Thinking differently about sustainability: experiences from the UK Open University

Systems thinking is often invoked as a panacea for dealing with issues of sustainable development. Imperatives towards being more holistic - getting the bigger picture – are often coupled with a need for greater interdisciplinarity - joined-up-thinking – particularly amongst triple bottom line disciplines of economics, social studies and natural sciences. So why are systems thinking courses not more prevalent? And how might the teaching of systems thinking enhance the value of thinking differently about sustainable development? The Open University, UK, is a recognised international leader in the provision of Systems education for over 40 years. More recent experiences with the launch of a postgraduate Systems Thinking in Practice suite of qualifications at Certificate, Diploma, and Masters level, suggest an appetite for systems thinking amongst mature-age part-time students from a variety of professional backgrounds with an interest in learning for sustainability. This paper outlines three key features of the two core modules of the programme - epistemic understanding, active pedagogy, and design praxis. Significantly, these attributes have helped to complement rather than replace existing skill-sets amongst professionals from different sectors working in the field of sustainable development

Teaching effective collaborative information delivery and management

This paper explores a pedagogical approach to teaching construction students how to plan, execute and monitor an efficient collaborative information delivery plan from the perspective of managing scope of work, time, resources and communication. This study extends the work of similar studies that tasked students with developing BIM process maps to gauge any shift in the students’ perception on their ability to map the process. In this context, students in the final year of an undergraduate construction management program participate in a team-based project to plan, execute, update and evaluate the efficiency of their collaborative information delivery plan. To plan this process, the students use references including both UK-based BIM Level 2 standards and US-based CIC BIM Project Execution Planning Guide. Through a semester-long sequence of modeling and planning activities, the students specifically aim to address the following learning objectives: (i) define and allocate project- and information delivery responsibilities; (ii) identify information workflows and respective tasks with estimated durations, and (iii) execute and update their plan to record actual tasks, durations and outcomes. Comparing the initial and executed plan would provide the students with the basis to reflect on the influence of formal planning guides on their understanding of efficient collaborative information management and delivery. In this aspect, the study contributes to the knowledge of how to pedagogically deploy industry-oriented process planning approaches for effectively teaching roles and responsibilities for engaging in interdisciplinary teams

Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma

BACKGROUND Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. METHODS We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. RESULTS Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2'antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). CONCLUSIONS Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renalcell carcinoma consisted of at least three subtypes based on molecular and phenotypic features

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Summary Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

Physician knowledge, practice patterns, and barriers encountered regarding guideline-concordant use of bone modifying agents for prostate cancer.

BACKGROUND: Guidelines recommend bone-modifying agents (BMAs) for patients with castrate-resistant prostate cancer (CRPC) and bone metastasis, but not for castrate-sensitive prostate cancer (CSPC). Physicians beliefs and practices regarding BMA therapy are poorly understood. METHODS: This was a qualitative interview study with embedded Likert-scale elements. Study participants were physicians who treat prostate cancer, located within an academic cancer center or an affiliated community-based network. Participants were asked about their experiences and practice patterns regarding BMA therapy. Participants used Likert-scale items to identify the most common barriers to guideline-concordant BMA use and the most effective potential interventions. Participants were subsequently asked to rank the three most common barriers and the three most effective interventions to reduce underuse (for CRPC) and overuse (for CSPC). RESULTS: Nineteen physicians were invited and 15 participated; one physician did not answer some questions as outside of their practice scope. All were aware of the recommendation for BMAs in CRPC. 14% (2/14) were unaware of the recommendation against BMA use for CSPC; an additional 29% (4/14) believed that BMA use could be appropriate for CSPC depending on the metastatic disease burden. 36% (5/14) were unaware of recommendations for screening and treatment of low bone mineral density. The most common barriers (occurring often or sometimes ) were obtaining dental clearance (11/15) and insufficient clinic time (6/15). The interventions identified as most effective to reduce underuse were dental navigation (11/15) and electronic medical record (EMR)-based guidance (9/15). The interventions identified as most effective to reduce overuse were peer-to-peer education (14/15) and EMR-based guidance (13/15). CONCLUSIONS: Awareness of guideline recommendations for screening and treatment of low bone mineral density and against BMA use for CSPC was good, but not complete. Dental navigation, peer-to-peer education, and EMR-based guidance were preferred intervention strategies to improve guideline-concordant use

The Salivary Mycobiome Contains 2 Ecologically Distinct Mycotypes.

A broad range of fungi has been detected in molecular surveys of the oral mycobiome. However, knowledge is still lacking on interindividual variability of these communities and the ecologic and clinical significance of oral fungal commensals. In this cross-sectional study, we use internal transcribed spacer 1 amplicon sequencing to evaluate the salivary mycobiome in 59 subjects, 36 of whom were scheduled to receive cancer chemotherapy. Analysis of the broad population structure of fungal communities in the whole cohort identified 2 well-demarcated genus-level community types (mycotypes), wit

The Salivary Mycobiome contains 2 ecologically distinct Mycotypes

A broad range of fungi has been detected in molecular surveys of the oral mycobiome. However, knowledge is still lacking on interindividual variability of these communities and the ecologic and clinical significance of oral fungal commensals. In this cross-sectional study, we use internal transcribed spacer 1 amplicon sequencing to evaluate the salivary mycobiome in 59 subjects, 36 of whom were scheduled to receive cancer chemotherapy. Analysis of the broad population structure of fungal communities in the whole cohort identified 2 well-demarcated genus-level community types (mycotypes), with Candida and Malassezia as the main taxa driving cluster partitioning. The Candida mycotype had lower diversity than the Malassezia mycotype and was positively correlated with cancer and steroid use in these subjects, smoking, caries, utilizing a removable prosthesis, and plaque index. Mycotypes were also associated with metabolically distinct bacteria indicative of divergent oral environments, with aciduric species enriched in the Candida mycotype and inflammophilic bacteria increased in the Malassezia mycotype. Similar to their fungal counterparts, coexisting bacterial communities associated with the Candida mycotype showed lower diversity than those associated with the Malassezia mycotype, suggesting that common environmental pressures affected bacteria and fungi. Mycotypes were also seen in an independent cohort of 24 subjects, in which cultivation revealed Malassezia as viable oral mycobiome members, although the low-abundance Malassezia sympodialis was the only Malassezia species recovered. There was a high degree of concordance between the molecular detection and cultivability of Candida, while cultivation showed low sensitivity for detection of the Malassezia mycotype. Overall, our work provides insights into the oral mycobiome landscape, revealing 2 community classes with apparently distinct ecologic constraints and specific associations with coexisting bacteria and clinical parameters. The utility of mycotypes as biomarkers for oral diseases warrants further study.United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Dental & Craniofacial Research (NIDCR) R01DE021578 UConn Health General Clinical Research Center M01RR00619