Development of local-global preference in vision and haptics

We aimed to advance our understanding of local-global preference by exploring its developmental path within and across sensory modalities: vision and haptics. Neurotypical individuals from six years of age through adulthood completed a similarity judgement task with hierarchical haptic or visual stimuli made of local elements (squares or triangles) forming a global shape (a square or a triangle). Participants chose which of two probes was more similar to a target: the one sharing the global shape (but different local shapes) or the one with the same local shapes (but different global shape). Across trials, we independently varied the size of the local elements and that of the global configuration-the latter was varied by manipulating local element density while keeping their numerosity constant. We found that the size of local elements (but not global size) modulates the effects of age and modality. For stimuli with smaller local elements, the proportion of global responses increased with age and was similar for visual and haptic stimuli. However, for stimuli made of our largest local elements, the global preference was reduced or absent, particularly in haptics, regardless of age. These results suggest that vision and haptics progressively converge toward similar global preference with age, but residual differences across modalities and across individuals may be observed, depending on the characteristics of the stimuli

Cognitive performance at first episode of psychosis and the relationship with future treatment resistance: Evidence from an international prospective cohort study

Background: Antipsychotic treatment resistance affects up to a third of individuals with schizophrenia, with recent research finding systematic biological differences between antipsychotic resistant and responsive patients. Our aim was to determine whether cognitive impairment at first episode significantly differs between future antipsychotic responders and resistant cases. Methods: Analysis of data from seven international cohorts of first-episode psychosis (FEP) with cognitive data at baseline (N = 683) and follow-up data on antipsychotic treatment response: 605 treatment responsive and 78 treatment resistant cases. Cognitive measures were grouped into seven cognitive domains based on the pre-existing literature. We ran multiple imputation for missing data and used logistic regression to test for associations between cognitive performance at FEP and treatment resistant status at follow-up. Results: On average patients who were future classified as treatment resistant reported poorer performance across most cognitive domains at baseline. Univariate logistic regressions showed that antipsychotic treatment resistance cases had significantly poorer IQ/general cognitive functioning at FEP (OR = 0.70, p = .003). These findings remained significant after adjusting for additional variables in multivariable analyses (OR = 0.76, p = .049). Conclusions: Although replication in larger studies is required, it appears that deficits in IQ/general cognitive functioning at first episode are associated with future treatment resistance. Cognitive variables may be able to provide further insight into neurodevelopmental factors associated with treatment resistance or act as early predictors of treatment resistance, which could allow prompt identification of refractory illness and timely interventions

Clinical predictors of antipsychotic treatment resistance: Development and internal validation of a prognostic prediction model by the STRATA-G consortium.

Our aim was to, firstly, identify characteristics at first-episode of psychosis that are associated with later antipsychotic treatment resistance (TR) and, secondly, to develop a parsimonious prediction model for TR. We combined data from ten prospective, first-episode psychosis cohorts from across Europe and categorised patients as TR or non-treatment resistant (NTR) after a mean follow up of 4.18 years (s.d. = 3.20) for secondary data analysis. We identified a list of potential predictors from clinical and demographic data recorded at first-episode. These potential predictors were entered in two models: a multivariable logistic regression to identify which were independently associated with TR and a penalised logistic regression, which performed variable selection, to produce a parsimonious prediction model. This model was internally validated using a 5-fold, 50-repeat cross-validation optimism-correction. Our sample consisted of N = 2216 participants of which 385 (17 %) developed TR. Younger age of psychosis onset and fewer years in education were independently associated with increased odds of developing TR. The prediction model selected 7 out of 17 variables that, when combined, could quantify the risk of being TR better than chance. These included age of onset, years in education, gender, BMI, relationship status, alcohol use, and positive symptoms. The optimism-corrected area under the curve was 0.59 (accuracy = 64 %, sensitivity = 48 %, and specificity = 76 %). Our findings show that treatment resistance can be predicted, at first-episode of psychosis. Pending a model update and external validation, we demonstrate the potential value of prediction models for TR

Development and Validation of Predictive Model for a Diagnosis of First Episode Psychosis Using the Multinational EU-GEI Case–control Study and Modern Statistical Learning Methods

Background and Hypothesis: It is argued that availability of diagnostic models will facilitate a more rapid identification of individuals who are at a higher risk of first episode psychosis (FEP). Therefore, we developed, evaluated, and validated a diagnostic risk estimation model to classify individual with FEP and controls across six countries. / Study Design: We used data from a large multi-center study encompassing 2627 phenotypically well-defined participants (aged 18-64 years) recruited from six countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions study. To build the diagnostic model and identify which of important factors for estimating an individual risk of FEP, we applied a binary logistic model with regularization by the least absolute shrinkage and selection operator. The model was validated employing the internal-external cross-validation approach. The model performance was assessed with the area under the receiver operating characteristic curve (AUROC), calibration, sensitivity, and specificity. / Study Results: Having included preselected 22 predictor variables, the model was able to discriminate adults with FEP and controls with high accuracy across all six countries (rangesAUROC=0.84-0.86). Specificity (range=73.9-78.0%) and sensitivity (range=75.6-79.3%) were equally good, cumulatively indicating an excellent model accuracy; though, calibration slope for the diagnostic model showed a presence of some overfitting when applied specifically to participants from France, the UK, and The Netherlands. / Conclusions: The new FEP model achieved a good discrimination and good calibration across six countries with different ethnic contributions supporting its robustness and good generalizability

