bluuebunny/crossref_metadata_2025_split huggingface dataset:
Major Histocompatibility Complex Class II Alleles Influence Induction of Pathogenic Antiphospholipid Antibodies in a Mouse Model of Thrombosis
Authors: Papalardo Elizabeth , Romay‐Penabad Zurina , Willis Rohan , Christadoss Premkumar , Carrera‐Marin Ana Laura , Reyes‐Maldonado Elba , Rudrangi Rajani , Alfieri‐Papalardo Silvana , Garcia‐Latorre Ethel , Blank Miri , Pierangeli Silvia , Brasier Allan R. , Gonzalez Emilio B. 
Published: June 2017

ObjectiveBoth environmental and genetic factors are important in the development of antiphospholipid antibodies (aPL) in patients with antiphospholipid syndrome (APS). Currently, the only available data on predisposing genetic factors have been obtained from epidemiologic studies, without mechanistic evidence. Therefore, we studied the influence of major histocompatibility complex (MHC) class II alleles on the production of aPL in a mouse model of APS.MethodsThree groups of mice, MHC class II–deficient (MHCII−/−) mice, MHCII−/− mice transgenic for human HLA–DQ6 (DQ6), DQ8, or DR4 alleles, and the corresponding wild‐type (WT) mouse strains were immunized; half were immunized with human β2‐glycoprotein I (β2GPI), and the other half were immunized with control ovalbumin (OVA) protein. Thrombus formation in vivo, tissue factor activity in carotid and peritoneal macrophages, and serum levels of tumor necrosis factor (TNF), IgG anticardiolipin (aCL), antibodies, and anti‐OVA antibodies were determined.ResultsImmunization with β2GPI induced significant production of aCL and anti‐β2GPI in WT mice compared with control mice immunized with OVA (P < 0.001) but diminished aCL (P < 0.001) and anti‐β2GPI (P = 0.016) production in MHCII−/− mice. Anti‐β2GPI production was fully restored in DQ6 and DQ8 mice, while levels of anti‐β2GPI in DR4 mice and aCL in all transgenic lines were only partially restored (P < 0.001 to P < 0.046). Thrombus size in WT mice was twice that in MHCII−/− mice (P < 0.001) but similar to that in all transgenic lines. Carotid and peritoneal macrophage tissue factor levels decreased by >50% in MHCII−/− mice compared with wild‐type B6 mice and were restored in DQ8 mice but not DR4 mice or DQ6 mice. TNF levels decreased 4‐fold in MHCII−/− mice (P < 0.001) and were not restored in transgenic mice.ConclusionOur mechanistic study is the first to show that MHC class II alleles influence not only quantitative aPL production but also the pathogenic capacity of induced aPL.
IM‐based and EDP‐based decision models for the verification of the seismic collapse safety of buildings
Authors: Dolšek Matjaž , Lazar Sinković Nuša , Žižmond Jure 
Published: June 2017

SummaryDecision models for the verification of seismic collapse safety of buildings are introduced. The derivations are based on the concept of the acceptable (target) annual probability of collapse, whereas the decision making involves comparisons between seismic demand and capacity, which is familiar to engineering practitioners. Seismic demand, which corresponds to the design seismic action associated with a selected return period, can be expressed either in terms of an intensity measure (IM) or an engineering demand parameter (EDP). Seismic capacity, on the other hand, is defined by dividing the near‐collapse limit‐state IM or EDP by an appropriate risk‐targeted safety factor (γim or γedp), which is the only safety factor used in the proposed decision model. Consequently, the seismic performance assessment of a building should be based on the best possible estimate. For a case study, it is shown that if the target collapse risk is set to 10−4 (0.5% over a period of 50 years), and if the seismic demand corresponds to a return period of 475 years (10% over a period of 50 years), then it can be demonstrated that γim is approximately equal to 2.5 for very stiff buildings, whereas for buildings with long periods the value of γim can increase up to a value of approximately 5. The model using γedp is equal to that using γim only if it can be assumed that displacements, with consideration of nonlinear behavior, are equal to displacements from linear elastic analysis.
A graph‐based postoptimization approach for covering arrays
Authors: Perez‐Torres Jose Carlos , Torres‐Jimenez Jose 
Published: June 2017

AbstractCovering arrays (CAs) are combinatorial objects with interesting features that have practical applications such as experimental design and fault detection in hardware and software. We introduce a graph‐based postoptimization (GBPO) approach to reduce the size of CAs exploiting the redundancy in CAs previously constructed. To evidence the advantages of using GBPO, we have instantiated it with 2 sets of CAs: (1) 560 CAs of strength 2≤t≤6, alphabet 2≤v≤6, and parameters 3≤k≤32 generated by an optimized version of In‐Parameter‐Order‐Generalized (IPOG‐F) and GBPO improved all CAs, and 37 cases matched the best‐known upper bounds; and (2) 32 CAs of strength t=2, alphabet 3≤v≤6, and number of parameters 8≤k≤146; in this set, 16 cases were improved, and 16 cases were matched.
Assertive Interventions for First Episode Psychoses: The Danish Experience
Authors: Nordentoft M. , Albert N. , Hjorthoj C. , Jensen H. , Melau M. 
Published: June 2017

Early Intervention services with team-based intensive case management and family involvement are superior to standard treatment in reducing psychotic and negative symptoms and comorbid substance abuse and improving social functioning and user satisfaction. The results of the OPUS-trial will be presented together with meta-analyses based on similar trials. The implementation of OPUS all over Denmark will be presented together with the Danish OPUS-fidelity study. Specialized elements are being are being developed such as inclusion of new methods in CBT for psychotic and negative symptoms, neurocognitive and social cognitive training programs, interventions for supported employment and focus on physical health. Results of long term follow-up studies indicate that the prognosis of first episode psychosis is very diverse with the extremes represented by one group being well functioning and able to quit medication without relapse; and another group having a long term chronic course of illness with a need for support to maintain daily activities. The Danish TAILOR-trial–testing dose reduction versus maintenance therapy will be presented. It will be of immense value to be able to intervene in risk groups identified in the premorbid phase, and there are few examples of ongoing trial for children of parent with schizophrenia and bipolar disorder.Disclosure of interestThe authors have not supplied their declaration of competing interest.
Inflammation and Pruning May Inform Risk to Psychiatric Disorders. Lessons From Large Genetic Data
Authors: Crisafulli C. 
Published: June 2017

BackgroundIt's known that psychiatric disorders are caused to either environmental and genetics factors. Through the years several hypotheses were tested and many genes were screened for association, resulting in a huge amount of data available for the scientific community. Despite that, the molecular mechanics behind psychiatric disorders remains largely unknown. Traditional association studies may be not enough to pinpoint the molecular underpinnings of psychiatric disorder. We tried to applying a methodology that investigates molecular-pathway-analysis that takes into account several genes per time, clustered in consistent molecular groups and may successfully capture the signal of a number of genetic variations with a small single effect on the disease. This approach might reveal more of the molecular basis of psychiatric disorders.Methodsi)We collected data on studies available in literature for the studied disorder (e.g. Schizophrenia, Bipolar Disorder);ii)We extracted a pool of genes that are likely involved with the disease;iii)We used these genes as starting point to map molecular cascades function-linked. The molecular cascades are then analyzed and pathways and sub-pathways, possibly involved with them, are identified and tested for association.Results/discussionWe obtained interesting results. In particular, signals of enrichment (association) were obtained multiple times on the molecular pathway associated with the pruning activity and inflammation. Molecular mechanics related to neuronal pruning were focused as a major and new hypothesis for the pathophysiology of psychiatric disorders and the role of inflammatory events has been extensively investigated in psychiatry. intersting, inflammatory mechanics in the brain may also play a role in neuronal pruning during the early development of CNS.Disclosure of interestThe author has not supplied his declaration of competing interest.
Frontostriatal Dysconnectivity in adolescent Onset Schizophrenia and its Associations with Cognition: An MRI Volumetric and Diffusion Tensor Imaging Study
Authors: James A. , Fernandes H.M. , Mota P. Alves Da , Hough M. 
Published: June 2017

