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As the nation’s public health agency, CDC recognizes that climate change poses a multifaceted and potentially significant threat to domestic public health. To facilitate climate change preparedness in public health, the agency developed the Climate and Health Program, which is housed in the National Center for Environmental Health. The Program’s mission is to translate science for public health partners, develop decision support tools to facilitate climate change adaptation in public health, and to serve as a credible leader in planning for the human health impacts of a changing climate. Since its formation, the Program has worked to articulate a public health approach to climate change and integrate science from public health and other sectors to facilitate public health adaptation efforts. The Program has developed an adaptive management framework for public health, the BRACE framework, and is working cooperatively with several state and local health departments to pursue an evidence-based approach to climate change adaptation. As public health’s expertise and experience grows, the Climate and Health Program will work to continue disseminating relevant information for the increasing number of public health practitioners focused on reducing the adverse health effects of climate change.

Innovative breeds of sugar cane yield up to 2.5 times as much organic matter as conventional breeds, resulting in a great potential for biogas production. The use of biogas production as a complementary solution to conventional and second-generation ethanol production in Brazil may increase the energy produced per hectare in the sugarcane sector. Herein, it was demonstrated that through ensiling, energy cane can be conserved for six months, the stored cane can then be fed into a continuous biogas process. This approach is necessary to achieve year-round biogas production at an industrial scale. Batch tests revealed specific biogas potentials between 400 and 600 LN/kgVS for both the ensiled and non-ensiled energy cane, and the specific biogas potential of a continuous biogas process fed with ensiled energy cane was in the same range. Peak biogas losses through ensiling of up to 27% after six months were observed. Finally, compared with second-generation ethanol production using energy cane, the results indicated that biogas production from energy cane may lead to higher energy yields per hectare, with an average energy yield of up to 162 MWh/ha. Finally, the Farm&sup2, CBG concept is introduced, showing an approach for decentralized biogas production.

A hallmark of metastasis is the adaptation of tumor cells to new environments. Although it is well established that the metabolic milieu of the brain is severely deprived of nutrients, particularly the amino acids serine and its catabolite glycine, how brain metastases rewire their metabolism to survive in the nutrient-limited environment of the brain is poorly understood. Here we demonstrate that cell-intrinsic de novo serine synthesis is a major determinant of brain metastasis. Whole proteome comparison of triple-negative breast cancer (TNBC) cells that differ in their capacity to colonize the brain reveals that 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes the rate-limiting step of glucose-derived serine synthesis, is the most significantly upregulated protein in cells that efficiently metastasize to the brain. Genetic silencing or pharmacological inhibition of PHGDH attenuated brain metastasis and improved overall survival in mice, whereas expression of catalytically active PHGDH in a non-brain trophic cell line promoted brain metastasis. Collectively, these findings indicate that nutrient availability determines serine synthesis pathway dependence in brain metastasis, and suggest that PHGDH inhibitors may be useful in the treatment of patients with cancers that have spread to the brain.Statement of SignificanceOur study highlights how limited serine and glycine availability within the brain microenvironment potentiates tumor cell sensitivity to serine synthesis inhibition. This finding underscores the importance of studying cancer metabolism in physiologically-relevant contexts, and provides a rationale for using PHGDH inhibitors to treat brain metastasis.

The metabolic milieu of the brain is severely deprived of nutrients, including the amino acids serine and its catabolite glycine. The metabolic rewiring required for tumor cells to survive in the nutrient-limited environment of the brain and the metabolic vulnerabilities this confers are poorly understood. Here we demonstrate that cell-intrinsic de novo serine synthesis is a major determinant of triple-negative breast cancer (TNBC) brain metastasis. Whole proteome comparison of TNBC cells that differ in their capacity to colonize the brain reveals that 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes the rate-limiting step of glucose-derived serine synthesis, is the most significantly upregulated protein in cells that efficiently metastasize to the brain. Expression of catalytically active PHGDH in a non-brain trophic cell line promoted brain metastasis. Furthermore, genetic silencing or pharmacological inhibition of PHGDH attenuated brain metastasis burden in mice. These findings indicate that nutrient availability determines serine synthesis pathway dependence in brain metastasis, and suggest that PHGDH inhibitors may be useful in the treatment of patients with cancers that have spread to the brain. Citation Format: Bryan Ngo, Eugenie Kim, Sophia Doll, Sophia Bustraan, Alba Luengo, Shawn M. Davidson, Ahmed Ali, Gino Ferraro, Diane Kang, Jing Ni, Roger Liang, Ariana Plasger, Edward R. Kastenhuber, Roozbeh Eskandari, Sarah Bacha, Roshan Sriram, Benjamin D. Stein, Samuel F. Bakhoum, Edouard Mullarky, Matija Snuderl, Nello Mainolfi, Vipin Suri, Adam Friedman, Mark Manfredi, David M. Sabatini, Drew Jones, Min Yu, Jean J. Zhao, Rakesh K. Jain, Matthew G. Vander Heiden, Matthias Mann, Lewis C. Cantley, Michael E. Pacold. Nutrient scarcity confers breast cancer brain metastasis sensitivity to serine synthesis pathway inhibition [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5712.

