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Evaluate the effects of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder (MDD) according to disease severity.
Pooled data (quetiapine XR 50, 150 and 300mg/day doses combined) from four 6- or 8-week placebo-controlled quetiapine XR monotherapy studies (D1448C00001, D1448C00002, D1448C00003, D1448C00004) were analysed. Key inclusion criterion for all 4 studies: HAM-D total score ≥22. Primary endpoint: change from randomisation in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. A post-hoc analysis assessed change from randomisation in MADRS total score and MADRS response (≥ 50% reduction in MADRS total score) at endpoint (Week 6 or Week 8) in 6 severity cohorts (defined by a MADRS total score at randomisation ≥24, ≥26, ≥28, ≥30, ≥32 or ≥34).
1752 patients (comprising the l’ all patients’ group) were evaluated (MADRS score ≥24 at randomisation, n=1601; ≥26, n=1467; ≥28, n=1269; ≥30, n=1038; ≥32, n=745; ≥34, n=500). Quetiapine XR significantly reduced mean MADRS total score at endpoint in lrsquo;all patients’ (p< 0.001 vs placebo) and in all 6 severity cohorts (≥24, ≥26, ≥28, ≥30 and ≥32, p< 0.001 vs placebo; ≥34, p< 0.01 vs placebo). MADRS response rates were significantly higher in the quetiapine XR group vs placebo in the ‘all patients’ group (p< 0.001 vs placebo) and in all 6 severity cohorts (≥24, ≥26, ≥28, ≥30 and ≥32, p< 0.001 vs placebo; ≥34, p=0.001 vs placebo).
Quetiapine XR monotherapy significantly improved depressive symptoms in patients with MDD irrespective of disease severity, including the most severe levels of depression.
Previous findings suggested that electrodermal hyporeactivity has a high sensitivity (up to 97%) and high raw specificity (up to 98%) for suicide.
To evaluate prevalence, sensitivity and specificity of electrodermal hyporeactivity for suicide and suicide attempt, with and without death intent and with violent method or not, in adult patients with a primary diagnosis of depression.
At each study site at least 100 patients with a primary diagnosis of depression, also in remission, will be recruited. Depressive symptomatology will be evaluated through the Montgomery-Asberg Depression Scale. Previous suicide attempts will be registered and the death intent of the worst attempt will be rated according to the first eight items of the Beck Suicide Intent Scale. The risk of suicide will be assessed according to rules and traditions at the centre. The EDOR Test (ElectroDermal Orienting Reactivity) will be performed. Two fingers are put on gold electrodes. Through headphones a moderately strong tone is presented now and then during the test. Sensors located within the electrodes are able to register the electrodermal response to those tones, measuring the skin conductance (i.e. electrodermal activity from sweat gland activity). Each patient will be followed up for one year for actions of intentional self-harm that require medical care and for suicide. The death intent will also be rated.
It is expected that the EDOR test detects a previously unknown neuropsychological dysfunction that is independent of the depressive state and can predict suicidality with a high sensitivity and specificity.
Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database.
The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared.
There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups.
These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.
Self-ratings of psychotic experiences might be biased by depressive symptoms.
Data from a large naturalistic multicentre trial on depressed inpatients (n = 488) who were assessed on a biweekly basis until discharge were analyzed. Self-rated psychotic symptoms as assessed with the 90-Item Symptom Checklist (SCL-90) were correlated with the SCL-90 total score, the SCL-90 depression score, the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale 21 item (HAMD-21) total score, the Montgomery Åsberg Depression Rating Scale (MADRS) total score and the clinician-rated paranoid-hallucinatory score of the Association for Methodology and Documentation in Psychiatry (AMDP) scale.
