| 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. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 4. |
- Belfrage, Sara, 1977-
(författare)
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In the name of research : Essays on the ethical treatment of human research subjects
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Essay 1: Traffic research shares a fundamental dilemma with other areas of empirical research in which humans are potentially put at risk. Research is justified because it can improve safety in the long run. Nevertheless, people can be harmed in the research situation. Hence, we need to balance short-term risks against long-term safety improvements, much as in other areas of research with human subjects. In this paper we focus on ethical issues that arise when human beings are directly affected in the performance of research by examining how the ethical requirements in biomedical research can inform traffic research. After introducing the basic ethical requirements on biomedical research, each of the major requirements is discussed in relation to traffic research. We identify the main areas where biomedical research and traffic research differ, and where the ethical requirements from the former cannot easily be transferred to the latter. We then point to some of the issues that need to be addressed for a systematic approach to the ethics of traffic research.Essay 2: The requirement of always obtaining participants’ informed consent in research with human subjects cannot always be met, for a variety of reasons. In this paper, research situations where informed consent is unobtainable are described and categorised. Some of these kinds of situations, common in biomedicine and psychology, have been previously much discussed, whereas others, more prevalent in for example infrastructure research, introduce new perspectives. The advancement of new technology may lead to an increase in research of these kinds. The paper also provides a review of methods intended to compensate for a lack of consent and their applicability and usefulness for the different categories of situations are discussed, thereby providing insights into one important aspect of relevance for the question of permitting research without informed consent: how well that which informed consent is meant to safeguard can be achieved by other means.Essay 3: This paper starts with the assumption that it is morally problematic when people in need are offered money in exchange for research participation if the amount offered is unfair. Such offers are called “coercive”, and the degree of coerciveness is said to be determined by the offer’s potential to cause exploitation and its irresistibility. Depending on what view we take on the possibility to compensate for the sacrifices made by research participants, a wish to avoid “coercive offers” leads to policy recommendations concerning payment for participation. For sacrifices considered compensable we ought to offer either no payment or payment at a level deemed fair, while for sacrifices deemed incompensable we always ought to offer no payment.Essay 4: It is commonly thought that transactions that are the result of voluntary gift-giving do not constitute exploitation. This paper argues that exploitation is indeed possible in such situations, by showing how gift-giving can fulfil the two commonly proposed criteria for exploitation, namely that in an interaction between two persons one receives disproportionally little and the other disproportionally much of the resulting benefits, and that this disproportion is caused by the latter making inappropriate use of a disadvantage of the former. A theoretical approach to what such inappropriate use would amount to in cases of gift-giving is lacking. The paper therefore aims at spelling out such an approach. The method of reflective equilibrium inspires this endeavour, which proceeds by testing intuitions about examples that embody a set of possible conditions. It is concluded that three of the conditions are necessary for exploitation of gift-giving, namely (1) the giver incurs a loss, (2) the recipient has aimed for the gift, and (3) the gift is undeserved.
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| 5. |
- Blomkvist, Katarina, et al.
(författare)
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The adventurous gene : Technological imprinting in the international growth of the multinational corporation.
- 2013
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Konferensbidrag (refereegranskat)abstract
- In this paper we explore the notion of imprinting in the multinational corporation (MNC), specifically how during the brief period when foreign subsidiaries turn into technologically advanced units they are influenced by the technological activities carried out at headquarters and home country units. We hypothesize and empirically show that during that period of transition the degree of adventurousness or explorative intensity of home country units is replicated and has a long-lasting effect on the type of technological work carried out by the foreign subsidiaries. The results suggest the systematic transfer of an ‘adventurous gene’ in the international growth of the MNC, with potentially broader implications for the study of foreign subsidiary development and a furthering of the evolutionary theory of the MNC.