Cairo's Urban Transformation: Mohandeseen and Zamalek Narratives

Im Gegensatz zu anderen Großstädten der Welt hat Kairo im Laufe seiner langen Geschichte einen bedeutenden Wandel durchlaufen. Während einige Elemente der Vergangenheit noch sichtbar sind, allen voran die Pyramiden von Gizeh, sind andere Elemente längst verschwunden. Es ist schwer vorstellbar, dass das historische Kairo einst das Zentrum einer fruchtbaren, von Seen durchzogenen Landschaft war, vor allem wenn man mit den heutigen Realitäten einer dichten, meist grauen Stadtlandschaft konfrontiert wird, die von einer dünnen Staubschicht und einer Vielzahl von Umweltproblemen bedeckt ist. Kairo ist die größte Mega-Stadt auf dem afrikanischen Kontinent und verändert sich weiterhin schnell, sowohl formal als auch informell. Um die Transformation Kairos zu steuern und die informelle Entwicklung auf dem verbleibenden fruchtbaren Land einzuschränken, werden neue staatlich finanzierte Wüstenstädte geplant, gebaut und bewohnt. Gleichzeitig haben massive Hochhäuser die einst charakteristischen großen, wohlhabenden Villensiedlungen in regulär entwickelten Kernstadtgebieten wie Zamalek und Mohandeseen ersetzt. In Zamalek hat sich diese Transformation dazu geführt, dass sich viele Bürger der Oberschicht in die Wüstenstädte zurückziehen und Spuren des Verfalls hinterlassen, während Mohandeseen zu einem der teuersten Gebiete in Kairo geworden ist, das fast keine Spuren des Garden City-Konzepts hinterlässt, das seine frühe Entwicklung bestimmt hat. Während viel Aufmerksamkeit auf die Erweiterung und Verbesserung informeller Gebiete und die Schaffung neuer Wüstenstädte gerichtet wird, ist es auch wichtig, aus der Vergangenheit zu lernen und die zukünftige Transformation von Kernstadtgebieten wie Mohandeseen und Zamalek zu steuern. Im Folgenden wird die Transformation ausgewählter Gebiete in Monhandeseen um die Libanon Street und den Assuan Square sowie um Zamalek im Norden des Gezira Sporting Club untersucht.Not unlike other major cities around the world, Cairo has undergone a significant transformation over the course of its long history. While some elements of the past are still visible, the most notable being the Pyramids of Giza, other elements have long since disappeared. It is hard to imagine that historic Cairo was once at the center of a fertile landscape dotted with lakes, especially when confronted with today’s realities of a dense mostly gray cityscape covered by a thin layer of dust and a host of environmental problems. Cairo is the largest mega-city on the African continent and it continues to transform rapidly, both formally and informally. In an effort to guide Cairo’s transformation and limit informal development on its remaining fertile land, new state funded desert cities are being planned, built and inhabited. At the same time, massive tower blocks have replaced the once characteristic large prosperous villa estates within formally developed core-city areas such as Zamalek and Mohandeseen. In Zamalek this transformation has caused many upper class residents to withdraw to the desert cities leaving behind signs of decay, while Mohandeseen has become one of the most expensive areas in Cairo leaving almost no trace of the Garden City concept which guided its early development. While much needed attention goes to the expansion and improvement of informal areas and to the creation of new desert cities, it is also important to learn from the past as well as to guide the future transformation of core-city areas such as Mohandeseen and Zamalek. The following investigates the transformation of select areas of Mohandeseen around Lebanon Street and Aswan Square in addition to Zamalek to the north of the Gezira Sporting Club

Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants With Treatment Resistance in Schizophrenia

Importance: About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts. Objective: To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples. Design, Setting, and Participants: Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10 501) and individuals with non-TRS (n = 20 325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]). Main Outcomes and Measures: GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition. Results: The study included a total of 85 490 participants (48 635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r2 = 2.03%; P = .001), which was replicated in the STRATA-G incidence sample (r2 = 1.09%; P = .04). Conclusions and Relevance: In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance

Seaweed polysaccharide-based hydrogels used for the regeneration of articular cartilage

This manuscript provides an overview of the in vitro and in vivo studies reported in the literature focusing on seaweed polysaccharides based hydrogels that have been proposed for applications in regenerative medicine, particularly, in the field of cartilage tissue engineering. For a better understanding of the main requisites for these specific applications, the main aspects of the native cartilage structure, as well as recognized diseases that affect this tissue are briefly described. Current available treatments are also presented to emphasize the need for alternative techniques. The following part of this review is centered on the description of the general characteristics of algae polysaccharides, as well as relevant properties required for designing hydrogels for cartilage tissue engineering purposes. An in-depth overview of the most well known seaweed polysaccharide, namely agarose, alginate, carrageenan and ulvan biopolymeric gels, that have been proposed for engineering cartilage is also provided. Finally, this review describes and summarizes the translational aspect for the clinical application of alternative systems emphasizing the importance of cryopreservation and the commercial products currently available for cartilage treatment.Authors report no declarations of interest. Authors thank the Portuguese Foundation for Science and Technology (FCT) for the PhD fellowship of Elena G. Popa (SFRH/BD/64070/2009) and research project (MIT/ECE/0047/2009). The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no REGPOT-CT2012-316331-POLARIS

Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = –0.45 to –0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = –0.14 to –0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = –0.88 to –0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = –0.13 to –0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = –0.21 to –0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe