Searching for the scale of homogeneity

We introduce a statistical quantity, known as the $K$ function, related to the integral of the two--point correlation function. It gives us straightforward information about the scale where clustering dominates and the scale at which homogeneity is reached. We evaluate the correlation dimension, $D_2$, as the local slope of the log--log plot of the $K$ function. We apply this statistic to several stochastic point fields, to three numerical simulations describing the distribution of clusters and finally to real galaxy redshift surveys. Four different galaxy catalogues have been analysed using this technique: the Center for Astrophysics I, the Perseus--Pisces redshift surveys (these two lying in our local neighbourhood), the Stromlo--APM and the 1.2 Jy {\it IRAS} redshift surveys (these two encompassing a larger volume). In all cases, this cumulant quantity shows the fingerprint of the transition to homogeneity. The reliability of the estimates is clearly demonstrated by the results from controllable point sets, such as the segment Cox processes. In the cluster distribution models, as well as in the real galaxy catalogues, we never see long plateaus when plotting $D_2$ as a function of the scale, leaving no hope for unbounded fractal distributions.Comment: 9 pages, 11 figures, MNRAS, in press; minor revision and added reference

Dealing with heterogeneity of cognitive dysfunction in acute depression : a clustering approach

Heterogeneity in cognitive functioning among major depressive disorder (MDD) patients could have been the reason for the small-to-moderate differences reported so far when it is compared to other psychiatric conditions or to healthy controls. Additionally, most of these studies did not take into account clinical and sociodemographic characteristics that could have played a relevant role in cognitive variability. This study aims to identify empirical clusters based on cognitive, clinical and sociodemographic variables in a sample of acute MDD patients. In a sample of 174 patients with an acute depressive episode, a two-step clustering analysis was applied considering potentially relevant cognitive, clinical and sociodemographic variables as indicators for grouping. Treatment resistance was the most important factor for clustering, closely followed by cognitive performance. Three empirical subgroups were obtained: cluster 1 was characterized by a sample of non-resistant patients with preserved cognitive functioning (n = 68, 39%); cluster 2 was formed by treatment-resistant patients with selective cognitive deficits (n = 66, 38%) and cluster 3 consisted of resistant (n = 23, 58%) and non-resistant (n = 17, 42%) acute patients with significant deficits in all neurocognitive domains (n = 40, 23%). The findings provide evidence upon the existence of cognitive heterogeneity across patients in an acute depressive episode. Therefore, assessing cognition becomes an evident necessity for all patients diagnosed with MDD, and although treatment resistant is associated with greater cognitive dysfunction, non-resistant patients can also show significant cognitive deficits. By targeting not only mood but also cognition, patients are more likely to achieve full recovery and prevent new relapses

A global descriptor of spatial pattern interaction in the galaxy distribution

We present the function J as a morphological descriptor for point patterns formed by the distribution of galaxies in the Universe. This function was recently introduced in the field of spatial statistics, and is based on the nearest neighbor distribution and the void probability function. The J descriptor allows to distinguish clustered (i.e. correlated) from ``regular'' (i.e. anti-correlated) point distributions. We outline the theoretical foundations of the method, perform tests with a Matern cluster process as an idealised model of galaxy clustering, and apply the descriptor to galaxies and loose groups in the Perseus-Pisces Survey. A comparison with mock-samples extracted from a mixed dark matter simulation shows that the J descriptor can be profitably used to constrain (in this case reject) viable models of cosmic structure formation.Comment: Significantly enhanced version, 14 pages, LaTeX using epsf, aaspp4, 7 eps-figures, accepted for publication in the Astrophysical Journa

If you feel you can’t, you won’t: the role of subjective and objective cognitive competence on psychosocial functioning in depression

