Ten years after the enactment of the Biologics Price Competition and Innovation Act, competition in biologics markets remains scant and far from sufficient for lowering prices of biologics to the level of 80-90% price drops seen in generic drug markets. This reality is not a result of one or two cardinal reasons, but many. If lowering the price of biologics is the goal and competition is the means by which we seek to achieve that goal, then there does not seem (...) to be a quick fix to address all of the many impediments to competition that plague biologics markets. Yet, certain changes to how the Food and Drug Administration evaluates and approves biologics may go a long way toward the creation of meaningful competition in biologics markets. One such change would be making original biologics' manufacturing information available to follow-on manufacturers.As recognized by several commentators, access to biologics manufacturing information is key to increasing competition in biologics markets. Without access to such information, making follow-on biologics is difficult and expensive, if not outright impossible. This is expected to be especially true for the highly anticipated class of interchangeable biologics, none of which has been approved by the FDA to date. Yet, it has long been the position of the brand-name pharmaceutical industry that biologics manufacturing information is proprietary and, thus, may not be shared. Congress has subscribed to the Industry's position, prohibiting the FDA from disclosing regulatory filings submitted by developers of original biologics, including manufacturing information, to third parties. That prohibition not only undermines competition in biologics markets, but is also wasteful, potentially unethical, and poses unnecessary risks to the health and safety of patients.This article makes the case for FDA sharing of original biologics manufacturing information with follow-on biologics developers. It is informed by the similar legal and commercial circumstances in the area of pesticides and the regulatory regime established by Congress in the Federal Insecticide, Fungicide and Rodenticide Act, which is administered by the Environmental Protection Agency. The article reviews the FIFRA regime, including its upholding as constitutional by the United States Supreme Court, and then examines its applicability to the area of biologics. The article concludes with a proposal for a similar regime to be incorporated into the pathway for approval of follow-on biologics as a means of increasing competition in biologics markets. (shrink)

This book offers a systematic account of Wittgenstein's unique ethical thought, both in his early and in his later writings.

Magnetic resonance imaging (MRI) is an imaging technique with a rapidly expanding application range. This methodology, which relies on quantum physics and substance magnetic properties, is now being routinely used in the clinics and medical research. With the advent of measuring functional brain activity with MRI (functional MRI), this methodology has reached a larger section of the neuroscience community (e.g. psychologists, neurobiologists). In the past, the use of MRI as a biomarker or as an assay to probe tissue pathophysiological condition (...) was limited. However, with the new applications of MRI: molecular imaging, contrast‐enhanced imaging and diffusion imaging, MRI is turning into a powerful tool for in vivo characterization of tissue pathophysiology. This review focuses on the diffusion MRI. Although it only measures the averaged Brownian translational motion of water molecules, using different analysis schemes, one can extract a wide range of quantitative indices that represent tissue morphology and compartmentalization. Statistical and visualization routines help to relate these indices to biologically relevant measures such as cell density, water content and size distribution. The aim of this review is to shed light on the potential of this methodology to be used in biological research. To that end, this review is intended for the non‐MRI specialists who wish to pursue biological research with this methodology. We will overview the current applications of diffusion MRI and its relation to cellular biology of brain tissue. BioEssays 30:1235–1245, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Shaul Magid's Meir Kahane: The Public Life and Political Thought of an American Jewish Radical (2021) stresses the American character of Kahane's thought. This review analyzes this claim in two ways. First, it offers a transnational perspective on Kahane's philosophy. Second, it examines Magid's concept of neo‐Kahanism in light of Kahane's legacy in Israel.

This article argues that constitutional mixture should be regarded as an inherent, inevitable feature of constitutions, and to some degree all constitutions are mixed. Thus, “mixed constitutions” should not be regarded as a distinct category of constitutions. Instead of asking whether a constitution is mixed, it might therefore be more useful to ask in which characteristics and to what extent a constitution is mixed. To demonstrate this, the article provides a preliminary typology of constitutional mixture considering the form or system (...) of government; the nature or character of government; the religious or secular identity; the flexibility or rigidity of the constitution; and its model of judicial enforcement—judicial or parliamentary supremacy. Examining these constitutional features, allows to shed light on the three different dimensions of “constitutional mixture”: First, the various features of the constitutional order do not function in a binary yes-or-no manner but appear and move along a spectrum. Second, the various features of the constitution change with time. Third, the various features of the constitutional text may be in tension with the features of the society. (shrink)

In a recent paper, Dylan Evans proposed that emotions could help solve what has been known as ‘the frame problem’. In the process, he first questioned the utility of using the frame problem as a framework. After tackling this issue, he provided an alternative terminology to the frame problem—termed ‘the search hypothesis of emotion’—in order to re-examine how emotions aid rational agents. His new terminology, however, opens itself to other critiques. While accepting the basic tenets of his analysis, I question (...) (i) whether a single search theory of emotion is adequate, and (ii) whether his theory would have been better termed ‘the search hypothesis of feeling’. Finally, I extend some of the ideas developed in Evans' paper. 1. Introduction 2. Emotion, reason and ends 3. The search hypothesis of emotion revisited 4. Conclusion. (shrink)

Hélé Béji est écrivain. Agrégée de lettres modernes, elle a enseigné la littérature à l'Université de Tunis avant de travailler à l'Unesco en tant que fonctionnaire internationale. En 1998, elle fonde le Collège international de Tunis, société littéraire où des penseurs tunisiens et étrangers viennent s’exprimer sur la culture et la politique contemporaines. Elle est l’auteur d´essais et récits qui brossent un portrait critique de la décolonisation et de l’identité culturelle. Elle consacre également des ouvrages à la question féminine, en (...) analysant les signes de sécularisation de la religion musulmane au sein des sociétés modernes. Parmi ses ouvrages publiés, on citera Désenchantement national (1982), L’imposture culturelle (1997), Nous, Décolonisés (2006), Islam Pride (2011). Nous l’avons rencontrée pour un entretien autour de son dernier ouvrage Dommage Tunisie. La dépression démocratique, Gallimard, 2019. (shrink)

ABSTRACT A common conclusion of lab dishonesty studies is that subjects cheat to a very modest extent even when they cannot get caught. The modest level of cheating is attributed to subjects’ moral feelings which restrict their cheating to a level that enables them to retain their self-image as honest individuals. The present paper questions this claim, reporting the results of two experiments which uncover a discrepancy between self-portrayed honesty and actual dishonest behavior. The experiments reveal, first, that self-portrayed honesty (...) is stricter than practical honesty, suggesting that when facing an opportunity to benefit from dishonest behavior, subjects trade off some of their self-image as honest persons for dishonestly-generated payoffs. Secondly, dishonesty out of lab, in subjects’ self-chosen environment, is greater than in the lab, with a considerable fraction of subjects cheating to the maximum extent possible. We suggest that it is not a concern about their self-image that holds subjects back from cheating maximally, but rather a concern about their social image. The modest level of dishonesty observed in the lab presumably reflects caution subjects exercise in an unsafe setup. Given an environment where they feel safe to reap the fruits of dishonesty without compromising their image as honest persons in the eyes of others, the image they have of themselves hardly plays a role in curbing their unethical behavior. (shrink)

As the COVID-19 pandemic was unfolding, a surge in scams was registered across the globe. While COVID-19 poses higher health risks for older adults, it is unknown whether older adults are also facing higher financial risks as a result of COVID-19 scams. Here, we examined age differences in vulnerability to COVID-19 scams and individual difference measures that might help explain them. A lifespan sample of sixty-eight younger, 79 middle-aged, and 63 older adults recruited through Prolific completed questions and questionnaires online. (...) In a within-subjects design, each participant responded to five COVID-19 solicitations, psychological measures, and demographic questions. Age group comparisons revealed that older adults were marginally less likely to perceive COVID-19 solicitations as genuine than middle-aged adults were. In addition, older adults perceived significantly fewer benefits than both younger and middle-aged adults did and perceived marginally higher risks than younger adults did. Hence, older adults did not exhibit greater vulnerability to COVID-19 scams. Regardless of age, intentions to respond to COVID-19 solicitations were positively predicted by higher levels of educational attainment, being married, past fraud victimization, and higher levels of positive urgency. As expected, stronger genuineness and benefit perceptions positively predicted action intentions, whereas stronger risk perceptions negatively predicted action intentions As such, COVID-19 scam susceptibility appears to be the result of a impulse control issue that is not easily inhibited, not even by past experiences of scam victimization. (shrink)

