| 1. |
- Wang, Li-San, et al.
(författare)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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| 2. |
- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 3. |
- Cantwell, John
(författare)
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Expressivism detrivialized
- 2015
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Ingår i: Logique et Analyse. - : Peeters Publishers. - 0024-5836 .- 2295-5836. ; 58:232, s. 487-508
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Tidskriftsartikel (refereegranskat)abstract
- It is argued that David Lewis' two triviality results (the probability of the conditional cannot be the conditional probability; desire cannot be belief) both present a potential problem for expressivism, are related, and can both be resolved in the same way: by allowing for gappy propositions (propositions that can lack truth value). In particular, a semantics for 'A is good' is provided that allows one to embrace the major premises leading up to Lewis' triviality result while avoiding its conclusion.
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| 4. |
- Cantwell, John
(författare)
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Making sense of (in)determinate truth : the semantics of free variables
- 2018
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Ingår i: Philosophical Studies. - : Springer. - 0031-8116 .- 1573-0883. ; 175:11, s. 2715-2741
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Tidskriftsartikel (refereegranskat)abstract
- It is argued that truth value of a sentence containing free variables in a context of use (or the truth value of the proposition it expresses in a context of use), just as the reference of the free variables concerned, depends on the assumptions and posits given by the context. However, context may under-determine the reference of a free variable and the truth value of sentences in which it occurs. It is argued that in such cases a free variable has indeterminate reference and a sentence in which it occurs may have indeterminate truth value. On letting, say, x be such that x(2) = 4, the sentence 'Either x = 2 or x = -2' is true but the sentence 'x = 2' has an indeterminate truth value: it is determinate that the variable x refers to either 2 or -2, but it is indeterminate which of the two it refers to, as a result 'x = 2' has a truth value but its truth value is indeterminate. The semantic indeterminacy is analysed in a 'radically' supervaluational (or plurivaluational) semantic framework closely analogous to the treatment of vagueness in McGee and McLaughlin (South J Philos 33: 203-251, 1994, Linguist Philos 27: 123-136, 2004) and Smith (Vagueness and degrees of truth, Oxford University Press, Oxford, 2008), which saves bivalence, the T-schema and the truth-functional analysis of the boolean connectives. It is shown that on such an analysis the modality 'determinately' is quite clearly not an epistemic modality, avoiding a potential objection raised by Williamson (Vagueness, Routledge, London, 1994) against such 'radically' supervaluational treatments of vagueness, and that determinate truth (rather than truth simpliciter) is the semantic value preserved in classically valid arguments. The analysis is contrasted with the epistemicist proposal of Breckenridge and Magidor (Philos Stud 158: 377-400, 2012) which implies that (in the given context) 'x = 2' has a determinate but unknowable truth value.
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| 5. |
- Cantwell, John, et al.
(författare)
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McGee's Counterexample to the Ramsey Test
- 2017
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Ingår i: Theoria. - : DPHT Stockholm. - 0040-5825 .- 1755-2567. ; 83:2, s. 154-168
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Tidskriftsartikel (refereegranskat)abstract
- Vann McGee has proposed a counterexample to the Ramsey Test. In the counterexample, a seemingly trustworthy source has testified that p and that if not-p, then q. If one subsequently learns not- p (and so learns that the source is wrong about p), then one has reason to doubt the trustworthiness of the source (perhaps even the identity of the source) and so, the argument goes, one has reason to doubt the conditional asserted by the source. Since what one learns is that the antecedent of the conditional holds, these doubts are contrary to the Ramsey Test. We argue that the counterexample fails. It rests on a principle of testimonial dependence that is not applicable when a source hedges his or her claims.
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| 6. |
- Cantwell, John, et al.