BackgroundAdolescent-onset schizophrenia (AOS) is associated with cognitive impairment and poor clinical outcome. Cognitive dysfunction is thought to reflect functional dysconnectivity between the frontal cortex and the striatum, Previous work [1] has shown frontostriatal dysconnectivity in large WM tracts explain core cognitive deficits, with processing speed, which is affected by alterations in WM connectivity, being an intermediary variable.ObjectiveTo undertake a follow-up MRI study using whole-brain structural connectomics to track topological changes in the follow-up (1st episode versus follow-up), in order to characterize the early stages (evolution of the first two years) of the disorder.DesignA follow-up study of 25 AOS subjects and 25 age and sex-matched healthy subjects.OutcomeNetwork theory will be applied to identify topological alterations in structural networks, including frontostriatal white matter (WM) tracts in relation to cognition and outcome measures.Disclosure of interestThe authors have not supplied their declaration of competing interest.
The Impact of the Change Trial on Physical Health in People With Schizophrenia
Authors: Nordentoft M. , Speyer H. , Norgaard H.C.B. , Birk M. , Mors O. 
Published: June 2017

Life expectancy in patients with schizophrenia is reduced by 20 years for men and 15 years for women compared to the general population. About 60% of the excess mortality is due to physical illnesses, with cardiovascular disease being dominant. The aim of this trial was to improve the cardiovascular risk profile.MethodsThe CHANGE trial was an investigator-initiated, randomised, parallel-group, superiority, multi-centre trial with blinded outcome assessment. Patients diagnosed with schizophrenia spectrum disorders and increased waist circumference according (>88 cm for women, >102 cm for men), were recruited and centrally randomised 1:1:1 to 12-months of lifestyle coaching plus care coordination versus care coordination alone versus treatment as usual. The primary outcome was 10-year risk of cardiovascular disease assessed post-treatment and standardised to age 60, secondary outcomes included cardiorespiratory fitness and physical activity. Clinical.Trials.gov NCT01585493.FindingsA total of 428 participants were randomly assigned to the CHANGE intervention (n = 138); care coordination (n = 142); or treatment as usual (n = 148). At 12 months, the mean 10 years risk of cardiovascular disease was 8.4% (SD 6.7) in the CHANGE group, 8.5% (SD 7.5) in the care coordination group and 8.0% (SD 6.5) in the treatment as usual group (P = 0.41). We found no intervention effects for any secondary or explorative outcomes, including weight, cardiorespiratory fitness, physical activity, diet or smoking.InterpretationThe CHANGE trial did not support individual lifestyle coaching or care coordination as superior compared with treatment as usual in reducing the cardiovascular risk in patients with schizophrenia and increased waist circumference.Disclosure of interestThe authors have not supplied their declaration of competing interest.
Neurobiological Correlates of Learning and Decision-making in Alcohol Dependence
Authors: Sebold M. , Nebe S. , Garbusow M. , Schad D. , Sommer C. , Rapp M. , Smolka M. , Huys Q. , Schlagenhauf F. , Heinz A. 
Published: June 2017

The mesolimbic dopaminergic system has been implicated in two kinds of reward processing, one in reinforcement learning (e.g prediction error) and another in incentive salience attribution (e.g. cue-reactivity). Both functions have been implicated in alcohol dependence with the former contributing to the persistence of chronic alcohol intake despite severe negative consequences and the latter playing a crucial role in cue-induced craving and relapse. The bicentric study “Learning in alcohol dependence (LeAD)” aims to bridge a gap between these processes by investigating reinforcement learning mechanisms and the influence that Pavlovian cues exert over behavior. We here demonstrate that alcohol dependent subjects show alterations in goal-directed, model-based reinforcement learning (Sebold et al., 2014) and demonstrate that prospective relapsing patients show reductions in the medial prefrontal cortex activation during goal-directed control. Moreover we show that in alcohol dependent patients compared to healthy controls, Pavlovian cues exert pronounced control over behavior (Garbusow et al., 2016). Again, prospective relapsing patients showed increased Nucleus accumbens activation during these cue-induced responses. These findings point to an important role of the mesolimbic dopaminergic system as a predictor of treatment outcome in alcohol dependence.Disclosure of interestThe authors have not supplied their declaration of competing interest.
Mental Health and Social Care Providers Facing Requests of Assisted suicide from Elderly in Nursing Homes in Switzerland
Authors: Castelli Dransart D.A. , Voélin S. , Elena S. 
Published: June 2017

