Tracer profiles across argillaceous formations: A tool to constrain transport processes.

The spatial distributions of non-reactive natural tracers (anions, stable water isotopes, noble gases) in pore water of clay-rich formations were studied at nine sites. Regular curved profiles were identified in most cases. Transport modeling considering diffusion, advection and available constraints on the paleo-hydrogeological evolution indicates generally that diffusion alone can explain the observations, whereas a marked advective component would distort the profiles and so is not consistent with the data.

Transcriptional profiles of cytokine/chemokine factors of immune cell-homing to the parasitic lesions: a comprehensive one-year course study in the liver of E. multilocularis-infected mice.

Pathogenesis of chronically developing alveolar echinococcosis (AE) is characterized by a continuous, granulomatous, periparasitic infiltration of immune cells surrounding the metacestode of Echinococcus multilocularis (E.multilocularis) in the affected liver. A detailed cytokine and chemokine profile analysis of the periparasitic infiltrate in the liver has, however, not yet been carried out in a comprehensive way all along the whole course of infection in E. multilocularis intermediate hosts. We thus assessed the hepatic gene expression profiles of 18 selected cytokine and chemokine genes using qRT-PCR in the periparasitic immune reaction and the subsequent adjacent, not directly affected, liver tissue of mice from day 2 to day 360 post intra-hepatic injection of metacestode. DNA microarray analysis was also used to get a more complete picture of the transcriptional changes occurring in the liver surrounding the parasitic lesions. Profiles of mRNA expression levels in the hepatic parasitic lesions showed that a mixed Th1/Th2 immune response, characterized by the concomitant presence of IL-12α, IFN-γ and IL-4, was established very early in the development of E. multilocularis. Subsequently, the profile extended to a combined tolerogenic profile associating IL-5, IL-10 and TGF-β. IL-17 was permanently expressed in the liver, mostly in the periparasitic infiltrate; this was confirmed by the increased mRNA expression of both IL-17A and IL-17F from a very early stage, with a subsequent decrease of IL-17A after this first initial rise. All measured chemokines were significantly expressed at a given stage of infection; their expression paralleled that of the corresponding Th1, Th2 or Th17 cytokines. In addition to giving a comprehensive insight in the time course of cytokines and chemokines in E. multilocularis lesion, this study contributes to identify new targets for possible immune therapy to minimize E. multilocularis-related pathology and to complement the only parasitostatic effect of benzimidazoles in AE.

Clinical and biochemical profiles suggest fibromuscular dysplasia is a systemic disease with altered TGF-β expression and connective tissue features.

Fibromuscular dysplasia (FMD) is a rare, nonatherosclerotic arterial disease for which the molecular basis is unknown. We comprehensively studied 47 subjects with FMD, including physical examination, spine magnetic resonance imaging, bone densitometry, and brain magnetic resonance angiography. Inflammatory biomarkers in plasma and transforming growth factor β (TGF-β) cytokines in patient-derived dermal fibroblasts were measured by ELISA. Arterial pathology other than medial fibrodysplasia with multifocal stenosis included cerebral aneurysm, found in 12.8% of subjects. Extra-arterial pathology included low bone density (P<0.001); early onset degenerative spine disease (95.7%); increased incidence of Chiari I malformation (6.4%) and dural ectasia (42.6%); and physical examination findings of a mild connective tissue dysplasia (95.7%). Screening for mutations causing known genetically mediated arteriopathies was unrevealing. We found elevated plasma TGF-β1 (P=0.009), TGF-β2 (P=0.004) and additional inflammatory markers, and increased TGF-β1 (P=0.0009) and TGF-β2 (P=0.0001) secretion in dermal fibroblast cell lines from subjects with FMD compared to age- and gender-matched controls. Detailed phenotyping of patients with FMD allowed us to demonstrate that FMD is a systemic disease with alterations in common with the spectrum of genetic syndromes that involve altered TGF-β signaling and offers TGF-β as a marker of FMD.

