The concentration of low‐density lipoprotein (LDL) cholesterol (C) in plasma is a key determinant of cardiovascular disease risk and human genetic studies have long endeavoured to elucidate the pathways that regulate LDL metabolism. Massive genome‐wide association studies (GWASs) of common genetic variation associated with LDL‐C in the population have implicated SORT1 in LDL metabolism. Using experimental paradigms and standards appropriate for understanding the mechanisms by which common variants alter phenotypic expression, three recent publications have presented divergent and (...) even contradictory findings. Interestingly, although these reports each linked SORT1 to LDL metabolism, they did not agree on a mechanism to explain the association. Here, we review recent mechanistic studies of SORT1 – the first gene identified by GWAS as a determinant of plasma LDL‐C to be evaluated mechanistically. (shrink)

Causal models have proven extremely useful in offering formal representations of causal relationships between a set of variables. Yet in many situations, there are non-causal relationships among variables. For example, we may want variables LDL, HDL, and TOT that represent the level of low-density lipoprotein cholesterol, the level of lipoprotein high-density lipoprotein cholesterol, and total cholesterol level, with the relation LDL+HDL=TOT. This cannot be done in standard causal models, because we can intervene (...) simultaneously on all three variables. The goal of this paper is to extend standard causal models to allow for constraints on settings of variables. Although the extension is relatively straightforward, to make it useful we have to define a new intervention operation that disconnects a variable from a causal equation. We give examples showing the usefulness of this extension, and provide a sound and complete axiomatization for causal models with constraints. (shrink)

Despite recent advances in the research related to air pollution and associated adverse cardiovascular events, the combined effects of air pollution, climate change, and SARS‐CoV‐2 infection on cardiovascular health need to be researched further. This Commentary addresses their impacts on cardiovascular health in the approximately 25 million people with a severe form of inherited hypercholesterolemia, called familial hypercholesterolemia (FH). The arterial endothelium in these individuals is potentially under multiple attacks caused by particles of both endogenous and exogenous origin. Thus, they (...) have a lifelong highly elevated level of circulating low density lipoprotein (LDL) cholesterol which drives premature atherosclerosis. The high levels of LDL particles, often associated with an elevated level of circulating lipoprotein(a) particles, are both capable of inducing and maintaining endothelial dysfunction. Such pre‐existing endothelial dysfunction can be exacerbated by exposure to SARS‐CoV‐2 viral particles, by exposure to fine particulate matter generated by climate change‐associated wildfires, and by dehydration during deadly heatwaves linked to the globally rising temperatures. The external factors can severely worsen the pre‐existing endothelial dysfunction, and thereby significantly increase the risk of a cardiovascular event in the exposed FH patients. (shrink)

Previous studies have found that serum lipid levels independently associate with mental health problems in adulthood. However, little is known about the association between serum lipid levels and positive aspects of mental health such as resilience and self-esteem, which develop in adolescence. The aim of this study is to examine the association between serum lipid levels and resilience and self-esteem in Japanese adolescents. Data were pooled data from the Adachi Child Health Impact of Living Difficulty study in 2016 and 2018, (...) a school-based, cross-sectional study in Adachi City, Tokyo, Japan. Resilience of the child was assessed by caregivers, and self-esteem was self-identified via questionnaires. Serum lipid levels [total cholesterol, low-density lipoproteins, and high-density lipoproteins ] were assessed in school health checkup, in addition to height and weight measurements. Multiple linear regression was applied to investigate the association between standardized serum lipid levels and resilience and self-esteem. LDL showed inverse association with resilience [β = −1.26, 95% confidence interval = −2.39 to −0.14] after adjusting for child’s BMI, month of birth, sex, absence of parent, household income, caregiver’s mental health, and lifestyle. We also found an inverse association of total cholesterol and higher LDL cholesterol with self-esteem. HDL cholesterol was not associated with resilience and self-esteem. Among Japanese adolescent, total and LDL cholesterol may be biomarkers of resilience and self-esteem. (shrink)

A common exhortation by conservationists suggests that we can solve ecological problems by returning to the attitudes of traditional societies: reverence for resources, and willingness to assume short-term individual costs for long-term, group-beneficial sustainable management. This paper uses the 186-society Standard Cross-Cultural Sample to examine resource attitudes and practices. Two main findings emerge: (1) resource practices are ecologically driven and do not appear to correlate with attitude (including sacred prohibition) and (2) the low ecological impact of many traditional societies results (...) not from conscious conservation efforts, but from various combinations of low population density, inefficient extraction technology, and lack of profitable markets for extracted resources. (shrink)

Lower plasma levels of high-density lipoproteins in adolescents with type 2 diabetes have been associated with a higher pulse wave velocity, a marker of arterial stiffness. Evidence suggests that HDL proteins or particle subspecies are altered in T2D and these may drive these relationships. In this work, we set out to reveal any specific proteins and subspecies that are related to arterial stiffness in youth with T2D from proteomics data. Plasma and PWV measurements were previously acquired from lean and (...) T2D adolescents. Each plasma sample was separated into 18 fractions and evaluated by mass spectrometry. Then, we applied a validated network-based computational approach to reveal HDL subspecies associated with PWV. Among 68 detected phospholipid-associated proteins, we found that seven were negatively correlated with PWV, indicating that they may be atheroprotective. Conversely, nine proteins show positive correlation with PWV, suggesting that they may be related to arterial stiffness. Intriguingly, our results demonstrate that apoA-I and histidine-rich glycoprotein may reverse their protective roles and become antagonistic in the setting of T2D. Furthermore, we revealed two arterial stiffness-associated HDL subspecies, each of which contains multiple PWV-related proteins. Correlation and disease association analyses suggest that these HDL subspecies might link T2D to its cardiovascular-related complications. (shrink)

To investigate the effects of two different modes of physical activity on body composition, physical fitness, cardiometabolic risk, and psychological responses in female adolescents participating in a multi-disciplinary program. The 12-week randomized intervention included 25-adolescents with overweight divided into two groups: sports practice-SPG and functional training-FTG. The SPG intervention was divided into three sports: basketball, handball, and futsal. SPG participants performed one sport 3-times/week, over the course of 1 month. The FTG performed concurrent exercises 3-times/week. This study was registered in (...) Clinical Trials Registry Platform under number: RBR-45ywtg and registered in Local Ethics Committee number: 2,505.200/2018. The intensity of physical exercises-PE was matched between groups by the rating of perceived exertion. The primary outcome was body composition, and secondary outcomes were physical fitness, cardiometabolic risk, and psychological responses. There was a significant time-effect for body mass, body mass index, and low-density lipoprotein, all being reduced. There were increases over time for musculoskeletal mass, aerobic fitness, and high-density lipoprotein. There was a group time interaction with body fat percentage being lower post-intervention in the SPG. No significant differences were observed for the other variables. Both physical activity models were effective in improving a subset of obesity-related health parameters. The findings should be extended by further investigation using more sophisticated measures of energy expenditure.Clinical Trial Registration:https://ensaiosclinicos.gov.br/, identifier: RBR-45ywtg. (shrink)

Atherosclerosis is the major cause of death in the industrialised world. Though much work on the pathogenesis of atherosclerosis points to 'oxidised' low density lipoprotein (LDL) as a key aetiological feature in the generation of the atherosclerotic plaque, the nature of this 'oxidised' LDL in vivo remains an enigma. We argue here that glycated LDL shows many of the characteristics attributed to 'oxidised LDL' and may be the source of the latter in vivo. These include the increased uptake (...) and impaired degradation of glycated LDL by macrophages and the stimulation of transendothelial chemotaxis of monocytes, cytokine secretion and platelet aggregation. We hypothesise that the covalent binding of glycated LDL to the endothelial cell wall may result in the formation of the early atherosclerotic lesion of the fatty streak and that apolipoprotein E may mediate the physiological clearance of glycated moieties. The proposed role of glycation in the pathogenesis of atherosclerosis would explain its high incidence among diabetics and the contentious epidemiological and experimental correlations between dietary sugar and atherosclerosis. (shrink)