(författare)
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Probability, coherent belief and coherent belief changes
- 2019
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Ingår i: Annals of Mathematics and Artificial Intelligence. - : Springer Netherlands. - 1012-2443 .- 1573-7470. ; 87, s. 259-291
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Tidskriftsartikel (refereegranskat)abstract
- This paper is about the statics and dynamics of belief states that are represented by pairs consisting of an agent’s credences (represented by a subjective probability measure) and her categorical beliefs (represented by a set of possible worlds). Regarding the static side, we argue that the latter proposition should be coherent with respect to the probability measure and that its probability should reach a certain threshold value. On the dynamic side, we advocate Jeffrey conditionalisation as the principal mode of changing one’s belief state. This updating method fits the idea of the Lockean Thesis better than plain Bayesian conditionalisation, and it affords a flexible method for adding and withdrawing categorical beliefs. We show that it fails to satisfy the traditional principles of Inclusion and Preservation for belief revision and the principle of Recovery for belief withdrawals, as well as the Levi and Harper identities. We take this to be a problem for the latter principles rather than for the idea of coherent belief change.
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| 7. |
- Hansson, Sven Ove, et al.
(författare)
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Self-Defeating Goals
- 2016
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Ingår i: Dialectica. - : Wiley-Blackwell. - 0012-2017 .- 1746-8361. ; 70:4, s. 491-512
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Tidskriftsartikel (refereegranskat)abstract
- The typical function of goals is to regulate action in a way that furthers goal achievement. Goals are typically set on the assumption that they will help bring the agent(s) closer to the desired state of affairs. However, sometimes endorsement of a goal, or the processes by which the goal is set, can obstruct its achievement. When this happens, the goal is self-defeating. Self-defeating goals are common in both private and social decision-making but have not received much attention by decision theorists. In this paper, we investigate different variants of three major types of self-defeating mechanisms: (1) The goal can be an obstacle to its own fulfilment (self-defeating goal endorsement), (2) goal-setting activities can impede goal achievement (self-defeating goal-setting), and (3) disclosure of the goal can interfere with its attainment (self-defeating goal disclosure). Different strategies against self-defeasance are tentatively explored, and their efficiency against different types of self-defeasance is investigated.
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| 8. |
- Heald, G. H., et al.
(författare)
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The LOFAR Multifrequency Snapshot Sky Survey (MSSS) : I. Survey description and first results
- 2015
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 582, s. 1-22
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Tidskriftsartikel (refereegranskat)abstract
- We present the Multifrequency Snapshot Sky Survey (MSSS), the first northern-sky Low Frequency Array (LOFAR) imaging survey. In this introductory paper, we first describe in detail the motivation and design of the survey. Compared to previous radio surveys, MSSS is exceptional due to its intrinsic multifrequency nature providing information about the spectral properties of the detected sources over more than two octaves (from 30 to 160 MHz). The broadband frequency coverage, together with the fast survey speed generated by LOFAR’s multibeaming capabilities, make MSSS the first survey of the sort anticipated to be carried out with the forthcoming Square Kilometre Array (SKA). Two of the sixteen frequency bands included in the survey were chosen to exactly overlap the frequency coverage of large-area Very Large Array (VLA) and Giant Metrewave Radio Telescope (GMRT) surveys at 74 MHz and 151 MHz respectively. The survey performance is illustrated within the MSSS Verification Field (MVF), a region of 100 square degrees centered at (α,δ)J2000 = (15h,69°). The MSSS results from the MVF are compared with previous radio survey catalogs. We assess the flux and astrometric uncertainties in the catalog, as well as the completeness and reliability considering our source finding strategy. We determine the 90% completeness levels within the MVF to be 100 mJy at 135 MHz with 108″ resolution, and 550 mJy at 50 MHz with 166″ resolution. Images and catalogs for the full survey, expected to contain 150 000–200 000 sources, will be released to a public web server. We outline the plans for the ongoing production of the final survey products, and the ultimate public release of images and source catalogs.