BackgroundThe purpose of this exploratory study is to examine the role of sociodemographic, clinical, and cognitive - both objective and subjective - factors in overall and in specific domains of psychosocial functioning, in patients with depression at different clinical states of the disease (remitted and non-remitted).MethodsA sample of 325 patients with major depressive disorder, 117 in remission and 208 in non-remission, were assessed with a semi-structured interview collecting sociodemographic, clinical, cognitive (with neuropsychological tests and the Perceived Deficit Questionnaire), and functional (Functioning Assessment Short Test) characteristics. Backward regression models were conducted to determine associations of global and specific areas of functioning with independent factors, for both clinical states.ResultsResidual depressive symptomatology and self-appraisal of executive competence were significantly associated with psychosocial functioning in remitted patients, in overall and some subdomains of functioning, particularly cognitive and interpersonal areas. While depressive symptoms, executive deficits and self-appraisal of executive function were significantly related to functional outcomes in non-remitted patients, both in overall functioning and in most of subdomains.DiscussionThis study evidences the strong association of one's appraisal of executive competence with psychosocial functioning, together with depressive symptoms, both in remitted and non-remitted patients with depression. Therefore, to achieve full recovery, clinical management of patients should tackle not only the relief of core depressive symptoms, but also the cognitive ones, both those that are objectified with neuropsychological tests and those that are reported by the patients themselves

Tumor microenvironment-targeted poly-L-glutamic acid-based combination conjugate for enhanced triple negative breast cancer treatment

[EN] The intrinsic characteristics of the tumor microenvironment (TME), including acidic pH and overexpression of hydrolytic enzymes, offer an exciting opportunity for the rational design of TME-drug delivery systems (DDS). We developed and characterized a pH-responsive biodegradable poly-L-glutamic acid (PGA)-based combination conjugate family with the aim of optimizing anticancer effects. We obtained combination conjugates bearing Doxorubicin (Dox) and aminoglutethimide (AGM) with two Dox loadings and two different hydrazone pH sensitive linkers that promote the specific release of Dox from the polymeric backbone within the TME. Low Dox loading coupled with a short hydrazone linker yielded optimal effects on primary tumor growth, lung metastasis (-90% reduction), and toxicological profile in a preclinical metastatic triple-negative breast cancer (TNBC) murine model. The use of transcriptomic analysis helped us to identify the molecular mechanisms responsible for such results including a differential immunomodulation and cell death pathways among the conjugates. This data highlights the advantages of targeting the TME, the therapeutic value of polymer-based combination approaches, and the utility of -omits-based analysis to accelerate anticancer DDS.The authors would like to thank Dr. Stuart P. Atkinson for his collaboration in manuscript preparation and English revision, and Irene Borreda for essential immunohistological support. This work has been supported by the European Research Council (grant ERC-CoG-2014-648831 "MyNano") and the Spanish Ministry of Science and Innovation (CTQ2010-18195, SAF2013-44848-R, BES-2008-006801, IPT-2012-0712-010000, Programa I3, and BIO2015-71658-R). LBN is funded through a University of South Florida-Helmsley Foundation award. FHL is funded through NIH grant. Part of the equipment employed in this work has been funded by Generalitat Valenciana and co-financed with FEDER funds (PO FEDER of Comunitat Valenciana 2014-2020).Arroyo-Crespo, JJ.; Armiñán, A.; Charbonnier, D.; Balzano-Nogueira, L.; Huertas-López, F.; Martí, C.; Tarazona Campos, S.... (2018). Tumor microenvironment-targeted poly-L-glutamic acid-based combination conjugate for enhanced triple negative breast cancer treatment. Biomaterials. 186:8-21. https://doi.org/10.1016/j.biomaterials.2018.09.02382118

Group and sex differences in social cognition in bipolar disorder, schizophrenia/schizoaffective disorder and healthy people

