Beyond empiricism: informing vaccine development through innate immunity research.

Although a great public heath success, vaccines provide suboptimal protection in some patient populations and are not available to protect against many infectious diseases. Insights from innate immunity research have led to a better understanding of how existing vaccines work and have informed vaccine development. New adjuvants and delivery systems are being designed based upon their capacity to stimulate innate immune sensors and target antigens to dendritic cells, the cells responsible for initiating adaptive immune responses. Incorporating these adjuvants and delivery systems in vaccines can beneficially alter the quantitative and qualitative nature of the adaptive immune response, resulting in enhanced protection.

Concepts, core knowledge, and the rationalism-empiricism debate.

While Spelke provides powerful support for concept nativism, her focus on understanding concept nativism through six innate core knowledge systems is too confining. There is also no reason to suppose that the curse of a compositional mind constitutes a principled reason for positing less innate structure in explaining the origins of concepts. Any solution to such problems must take into account poverty of the stimulus considerations, which argue for postulating more innate structure, not less.

What counts as relevant criticism? Longino's critical contextual empiricism and the feminist criticism of mainstream economics.

I identify and resolve an internal tension in Critical Contextual Empiricism (CCE) - the normative account of science developed by Helen Longino. CCE includes two seemingly conflicting principles: on one hand, the cognitive goals of epistemic communities should be open to critical discussion (the openness of goals to criticism principle, OGC); on the other hand, criticism must be aligned with the cognitive goals of that community to count as "relevant" and thus require a response (the goal-relativity of response-requiring criticism principle, GRC). The co-existence of OGC and GRC enables one to draw both approving and condemning judgments about a situation in which an epistemic community ignores criticism against its goals. This tension results from conflating two contexts of argumentation that require different regulative standards. In the first-level scientific discussion, GRC is a reasonable principle but OGC is not; in the meta-level discussion about science, the reverse holds. In meta-level discussion, the relevance of criticism can be established by appealing to goals of science that are more general than the goals of a specific epistemic community. To illustrate my revision of CCE, I discuss why feminist economists' criticism of the narrowness of the goals pursued in mainstream economics is relevant criticism.

The notorious man-in-the-street: Hermann Weyl and the problem of knowledge.

Hermann Weyl's philosophical reflections remain a topic of considerable interest in the history and philosophy of science. In particular, Weyl's commitment to a form of idealism, as it pertains to his reading of Husserl and Fichte, has garnered much discussion. However, much less attention has been given to Weyl's later, and at that only partial, turn towards a form of empiricism (i.e. from the late 1920s onward). This lack of focus on Weyl's later philosophy has tended to obscure some of the most significant lessons that Weyl sought to draw from his decades of research in the foundations of mathematics and physics. In this paper, I develop some aspects of what I will term as Weyl's 'modest' empiricism. I will argue that Weyl's turn toward empiricism can be read in the context of a development of Helmholtz's epistemological program and his unique form of 'Kantianism'. The hope is that this reading will not only provide a better understanding of Weyl's later thought, especially his (1954) criticism of Cassirer, but that it may also provide the basis for a novel 'Weylian' account of the mathematization of nature underwriting the group-theoretic methodology of parts of modern physics.

Prophecy or empiricism? Clinical value of predicting versus determining genetic variant functions.

The recent explosion of epilepsy genetic testing has created challenges for interpretation of gene variants. Assessments of the functional consequences of genetic variants either by predictive or experimental strategies can contribute to estimating pathogenicity, but there is no consensus on which approach is best. The Special Interest Group on Epilepsy Genetics hosted a session during the Annual American Epilepsy Society Meeting in December 2022 to discuss this topic. The session featured a debate of the relative advantages and limitations of predicting (prophecy) versus experimentally determining (empiricism) variant function using ion channel gene variants as examples. This commentary summarizes these discussions.

Neither neural networks nor the language-of-thought alone make a complete game.

Cognitive science has evolved since early disputes between radical empiricism and radical nativism. The authors are reacting to the revival of radical empiricism spurred by recent successes in deep neural network (NN) models. We agree that language-like mental representations (language-of-thoughts [LoTs]) are part of the best game in town, but they cannot be understood independent of the other players.

TTP: From empiricism for an enigmatic disease to targeted molecular therapies.