At discharge the SCL-90 psychosis score correlated highest with the SCL-90 depression score (0.78, P<0.001) and with the BDI total score (0.64, P<0.001). Moderate correlations were found for the MADRS (0.34, P<0.001), HAMD (0.37, P<0.001) and AMDP depression score (0.33, P<0.001). Only a weak correlation was found between the SCL-90 psychosis score and the AMDP paranoid-hallucinatory syndrome score (0.15, P<0.001). Linear regression showed that change in self-rated psychotic symptoms over the treatment course was best explained by a change in the SCL-90 depression score (P<0.001). The change in clinician-rated AMDP paranoid-hallucinatory score had lesser influence (P = 0.02).
In depressed patients self-rated psychotic symptoms correlate poorly with clinician-rated psychotic symptoms. Caution is warranted when interpreting results from epidemiological surveys using self-rated psychotic symptom questionnaires as indicators of psychotic symptoms. Depressive symptoms which are highly prevalent in the general population might influence such self-ratings.
Neuroprotective effects of lithium have been well documented in tissue cultures and animal models. The evidence for lithium related neuroprotection in human subjects is limited and inconsistent, likely due to methodological heterogeneity.
To investigate the effects of lithium on brain chemistry and structure, we recruited bipolar patients selected for substantial illness burden and varied the exposure to lithium by using strict inclusion criteria.
We obtained 1.5T magnetic resonance imaging data from 27 bipolar patients with at least 2 years of ongoing lithium treatment (Li group), 16 subjects with < 3 months lifetime exposure to lithium >2 years ago (non-Li group) and 21 healthy controls. Patient groups had to have at least 10 years of illness and 5 episodes.
The non-Li group had significantly lower hippocampal volumes (t = 4.68,corrected p < 0.05) and prefrontal cortex N-acetyl aspartate (NAA) levels (t = −2.91,corrected p < 0.05) than controls, who showed comparable hippocampal volumes and NAA levels to the Li treated subjects. Duration of illness was negatively associated with NAA levels only in the non-Li, but not the Li group.
Among patients selected for substantial illness burden, only those with no or minimal lifetime Li exposure had significantly lower prefrontal NAA levels and hippocampal volumes than controls. Patients with at least 2 years of ongoing Li treatment showed no such changes, despite substantial burden of illness. These findings provide indirect support for neuroprotective effects of lithium and negative effects of illness burden on brain chemistry and structure in patients with bipolar disorders.
First rank symptoms (FRS) of schizophrenia have been used for decades for diagnostic purposes. In the new version of the DSM-5, the American Psychiatric Association (APA) has abolished any further reference to FRS of schizophrenia and treats them like any other “criterion A” symptom (e.g. any kind of hallucination or delusion) with regard to their diagnostic implication. The ICD-10 is currently under revision and may follow suit. In this review, we discuss central points of criticism that are directed against the continuous use of first rank symptoms (FRS) to diagnose schizophrenia.
We describe the specific circumstances in which Schneider articulated his approach to schizophrenia diagnosis and discuss the relevance of his approach today. Further, we discuss anthropological and phenomenological aspects of FRS and highlight the importance of self-disorder (as part of FRS) for the diagnosis of schizophrenia. Finally, we will conclude by suggesting that the theory and rationale behind the definition of FRS is still important for psychopathological as well as neurobiological approaches today.
Results of a pivotal meta-analysis and other studies show relatively poor sensitivity, yet relatively high specificity for FRS as diagnostic marker for schizophrenia. Several methodological issues impede a systematic assessment of the usefulness of FRS in the diagnosis of schizophrenia. However, there is good evidence that FRS may still be useful to differentiate schizophrenia from somatic causes of psychotic states. This may be particularly important in countries or situations with little access to other diagnostic tests. FRS may thus still represent a useful aid for clinicians in the diagnostic process.
