Teaching the Newly Essential Knowledge, Skills, and Values in a Changing World

This chapter of Building on Best Practices: Transforming Legal Education in a Changing World has contributions from many authors: Section A, Professional Identity Formation, includes: Teaching Knowledge, Skills, and Values of Professional Identity Formation, by Larry O. Natt Gantt, II & Benjamin V. Madison III, Integrating Professionalism into Doctrinally-Focused Courses, by Paula Schaefer, Learning Professional Responsibility, by Clark D. Cunningham, and Teaching Leadership, by Deborah L. Rhode. Section B, Pro Bono as a Professional Value, is by Cynthia F. Adcock, Eden E. Harrington, Elizabeth Kane, Susan Schechter, David S. Udell & Eliza Vorenberg. Section C, The Relational Skills of the Law, includes: Teaching Relational Skills: The Evidence, by Susan Daicoff, and Cultivating Students\u27 Relational Skills, by Susan L. Brooks. Section D, Teamwork, is by Linda Morton & Janet Weinstein. Section E, Intercultural Effectiveness, is by Mary A. Lynch with Robin Boyle, Rhonda Magee & Antoinette Sedillo López. Section F, Social Justice Across the Curriculum, is by Susan Bryant. Section G, Problem-Solving and Conflict Resolution, includes: Teaching Students to Be Healers: The Comprehensive Law Movement, by Susan Daicoff, Teaching Alternative Dispute Resolution, by Andrea Kupfer Schneider, and Integrating Alternative Dispute Resolution and Problem-Solving Across the Curriculum, by Jill Gross & John Lande Section H, Interprofessional Education, is by Lisa Radtke Bliss, Sylvia B. Caley, Patty Roberts, Emily F. Suski & Robert Pettignano. Section I, Technology in the Profession, is by Conrad Johnson. Section J, Business and Financial Literacy, is by Dwight Drake. Chapter 1 is available at: http://ssrn.com/abstract=2637100 Chapter 2 is available at: http://ssrn.com/abstract=2637068 Chapter 3 is available at: http://ssrn.com/abstract=2637102 Chapter 4 is available at: http://ssrn.com/abstract=2637490 Chapter 5 is available at: http://ssrn.com/abstract=2637495 Chapter 7 is available at: http://ssrn.com/abstract=2637541 Chapter 8 is available at: http://ssrn.com/abstract=2637544 The content of this SSRN posting is material that was published in the book Building on Best Practices: Transforming Legal Education in a Changing World, Maranville, et al., Lexis Nexis 2015. The content has been posted on SSRN with the express permission of Lexis Nexis and of Carolina Academic Press, publisher of the book as of January 1, 2016

Updated standardized definitions for efficacy endpoints in adjuvant breast cancer clinical trials: STEEP Version 2.0

Purpose The Standardized Definitions for Efficacy End Points (STEEP) criteria, established in 2007, provide standardized definitions of adjuvant breast cancer clinical trial end points. Given the evolution of breast cancer clinical trials and improvements in outcomes, a panel of experts reviewed the STEEP criteria to determine whether modifications are needed.Methods We conducted systematic searches of ClinicalTrials.gov for adjuvant systemic and local-regional therapy trials for breast cancer to investigate if the primary end points reported met STEEP criteria. On the basis of common STEEP deviations, we performed a series of simulations to evaluate the effect of excluding non-breast cancer deaths and new nonbreast primary cancers from the invasive disease-free survival end point.Results Among 11 phase III breast cancer trials with primary efficacy end points, three had primary end points that followed STEEP criteria, four used STEEP definitions but not the corresponding end point names, and four used end points that were not included in the original STEEP manuscript. Simulation modeling demonstrated that inclusion of second nonbreast primary cancer can increase the probability of incorrect inferences, can decrease power to detect clinically relevant efficacy effects, and may mask differences in recurrence rates, especially when recurrence rates are low.Conclusion We recommend an additional end point, invasive breast cancer-free survival, which includes all invasive disease-free survival events except second nonbreast primary cancers. This end point should be considered for trials in which the toxicities of agents are well-known and where the risk of second primary cancer is small. Additionally, we provide end point recommendations for local therapy trials, low-risk populations, noninferiority trials, and trials incorporating patient-reported outcomes

Two-Body B Meson Decays to η\eta and η′\eta^{'} -- Observation of B→ηB\to \eta{'}K$

In a sample of 6.6 million produced B mesons we have observed decays B -> eta' K, with branching fractions BR(B+ -> eta' K+ = 6.5 +1.5 -1.4 +- 0.9) x $10^{-5}$ and BR(B0 -> eta' K0 = 4.7 +2.7 -2.0 +- 0.9) x $10^{-5}$. We have searched with comparable sensitivity for 17 related decays to final states containing an eta or eta' meson accompanied by a single particle or low-lying resonance. Our upper limits for these constrain theoretical interpretations of the B -> eta' K signal.Comment: 12 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Enhanced Hippocampal Long-Term Potentiation and Fear Memory in Btbd9 Mutant Mice