Climate change is anticipated to have several adverse health impacts. Managing these risks to public health requires an iterative approach. As with many risk management strategies related to climate change, using modeling to project impacts, engaging a wide range of stakeholders, and regularly updating models and risk management plans with new information—hallmarks of adaptive management—are considered central tenets of effective public health adaptation. The Centers for Disease Control and Prevention has developed a framework, entitled Building Resilience Against Climate Effects, or BRACE, to facilitate this process for public health agencies. Its five steps are laid out here. Following the steps laid out in BRACE will enable an agency to use the best available science to project likely climate change health impacts in a given jurisdiction and prioritize interventions. Adopting BRACE will also reinforce public health’s established commitment to evidence-based practice and institutional learning, both of which will be central to successfully engaging the significant new challenges that climate change presents.

Concentrations of 24 trace metals were assessed in gravid ovaries and in muscle of female juvenile and adult female goldeye (Hiodon alosoides), a fish with both low annual growth (16 g/year as adults) and a long life span (maximum longevity of 30 years). It was hypothesized that adult fish with these life-history characteristics would maintain stable concentrations of metals in their tissues with higher levels of essential elements compared with those that are potentially toxic. As hypothesized, the concentration of most metals in muscle of adult female goldeye was similar at all ages, suggesting that uptake and excretion of metals was equal. Mercury was a notable exception. Total Hg concentrations in muscle of adults increased throughout life from a mean of 206 ng/g wet weight at age 8 to 809 ng/g at age 28, or by 26.2 ng/g/year. Concentrations of Hg were low in ovaries (mean 21.1 ng/g wet wt) compared to the mean for muscle, only 7% of the concentration in muscle. This was the lowest percent of muscle concentration of all 24 metals. Concentrations of Al, Ba, La, V, and Mn were significantly greater in muscle of juveniles and in ovaries than in muscle of adults. Concentrations of 13 metals were higher in ovaries relative to muscle, seven were similar, and four were depleted. Silver was enriched by over 50-fold in ovaries. Overall, the present study suggests that low concentrations of some metals in muscle of adult female goldeye, relative to concentrations in female juveniles and ovaries, may be maintained in part by transfer of metals to the external environment in eggs at spawning.

Sediment traps were deployed in the three major basins of Lake Erie, and the central (Mississauga) basin of Lake Ontario, and refurbished seasonally over the period 2000-2002. In Lake Ontario, sediment down-flux rates and corresponding contaminant down-flux rates were highest in winter during periods of unstratified thermal conditions, and generally increased with depth due to the influence of resuspended bottom sediments during all sampling periods. Lake Ontario suspended sediments exhibited the highest concentrations of metals; concentrations of mercury and lead frequently exceeded guideline values for bottom sediments. Contaminant levels in Lake Ontario suspended sediments were similar to concentrations in bottom sediments in the same area. There was a spatial trend toward higher suspended sediment metals concentrations from the eastern basin to the western basin of Lake Erie, which is similar to the trend in bottom sediment contamination. In the eastern basin of Lake Erie, which is the deepest area of the lake, there was no trend in down-flux rate with depth in 2001; however, down-flux rates increased with depth in 2002. Suspended sediments in the western basin of Lake Erie were determined to be largely resuspended bottom sediments; all western basin samples collected in the study exceeded the guideline value for mercury (0.486 microg/g).

A common way to model infill-frame interaction is the use equivalent strut macromodels. In most cases these are compression only resistant truss elements defined with a multi-linear axial-force / axial-displacement law. The main difficulty in using this approach is to correctly calibrate such a force-displacement curve (slope of ascending and post-peak branches, critical yielding, peak and residual forces) because of the large number of variables (mechanical and elastic properties of materials) and the different possible damage mechanisms activated for the frame-infill system. Another possible way is using fiber-section elements as diagonal struts. In this case the force-displacement law is substituted by a stressstrain curve. In both cases a reliable definition of inelastic response of the strut, based on mechanical approaches, which are valid in general is not easy, as most of models provide rules valid for specific typologies of infills (e.g. weak or strong infills) and frames (e.g. concrete or steel frames). Based on this, the paper proposes the use of fiber-section diagonal struts with a concrete-type stress-strain relationship calibrated using a semi-empirical approach. The Kent-Scott-Park model, depending on four parameters, is used as reference constitutive law for the strut. Experimental data and additional numerical simulations are used to derive semiempirical correlations linking geometrical and mechanical properties of the frame-infill system to the aforementioned parameters governing nonlinear response of the diagonal. Analytical expressions of the best fitting curves are finally provided and suggested as design equation.