OBJECTIVES/GOALS: Antibiotic treatment sets the stage for intestinal domination by Candida albicanswhich is necessary for development of invasive disease, but the resources driving this bloom remain poorly defined. We sought to determine these factors in order to design novel prophylaxis strategies for reducing gastrointestinal (GI) colonization. METHODS/STUDY POPULATION: We initially developed a generalizable framework, termed metabolic footprinting to determine the metabolites C. albicanspreferentially uses in the mouse GI tract. After identifying the metabolites C. albicansutilizes, we usedin vitro growth assays in the presence and absence of oxygen to validate out metabolomics findings. We next determined if a probiotic E. coli that utilizes oxygen would reduce C. albicanscolonization compared to a mutant E. coli that could not respire oxygen. Finding that oxygen was a necessary resource, we utilized germ-free mice to determine if Clostridiaspp. known to reduce GI oxygen would prevent C. albicanscolonization. Lastly, we sought to see if 5-aminosalicylic acid (5-ASA) could prevent C. albicanscolonization. RESULTS/ANTICIPATED RESULTS: We found that C. albicans preferentially utilizes simple carbohydrates including fructo-oligosaccharides (e.g., 1-kestose), disaccharides (e.g., β-gentiobiose), and alcoholic sugars (e.g., sorbitol) and is able to grow in vitro on minimal media supplemented with either of these nutrients. However, in the hypoxic environment that is found in the “healthy” colon, C. albicans cannot utilize these nutrients. We next found that pre-colonization in a mouse model with a probiotic E. coli significantly reduced C. albicanscolonization, but the mutant E. coli had no effect on colonization. We next showed that Clostridia supplementation restored GI hypoxia and reduced C. albicanscolonization. Remarkably, we found that 5-ASA significantly reduced GI colonization of C. albicans. DISCUSSION/SIGNIFICANCE: We have shown that C. albicans requires oxygen to colonize the GI tract. Importantly, we found that 5-ASA can prevent an antibiotic mediated bloom of C. albicans by restoring GI hypoxia, which warrants additional studies to determine if 5-ASA can be used as an adjunctive prophylactic treatment in high risk patients.

The personalised oncology paradigm remains challenging to deliver despite technological advances in genomics-based identification of actionable variants combined with the increasing focus of drug development on these specific targets. To ensure we continue to build concerted momentum to improve outcomes across all cancer types, financial, technological and operational barriers need to be addressed. For example, complete integration and certification of the ‘molecular tumour board’ into ‘standard of care’ ensures a unified clinical decision pathway that both counteracts fragmentation and is the cornerstone of evidence-based delivery inside and outside of a research setting. Generally, integrated delivery has been restricted to specific (common) cancer types either within major cancer centres or small regional networks. Here, we focus on solutions in real-world integration of genomics, pathology, surgery, oncological treatments, data from clinical source systems and analysis of whole-body imaging as digital data that can facilitate cost-effectiveness analysis, clinical trial recruitment, and outcome assessment. This urgent imperative for cancer also extends across the early diagnosis and adjuvant treatment interventions, individualised cancer vaccines, immune cell therapies, personalised synthetic lethal therapeutics and cancer screening and prevention. Oncology care systems worldwide require proactive step-changes in solutions that include inter-operative digital working that can solve patient centred challenges to ensure inclusive, quality, sustainable, fair and cost-effective adoption and efficient delivery. Here we highlight workforce, technical, clinical, regulatory and economic challenges that prevent the implementation of precision oncology at scale, and offer a systematic roadmap of integrated solutions for standard of care based on minimal essential digital tools. These include unified decision support tools, quality control, data flows within an ethical and legal data framework, training and certification, monitoring and feedback. Bridging the technical, operational, regulatory and economic gaps demands the joint actions from public and industry stakeholders across national and global boundaries.

Until the past half-century, all agriculture and land management was framed by local institutions strong in social capital. But neoliberal forms of development came to undermine existing structures, thus reducing sustainability and equity. The past 20 years, though, have seen the deliberate establishment of more than 8 million new social groups across the world. This restructuring and growth of rural social capital within specific territories is leading to increased productivity of agricultural and land management systems, with particular benefits for those previously excluded. Further growth would occur with more national and regional policy support.

Little is known about terrestrial climate dynamics in the Levant during the penultimate interglacial-glacial period. To decipher the palaeoclimatic history of the Marine Oxygen Isotope Stage (MIS) 6 glacial period, a well-dated stalagmite (~194 to ~154 ka) from Kanaan Cave on the Mediterranean coast in Lebanon was analyzed for its petrography, growth history, and stable isotope geochemistry. A resolved climate record has been recovered from this precisely U–Th dated speleothem, spanning the late MIS 7 and early MIS 6 at low resolution and the mid–MIS 6 at higher resolution. The stalagmite grew discontinuously from ~194 to ~163 ka. More consistent growth and higher growth rates between ~163 and ~154 ka are most probably linked to increased water recharge and thus more humid conditions. More distinct layering in the upper part of the speleothem suggests strong seasonality from ~163 ka to ~154 ka. Short-term oxygen and carbon isotope excursions were found between ~155 and ~163 ka. The inferred Kanaan Cave humid intervals during the mid–MIS 6 follow variations of pollen records in the Mediterranean basins and correlate well with the synthetic Greenland record and East Asian summer monsoon interstadial periods, indicating short warm/wet periods similar to the Dansgaard-Oeschger events during MIS 4–3 in the eastern Mediterranean region.

Investigating the human dimension of conservation science warrants an interdisciplinary approach. Criminologists and criminal justice scholars have begun to empirically examine various issues that are directly related to conservation, including wildlife law enforcement. This qualitative study of job satisfaction among law enforcement rangers in a protected area in Uganda contributes to both criminal justice and conservation science. Based on interviews and participant observation we identified four main themes that contributed positively to the job satisfaction of rangers: their role in aiding Uganda's conservation efforts and national development; financial stability and familial support; conducting frontline work and establishing ownership of the Park; and opportunities for personal and social development. We discuss the implications of our findings for Park management capacity building as well as for future interdisciplinary and qualitative scholarship in conservation science.