EVMDD-based analysis and diagnosis methods of multi-state systems with multi-state components

A multi-state system with multi-state components is a model of systems, where performance, capacity, or reliability levels of the systems are represented as states. It usually has more than two states, and thus can be considered as a multi-valued function, called a structure function. Since many structure functions are monotone increasing, their multi-state systems can be represented compactly by edge-valued multi-valued decision diagrams (EVMDDs). This paper presents an analysis method of multi-state systems with multi-state components using EVMDDs. Experimental results show that, by using EVMDDs, structure functions can be represented more compactly than existing methods using ordinary MDDs. Further, EVMDDs yield comparable computation time for system analysis. This paper also proposes a new diagnosis method using EVMDDs, and shows that the proposed method can infer the most probable causes for system failures more efficiently than conventional methods based on Bayesian networks.Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology (MEXT)Hiroshima City UniversityGrant-in Aid No. 2500050 (MEXT)Grant no. 0206 (HCU)Grant in Aid for Scientific Research (JSPS

Cognitive, behavioral, and autonomic correlates of mind wandering and perseverative cognition in major depression

Autonomic dysregulation has been hypothesized to play a role in the relationships between psychopathology and cardiovascular risk. An important transdiagnostic factor that has been associated with autonomic dysfunction is perseverative cognition (PC), mainly present in Major Depressive Disorder (MDD) in the form of rumination. As the ability to adaptively let our mind wander without ruminating is critical to mental health, this study aimed to examine the autonomic concomitants of functional vs. dysfunctional intrusive thoughts in MDD. Ambulatory heart rate (HR) and variability (HRV) of 18 MDD subjects and 18 healthy controls were recorded for 24 h. Approximately every 30 min during waking hours subjects reported their ongoing thoughts and moods using electronic diaries. Random regression models were performed. Compared to controls, MDD subjects were more often caught during episodes of PC. In both groups, PC required more effort to be inhibited and interfered more with ongoing activities compared to mind wandering (MW) (ps < 0.0001). This cognitive rigidity was mirrored by autonomic inflexibility, as PC was characterized by lower HRV (p < 0.0001) compared to MW. A worse mood was reported by MDD patients compared to controls, independently of their ongoing cognitive process. Controls, however, showed the highest mood worsening during PC compared to being on task and MW. HRV during rumination correlated with self-reported somatic symptoms on the same day and several dispositional traits. MDD subjects showed lower HRV during sleep, which correlated with hopelessness rumination. Results show that PC is associated with autonomic dysfunctions in both healthy and MDD subjects. Understanding when spontaneous thought is adaptive and when it is not may clarify its role in the etiology of mood disorders, shedding light on the still unexplained association between psychopathology, chronic stress, and risk for health

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Developing a distributed electronic health-record store for India

The DIGHT project is addressing the problem of building a scalable and highly available information store for the Electronic Health Records (EHRs) of the over one billion citizens of India

A study of recurrent unipolar major depression and executive functions

Background: Unipolar major depression is a prevalent disorder and is in the World Health Organisation’s (WHO) top five on their global burden of disease-list. For more than three decades, assessment of neurocognitive functioning in patients with mental disorders by use of neuropsychological tests has been performed for research purposes. Patients with schizophrenia have been extensively studied, but a substantial amount of research has also been performed on depressed patients. In patients with unipolar major depression, performance below that of healthy controls has been shown on tests measuring memory, attention, psychomotor speed and executive functions. Executive Functions (EF) are higher order neurocognitive functions that control and integrate other neurocognitive functions; dysfunctions have been associated with frontal lobe dysfunction. Still, there is a lack of studies investigating EF in the most prevalent form of unipolar major depression, patients with recurrent subtype. This thesis is based on four original research papers published in referee based international journals. In paper I, we question whether executive dysfunctions also are present in patients with recurrent unipolar major depression compared to healthy controls. The investigation includes pattern and severity of executive dysfunction. In paper II, we consider whether all patients with recurrent unipolar major depression have impairment of EF. Mental disorders can be regarded as both categorical and dimensional conditions: according to the continuum model unipolar major depression and schizophrenia can be viewed as different levels of general psychopathology (LGP). Paper III explores the continuum model of mental disorders. We investigate whether LGP explains more of the variance in EF than diagnosis (unipolar major depression versus schizophrenia). Elevated levels of the stress hormone cortisol are often found among depressed patients, and there is evidence that prolonged hypercortisolemia can be neurotoxic. Specifically, recurrent depression episodes may lead to progressive brain damage. It is uncertain if executive dysfunctions in recurrent unipolar major depression are associated with elevated cortisol levels. Therefore, the aim of paper IV was to explore whether level of saliva cortisol is correlated with level of executive dysfunctions in recurrent unipolar major depression. Method: Data were collected in the context of a Norwegian, cross-sectional, multi-centre study, the BOP, starting in 1998. In the BOP, patients with either a diagnosis of unipolar major depressive disorder (MDD), recurrent type (N=50) or schizophrenia (N=53) and healthy controls (N=50) were included. The patients were diagnosed by the Structured Clinical Interview for DSM-IV Axis I Disorders. Depressed patients scoring above 18 points on both the Hamilton Depression Rating Scale and Montgomery-Åsberg Depression Rating Scale were included. Other inclusion criteria were: age between 20 and 50, Norwegian language and normal vision and hearing. Patients were excluded if they had a history of head trauma, neurological disorder or developmental dysfunction, present alcohol or substance abuse, other medical conditions likely to affect neurocognitive functions or if they recently had received electro convulsive treatment. The clinical psychiatric evaluation was performed by five trained psychiatrists. In the BOP, a broad neuropsychological test battery was used to measure several domains of neurocognitive function. In this thesis, mainly tests assessing components of EF are used. The tests were administered by a licensed clinical neuropsychologists, a graduate psychology student or a medical doctor (Kirsten Irene Stordal) supervised by a neuropsychologists. Results: There was a tendency for patients with recurrent MDD to perform below healthy controls on all measures of EF (Paper I). A significant group difference was found for eight of ten measures. The executive dysfunctions were within -1.0 SD from the mean of the control group. While the components verbal fluency, inhibition, set-maintenance and working memory were affected in recurrent MDD, set-shifting and planning seemed to be spared. Whether this dysfunction could be found in all patients with recurrent episodes of depression, was uncertain. This was explored in the following paper, the result being that more than half of the patients with recurrent MDD had unimpaired EF when unimpairment was defined as performance above -1.0 SD of the sample mean of the control group on more than one component of EF (Paper II). The sub-group of patients without impairment of EF was characterised by higher intellectual abilities and fewer episodes of depression than the subgroup with EF impairment. In paper III we found EF impairment to be more strongly related to LGP than to diagnosis (MDD versus schizophrenia). In the last paper an inverse correlation between saliva cortisol and EF was found (Paper IV). Discussion: All the papers add to current knowledge in this field: The first paper in that patients with recurrent MDD have mild executive dysfunctions, and that seemingly all components of EF are affected. The second paper shows that more than half of patients with recurrent MDD have unimpaired EF when depressed, and that this subgroup has higher intellectual abilities and a history of fewer depression episodes. The novel finding in the third paper is that EF impairment is more strongly related to LGP than diagnosis (comparing MDD and schizophrenia). This finding is in line with the continuum hypothesis in psychiatry. In recurrent MDD, the level of performance on tests assessing EF seems to be inversely correlated with the level of saliva cortisol. Thus, this fourth study directly and indirectly gave support to the cortisol hypothesis. There is little evidence that unipolar major depression is uniquely associated with executive dysfunctions due to that 1) most components of EF are affected, 2) not all patients have executive dysfunctions, 3) executive dysfunctions are not specific to depression as they are also found in other mental disorders and in somatic disorders and 4) not all depressed patients have elevated levels of cortisol associated with executive dysfunctions. Future studies of the association between mental disorders and neurocognitive dysfunction should avoid restrictions resulting from imperfect diagnostic classifications for mental disorders, i.e. focusing on similarities in neurocognitive dysfunctions across psychiatric diagnoses rather than within one mental disorder at the time

