The blended phenotype of a germline RIT1 and a mosaic PIK3CA variant

We report a patient with a germline RIT1 and a mosaic PIK3CA variant. The diagnosis of the RASopathy was confirmed by targeted sequencing following the identification of transient cardiomyopathy in a patient with PIK3CA-related overgrowth spectrum (PROS). Our observation confirms that the PIK3CA gain-of-function (GoF) variant effects dominate those of the RASopathy, and the resulting blended phenotype mostly resembles megalencephaly-capillary malformation syndrome (MCAP PROS). There appears to be interaction between RIT1 and PI3K-AKT because the latter pathway is needed for the growth-promoting activity of the first, at least in adenocarcinomas, but the details of this interaction are not known. If so, the PIK3CA somatic variant may not be just a chance event. It could also be of etiological relevance that Rit activation mediates resistance to cellular stress—that is, promotes cell survival. This anti-apoptotic effect could also make it more likely that a cell that spontaneously acquires a PIK3CA GoF variant will survive and proliferate. We aim to encourage clinicians to investigate atypical findings in individuals with PROS. If further similar cases are reported, this would suggest that the establishment of PROS mosaicism is facilitated by the background of a RASopathy.

Teaching for Complex Systems Thinking

What do a short car trip, a pandemic, the wood-wide fungal web, a challenging learning experience, a storm, transport logistics, and the language(s) we speak have in common? All of them are systems, or multiple sets of systems within systems. What happens in any set of circumstances will depend on a mix of initial conditions, complexity dynamics, and the odd wild card (e.g., a chance event). While it is possible to model and predict what might or perhaps should happen, it is impossible to be certain. “It depends” thinking needs to be applied. Future-focused literature identifies complex systems thinking as an essential capability for citizenship, and this book sets out to show teachers how they might foster it—for themselves as well as for their students. There are implications for pedagogy, curriculum, and assessment. Multiple examples show what changes might look like, for students of different ages, and in different subject contexts. This is a book of several layers: It is both practical and philosophical. There is explicit discussion of parallels between complexity science and indigenous knowledge systems (specifically mātauranga Māori in the New Zealand context). The many examples are designed to appeal to general readers with an interest in the complex challenges facing contemporary societies, as well as to teachers at all levels of the education system.

Stagnation of life expectancy in Korea in 2018: A cause-specific decomposition analysis

According to the most recent annual report released by Korea Statistics, the life expectancy at birth (for both sexes) in 2018 was 82.7 years, an increase of 0.0 years over 2017, reflecting the first stagnation in life expectancy since 1960. In this study, a time-series analysis was conducted of trends in life expectancy from 2003 to 2018, and causes of death were analyzed using the Kannisto-Thatcher method and the Arriaga decomposition method. The time trend analysis of yearly life expectancy changes indicated that, in Korea, there was a tendency for the yearly increase in life expectancy between 2003 and 2018 to decrease by 0.0211 years per calendar year. The contribution of cardiovascular diseases, the most important contributor to the life expectancy increase in Korea, gradually decreased over this period. The contribution of cardiovascular diseases to the life expectancy increase was 0.506 years in 2003–2006, but this contribution decreased to 0.218 years in 2015–2018. The positive contributions of ill-defined causes and external causes to life expectancy increase detected in previous periods were not evident in 2015–2018. Diseases of the respiratory system made the largest negative contribution both between 2015 and 2018 and between 2017–2018. The life expectancy stagnation in 2018 could be understood as the combined effect of (a) decreasing momentum in the increase of life expectancy and (b) a chance event in 2018 involving life expectancy. Currently, it is difficult to judge whether the stagnation of life expectancy in 2018 is temporary, and further analyses of life expectancy and contributing causes of death in the future are needed.

β-glucan dependent shuttling of conidia from neutrophils to macrophages occurs during fungal infection establishment

The initial host response to fungal pathogen invasion is critical to infection establishment and outcome. However, the diversity of leukocyte-pathogen interactions is only recently being appreciated. We describe a new form of interleukocyte conidial exchange called “shuttling”. In Talaromyces marneffei and Aspergillus fumigatus zebrafish in vivo infections, live imaging demonstrated conidia initially phagocytosed by neutrophils were transferred to macrophages. Shuttling is unidirectional, not a chance event, involves alterations of phagocyte mobility, inter-cellular tethering, and phagosome transfer. Shuttling kinetics were fungal species-specific, implicating a fungal determinant. β-glucan serves as a fungal-derived signal sufficient for shuttling. Murine phagocytes also shuttled in vitro. The impact of shuttling for microbiological outcomes of in vivo infections is difficult to specifically assess experimentally, but for these two pathogens, shuttling augments initial conidial redistribution away from fungicidal neutrophils into the favourable macrophage intracellular niche. Shuttling is a frequent host/pathogen interaction contributing to fungal infection establishment patterns.

Intimate Relations: Psychoanalysis Deconstruction / La psychanalyse la déconstruction

This essay will concentrate, somewhat voyeuristically, on a particular and very special textual encounter. For if there is one text in the psychoanalytic tradition that will have caused Derrida to spill more ink than any other – it's Freud's Beyond the Pleasure Principle (1920). For ten years, from 1970–1980, Derrida returns not once but three times, on three separate occasions, in three different contexts, to Freud's text on repetition compulsion and the death drive, each time devoting more time and energy – that is to say, more pages – to it. As we will see in this essay, what emerges from this textual encounter is not only a new kind of pleasure; it is also a chance event of repetition that brings with it something strikingly new.

Aristotle on the Indetermination of Accidental Causes and Chance

This article offers an interpretation of Aristotle’s tenet that chance and accidental causes are indeterminate. According to one existing reading, the predicate ‘indeterminate’ is said of the effect of chance (and of accidental causes), meaning ‘causally indeterminate.’ Another reading claims instead that the predicate ‘indeterminate’ is said of the cause of a chance event, meaning something close to ‘potentially infinite in number.’ For my part, I contend that the predicate ‘indeterminate,’ when applied to Aristotle’s concept of accidental cause and to chance, is best understood as a second-order predicate. More precisely, Aristotle uses ‘indeterminate’ to qualify a certain type of causal relation, rather than to indicate a quality of the causal power or of the effect. As a preparatory step in my argument, I contend that ‘accidental’ and ‘per se’ are also best understood as second-order predicates of ‘cause,’ and as a corollary of my main thesis I offer an interpretation of how chance involves an infinite number of possible causes.

‘Chance Tourism’: Lucky enough to have seen what you will never see

The quest for tourist destinations that few have visited, and the experience of a journey that few can share, is becoming even more difficult for those individuals who seek a reputation as tourists. Although this search for authenticity has already been studied, there is still much to be explored. Tourists can enhance their identity as travellers by place attachment with destinations they have visited, and that no longer exist. The fact that these destinations have vanished makes their experiences unrepeatable, turning them into connoisseurs of a gone place. The narration of that past visit enters into a re-interpretation process, especially by those who have not been to these places. Through this transformation of the visit into a chance event, this article shows the connection between chance, tourism and social spatialization. Through a content analysis approach, visitors’ online comments to three tourist sites are used: the World Trade Centre in New York before 9/11, the historical sites of Nepal before the destructive earthquake of 2015 and the ‘Pioneer Cabin Tree’, a giant thousand-year-old sequoia in Calaveras Big Trees State Park, before it was blown down in a storm in 2017.

Using Lotteries in Logic of Halakhah Law. The Meaning of Randomness in Judaism

There are many phenomena in the Bible connected to the idea of the random, generally in a positive light, but sometimes in a negative one. Both in the Talmudic literature and in the Halakhah texts, the ḥazal (the Sages) also relate to random processes. As we will see here, for them every chance event has a clear meaning, usually even a holy one. In fact, every culture in the world relates to randomness. However, from the Greek philosophers until the rationalism of the 19th century, a process of denuding randomness of its holiness has been taking place. In Judaism, a lottery is not a blind process; moreover the randomness has a clear and profound theological meaning.

Why do we find ourselves around a yellow star instead of a red star?

M-dwarf stars are more abundant than G-dwarf stars, so our position as observers on a planet orbiting a G-dwarf raises questions about the suitability of other stellar types for supporting life. If we consider ourselves as typical, in the anthropic sense that our environment is probably a typical one for conscious observers, then we are led to the conclusion that planets orbiting in the habitable zone of G-dwarf stars should be the best place for conscious life to develop. But such a conclusion neglects the possibility that K-dwarfs or M-dwarfs could provide more numerous sites for life to develop, both now and in the future. In this paper we analyse this problem through Bayesian inference to demonstrate that our occurrence around a G-dwarf might be a slight statistical anomaly, but only the sort of chance event that we expect to occur regularly. Even if M-dwarfs provide more numerous habitable planets today and in the future, we still expect mid G- to early K-dwarfs stars to be the most likely place for observers like ourselves. This suggests that observers with similar cognitive capabilities as us are most likely to be found at the present time and place, rather than in the future or around much smaller stars.