APPLICATION OF BIODYNAMIC IMAGING FOR PERSONALIZED CHEMOTHERAPY IN CANINE LYMPHOMA

Biodynamic imaging (BDI) is a novel phenotypic cancer profiling technology which characterizes changes in cellular and subcellular motion in living tumor tissue samples following in vitro or ex vivo treatment with chemotherapeutics. The ability of BDI to predict clinical response to single-agent doxorubicin chemotherapy was tested in ten dogs with naturally-occurring non-Hodgkin’s lymphomas (NHL). Pre-treatment tumor biopsy samples were obtained from all dogs and treated with doxorubicin (10 M) ex vivo. BDI captured cellular and subcellular motility measures on all biopsy samples at baseline and at regular intervals for 9 hours following drug application. All dogs subsequently received treatment with a standard single-agent doxorubicin protocol. Objective response (OR) to doxorubicin and progression-free survival time (PFST) following chemotherapy were recorded for all dogs. The dynamic biomarkers measured by BDI were entered into a multivariate logistic model to determine the extent to which BDI predicted OR and PFST following doxorubicin therapy. The model showed that the sensitivity, specificity, and accuracy of BDI for predicting treatment outcome were 95%, 91%, and 93%, respectively. To account for possible over-fitting of data to the predictive model, cross-validation with a one-left-out analysis was performed, and the adjusted sensitivity, specificity, and accuracy following this analysis were 93%, 87%, and 91%, respectively. These findings suggest that BDI can predict, with high accuracy, treatment outcome following single-agent doxorubicin chemotherapy in a relevant spontaneous canine cancer model, and is a promising novel technology for advancing personalized cancer medicine

Mobile Agents for Mobile Tourists: A User Evaluation of Gulliver's Genie

How mobile computing applications and services may be best designed, implemented and deployed remains the subject of much research. One alternative approach to developing software for mobile users that is receiving increasing attention from the research community is that of one based on intelligent agents. Recent advances in mobile computing technology have made such an approach feasible. We present an overview of the design and implementation of an archetypical mobile computing application, namely that of an electronic tourist guide. This guide is unique in that it comprises a suite of intelligent agents that conform to the strong intentional stance. However, the focus of this paper is primarily concerned with the results of detailed user evaluations conducted on this system. Within the literature, comprehensive evaluations of mobile context-sensitive systems are sparse and therefore, this paper seeks, in part, to address this deficiency

Early interpersonal trauma reduces temporoparietal junction activity during spontaneous mentalising

Experience of interpersonal trauma and violence alters self-other distinction and mentalising abilities (also known as theory of mind, or ToM), yet little is known about their neural correlates. This fMRI study assessed temporoparietal junction (TPJ) activation, an area strongly implicated in interpersonal processing, during spontaneous mentalising in 35 adult women with histories of childhood physical, sexual, and/or emotional abuse (childhood abuse; CA) and 31 women without such experiences (unaffected comparisons; UC). Participants watched movies during which an agent formed true or false beliefs about the location of a ball, while participants always knew the true location of the ball. As hypothesised, right TPJ activation was greater for UCs compared to CAs for false vs true belief conditions. In addition, CAs showed increased functional connectivity relative to UCs between the rTPJ and dorsomedial prefrontal cortex. Finally, the agent’s belief about the presence of the ball influenced participants’ responses (ToM index), but without group differences. These findings highlight that experiencing early interpersonal trauma can alter brain areas involved in the neural processing of ToM and perspective-taking during adulthood

Marcadores inflamatórios como fatores preditivos para o efeito antidepressivo dos inibidores seletivos da recaptura de serotonina (ISRS)

