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

The Theory of the Interleaving Distance on Multidimensional Persistence Modules

In 2009, Chazal et al. introduced $\epsilon$-interleavings of persistence modules. $\epsilon$-interleavings induce a pseudometric $d_I$ on (isomorphism classes of) persistence modules, the interleaving distance. The definitions of $\epsilon$-interleavings and $d_I$ generalize readily to multidimensional persistence modules. In this paper, we develop the theory of multidimensional interleavings, with a view towards applications to topological data analysis. We present four main results. First, we show that on 1-D persistence modules, $d_I$ is equal to the bottleneck distance $d_B$. This result, which first appeared in an earlier preprint of this paper, has since appeared in several other places, and is now known as the isometry theorem. Second, we present a characterization of the $\epsilon$-interleaving relation on multidimensional persistence modules. This expresses transparently the sense in which two $\epsilon$-interleaved modules are algebraically similar. Third, using this characterization, we show that when we define our persistence modules over a prime field, $d_I$ satisfies a universality property. This universality result is the central result of the paper. It says that $d_I$ satisfies a stability property generalizing one which $d_B$ is known to satisfy, and that in addition, if $d$ is any other pseudometric on multidimensional persistence modules satisfying the same stability property, then $d\leq d_I$. We also show that a variant of this universality result holds for $d_B$, over arbitrary fields. Finally, we show that $d_I$ restricts to a metric on isomorphism classes of finitely presented multidimensional persistence modules.Comment: Major revision; exposition improved throughout. To appear in Foundations of Computational Mathematics. 36 page

The persistence landscape and some of its properties

Persistence landscapes map persistence diagrams into a function space, which may often be taken to be a Banach space or even a Hilbert space. In the latter case, it is a feature map and there is an associated kernel. The main advantage of this summary is that it allows one to apply tools from statistics and machine learning. Furthermore, the mapping from persistence diagrams to persistence landscapes is stable and invertible. We introduce a weighted version of the persistence landscape and define a one-parameter family of Poisson-weighted persistence landscape kernels that may be useful for learning. We also demonstrate some additional properties of the persistence landscape. First, the persistence landscape may be viewed as a tropical rational function. Second, in many cases it is possible to exactly reconstruct all of the component persistence diagrams from an average persistence landscape. It follows that the persistence landscape kernel is characteristic for certain generic empirical measures. Finally, the persistence landscape distance may be arbitrarily small compared to the interleaving distance.Comment: 18 pages, to appear in the Proceedings of the 2018 Abel Symposiu

Immune modulation via T regulatory cell enhancement:Disease-modifying therapies for autoimmunity and their potential for chronic allergic and inflammatory diseases-An EAACI position paper of the Task Force on Immunopharmacology (TIPCO)

Therapeutic advances using targeted biologicals and small-molecule drugs have achieved significant success in the treatment of chronic allergic, autoimmune, and inflammatory diseases particularly for some patients with severe, treatment-resistant forms. This has been aided by improved identification of disease phenotypes. Despite these achievements, not all severe forms of chronic inflammatory and autoimmune diseases are successfully targeted, and current treatment options, besides allergen immunotherapy for selected allergic diseases, fail to change the disease course. T cell–based therapies aim to cure diseases through the selective induction of appropriate immune responses following the delivery of engineered, specific cytotoxic, or regulatory T cells (Tregs). Adoptive cell therapies (ACT) with genetically engineered T cells have revolutionized the oncology field, bringing curative treatment for leukemia and lymphoma, while therapies exploiting the suppressive functions of Tregs have been developed in nononcological settings, such as in transplantation and autoimmune diseases. ACT with Tregs are also being considered in nononcological settings such as cardiovascular disease, obesity, and chronic inflammatory disorders. After describing the general features of T cell–based approaches and current applications in autoimmune diseases, this position paper reviews the experimental models testing or supporting T cell–based approaches, especially Treg-based approaches, in severe IgE-mediated responses and chronic respiratory airway diseases, such as severe asthma and COPD. Along with an assessment of challenges and unmet needs facing the application of ACT in these settings, this article underscores the potential of ACT to offer curative options for patients with severe or treatment-resistant forms of these immune-driven disorders

Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology

The accumulation of senescent cells drives inflammaging and increases morbidity of chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy and substrates for cell proliferation, differentiation, and activation. Metabolic changes imposed by environmental stress and inflammation on immune cells and tissue microenvironment are thus chiefly involved in the pathophysiology of allergic and other immune‐driven diseases. Altered cell metabolism is also a hallmark of cell senescence, a condition characterized by loss of proliferative activity in cells that remain metabolically active. Accelerated senescence can be triggered by acute or chronic stress and inflammatory responses. In contrast, replicative senescence occurs as part of the physiological aging process and has protective roles in cancer surveillance and wound healing. Importantly, cell senescence can also change or hamper response to diverse therapeutic treatments. Understanding the metabolic pathways of senescence in immune and structural cells is therefore critical to detect, prevent, or revert detrimental aspects of senescence‐related immunopathology, by developing specific diagnostics and targeted therapies. In this paper, we review the main changes and metabolic alterations occurring in senescent immune cells (macrophages, B cells, T cells). Subsequently, we present the metabolic footprints described in translational studies in patients with chronic asthma and chronic obstructive pulmonary disease (COPD), and review the ongoing preclinical studies and clinical trials of therapeutic approaches aiming at targeting metabolic pathways to antagonize pathological senescence. Because this is a recently emerging field in allergy and clinical immunology, a better understanding of the metabolic profile of the complex landscape of cell senescence is needed. The progress achieved so far is already providing opportunities for new therapies, as well as for strategies aimed at disease prevention and supporting healthy aging

