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Cannabis use during adolescence is associated with an increased risk of developing psychosis. According to a current hypothesis, this results from detrimental effects of early cannabis use on brain maturation during this vulnerable period. However, studies investigating the interaction between early cannabis use and brain structural alterations hitherto reported inconclusive findings. We investigated effects of age of cannabis initiation on psychosis using data from the multicentric Personalized Prognostic Tools for Early Psychosis Management (PRONIA) and the Cannabis Induced Psychosis (CIP) studies, yielding a total sample of 102 clinically-relevant cannabis users with recent onset psychosis. GM covariance underlies shared maturational processes. Therefore, we performed source-based morphometry analysis with spatial constraints on structural brain networks showing significant alterations in schizophrenia in a previous multisite study, thus testing associations of these networks with the age of cannabis initiation and with confounding factors. Earlier cannabis initiation was associated with more severe positive symptoms in our cohort. Greater gray matter volume (GMV) in the previously identified cerebellar schizophrenia-related network had a significant association with early cannabis use, independent of several possibly confounding factors. Moreover, GMV in the cerebellar network was associated with lower volume in another network previously associated with schizophrenia, comprising the insula, superior temporal, and inferior frontal gyrus. These findings are in line with previous investigations in healthy cannabis users, and suggest that early initiation of cannabis perturbs the developmental trajectory of certain structural brain networks in a manner imparting risk for psychosis later in life.

In schizophrenia, neurocognitive subtypes can be distinguished based on cognitive performance and they are associated with neuroanatomical alterations. We investigated the existence of cognitive subtypes in shortly medicated recent onset psychosis patients, their underlying gray matter volume patterns and clinical characteristics. We used a K-means algorithm to cluster 108 psychosis patients from the multi-site EU PRONIA (Prognostic tools for early psychosis management) study based on cognitive performance and validated the solution independently (N = 53). Cognitive subgroups and healthy controls (HC; n = 195) were classified based on gray matter volume (GMV) using Support Vector Machine classification. A cognitively spared (N = 67) and impaired (N = 41) subgroup were revealed and partially independently validated (Nspared = 40, Nimpaired = 13). Impaired patients showed significantly increased negative symptomatology (pfdr = 0.003), reduced cognitive performance (pfdr pfdr p = 0.01) separating impaired patients from HC revealed increases and decreases across several fronto-temporal-parietal brain areas, including basal ganglia and cerebellum. Cognitive and functional disturbances alongside brain morphological changes in the impaired subgroup are consistent with a neurodevelopmental origin of psychosis. Our findings emphasize the relevance of tailored intervention early in the course of psychosis for patients suffering from the likely stronger neurodevelopmental character of the disease.

Planetesimals, the smallest building blocks of planets that are gravitationally bound, are believed to be needed in order to form planets. The spacial distribution of these objects that are typically 100 km in diameter is important for the outcome of planet formation. There exist an entire zoo of different disk instabilities that can cause vortices or zonal flow within which pebbles can be trapped and form planetesimals via gravitational instability. We parameterized these traps and implemented a pebble flux-regulated planetesimal formation rate into a dust and gas evolution code. We found that the radial planetesimal distribution spans from the regions of terrestrial planet formation up to the Kuiper belt and is steeper than the initial profile of dust and gas. The latter finding indicates that the feeding zone, i.e. the region from which the material forming planetesimals originates, can be large. The final spacial planetesimal distribution strongly depends on the turbulence strength from which we can conclude that the Solar Nebula was not very turbulent (α-2).

