Disputation Arenas: Harnessing Conflict and Competitiveness for Society's Benefit

Published in cooperation with the American Bar Association Section of Dispute Resolutio

Commentary on Robert Riley's article "A personal account of the discovery of hyperbolic structures on some knot complements"

We give some background and biographical commentary on the postumous article that appears in this [journal issue | ArXiv] by Robert Riley on his part of the early history of hyperbolic structures on some compact 3-manifolds. A complete list of Riley's publications appears at the end of the article.Comment: 5 page

Lehman Brothers: Peeking Under the Board Facade

Closer Look Series: Topics, Issues, and Controversies in Corporate Governanc

Concepts et méthodes de l’écologie des paysages pour aider à mieux gérer les services écosystémiques

Concepts et méthodes de l’écologie des paysages pour aider à mieux gérer les services écosystémique

Primary Alcohol-Activated Human and Mouse Hepatic Stellate Cells Share Similarities in Gene-Expression Profiles.

Alcoholic liver disease (ALD) is a leading cause of cirrhosis in the United States, which is characterized by extensive deposition of extracellular matrix proteins and formation of a fibrous scar. Hepatic stellate cells (HSCs) are the major source of collagen type 1 producing myofibroblasts in ALD fibrosis. However, the mechanism of alcohol-induced activation of human and mouse HSCs is not fully understood. We compared the gene-expression profiles of primary cultured human HSCs (hHSCs) isolated from patients with ALD (n = 3) or without underlying liver disease (n = 4) using RNA-sequencing analysis. Furthermore, the gene-expression profile of ALD hHSCs was compared with that of alcohol-activated mHSCs (isolated from intragastric alcohol-fed mice) or CCl4-activated mouse HSCs (mHSCs). Comparative transcriptome analysis revealed that ALD hHSCs, in addition to alcohol-activated and CCl4-activated mHSCs, share the expression of common HSC activation (Col1a1 [collagen type I alpha 1 chain], Acta1 [actin alpha 1, skeletal muscle], PAI1 [plasminogen activator inhibitor-1], TIMP1 [tissue inhibitor of metalloproteinase 1], and LOXL2 [lysyl oxidase homolog 2]), indicating that a common mechanism underlies the activation of human and mouse HSCs. Furthermore, alcohol-activated mHSCs most closely recapitulate the gene-expression profile of ALD hHSCs. We identified the genes that are similarly and uniquely up-regulated in primary cultured alcohol-activated hHSCs and freshly isolated mHSCs, which include CSF1R (macrophage colony-stimulating factor 1 receptor), PLEK (pleckstrin), LAPTM5 (lysosmal-associated transmembrane protein 5), CD74 (class I transactivator, the invariant chain), CD53, MMP9 (matrix metallopeptidase 9), CD14, CTSS (cathepsin S), TYROBP (TYRO protein tyrosine kinase-binding protein), and ITGB2 (integrin beta-2), and other genes (compared with CCl4-activated mHSCs). Conclusion: We identified genes in alcohol-activated mHSCs from intragastric alcohol-fed mice that are largely consistent with the gene-expression profile of primary cultured hHSCs from patients with ALD. These genes are unique to alcohol-induced HSC activation in two species, and therefore may become targets or readout for antifibrotic therapy in experimental models of ALD

Complaint risk among mental health practitioners compared with physical health practitioners::A retrospective cohort study of complaints to health regulators in Australia

Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. To understand complaint risk among mental health practitioners compared with physical health practitioners. Design Retrospective cohort study, using incidence rate ratios (IRRs) to analyse complaint risk and a multivariate regression model to identify predictors of complaints. Setting National study using complaints data from health regulators in Australia. Participants All psychiatrists and psychologists (a € mental health practitioners\u27) and all physicians, optometrists, physiotherapists, osteopaths and chiropractors (a € physical health practitioners\u27) registered to practice in Australia between 2011 and 2016. Outcome measures Incidence rates, source and nature of complaints to regulators. Results In total, 7903 complaints were lodged with regulators over the 6-year period. Most complaints were lodged by patients and their families. Mental health practitioners had a complaint rate that was more than twice that of physical health practitioners (complaints per 1000 practice years: psychiatrists 119.1 vs physicians 48.0, p\u3c0.001; psychologists 21.9 vs other allied health 7.5, p\u3c0.001). Their risk of complaints was especially high in relation to reports, records, confidentiality, interpersonal behaviour, sexual boundary breaches and the mental health of the practitioner. Among mental health practitioners, male practitioners (psychiatrists IRR: 1.61, 95% CI 1.39 to 1.85; psychologists IRR: 1.85, 95% CI 1.65 to 2.07) and older practitioners (≥65 years compared with 36-45 years: psychiatrists IRR 2.37, 95% CI 1.95 to 2.89; psychologists IRR 1.78, 95% CI 1.47 to 2.14) were at increased risk of complaints. Conclusions Mental health practitioners were more likely to be the subject of complaints than physical health practitioners. Areas of increased risk are related to professional ethics, communication skills and the health of mental health practitioners themselves. Further research could usefully explore whether addressing these risk factors through training, professional development and practitioner health initiatives may reduce the risk of complaints about mental health practitioners

Rationale and design of a prospective study: Cervical Dystonia Patient Registry for Observation of OnaBotulinumtoxinA Efficacy (CD PROBE)

<p>Abstract</p> <p>Background</p> <p>A registry of patients with cervical dystonia (Cervical Dystonia Patient Registry for Observation of onaBotulinumtoxinA Efficacy [CD PROBE]) was initiated to capture data regarding physician practices and patient outcomes with onabotulinumtoxinA (BOTOX^®, Allergan, Inc., Irvine, CA, USA). Methods and baseline demographics from an interim analysis are provided.</p> <p>Methods/Design</p> <p>This is a prospective, multicenter, clinical registry in the United States enrolling subjects with cervical dystonia (CD) who are toxin naïve and/or new to the physicians' practices, or who had been in a clinical trial but received their last injection ≥ 16 weeks prior to enrollment. Subjects are followed over 3 injection cycles of onabotulinumtoxinA, with assessments at time of injection and 4-6 weeks later. Information on physician's practice, patient demographics, CD disease history, duration of treatment intervals and neurotoxin dose, dilution, use of electromyography, and muscles injected are collected. Outcomes are assessed by physicians and subjects using various questionnaires.</p> <p>Discussion</p> <p>This ongoing registry includes 609 subjects with the following baseline data: 75.9% female, 93.6% Caucasian, mean age 57.6 ± 14.3, age at symptom onset 48.3 ± 16.2, and time to diagnosis 5.4 ± 8.6 years, with an additional 1.0 ± 3.5 years before treatment. Of those employed at the time of diagnosis, 36.6% stopped working as a result of CD. CD PROBE, the largest clinical registry of CD treatment, will provide useful data on current treatment practices with onabotulinumtoxinA, potentially leading to refinements for optimization of outcomes.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00836017">NCT00836017</a></p

Front propagation in a phase field model with phase-dependent heat absorption

Copyright © 2006 Elsevier. NOTICE: This is the author’s version of a work accepted for publication by Elsevier. Changes resulting from the publishing process, including peer review, editing, corrections, structural formatting and other quality control mechanisms, may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Physica D, Vol 215, Issue 2, 2006, DOI: 10.1016/j.physd.2006.01.024We present a model for the spatio-temporal behaviour of films exposed to radiative heating, where the film can change reversibly between amorphous (glassy) and crystalline states. Such phase change materials are used extensively in read-write optical disk technology. In cases where the heat absorption of the crystal phase is less than that in the amorphous state we find that there is a bi-stability of the phases. We investigate the spatial behaviours that are a consequence of this property and use a phase field model for the spatio-temporal dynamics in which the phase variable is coupled to a suitable temperature field. It is shown that travelling wave solutions of the system are possible and, depending on the precise system parameters, these waves can take a range of forms and velocities. Some examples of possible dynamical behaviours are discussed and we show, in particular, that the waves may collide and annihilate. The longitudinal and transverse stability of the travelling waves are examined using an Evans function method which suggests that the fronts are stable structures

Treatment of Chronic Migraine with Botox (Onabotulinumtoxina): Development, Insights, and Impact

Chronic migraine (CM) is a neurological disease characterized by frequent migraine attacks that prevent affected individuals from performing daily activities of living, significantly diminish quality of life, and increase familial burden. Before onabotulinumtoxinA was approved for CM, there were few treatment options for these seriously disabled patients and none had regulatory approval. The terminology and recognition of CM evolved in parallel with the onabotulinumtoxinA clinical development program. Because there were no globally accepted classification criteria for CM when onabotulinumtoxinA was in development, the patient populations for the trials conducted by Allergan were determined by the Allergan migraine team in collaboration with headache scientists and clinicians. These trials and collaborations ultimately led to improvements in CM classifications. In 2010, onabotulinumtoxinA became the first medication and first biologic approved specifically to prevent headaches in patients with CM. Approval was based on 2 similarly designed phase 3, double-blind, randomized, placebo-controlled, multicenter clinical studies. Both studies showed significantly greater improvements in mean change from baseline in headache-day frequency in patients with CM receiving onabotulinumtoxinA compared with those receiving placebo. The safety and effectiveness of onabotulinumtoxinA have been established globally in \u3e5000 patients with CM with or without medication overuse treated in clinical and observational studies. Benefits also include improvements in quality of life, fewer psychiatric comorbidities, and reduced healthcare resource utilization. Across studies, onabotulinumtoxinA was well tolerated; adverse events tended to be mild or moderate in severity and to decline over subsequent treatment cycles

Evolution favors protein mutational robustness in sufficiently large populations

BACKGROUND: An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar proteins can differ substantially in their robustness to mutations and capacity to evolve new functions, but it has remained unclear whether any of these differences might be due to evolutionary selection for these properties. RESULTS: Here we use laboratory experiments to demonstrate that evolution favors protein mutational robustness if the evolving population is sufficiently large. We neutrally evolve cytochrome P450 proteins under identical selection pressures and mutation rates in populations of different sizes, and show that proteins from the larger and thus more polymorphic population tend towards higher mutational robustness. Proteins from the larger population also evolve greater stability, a biophysical property that is known to enhance both mutational robustness and evolvability. The excess mutational robustness and stability is well described by existing mathematical theories, and can be quantitatively related to the way that the proteins occupy their neutral network. CONCLUSIONS: Our work is the first experimental demonstration of the general tendency of evolution to favor mutational robustness and protein stability in highly polymorphic populations. We suggest that this phenomenon may contribute to the mutational robustness and evolvability of viruses and bacteria that exist in large populations