In conclusion, we suggest to continue a tradition of careful clinical observation and fine-grained psychopathological assessment, including a focus on symptoms regarding self-disorders, which reflects a key aspect of psychosis. We suggest that the importance of FRS may indeed be scaled down to a degree that the occurrence of a single FRS alone should not suffice to diagnose schizophrenia, but, on the other hand, absence of FRS should be regarded as a warning sign that the diagnosis of schizophrenia or schizoaffective disorder is not warranted and requires specific care to rule out other causes, particularly neurological and other somatic disorders. With respect to the current stage of the development of ICD-11, we appreciate the fact that self-disorders are explicitly mentioned (and distinguished from delusions) in the list of mandatory symptoms but still feel that delusional perceptions and complex hallucinations as defined by Schneider should be distinguished from delusions or hallucinations of “any kind”. Finally, we encourage future research to explore the psychopathological context and the neurobiological correlates of self-disorders as a potential phenotypic trait marker of schizophrenia.
Although accumulating evidence supports the hypothesis that immune/inflammatory mechanisms are associated with the pathophysiology of bipolar disorder (BD), data about the profile of chemokines (chemotactic cytokines) and chemokine receptors are still scarce. The current study was designed to evaluate the expression of chemokine receptors on lymphocytes of patients with BD in comparison with controls.
Thirty-three patients with type I BD (N = 21 in euthymia; N = 6 in mania/hypomania; N = 6 in depression) and 22 age- and sex-matched controls were subjected to clinical evaluation and peripheral blood draw. The expression of chemokine receptors CCR3, CCR5, CXCR4, and CXCR3 on CD4+ and CD8+ lymphocytes was assessed by flow cytometry.
Patients with BD had decreased percentage of CD4+CXCR3+ (p = 0.024), CD4+CCR3+ (p = 0.042), and CD4+CCR5+ (0.013) lymphocytes in comparison with controls. The percentage of both CD4+ and CD8+ lymphocytes expressing the chemokine receptor CXCR4 was similar in patients with BD and controls. Likewise, the percentages of CD8+CXCR3+, CD8+CCR3+, and CD8+CCR5+ lymphocytes were similar in patients with BD and controls.
Our findings reinforce the hypothesis that immune pathways, especially involving CD4+ lymphocytes, are involved in the physiopathology of BD.
Wearable devices are fast evolving to address mobility and autonomy needs of elderly people who would benefit from physical assistance. Recent developments in soft robotics provide important opportunities to develop soft exoskeletons (also called exosuits) to enable both physical assistance and improved usability and acceptance for users. The XoSoft EU project has developed a modular soft lower limb exoskeleton to assist people with low mobility impairments. In this paper, we present the design of a soft modular lower limb exoskeleton to improve person’s mobility, contributing to independence and enhancing quality of life. The novelty of this work is the integration of quasi-passive elements in a soft exoskeleton. The exoskeleton provides mechanical assistance for subjects with low mobility impairments reducing energy requirements between 10% and 20%. Investigation of different control strategies based on gait segmentation and actuation elements is presented. A first hip–knee unilateral prototype is described, developed, and its performance assessed on a post-stroke patient for straight walking. The study presents an analysis of the human–exoskeleton energy patterns by way of the task-based biological power generation. The resultant assistance, in terms of power, was 10.9% ± 2.2% for hip actuation and 9.3% ± 3.5% for knee actuation. The control strategy improved the gait and postural patterns by increasing joint angles and foot clearance at specific phases of the walking cycle.
Douglas Nakashima, United Nations Educational, Scientific and Cultural Organization (UNESCO), France,Igor Krupnik, Smithsonian Institution, Washington DC,Jennifer T. Rubis, United Nations Educational, Scientific and Cultural Organization (UNESCO), France
The Dark Energy Survey is undertaking an observational programme imaging 1/4 of the southern hemisphere sky with unprecedented photometric accuracy. In the process of observing millions of faint stars and galaxies to constrain the parameters of the dark energy equation of state, the Dark Energy Survey will obtain pre-discovery images of the regions surrounding an estimated 100 gamma-ray bursts over 5 yr. Once gamma-ray bursts are detected by, e.g., the Swift satellite, the DES data will be extremely useful for follow-up observations by the transient astronomy community. We describe a recently-commissioned suite of software that listens continuously for automated notices of gamma-ray burst activity, collates information from archival DES data, and disseminates relevant data products back to the community in near-real-time. Of particular importance are the opportunities that non-public DES data provide for relative photometry of the optical counterparts of gamma-ray bursts, as well as for identifying key characteristics (e.g., photometric redshifts) of potential gamma-ray burst host galaxies. We provide the functional details of the DESAlert software, and its data products, and we show sample results from the application of DESAlert to numerous previously detected gamma-ray bursts, including the possible identification of several heretofore unknown gamma-ray burst hosts.