Background: Impairment of social cognition is documented in bipolar disorder (BD) and schizophrenia/schizoaffective disorder (SCH). In healthy individuals, women perform better than men in some of its sub-domains. However, in BD and SCH the results are mixed. Our aim was to compare emotion recognition, affective Theory of Mind (ToM) and first- and second-order cognitive ToM in BD, SCH and healthy subjects, and to investigate sex-related differences. Methods: 120 patients (BD = 60, SCH = 60) and 40 healthy subjects were recruited. Emotion recognition was assessed by the Pictures of Facial Affect (POFA) test, affective ToM by the Reading the Mind in the Eyes Test (RMET) and cognitive ToM by several false-belief stories. Group and sex differences were analyzed using parametric (POFA, RMET) and non-parametric (false-belief stories) tests. The impact of age, intelligence quotient (IQ) and clinical variables on patient performance was examined using a series of linear/logistic regressions. Results: Both groups of patients performed worse than healthy subjects on POFA, RMET and second-order false-belief (p < 0.001), but no differences were found between them. Instead, their deficits were related to older age and/or lower IQ (p < 0.01). Subthreshold depression was associated with a 6-fold increased risk of first-order false-belief failure (p < 0.001). Sex differences were only found in healthy subjects, with women outperforming men on POFA and RMET (p ≤ 0.012), but not on first/second-order false-belief. Limitations: The cross-sectional design does not allow for causal inferences. Conclusion: BD and SCH patients had deficits in emotion recognition, affective ToM, and second-order cognitive ToM, but their performance was comparable to each other, highlighting that the differences between them may be subtler than previously thought. First-order cognitive ToM remained intact, but subthreshold depression altered their normal functioning. Our results suggest that the advantage of healthy women in the emotional and affective aspects of social cognition would not be maintained in BD and SCH

Testing the efficacy of INtegral Cognitive REMediation (INCREM) in major depressive disorder : study protocol for a randomized clinical trial

Given the limitation of pharmacological treatments to treat cognitive symptoms in patients with Major Depressive Disorder (MDD), cognitive remediation programs has been proposed as a possible procognitive intervention but findings are not conclusive. This study investigates the efficacy of an INtegral Cognitive REMediation (INCREM) that includes a combination of a Functional Remediation (FR) strategy plus a Computerized Cognitive Training (CCT) in order to improve not only cognitive performance but also the psychosocial functioning and the quality of life. A single blind randomized controlled clinical trial in 81 patients with a diagnosis of MDD in clinical remission or in partial remission. Participants will be randomized to one of three conditions: INCREM (FR + CCT), Psychoeducation plus online games and Treatment As Usual (TAU). Intervention will consist in 12 group sessions, of approximately 110 min once a week. The primary outcome measure will be % of change in psychosocial functioning after treatment measured by the Functional Assessment Short Test (FAST); additionally, number of sick leaves and daily activities will also be recorded as pragmatic outcomes. To our knowledge, this is the first randomized controlled clinical trial using a combination of two different approaches (FR + CCT) to treat the present cognitive deficits and to promote their improvements into a better psychosocial functioning. Clinical Trials . Date registered 10th of August 2018 and last updated 24th August 2018

Targeting Alzheimer's disease with multimodal polypeptide-based nanoconjugates

Alzheimer’s disease (AD), the most prevalent form of dementia, remains incurable mainly due to our failings in the search for effective pharmacological strategies. Here, we describe the development of targeted multimodal polypeptide-based nanoconjugates as potential AD treatments. Treatment with polypeptide nanoconjugates bearing propargylamine moieties and bisdemethoxycurcumin or genistein afforded neuroprotection and displayed neurotrophic effects, as evidenced by an increase in dendritic density of pyramidal neurons in organotypic hippocampal culture. The additional conjugation of the Angiopep-2 targeting moiety enhanced nanoconjugate passage through the blood-brain barrier and modulated brain distribution with nanoconjugate accumulation in neurogenic areas, including the olfactory bulb. Nanoconjugate treatment effectively reduced neurotoxic β amyloid aggregate levels and rescued impairments to olfactory memory and object recognition in APP/PS1 transgenic AD model mice. Overall, this study provides a description of a targeted multimodal polyglutamate-based nanoconjugate with neuroprotective and neurotrophic potential for AD treatment