ntroduction: Data have supported the influence of inflammation in the pathophysiology of depression and also the influence of depression in the development of a pro-inflammatory state. Major depressive disorder (MDD), the core depressive condition, has selective serotonin reuptake inhibitors (SSRI) as its first line pharmacological treatment. Efforts have been made to identify predictive factors for the responsiveness to SSRI. Therefore, we conducted this review to evaluate the hypothesis that baseline levels of inflammatory markers predict the responsiveness of MDD to SSRI treatment. Methods: A search in the PubMed database was made including the keywords (“SSRI” or “sertraline” or “citalopram” or “fluvoxamine” or “escitalopram” or “fluoxetine” or “paroxetine”) and (“cytokines” or “CRP” or “TNF” or “inflammatory”) and (“major depressive disorder” or “major depression”). Results: The search retrieved 245 manuscripts, from which 12 fulfilled our inclusion criteria. The analysis of these manuscripts suggested that high levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α) and c-reactive protein (CRP) at baseline might predict low responsiveness of MDD to SSRI treatment. Confounders such as cognitive impairment, chronicity and severity of depression, melancholic subtype, age and gender were not systematically included in the studies. Conclusion: Findings of this review suggest that high levels of pro-inflammatory markers at baseline might predict low responsiveness of MDD to SSRI treatment. Studies with adequate control for confounders are needed.A influência da inflamação na fisiopatologia da depressão e o papel da depressão no desenvolvimento de um estado pró-inflamatório têm sido apoiados por diversos estudos. O transtorno depressivo maior (TDM), principal diagnóstico de depressão, tem os inibidores seletivos da recaptação de serotonina (ISRS) como tratamento farmacológico de primeira linha. Esforços têm sido feitos para identificar fatores preditivos da responsividade ao tratamento antidepressivo os ISRS. Portanto, esta revisão tem como objetivo avaliar a hipótese de que níveis basais de marcadores inflamatórios predizem a responsividade do TDM ao tratamento com ISRS. Métodos: Pesquisamos o banco de dados PubMed, incluindo as palavras-chave (“ISRS” ou “sertralina” ou “citalopram” ou “fluvoxamina” ou “escitalopram” ou “fluoxetina” ou “paroxetina”) e (“citocinas” ou “CRP” ou “TNF” ou “inflamatório”) e (“transtorno depressivo maior” ou “depressão maior”). Resultados: A pesquisa identificou 245 manuscritos, dos quais 12 satisfizeram os critérios de inclusão e exclusão e foram incluídos nesta revisão. A análise destes manuscritos sugeriu que níveis elevados de interleucina 6 (IL-6),  interleucina 1β (IL-1β), fator de necrose tumoral – alfa (TNF-α) e proteína C-reativa (PCR) na avaliação basal podem prever baixa responsividade da depressão ao tratamento com ISRS. Fatores de confusão como deficiência cognitiva, cronicidade e gravidade da depressão, subtipo melancólico, idade e sexo, não foram sistematicamente incluídos nos estudos. Conclusão: Os achados desta revisão sugerem que níveis elevados de marcadores pró-inflamatórios na avaliação basal podem predizer baixa responsividade do TDM ao tratamento com ISRS. Estudos com controle adequado para fatores de confusão são necessários

The Influence of Parent-Child Relatedness and Social Support on Depressive Symptoms in Asthmatic Children: Tests of Moderation

The Brofenbrenner(1979) ecological theory was applied to examine the relationship between parent and child depressive mood and the moderation of relational quality at two levels; 1) parent-child (within family) and 2) family-social support (outside family) levels. It was hypothesized that both levels would buffer the predictive association of parent to child depressive mood. At the first level, the parent-child depressive mood association was qualified by an interaction with relatedness (categorized as inadequate and adequate) that approached a conventional level of significance, R2 = .023, F(1,101) = 2.77, p = .099. At the second level, the addition of social support as a moderator yielded a R2 =.028, F(1,101) = 3.11, p = .081. Exploratory analyses were performed to clarify each moderation. The findings suggest that relational quality within and outside the family have the potential to serve as protective factors in regards to depressive symptoms for children with asthma

Factors that Contribute to Susceptibility of the Placebo/Nocebo Effect in Experimentally Induced Ischemic Arm Pain

Placebo’s (positive expectancies producing positive outcomes) and nocebo’s (negative expectancies producing negative outcomes) are real and measurable effects. Real as these effects may be, predicting individuals that may be susceptible to placebo/nocebo effects has been inconsistent. The present study examined whether measures designed to assess somatization (MSPQ), catastrophizing (PCS) and childhood trauma (CTQ) would predict placebo and nocebo membership. In addition, measures designed to assess anxiety (ASI) anxiety about pain (PASS) and depression (BDI) were evaluated to determine whether anxiety or depression mediates responsiveness. The Hargreaves Thermal Withdrawal test and the submaximal effort tourniquet technique were employed as pain vehicles for the measurement of group differences. No significant effects of planned analyses were observed. However, unplanned analyses of childhood trauma subscales indicated that physical and emotional abuse predicted placebo response. Additionally, emotional neglect trended toward predicting nocebo responsiveness. These results indicate that further studies, correcting for weaknesses, is warranted

Factors that Contribute to Susceptibility of the Placebo/Nocebo Effect in Experimentally Induced Ischemic Arm Pain

Placebo’s (positive expectancies producing positive outcomes) and nocebo’s (negative expectancies producing negative outcomes) are real and measurable effects. Real as these effects may be, predicting individuals that may be susceptible to placebo/nocebo effects has been inconsistent. The present study examined whether measures designed to assess somatization (MSPQ), catastrophizing (PCS) and childhood trauma (CTQ) would predict placebo and nocebo membership. In addition, measures designed to assess anxiety (ASI) anxiety about pain (PASS) and depression (BDI) were evaluated to determine whether anxiety or depression mediates responsiveness. The Hargreaves Thermal Withdrawal test and the submaximal effort tourniquet technique were employed as pain vehicles for the measurement of group differences. No significant effects of planned analyses were observed. However, unplanned analyses of childhood trauma subscales indicated that physical and emotional abuse predicted placebo response. Additionally, emotional neglect trended toward predicting nocebo responsiveness. These results indicate that further studies, correcting for weaknesses, is warranted

Low-grade inflammation as a predictor of antidepressant and anti- inflammatory therapy response in MDD patients: a systematic review of the literature in combination with an analysis of experimental data collected in the EU-MOODINFLAME consortium

