Hendrik Müller

Purpose: This conceptual-epistemological paper deals with the old problem of inversion of thinking, as typified by traditional metaphysics-ontology. It is proposed that a thorough constructivism -- which views structures of mind, nature, and all, as not derived from (not referring to) any pre-structured given mind-independent reality (zero-derivation, 0-D) -- can go beyond this conceptual impasse; it can also serve as a fall-back position for positive ontologies. Practical implications: The practical result of 0-D is that all structures of experience are understood as tools serving individual and collective subjects. Conclusion: This conceptual correction results in a simplification for the understanding of some conceptual puzzles, such as the mind-brain relation, but also in a considerable increase of responsibility, because entities and agents formerly considered responsible, and outside the mind, are recognized to be extensions of the subjects.

INTRODUCTION: We have previously shown that a tag single nucleotide polymorphism, which maps to the CYP3A locus, was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years.METHODS: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics.RESULTS: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios were OR = 0.98 and OR = 0.80, respectively = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls = 0.005) but not cases = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years = 0.84, 95% CI 0.75, 0.94; OR = 0.81, 95% CI 0.51, 1.30; P = 0.002) but not for those who had their menarche age ≤11 years = 1.06, 95% CI 0.95, 1.19, OR = 1.07, 95% CI 0.67, 1.72; P = 0.29).CONCLUSIONS: To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.

© 2014 Johnson et al.Introduction: We have previously shown that a tag single nucleotide polymorphism, which maps to the CYP3A locus, was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years. Methods: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics. Results: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios were OR = 0.98 and OR = 0.80, respectively. There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls but not cases. Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche ; the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years but not for those who had their menarche age ≤11 years. Conclusions: To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.

Purpose: Understanding the place of Ernst von Glasersfeld's Radical Constructivism (RC), and some of its implications, in the development of epistemology. Design: Characterization of two main options for the content of "knowledge" (without and with belief in mind-independent structures), sketch of their history in occidental thought; comparison of their properties concerning subjectivity, objectivity, second-order cybernetics, reliability of mental tools, and the needs and mechanisms for certainty and overall structures. Findings: Awareness that we structure mental working tools can, as RC suggests, replace belief in mind-independent reality, and this change dissolves the conceptual problem of metaphysics-ontology, but also eliminates the certainty expected from it, which raises the possibility of relativism. Working-concepts cannot be deconstructed because they imply no ontological claims. Subject(s) are necessarily included in all knowledge (which does not mean solipsism): because subjective experience encompasses all mental tools, including those of objectivity and mathematics, while in contrast the subject itself cannot become an objective system. Practical reliability of mental tools differs from subjective certainty, which requires an ontological leap of faith to positive beliefs: for specific tools including automata, and for positive holistic structures. However, in agreement with the constructivist view, holistic views can instead have an unstructured center, with reliability = viability, which prevents relativism. In sum, belief in mid-independent reality is needed for certainty if desired; for all other purposes constructivism is more helpful. Implications: The change in view suggested by von Glasersfeld's work is of relevance for a number of fields of study with conceptual problems (such as the mind-brain relation). However, due to their generality, the implications will need evaluation in specific instances. The question of certainty needs attention for practical reasons

Purpose: To show that the mind--brain relation can be understood from a perspective that keeps the mind at the center. Problem: Since at least the time of Augustine, the puzzle of the mind--brain relation has been how the mind is attached to, or originates from, the body or brain. This is still the prevalent scientific question. It implies assumption of a primary (ontological) subject--object split, and furthermore that subjective experience can be derived from, or even reduced to, a fictitious mind-independently pre-structured reality. This belief in mind-independent reality is closely related to the development and use of language. It in turn means that the mind cannot be real because it cannot be mind-independent and so disappears from discussion, preventing access to the mind--brain question. Solution: The problem requires an epistemology which keeps subjective experience at the center but does not interfere with objective methods. The un-testable proposition of mind-independent structures can be re-formulated as the use of templates for thinking: a method created by humans, a knowable tool, that is, "working" or "as-if" ontology-metaphysics. Truth and reality, including the reality of objective brain activity, then become working tools within ongoing subject-inclusive encompassing experience. Conclusion: The traditional mind--brain puzzle is the result of erroneous premises, and can be replaced by the question: how does working-objective knowledge originate within encompassing experience? This is a novel and contradiction-free approach to studies of the mind--brain relation and related questions

This paper wants to shed light on the way the philosophical school of Stoicsm in Greco-Roman antiquity has dealt with the relationship of men and nature by pointing out to some of the key texts in which these issues are mentioned. Although the modern concept of sustainability or environmental protection did not really exist in antiquity, the Stoa was convinced that individual decisions had a direct impact on this world. Following the concept of environmental humanities, the ancient texts and authors are collected as historical ideas of the multifaceted interactions between nature and men that can be fruitfully mirrored with the arguments of the current Anthropocene discourse and its focus on (post)industrialism. By doing so we might come across helpful approaches deeply rooted in our cultural heritage that we could possibly adopt and find practical answers for our age in terms of individual behaviour as well as management decisions to face the ecological and social challenges ahead.