Tracking water pathways in steep hillslopes by d18O depth profiles of soil water

Assessing temporal variations in soil water flow is important, especially at the hillslope scale, to identify mechanisms of runoff and flood generation and pathways for nutrients and pollutants in soils. While surface processes are well considered and parameterized, the assessment of subsurface processes at the hillslope scale is still challenging since measurement of hydrological pathways is connected to high efforts in time, money and personnel work. The latter might not even be possible in alpine environments with harsh winter processes. Soil water stable isotope profiles may offer a time-integrating fingerprint of subsurface water pathways. In this study, we investigated the suitability of soil water stable isotope (d18O) depth profiles to identify water flow paths along two transects of steep subalpine hillslopes in the Swiss Alps. We applied a one-dimensional advection–dispersion model using d18O values of precipitation (ranging from _24.7 to _2.9‰) as input data to simulate the d18O profiles of soil water. The variability of d18O values with depth within each soil profile and a comparison of the simulated and measured d18O profiles were used to infer information about subsurface hydrological pathways. The temporal pattern of d18O in precipitation was found in several profiles, ranging from _14.5 to _4.0‰. This suggests that vertical percolation plays an important role even at slope angles of up to 46_. Lateral subsurface flow and/or mixing of soil water at lower slope angles might occur in deeper soil layers and at sites near a small stream. The difference between several observed and simulated d18O profiles revealed spatially highly variable infiltration patterns during the snowmelt periods: The d18O value of snow (_17.7 ± 1.9‰) was absent in several measured d18O profiles but present in the respective simulated d18O profiles. This indicated overland flow and/or preferential flow through the soil profile during the melt period. The applied methods proved to be a fast and promising tool to obtain time-integrated information on soil water flow paths at the hillslope scale in steep subalpine slopes.

Declining transition rates to psychosis: The role of diagnostic spectra and symptom overlaps in individuals with attenuated psychosis syndrome

Transition to psychosis in at-risk individuals has markedly declined in recent years. So far it has never been discussed in detail that with the growing awareness and increasing availability of early psychosis services, a much broader diagnostic spectrum is now being seen in these services. Subsequently, subjects present with symptoms that meet psychosis risk on a purely psychometric basis but may be the phenotypical expression of another underlying mental disorder. Here we critically review four groups of symptoms and clinical features that are frequently reported by individuals with suspected psychosis risk states, yet share strong commonalities with other mental disorders and conditions: isolated hallucinations; unusual bodily perceptions, hypochondriatic fears and cenesthetic psychotic symptoms; depersonalization; obsessive–compulsive, overvalued and delusional ideas. Of the 616 individuals so far assessed in the Bruderholz Early Psychosis Outpatient Service for Adolescents and Young Adults, 218 (30.5%) met ultra-high risk (UHR) criteria, 188 (86.2%) of whom suffered from one of the four above-mentioned symptom groups. The appraisal of the diagnostic spectra and their overlapping symptoms constitute a tremendous challenge in the clinical assessment of each referred individual. The final conclusion of a clinical assessment should not end with the mere assignment – or non-assignment – to a presumed psychosis risk group, but needs to take into account the ‘Gestalt’ of these particular symptoms and clinical features and thus be based on many more facets than solely a psychometric or nosological approach. Such an approach may break down the heterogeneous psychosis risk group and enable appropriate treatment regimes.

General distress, hopelessness—suicidal ideation and worrying in adolescence: Concurrent and predictive validity of a symptom-level bifactor model for clinical diagnoses

BACKGROUND: Clinical disorders often share common symptoms and aetiological factors. Bifactor models acknowledge the role of an underlying general distress component and more specific sub-domains of psychopathology which specify the unique components of disorders over and above a general factor. METHODS: A bifactor model jointly calibrated data on subjective distress from The Mood and Feelings Questionnaire and the Revised Children's Manifest Anxiety Scale. The bifactor model encompassed a general distress factor, and specific factors for (a) hopelessness-suicidal ideation, (b) generalised worrying and (c) restlessness-fatigue at age 14 which were related to lifetime clinical diagnoses established by interviews at ages 14 (concurrent validity) and current diagnoses at 17 years (predictive validity) in a British population sample of 1159 adolescents. RESULTS: Diagnostic interviews confirmed the validity of a symptom-level bifactor model. The underlying general distress factor was a powerful but non-specific predictor of affective, anxiety and behaviour disorders. The specific factors for hopelessness-suicidal ideation and generalised worrying contributed to predictive specificity. Hopelessness-suicidal ideation predicted concurrent and future affective disorder; generalised worrying predicted concurrent and future anxiety, specifically concurrent generalised anxiety disorders. Generalised worrying was negatively associated with behaviour disorders. LIMITATIONS: The analyses of gender differences and the prediction of specific disorders was limited due to a low frequency of disorders other than depression. CONCLUSIONS: The bifactor model was able to differentiate concurrent and predict future clinical diagnoses. This can inform the development of targeted as well as non-specific interventions for prevention and treatment of different disorders.

