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Children born very preterm (VP) display altered growth in corticolimbic structures compared with full-term peers. Given the association between the cortiocolimbic system and anxiety, this study aimed to compare developmental trajectories of corticolimbic regions in VP children with and without anxiety diagnosis at 13 years.
MRI data from 124 VP children were used to calculate whole brain and corticolimbic region volumes at term-equivalent age (TEA), 7 and 13 years. The presence of an anxiety disorder was assessed at 13 years using a structured clinical interview.
VP children who met criteria for an anxiety disorder at 13 years (n = 16) displayed altered trajectories for intracranial volume (ICV, p < 0.0001), total brain volume (TBV, p = 0.029), the right amygdala (p = 0.0009) and left hippocampus (p = 0.029) compared with VP children without anxiety (n = 108), with trends in the right hippocampus (p = 0.062) and left medial orbitofrontal cortex (p = 0.079). Altered trajectories predominantly reflected slower growth in early childhood (0–7 years) for ICV (β = −0.461, p = 0.020), TBV (β = −0.503, p = 0.021), left (β = −0.518, p = 0.020) and right hippocampi (β = −0.469, p = 0.020) and left medial orbitofrontal cortex (β = −0.761, p = 0.020) and did not persist after adjusting for TBV and social risk.
Region- and time-specific alterations in the development of the corticolimbic system in children born VP may help to explain an increase in anxiety disorders observed in this population.
In this paper I challenge the notion that medieval philosophy was characterized by strict adherence to authority. In particular, I argue that to the contrary, self-consciously critical reflection on authority was a widespread intellectual virtue in the Islamic world. The contrary vice, called ‘taqlīd’, was considered appropriate only for those outside the scholarly elite. I further suggest that this idea was originally developed in the context of Islamic law and was then passed on to authors who worked within the philosophical tradition.
OBJECTIVES/SPECIFIC AIMS: The development of new anti-cancer agents for children requires an inherently longer timeline than in adults. The 3+3 study design for Phase 1 dose escalation trials is commonly used to estimate the maximum tolerated dose and assess safety. The Rolling 6 study design was developed to shorten the study conduct timeline. METHODS/STUDY POPULATION: This study compares twenty Phase 1 COG Pilot and Phase 1 Consortium trials that employed the Rolling 6 design with hypothetical results under the assumption that a 3+3 design had been executed. The number of evaluable patients required to complete the study, number of DLTs, number of inevaluable patients, overall study duration, time suspended to enrollment (i.e., waiting for DLT evaluation), and DLT risk are compared between study designs using Wilcoxon’s signed rank test. RESULTS/ANTICIPATED RESULTS: The Rolling 6 study design required less time to complete the studies compared with 3+3 design (median 273 vs. 297 days, P = 0.01). In general, the Rolling 6 study design required more patients, had more inevaluable patients, and there were more dose limiting toxicity (DLT) events. However, there was no significant difference in DLT risk (median 0.15 vs. 0.17, P = 0.72). DISCUSSION/SIGNIFICANCE OF IMPACT: The Rolling 6 study design effectively shortens the study conduct timeline compared with the traditional 3+3 design for Phase 1 COG Pilot and Phase 1 Consortium trials without increasing the risk of toxicity.
Introduction to the book, explaining the selection of topics and approach taken to Averroes' thought, namely to contextualize his writings within the culture of Islamic Spain. Also provides a brief summary of each of the following chapters.
Averroes seeks to ground philosophical theology in Aristotelian premises, by reconciling the treatment of God in metaphysics as a pure intellect with the portrayal of God in Aristotle's Physics as a cause of heavenly motion. Averroes’ solution to this problem appeals to the central Aristotelian distinction between four kinds of cause, namely formal, final, efficient, and material. In physics He is approached as an efficient cause of motion, while in metaphysics He appears as an efficient, formal, and final cause of being and unity.
This volume brings together world-leading scholars on the thought of Averroes, the greatest medieval commentator on Aristotle but also a major scholar of Islam. The collection situates him in his historical context by emphasizing the way that he responded to the political situation of twelfth-century Islamic Spain and the provocations of Islamic theology. It also sheds light on the interconnections between aspects of his work that are usually studied separately, such as his treatises on logic and his legal writings. Advanced students and scholars will find authoritative and insightful treatments of Averroes' philosophy, tackled from multiple perspectives and written in a clear and accessible way that will appeal to those encountering his work for the first time as well as to anyone looking for new critical approaches to Averroes and his thinking.
Alongside his much-discussed theory that humans are permanently, if only tacitly, self-aware, Avicenna proposed that in actively conscious self-knowers the subject and object of thought are identical. He applies to both humans and God the slogan that the self-knower is “intellect, intellecting, and object of intellection (‘aql, ‘āqil, ma‘qūl)”. This paper examines reactions to this idea in the Islamic East from the 12th-13th centuries. A wide range of philosophers such as Abū l-Barakāt al-Baghdādī, Faḫr al-Dīn al-Rāzī, al-Šahrastānī, Šaraf al-Dīn al-Mas‘ūdī, al-Abharī, al-Āmidī, and Naṣīr al-Dīn al-Ṭūsī raised and countered objections to Avicenna's position. One central problem was that on widely accepted definitions of knowledge – according to which knowledge is representational or consists in a relation – it seems impossible for the subject and object of knowledge to be the same. Responses to this difficulty included the idea that a self-knower is “present” to itself, or that here subject and object are different only in “aspect (i‘tibār)”.
No argument from the Arabic philosophical tradition has received more scholarly attention than Avicenna's ‘flying man’ thought experiment, in which a human is created out of thin air and is able to grasp his existence without grasping that he has a body. This paper offers a new interpretation of the version of this thought experiment found at the end of the first chapter of Avicenna's treatment of soul in the Healing. We argue that it needs to be understood in light of an epistemological theory set out elsewhere by Avicenna, which allows that all the constitutive properties of an essence will be clear to someone who understands and considers that essence. On our reading, this theory is put to work in the ‘flying man’: because the flying man would grasp that his own essence has existence without grasping that he has a body, connection to body cannot be constitutive of the essence.
The twelfth century philosopher-theologian Fakhr al-Dīn al-Rāzī is well known for his critique of Avicennan metaphysics. In this paper, I examine his critique of Avicenna's physics, and in particular his rejection of the Avicennan and Aristotelian theory of place as the inner boundary of a containing body. Instead, Fakhr al-Dīn defends a definition of place as self-subsisting extension, an idea explicitly rejected by Aristotle and Avicenna after him. Especially in his late work, the Maṭālib, Fakhr al-Dīn explores a number of important philosophical issues with reference to this theory of place, including the principle that two indiscernible things (in this case two overlapping extensions) must be identical and the idea that motion and rest are always relative.
This paper provides an analysis and translation of a previously edited, but otherwise unstudied work by Miskawayh (d. 1030) entitled On Pleasures and Pains (Fī al-Laḏḏāt wa-al-ālām). After a brief orientation regarding the Aristotelian account of pleasure in the Nicomachean Ethics, which is Miskawayh's main source, the theory of pleasure set out in On Pleasures and Pains is compared to the discussion of pleasure in Miskawayh's better known Refinement of Character (Tahḏīb al-aḫlāq). Despite considerable harmony between the two texts, their treatments of pleasure differ in that the Refinement accepts, whereas On Pleasures and Pains rejects, the “restoration” theory of pleasure of Plato's Timaeus.