Elselijn Kingma argues that Christopher Boorse’s biostatistical theory (the BST) does not show how the reference classes it uses are objective and naturalistic. Recently, philosophers of medicine have attempted to rebut Kingma’s concerns. I argue that these rebuttals are theoretically unconvincing, and that there are clear examples of physicians adjusting their reference classes according to their prior knowledge of health and disease. I focus on the use of age-adjusted reference classes to diagnose low bone mineral density in children. In (...) addition to using the BST’s age, sex, and species, physicians also choose to use other factors to define reference classes, such as pubertal status, bone age, body size, and muscle mass. I show that physicians calibrate the reference classes they use according to their prior knowledge of health and disease. Reference classes are also chosen for pragmatic reasons, such as to predict fragility fractures. (shrink)

In noun phrase coordinate constructions, there is a strong tendency for the syntactic structure of the second conjunct to match that of the first; the second conjunct in such constructions is therefore low in syntactic information. The theory of uniform information density predicts that low-information syntactic constructions will be counterbalanced by high information in other aspects of that part of the sentence, and high-information constructions will be counterbalanced by other low-information components. Three predictions follow: lexical probabilities will be lower (...) in second conjuncts than first conjuncts; lexical probabilities will be lower in matching second conjuncts than nonmatching ones; and syntactic repetition should be especially common for low-frequency NP expansions. Corpus analysis provides support for all three of these predictions. (shrink)

The presence of agriculture is diminishing in today’s society: it provides only a small percentage of jobs, and the number of visible farms that can provide exposure to agricultural processes is continuously decreasing. We hypothesize that the direct involvement with farm activities or interaction with farmers and visual appreciation of agricultural processes of all kinds, influences rural inhabitants’ relationship to agriculture. We assume that the latter plays a role in how far inhabitants are attached to their place, and more specifically, (...) perceive rural place. In this paper, we aim to initiate a discussion on this complex social relationship and suggest a model to capture fine interactions between relationship to agriculture and rural place attachment. We examine the direct and indirect effects from the density of resident farmers on these interactions. We set up a model using data from empirical research in Germany conducted in 2016. We surveyed rural inhabitants and interviewed farmers in villages purposefully sampled based on high and low density of resident farmers. To reveal underlying relationships among the latent constructs and more directly measurable indicators, as well as the indirect effect of farm presence on place attachment through its effect on forming perceptions about agriculture, we operationalized our analysis using a structural equation model. Besides a good model fit, our initial results indicate that rural inhabitants form stronger relationship to agriculture when the density of resident farmers is higher. Further, farm presence and attachment to rural place are positively related, but needs to be better captured. (shrink)

The close link between signaling by the developmental regulators of the Hedgehog family and cholesterol biochemistry has been known for some time. The morphogen is covalently attached to cholesterol in a peculiar autocatalytic reaction and embryonal disruption of cholesterol synthesis leads to malformations that mimic Hh signaling defects. Recently, it was furthermore shown that secreted Hh could hitchhike on lipoprotein particles to establish its morphogenic gradient in the developing embryo. Additionally, there is new evidence that the (...) Hh‐receptor Patched transmits the Hh signal by modulating the secretion of an inhibitory sterol molecule from the receiving cells. Here we present some of the most recent discoveries on the Hh–sterol link and discuss their implications from a systems design perspective. We predict that a robust functioning of the Hh pathway will require the involvement of more sterol metabolites, and these should be the subject of future research. BioEssays 29:1085–1094, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Sterols and the reductant nicotinamide adenine dinucleotide phosphate (NADPH), essential for eukaryotic life, arose because of, and as an adaptation to, rising levels of molecular oxygen (O2). Hence, the NADPH and O2‐intensive process of sterol biosynthesis is inextricably linked to redox status. In mammals, cholesterol biosynthesis is exquisitely regulated post‐translationally by multiple E3 ubiquitin ligases, with membrane associated Really Interesting New Gene (RING) C3HC4 finger 6 (MARCHF6) degrading at least six enzymes in the pathway. Intriguingly, all these MARCHF6‐dependent enzymes (...) require NADPH. Moreover, MARCHF6 is activated by NADPH, although what this means for control of cholesterol synthesis is unclear. Indeed, this presents a paradox for how NADPH regulates this vital pathway, since NADPH is a cofactor in cholesterol biosynthesis and yet, low levels of NADPH should spare cholesterol biosynthesis enzymes targeted by MARCHF6 by reducing its activity. We speculate MARCHF6 helps mammalian cells adapt to oxidative stress (signified by low NADPH levels) by reducing degradation of cholesterogenic enzymes, thereby maintaining synthesis of protective cholesterol. (shrink)

