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"Howe, Kenneth R. (Kenneth Ross)"
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RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer
Tyrosine kinase inhibitors are effective treatments for non-small-cell lung cancers (NSCLCs) with
epidermal growth factor receptor
(
EGFR
) mutations. However, relapse typically occurs after an average of 1 year of continuous treatment. A fundamental histological transformation from NSCLC to small-cell lung cancer (SCLC) is observed in a subset of the resistant cancers, but the molecular changes associated with this transformation remain unknown. Analysis of tumour samples and cell lines derived from resistant
EGFR
mutant patients revealed that Retinoblastoma (RB) is lost in 100% of these SCLC transformed cases, but rarely in those that remain NSCLC. Further, increased neuroendocrine marker and decreased
EGFR
expression as well as greater sensitivity to BCL2 family inhibition are observed in resistant SCLC transformed cancers compared with resistant NSCLCs. Together, these findings suggest that this subset of resistant cancers ultimately adopt many of the molecular and phenotypic characteristics of classical SCLC.
Resistance to tyrosine kinase inhibitors occurs in treatments of non-small-cell lung cancers (NSCLCs) with EGFR mutations but the mechanisms underlying this acquired resistance are unknown. Here the authors examine the molecular changes that occur in resistant cancers that transition from NSCLC to small-cell lung cancer phenotype and implicate loss of retinoblastoma in this process.
Journal Article
Values in evaluation and social research
Using the tools of philosophy and the insights from evaluation practice this book examines the concept of value in program evaluation. The authors analyze four views of facts and values in evaluation: those rooted in a fact-value dichotomy; those of radical constructivists; those of postmodernists; and those of deliberative democrats.
eBook
Educational Equality
Educational Equality and the New Selective Schooling by Harry Brighouse was initially published by the Philosophy of Education Society of Great Britain in 2000. In this new edition, Brighouse has updated his argument, Kenneth R Howe and James Tooley have contributed counter-arguments and Graham Haydon has provided an introduction and afterword drawing the debates together. The issues debated in this new edition of Educational Equality include: What is Educational Equality? Why Does Educational Equality Matter? Is Educational Equality Possible? Educational Equality raises issues which will be of interest to all involved in educational equality, including teachers, policy makers and educationalists.
eBook
Building consensus around the assessment and interpretation of Symbiodiniaceae diversity
Within microeukaryotes, genetic variation and functional variation sometimes accumulate more quickly than morphological differences. To understand the evolutionary history and ecology of such lineages, it is key to examine diversity at multiple levels of organization. In the dinoflagellate family Symbiodiniaceae, which can form endosymbioses with cnidarians ( e.g ., corals, octocorals, sea anemones, jellyfish), other marine invertebrates ( e.g. , sponges, molluscs, flatworms), and protists ( e.g ., foraminifera), molecular data have been used extensively over the past three decades to describe phenotypes and to make evolutionary and ecological inferences. Despite advances in Symbiodiniaceae genomics, a lack of consensus among researchers with respect to interpreting genetic data has slowed progress in the field and acted as a barrier to reconciling observations. Here, we identify key challenges regarding the assessment and interpretation of Symbiodiniaceae genetic diversity across three levels: species, populations, and communities. We summarize areas of agreement and highlight techniques and approaches that are broadly accepted. In areas where debate remains, we identify unresolved issues and discuss technologies and approaches that can help to fill knowledge gaps related to genetic and phenotypic diversity. We also discuss ways to stimulate progress, in particular by fostering a more inclusive and collaborative research community. We hope that this perspective will inspire and accelerate coral reef science by serving as a resource to those designing experiments, publishing research, and applying for funding related to Symbiodiniaceae and their symbiotic partnerships.
Journal Article