O značenju i nekim kontekstima termina ‘autonomija’. Konceptualno istraživanje

The paper aims to analyse conceptually the meaning of the term ‘autonomy’ and to examine critically its relations with other ethical norms. The question posed is whether autonomy is a right, or an ability, or a capacity, or an achievement, and whether it ought to be distinguished from self-determination. It is shown that autonomy is an anthropological principle, and that self-determination as its manifestation is a human right. As to its relation with other ethical norms, it is shown that there are possible conflicts between a patient’s and his doctor’s autonomies, as well as between autonomy and the duty to protect life, and between autonomy and care, so that trust plays an important role. The author concludes that man is autonomous not if and only if he is able to determine himself, but rather that he has the right to determine himself because he is autonomous. This holds for everybody from their beginning to their end, irrespective of what they are able to do and the situation they may be in. Since every human being is autonomous, autonomy entails self-limitation, and so it does not mean independence, but interdependence. As to trust, autonomy is to be acknowledged, while trust is to be practiced, since autonomy is of people, while trust is in people.Cet article tente d’analyser de manière conceptuelle la signification du terme d’autonomie et de questionner ses rapports avec d’autres normes éthiques. La question est de savoir si l’autonomie est un droit, une faculté ou une possibilité, et s’il faut la différencier de l’autodétermination. Il est montré que l’autonomie est un principe anthropologique et que l’autodétermination, qui en est sa manifestation, est un droit humain. En ce qui concerne ses rapports avec d’autres normes éthiques, il est montré que d’autres conflits sont possibles, des conflits entre l’autonomie du patient et l’autonomie du médecin, entre l’autonomie et les devoirs de protection de la vie, mais aussi entre l’autonomie et les soins. Ainsi, un rôle important revient à la confiance. L’auteur conclut que l’homme n’est pas autonome, si et seulement si, il est capable d’autodétermination, mais c’est bien parce qu’il a un droit à l’autodétermination qu’il est autonome. Cela vaut pour chacun depuis ses débuts jusqu’à ses fins, indépendamment de ce dont il est capable de faire et de la situation dans laquelle il peut se trouver. Étant donné que chaque être humain est autonome, l’autonomie entraîne à ses côtés l’autolimitation, de telle manière qu’il ne s’agit pas d’indépendance mais d’interdépendance. En ce qui concerne la confiance, l’autonomie doit être reconnue, et la confiance doit être pratiquée, car ce dont il s’agit c’est d’autonomie des personnes, et c’est bien en la personne que l’on a confiance.Der Beitrag gilt einer Analyse der Bedeutung des Terminus ‚Autonomie’ sowie einer kritischen Prüfung seiner Beziehungen zu anderen ethischen Normen. Zu klären ist, ob Autonomie ein Recht, eine Fähigkeit, ein Vermögen oder eine Errungenschaft darstellt und ob man zwischen Autonomie und Selbstbestimmung unterscheiden muss. Es wird gezeigt, dass Autonomie ein anthropologisches Prinzip ist und Selbstbestimmung als Manifestation von Autonomie ein menschliches Recht. Was die Beziehungen zu anderen ethischen Normen angeht, so zeigen sich mögliche ethische Konflikte zwischen Patienten- und Arztautonomie, zwischen Autonomie und der Pflicht zum Lebensschutz und zwischen Autonomie und Fürsorge, was der Norm des Vertrauens eine wichtige Rolle zuweist. Der Autor gelangt zu dem Ergebnis, dass der Mensch nicht deswegen noch dann autonom ist, wenn er sich selbst zu bestimmen in der Lage ist, sondern dass er das Recht zur Selbstbestimmung besitzt, weil er autonom ist. Dies gilt für jedermann, unabhängig von seinem Können oder seiner Lebenssituation, vom Anfang bis zum Ende seines Lebens. Da jedes menschliche Wesen in diesem Sinne autonom ist, impliziert Autonomie Selbstbegrenzung und somit nicht Unabhängigkeit, sondern Interdependenz. Was die Norm des Vertrauens angeht, so muss Autonomie anerkannt, Vertrauen hingegen praktiziert werden. Denn: Autonomie gehört untrennbar zum Menschen, Vertrauen gilt dem Menschen.Članak nastoji konceptualno analizirati značenje termina ‘autonomija’ i kritički ispitati njegove odnose s drugim etičkim normama. Postavlja se pitanje je li autonomija pravo ili sposobnost ili mogućnost te da li bi ju trebalo razlikovati od samoodređenja. Pokazuje se da je autonomija antropološki princip te da je samoodređenje kao njezina manifestacija ljudsko pravo. Što se tiče njezina odnosa s drugim etičkim normama, pokazuje se da su mogući sukobi između autonomije pacijenta i autonomije liječnika, kao i između autonomije i dužnosti zaštite života te između autonomije i skrbi, tako da važnu ulogu igra povjerenje. Autor zaključuje da čovjek nije autonoman ako i samo ako je sposoban za samoodređenje nego da ima pravo na samoodređenje zato što je autonoman. To važi za svakoga od njegova početka do njegova kraja, bez obzira na to što je sposoban učiniti i situaciju u kojoj se može naći. Budući da je svako ljudsko biće autonomno, autonomija za sobom povlači samoograničavanje, tako da ne znači nezavisnost, nego međuzavisnost. Što se tiče povjerenja, autonomiju treba priznavati, a povjerenje treba prakticirati zato što se radi o autonomiji ljudi, a povjerenje se ima u ljude

Bounded Arithmetic in Free Logic

One of the central open questions in bounded arithmetic is whether Buss' hierarchy of theories of bounded arithmetic collapses or not. In this paper, we reformulate Buss' theories using free logic and conjecture that such theories are easier to handle. To show this, we first prove that Buss' theories prove consistencies of induction-free fragments of our theories whose formulae have bounded complexity. Next, we prove that although our theories are based on an apparently weaker logic, we can interpret theories in Buss' hierarchy by our theories using a simple translation. Finally, we investigate finitistic G\"odel sentences in our systems in the hope of proving that a theory in a lower level of Buss' hierarchy cannot prove consistency of induction-free fragments of our theories whose formulae have higher complexity

Towards robust and replicable sex differences in the intrinsic brain function of autism.

BACKGROUND: Marked sex differences in autism prevalence accentuate the need to understand the role of biological sex-related factors in autism. Efforts to unravel sex differences in the brain organization of autism have, however, been challenged by the limited availability of female data. METHODS: We addressed this gap by using a large sample of males and females with autism and neurotypical (NT) control individuals (ABIDE; Autism: 362 males, 82 females; NT: 409 males, 166 females; 7-18 years). Discovery analyses examined main effects of diagnosis, sex and their interaction across five resting-state fMRI (R-fMRI) metrics (voxel-level Z > 3.1, cluster-level P < 0.01, gaussian random field corrected). Secondary analyses assessed the robustness of the results to different pre-processing approaches and their replicability in two independent samples: the EU-AIMS Longitudinal European Autism Project (LEAP) and the Gender Explorations of Neurogenetics and Development to Advance Autism Research. RESULTS: Discovery analyses in ABIDE revealed significant main effects of diagnosis and sex across the intrinsic functional connectivity of the posterior cingulate cortex, regional homogeneity and voxel-mirrored homotopic connectivity (VMHC) in several cortical regions, largely converging in the default network midline. Sex-by-diagnosis interactions were confined to the dorsolateral occipital cortex, with reduced VMHC in females with autism. All findings were robust to different pre-processing steps. Replicability in independent samples varied by R-fMRI measures and effects with the targeted sex-by-diagnosis interaction being replicated in the larger of the two replication samples-EU-AIMS LEAP. LIMITATIONS: Given the lack of a priori harmonization among the discovery and replication datasets available to date, sample-related variation remained and may have affected replicability. CONCLUSIONS: Atypical cross-hemispheric interactions are neurobiologically relevant to autism. They likely result from the combination of sex-dependent and sex-independent factors with a differential effect across functional cortical networks. Systematic assessments of the factors contributing to replicability are needed and necessitate coordinated large-scale data collection across studies

Reduced fronto-striatal volume in attention-deficit/hyperactivity disorder in two cohorts across the lifespan

Attention-Deficit/Hyperactivity Disorder (ADHD) has been associated with altered brain anatomy in neuroimaging studies. However, small and heterogeneous study samples, and the use of region-of-interest and tissue-specific analyses have limited the consistency and replicability of these effects. We used a data-driven multivariate approach to investigate neuroanatomical features associated with ADHD in two independent cohorts: the Dutch NeuroIMAGE cohort (n = 890, 17.2 years) and the Brazilian IMpACT cohort (n = 180, 44.2 years). Using independent component analysis of whole-brain morphometry images, 375 neuroanatomical components were assessed for association with ADHD. In both discovery (corrected-p = 0.0085) and replication (p = 0.032) cohorts, ADHD was associated with reduced volume in frontal lobes, striatum, and their interconnecting white-matter. Current results provide further evidence for the role of the fronto-striatal circuit in ADHD in children, and for the first time show its relevance to ADHD in adults. The fact that the cohorts are from different continents and comprise different age ranges highlights the robustness of the findings

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition