Evaluative Standards In Art Criticism: A Defence

To a superficial consideration, art criticism might appear as a profession of a parasitic nature, nourishing itself on what is produced by others: by artists. In fact, however, the relation between artistic practice and its criticism is more adequately conceived of as a sort of symbiosis. For, while it is true that criticism depends on and presupposes the existence of its objects - that is, works of art - on the other hand nothing would prevent good art from being equated with and contaminated by bad art if critics ceased to draw a distinction between the two

Reaching and influencing consumers in the prescription medicine market

Purpose &ndash; Celebrex became the first of a new class of drugs known as COX-2 selective non-steroidal anti-inflammatory drugs. It improves treatment for arthritis sufferers without compromising the protective lining of the stomach. The purpose of this paper is to illustrate how direct-to-consumer advertising (DTCA) of prescription medicines can be used to rebuild faith in the cyclooxygenase-2 (COX-2) product category. Design/methodology/approach &ndash; The case is developed using published sources and no input is required from company representatives. The presentation style follows the classic comprehensive case format used in postgraduate teaching programmes. Findings &ndash; Business executives and strategic marketing students would benefit from a discussion on how external environmental factors can suddenly impose a review of marketing strategy. The reader learns how management addresses the business dilemma using DTCA. Research limitations/implications &ndash; A blockbuster rival drug Vioxx is withdrawn due to cardiovascular (CV) health safety concerns. A resulting dominant market situation soon becomes a business dilemma. The Federal Drug Administration calls for a &ldquo;black box&rdquo; warning label on Celebrex, the most serious type of warning. Practical implications &ndash; The implications are that having a product in a class of its own is not enough. It highlights the need to communicate to different audiences, to both the medical profession and the end-user. Getting doctors to recommend the medicine and pulling the product through the channel by stimulating patient demand after a health scare are paramount. Originality/value &ndash; This is the first pharmaceutical business case where the withdrawal of a rival product leaves the dominant competitor in a monopoly situation. Contrary to expectation, market share plummets despite the absence of competition.<br /

‘Doble afectación’: living with disasters and conflict in Colombia

Colombia is considered one of the most advanced countries in Latin America for disaster risk reduction (DRR). Decades of state engagement in large-scale disasters has generated a relatively mature legal and institutional framework governing disaster response and risk reduction, developed over the past 20–30 years. However, the country also has a long history of conflict, involving targeted killings, generalised violence, kidnapping and extortion. Despite a recent peace process, violence continues.As in many other parts of the world, Colombia’s current DRR policy and practice fail to take adequate account of the conflict situation. As a result, large numbers of conflict-displaced people (an estimated 15% of the country’s population is internally displaced) are highly vulnerable, with scant protection against the devastating effects of disasters. Colombia’s conflict-affected poor are forced to live in locations that increase their exposure to natural hazards. This case study sheds light on why disaster risk is so high in Colombia, and how disasters and conflict interact to increase vulnerability. In addition to exploring the current national institutional and policy frameworks for DRR, it includes a critical analysis of two recent disasters: a landslide in the Mocoa area in 2017 and the structural failure of a dam resulting in severe flooding of the Cauca River in 2018. The findings highlight the complex and inherently political nature of DRR efforts in a context of conflict, protracted displacement and troubled state–society relations. The study highlights the need for an approach that goes beyond technocratic solutions; the reality that there are competing visions for DRR in conflict situations; and the fundamental necessity of rebuilding the social contract and recognising the rights and voices of affected citizens