We derive zphot for sources in the entire (~0.4 deg2) H-HDF-N field with the EAzY code, based on PSF-matched broad-band (U band to IRAC 4.5 μm) photometry. Our catalog consists of a total of 131,678 sources. We find σNMAD = 0.029 for non-X-ray sources. We also classify each object as a star or galaxy through SED fitting. Furthermore, we match our catalog with the 2 Ms CDF-N main X-ray catalog. For the 462 matched non-stellar X-ray sources, we improve their zphot quality (σNMAD = 0.035) by adding three additional AGN templates. We make our photometry and zphot catalog publicly available.
Concerning a materials ability to convert heat to electrical energy, the electrical power factor S2/ρ as well as the thermal conductivity at elevated temperatures are of special interest. Since Flash experiments measure the thermal diffusivity and standard steady-state heat-flow experiments are inaccurate at elevated temperatures due to radiation errors inherent to this technique, direct and accurate thermal conductivity data on type-I clathrate single crystals at elevated temperatures are scarce in literature. Here we report 3ω thermal conductivity data on single crystalline Ba8Cu5.09Ge40.91 (BCG), La1.23Ba6.99Au5.91Si39.87, and Ce1.06Ba6.91Au5.56Si40.47 in the temperature range between 80 and 330 K, and specific heat data on BCG between 2 and 300 K. The comparison of our room temperature phonon thermal conductivity data (κph) to results on transition metal (TM) free type-I clathrates in terms of the guest free space (Rfree) suggests a stronger dependence of κph on Rfree for the clathrates containing TM elements.
In 1954, B K Thapar excavated the multicomponent site of Maski (Raichur District, Karnataka) to establish an archaeological sequence for the southern Deccan region of India. Thapar identified four major periods of occupation, now known as the Neolithic (3000–1200 BC), Iron Age (1200–300 BC), Early Historic (300 BC to AD 500), and the Medieval periods (AD 500–1600). Renewed research at the site by the Maski Archaeological Research Project (F.1/8/2009-EE) has investigated the development of social differences and inequalities in south Indian prehistory. This article reports the first ever radiocarbon assays from habitation and megalithic burial contexts in the vicinity of Maski. Accelerator mass spectrometry (AMS) dates of charcoal sampled from exposed occupational strata on Maski's Durgada Gudda hill and subsequent Bayesian analyses indicate that the site was extensively occupied during the 14th century AD, corroborating interpretations of numismatic and inscriptional materials. Associated artifacts with these 14C samples have significant implications for recognizing late Medieval period ceramics and occupation in the region. AMS assays of four charcoal samples from exposed megalithic burials just south of the Durgada Gudda hill, similar to those recognized by Thapar, indicate that burial practices commonly attributed to the Iron Age predate the period, and thus are not precise chronological markers. However, the results also suggest that megalithic burial practices became more labor intensive during the Iron Age, creating a cultural context for the generation of new forms of social affiliations and distinctions through differential participation in the production of commemorative places.
The study of variable stars in open clusters via asteroseismology is a powerful tool for the study of stellar evolution and stars in general. That is because stars in clusters can be assumed to originate from the same interstellar cloud, so they share similar properties such as age and overall metallicity. We performed a search for variable stars in the field of the young open star cluster Roslund 2, with photoelectric and CCD photometry acquired at two different telescopes. Within the resulting light curves we have found 12 variable stars. Our measurements confirm three previously known variables.
