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Eighty percent of all patients suffering from major depressive disorder (MDD) relapse at least once in their lifetime. Thus, understanding the neurobiological underpinnings of the course of MDD is of utmost importance. A detrimental course of illness in MDD was most consistently associated with superior longitudinal fasciculus (SLF) fiber integrity. As similar associations were, however, found between SLF fiber integrity and acute symptomatology, this study attempts to disentangle associations attributed to current depression from long-term course of illness.
A total of 531 patients suffering from acute (N = 250) or remitted (N = 281) MDD from the FOR2107-cohort were analyzed in this cross-sectional study using tract-based spatial statistics for diffusion tensor imaging. First, the effects of disease state (acute v. remitted), current symptom severity (BDI-score) and course of illness (number of hospitalizations) on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity were analyzed separately. Second, disease state and BDI-scores were analyzed in conjunction with the number of hospitalizations to disentangle their effects.
Disease state (pFWE < 0.042) and number of hospitalizations (pFWE< 0.032) were associated with decreased FA and increased MD and RD in the bilateral SLF. A trend was found for the BDI-score (pFWE > 0.067). When analyzed simultaneously only the effect of course of illness remained significant (pFWE < 0.040) mapping to the right SLF.
Decreased FA and increased MD and RD values in the SLF are associated with more hospitalizations when controlling for current psychopathology. SLF fiber integrity could reflect cumulative illness burden at a neurobiological level and should be targeted in future longitudinal analyses.
Schizotypy is a putative risk phenotype for psychosis liability, but the overlap of its genetic architecture with schizophrenia is poorly understood.
We tested the hypothesis that dimensions of schizotypy (assessed with the SPQ-B) are associated with a polygenic risk score (PRS) for schizophrenia in a sample of 623 psychiatrically healthy, non-clinical subjects from the FOR2107 multi-centre study and a second sample of 1133 blood donors.
We did not find correlations of schizophrenia PRS with either overall SPQ or specific dimension scores, nor with adjusted schizotypy scores derived from the SPQ (addressing inter-scale variance). Also, PRS for affective disorders (bipolar disorder and major depression) were not significantly associated with schizotypy.
This important negative finding demonstrates that despite the hypothesised continuum of schizotypy and schizophrenia, schizotypy might share less genetic risk with schizophrenia than previously assumed (and possibly less compared to psychotic-like experiences).
Subclinical psychotic-like experiences (PLE), resembling key symptoms of psychotic disorders, are common throughout the general population and possibly associated with psychosis risk. There is evidence that such symptoms are also associated with structural brain changes.
In 672 healthy individuals, we assessed PLE and associated distress with the symptom-checklist-90R (SCL-90R) scales ‘schizotypal signs’ (STS) and ‘schizophrenia nuclear symptoms’ (SNS) and analysed associations with voxel- and surfaced-based brain structural parameters derived from structural magnetic resonance imaging at 3 T with CAT12.
For SNS, we found a positive correlation with the volume in the left superior parietal lobule and the precuneus, and a negative correlation with the volume in the right inferior temporal gyrus [p < 0.05 cluster-level Family Wise Error (FWE-corrected]. For STS, we found a negative correlation with the volume of the left and right precentral gyrus (p < 0.05 cluster-level FWE-corrected). Surface-based analyses did not detect any significant clusters with the chosen statistical threshold of p < 0.05. However, in exploratory analyses (p < 0.001, uncorrected), we found a positive correlation of SNS with gyrification in the left insula and rostral middle frontal gyrus and of STS with the left precuneus and insula, as well as a negative correlation of STS with gyrification in the left temporal pole.
Our results show that brain structures in areas implicated in schizophrenia are also related to PLE and its associated distress in healthy individuals. This pattern supports a dimensional model of the neural correlates of symptoms of the psychotic spectrum.
Porous metals represent a class of materials where the interplay of ligament length, width, node structure, and local geometry/curvature offers a rich parameter space for the study of critical length scales on mechanical behavior. Colloidal crystal templating of three-dimensionally ordered macroporous (3DOM, i.e., inverse opal) tungsten provides a unique structure to investigate the mechanical behavior at small length scales across the brittle–ductile transition. Micropillar compression tests show failure at 50 MPa contact pressure at 30 °C, implying a ligament yield strength of approximately 6.1 GPa for a structure with 5% relative density. In situ SEM frustum indentation tests with in-plane strain maps perpendicular to loading indicate local compressive strains of approximately 2% at failure at 30 °C. Increased sustained contact pressure is observed at 225 °C, although large (20%) nonlocal strains appear at 125 °C. The elevated-temperature mechanical performance is limited by cracks that initiate on planes of greatest shear under the indenter.
