Relativity of a Free Will Concept Depending on Both Conscious Indeterminism and Unconscious Determinism

Free will is difficult to classify with respect to determinism or indeterminism, and its phenomenology in consciousness often shows both aspects. Initially, it is felt as unlimited and indeterminate will power, with the potentiality of multiple choices. Thereafter, reductive deliberation is led by determinism to the final decision, which realises only one of the potential choices. The reductive deliberation phase tries to find out the best alternative and simultaneously satisfying vague motivations, contextual conditions and personal preferences. The essential sense of free will is the introduction of personal preferences, which allows a higher diversity of reactions to vague motivations. With an oversimplified model of determinism as a chain of events, incompatibilists define “free” as “undetermined” so that determinism becomes incompatible with any free choice between alternatives. In consciousness, free will requires a more complex model of network determinism as well as the consideration of unconsciousness as a causal factor. When “free” defined as “undetermined” is applied to the context of consciousness, it should be reinterpreted as “unconscious of being determined” or not aware of underlying determinism. Lacking information on determinism generates a feeling of “free” in consciousness and, therefore, gives the impression of indeterminism. Lacking information may be induced by an uncertain future without determined events—an unconscious past with biological reactions suddenly emerging from the unconsciousness or an unknown present unable to distinguish determinism of complex events. Therefore, at the level of human consciousness, the experience of free will is associated with apparent indeterminism although it is based on unconscious determinism. The concepts of compatibilism and incompatibilism are only two different aspects of the same phenomenon and correspond to consciousness and unconsciousness. Nevertheless, they can be considered together with a free will concept based on relativity depending on two different reference frames—the first person’s experience frame or the Laplace’s demon frame with knowledge on every molecule of the universe. Only relativity of the free will concept avoids the contradiction between “free” and “unfree” for the same phenomenon and could be a compromise for considering compatibilism and incompatibilism equally

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s=7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb(-1) of root s = 7 TeV proton-proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s=7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb-1 of sqrt(s) = 7 TeV proton-proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Lyme-Borreliose: Forschungsbedarf und Forschungsansätze

Die Lyme-Borreliose ist in der nördlichen Hemisphäre nach aktuellem Kenntnisstand die häufigste durch Zecken übertragene Infektionskrankheit. Deutschland ist neben anderen europäischen Ländern ein Hochendemie-Gebiet, daher muss von einer hohen Krankheitslast und entsprechend hohen Kosten für das Gesundheitssystem ausgegangen werden. Der vorliegende Beitrag fasst die Ergebnisse eines interdisziplinären Workshops zur Lyme-Borreliose zusammen, der am 8. und 9. Oktober 2007 am Robert Koch-Institut (RKI) durchgeführt wurde. Ziel des Treffens war es, Forschungsdefizite zur Lyme-Borreliose zu identifizieren und Prioritäten für zukünftige Forschungsprojekte zu setzen. Handlungsbedarf wurde von den Teilnehmern auf unterschiedlichsten Gebieten gesehen: Diagnose, Epidemiologie, Immunologie, Klinik, Ökologie und Versorgungsforschung. Beispiele für Gebiete, die nach Expertenmeinung mit Vorrang zu bearbeiten sind, sind die Standardisierung der serologischen Tests, die Entwicklung von Markern für eine aktive Infektion, die Verbesserung der Datengrundlage zum Vorkommen der Lyme-Borreliose in Deutschland und Untersuchungen zur Bestimmung der Krankheitslast.Lyme borreliosis is currently the most frequent tick-transmitted zoonosis in the northern hemisphere. Germany and other European countries are regarded as highly endemic areas; therefore the burden of disease and consequently the costs for the health systems are considered to be high. This report summarises the results of an interdisciplinary workshop on Lyme borreliosis which aimed to identify research deficits and to prioritise areas which need to be addressed. Research needs have been recognised for different areas: diagnosis, epidemiology, immunology, clinics, ecology and health services research. Examples of research areas which have priority are the standardisation of diagnostic tests, the development of markers to detect an active infection, the improvement of the epidemiological database and the analysis of the burden of disease