Neuroimaging studies have demonstrated an association between lithium (Li) treatment and brain structure in human subjects. A crucial unresolved question is whether this association reflects direct neurochemical effects of Li or indirect effects secondary to treatment or prevention of episodes of bipolar disorder (BD).
To address this knowledge gap, we compared manually traced hippocampal volumes in 37 BD patients with at least 2 years of Li treatment (Li group), 19 BD patients with <3 months of lifetime Li exposure over 2 years ago (non-Li group) and 50 healthy controls. All BD participants were followed prospectively and had at least 10 years of illness and a minimum of five episodes. We established illness course and long-term treatment response to Li using National Institute of Mental Health (NIMH) life charts.
The non-Li group had smaller hippocampal volumes than the controls or the Li group (F2,102 = 4.97, p = 0.009). However, the time spent in a mood episode on the current mood stabilizer was more than three times longer in the Li than in the non-Li group (t51 = 2.00, p = 0.05). Even Li-treated patients with BD episodes while on Li had hippocampal volumes comparable to healthy controls and significantly larger than non-Li patients (t43 = 2.62, corrected p = 0.02).
Our findings support the neuroprotective effects of Li. The association between Li treatment and hippocampal volume seems to be independent of long-term treatment response and occurred even in subjects with episodes of BD while on Li. Consequently, these effects of Li on brain structure may generalize to patients with neuropsychiatric illnesses other than BD.
Leptin is thought to act as an important mediator in stress reactions. To date, no study has examined the association between psychological stress and leptin levels in children. This study aimed to assess the association between emotional symptoms and peer problems and serum leptin levels in children aged 10 years of the two population-based GINI-plus and LISA-plus birth cohorts.
Cross-sectional data from 2827 children aged 10 years were assessed with regard to leptin concentrations in serum and behavioral problems using the parent-reported Strengths and Difficulties Questionnaire (SDQ). Linear regression modeling was applied to determine the likelihood of elevated leptin levels in children with emotional symptoms and peer problems, controlling for socio-economic status (SES), body mass index (BMI), fasting serum leptin levels, pubertal development and sex hormones.
We found that increases in emotional symptoms (exp βadj = 1.03, s.e. = 0.02, p < 0.04) and peer problems (exp βadj = 1.05, s.e. = 0.01, p = 0.0001) were significantly associated with higher serum leptin levels controlled for BMI and sociodemographic factors. Similar results were found when the fasting serum leptin sample was examined (exp βadj = 1.08, s.e. = 0.04, p = 0.0294). Gender-stratified analyses showed a significant relationship between serum leptin and peer problems in girls (exp βadj = 1.05, s.e. = 0.02, p = 0.03), and a borderline significant association in boys (exp βadj = 1.04, s.e. = 0.02, p = 0.05).
Children with peer problems have higher stress and eat more, acquire a higher body fat mass and thus, through increased leptin resistance, exhibit higher leptin levels.
Multivariate statistical analysis (MSA) is applied to the extraction of chemically relevant signals acquired with a micro-X-ray fluorescence (μ-XRF) mapping (full-spectral imaging) system. The separation of components into individual histograms enables separation of overlapping peaks, which is useful in qualitatively determining the presence of chemical species that have overlapping emission lines, and holds potential for quantitative analysis of constituent phases via these same histograms. The usefulness of MSA for μ-XRF analysis is demonstrated by application to a geological rock core obtained from a subsurface compressed air energy storage (CAES) site. Coupling of the μ-XRF results to those of quantitative powder X-ray diffraction analysis enables improved detection of trace phases present in the geological specimen. The MSA indicates that the spatial distribution of pyrite, a potentially reactive phase by oxidation, has low concentration and thus minimal impact on CAES operations.