Manganese (Mn) enrichments in sediments of the deep basins of the Baltic Sea are believed to consist of Ca-Mn-carbonates that form from Mn oxides following periodic inflows of oxygen-rich North Sea waters. However, a range of Mn-bearing mineral phases, that besides Mn-carbonates (e. g. Ca-rhodochrosite), can include Mn-sulfides are known to be present in marine sediments, with formation mechanisms that are sensitive to redox conditions. In this study, we use high resolution synchrotron EXAFS and XANES combined with LA-ICP-MS and micro-XRF, to investigate the nature of the Mn enrichments in sediments from the Holocene Thermal Maximum (approx. 8000-4000 cal. yr BP) at a site in the northern Gotland Basin. Analyses were performed on epoxy-embedded sediment sequences. We specifically address the role of changes in redox conditions in bottom waters, as inferred from sediment molybdenum(Mo) contents, for Mn sequestration. We find that an up-core increase in Mo, indicating a transition into more anoxic and sulfidic (euxinic) bottom water conditions, is accompanied by a decline in total sediment Mn contents. While Mn-carbonates dominate the Mn mineral fraction in the low-Mo interval, in the more sulfidic, high Mo interval, Mn is associated with framboidal pyrite. Mn/Fe ratios in the sulfidic interval vary between the investigated sequences but reach values of up to 7.7 mol%. This exceeds ratios previously reported for sedimentary pyrite and EXAFS spectra indicate that sulfide bound Mn is predominately tetrahedrally coordinated when Mn/Fe ratios are high. This suggests that Mn is incorporated in other Fe-S phases such as mackinawite besides pyrite. There is also evidence for the presence of a low concentration of Mn associated with detrital aluminosilicates throughout the investigated intervals. Our results suggest that increased bottom water euxinia inhibited the formation of Mn-carbonate at this site during the Holocene Thermal Maximum, possibly due to a more rapid reduction of Mn oxides in more sulfidic bottom waters. (C) 2014 Elsevier B.V. All rights reserved. (Less)

Wnt/beta-catenin signaling has a central role in the development and progression of most colon cancers (CCs). Germline variants in Wnt/beta-catenin pathway genes may result in altered gene function and/or activity, thereby causing inter-individual differences in relation to tumor recurrence capacity and chemoresistance. We investigated germline polymorphisms in a comprehensive panel of Wnt/beta-catenin pathway genes to predict time to tumor recurrence (TTR) in patients with stage III and high-risk stage II CC. A total of 234 patients treated with 5-fluorouracil-based chemotherapy were included in this study. Whole-blood samples were analyzed for putative functional germline polymorphisms in SFRP3, SFRP4, DKK2, DKK3, Axin2, APC, TCF7L2, WNT5B, CXXC4, NOTCH2 and GLI1 genes by PCR-based restriction fragment-length polymorphism or direct DNA sequencing. Polymorphisms with statistical significance were validated in an independent study cohort. The minor allele of WNT5B rs2010851 T > G was significantly associated with a shorter TTR (10.7 vs 4.9 years; hazard ratio: 2.48; 95% CI, 0.96-6.38; P=0.04) in high-risk stage II CC patients. This result remained significant in multivariate Cox's regression analysis. This study shows that the WNT5B germline variant rs2010851 was significantly identified as a stage-dependent prognostic marker for CC patients after 5-fluorouracil-based adjuvant therapy.

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Changing the Medicaid program is a top priority for the Republican party. Common themes from GOP proposals include converting Medicaid from a jointly financed entitlement benefit to a form of capped federal financing. While proponents of this reform argue that it would provide greater flexibility and a more predictable budget for state governments, serious consequences would likely result for Medicaid enrollees and state governments. Under all three scenarios promoted by Republicans--block grants, capped allotments, and per capita caps—most states would face increased costs. For all three scenarios, the capped nature of the funding guarantees that the real value of funds would decrease in future years relative to what would be expected from growth under the current program. Although the federal government would undoubtedly realize savings from all three scenarios, the impact might lead states to reduce benefits and services, create waiting lists, impose cost-sharing on a traditionally low-income enrollee population, or impose other obstacles to coverage. Nationally, as many as 20.5 million Americans stand to lose coverage under the proposed Medicaid changes. In California, up to 6 million people could lose coverage if changes to the Medicaid program were coupled with the repeal of coverage for the expansion population.