Phospholipase A 2 in der Parvovirus MVMp induzierten Zelllyse

Das autonome Parvovirus Minute Virus of Mice MVMp ist ein onkolytisches Virus, da es selektiv neoplastisch transformierte Zellen infiziert und tötet. Während viele zytotoxische Effekte, die eine MVMp Infektion hervorruft, auf Aktivitäten des viralen NS1 Proteins zurückgeführt wurden, sind die Ursachen der MVMp induzierten Wirtszelllyse und ihr Mechanismus bisher unklar. Das Ziel der vorliegenden Arbeit war, virale und zelluläre Faktoren der MVMp induzierten Zelllyse zu identifizieren. Es wurde vermutet, dass Phospholipase A2 (PLA2) Enzyme, die in sekretorische sPLA2, zytosolische cPLA2 und Ca2+-unabhängige iPLA2 unterteilt werden, aus den folgenden Gründen für diesen Zusammenhang von Bedeutung sein könnten. Zum einen sind sie als Phospholipidhydrolasen, neben der Produktion von Lipidsignalmediatoren, auch als wichtige Effektoren schwerwiegender Membranveränderungen in der Zelle bekannt. Zum anderen verfügt das parvovirale Kapsidprotein VP1 im N-terminalen Bereich selbst über ein PLA2 Motiv. Die in dieser Arbeit erzielten Ergebnisse zeigten, dass die N-terminale Domäne von VP1 einen essentiellen Beitrag zur MVMp induzierten Zelllyse leistet. Rekombinante MVMp Viren, die für den N-terminalen VP1 Bereich kodierten, wiesen im Vergleich zu Viren, die ausschließlich die NS Proteine exprimierten, eine stark erhöhte lytische Aktivität auf. Experimente mit rekombinanten Viren, die eine inaktivierende Mutation in der katalytischen Domäne dieses PLA2 Motivs enthielten, ließen jedoch darauf schließen, dass der Beitrag dieses Motivs zur Zelllyse nicht in seiner enzymatischen Aktivität begründet ist. Dieses Ergebnis ließ als Ursache für die beobachtete massive Freisetzung von Arachidonsäure (AA) nach der MVMp Infektion, eine Aktivität zellulärer PLA2 vermuten. AA ist ein gängiges Produkt der PLA2 katalysierten Phospholipidhydrolyse und konnte, korrelierend mit der virusinduzierten Zelllyse, im Kulturüberstand infizierter Zellen detektiert werden. Dass es sich hierbei nicht um einen Nebeneffekt der Zelllyse, sondern einen enzymatisch regulierten Prozess in den noch intakten Zellen handelte, konnte durch den Nachweis einer virusinduzierten, starken Freisetzung von Prostaglandin E2, einem Produkt des AA Metabolismus, bekräftigt werden. In anschließenden Experimenten konnte unter Verwendung etablierter selektiver PLA2 Inhibitoren sowohl die virusinduzierte AA-Freisetzung als auch die Zelllyse gehemmt werden. Die genaue Untersuchung im Hinblick auf die Aktivierung dieser Enyzme ergab, dass cPLA2 infolge der MVMp Infektion an einer für die katalytische Aktivität essentiellen Phosphorylierungsstelle phosphoryliert wird und an intrazellulären Membrankompartimenten akkumuliert. Der Nachweis einer Aktivierung von p38 und p44/42 MAPK, einem der cPLA2 Phosphorylierung vorgeschalteten Ereignis, bestätigte dieses Ergebnis. Während ein Beitrag zellulärer iPLA2 ausgeschlossen wurde, konnte die Bedeutung zellulärer sekretorischer sPLA2 hingegen nicht vollständig klargestellt werden. Basierend auf den hier gezeigten Ergebnissen muss davon ausgegangen werden, dass die MVMp Infektion keine Sekretion des Enzyms hervorruft. Eine intrazelluläre Funktion einzelner sPLA2 Subtypen konnte allerdings nicht ausgeschlossen werden. Des Weiteren geben Untersuchungen mit einem in den NS Proteinen mutierten, hypolytischen MVMp Virus Hinweise darauf, dass auch die viralen NS Proteine eine wichtige Rolle in der MVMp induzierten Zelllyse spielen, da die bei einer wildtyp MVMp Infektion nachgewiesene Stimulation der MAPK und Aktivierung der cPLA2 bei einer Infektion mit diesem Virus ausbleiben. In der vorliegenden Arbeit wurde erstmalig gezeigt, dass cPLA2 Enzyme, als zelluläre Faktoren, und die N-terminale Domäne des VP1 Proteins, als viraler Faktor, erheblich zur Parvovirus MVMp induzierten Zelllyse beitragen

Encounters Between Experiences and Measurements: The Role of Local Knowledge in Climate Change Research