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| 6. |
- Cantwell, John
(författare)
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A Formal Model of Multi-Agent Belief-Interaction
- 2006
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Ingår i: Journal of Logic, Language and Information. - : Springer Science and Business Media LLC. - 0925-8531 .- 1572-9583. ; 15:4, s. 303-329
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Tidskriftsartikel (refereegranskat)abstract
- A semantics is presented for belief revision in the face of common announcements to a group of agents that have beliefs about each other's beliefs. The semantics is based on the idea that possible worlds can be viewed as having an internal-structure, representing the belief independent features of the world, and the respective belief states of the agents in a modular fashion. Modularity guarantees that changing one aspect of the world (a belief independent feature or a belief state) has no effect on any other aspect of the world. This allows us to employ an AGM-style selection function to represent revision. The semantics is given a complete axiomatisation (identical to the axiomatisation found by Gerbrandy and Groeneveld for a semantics based on non-wellfounded set theory) for the special case of expansion.
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| 7. |
- Cantwell, John
(författare)
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A model for updates in a multi-agent setting
- 2007
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Ingår i: Journal of Applied Non-Classical Logics. - : Informa UK Limited. - 1166-3081 .- 1958-5780. ; 17:2, s. 183-196
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Cantwell, John
(författare)
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An Expressivist Analysis Of The Indicative Conditional With A Restrictor Semantics
- 2021
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Ingår i: The Review of Symbolic Logic. - : Cambridge University Press (CUP). - 1755-0203 .- 1755-0211. ; 14:2, s. 487-530
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Tidskriftsartikel (refereegranskat)abstract
- A globally expressivist analysis of the indicative conditional based on the Ramsey Test is presented. The analysis is a form of 'global' expressivism in that it supplies acceptance and rejection conditions for all the sentence forming connectives of propositional logic (negation, disjunction, etc.) and so allows the conditional to embed in arbitrarily complex sentences (thus avoiding the Frege-Geach problem). The expressivist framework is semantically characterized in a restrictor semantics due to Vann McGee, and is completely axiomatized in a logic dubbed ICL ('Indicative Conditional Logic'). The expressivist framework extends the AGM (after Alchourron, Gardenfors, Makinson) framework for belief revision and so provides a categorical ('yes'-'no') epistemology for conditionals that complements McGee's probabilistic framework while drawing on the same semantics. The result is an account of the semantics and acceptability conditions of the indicative conditional that fits well with the linguistic data (as pooled by linguists and from psychological experiments) while integrating both expressivist and semanticist perspectives.
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| 9. |
- Cantwell, John
(författare)
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An Expressivist Bilateral Meaning-is-Use Analysis of Classical Propositional Logic
- 2014
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Ingår i: Journal of Logic, Language and Information. - : Springer Science and Business Media LLC. - 0925-8531 .- 1572-9583. ; 24:1, s. 27-51
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Tidskriftsartikel (refereegranskat)abstract
- The connectives of classical propositional logic are given an analysis in terms of necessary and sufficient conditions of acceptance and rejection, i.e. the connectives are analyzed within an expressivist bilateral meaning-is-use framework. It is explained how such a framework differs from standard (bilateral) inferentialist frameworks and it is argued that it is better suited to address the particular issues raised by the expressivist thesis that the meaning of a sentence is determined by the mental state that it is conventionally used to express. Furthermore, it is shown that the classical requirements governing the connectives completely characterize classical logic, are conservative (indeed make the connectives redundant) and separable, are in bilateral harmony, are structurally preservative with respect to the classical coordination requirements and resolve the categoricity problem. These results are taken to show that one can give an expressivist bilateral meaning-is-use analysis of the connectives that confer on them a determinate coherent classical interpretation.
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| 10. |
- Cantwell, John
(författare)
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Changing the modal context
- 2008
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Ingår i: Theoria. - : Wiley. - 0040-5825 .- 1755-2567. ; 74:4, s. 331-351
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Tidskriftsartikel (refereegranskat)abstract
- Conditionals that contain a modality in the consequent give rise to a particular semantic phenomenon whereby the antecedent of the conditional blocks possibilities when interpreting the modality in the consequent. This explains the puzzling logical behaviour of constructions like "If you don't buy a lottery ticket, you can't win", "If you eat that poison, it is unlikely that you will survive the day" and "If you kill Harry, you ought to kill him gently". In this paper it is argued that a semantic version of the Ramsey Test provides a key in the analysis of such constructions. The logic for this semantics is axiomatized and some examples are studied, among them a well-known puzzle for contrary-to-duty obligations.
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