Terapia antiinflamatoria; Terapia antidepresiva; InflamaciónAnti-inflammatory therapy; Antidepressant therapy; InflammationTeràpia antiinflamatòria; Teràpia antidepressiva; InflamacióLow-grade inflammation plays a role not only in the pathogenesis of major depressive disorder (MDD) but probably also in the poor responsiveness to regular antidepressants. There are also indications that anti-inflammatory agents improve the outcomes of antidepressants. Aim: To study whether the presence of low-grade inflammation predicts the outcome of antidepressants, anti-inflammatory agents, or combinations thereof. Methods: We carried out a systematic review of the literature on the prediction capability of the serum levels of inflammatory compounds and/or the inflammatory state of circulating leukocytes for the outcome of antidepressant/anti-inflammatory treatment in MDD. We compared outcomes of the review with original data (collected in two limited trials carried out in the EU project MOODINFLAME) on the prediction capability of the inflammatory state of monocytes (as measured by inflammatory gene expression) for the outcome of venlafaxine, imipramine, or sertraline treatment, the latter with and without celecoxib added. Results: Collectively, the literature and original data showed that: 1) raised serum levels of pro-inflammatory compounds (in particular of CRP/IL-6) characterize an inflammatory form of MDD with poor responsiveness to predominately serotonergic agents, but a better responsiveness to antidepressant regimens with a) (add-on) noradrenergic, dopaminergic, or glutamatergic action or b) (add-on) anti-inflammatory agents such as infliximab, minocycline, or eicosapentaenoic acid, showing—next to anti-inflammatory—dopaminergic or lipid corrective action; 2) these successful anti-inflammatory (add-on) agents, when used in patients with low serum levels of CRP/IL-6, decreased response rates in comparison to placebo. Add-on aspirin, in contrast, improved responsiveness in such “non-inflammatory” patients; 3) patients with increased inflammatory gene expression in circulating leukocytes had a poor responsiveness to serotonergic/noradrenergic agents. Conclusions: The presence of inflammation in patients with MDD heralds a poor outcome of first-line antidepressant therapies. Immediate step-ups to dopaminergic or glutamatergic regimens or to (add-on) anti-inflammatory agents are most likely indicated. However, at present, insufficient data exist to design protocols with reliable inflammation parameter cutoff points to guide such therapies, the more since detrimental outcomes are possible of anti-inflammatory agents in “non-inflamed” patients.This study was financially supported by the EU via the MOODINFLAME project (EU-FP7-HEALTH-F2-2008-222963), the PSYCHAID (EU-FP7-PEOPLE-2009-IAPP-MarieCurie-286334), and the MOODSTRATIFICATION project (H2020-EU. 3.1.1., GA754740). NM and GA were additionally supported by the foundation "Immunitat und Seele." The funders had no role in study design, data collection, analysis and interpretation of data, the writing of the report, and the decision to submit the paper for publication

Multi-Agent-Based CBR Recommender System for Intelligent Energy Management in Buildings

This paper proposes a novel case-based reasoning (CBR) recommender system for intelligent energy management in buildings. The proposed approach recommends the amount of energy reduction that should be applied in a building in each moment, by learning from previous similar cases. The k-nearest neighbor clustering algorithm is applied to identify the most similar past cases, and an approach based on support vector machines is used to optimize the weight of different parameters that characterize each case. An expert system composed by a set of ad hoc rules guarantees that the solution is adequate and applicable to the new case scenario. The proposed CBR methodology is modeled through a dedicated software agent, thus enabling its integration in a multi-agent systems society for the study of energy systems. Results show that the proposed approach is able to provide suitable recommendations on energy reduction, by comparing its results with a previous approach based on particle swarm optimization and with the real reduction in past cases. The applicability of the proposed approach in real scenarios is also assessed through the application of the results provided by the proposed approach on a house energy resources management system.This work was supported in part by the EU's H 2020 research and innovation programme under the Marie SklodowskaCurie Grant Agreement 641794 (project DREAM-GO) and Grant Agreement 703689 (project ADAPT), in part by the FEDER Funds through COMPETE program, and in part by the National Funds through FCT under the Project UID/EEA/00760/2013. (Corresponding author: Tiago Pinto.)info:eu-repo/semantics/publishedVersio

Multi-Agent-Based CBR Recommender System for Intelligent Energy Management in Buildings

[EN] This paper proposes a novel case-based reasoning (CBR) recommender system for intelligent energy management in buildings. The proposed approach recommends the amount of energy reduction that should be applied in a building in each moment, by learning from previous similar cases. The k-nearest neighbor clustering algorithm is applied to identify the most similar past cases, and an approach based on support vector machines is used to optimize the weight of different parameters that characterize each case. An expert system composed by a set of ad hoc rules guarantees that the solution is adequate and applicable to the new case scenario. The proposed CBR methodology is modeled through a dedicated software agent, thus enabling its integration in a multi-agent systems society for the study of energy systems. Results show that the proposed approach is able to provide suitable recommendations on energy reduction, by comparing its results with a previous approach based on particle swarm optimization and with the real reduction in past cases. The applicability of the proposed approach in real scenarios is also assessed through the application of the results provided by the proposed approach on a house energy resources management system