Parts, places, and perspectives : a theory of spatial relations based an mereotopology and convexity

This thesis suggests to carry on the philosophical work begun in Casati's and Varzi's seminal book Parts and Places, by extending their general reflections on the basic formal structure of spatial representation beyond mereotopology and absolute location to the question of perspectives and perspective-dependent spatial relations. We show how, on the basis of a conceptual analysis of such notions as perspective and direction, a mereotopological theory with convexity can express perspectival spatial relations in a strictly qualitative framework. We start by introducing a particular mereotopological theory, AKGEMT, and argue that it constitutes an adequate core for a theory of spatial relations. Two features of AKGEMT are of particular importance: AKGEMT is an extensional mereotopology, implying that sameness of proper parts is a sufficient and necessary condition for identity, and it allows for (lower- dimensional) boundary elements in its domain of quantification. We then discuss an extension of AKGEMT, AKGEMTS, which results from the addition of a binary segment operator whose interpretation is that of a straight line segment between mereotopological points. Based on existing axiom systems in standard point-set topology, we propose an axiomatic characterisation of the segment operator and show that it is strong enough to sustain complex properties of a convexity predicate and a convex hull operator. We compare our segment-based characterisation of the convex hull to Cohn et al.'s axioms for the convex hull operator, arguing that our notion of convexity is significantly stronger. The discussion of AKGEMTS defines the background theory of spatial representation on which the developments in the second part of this thesis are built. The second part deals with perspectival spatial relations in two-dimensional space, i.e., such relations as those expressed by 'in front of, 'behind', 'to the left/right of, etc., and develops a qualitative formalism for perspectival relations within the framework of AKGEMTS. Two main claims are defended in part 2: That perspectival relations in two-dimensional space are four- place relations of the kind R(x, y, z, w), to be read as x is i?-related to y as z looks at w; and that these four-place structures can be satisfactorily expressed within the qualitative theory AKGEMTS. To defend these two claims, we start by arguing for a unified account of perspectival relations, thus rejecting the traditional distinction between 'relative' and 'intrinsic' perspectival relations. We present a formal theory of perspectival relations in the framework of AKGEMTS, deploying the idea that perspectival relations in two-dimensional space are four-place relations, having a locational and a perspectival part and show how this four-place structure leads to a unified framework of perspectival relations. Finally, we present a philosophical motivation to the idea that perspectival relations are four-place, cashing out the thesis that perspectives are vectorial properties and argue that vectorial properties are relations between spatial entities. Using Fine's notion of "qua objects" for an analysis of points of view, we show at last how our four-place approach to perspectival relations compares to more traditional understandings.

Heidelberg Retina Tomograph in Glaucoma Case-finding

Purpose: To compare the disease classification using optic nerve head imaging against clinical examination combined with perimetry in the case-finding environment.Methods: During a glaucoma screening event at the University Hospital in Lausanne 148 attendees opted to undergo an extended screening exam consisting of perimetry with Octopus (Haag-Streit, Koeniz, Switzerland), tonometry, gonioscopy, slit-lamp optic nerve head examination and Heidelberg Retinal Tomorgraph (HRT, Heidelberg engineering). Classification criteria of an abnormal clinical exam consisted of a cup to disc ratio > 0.6, other disc abnormality (e.g. notching), closed angles, Van Herrick < ¼ and intraocular pressure >21mmHg. In perimetry a square root loss variance (sLV) >3.0 dB was considered abnormal. Those cases with both an abnormal clinical exam and abnormal perimetric results were considered to be glaucoma suspects. An abnormal HRT exam was a global Moorfields Regression Analysis (MRA) result of "outside normal limits". The results from the worse eye for each instrument are reported.Results: The mean age of the patients was 59.9 years (SD ±14.8years). 46 subjects failed the clinical exam. 55 subjects had sLV>3.0dB. 86 subjects failed one or more of the testing components, 21 subjects failed both the clinical exam and perimetry. Two cases of advanced glaucoma were diagnosed on the day of the event. 20 subjects were referred due to other ocular pathology (10 cataract; 2 AMD; 8 other). 16 subjects were outside normal limits with the HRT, of which 11 failed the clinical exam, 9 failed the perimetric exam and 7 failed all three. HRT had a sensitivity of 33% CI [15%,57%] with a specificity of 93% CI [87%,97%].Conclusions: HRT shows good specificity, however the low sensitivity makes it of limited use in the proposed case finding scenario.

Fitness and the level of homozygosity in a social insect.

To date very few studies have addressed the effects of inbreeding in social Hymenoptera, perhaps because the costs of inbreeding are generally considered marginal owing to male haploidy whereby recessive deleterious alleles are strongly exposed to selection in males. Here, we present one of the first studies on the effects of queen and worker homozygosity on colony performance. In a wild population of the ant Formica exsecta, the relative investment of single-queen colonies in sexual production decreased with increased worker homozygosity. This may either stem from increased homozygosity decreasing the likelihood of diploid brood to develop into queens or a lower efficiency of more homozygous workers at feeding larvae and thus a lower proportion of the female brood developing into queens. There was also a significant negative association between colony age and the level of queen but not worker homozygosity. This association may stem from inbreeding affecting queen lifespan and/or their fecundity, and thus colony survival. However, there was no association between queen homozygosity and colony size, suggesting that inbreeding affects colony survival as a result of inbred queens having a shorter lifespan rather than a lower fecundity. Finally, there was no significant association between either worker or queen homozygosity and the probability of successful colony founding, colony size and colony productivity, the three other traits studied. Overall, these results indicate that inbreeding depression may have important effects on colony fitness by affecting both the parental (queen) and offspring (worker)generations cohabiting within an ant colony.