Based on electrophysiological and anatomical studies, a prevalent conception is that the visual system recovers features of the world from retinal images to generate perceptions and guide behavior. This paradigm, however, is unable to explain why visual perceptions differ from physical measurements, or how behavior could routinely succeed on this basis. An alternative is that vision does not recover features of the world, but assigns perceptual qualities empirically by associating frequently occurring stimulus patterns with useful responses on the basis of (...) survival and reproductive success. The purpose of the present article is to briefly describe this strategy of vision and the evidence for it. (shrink)

The world is experiencing a crisis of constitutional democracies. Populist leaders are abusing constitutional mechanisms, such as formal procedures of constitutional change, in order to erode the democratic order. The changes are, very often, gradual, incremental, and subtle. Each constitutional change, on its own, may not necessarily amount to a serious violation of essential democratic values. Yet, when examined in the context of an ongoing process, such constitutional changes may prove to be part of the incremental, gradual process of democratic (...) erosion in which the whole is greater than the sum of its parts. This Article explores how courts can respond to such constitutional changes. We argue the Unconstitutional Constitutional Amendment Doctrine should be adapted to respond to existing constitutional practices that utilize incremental and subtle amendments to dismantle the democratic order. We suggest that an aggregated judicial review should be developed. We must also rethink the automatic immunity – the result of two hundred years of revolutionary constitutional theory – provided to complete constitutional replacement from constitutional restrictions and scrutiny. Finally, as opposed to the instinct to require judicial self-restraint with respect to constitutional changes that concern the judiciary itself, we suggest that this is perhaps the type of changes that require strictest scrutiny. (shrink)

Numerous liver specific genes are transcriptionally activated by the binding to their promoter or enhancer of Hepatic Nuclear Factor 1 (HNF1). HNF1 contains a variant homeo‐domain and binds to DNA as either a homod‐imer or a heterodimer with the vHNF1 protein. Surprisingly, HNF1 is not restricted to hepatocytes but is expressed in epithelial cells of several endoderm derived organs and in mesoderm derived kidney tubules. Hence, HNF1 alone can not account for the differentiated state of the hepatic cells. In fact, (...) several other liver‐enriched transcription factors have been cloned. The hepatic phenotype could result from the combinatorial. expression of these regulators. Possible involvement of these trans‐acting factors in liver organogenesis and hepatic differentiation is discussed. (shrink)

ObjectivesTo examine implicit and explicit attitudes toward gay men and lesbian women among heterosexual undergraduate and graduate psychology and nursing students.MethodsImplicit attitudes were measured via the Implicit Association Test and explicit attitudes via the Attitudes Toward Lesbian Women and Gay questionnaire.Main resultsAll groups held negative implicit attitudes toward gay men and lesbian women. Among undergraduates, nursing students reported holding more negative explicit attitudes toward gay men and lesbian women than psychology students.ConclusionThe curricula in both nursing and psychology studies need to (...) address the medical and paramedical needs and issues of sexual minorities. (shrink)

Autonomous vehicles (AV) offer promising benefits to society in terms of safety, environmental impact and increased mobility. However, acute challenges persist with any novel technology, inlcuding the perceived risks and trust underlying public acceptance. While research examining the current state of AV public perceptions and future challenges related to both societal and individual barriers to trust and risk perceptions is emerging, it is highly fragmented across disciplines. To address this research gap, by using the Web of Science database, our study (...) undertakes a bibliometric and performance analysis to identify the conceptual and intellectual structures of trust and risk narratives within the AV research field by investigating engineering, social sciences, marketing, and business and infrastructure domains to offer an interdisciplinary approach. Our analysis provides an overview of the key research area across the search categories of ‘trust’ and ‘risk’. Our results show three main clusters with regard to trust and risk, namely, behavioural aspects of AV interaction; uptake and acceptance; and modelling human–automation interaction. The synthesis of the literature allows a better understanding of the public perception of AV and its historical conception and development. It further offers a robust model of public perception in AV, outlining the key themes found in the literature and, in turn, offers critical directions for future research. (shrink)

Perceptual conscious experiences result from non-conscious processes that precede them. We document a new characteristic of the cognitive system: the speed with which visual meaningful stimuli are prioritized to consciousness over competing noise in visual masking paradigms. In ten experiments (N = 399) we find that an individual's non-conscious visual prioritization speed (NVPS) is ubiquitous across a wide variety of stimuli, and generalizes across visual masks, suppression tasks, and time. We also find that variation in NVPS is unique, in that (...) it cannot be explained by variation in general speed, perceptual decision thresholds, short-term visual memory, or three networks of attention (alerting, orienting and executive). Finally, we find that NVPS is correlated with subjective measures of sensitivity, as they are measured by the Highly Sensitive Person scale. We conclude by discussing the implications of variance in NVPS for understanding individual variance in behavior and the neural substrates of consciousness. (shrink)

In two studies we investigated the association between physical cleansing and moral and immoral behavior in real-life situations. In Study 1, after a workout at the gym, participants cheated more after taking a shower than before taking one. In the second study, participants donated more money to charity before rather than after they bathed for religious purification. The results extend previous findings about moral cleansing and moral licensing and are discussed within the framework of conceptual metaphor theory.

The five of us research and teach risk analysis with an eye towards decision support. Our work has been dedicated to taming risks and helping to make challenging decisions. But nothing had prepared us for the Covid-19 pandemic. We first had to grapple with the news coming from abroad, including, for some of us, our home countries. Then, some information and research, but mostly opinions, started coming in from our academic community, and we felt the tensions. Finally, the UK went (...) into an unofficial and then official lockdown, and all University staff were asked to redirect their research capacity so as to support the national effort for risk analysis and decision support. As we write this on the 20th of April, many countries, including the UK, are starting to consider how to get out of lockdown. Like the previous stages of the pandemic, there is little data, perhaps a bit more research, surely many more opinions, and definitely an overwhelming amount of personal experiences and thoughts. Here we reflect on all of the above, just in case it can help the readers of this Minds in Society flash editorial to think and act, or at least, to not have to do so entirely on their own. As it can be expected, our collage introduces more questions than it can answer. (shrink)

The exact process that leads to the eruption of autoimmune reactions against β cells and the evolution of diabetes is not fully understood. Macrophages and T cells may launch an initial immune reaction against the pancreatic islets of Langerhans, provoking inflammation and destructive insulitis. The information on the molecular mechanisms of the emergence of β cell injury is controversial and points to possibly important roles for the perforin–granzyme, Fas–Fas-ligand (FasL) and tumor-necrosis-factor-mediated apoptotic pathways. FasL has several unique features that make (...) it a potentially ideal immunomodulatory tool. Most important, FasL is selectively toxic to cytotoxic T cells and less harmful to regulatory T cells. This review discusses the intrinsic sensitivity of β cells to FasL-mediated apoptosis, the conditions that underlie this β cell sensitivity, and the feasibility of using FasL to arrest autoimmunity and prevent islet allograft rejection. In both the autoimmune and transplant settings, it is imperative to progress from the administration of nonspecific immunosuppressive therapy to the concept of β-cell-specific immunomodulation. FasL evolves as a prime candidate for antigen-specific immunomodulation. BioEssays 28: 211–222, 2006. © 2006 Wiley periodicals, Inc. (shrink)