Combining polynomial chaos expansions and genetic algorithm for the coupling of electrophysiological models

The number of computational models in cardiac research has grown over the last decades. Every year new models with di erent assumptions appear in the literature dealing with di erences in interspecies cardiac properties. Generally, these new models update the physiological knowledge using new equations which reect better the molecular basis of process. New equations require the fi tting of parameters to previously known experimental data or even, in some cases, simulated data. This work studies and proposes a new method of parameter adjustment based on Polynomial Chaos and Genetic Algorithm to nd the best values for the parameters upon changes in the formulation of ionic channels. It minimizes the search space and the computational cost combining it with a Sensitivity Analysis. We use the analysis of di ferent models of L-type calcium channels to see that by reducing the number of parameters, the quality of the Genetic Algorithm dramatically improves. In addition, we test whether the use of the Polynomial Chaos Expansions improves the process of the Genetic Algorithm search. We conclude that it reduces the Genetic Algorithm execution in an order of 103 times in the case studied here, maintaining the quality of the results. We conclude that polynomial chaos expansions can improve and reduce the cost of parameter adjustment in the development of new models.Peer ReviewedPostprint (author's final draft

Gender Differences in Er Psychiatric Consultations Among Suicide Attempters

Purpose: Suicide attempts are extremely prevalent and associated with many risk factors that vary with age and gender, occur in combination, and may change over time. The aim of the present study was to describe gender differences among psychiatric ER users at the AOU Maggiore della Carità Hospital in Novara for attempted suicide with regard to intentions and methods of attempting. Methods: Determinants of ER psychiatric consultations were studied prospectively during the period 2008- 2014 at the 'Maggiore” Hospital in Novara. Comparison of qualitative data was performed by means of the χ2 test. Statistical significance was set at p≤0.05. Results: We have already gathered data from more than 2000 ER psychiatric consultations. Preliminary results suggest that suicide attempts are more common in females than in males, although through the years there seems to be a trend towards increase of attempts even in males. Surprisingly, suicide attempts are found to be more common in employed subjects than in unemployed ones. Reasons for self-harming are associated with relational problems rather than psychiatric symptoms. Drugs poisoning seems to be the preferred suicide method. Conclusions: The results described above should be considered as preliminary, as data collection and statistical analyses are still ongoing. Anyway, the possible correlation between employment and suicide attempt, and the growing frequency of attempts in males seem to be particularly interesting. Implications will be discussed

Asenapine in Clinical Practice: Responders Vs Non-responders

ntroduction Asenapine is a second-generation antipsychotic approved in Europe for the treatment of manic or mixed episodes. Objective To describe the clinical features of Asenapine responders and non-responders. Methods A naturalistic, observational study is ongoing in patients treated with Asenapine. We have already recruited 37 manic patients with a lifetime diagnosis of Bipolar I (BDI) or Schizoaffective Disorder referring to our Psychiatric Ward. Patients are assessed with the Young Mania Rating Scale (YMRS) at baseline (T0), and after 1 (T1) and 4 weeks (T2) of treatment. According to YMRS scores, patients are classified as responders and non-responders. Results The preliminary results highlight a significant improvement of the YMRS score from T0 to T2 in most patients. Asenapine seems particularly effective in patients with less severe manic symptoms, and responders are more likely to have lower baseline YMRS score. No correlation has currently emerged between responder status and diagnosis. Non-responders in our sample are females sharing some clinical features: early onset BDI diagnosis, several previous treatments (antipsychotics, mood stabilizers), initial cognitive impairment confirmed with the Mini Mental State Examination, Alzheimer Disease Assessment Scale and neuroimaging. Conclusions Elderly manic patients with neurological impairment and/or dementia may have poorer therapeutic outcomes and poorer response to pharmacological treatment, which may prove effective in reducing agitation but not mania ratings. Diagnosis (BDI or schizoaffective disorder) does not seem to have a significant impact on Asenapine efficacy. The further recruitment and assessment of patients is expected to support the results described above

Psychosocial Suicide Prevention Interventions in the Elderly: A Mini-Review of the Literature