Polymorphisms in BTBD9 have recently been associated with higher risk of restless legs syndrome (RLS), a neurological disorder characterized by uncomfortable sensations in the legs at rest that are relieved by movement. The BTBD9 protein contains a BTB/POZ domain and a BACK domain, but its function is unknown. To elucidate its function and potential role in the pathophysiology of RLS, we generated a line of mutant Btbd9 mice derived from a commercial gene-trap embryonic stem cell clone. Btbd9 is the mouse homolog of the human BTBD9. Proteins that contain a BTB/POZ domain have been reported to be associated with synaptic transmission and plasticity. We found that Btbd9 is naturally expressed in the hippocampus of our mutant mice, a region critical for learning and memory. As electrophysiological characteristics of CA3-CA1 synapses of the hippocampus are well characterized, we performed electrophysiological recordings in this region. The mutant mice showed normal input-output relationship, a significant impairment in pre-synaptic activity, and an enhanced long-term potentiation. We further performed an analysis of fear memory and found the mutant mice had an enhanced cued and contextual fear memory. To elucidate a possible molecular basis for these enhancements, we analyzed proteins that have been associated with synaptic plasticity. We found an elevated level of dynamin 1, an enzyme associated with endocytosis, in the mutant mice. These results suggest the first identified function of Btbd9 as being involved in regulating synaptic plasticity and memory. Recent studies have suggested that enhanced synaptic plasticity, analogous to what we have observed, in other regions of the brain could enhance sensory perception similar to what is seen in RLS patients. Further analyses of the mutant mice will help shine light on the function of BTBD9 and its role in RLS

Kuhnian revolutions in neuroscience: the role of tool development.

The terms "paradigm" and "paradigm shift" originated in "The Structure of Scientific Revolutions" by Thomas Kuhn. A paradigm can be defined as the generally accepted concepts and practices of a field, and a paradigm shift its replacement in a scientific revolution. A paradigm shift results from a crisis caused by anomalies in a paradigm that reduce its usefulness to a field. Claims of paradigm shifts and revolutions are made frequently in the neurosciences. In this article I will consider neuroscience paradigms, and the claim that new tools and techniques rather than crises have driven paradigm shifts. I will argue that tool development has played a minor role in neuroscience revolutions.The work received no fundin

Human Umbilical Cord Blood Cells Restore Brain Damage Induced Changes in Rat Somatosensory Cortex

Intraperitoneal transplantation of human umbilical cord blood (hUCB) cells has been shown to reduce sensorimotor deficits after hypoxic ischemic brain injury in neonatal rats. However, the neuronal correlate of the functional recovery and how such a treatment enforces plastic remodelling at the level of neural processing remains elusive. Here we show by in-vivo recordings that hUCB cells have the capability of ameliorating the injury-related impairment of neural processing in primary somatosensory cortex. Intact cortical processing depends on a delicate balance of inhibitory and excitatory transmission, which is disturbed after injury. We found that the dimensions of cortical maps and receptive fields, which are significantly altered after injury, were largely restored. Additionally, the lesion induced hyperexcitability was no longer observed in hUCB treated animals as indicated by a paired-pulse behaviour resembling that observed in control animals. The beneficial effects on cortical processing were reflected in an almost complete recovery of sensorimotor behaviour. Our results demonstrate that hUCB cells reinstall the way central neurons process information by normalizing inhibitory and excitatory processes. We propose that the intermediate level of cortical processing will become relevant as a new stage to investigate efficacy and mechanisms of cell therapy in the treatment of brain injury

The A-Current Modulates Learning via NMDA Receptors Containing the NR2B Subunit

Synaptic plasticity involves short- and long-term events, although the molecular mechanisms that underlie these processes are not fully understood. The transient A-type K+ current (IA) controls the excitability of the dendrites from CA1 pyramidal neurons by regulating the back-propagation of action potentials and shaping synaptic input. Here, we have studied how decreases in IA affect cognitive processes and synaptic plasticity. Using wild-type mice treated with 4-AP, an IA inhibitor, and mice lacking the DREAM protein, a transcriptional repressor and modulator of the IA, we demonstrate that impairment of IA decreases the stimulation threshold for learning and the induction of early-LTP. Hippocampal electrical recordings in both models revealed alterations in basal electrical oscillatory properties toward low-theta frequencies. In addition, we demonstrated that the facilitated learning induced by decreased IA requires the activation of NMDA receptors containing the NR2B subunit. Together, these findings point to a balance between the IA and the activity of NR2B-containing NMDA receptors in the regulation of learning

α1A-Adrenergic Receptor Induces Activation of Extracellular Signal-Regulated Kinase 1/2 through Endocytic Pathway

G protein-coupled receptors (GPCRs) activate mitogen-activated protein kinases through a number of distinct pathways in cells. Increasing evidence has suggested that endosomal signaling has an important role in receptor signal transduction. Here we investigated the involvement of endocytosis in α1A-adrenergic receptor (α1A-AR)-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2). Agonist-mediated endocytic traffic of α1A-AR was assessed by real-time imaging of living, stably transfected human embryonic kidney 293A cells (HEK-293A). α1A-AR was internalized dynamically in cells with agonist stimulation, and actin filaments regulated the initial trafficking of α1A-AR. α1A-AR-induced activation of ERK1/2 but not p38 MAPK was sensitive to disruption of endocytosis, as demonstrated by 4°C chilling, dynamin mutation and treatment with cytochalasin D (actin depolymerizing agent). Activation of protein kinase C (PKC) and C-Raf by α1A-AR was not affected by 4°C chilling or cytochalasin D treatment. U73122 (a phospholipase C [PLC] inhibitor) and Ro 31–8220 (a PKC inhibitor) inhibited α1B-AR- but not α1A-AR-induced ERK1/2 activation. These data suggest that the endocytic pathway is involved in α1A-AR-induced ERK1/2 activation, which is independent of Gq/PLC/PKC signaling