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"Phillips, D. C."
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Research in the Hard Sciences, and in Very Hard \Softer\ Domains
The author of this commentary argues that physical scientists are attempting to advance knowledge in the so-called hard sciences, whereas education researchers are laboring to increase knowledge and understanding in an \"extremely hard\" but softer domain. Drawing on the work of Popper and Dewey, this commentary highlights the relative similarities between hard sciences and education research in their rhetorical nature, while acknowledging the divergent paths of these two fields of inquiry with regard to prediction and generalizability. The author suggests that given the highly contextualized nature of educational processes, embedded in shifting complex social settings, and the relevance of all variables, very little education research is able to pursue predictive power.
Journal Article
On the Science of Education Design Studies
The authors argue that design studies, like all scientific work, must comport with guiding scientific principles and provide adequate warrants for their knowledge claims. The issue is whether their knowledge claims can be warranted. By their very nature, design studies are complex, multivariate, multilevel, and interventionist, making warrants particularly difficult to establish. Moreover, many of these studies, intended or not, rely on narrative accounts to communicate and justify their findings. Although narratives often purport to be true, there is nothing in narrative form that guarantees veracity. The authors provide a framework that links design-study research questions as they evolve over time with corresponding research methods. In this way, an integration can be seen of research methods focused on discovery with methods focused on validation of claims.
Journal Article
Learning from Our Differences: A Dialogue across Perspectives on Quality in Education Research
The dialogue re-presented in this article is intended to foster mutual engagement-and opportunity for learning-across different perspectives on research within the education research community. Participants in the dialogue each addressed the following questions: (1) What are the touchstones by which you judge quality or rigor in education research (for a single study, a set of studies, or a \"field\" or community of researchers in dialogue)? What is your chief concern or fear that the touchstones guard against? (2) Where do you see challenges to your perspective in the perspectives of other members of the panel? How might your perspective evolve to respond to those challenges? Given all of this, what are the implications for the preparation of education researchers? Opening and closing comments set the dialogue in historical context, highlight issues raised, and suggest next steps for collaborative learning from the diversity of perspectives in our field.
Journal Article
Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax)
The anti-apoptotic protein MCL-1 is a key regulator of cancer cell survival and a known resistance factor for small-molecule BCL-2 family inhibitors such as ABT-263 (navitoclax), making it an attractive therapeutic target. However, directly inhibiting this target requires the disruption of high-affinity protein–protein interactions, and therefore designing small molecules potent enough to inhibit MCL-1 in cells has proven extremely challenging. Here, we describe a series of indole-2-carboxylic acids, exemplified by the compound A-1210477, that bind to MCL-1 selectively and with sufficient affinity to disrupt MCL-1–BIM complexes in living cells. A-1210477 induces the hallmarks of intrinsic apoptosis and demonstrates single agent killing of multiple myeloma and non-small cell lung cancer cell lines demonstrated to be MCL-1 dependent by BH3 profiling or siRNA rescue experiments. As predicted, A-1210477 synergizes with the BCL-2/BCL-X
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inhibitor navitoclax to kill a variety of cancer cell lines. This work represents the first description of small-molecule MCL-1 inhibitors with sufficient potency to induce clear on-target cellular activity. It also demonstrates the utility of these molecules as chemical tools for dissecting the basic biology of MCL-1 and the promise of small-molecule MCL-1 inhibitors as potential therapeutics for the treatment of cancer.
Journal Article
New developments in the neuroradiological diagnosis of craniocerebral trauma
Accurate radiographic diagnosis is a cornerstone of the clinical management and outcome prediction of the head-injured patient. New technological advances, such as multi-detector computed tomography (MDCT) scanning and diffusion-weighted magnetic resonance imaging (MRI) have influenced imaging strategy. In this article we review the impact of these developments on the neuroradiological diagnosis of acute head injury. In the acute phase, multi-detector CT has supplanted plain X-ray films of the skull as the initial imaging study of choice. MRI, including fluid-attenuated inversion recovery, gradient echo T2* and diffusion-weighted sequences, is useful in determining the severity of acute brain tissue injury and may help to predict outcome. The role of MRI in showing diffuse axonal injuries is emphasized. We review the different patterns of primary and secondary extra-axial and intra-axial traumatic brain lesions and integrate new insights. Assessment of intracranial hypertension and cerebral herniation are of major clinical importance in patient management. We discuss the issue of pediatric brain trauma and stress the importance of MRI in non-accidental injury. In summary, new developments in imaging technology have advanced our understanding of the pathophysiology of brain trauma and contribute to improving the survival of patients with craniocerebral injuries.
Journal Article