IntroductionIn some Swiss states, right-to-die associations are allowed to assist older people in nursing homes provided that certain requirements are fulfilled.ObjectivesTo investigate how health and social care providers and their institutions reacted to and dealt with requests of assisted suicide.MethodAn exploratory qualitative study was carried out in the States of Fribourg and Vaud among 40 professionals working in nursing homes, home care services or social welfare agencies.ResultsThe requests of assisted suicide questioned the professional mission, the quality of accompaniment provided to the older people and both professional and personal values. Health and social care providers were required to ponder over ethical dilemmas or decisions. Several challenges were reported, such as: taking into account and articulating personal freedom or needs with collective functioning or organizational constraints before, during and after the assisted suicide; reconciliating self-determination with protection towards vulnerable people (beneficere, non maleficere).ConclusionsAssisted suicide challenges and changes professional end-of-life practices. Education and support should be provided to health and social care providers faced with it.Disclosure of interestThe authors have not supplied their declaration of competing interest.
How long is the interval between the onset and the initial management of bipolar disorder? A meta-analysis
Authors: De Girolamo G. , Signorini G. , Dagani J. , Faustini F. 
Published: June 2017

ObjectiveTo evaluate the length of the interval between the onset and the initial management of bipolar disorder (BD).MethodWe conducted a meta-analysis using the preferred reporting items for systematic reviews and meta-analyses guidelines. Systematic searches located studies reporting estimates of the age of onset (AOO) and indicators of the age at initial management of BD. We calculated a pooled estimate of the interval between AOO and age at management. Factors influencing between-study heterogeneity were investigated using sensitivity analyses, meta-regression, and multiple meta–regression.ResultsTwenty-seven studies, reporting 51 samples and a total of 9415 patients, met the inclusion criteria. The pooled estimate for the interval between the onset of BD and its management was 5–8 years (standardized difference, .53; 95% confidence interval, .45 to .62). There was very high between-sample heterogeneity (I2 ¼ 92.6; Q ¼ 672). A longer interval was found in studies that defined the onset according to the first episode (compared to onset of symptoms or illness) and defined management as age at diagnosis (rather than first treatment or first hospitalization). A longer interval was reported among more recently published studies, among studies that used a systematic method to establish the chronology of illness, among studies with a smaller proportion of bipolar I patients, and among studies with an earlier mean AOO.ConclusionsThere is currently little consistency in the way researchers report the AOO and initial management of BD. However, the large interval between onset and management of BD presents an opportunity for earlier intervention.Disclosure of interestThe authors have not supplied their declaration of competing interest.
Perfusion SPECT in the Differential Diagnosis of Dementia
Authors: Brigadeiro D. , Nunes J. , Ventura Gil T. , Costa P. 
Published: June 2017

Dementia is a syndrome–usually of a chronic or progressive nature–in which there is deterioration in cognitive function beyond what might be expected from normal ageing (WHO). As the world population ages, the number of people afflicted with dementing illnesses will increase. This neurodegenerative disease is one of the major causes of disability and dependency among older people worldwide. Brain single-photon emission computed tomography (SPECT) allows the study of regional cerebral blood flow, providing functional information. Each of the different types of dementia has a distinct blood flow pattern that is revealed with SPECT imaging and which can be used for differential diagnoses. This imaging technique can also be used to differentiate dementia from pseudodementia. The use of SPECT has been recommended in various guidelines to help in differential diagnosis of dementia. The National Institute for Health and Clinical Excellence in the UK recommend the use of SPECT or positron emission tomography (PET) to help differentiate Alzheimer's disease (AD) from frontotemporal dementia and vascular dementia when there is diagnostic doubt (NICE, 2006). The European Federation of the Neurological Societies guidelines for diagnosis also supports the use of FDG-PET (18F fluorodeoxyglucose positron emission tomography) or perfusion SPECT when clarifying a diagnosis of AD. This review describes the utility of perfusion SPECT in differential diagnosis of neurodegenerative dementias.Disclosure of interestThe authors have not supplied their declaration of competing interest.
Association Between Multiple Sclerosis and Depression
Authors: Fornelos A. , Espírito Santo V. , Silva M. , Roque M. 
Published: June 2017