Disclosure attitudes and social acknowledgement as predictors of posttraumatic stress disorder symptom severity in Chinese and German crime victims

Objective: Only rare data exist comparing cross-cultural aspects of civilian traumatization. We compared prevalence rates of posttraumatic stress disorder (PTSD) in German and Chinese crime victims, and investigated the cross-cultural effect of 2 interpersonal predictors. Method: German (n = 151) and Chinese (n = 144) adult crime victims were assessed several months postcrime. The parallel questionnaire set assessed PTSD symptom severity, disclosure attitudes, social acknowledgement, and demographic and crime characteristics. Results: German and Chinese participants differed significantly in their PTSD symptom severity. However, in both samples, disclosure attitudes and social acknowledgement predicted PTSD symptom severity with a similar strength, in addition to the effects of other PTSD predictors. Conclusions: The results suggest that interpersonal variables are predictors of PTSD symptom severity in both cultures and should be included in etiologic models of PTSD.

Melanotic tumors of the nervous system are characterized by distinct mutational, chromosomal and epigenomic profiles.

Melanotic tumors of the nervous system show overlapping histological characteristics but differ substantially in their biological behavior. In order to achieve a better delineation of such tumors, we performed an in-depth molecular characterization. Eighteen melanocytomas, 12 melanomas, and 14 melanotic and 14 conventional schwannomas (control group) were investigated for methylome patterns (450k array), gene mutations associated with melanotic tumors and copy number variants (CNVs). The methylome fingerprints assigned tumors to entity-specific groups. Methylation groups also showed a substantial overlap with histology-based diagnosis suggesting that they represent true biological entities. On the molecular level, melanotic schwannomas were characterized by a complex karyotype with recurrent monosomy of chromosome 22q and variable whole chromosomal gains and recurrent losses commonly involving chromosomes 1, 17p and 21. Melanocytomas carried GNAQ/11 mutations and presented with CNV involving chromosomes 3 and 6. Melanomas were frequently mutated in the TERT promoter, harbored additional oncogene mutations and showed recurrent chromosomal losses involving chromosomes 9, 10 and 6q, as well as gains of 22q. Together, melanotic nervous system tumors have several distinct mutational and chromosomal alterations and can reliably be distinguished by methylome profiling.

Temperature and precipitation effects on δ13C depth profiles in SOM under temperate beech forests

Enrichment of 13C in SOM with soil depth is related to interacting processes influenced by temperature and precipitation. Our objectives were to derive climate effects on patterns of vertical δ13C values of soil organic matter (SOM) while minimizing the effect of confounding variables. We investigated vertical changes in δ13C values of SOM in 1-cm depth intervals in silvicultural mature beech (Fagus sylvatica L.) forest ecosystems in northern Rhineland-Palatinate across gradients of MAT (7.9 to 9.7 °C mean annual temperature) and MAP (607 to 1085 mm mean annual precipitation) in winter 2011. Forest stands (n = 10) were chosen based on data sets provided by the Rhineland-Palatinate Forest Administration so that variations in these gradients occurred while other environmental factors like physico-chemical soil properties, tree species, stand age, exposition and precipitation (for the temperature gradient) or temperature (for the precipitation gradient) did not differ among study sites. From litter down to the mineral soil at 10 cm depth, soil organic carbon (SOC) content decreased (47.5 ± SE 0.1% to 2.5 ± 0.1%) while the δ13C values increased (− 29.4 ± 0.1‰ to − 26.1 ± 0.1‰). Litter of sites under higher MAP/lower MAT had lower δ13C values which was in line with literature data on climate driven plant physiological process. To compare the dimension of the vertical 13C enrichment, δ13C values were regressed linearly against log-transformed carbon contents yielding absolute values of these slopes (beta). Beta values ranged between 0.6 and 4.5 (range of r from − 0.7 to − 1.0; p < 0.01). Due to an assumed decay continuum and similar variations of δ13C values in litter and in 10 cm depth, we conclude that effects on isotope composition in the Oi layer continue vertically and therefore, δ13C values in litter do not solely control beta values. Beta values decreased with increasing MAT (r = − 0.83; p < 0.05). Reduced soil moisture and therefore both, reduced microbial activity and reduced downward transport of microbial cycled DOM (=13C enriched) might be responsible for less pronounced δ13C depth profiles in case of high temperatures. Greater C:N ratios (lower degradability) of the litter under higher temperatures likely contributed to these depth trends. Beta values increased with increasing MAP (r = 0.73; p < 0.05). We found decreasing C:N ratios in the mineral soil that possibly indicates higher decomposition under higher precipitation. Exclusion of the organic layers from linear regressions indicated a stronger impact of MAP on the development of δ13C depth profiles. Our results confirm temperature and precipitation effects on δ13C depth profiles and indicate stronger 13C enrichment under lower MAT/higher MAP. Therefore, time series of vertical δ13C depth profiles might provide insights into climate change effects.