Brain function depends on the cooperation between highly specialized cells. Neurons generate electrical signals and glial cells provide structural and metabolic support. Here, I propose a new kind of job‐sharing between neurons and astrocytes. Recent studies on primary cultures of highly purified neurons from the rodent central nervous system (CNS) suggest that, during development, neurons reduce or even abandon cholesterol synthesis to save energy and import cholesterol from astrocytes via lipoproteins. The cholesterol shuttle may be restricted to (...) compartments distant from the soma including synapses and may be regulated by electrical activity. Testing these hypotheses will help to improve our still insufficient understanding of brain cholesterol metabolism and its role in neurodegeneration. BioEssays 25:72–78, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

Many industrial processes are operated in multiple modes due to different manufacturing strategies. Multimodality of process data is often accompanied with nonlinear and non-Gaussian characteristics, which makes data-driven monitoring more complicated. In this paper, statistics pattern analysis is introduced to extract low- and high-order statistics from raw process data. Support vector data description, which can deal with nonlinear and non-Gaussian problems, is applied to monitor multimode process in this paper. To improve detection performance of SVDD for training multimode data with (...) outliers, modified local reachability density ratio is proposed as a weight factor to be embedded in the weighted-SVDD model, in which the local neighbors in terms of both space and time are considered. Finally, the effectiveness and superiority of our proposed method are demonstrated by the Tennessee-Eastman process and wastewater treatment process. (shrink)

The wavefunction is the central mathematical entity of quantum mechanics, but it still lacks a universally accepted interpretation. Much effort is spent on attempts to probe its fundamental nature. Here I investigate the consequences of a matter ontology applied to spherical masses of constant bulk density. The governing equation for the center-of-mass wavefunction is derived and solved numerically. The ground state wavefunctions and resulting matter densities are investigated. A lowering of the density from its bulk value is found (...) for low masses due to increased spatial spreading. A discussion of the possibility to experimentally observe these effects is given and the possible consequences for choosing an ontological interpretation for quantum mechanics are commented upon. (shrink)

Words associated with perceptually salient, highly imageable concepts are learned earlier in life, more accurately recalled, and more rapidly named than abstract words (R. W. Brown, 1976; Walker & Hulme, 1999). Theories accounting for this concreteness effect have focused exclusively on semantic properties of word referents. A novel possibility is that word structure may also contribute to the effect. We report a corpus-based analysis of the phonological and morphological structures of a large set of nouns with imageability ratings (N = (...) 2,023). High- and low-imageability nouns differed by length, etymology, prosody, affixation, phonological neighborhood density, and rates of consonant clustering. On average, nouns denoting abstract concepts were longer, more derivationally complex, and emerged in English from a different distribution of languages than did concrete nouns. We address implications for interactivity of word form and meaning as pertain to theories of word concreteness, lexical acquisition, and word processing. (shrink)

Truth depends in some sense on reality. But it is a rather delicate matter to spell this intuition out in a plausible and precise way. According to the theory of truth-making this intuition implies that either every truth or at least every truth of a certain class of truths has a so-called truth-maker, an entity whose existence accounts for truth. This book aims to provide several ways of assessing the correctness of this controversial claim. This book presents a detailed introduction (...) to the theory of truth-making, which outlines truth-maker relations, the ontological category of truth-making entities, and the scope of a truth-maker theory. The essays brought together here represent the most important articles on truth-making in the last three decades as well as new essays by leading researchers in the field of the theory of truth and of truth-making. (shrink)

Words associated with perceptually salient, highly imageable concepts are learned earlier in life, more accurately recalled, and more rapidly named than abstract words (R. W. Brown, 1976; Walker & Hulme, 1999). Theories accounting for this concreteness effect have focused exclusively on semantic properties of word referents. A novel possibility is that word structure may also contribute to the effect. We report a corpus-based analysis of the phonological and morphological structures of a large set of nouns with imageability ratings (N = (...) 2,023). High- and low-imageability nouns differed by length, etymology, prosody, affixation, phonological neighborhood density, and rates of consonant clustering. On average, nouns denoting abstract concepts were longer, more derivationally complex, and emerged in English from a different distribution of languages than did concrete nouns. We address implications for interactivity of word form and meaning as pertain to theories of word concreteness, lexical acquisition, and word processing. (shrink)

Children who live on the margins of society are disadvantaged in achieving their developmental potential because of the lack of a necessary stable environment and nurturing care. Many early prevention programs aim at mitigating such effects, but often the evaluation of their long-term effect is missing. The aim of the study presented here was to evaluate such long-term effects in two prevention programs for children-at-risk growing up in deprived social environments focusing on child attachment representation as the primary outcome as (...) well as on self-reflective capacities of teachers taking care of these children. The latter was a key component for promoting resilient behavior in children. Five hundred and twenty-six children aged 36 to 60 months at risk due to immigration status, low family socio-economic status and child behavior were examined in a cluster-randomized study comparing two preventions, the psychodynamic, attachment-based holistic approach EARLY STEPS (ES) with the classroom based FAUSTLOS (FA) for their efficacy. Primary outcome was the child attachment representation measured by the Manchester Child Attachment Story Task (MCAST). Secondary outcomes were derived from (a) the Caregiver-Teacher Report Form (C-TRF: problem behaviors, including anxiety/depressive symptoms, emotional-reactive and somatic problems, social withdrawal, aggressive behavior, and attention deficit), from (b) the Strength and Difficulties Questionnaire (SDQ, parent version: resilience and wellbeing) and (c) Self-Reflective Scales for teachers (SRS: self-reflective capacities of teachers). Compared to baseline, attachment and behavioral problems improved in both programs. ES led to more secure and more organized attachment representations (medium effect sizes). Aggressive behavior and externalizing problems were reduced in the FA group compared with ES, particularly in boys (medium effect sizes). Self-reflective capacities of the teachers increased only in the ES group. High correlation between children’s attachment type with the number of social risk factors and the increase of problematic social behavior strongly indicate that an increase in teachers’ self-reflective capacities helps to change children’s attachment patterns which thus strengthens the resilience of these children-at-risk [An ethical vote from LPPKJP 2009-02-25 was obtained and the trial registered; Clinical trial registration information: The trial was registered 14.02.2012 (DRKS00003500;https://www.drks.de)]. (shrink)

After showing the downwards density of nonhemimaximal degrees, Downey and Stob continued to prove that the existence of a low₂, but not low, nonhemimaximal degree, and their proof uses the fact that incomplete m-topped degrees are low₂ but not low. As commented in their paper, the construction of such a nonhemimaximal degree is actually a primitive 0''' argument. In this paper, we give another construction of such degrees, which is a standard 0''-argument, much simpler than Downey and Stob's construction (...) mentioned above. (shrink)

This paper tries to investigate the future development tendency of five typical industries in China and find out whether there exists a different innovation strategy preference between Chinese firms of low- and high-knowledge density industry in the background of low-carbon sustainable development. First, this paper finds that the innovation driven-based trend of industrial development is further accelerated in China. Firms in industries with high knowledge and technology density, such as specialized-supplier, scale-intensive, and science-based industries, are more likely to (...) choose exploratory innovation strategy than exploitative innovation strategy. Firms in industries with low knowledge and technology density like service- and supplier-dominated industries are more likely to choose the exploitative innovation strategy. Second, results indicate that exploratory innovation can bring higher technological innovation performance than exploitative innovation. And the effect of the ambidextrous strategy is better than the single exploitative strategy in industries with high knowledge and technology density like specialized-supplier, scale-intensive, and science-based industries. Third, this paper suggests that innovation strategy preference plays a mediating role between industry type and technology innovation and a moderating effect of knowledge management capacity between innovation strategy and firms’ technology innovation. (shrink)

Conventional wisdom suggests mid-task rest as a potential approach to relieve the time-on-task (TOT) effect while accumulating evidence indicated that acute exercise might also effectively restore mental fatigue. However, few studies have explored the neural mechanism underlying these different break types, and the results were scattered. This study provided one of the first looks at how different types of fatigue-recovery break exerted influence on the cognitive processes by evaluating the corresponding behavioral improvement and neural response (EEG power spectral) in a (...) sustained attention task. Specifically, 19 participants performed three sessions of psychomotor vigilance tasks (PVT), with one session including a continuous 30-min PVT while the other two sessions additionally inserted a 15-min mid-task cycling and rest break, respectively. For behavioral performance, both types of break could restore objective vigilance transiently, while subjective feeling was only maintained after mid-task rest. Moreover, divergent patterns of EEG change were observed during post-break improvement. In detail, relative theta decreased and delta increased immediately after mid-task exercise, while decreased delta was found near the end of the rest-inserted task. Meanwhile, theta and delta could serve as neurological indicators to predict the reaction time change for exercise and rest intervention, respectively. In sum, our findings provided novel evidence to demonstrate divergent neural patterns following the mid-task exercise and rest intervention to counter TOT effects, which might lead to new insights into the nascent field of neuroergonomics for mental fatigue restoration. (shrink)

Jonathan Lowe argues that metaphysics should be restored to a central position in philosophy, as the most fundamental form of rational inquiry, whose findings underpin those of all other disciplines. He portrays metaphysics as charting the possibilities of existence, by idetifying the categories of being and the relations of ontological dependency between entities of different categories. He proceeds to set out a unified and original metaphysical system: he defends a substance ontology, according to which the existence of the world s (...) one world in time depends upon the existence of persisting things which retain their identity over time and through processes of qualitative change. And he contends that even necessary beings, such as the abstract objects of mathematics, depend ultimately for their existence upon there being a concrete world of enduring substances. Within his system of metaphysics Lowe seeks to answer many of the deepest and most challenging questions in philosophy. (shrink)

E. J. Lowe; The problem of the many and the vagueness of constitution, Analysis, Volume 55, Issue 3, 1 July 1995, Pages 179–182, https://doi.org/10.1093/analys/.

E. J. Lowe; Impredicative identity criteria and Davidson's criterion of event identity, Analysis, Volume 49, Issue 4, 1 October 1989, Pages 178–181, https://doi.

In this paper, rather than focusing on genes as an organising concept around which historical considerations of theory and practice in genetics are elucidated, we place genetic markers at the heart of our analysis. This reflects their central role in the subject of our account, livestock genetics concerning the domesticated pig, Sus scrofa. We define a genetic marker as a element existing in different forms in the genome, that can be identified and mapped using a variety of quantitative, classical and (...) molecular genetic techniques. The conjugation of pig genome researchers around the common object of the marker from the early-1990s allowed the distinctive theories and approaches of quantitative and molecular genetics concerning the size and distribution of gene effects to align in projects to populate genome maps. Critical to this was the nature of markers as ontologically inert, internally heterogeneous and relational. Though genes as an organising and categorising principle remained important, the particular concatenation of limitations, opportunities, and intended research goals of the pig genetics community, meant that a progressively stronger focus on the identification and mapping of markers rather than genes per se became a hallmark of the community. We therefore detail a different way of doing genetics to more gene-centred accounts. By doing so, we reveal the presence of practices, concepts and communities that would otherwise be hidden. (shrink)

In this paper, rather than focusing on genes as an organising concept around which historical considerations of theory and practice in genetics are elucidated, we place genetic markers at the heart of our analysis. This reflects their central role in the subject of our account, livestock genetics concerning the domesticated pig, Sus scrofa. We define a genetic marker as a element existing in different forms in the genome, that can be identified and mapped using a variety of quantitative, classical and (...) molecular genetic techniques. The conjugation of pig genome researchers around the common object of the marker from the early-1990s allowed the distinctive theories and approaches of quantitative and molecular genetics concerning the size and distribution of gene effects to align in projects to populate genome maps. Critical to this was the nature of markers as ontologically inert, internally heterogeneous and relational. Though genes as an organising and categorising principle remained important, the particular concatenation of limitations, opportunities, and intended research goals of the pig genetics community, meant that a progressively stronger focus on the identification and mapping of markers rather than genes per se became a hallmark of the community. We therefore detail a different way of doing genetics to more gene-centred accounts. By doing so, we reveal the presence of practices, concepts and communities that would otherwise be hidden. (shrink)

How could the self be a substance? There are various ways in which it could be, some familiar from the history of philosophy. I shall be rejecting these more familiar substantivalist approaches, but also the non-substantival theories traditionally opposed to them. I believe that the self is indeed a substance—in fact, that it is a simple or noncomposite substance—and, perhaps more remarkably still, that selves are, in a sense, self-creating substances. Of course, if one thinks of the notion of substance (...) as an outmoded relic of prescientific metaphysics—as the notion of some kind of basic and perhaps ineffablestuff—then the suggestion that the self is a substance may appear derisory. Even what we ordinarilycall‘stuffs’—gold and water and butter and the like—are, it seems, more properly conceived of as aggregates of molecules or atoms, while the latter are not appropriately to be thought of as being ‘made’ of any kind of ‘stuff’ at all. But this only goes to show that we need to think in terms of a more sophisticated notion of substance—one which may ultimately be traced back to Aristotle's conception of a ‘primary substance’ in theCategories, and whose heir in modern times is W. E. Johnson's notion of the ‘continuant’. It is the notion, that is, of a concrete individual capable of persisting identically through qualitative change, a subject of alterable predicates that is not itself predicable of any further subject. (shrink)

E. J. Lowe; Are the natural numbers individuals or sorts?, Analysis, Volume 53, Issue 3, 1 July 1993, Pages 142–146, https://doi.org/10.1093/analys/53.3.142.

E. J. Lowe, a prominent figure in contemporary metaphysics, sets out and defends his theory of what there is. His four-category ontology is a metaphysical system which recognizes four fundamental categories of beings: substantial and non-substantial particulars and substantial and non-substantial universals. Lowe argues that this system has an explanatory power which is unrivalled by more parsimonious theories and that this counts decisively in its favour. He shows that it provides a powerful explanatory framework for a unified account of causation, (...) dispositions, natural laws, natural necessity and many other related matters, thus constituting a full metaphysical foundation for natural science. (shrink)

We show that the theories ZF and ZFU are synonymous, answering a question of Visser.

Jonathan Lowe argues that metaphysics should be restored to a central position in philosophy, as the most fundamental form of inquiry, whose findings underpin those of all other disciplines. He portrays metaphysics as charting the possibilities of existence, by identifying the categories of being and the relations between them. He sets out his own original metaphysical system, within which he seeks to answer many of the deepest questions in philosophy. 'a very rich book... deserves to be read carefully by anyone (...) interested in any of the many subjects he discusses.' Katherine Hawley, British Journal of the Philosophy of Science. (shrink)