In Europe the elderly population is projected to increase from 18.5% (93.9 million) in 2014 to 28.7% (149.1 million) by 2080. In the United States it is estimated that by 2030 more than 20% of the population will be aged 65 years or over. This specific population is at high risk of unrecognized or untreated psychiatric illnesses and suicide. It is well known that completed suicide rate increases with age in both men and women. Although elderly people attempt suicide less often than other age groups, they show a higher completion rate. Generally, the methods chosen by elderly are more lethal, the intent is more serious, they are more determined, and they show fewer warning signs than the younger population. A recent systematic review and meta-analysis of psychosocial intervention, following self-harm in adults, found that cognitive behavioral therapy was the most effective therapy in these patients. Unfortunately, there have been few reported trials of other potentially effective interventions. Because the scientific literature on psychosocial suicide prevention interventions in the elderly is still scant, we conducted a mini-review in order to take stock of the situation. Studies were identified through electronic searches of the Cochrane library, MEDLINE, Scopus and the Web of Science databases. PRISMA guidelines were followed and only seven articles met the inclusion criteria. No firm conclusions can be drawn about this topic because there is still very little data and studies use inconsistent outcome measures and designs. Nonetheless, the existing data suggests that psychosocial interventions are promising

Asenapine Effects On Peroxidation and Calcium Movements in HL-1 Cells

Introduction Bipolar patients are at higher risk for cardiovascular morbidity and mortality than their counterparts in the general population. In a recent in vitro study, Asenapine, a new antipsychotic for the treatment of mania/mixed mania, was found to keep physiological endothelial function by activation of eNOS-related NO release and to protect endothelial cells against peroxidation by interference with mitochondria, apoptosis and cell survival. Objectives To examine the cardiac protective effects elicited by Asenapine against peroxidation and on the Ca2+ movements. Methods In HL-1 that had undergone oxidative stress by 20 min hydrogen peroxide the effects of 30 min pre-treatment with Asenapine on survival and proliferation will be examined. In Fura-2AM loaded HL-1 we will next analyze the effects of Asenapine on Ca2+ movements and the related involvement of cAMP/PKA and PLC pathways, CaMKII, L and T type Ca2+ channels and 5HT1A receptors. The role of 'capacitative” Ca2+ entry, plasma-membrane Ca2+ pump inhibitor (PMCA) and Na+/Ca2+ exchanger will be analyzed. Changes of membrane potential caused by interference with K+ channels will be examined, as well. Results We expect to find a proliferative and anti-peroxidative effect of Asenapine in HL-1 cells. Asenapine could also affect Ca2+ movements through cAMP/PKA and PLC-dependent signalling and the involvement of 5HT1A receptors. The effects of Asenapine could also be related to changes of plasma membrane by interference with K+ channels and the modulation of PMCA activity and Na+/Ca2+ exchanger. Conclusions We expect to further confirm the protective effect of Asenapine against peroxidative injuries.Implications will be discusse

Early Rehabilitation in a Psychiatric Ward for Acute Patients: the Experience of the S.C. Psichiatria, Aou Maggiore Della Carit\ue0, Novara, Italy

Introduction Our Psychiatry Ward (SC Psichiatria, Maggiore della Carit\ue0 Hospital, Novara) has a longstanding tradition in the training of clinicians (psychiatrists, but also non-psychiatrists) about the importance of the approach in helping relationships. This tradition reflects itself in the organization of the assistance to the acute psychiatric inpatients admitted to the Ward. In addition to treatment as usual, patients have the opportunity of being involved in several group activities. The activities are proposed to them, with an approach that varies according to the patient's lifetime diagnosis, current conditions, relational difficulties, etc. In other words, different activities may be proposed to different patients, in different ways. Aims To describe the integrated treatment approach we use in our Psychiatry Ward. Methods Group activities are guided by a group leader who is supported by one or two assistants whose role is to facilitate discussion. Activities include: Newspaper Reading (everyday in the morning, 1 hour); Music Listening Group (once a week; 1 hour); Cinema Group (once a week; 2 hours and a half); Fairytale Group (on alternating days in the evening, 1 hour). Results More details will be supplied regarding the theoretical background for the group, the group features/implementation, and its specific objectives. Conclusions All the group activities integrate themselves in an early rehabilitation project tailored to each patients' characteristics and needs. Briefly, their main objectives include: 1) to help patients endorse their cognitive, emotional and relational skills; 2) to offer support to the crisis they are experiencing, which led them to admission to the Ward

Social cognition in people with schizophrenia: A cluster-analytic approach

Background The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. Method A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. Results We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. Conclusions If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person