Effects of inbreeding on aversive learning in Drosophila.

Inbreeding adversely affects life history traits as well as various other fitness-related traits, but its effect on cognitive traits remains largely unexplored, despite their importance to fitness of many animals under natural conditions. We studied the effects of inbreeding on aversive learning (avoidance of an odour previously associated with mechanical shock) in multiple inbred lines of Drosophila melanogaster derived from a natural population through up to 12 generations of sib mating. Whereas the strongly inbred lines after 12 generations of inbreeding (0.75<F<0.93) consistently showed reduced egg-to-adult viability (on average by 28%), the reduction in learning performance varied among assays (average=18% reduction), being most pronounced for intermediate conditioning intensity. Furthermore, moderately inbred lines (F=0.38) showed no detectable decline in learning performance, but still had reduced egg-to-adult viability, which indicates that overall inbreeding effects on learning are mild. Learning performance varied among strongly inbred lines, indicating the presence of segregating variance for learning in the base population. However, the learning performance of some inbred lines matched that of outbred flies, supporting the dominance rather than the overdominance model of inbreeding depression for this trait. Across the inbred lines, learning performance was positively correlated with the egg-to-adult viability. This positive genetic correlation contradicts a trade-off observed in previous selection experiments and suggests that much of the genetic variation for learning is owing to pleiotropic effects of genes affecting functions related to survival. These results suggest that genetic variation that affects learning specifically (rather than pleiotropically through general physiological condition) is either low or mostly due to alleles with additive (semi-dominant) effects.

Quantitative genetics of learning ability and resistance to stress in Drosophila melanogaster.

Even though laboratory evolution experiments have demonstrated genetic variation for learning ability, we know little about the underlying genetic architecture and genetic relationships with other ecologically relevant traits. With a full diallel cross among twelve inbred lines of Drosophila melanogaster originating from a natural population (0.75 < F < 0.93), we investigated the genetic architecture of olfactory learning ability and compared it to that for another behavioral trait (unconditional preference for odors), as well as three traits quantifying the ability to deal with environmental challenges: egg-to-adult survival and developmental rate on a low-quality food, and resistance to a bacterial pathogen. Substantial additive genetic variation was detected for each trait, highlighting their potential to evolve. Genetic effects contributed more than nongenetic parental effects to variation in traits measured at the adult stage: learning, odorant perception, and resistance to infection. In contrast, the two traits quantifying larval tolerance to low-quality food were more strongly affected by parental effects. We found no evidence for genetic correlations between traits, suggesting that these traits could evolve at least to some degree independently of one another. Finally, inbreeding adversely affected all traits.

Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer's disease: a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial.

BACKGROUND: Three small trials suggest that intravenous immunoglobulin can affect biomarkers and symptoms of mild-to-moderate Alzheimer's disease. We tested the safety, effective dose, and infusion interval of intravenous immunoglobulin in such patients. METHODS: We did a multicentre, placebo-controlled phase 2 trial at seven sites in the USA and five in Germany. Participants with probable Alzheimer's disease aged 50-85 years were randomly assigned (by a computer-generated randomisation sequence, with block sizes of eight) to infusions every 4 weeks (0·2, 0·5, or 0·8 g intravenous immunoglobulin per kg bodyweight, or placebo) or infusions every 2 weeks (0·1, 0·25, or 0·4 g/kg, or placebo). Patients, caregivers, investigators assessing outcomes, and staff at imaging facilities and the clinical research organisation were masked to treatment allocation, but dispensing pharmacists, the statistician, and the person responsible for final PET analyses were not. Treatment was masked with opaque pouches and infusion lines. The primary endpoint was median area under the curve (AUC) of plasma amyloid β (Aβ)(1-40) between the last infusion and the final visit (2 weeks or 4 weeks depending on infusion interval) in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT00812565) and controlled-trials.com (ISRCTN64846759). FINDINGS: 89 patients were assessed for eligibility, of whom 58 were enrolled and 55 included in the primary analysis. Median AUC of plasma Aβ(1-40) was not significantly different for intravenous immunoglobulin compared with placebo for five of the six intervention groups (-18·0 [range -1347·0 to 1068·5] for 0·2 g/kg, -364·3 [-5834·5 to 1953·5] for 0·5 g/kg, and -351·8 [-1084·0 to 936·5] for 0·8 g/kg every 4 weeks vs -116·3 [-1379·0 to 5266·0] for placebo; and -13·8 [-1729·0 to 307·0] for 0·1 g/kg, and -32·5 [-1102·5 to 451·5] for 0·25 g/kg every 2 weeks vs 159·5 [51·5 to 303·0] for placebo; p>0·05 for all). The difference in median AUC of plasma Aβ(1-40) between the 0·4 g/kg every 2 weeks group (47·0 [range -341·0 to 72·5]) and the placebo group was significant (p=0·0216). 25 of 42 (60%) patients in the intervention group versus nine of 14 (64%) receiving placebo had an adverse event. Four of 42 (10%) patients in the intravenous immunoglobulin group versus four of 14 (29%) receiving placebo had a serious adverse event, including one stroke in the intervention group. INTERPRETATION: Intravenous immunoglobulin may have an acceptable safety profile. Our results did not accord with those from previous studies. Longer trials with greater power are needed to assess the cognitive and functional effects of intravenous immunoglobulin in patients with Alzheimer's disease.