The 100th anniversary of the first description of Thrombotic Thrombocytopenic Purpura (TTP) as a disease by Dr. Eli Moschcowitz approaches. For many decades, TTP remained mostly a mysterious fatal condition, where diagnosis was often post-mortem. Initially a pentad of symptoms was identified, a pattern that later revealed to be fallible. Sporadic observations led to empiric interventions that allowed for the first impactful breakthrough in TTP treatment, almost 70 years after its first description: the introduction of plasma exchange and infusions as treatments. The main body of knowledge within the field was gathered in the latest three decades: patient registries were set and proved crucial for advancements; the general mechanisms of disease have been described; the diagnosis was refined; new treatments and biomarkers with improvements on prognosis and management were introduced. Further changes and improvements are expected in the upcoming decades. In this review, we provide a brief historic overview of TTP, as an illustrative example of the success of translational medicine enabling to rapidly shift from a management largely based on empiricism to targeted therapies and personalized medicine, for the benefit of patients. Current management options and present and future perspectives in this still evolving field are summarized.

A Contemporary Message from Mendel's Logical Empiricism.

The gene is one of the most fundamental concepts in life sciences, having been developed in the mold of the Mendelian paradigm of heredity, which shaped genetics across 150 years. How could Mendel possibly be so prophetic in the middle of 19th century, using only the small garden of the monastery as his experimental breeding field? I believe that we are indebted to Mendel's mastery of the scientific method, which was far ahead of his time. Although his experimental technology was literally garden-variety, Mendel's excellence in the method of science, algebra, and logical analysis helped him in designing the right experiment and in interpreting the results insightfully. This may be valuable to recall in today's technology-focused culture, where the center of interest tends to be on the generation and description of high-throughput datasets from specialized genomics screens. As Mendel's story suggests, progress in 21st century genetics may also depend on the development of robust concepts and generalizations.

[Therapeutic injections and manual medicine in low-back pain : Bimodal synergies between evidence and empiricism]. / Therapeutische Injektion und Manuelle Medizin beim tiefen Rückenschmerz : Bimodale Synergien zwischen Evidenz und Empirie.

BACKGROUND: Oriented towards the therapy planning and management of rheumatic patients, and based on the differentiated therapeutic principles of manual medicine (MM) with knowledge on evidence of therapeutic local infiltration techniques (TLI), the author pleads for the establishment of a structured, mechanism-based therapy concept in the sense of "treat to target" (T2T) for patients with (chronic) degenerative low-back pain (LBP) in outpatient pain therapy care. DIAGNOSTICS: This requires a consistent (primary) diagnosis with pain analysis under the premise that LBP is always specific if it is structurally and functionally conditioned. A broad bio-psycho-social anamnesis and structure-based clinical diagnosis (imaging) with functional differentiation according to MM principles and, if necessary, interventional blocks, should result in the expression of a three-level diagnosis as a prerequisite for a mechanism-based, hierarchic step therapy in LBP. In this article, this is presented in a pragmatic, case-oriented manner, with the implementation of techniques and evidence of TLI and MM.

Holography, application, and string theory's changing nature.

Based on string theory's framework, the gauge/gravity duality, also known as holography, has the ability to solve practical problems in low energy physical systems like metals and fluids. Holographic applications open a path for conversation and collaboration between the theory-driven, high energy culture of string theory and fields like nuclear and condensed matter physics, which in contrast place great emphasis on the empirical evidence that experiment provides. This paper takes a look at holography's history, from its roots in string theory to its present-day applications that are challenging the cultural identity of the field. I will focus on two of these applications: holographic QCD and holographic superconductivity, highlighting some of the (often incompatible) historical influences, motives, and epistemic values at play, as well as the subcultural shifts that help the collaborations work. The extent to which holographic research - arguably string theory's most successful and prolific area - must change its subcultural identity in order to function in fields outside of string theory reflects its changing nature and the uncertain future of the field. Does string theory lose its identity in the low-energy applications that holography provides? Does holography still belong under string theory's umbrella, or is it destined to form new subcultures with each of its fields of application? I find that the answers to these questions are dynamic, interconnected, and highly dependent on string theory's relationship with its field of application. In some cases, holography can maintain the goals and values it inherited from string theory. In others, it instead adopts the goals and values of the field in which it is applied. These examples highlight a growing need for the STS community to expand its treatment of string theory regarding its relationship with empiricism and role as a theory of quantum gravity.1.

Kant's pragmatic use of reason from a sociological point of view: Third way or methodological impasse?

The paper focuses on the relevance of Kant's anthropologically oriented idea of the pragmatic use of reason for specific theoretical approaches in sociology. As I show in the first part, Kant's explicit presence in 20th-century sociology does not refer much to his anthropology and specifically to its cornerstone - the pragmatic use of reason which establishes a subtle connection between the theoretical and practical functions of reason. As an instrument for gaining systematic knowledge about the social world and ourselves as beings both passively and actively involved in this process, Kant's pragmatic use of reason serves a specific form of the theoretical use of reason. At the same time, it embodies a kind of practical reasoning concerning the "general welfare" in the social sphere. Building on the key arguments in the first part, I then address the question of whether we can view Kant's pragmatic approach as a possible third way for sociology today, beyond the simplifying opposition of 'theoretical' normativity and 'realistic' empiricism, and whether this third way can help us in clearing specific sociological issues. Here, I focus on two examples, namely the use of Kant's notion of "unsocial sociability" in Ralf Dahrendorf's conflict theory and on the criticism of Kant's cosmopolitanism in Ulrich Beck's reformed sociology of cosmopolitanism.

Why control an experiment?: From empiricism, via consciousness, toward Implicate Order.

Empirical research is based on observation and experimentation. Yet, experimental controls are essential for overcoming our sensory limits and generating reliable, unbiased and objective results.

Technoscientific control of nature: The ultimate paradox.

The current interlinked environmental and socioeconomic global crises constitute the gravest threat to humanity's well-being, indeed survival, today. Studies of the historical roots and contemporary manifestations of the various elements of these crises-including accelerating environmental degradation, unfettered capitalist technoscientific/industrial expansion, overpopulation, and overconsumption-are plentiful. Also well-known is the influence of Francis Bacon's writings, particularly The Advancement of Learning (1605), Novum Organon (1620), and the utopian New Atlantis (1627), on the development of empiricism and the modern scientific method as well as the reform and organization of scientific research. Bacon's significance for the founding of the Royal Society of London (1660) and for the plan and structure of the Encyclopedie (1751-1772), coupled with his oft-cited aphoristic injunctions to study nature to control/dominate it, are staples in the lore and justification of technoscience. I argue that the enduring appeal of so-called Baconianism derives, in part, from a fundamental misappropriation of certain of Bacon's original ideas. Specifically, the complex ethical and religious framework within which Bacon situated his vision of scientific and technological development was discarded (or ignored) so that, by the early decades of the 18th century, Baconianism had come to be understood almost exclusively for its utilitarian role in society. This deracinated version became the familiar trope of technoscience's unlimited potential to transform nature (including human nature and behavior) in the service of an ideology of industrial/consumerist expansion since then. Linkage between the history of science/technology and addictive consumerism, apparent by the close of the 19th century, has been insufficiently examined. Such addictive consumerist behavior and continued virtually unregulated industrialization and production, were effectively removed from ethical scrutiny and a high degree of material acquisition and personal/societal rapaciousness became the norm rather than the exception in most countries. I suggest that further historical deconstruction of this denuded Baconianism will yield important insights in the search for viable solutions to the present global socioenvironmental crises.

Scientific realism and empirical confirmation: A puzzle.

Scientific realism driven by inference to the best explanation (IBE) takes empirically confirmed objects to exist, independent, pace empiricism, of whether those objects are observable or not. This kind of realism, it has been claimed, does not need probabilistic reasoning to justify the claim that these objects exist. But I show that there are scientific contexts in which a non-probabilistic IBE-driven realism leads to a puzzle. Since IBE can be applied in scientific contexts in which empirical confirmation has not yet been reached, realists will in these contexts be committed to the existence of empirically unconfirmed objects. As a consequence of such commitments, because they lack probabilistic features, the possible empirical confirmation of those objects is epistemically redundant with respect to realism.

Sexual division and the new mythology: Goethe and Schelling.

The new mythology for which the German Romantic period called was not envisioned as antithetical to empiricism or experiential/experimental knowledge, but rather as emerging in dialogue with it to form a cultural foundation for such inquiry. Central to the mytho-scientific project were problematic theories of sexual division and generativity that established cultural baselines. This article examines the mythological investments of two influential thinkers of the period-Goethe and Schelling. It then analyzes Goethe's unique merger of mythological approaches to sex and generation with empirical observation in The Metamorphosis of Plants. It next traces Schelling's expansion of Goethe's theories of nature beyond their empirical justifications to develop a metaphysics of sexual differentiation. Finally, the article illuminates Goethe's final reply to the sexual dynamics of Naturphilosophie at the end of his life, through the analysis of a single poem, "Finding Again," in the collection God and World. Ultimately and in spite of its empirical commitments, Goethe's more flexible view of sexual correlations would lose ground to the powerful metaphysical mythology of sexual opposition as both scientific and cultural bedrock.