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

The management of major depressive disorder in cancer patients: a randomised trial

The overall aim was to improve the management of depression in patients with cancer. The specific objective was to:1. Test the efficacy of this intervention model for the treatment of MDD in cancer patients of mixed diagnoses in a randomised controlled trial by comparing usual care with usual care plus the nurse-delivered, psychiatrist-supervised multi-component intervention by:A. MEASURING THE PRIMARY OUTCOME OF TRIAL PARTICIPANTS AT 3 AND 6 MONTHS The efficacy of the intervention model was tested at three months using the primary outcome measure of the SCL-20. A substantially better and statistically significantly better outcome was obtained for those patients receiving the additional intervention with the benefit being sustained at the six-month follow-up. The main hypothesis that usual care plus a nurse-delivered, psychiatrist-supervised multi-component treatment intervention would reduce symptoms of major depressive disorder in patients with cancer to a greater extent than usual care alone was supported.b. Measuring other outcomes at 3 and 6 months, specifically: I. CLINICALLY RELEVANT RESPONSE TO TREATMENT AND REMISSION OFDEPRESSIVE SYMPTOMS The efficacy of the intervention model was tested at three months using clinically important criteria of treatment response and remission. There was a statistically 196 significant difference in proportions of patients achieving the pre-specified secondary outcomes between the groups at three months. Observing convergence of the results has provided robustness and clinical validity to the findings of the primary outcome. Furthermore, the findings suggest that the differences in benefit may even be larger at six months. The hypothesis is shown to be supported that at the 6 month followup, patients treated with the additional nurse-delivered intervention will maintain the benefit and have benefit superior to those patients who were allocated to usual care only.II. ANXIETY, PHYSICALFUNCTIONING, COPING, PROBLEM SOLVING ABILITY AND SATISFACTION WITH TREATMENT The efficacy of the intervention model was tested at three months using measures of anxiety, physical functioning, coping and problem-solving. A greater reduction in anxiety and a greater increase in all coping measures were observed in the intervention group. However, no significant differences were observed on the measure of physical functioning between treatment groups at three months. This was not a surprising finding and reinforces findings of similar trials in chronic illness. Although no formal significance testing was performed at six months, the treatment effect for physical functioning was larger in favour of the intervention group.Satisfaction with treatment measured at six months found that the satisfaction of patients receiving the intervention was greater than those receiving usual care.III. THE ASSOCIATION BETWEEN IMPROVEMENT IN DEPRESSION SCORES AND ASPECTS OF CONFIDENCE, COPING AND SUPPORT The associations between improvement in depression scores and measures of confidence, coping and support were explored at three months. A correlation was found between improvement in depression outcome and change in measures of confidence but not of support and coping, suggesting that increasing patients' confidence may have had an influence on outcome. The hypothesis that the additional nurse intervention improves outcome by a) increasing the patient's confidence to cope with concerns and b) increasing their coping skills by teaching them a skill to tackle their concerns and c) increasing their access to and use of social support therefore receives some support and can only be considered as exploratory findings.IV. THE EXTENT TO WHICH BASELINEFACTORS PREDICT A GOOD OUTCOME AT 3 MONTHS (ALTHOUGH THIS WAS EXPLORATORY AND NOTPART OFTHE PRE-SPECIFIED STATISTICAL ANALYSIS PLAN) At the 3 month outcome, exploratory analysis suggested that the principal independent predictors of good outcome were: allocation to the additional intervention arm; no previous history of depression; a current episode of less than one year's duration; and a low baseline depression severity score. It was surprising that neither gender, nor any cancer related variables such as extent of disease nor whether the patient was receiving active anti-cancer treatment emerged as predictors of response.In conclusion the overall aim which was to improve the management of depression in cancer has been largely achieved. However, a large effectiveness trial is now required to determine whether the intervention is effective when implemented outwith a research environment in the 'real world' of a health care system.In summary, there is a robust body of evidence to support the effectiveness of collaborative depression care in primary care but only limited evidence of its efficacy and effectiveness in patients with comorbid medical conditions and next to none in cancer patients. There is therefore a pressing need for research into the management of depression in patients with cance