An obscured genesis : Deleuze from the dialectic to the problematic

This thesis suggests that Deleuze’s early philosophy, culminating in Difference and Repetition and The Logic of Sense, unfolds as a polemic between two structural positions – the problematic and the dialectic. This polemic sheds light on “political” aspects in Deleuze’s work as a student of authors such as Jean Hyppolite, Jean Wahl, Martial Guéroult and Ferdinand Alquié, in a period in which he places critical weight on the attempt to escape the constraining influence of their positions. Reading Bergson, Nietzsche, Hume, Kant and Hegel through his teachers, Deleuze seeks to expunge from his thought every trace of their mediation, so as to be able to pose new problems for philosophy. To this end Deleuze puts forward the notion of philosophy as being essentially problematic, irreducible to empiricist, transcendentalist or dialectic dispositions and delineated by unique problems. This notion is established as a calculated move marked by an anti-Hegelian rhetoric, Hegel being the epitome of “old” metaphysical problems that must be overcome. The introduction of Deleuze’s critique of his teachers, who could be considered somewhat marginalised authors from the more recent history of French philosophy, and the establishment of the problematic-dialectic dyad as fundamental to Deleuze’s development as a philosopher, hopes to bring out critical aspects of his work that remain strategically buried in the text. Chapter one introduces Deleuze’s triangulation of Hyppolite-Guéroult-Alquié starting from his confrontation with Hyppolite’s Logic and Existence and continuing to his early efforts to put forward a satisfying “middle ground” with respect to these authors’ disparate positions, from which emerges a unique preoccupation with problems that will persist in Deleuze’s work throughout the 1950s and 60s. Chapter two examines the extent to which Nietzsche and Philosophy is a critical response to Hyppolite’s renowned interpretation of Hegel’s The Phenomenology of Spirit, Genesis and Structure, a response which amounts to Deleuze’s interpretation of eternal recurrence as an anti- Hegelian mode of problematization, and which would later be transformed into the Deleuzian project of the overturning of Platonism. Chapter three is a reading of Empiricism and Subjectivity as an anti-Hegelian polemic profoundly inspired by Wahl’s vision of empiricism as a problematic and problematizing theory that responds to Hegel’s critique of “self-certainty” and of empiricism in general. Chapter four considers Deleuze’s Kantianism a strategic endeavour to shift the tectonics of philosophical rigor from a preoccupation with the Absolute as the ultimate ground for knowledge, to a revival of the problematic Idea as that which incites experimentation with the “thickness” of sensibility demolished in the first moment of the Hegelian dialectic, a shift whose successfulness is placed in question

Rapid diagnostic susceptibility testing of bacteria and fungi from clinical samples using silicon gratings

Bacterial and fungal infections persistently plague society and have amounted to one of the most prevalent issues in healthcare today. Thus, significant research effort is directed towards developing rapid diagnostic techniques for determination of the correct antibiotic (or antifungal) for a patient-tailored therapy. We have developed a rapid phenotypic antimicrobial susceptibility testing (AST) in which photonic 2D silicon microarrays are employed as both the optical transducer element and as a preferable solid-liquid interface for bacterial/fungal colonization. We harness the intrinsic ability of the micro-architectures to relay optical phase-shift reflectometric interference spectroscopic measurements (termed PRISM) and incorporate it into a platform for culture-free, label-free tracking of bacterial/fungal colonization, proliferation, and death. For example, bacteria proliferation within the microtopologies results in an increase in refractive index of the medium, yielding an increase in optical path difference, while cell death or bacteriostatic activity results in decreasing or unchanged values. The optical responses of bacteria, including clinical isolates and samples derived from patients at neighboring hospitals, to various concentrations of relevant antibiotics are tracked in real time, allowing for accurate determination of the minimum inhibitory concentration (MIC) values within 2-3 hours in comparison to assay times of <8 hours (using standard broth microdilution techniques or state-of-the-art clinical automated systems. This has opened the door to the observation of unique bacterial behaviors, as we can evaluate bacterial adhesion, growth, and antibiotic resistance on different micro-architectures, different surface chemistries, and even different strains. Motility, charge, and biofilm abilities have been explored for their effect of bacterial adhesion to the microstructures as we further develop our method of rapid, label-free AST for full clinical application. © 2019 SPIE

Comparative Genome Analysis of Lactobacillus reuteri and Lactobacillus fermentum Reveal a Genomic Island for Reuterin and Cobalamin Production