Suppression of High Transverse Momentum π0\pi^0 Spectra in Au+Au Collisions at RHIC

Au+Au, $s^{1/2} = 200$ A GeV measurements at RHIC, obtained with the PHENIX, STAR, PHOBOS and BRAHMS detectors, have all indicated a suppression of neutral pion production, relative to an appropriately normalized NN level. For central collisions and vanishing pseudo-rapidity these experiments exhibit suppression in charged meson production, especially at medium to large transverse momenta. In the PHENIX experiment similar behavior has been reported for $\pi^0$ spectra. In a recent work on the simpler D+Au interaction, to be considered perhaps as a tune-up for Au+Au, we reported on a pre-hadronic cascade mechanism which explains the mixed observation of moderately reduced $p_\perp$ suppression at higher pseudo-rapidity as well as the Cronin enhancement at mid-rapidity. Here we present the extension of this work to the more massive ion-ion collisions. Our major thesis is that much of the suppression is generated in a late stage cascade of colourless pre-hadrons produced after an initial short-lived coloured phase. We present a pQCD argument to justify this approach and to estimate the time duration $\tau_p$ of this initial phase. Of essential importance is the brevity in time of the coloured phase existence relative to that of the strongly interacting pre-hadron phase. The split into two phases is of course not sharp in time, but adequate for treating the suppression of moderate and high $p_\perp$ mesons.Comment: 19 pages, 10 figure

Innate immunity but not NLRP3 inflammasome activation correlates with severity of stable COPD

Background In models of COPD, environmental stressors induce innate immune responses, inflammasome activation and inflammation. However, the interaction between these responses and their role in driving pulmonary inflammation in stable COPD is unknown. Objectives To investigate the activation of innate immunity and inflammasome pathways in the bronchial mucosa and bronchoalveolar lavage (BAL) of patients with stable COPD of different severity and control healthy smokers and non-smokers. Methods Innate immune mediators (interleukin (IL)-6, IL-7, IL-10, IL-27, IL-37, thymic stromal lymphopoietin (TSLP), interferon γ and their receptors, STAT1 and pSTAT1) and inflammasome components (NLRP3, NALP7, caspase 1, IL-1β and its receptors, IL-18, IL-33, ST2) were measured in the bronchial mucosa using immunohistochemistry. IL-6, soluble IL-6R, sgp130, IL-7, IL-27, HMGB1, IL-33, IL-37 and soluble ST2 were measured in BAL using ELISA. Results In bronchial biopsies IL-27+ and pSTAT1+ cells are increased in patients with severe COPD compared with control healthy smokers. IL-7+ cells are increased in patients with COPD and control smokers compared with control non-smokers. In severe stable COPD IL-7R+, IL-27R+ and TSLPR+ cells are increased in comparison with both control groups. The NALP3 inflammasome is not activated in patients with stable COPD compared with control subjects. The inflammasome inhibitory molecules NALP7 and IL-37 are increased in patients with COPD compared with control smokers. IL-6 levels are increased in BAL from patients with stable COPD compared with control smokers with normal lung function whereas IL-1β and IL-18 were similar across all groups. Conclusions Increased expression of IL-27, IL-37 and NALP7 in the bronchial mucosa may be involved in progression of stable COPD

Haemophilus influenzae and Moraxella catarrhalis in sputum of severe asthma with inflammasome and neutrophil activation

BACKGROUND: Because of altered airway microbiome in asthma, we analysed the bacterial species in sputum of patients with severe asthma. METHODS: Whole genome sequencing was performed on induced sputum from non-smoking (SAn) and current or ex-smoker (SAs/ex) severe asthma patients, mild/moderate asthma (MMA) and healthy controls (HC). Data were analysed by asthma severity, inflammatory status and transcriptome-associated clusters (TACs). RESULTS: α-diversity at the species level was lower in SAn and SAs/ex, with an increase in Haemophilus influenzae and Moraxella catarrhalis, and Haemophilus influenzae and Tropheryma whipplei, respectively, compared to HC. In neutrophilic asthma, there was greater abundance of Haemophilus influenzae and Moraxella catarrhalis and in eosinophilic asthma, Tropheryma whipplei was increased. There was a reduction in α-diversity in TAC1 and TAC2 that expressed high levels of Haemophilus influenzae and Tropheryma whipplei, and Haemophilus influenzae and Moraxella catarrhalis, respectively, compared to HC. Sputum neutrophils correlated positively with Moraxella catarrhalis and negatively with Prevotella, Neisseria and Veillonella species and Haemophilus parainfluenzae. Sputum eosinophils correlated positively with Tropheryma whipplei which correlated with pack-years of smoking. α- and β-diversities were stable at one year. CONCLUSIONS: Haemophilus influenzae and Moraxella catarrhalis were more abundant in severe neutrophilic asthma and TAC2 linked to inflammasome and neutrophil activation, while Haemophilus influenzae and Tropheryma whipplei were highest in SAs/ex and in TAC1 associated with highest expression of IL-13 type 2 and ILC2 signatures with the abundance of Tropheryma whipplei correlating positively with sputum eosinophils. Whether these bacterial species drive the inflammatory response in asthma needs evaluation