The aim of this paper was to provide a systematic review and update on the pharmacotherapy of social anxiety disorder (SAD), including the efficacy and tolerability of these agents, the ranking of interventions, and the grading of results by quality of evidence.
The Common Mental Disorder Controlled Trial Register and two trial registries were searched for randomised controlled trials (RCTs) comparing any pharmacological intervention or placebo in the treatment of SAD. We performed a standard pairwise meta-analysis using a random effects model and carried out a network meta-analysis (NMA) using the statistical package, R. Quality of evidence was also assessed.
We included 67 RCTs in the review and 21 to 45 interventions in the NMA. Paroxetine was most effective in the reduction of symptom severity as compared to placebo. Superior response to treatment was also observed for paroxetine, brofaromine, bromazepam, clonazepam, escitalopram, fluvoxamine, phenelzine, and sertraline. Higher dropout rates were found for fluvoxamine. Brofaromine, escitalopram, fluvoxamine, paroxetine, pregabalin, sertraline, and venlafaxine performed worse in comparison to placebo for the outcome of dropouts due to adverse events. Olanzapine yielded a relatively high rank for treatment efficacy and buspirone the worse rank for dropouts due to any cause.
The differences between drugs and placebo were small, apart from a significant reduction in symptom severity and response for paroxetine. We suggest paroxetine as a first-line treatment of SAD, with the consideration of future research on the drug olanzapine as well as brofaromine, bromazepam, clonazepam, escitalopram, fluvoxamine, phenelzine, and sertraline because we observed a response to treatment.
In his treatment of subjective mind, Hegel argues that the development that characterizes the vital process of a human individual is logically unique in that it dissolves the contradiction between two logical determinations that characterize any vital activity: the contradiction between the ‘immediate singularity’ of the subject of this process and its ‘abstract generality’. Hegel employs the term Bildung to characterize any vital activity that has this form. The idea that the distinction between human life and non-human life is a logical distinction is one of the main lessons that Hegel thinks we should learn from Aristotle's treatment of the idea of life. In this article I distinguish between two contemporary varieties of this Aristotelian idea: a sophisticated variety that emphasizes the idea of second nature in order to characterize the distinctiveness of the human, and a naive variety that thinks of the human's uniqueness in terms of characterizations that already belong to its first nature. I argue that Hegel is neither sophisticated nor naive but offers a third variety of Neo-Aristotelianism that solves the difficulties of the other two. This has decisive consequences for his understanding of Bildung. Although the notion of Bildung describes an empirical process, Hegel argues, it is not an empirical concept. Rather, it is the concrete concept of the process of actualization that characterizes a self-conscious form of life that reflects the inner temporality of this form's actuality.
Guidelines about post-traumatic stress disorder (PTSD) recommend broad categories of drugs, but uncertainty remains about what pharmacological treatment to select among all available compounds.
Cochrane Central Register of Controlled Trials register, MEDLINE, PsycINFO, National PTSD Center Pilots database, PubMed, trial registries, and databases of pharmaceutical companies were searched until February 2016 for double-blind randomised trials comparing any pharmacological intervention or placebo as oral therapy in adults with PTSD. Initially, we performed standard pairwise meta-analyses using a random effects model. We then carried out a network meta-analysis. The main outcome measures were mean change on a standardised scale and all-cause dropout rate. Acute treatment was defined as 8-week follow up.
Desipramine, fluoxetine, paroxetine, phenelzine, risperidone, sertraline, and venlafaxine were more effective than placebo; phenelzine was better than many other active treatments and was the only drug, which was significantly better than placebo in terms of dropouts (odds ratio 7.50, 95% CI 1.72–32.80). Mirtazapine yielded a relatively high rank for efficacy, but the respective value for acceptability was not among the best treatments. Divalproex had overall the worst ranking.
The efficacy and acceptability hierarchies generated by our study were robust against many sources of bias. The differences between drugs and placebo were small, with the only exception of phenelzine. Considering the small amount of available data, these results are probably not robust enough to suggest phenelzine as a drug of choice. However, findings from this review reinforce the idea that phenelzine should be prioritised in future trials in PTSD.
Although evidence exists for abnormal brain function across various
anxiety disorders, direct comparison of neural function across diagnoses
is needed to elicit abnormalities common across disorders and those
distinct to a particular diagnosis.
To delineate common and distinct abnormalities within generalised anxiety
(GAD), panic and social anxiety disorder (SAD) during affective
Fifty-nine adults (15 with GAD, 15 with panic disorder, 14 with SAD, and
15 healthy controls) underwent functional magnetic resonance imaging
while completing a facial emotion matching task with fearful, angry and
Greater differential right amygdala activation to matching fearful
v. happy facial expressions related to greater
negative affectivity (i.e. trait anxiety) and was heightened across all
anxiety disorder groups compared with controls. Collapsing across
emotional face types, participants with panic disorder uniquely displayed
greater posterior insula activation.
These preliminary results highlight a common neural basis for clinical
anxiety in these diagnoses and also suggest the presence of
We characterized post-infancy child growth patterns and determined the incidence of becoming stunted and of recovery from stunting.
Data came from Young Lives, a longitudinal study of childhood poverty in four low- and middle-income countries.
We analysed length/height measurements for children at ages 1, 5 and 8 years.
Children (n 7171) in Ethiopia, India, Peru and Vietnam.
Mean height-for-age Z-score (HAZ) at age 1 year ranged from −1·51 (Ethiopia) to −1·08 (Vietnam). From age 1 to 5 years, mean HAZ increased by 0·27 in Ethiopia (P < 0·001) and decreased among the other cohorts (range: −0·19 (Peru) to −0·32 (India); all P < 0·001). From 5 to 8 years, mean HAZ increased in all cohorts (range: 0·19 (India) to 0·38 (Peru); all P < 0·001). Prevalence of stunting (HAZ<−2·0) at 1 year ranged from 21 % (Vietnam) to 46 % (Ethiopia). From age 1 to 5 years, stunting prevalence decreased by 15·1 percentage points in Ethiopia (P < 0·001) and increased in the other cohorts (range: 3·0 percentage points (Vietnam) to 5·3 percentage points (India); all P ≤ 0·001). From 5 to 8 years, stunting prevalence decreased in all cohorts (range: 5·0 percentage points (Vietnam) to 12·7 percentage points (Peru); all P < 0·001). The incidence of becoming stunted between ages 1 to 5 years ranged from 11 % (Vietnam) to 22 % (India); between ages 5 to 8 years, it ranged from 3 % (Peru) to 6 % (India and Ethiopia). The incidence of recovery from stunting between ages 1 and 5 years ranged from 27 % (Vietnam) to 53 % (Ethiopia); between ages 5 and 8 years, it ranged from 30 % (India) to 47 % (Ethiopia).
We found substantial recovery from early stunting among children in four low- and middle-income countries.
Solar energy is abundant and offers significant potential for near-term (2020) and long-term (2050) climate change mitigation. There are a wide variety of solar technologies of varying maturities that can, in most regions of the world, contribute to a suite of energy services. Even though solar energy generation still only represents a small fraction of total energy consumption, markets for solar technologies are growing rapidly. Much of the desirability of solar technology is its inherently smaller environmental burden and the opportunity it offers for positive social impacts. The cost of solar technologies has been reduced significantly over the past 30 years and technical advances and supportive public policies continue to offer the potential for additional cost reductions. Potential deployment scenarios range widely—from a marginal role of direct solar energy in 2050 to one of the major sources of energy supply. The actual deployment achieved will depend on the degree of continued innovation, cost reductions and supportive public policies.
Solar energy is the most abundant of all energy resources. Indeed, the rate at which solar energy is intercepted by the Earth is about 10,000 times greater than the rate at which humankind consumes energy. Although not all countries are equally endowed with solar energy, a significant contribution to the energy mix from direct solar energy is possible for almost every country. Currently, there is no evidence indicating a substantial impact of climate change on regional solar resources.
Usually, single-phase intermetallics in bulk form can easily be crushed into powder by hammering. It was therefore quite a surprise when we found that a bulk sample of the monoclinic intermetallic compound Nb2Co7 could be extensively deformed at room temperature without shattering or fracturing. In a previous paper, results of microhardness, compression, tensile and bending tests were provided and discussed . In order to understand the observed unusual deformation behavior of this intermetallic phase, its hitherto unknown crystal structure has been studied and the microstructure of undeformed and deformed samples has been analyzed in the present investigation by light-optical, scanning electron and transmission electron microscopy.