Lactobacillus reuteri is a heterofermentative lactic acid bacterium that naturally inhabits the gut of humans and other animals. The probiotic effects of L. reuteri have been proposed to be largely associated with the production of the broad-spectrum antimicrobial compound reuterin during anaerobic metabolism of glycerol. We determined the complete genome sequences of the reuterin-producing L. reuteri JCM 1112T and its closely related species Lactobacillus fermentum IFO 3956. Both are in the same phylogenetic group within the genus Lactobacillus. Comparative genome analysis revealed that L. reuteri JCM 1112T has a unique cluster of 58 genes for the biosynthesis of reuterin and cobalamin (vitamin B12). The 58-gene cluster has a lower GC content and is apparently inserted into the conserved region, suggesting that the cluster represents a genomic island acquired from an anomalous source. Two-dimensional nuclear magnetic resonance (2D-NMR) with 13C3-glycerol demonstrated that L. reuteri JCM 1112T could convert glycerol to reuterin in vivo, substantiating the potential of L. reuteri JCM 1112T to produce reuterin in the intestine. Given that glycerol is shown to be naturally present in feces, the acquired ability to produce reuterin and cobalamin is an adaptive evolutionary response that likely contributes to the probiotic properties of L. reuteri

Complete sequence of the 22q11.2 allele in 1,053 subjects with 22q11.2 deletion syndrome reveals modifiers of conotruncal heart defects

The 22q11.2 deletion syndrome (22q11.2DS) results from non-allelic homologous recombination between low-copy repeats termed LCR22. About 60%-70% of individuals with the typical 3 megabase (Mb) deletion from LCR22A-D have congenital heart disease, mostly of the conotruncal type (CTD), whereas others have normal cardiac anatomy. In this study, we tested whether variants in the hemizygous LCR22A-D region are associated with risk for CTDs on the basis of the sequence of the 22q11.2 region from 1,053 22q11.2DS individuals. We found a significant association (FDR p &lt; 0.05) of the CTD subset with 62 common variants in a single linkage disequilibrium (LD) block in a 350 kb interval harboring CRKL. A total of 45 of the 62 variants were associated with increased risk for CTDs (odds ratio [OR) ranges: 1.64-4.75). Associations of four variants were replicated in a meta-analysis of three genome-wide association studies of CTDs in affected individuals without 22q11.2DS. One of the replicated variants, rs178252, is located in an open chromatin region and resides in the double-elite enhancer, GH22J020947, that is predicted to regulate CRKL (CRK-like proto-oncogene, cytoplasmic adaptor) expression. Approximately 23% of patients with nested LCR22C-D deletions have CTDs, and inactivation of Crkl in mice causes CTDs, thus implicating this gene as a modifier. Rs178252 and rs6004160 are expression quantitative trait loci (eQTLs) of CRKL. Furthermore, set-based tests identified an enhancer that is predicted to target CRKL and is significantly associated with CTD risk (GH22J020946, sequence kernal association test (SKAT) p = 7.21&nbsp;× 10-5) in the 22q11.2DS cohort. These findings suggest that variance in CTD penetrance in the 22q11.2DS population can be explained in part by variants affecting CRKL expression

WSES Guidelines for the management of acute left sided colonic diverticulitis in the emergency setting

Acute left sided colonic diverticulitis is one of the most common clinical conditions encountered by surgeons in acute setting. A World Society of Emergency Surgery (WSES) Consensus Conference on acute diverticulitis was held during the 3rd World Congress of the WSES in Jerusalem, Israel, on July 7th, 2015. During this consensus conference the guidelines for the management of acute left sided colonic diverticulitis in the emergency setting were presented and discussed. This document represents the executive summary of the final guidelines approved by the consensus conference.Peer reviewe

Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj = 6.73 × 10−6). Novel reciprocal case–control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present

The complexity of the interaction between binge-eating and attention.

ObjectiveTo investigate whether binge-eating in patients with eating disorders (EDs) is associated with attentional deficits.MethodsWe studied ED patients with binge-eating (n = 51), no binge-eating (n = 59) and controls (n = 58). ED patients were assessed following the stabilization of weight and ED pathology. Attention assessment included evaluation of attention deficit hyperactivity disorder (ADHD) diagnosis, the Adult ADHD Self-Report (ASRS) and ADHD Rating Scale-IV-Home Version (ADHD-RS) questionnaires, and attention functioning assessed with neuropsychological tools. The severity of eating-related pathology, depression, anxiety and obsessionality was also monitored.ResultsPatients with binge-eating showed more ADHD symptomatology on the ADHD-RS compared with non-binge-eating patients. No differences were found between binge-eating and non-binge-eating patients in ADHD diagnosis and neuropsychological functioning. Among the specific ED subtypes, patients with anorexia nervosa binge/purge type (AN-B/P) showed the highest rates of ADHD symptomatology on the ADHD-RS, and were characterized with sustained attention deficits.ConclusionBinge-eating is not associated with attention deficits as measured by objective neuropsychological tools. Nonetheless, it is associated with attentional difficulties as measured with the self-reported ADHD-RS. AN-B/P patients are the only ED category showing objective sustained attention deficits