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| 9. |
- Jerkert, Jesper
(författare)
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Philosophical Issues in Medical Intervention Research
- 2015
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The thesis consists of an introduction and two papers. In the introduction a brief historical survey of empirical investigations into the effectiveness of medicinal interventions is given. Also, the main ideas of the EBM (evidence-based medicine) movement are presented. Both included papers can be viewed as investigations into the reasonableness of EBM and its hierarchies of evidence.Paper I: Typically, in a clinical trial patients with specified symptoms are given either of two or more predetermined treatments. Health endpoints in these groups are then compared using statistical methods. Concerns have been raised, not least from adherents of so-called alternative medicine, that clinical trials do not offer reliable evidence for some types of treatment, in particular for highly individualized treatments, for example traditional homeopathy. It is argued that such concerns are unfounded. There are two minimal conditions related to the nature of the treatments that must be fulfilled for evaluability in a clinical trial, namely (1) the proper distinction of the two treatment groups and (2) the elimination of confounding variables or variations. These are delineated, and a few misunderstandings are corrected. It is concluded that the conditions do not preclude the testing of alternative medicine, whether individualized or not.Paper II: Traditionally, mechanistic reasoning has been assigned a negligible role in standard EBM literature, although some recent authors have argued for an upgrading. Even so, mechanistic reasoning that has received attention has almost exclusively been positive -- both in an epistemic sense of claiming that there is a mechanistic chain and in a health-related sense of there being claimed benefits for the patient. Negative mechanistic reasoning has been neglected, both in the epistemic and in the health-related sense. I distinguish three main types of negative mechanistic reasoning and subsume them under a new definition of mechanistic reasoning in the context of assessing medical interventions. Although this definition is wider than a previous suggestion in the literature, there are still other instances of reasoning that concern mechanisms but do not (and should not) count as mechanistic reasoning. One of the three distinguished types, which is negative only in the health-related sense, has a corresponding positive counterpart, whereas the other two, which are epistemically negative, do not have such counterparts, at least not that are particularly interesting as evidence. Accounting for negative mechanistic reasoning in EBM is therefore partly different from accounting for positive mechanistic reasoning. Each negative type corresponds to a range of evidential strengths, and it is argued that there are differences with respect to the typical strengths. The variety of negative mechanistic reasoning should be acknowledged in EBM, and presents a serious challenge to proponents of so-called medical hierarchies of evidence.
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| 10. |
- Mebius, Alexander
(författare)
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Philosophical controversies in the evaluation of medical treatments : With a focus on the evidential roles of randomization and mechanisms in Evidence-Based Medicine
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis examines philosophical controversies surrounding the evaluation of medical treatments, with a focus on the evidential roles of randomised trials and mechanisms in Evidence-Based Medicine. Current 'best practice' usually involves excluding non-randomised trial evidence from systematic reviews in cases where randomised trials are available for inclusion in the reviews. The first paper challenges this practice and evaluates whether adding of evidence from non-randomised trials might improve the quality and precision of some systematic reviews. The second paper compares the alleged methodological benefits of randomised trials over observational studies for investigating treatment benefits. It suggests that claims about the superiority of well-conducted randomised controlled trials over well-conducted observational studies are justified, especially when results from the two methods are contradictory. The third paper argues that postulating the unpredictability paradox in systematic reviews when no detectable empirical differences can be found requires further justification. The fourth paper examines the problem of absence causation in the context of explaining causal mechanisms and argues that a recent solution (Barros 2013) is incomplete and requires further justification. Solving the problem by describing absences as causes of 'mechanism failure' fails to take into account the effects of absences that lead to vacillating levels of mechanism functionality (i.e. differences in effectiveness or efficiency). The fifth paper criticises literature that has emphasised functioning versus 'broken' or 'non-functioning' mechanisms emphasising that many diseases result from increased or decreased mechanism function, rather than complete loss of function. Mechanistic explanations must account for differences in the effectiveness of performed functions, yet current philosophical mechanistic explanations do not achieve this. The last paper argues that the standard of evidence embodied in the ICE theory of technological function (i.e. testimonial evidence and evidence of mechanisms) is too permissive for evaluating whether the proposed functions of medical technologies have been adequately assessed and correctly ascribed. It argues that high-quality evidence from clinical studies is necessary to justify functional ascriptions to health care technologies.
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