Single-phase specimens deformed at very different strain rates (hammering and conventional compression testing) both show the occurrence of microcracks along grain boundaries which, in compression-deformed specimens, are strongly localized in extended shear bands oriented approximately 45° to the compression axis. The grains adjacent to the microcracks are heavily deformed whereas, away from the sheared regions, the samples remain free of any indication of plastic deformation.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
Cell surface carbohydrates play unique roles in a host of biologically relevant events such as cell differentiation, adhesion and development. They also mediate many undesired processes such as pathogenic infection and tumor metastasis. A common feature of all tumor cells is the altered expression and presentation of surface glycans that serve as “non-self” structures that can be recognized by the immune system. For many years, these tumor-associated carbohydrate antigens (TACA’s) have been employed in the development of tumor vaccines with varying degrees of success. In addition, these sugars may mediate tumor cell adhesion during the metastatic cascade. We have previously succeeded in preparing both gold nanoparticles and quantum dot nanocrystals that were coated with specific TACA’s. We have concentrated on the Thomsen Friedenreich (TF) antigen disaccharide (Galβ1-3GalNAcα-O-Ser/Thr) and have shown that gold particles coated with TF antigen can either promote or inhibit metastasis in vivo. Here we describe our progress toward the synthesis of a number of these multivalent nanoscaffolds and report on our characterization efforts and how the size and surface chemistry of the particles relates to their biological activities.
The mammary gland undergoes extensive tissue remodelling during each lactation cycle. During pregnancy, the epithelial compartment of the gland is vastly expanded (Benaud et al. 1998). At the end of lactation the epithelial cells undergo apoptosis and adipocyte differentiation is induced (Lilla et al. 2002). Ductal and alveolar growth during puberty and pregnancy, and the involution process require the action of proteolytic enzymes (including matrix metalloproteinases, plasminogen and membrane-peptidases) and the corresponding genes are activated during these periods (Benaud et al. 1998; Alexander et al. 2001). Matrix metalloproteinases (MMP) are expressed in several cell types of the mammary gland including stromal fibroblasts (e.g., MMP3, MMP2), epithelial cells (e.g., MMP7 or MMP9), adipocytes (e.g., MMP2) and lymphoid cells (e.g., MMP9) (Crawford et al. 1996; Lund et al. 1996; Wiseman et al. 2003). A number of knock-out mice, which are deficient for individual MMP genes (e.g., MMP2, MMP3) or plasminogen, display alterations to mammary gland structure and impairment of lactation (Lund et al. 1999; Wiseman et al. 2003).
Grush describes a variety of different systems that illustrate his vision of representation through emulation. These individual data points are not necessarily sufficient to determine what level of detail is required for a representation to count as emulation. By examining one of his examples closely, this commentary suggest that salience of the information supplied is a critical dimension.
Depth-sensing indentation was applied to three-dimensionally ordered silica foams of two different pore diameters—500 nm and 850 nm—formed by colloidal crystal templating. The contact responses of indentations with Berkovich and hemispherical indentation tips are presented over a load range of 1 mN to 100 mN. Scanning electron microscopy images of residual indentation impressions showed homogeneous deformation for small loads in which the peak displacement was shallow relative to the film–substrate interface. The characteristics of the load–displacement responses changed from periodic discontinuities, associated with cell wall fracture and pore collapse, to smooth and increased stiffness, as a result of densification due to the accumulation of material under the indentation tip and proximity (and contact) of the substrate. Load–displacement responses were translated into pressure–volume space, in which the average pressure during indentation is a measure of the crushing pressure of the cell walls.
The construct of quality of life (QOL), which has both subjective and objective components, has gained increasing importance in psychiatric research for several important reasons, not the least being the current importance of pharmacoeconomic issues. Obsessive-compulsive disorder (OCD) has been suggested to be the worlds 10th most disabling disorder, and pharmacoeconomic studies have indicated that its cost to the world economy runs into the billions of dollars. The use of QOL scales derived from general medicine and other areas of psychiatry has demonstrated the enormous negative impact of OCD on several domains, including occupational function, social function, and family function. Further work to ascertain the extent of changes in QOL during treatment of OCD is necessary.