Determinism and inevitability

In Freedom Evolves, Dan Dennett embarks on his second book-length attempt to lay to rest the deep metaphysical concerns that many philosophers have expressed about the possibility of human freedom.One of his main objectives in the earlier chapters of the book is to make determinism appear less threatening to our prospects for free agency than it has sometimes seemed, by attempting to show that a deterministic universe would not necessarily be a universe of which it could truly be said that everything that occurs in it is inevitable. In this paper, I want to consider Dennett’s striking argument for this conclusion in some detail. I shall begin by suggesting that on its most natural interpretation, the argument is vulnerable to a serious objection. I shall then develop a second interpretation which is more promising than the first, but will argue that without placing more weight on etymological considerations than they can really bear, it can deliver, at best, only a significantly qualified version of the conclusion that Dennett is seeking. However, although I shall be arguing that his central argument fails, it is also part of the purpose of this paper to build on what I regard as some rather insightful and suggestive material which is developed by Dennett in the course of elaborating his views. His own development of these ideas is hampered, so I shall argue, by a framework for thinking about possibility that is too crude to accommodate the immense subtlety and complexity which is exhibited by the workings of the modal verb ‘can’ and its past tense form, ‘could’; and also, I believe, by the mistaken conviction, on Dennett’s part, that any naturalistically respectable solution to the problem of free will would have to be of a compatibilist stripe. I shall attempt, in the second half of the paper, to explain what seems to me to be wrong with the framework, and to make some points about the functioning of ‘can’ and ‘could’, which I believe any adequate replacement for Dennett’s framework must respect. Ironically, though, I shall argue that it is the rejection of Dennett’s own framework which holds the key to understanding how to defend the spirit (if not the letter) of his thoughts about the invulnerability of our ordinary modal thinking to alleged threats from determinism

Can forest management based on natural disturbances maintain ecological resilience?

Given the increasingly global stresses on forests, many ecologists argue that managers must maintain ecological resilience: the capacity of ecosystems to absorb disturbances without undergoing fundamental change. In this review we ask: Can the emerging paradigm of natural-disturbance-based management (NDBM) maintain ecological resilience in managed forests? Applying resilience theory requires careful articulation of the ecosystem state under consideration, the disturbances and stresses that affect the persistence of possible alternative states, and the spatial and temporal scales of management relevance. Implementing NDBM while maintaining resilience means recognizing that (i) biodiversity is important for long-term ecosystem persistence, (ii) natural disturbances play a critical role as a generator of structural and compositional heterogeneity at multiple scales, and (iii) traditional management tends to produce forests more homogeneous than those disturbed naturally and increases the likelihood of unexpected catastrophic change by constraining variation of key environmental processes. NDBM may maintain resilience if silvicultural strategies retain the structures and processes that perpetuate desired states while reducing those that enhance resilience of undesirable states. Such strategies require an understanding of harvesting impacts on slow ecosystem processes, such as seed-bank or nutrient dynamics, which in the long term can lead to ecological surprises by altering the forest's capacity to reorganize after disturbance

Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis

Alcoholic hepatitis (AH) is a life-threatening condition characterized by profound hepatocellular dysfunction for which targeted treatments are urgently needed. Identification of molecular drivers is hampered by the lack of suitable animal models. By performing RNA sequencing in livers from patients with different phenotypes of alcohol-related liver disease (ALD), we show that development of AH is characterized by defective activity of liver-enriched transcription factors (LETFs). TGFβ1 is a key upstream transcriptome regulator in AH and induces the use of HNF4α P2 promoter in hepatocytes, which results in defective metabolic and synthetic functions. Gene polymorphisms in LETFs including HNF4α are not associated with the development of AH. In contrast, epigenetic studies show that AH livers have profound changes in DNA methylation state and chromatin remodeling, affecting HNF4α-dependent gene expression. We conclude that targeting TGFβ1 and epigenetic drivers that modulate HNF4α-dependent gene expression could be beneficial to improve hepatocellular function in patients with AH

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: The ZIKAlliance consortium

Background: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. Methods: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmissio