The transferencial relation beyond the interpretation : reflections from the theory of Winnicott.

Este artigo reflete sobre a importância de pensar a relação transferencial na clínica psicanalítica para além da interpretação. Para isso, utiliza-se a concepção de Winnicott como referencial teórico, sendo ressaltadas a noção de holding, a regressão à dependência e a questão do uso de objetos e sua influência sobre a técnica da interpretação. Winnicott revela que na clínica com alguns pacientes, em especial os autistas e psicóticos, o objetivo da análise, antes de fornecer interpretações, é proporcionar um ambiente suficientemente bom a partir do qual o sujeito pode retomar o processo de constituição de si mesmo e da externalidade do mundo.This article reflects about the importance of thinking the transferencial relation in the psychoanalytic clinic beyond the interpretation. For this, the Winnicott’s concept is used as theoretical reference, highlighting the concept of holding, regression to dependence and the question of the use of objects and its influence on the technique of interpretation. Winnicott shows that in the clinic, with some patients, particularly autistic and psychotic, before providing interpretation, the objective of the analysis is to provide a good environment from which the subject can retake the constitution process of himself/herself and of the externality of the world

Approximation Algorithms for Generalized MST and TSP in Grid Clusters

We consider a special case of the generalized minimum spanning tree problem (GMST) and the generalized travelling salesman problem (GTSP) where we are given a set of points inside the integer grid (in Euclidean plane) where each grid cell is $1 \times 1$. In the MST version of the problem, the goal is to find a minimum tree that contains exactly one point from each non-empty grid cell (cluster). Similarly, in the TSP version of the problem, the goal is to find a minimum weight cycle containing one point from each non-empty grid cell. We give a $(1+4\sqrt{2}+\epsilon)$ and $(1.5+8\sqrt{2}+\epsilon)$-approximation algorithm for these two problems in the described setting, respectively. Our motivation is based on the problem posed in [7] for a constant approximation algorithm. The authors designed a PTAS for the more special case of the GMST where non-empty cells are connected end dense enough. However, their algorithm heavily relies on this connectivity restriction and is unpractical. Our results develop the topic further

A Novel Genome-Wide Association Study Approach Using Genotyping by Exome Sequencing Leads to the Identification of a Primary Open Angle Glaucoma Associated Inversion Disrupting ADAMTS17

Closed breeding populations in the dog in conjunction with advances in gene mapping and sequencing techniques facilitate mapping of autosomal recessive diseases and identification of novel disease-causing variants, often using unorthodox experimental designs. In our investigation we demonstrate successful mapping of the locus for primary open angle glaucoma in the Petit Basset Griffon Vendéen dog breed with 12 cases and 12 controls, using a novel genotyping by exome sequencing approach. The resulting genome-wide association signal was followed up by genome sequencing of an individual case, leading to the identification of an inversion with a breakpoint disrupting the ADAMTS17 gene. Genotyping of additional controls and expression analysis provide strong evidence that the inversion is disease causing. Evidence of cryptic splicing resulting in novel exon transcription as a consequence of the inversion in ADAMTS17 is identified through RNAseq experiments. This investigation demonstrates how a novel genotyping by exome sequencing approach can be used to map an autosomal recessive disorder in the dog, with the use of genome sequencing to facilitate identification of a disease-associated variant

Forward Analysis and Model Checking for Trace Bounded WSTS

We investigate a subclass of well-structured transition systems (WSTS), the bounded---in the sense of Ginsburg and Spanier (Trans. AMS 1964)---complete deterministic ones, which we claim provide an adequate basis for the study of forward analyses as developed by Finkel and Goubault-Larrecq (Logic. Meth. Comput. Sci. 2012). Indeed, we prove that, unlike other conditions considered previously for the termination of forward analysis, boundedness is decidable. Boundedness turns out to be a valuable restriction for WSTS verification, as we show that it further allows to decide all $\omega$-regular properties on the set of infinite traces of the system

Mutations in the SLC2A9 Gene Cause Hyperuricosuria and Hyperuricemia in the Dog

Allantoin is the end product of purine catabolism in all mammals except humans, great apes, and one breed of dog, the Dalmatian. Humans and Dalmatian dogs produce uric acid during purine degradation, which leads to elevated levels of uric acid in blood and urine and can result in significant diseases in both species. The defect in Dalmatians results from inefficient transport of uric acid in both the liver and renal proximal tubules. Hyperuricosuria and hyperuricemia (huu) is a simple autosomal recessive trait for which all Dalmatian dogs are homozygous. Therefore, in order to map the locus, an interbreed backcross was used. Linkage mapping localized the huu trait to CFA03, which excluded the obvious urate transporter 1 gene, SLC22A12. Positional cloning placed the locus in a minimal interval of 2.5 Mb with a LOD score of 17.45. A critical interval of 333 kb containing only four genes was homozygous in all Dalmatians. Sequence and expression analyses of the SLC2A9 gene indicated three possible mutations, a missense mutation (G616T;C188F) and two promoter mutations that together appear to reduce the expression levels of one of the isoforms. The missense mutation is associated with hyperuricosuria in the Dalmatian, while the promoter SNPs occur in other unaffected breeds of dog. Verification of the causative nature of these changes was obtained when hyperuricosuric dogs from several other breeds were found to possess the same combination of mutations as found in the Dalmatian. The Dalmatian dog model of hyperuricosuria and hyperuricemia underscores the importance of SLC2A9 for uric acid transport in mammals

How brains make decisions

This chapter, dedicated to the memory of Mino Freund, summarizes the Quantum Decision Theory (QDT) that we have developed in a series of publications since 2008. We formulate a general mathematical scheme of how decisions are taken, using the point of view of psychological and cognitive sciences, without touching physiological aspects. The basic principles of how intelligence acts are discussed. The human brain processes involved in decisions are argued to be principally different from straightforward computer operations. The difference lies in the conscious-subconscious duality of the decision making process and the role of emotions that compete with utility optimization. The most general approach for characterizing the process of decision making, taking into account the conscious-subconscious duality, uses the framework of functional analysis in Hilbert spaces, similarly to that used in the quantum theory of measurements. This does not imply that the brain is a quantum system, but just allows for the simplest and most general extension of classical decision theory. The resulting theory of quantum decision making, based on the rules of quantum measurements, solves all paradoxes of classical decision making, allowing for quantitative predictions that are in excellent agreement with experiments. Finally, we provide a novel application by comparing the predictions of QDT with experiments on the prisoner dilemma game. The developed theory can serve as a guide for creating artificial intelligence acting by quantum rules.Comment: Latex file, 20 pages, 3 figure

Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Findings: Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none). Interpretation: Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy. Funding: Clovis Oncology