This paper presents an optimization framework for prioritizing sites for wetlands restoration on a watershed or landscape scale. The framework is designed for analyzing the potential environmental ...impacts of alternative management strategies while accounting for economic constraints, thereby aiding decision makers in explicitly considering multiple management objectives. The modeling strategy consists of two phases. First, relationships between the configuration of land use types in a watershed and valued ecosystem services are specified mathematically. Second, those functions are incorporated into a spatial optimization model that allows comparisons of the expected environmental impacts and economic costs of management strategies that change the configuration of land use in the watershed. By way of a stylized example, this paper develops the general structure of the framework, presents simulation results based on two production functions for ecosystem services, and discusses the potential utility of the methodology for watershed management.
This paper presents an optimization framework for prioritizing sites for wetlands restoration on a watershed or landscape scale. The framework is designed for analyzing the potential environmental ...impacts of alternative management strategies while accounting for economic constraints, thereby aiding decision makers in explicitly considering multiple management objectives. The modeling strategy consists of two phases. First, relationships between the configuration of land use types in a watershed and valued ecosystem services are specified mathematically. Second, those functions are incorporated into a spatial optimization model that allows comparisons of the expected environmental impacts and economic costs of management strategies that change the configuration of land use in the watershed. By way of a stylized example, this paper develops the general structure of the framework, presents simulation results based on two production functions for ecosystem services, and discusses the potential utility of the methodology for watershed management.
Summary Background Invasive meningococcal disease (IMD) is a worldwide health issue that is potentially preventable with vaccination. In view of its sporadic nature and the high diversity of ...Neisseria meningitidis , epidemiological surveillance incorporating detailed isolate characterisation is crucial for effective control and understanding the evolving epidemiology of IMD. The Meningitis Research Foundation Meningococcus Genome Library (MRF-MGL) exploits whole-genome sequencing (WGS) for this purpose and presents data on a comprehensive and coherent IMD isolate collection from England and Wales via the internet. We assessed the contribution of these data to investigating IMD epidemiology. Methods WGS data were obtained for all 899 IMD isolates available for England and Wales in epidemiological years 2010–11 and 2011–12. The data had been annotated at 1720 loci, analysed, and disseminated online. Information was also available on meningococcal population structure and vaccine (Bexsero, GlaxoSmithKline, Brentford, Middlesex, UK) antigen variants, which enabled the investigation of IMD-associated genotypes over time and by patients' age groups. Population genomic analyses were done with a hierarchical gene-by-gene approach. Findings The methods used by MRF-MGL efficiently characterised IMD isolates and information was provided in plain language. At least 20 meningococcal lineages were identified, three of which (hyperinvasive clonal complexes 41/44 lineage 3, 269 lineage 2, and 23 lineage 23) were responsible for 528 (59%) of IMD isolates. Lineages were highly diverse and showed evidence of extensive recombination. Specific lineages were associated with IMD in particular age groups, with notable diversity in the youngest and oldest individuals. The increased incidence of IMD from 1984 to 2010 in England and Wales was due to successive and concurrent epidemics of different lineages. Genetically, 74% of isolates were characterised as encoding group B capsules: 16% group Y, 6% group W, and 3% group C. Exact peptide matches for individual Bexsero vaccine antigens were present in up to 26% of isolates. Interpretation The MRF-MGL represents an effective, broadly applicable model for the storage, analysis, and dissemination of WGS data that can facilitate real-time genomic pathogen surveillance. The data revealed information crucial to effective deployment and assessment of vaccines against N meningitidis. Funding Meningitis Research Foundation, Wellcome Trust, Public Health England, European Union.
Acetylation of histones by lysine acetyltransferases (KATs) is essential for chromatin organization and function
. Among the genes coding for the MYST family of KATs (KAT5-KAT8) are the oncogenes ...KAT6A (also known as MOZ) and KAT6B (also known as MORF and QKF)
. KAT6A has essential roles in normal haematopoietic stem cells
and is the target of recurrent chromosomal translocations, causing acute myeloid leukaemia
. Similarly, chromosomal translocations in KAT6B have been identified in diverse cancers
. KAT6A suppresses cellular senescence through the regulation of suppressors of the CDKN2A locus
, a function that requires its KAT activity
. Loss of one allele of KAT6A extends the median survival of mice with MYC-induced lymphoma from 105 to 413 days
. These findings suggest that inhibition of KAT6A and KAT6B may provide a therapeutic benefit in cancer. Here we present highly potent, selective inhibitors of KAT6A and KAT6B, denoted WM-8014 and WM-1119. Biochemical and structural studies demonstrate that these compounds are reversible competitors of acetyl coenzyme A and inhibit MYST-catalysed histone acetylation. WM-8014 and WM-1119 induce cell cycle exit and cellular senescence without causing DNA damage. Senescence is INK4A/ARF-dependent and is accompanied by changes in gene expression that are typical of loss of KAT6A function. WM-8014 potentiates oncogene-induced senescence in vitro and in a zebrafish model of hepatocellular carcinoma. WM-1119, which has increased bioavailability, arrests the progression of lymphoma in mice. We anticipate that this class of inhibitors will help to accelerate the development of therapeutics that target gene transcription regulated by histone acetylation.
The general equilibrium (GE) effects of environmental policies have long been a concern of stake-holders and researchers due to the potential for economy-wide feedbacks that could affect the ...efficiency and incidence of those policy interventions. Concerns about the potential economy-wide effects of environmental regulations are most often focused on the costs of compliance, while the beneficial outcomes of these policies are typically excluded from GE analyses. However, both regulators and researchers have recently shown interest in general equilibrium (GE) assessments of the benefits and economy-wide impacts of mortality risk reductions. GE models are able to capture feedbacks that may be important for understanding the welfare implications of environmental policies. In a study of the cumulative effects of the Clean Air Act, the U.S. Environmental Protection Agency found estimates for the benefits of air quality improvements that were more than an order of magnitude smaller under a GE approach com- pared with a traditional partial equilibrium (PE) approach. It has been suggested that these results are evidence that the PE benefits of environmental regulations are implausibly large. However, previous GE analyses of environmental or public health policies have characterized the expected health improvements using highly simplified approximations whose validity have yet to be closely examined. We present the first explicit characterization of mortality risk changes in a GE model applied to environmental regulations. We find that reductions in mortality risks can have significant GE feedbacks and that these effects are important for estimating the benefits, economic impacts, and potentially the costs of environmental policies. Our results suggest that the previously used approximations for incorporating mortality risk reductions in GE models may be the main source of the large discrepancies between GE and PE benefits estimates in previous studies, and may introduce sign
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