The interplay among psychopathology, personal resources, context-related factors and real-life functioning in schizophrenia: stability in relationships after 4 years and differences in network structure between recovered and non-recovered patients

Improving real-life functioning is the main goal of the most advanced integrated treatment programs in people with schizophrenia. The Italian Network for Research on Psychoses previously explored, by using network analysis, the interplay among illness-related variables, personal resources, context-related factors and real-life functioning in a large sample of patients with schizophrenia. The same research network has now completed a 4-year follow-up of the original sample. In the present study, we used network analysis to test whether the pattern of relationships among all variables investigated at baseline was similar at follow-up. In addition, we compared the network structure of patients who were classified as recovered at follow-up versus those who did not recover. Six hundred eighteen subjects recruited at baseline could be assessed in the follow-up study. The network structure did not change significantly from baseline to follow-up, and the overall strength of the connections among variables increased slightly, but not significantly. Functional capacity and everyday life skills had a high betweenness and closeness in the network at follow-up, as they had at baseline, while psychopathological variables remained more peripheral. The network structure and connectivity of non-recovered patients were similar to those observed in the whole sample, but very different from those in recovered subjects, in which we found few connections only. These data strongly suggest that tightly coupled symptoms/dysfunctions tend to maintain each other's activation, contributing to poor outcome in schizophrenia. Early and integrated treatment plans, targeting variables with high centrality, might prevent the emergence of self-reinforcing networks of symptoms and dysfunctions in people with schizophrenia

The association between insight and depressive symptoms in schizophrenia: Undirected and Bayesian network analyses

Background. Greater levels of insight may be linked with depressive symptoms among patients with schizophrenia, however, it would be useful to characterize this association at symptom-level, in order to inform research on interventions. Methods. Data on depressive symptoms (Calgary Depression Scale for Schizophrenia) and insight (G12 item from the Positive and Negative Syndrome Scale) were obtained from 921 community-dwelling, clinically-stable individuals with a DSM-IV diagnosis of schizophrenia, recruited in a nationwide multicenter study. Network analysis was used to explore the most relevant connections between insight and depressive symptoms, including potential confounders in the model (neurocognitive and social-cognitive functioning, positive, negative and disorganization symptoms, extrapyramidal symptoms, hostility, internalized stigma, and perceived discrimination). Bayesian network analysis was used to estimate a directed acyclic graph (DAG) while investigating the most likely direction of the putative causal association between insight and depression. Results. After adjusting for confounders, better levels of insight were associated with greater self-depreciation, pathological guilt, morning depression and suicidal ideation. No difference in global network structure was detected for socioeconomic status, service engagement or illness severity. The DAG confirmed the presence of an association between greater insight and self-depreciation, suggesting the more probable causal direction was from insight to depressive symptoms. Conclusions. In schizophrenia, better levels of insight may cause self-depreciation and, possibly, other depressive symptoms. Person-centered and narrative psychotherapeutic approaches may be particularly fit to improve patient insight without dampening self-esteem

The interplay among psychopathology, personal resources, context-related factors and real-life functioning in schizophrenia: stability in relationships after 4 years and differences in network structure between recovered and non-recovered patients

Improving real-life functioning is the main goal of the most advanced integrated treatment programs in people with schizophrenia. The Italian Network for Research on Psychoses previously explored, by using network analysis, the interplay among illness-related variables, personal resources, context-related factors and real-life functioning in a large sample of patients with schizophrenia. The same research network has now completed a 4-year follow-up of the original sample. In the present study, we used network analysis to test whether the pattern of relationships among all variables investigated at baseline was similar at follow-up. In addition, we compared the network structure of patients who were classified as recovered at follow-up versus those who did not recover. Six hundred eighteen subjects recruited at baseline could be assessed in the follow-up study. The network structure did not change significantly from baseline to follow-up, and the overall strength of the connections among variables increased slightly, but not significantly. Functional capacity and everyday life skills had a high betweenness and closeness in the network at follow-up, as they had at baseline, while psychopathological variables remained more peripheral. The network structure and connectivity of non-recovered patients were similar to those observed in the whole sample, but very different from those in recovered subjects, in which we found few connections only. These data strongly suggest that tightly coupled symptoms/dysfunctions tend to maintain each other's activation, contributing to poor outcome in schizophrenia. Early and integrated treatment plans, targeting variables with high centrality, might prevent the emergence of self-reinforcing networks of symptoms and dysfunctions in people with schizophrenia