The theorical-methodological construction of theses and dissertations and their epistemological problems.

This essay discusses the problem of the lack of dialogue between theory/empirical reality in the construction of the theoretical structure of dissertations and doctorates in Human Sciences in Brazil; taking Geography as an example, Santos (2000) observed this problem, which persists at the national level. The proposal is to present the question and to suggest the relationship between theory/empirical reality coming of the dialogue with specific research questions. It is these research questions that will define the limitations, factors, agents, processes and structures that will be studied. The relationship between the construction of the theoretical references with specific problems allowing theoretical-methodological advances, thus adapting the reading of the general theory to empirical situations. This appropriation generates both methodological directions for how to treat the empirical and the understandings that will be used in the discussion of the results. The confrontation and discussion of the results will suggest affirmations, questions and new perceptions for the theory.

Empiricism, sciences, and engineering: cognitive science as a zone of integration.

An article by Alexandra Kirsch accepted for publication in Cognitive Processing occasioned debate among reviewers about broad methodological issues in cognitive science. One of these issues is the proper place of Popperian falsificationism in the interdisciplinary cluster. Another is the tension between abstract models and theories that apply to wide classes of cognitive systems, and models of more restricted scope intended to predict specifically human patterns of thought and behavior. The lead editorial in a Commentary debate invited by the journal's editors considers these issues from the perspective of a pragmatist philosophy of science inspired by Herbert Simon's classic (The sciences of the artificial (2nd edition 1981; 3rd edition 1996), MIT Press, Cambridge, 1969) reflections on the blurring of the distinction between science and engineering in cognitive science.

A balanced time perspective: Is it an exercise in empiricism, and does it relate meaningfully to health and well-being outcomes?

Time perspective research assesses the degree to which thoughts and feelings about the past, present and future influence behaviour, and a balanced time perspective profile has been posited as being ideal. Although this area of research has seen a move towards person-centred analyses, using either cluster analyses or a deviation from balanced time perspective (DBTP) approach, there are a number of theoretical and methodological issues that must be addressed. Using data from diverse samples in four countries, the present study used both cluster analyses and the DBTP approach to assess how cluster membership and DBTP scores related to a range of health and well-being outcomes. As in previous studies, a balanced profile only emerged once in cluster analyses, and positive-oriented profiles were associated with optimal outcomes. The study also found evidence of a relationship between DBTP scores and scores on well-being indicators. However, results gained after manipulating the DBTP equation in two different ways again indicated that higher than expected positive past and present or past and future scores were responsible for the positive outcomes. As such, these findings raise concerns regarding the use of the DBTP construct within clinical settings.

Treating invasive aspergillosis in patients with hematologic malignancy: diagnostic-driven approach versus empiric therapies.

BACKGROUND: Early antifungal therapy for invasive aspergillosis (IA) has been associated with improved outcome. Traditionally, of empiric antifungal therapy has been used for clinically suspected IA. We compared outcomes of patients with hematologic malignancy and IA who were treated with voriconazole using the diagnostic driven DDA (DDA-Vori) that includes galactomannan testing vs. empiric therapy with a non-voriconazole-containing regimen (EMP-non-Vori) or empiric therapy with voriconazole (EMP-Vori). METHODS: We retrospectively reviewed the medical records of 342 hematologic malignancy patients diagnosed with proven, or probable IA between July 1993 and February 2016 at our medical center who received at least 7 days of DDA-Vori, EMP-Vori, or EMP-non-Vori. Outcome assessment included response to therapy (clinical and radiographic), all-cause mortality, and IA-attributable mortality. RESULTS: By multivariate analysis, factors predictive of a favorable response included localized/sinus IA vs. disseminated/pulmonary IA (p <  0.0001), not receiving white blood cell transfusion (p <  0.01), and DDA-Vori vs. EMP-non-Vori (p < 0.0001). In contrast, predictors of mortality within 6 weeks of initiating IA therapy included disseminated/pulmonary infection vs. localized/sinus IA (p < 0.01), not undergoing stem cell transplantation within 1 year before IA (p = 0.01), and EMP-non-Vori vs. DDA-Vori (p < 0.001). CONCLUSIONS: DDA-Vori was associated with better outcome (response and survival) compared with EMP-non-Vori and with equivalent outcome to EMP-Vori in hematologic malignancy patients. These outcomes associated with the implementation of DDA could lead to a reduction in the unnecessary costs and adverse events associated with the widespread use of empiric therapy.