The fate of steroid estrogens: Partitioning during wastewater treatment and onto river sediments

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Springer Science+Business Media B.V.The partitioning of steroid estrogens in wastewater treatment and receiving waters is likely to influence their discharge to, and persistence in, the environment. This study investigated the partitioning behaviour of steroid estrogens in both laboratory and field studies. Partitioning onto activated sludge from laboratory-scale Husmann units was rapid with equilibrium achieved after 1 h. Sorption isotherms and Kd values decreased in the order 17α-ethinyl estradiol > 17α-estradiol > estrone > estriol without a sorption limit being achieved (1/n >1). Samples from a wastewater treatment works indicated no accumulation of steroid estrogens in solids from primary or secondary biological treatment, however, a range of steroid estrogens were identified in sediment samples from the River Thames. This would indicate that partitioning in the environment may play a role in the long-term fate of estrogens, with an indication that they will be recalcitrant in anaerobic conditions.EPSR

Interpreting Cancer Genomes Using Systematic Host Perturbations by Tumour Virus Proteins

Genotypic differences greatly influence susceptibility and resistance to disease. Understanding genotype-phenotype relationships requires that phenotypes be viewed as manifestations of network properties, rather than simply as the result of individual genomic variations. Genome sequencing efforts have identified numerous germline mutations associated with cancer predisposition and large numbers of somatic genomic alterations. However, it remains challenging to distinguish between background, or “passenger” and causal, or “driver” cancer mutations in these datasets. Human viruses intrinsically depend on their host cell during the course of infection and can elicit pathological phenotypes similar to those arising from mutations. To test the hypothesis that genomic variations and tumour viruses may cause cancer via related mechanisms, we systematically examined host interactome and transcriptome network perturbations caused by DNA tumour virus proteins. The resulting integrated viral perturbation data reflects rewiring of the host cell networks, and highlights pathways that go awry in cancer, such as Notch signalling and apoptosis. We show that systematic analyses of host targets of viral proteins can identify cancer genes with a success rate on par with their identification through functional genomics and large-scale cataloguing of tumour mutations. Together, these complementary approaches result in increased specificity for cancer gene identification. Combining systems-level studies of pathogen-encoded gene products with genomic approaches will facilitate prioritization of cancer-causing driver genes so as to advance understanding of the genetic basis of human cancer

Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins

Genotypic differences greatly influence susceptibility and resistance to disease. Understanding genotype-phenotype relationships requires that phenotypes be viewed as manifestations of network properties, rather than simply as the result of individual genomic variations. Genome sequencing efforts have identified numerous germline mutations, and large numbers of somatic genomic alterations, associated with a predisposition to cancer. However, it remains difficult to distinguish background, or 'passenger', cancer mutations from causal, or 'driver', mutations in these data sets. Human viruses intrinsically depend on their host cell during the course of infection and can elicit pathological phenotypes similar to those arising from mutations. Here we test the hypothesis that genomic variations and tumour viruses may cause cancer through related mechanisms, by systematically examining host interactome and transcriptome network perturbations caused by DNA tumour virus proteins. The resulting integrated viral perturbation data reflects rewiring of the host cell networks, and highlights pathways, such as Notch signalling and apoptosis, that go awry in cancer. We show that systematic analyses of host targets of viral proteins can identify cancer genes with a success rate on a par with their identification through functional genomics and large-scale cataloguing of tumour mutations. Together, these complementary approaches increase the specificity of cancer gene identification. Combining systems-level studies of pathogen-encoded gene products with genomic approaches will facilitate the prioritization of cancer-causing driver genes to advance the understanding of the genetic basis of human cancer

Building a Clinical Research Network in Trauma Orthopaedics: The Major Extremity Trauma Research Consortium (METRC)

OBJECTIVESLessons learned from battle have been fundamental to advancing the care of injuries that occur in civilian life. Equally important is the need to further refine these advances in civilian practice, so they are available during future conflicts. The Major Extremity Trauma Research Consortium (METRC) was established to address these needs.METHODSMETRC is a network of 22 core level I civilian trauma centers and 4 core military treatment centers-with the ability to expand patient recruitment to more than 30 additional satellite trauma centers for the purpose of conducting multicenter research studies relevant to the treatment and outcomes of orthopaedic trauma sustained in the military. Early measures of success of the Consortium pertain to building of an infrastructure to support the network, managing the regulatory process, and enrolling and following patients in multiple studies.RESULTSMETRC has been successful in maintaining the engagement of several leading, high volume, level I trauma centers that form the core of METRC; together they operatively manage 15,432 major fractures annually. METRC is currently funded to conduct 18 prospective studies that address 6 priority areas. The design and implementation of these studies are managed through a single coordinating center. As of December 1, 2015, a total of 4560 participants have been enrolled.CONCLUSIONSSuccess of METRC to date confirms the potential for civilian and military trauma centers to collaborate on critical research issues and leverage the strength that comes from engaging patients and providers from across multiple centers