IntroductionMultiple Sclerosis (MS) is considered an autoimmune inflammatory disease and it is the most common demyelinating disease of the central nervous system. Although its aetiology remains unknown, it has been considered to be multifactorial. MS tends to be more commonly diagnosed in young Caucasian women. It has been described four clinical courses: relapsing-remitting MS, primary progressive MS, secondary progressive MS and progressive remitting MS based on the temporal sequence in which the symptoms arise. Clinic is also very different because it depends on the sites where the lesions occur. The most frequent signs and symptoms are motor and visual deficits, paraesthesia, gait ataxia, diplopia, dizziness and bladder dysfunction. Depressive symptomatology is also among the most common symptoms of MS.ObjectivesShow the importance of depressive symptomatology in patients with MS.AimsEvaluation the connection between MS and depression.MethodsSearch for articles concerning MS and depression on Pubmed and Scielo databases from July 2014 through October 2016.ResultsPsychiatric manifestations, and especially depressive symptoms, affect almost 40% of MS patients in remission, and about 90% of those in a flare-up. This may be due to the diagnosis itself, with its large amount of symptoms and its variable progression, but also due to side effects of therapy. It gives a major contribute to suicidality (7.5%) when compared to the general population.ConclusionA combined approach and treatment is in order to diminish the incapacity caused by both these illnesses in every single patient.Disclosure of interestThe authors have not supplied their declaration of competing interest.
Neuropsychiatric Symptoms in Fahr's Syndrome
Authors: Lopes A. , Trindade R. , Barcelos A. 
Published: June 2017

Objectives and methodologyTo review the neuropsychiatric symptoms of Fahr's syndrome.Results/discussionFahr's Syndrome is a rare degenerative neuropsychiatric condition, characterized by bilateral and symmetrical calcifications of the basal ganglia. It can be associated with several metabolic, infectious or genetic conditions. It is clinically manifested by movement disorders, psychosis, cognitive impairment, mood disorders, personality dysfunction or obsessive-compulsive spectrum disturbances. First presentation can be psychiatric in approximately 40% of the cases. Cognitive dysfunction, mood disorders and psychosis are the most common presentations. In the present case, depression, dementia and movement disorders were the main clinical pictures. This report alerts for the significance of neuropsychiatric symptoms within this diagnosis, considering the multisystemic approach of the illness.Disclosure of interestThe authors have not supplied their declaration of competing interest.
The Differential Effect of Event Rate on Pupil Dilation Patterns Suggests Effort Dysregulation Problems in ADHD
Authors: Metin B. , Sonuga-Barke E. , Wiersema J.R. , Roeyers H. , Vermeir S. 
Published: June 2017

IntroductionThe state regulation model postulates that ADHD performance difficulties result from failures to regulate activation states in response to changing environmental conditions – producing poor performance under sub-optimal conditions. Behavioral and electrophysiological studies involving the manipulation of event rate (ER) lend support to this idea.AimIn this preliminary study, we extended this investigation by comparing pupil dilation, an established marker of cognitive effort allocation, in individuals with ADHD, and controls, in response to varying ERs on a simple cognitive task.MethodsNineteen children with ADHD (age range: 8–14 years) and 21 controls (age range: 10–16 years) completed a target detection task under three different ERs (1300, 4000, and 8000 msec). Pupil dilation was monitored using an eye-tracker.ResultsOur results show that for controls, pupil dilation to targets varied as a function of ER according to a “U” function – with fast and slow ERs inducing greater phasic dilation than the moderate ER. However, for children with ADHD the relationship was linear with dilation increasing as ER decreased.ConclusionsThe results provide the first pupillary evidence suggestive of effort allocation dysregulation in ADHD especially under fast event rate conditions. Future studies should explore interventions to overcome effort allocation problems.Disclosure of interestThe authors have not supplied their declaration of competing interest.