Innovative approaches could enhance scientific insights into how climate change affects mountain ecosystems and livelihoods and enrich climate action. Using an inter- and transdisciplinary approach in a remote tropical dry forest region of the Andes in southern Ecuador, this article combines local knowledge about climate change and adaptation, based on perceptions and experiences, with quantitative climate measurements. Our theoretical framework is based on the concept of vulnerability and sustainable livelihoods perspectives. Methodologically, we draw on the Participatory Rural Appraisal approach. Participatory workshops and qualitative interviews were carried out in the canton of Macará between 2015 and 2017. Local and regional climate data series were analyzed for climate trends and extreme events. Our study improves understanding of the social and physical dimension of climate change. Especially in mountain areas, differing scales of climate data must be considered to capture local climate conditions and changes. Thus, local knowledge could make a major contribution to selecting representative climate datasets, estimating local impacts of climate change, and developing adaptation policies

A placebo-controlled trial of folic acid and betaine in identical twins with Angelman syndrome.

BackgroundAngelman syndrome (AS) is a neurodevelopmental disorder that is caused by maternal genetic deficiency of a gene that encodes E6-AP ubiquitin-protein ligase (gene symbol UBE3A) mapping to chromosome 15q11-q13. AS leads to stiff and jerky gait, excess laughter, seizures, and severe intellectual disability. In some parts of the brain, the paternally inherited UBE3A gene is subject to genomic imprinting by the action of the UBE3A-antisense transcript (UBE3A-ATS) on the paternally inherited allele. Consequently, only the maternally inherited UBE3A gene is expressed in mature neurons. AS occurs due to deletions of the maternal 15q11 - 13 region, paternal uniparental disomy (UPD), imprinting center defects, mutations in the maternal UBE3A gene, or other unknown genetic malfunctions that result in a silenced maternal UBE3A gene in the specific imprinted regions of the brain.ResultsA potential treatment strategy for AS is to increase methylation of UBE3A-ATS to promote expression of the paternal UBE3A gene and thus ameliorate the clinical phenotypes of AS. We treated two sets of male identical twins with class I deletions with a 1 year treatment trial of either betaine and folic acid versus placebo. We found no statistically significant changes in the clinical parameters tested at the end of the 1 year trial, nor did we find any significant adverse events.ConclusionsThis study tested the hypothesis that by increasing the methylation of the UBE3A-antisense transcript in Angelman syndrome to promote expression of the silenced paternal UBE3A gene we may ameliorate the clinical phenotypes of AS. We treated two sets of identical twins with placebo versus betaine and folic acid. Although this study represented a novel approach to treating Angelman syndrome, the differences in the developmental testing results was not significant. This paper also discusses the value of monozygotic twin studies in minimizing confounding variables and its utility in conducting small treatment studies.Trial registrationNCT00348933 . Registered 6 July 2006

Information-Theoretic Safe Exploration with Gaussian Processes

We consider a sequential decision making task where we are not allowed to evaluate parameters that violate an a priori unknown (safety) constraint. A common approach is to place a Gaussian process prior on the unknown constraint and allow evaluations only in regions that are safe with high probability. Most current methods rely on a discretization of the domain and cannot be directly extended to the continuous case. Moreover, the way in which they exploit regularity assumptions about the constraint introduces an additional critical hyperparameter. In this paper, we propose an information-theoretic safe exploration criterion that directly exploits the GP posterior to identify the most informative safe parameters to evaluate. Our approach is naturally applicable to continuous domains and does not require additional hyperparameters. We theoretically analyze the method and show that we do not violate the safety constraint with high probability and that we explore by learning about the constraint up to arbitrary precision. Empirical evaluations demonstrate improved data-efficiency and scalability.Comment: Submitted to NeurIPS 202

Value-Distributional Model-Based Reinforcement Learning

Quantifying uncertainty about a policy's long-term performance is important to solve sequential decision-making tasks. We study the problem from a model-based Bayesian reinforcement learning perspective, where the goal is to learn the posterior distribution over value functions induced by parameter (epistemic) uncertainty of the Markov decision process. Previous work restricts the analysis to a few moments of the distribution over values or imposes a particular distribution shape, e.g., Gaussians. Inspired by distributional reinforcement learning, we introduce a Bellman operator whose fixed-point is the value distribution function. Based on our theory, we propose Epistemic Quantile-Regression (EQR), a model-based algorithm that learns a value distribution function that can be used for policy optimization. Evaluation across several continuous-control tasks shows performance benefits with respect to established model-based and model-free algorithms