges, universities, and industry partners. The series consisted of two webinars (August 2017 and September 2017) leading up to a workshop (November 2017) exploring the future of data science education and workforce at institutions of higher learning that are primarily teaching-focused. A third follow-up webinar was held after the workshop (January 2018) to report on outcomes and next steps. Program committee members were chosen to represent a broad spectrum of communities with a diversity of geography (West, Northeast, Midwest, and South), discipline (Computer Science, Math, Statistics, and Domains), as well as institution type (Historically Black Colleges and Universities (HBCU’s), Hispanic-Serving Institutions (HSI’s), other Minority-Serving Institutions (MSI\u27s), Community College\u27s (CC’s), 4-year colleges, Tribal Colleges, R1 Universities, Government and Industry Partners)

Keeping Data Science Broad: Negotiating the Digital and Data Divide Among Higher Education Institutions

The goal of the “Keeping Data Science Broad” series of webinars and workshops was to garner community input into pathways for keeping data science education broadly inclusive across sectors, institutions, and populations. Input was collected from data science programs across the nation, either traditional or alternative, and from a range of institution types including community colleges, minority-led and minority-serving institutions, liberal arts colleges, tribal colleges, universities, and industry partners. The series consisted of two webinars (August 2017 and September 2017) leading up to a workshop (November 2017) exploring the future of data science education and workforce at institutions of higher learning that are primarily teaching-focused. A third follow-up webinar was held after the workshop (January 2018) to report on outcomes and next steps. Program committee members were chosen to represent a broad spectrum of communities with a diversity of geography (West, Northeast, Midwest, and South), discipline (Computer Science, Math, Statistics, and Domains), as well as institution type (Historically Black Colleges and Universities (HBCU’s), Hispanic-Serving Institutions (HSI’s), other Minority-Serving Institutions (MSI\u27s), Community College\u27s (CC’s), 4-year colleges, Tribal Colleges, R1 Universities, Government and Industry Partners)

The evolution of lung cancer and impact of subclonal selection in TRACERx

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource

The evolution of non-small cell lung cancer metastases in TRACERx

Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

A study of the use of colour in seriously-ill, ill and healthy children's spontaneous drawings

This exploratory study examined whether the number of colours seriously-ill and ill children used in their spontaneous drawings varied from those used by healthy children. The potential influence of sex, intellectual ability, anxiety and severity of illness was also examined. Thirty children aged from 4-12, took part in the study. The results confirmed a statistically significant association between illness and a lower number of colours used by children in their first free drawing (p .01) but the level of significance faded over time (drawing No 2 p<.02 and for drawing No. 3 p <.03). However, post-hoc comparisons supported the differences in colour use between ill and healthy children. The investigation also showed that anxiety may have an effect but whether this is related to the size of figures or indeed the size of children's drawings on a page rather than their use of colour is not known. Given that this was an exploratory study using basic measures many questions remain, but the association between colour use in children's drawings and their state of health has been placed on a research footing, and further studies are suggested. The overall aim has been to broaden the field of enquiry into children's drawings to include colour content, placing this clearly within the field of developmental psychology

Enhancing Undergraduate Student Success in STEM Fields through Growth-Mindset and Grit

Concern about graduation rates in higher education has led universities to offer courses that help students develop success skills. Scientist Life Skills, a new course for freshman at Florida A&amp;M University, focuses on helping students matriculate into majors via development of growth mindset, grit, and critical thinking. Here, we assessed the outcomes of this course and explored the associations between building life skills and student success. A series of mindset, grit, and critical-thinking assessment measures were used to collect data before and after the course. Our results showed that the new course achieved its intended goals of providing STEM students with a set of tools that help them seamlessly transition into the university and successfully matriculate through their majors. Specifically, the course design significantly moved students toward a growth-mindset, increased their critical thinking, and their second-semester grade point averages (GPAs). This model life skills course can be adopted in non-STEM areas as well

Cross-Sectional Study of Homeless High Service Utilizers in Los Angeles County Jails: Race, Marginalization and Opportunities for Diversion.

OBJECTIVE: To describe the demographic, legal, and clinical characteristics of a cross-section of incarcerated homeless individuals with the highest utilization of Los Angeles (LA) County public services in order to increase opportunities for focused jail diversion. METHODS: The 5% list (N=5,905 in February 2018), LA Countys list of homeless individuals with the highest 5% utilization of public services, was cross-matched with the total jail population to obtain a sample of 333 homeless high-utilizing individuals. This sample was compared with the overall jail population (N=17,121) from publicly available aggregate data by Chi-square testing. RESULTS: 84% of the high-utilizing sample were male, 38% Black, 37% Hispanic, 21% White. 67% were prescribed psychiatric medication. Compared with the overall jail population, the sample was significantly older, with a greater proportion of Black and White persons, and a lesser proportion of Hispanic individuals relative to the overall jail population. A significantly greater proportion of high-utilizing individuals faced misdemeanor charges. CONCLUSION: These data highlight the compounding effects of homelessness, race, and mental illness on carceral and social vulnerability. Findings suggest homeless high utilizers in jail with mental illness are likely to benefit from court-based diversion efforts aimed at housing and treatment

Climate science information needs among natural resource decision-makers in the Northwest US

Managing water resources, air quality, forests, rangelands and agricultural systems in the context of climate change requires a new level of integrated knowledge. In order to articulate a role for university-based research teams as providers of climate services, this paper analyzes environmental change concerns and expectations about climate models among natural resources decision-makers in the Northwest US. Data were collected during a series of workshops organized by researchers from BioEarth, a regional earth systems modeling initiative. Eighty-three stakeholders from industry, government agencies and non-governmental organizations engaged with a team of academic researchers developing integrated biophysical and economic climate modeling tools. Analysis of transcripts of workshop discussions, surveys, and questionnaires reveals diverse attitudes among stakeholders about: 1) preferred modes of engaging in climate science research, 2) specific concerns and questions about climate change impacts, and 3) the most relevant and usable scope and scale of climate change impacts projections. Diverse concerns and information needs among natural resource decision-makers highlight the need for research teams to define clear and precise goals for stakeholder engagement. Utilizing the skills of research team members who have communication and extension expertise is pivotally important. We suggest impactful opportunities for research teams and natural resource decision-makers to interface and learn from one another. Effective approaches include structuring group discussions to identify gaps in existing climate change impacts information, explicitly considering changing policies, technologies and management practices, and exploring possible unintended consequences of decisions