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.

The sediment record of the past 200 years in a Swiss high-alpine lake: Hagelseewli (2339 ma.s.l.)

Sediment cores spanning the last two centuries were taken in Hagelseewli, a high-elevation lake in the Swiss Alps. Contiguous 0.5 cm samples were analysed for biological remains, including diatoms, chironomids, cladocera, chrysophyte cysts, and fossil pigments. In addition, sedimentological and geochemical variables such as loss-on-ignition, total carbon, nitrogen, sulphur, grain-size and magnetic mineralogy were determined. The results of these analyses were compared to a long instrumental air temperature record that was adapted to the elevation of Hagelseewli by applying mean monthly lapse rates. During much of the time, the lake is in the shadow of a high cliff to the south, so that the lake is ice-covered during much of the year and thus decoupled from climatic forcing. Lake biology is therefore influenced more by the duration of ice-cover than by direct temperature effects during the short open-water season. Long periods of ice-cover result in anoxic water conditions and dissolution of authigenic calcites, leading to carbonate-free sediments. The diversity of chironomid and cladoceran assemblages is extremely low, whereas that of diatom and chrysophyte cyst assemblages is much higher. Weak correlations were observed between the diatom and chrysophyte cyst assemblages on the one hand and summer or autumn air temperatures on the other, but the proportion of variance explained is low, so that air temperature alone cannot account for the degree of variation observed in the paleolimnological record. Analyses of mineral magnetic parameters, spheroidal carbonaceous particles and lead suggest that atmospheric pollution has had a significant effect on the sediments of Hagelseewli, but little effect on the water quality as reflected in the lake biota.

Malnutrition Predicts Clinical Outcome in Patients with Neuroendocrine Neoplasias.

Malnutrition is a common problem in oncologic diseases influencing treatment outcomes, treatment complications, quality of life and survival. The potential role of malnutrition has not yet systematically been studied in neuroendocrine neoplasms (NEN), which due to growing prevalence and additional therapeutic options provide an increasing clinical challenge for diagnosis and management. The aim of this cross-sectional observational study, which included a long-term follow-up, was therefore to define the prevalence of malnutrition in 203 patients with NEN using various methodological approaches and to analyze the short- and long-term outcome of malnourished patients. A detailed subgroup analysis was also performed to define risk factors for poorer outcome. By applying malnutrition screening scores 21-25% of NEN-patients were at risk of or demonstrated manifest malnutrition. This was confirmed by anthropometric measurements, determination of serum surrogate parameters such as albumin and bioelectrical impedance analysis particularly phase angle α. Length of hospital stay (LoS) was significantly longer in malnourished NEN-patients while long-term overall survival was highly significantly reduced. Patients with high-grade (G3) neuroendocrine carcinomas, progressive disease and undergoing chemotherapy were at particular risk for malnutrition associated with a poorer outcome. Multivariate analysis confirmed the important and highly significant role of malnutrition as an independent prognostic factor for NEN besides proliferative capacity (G3-NEC). Malnutrition is therefore an underrecognized problem in NEN-patients, which should systematically be diagnosed by widely available standard methods such Nutritional Risk Screening (NRS) score, serum albumin levels and bioelectrical impedance analysis (BIA) and treated to improve both short- and long-term outcomes.

The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients.

BACKGROUND Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. METHODS Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency. RESULTS One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still TOL. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively. CONCLUSIONS In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival.

Sedimentological and biostratigraphical analyses of short sediment cores from Hagelseewli (2339 m a.s.l.) in the Swiss Alps

Several short sediment cores of between 35 and 40 cm from Hagelseewli, a small, remote lake in the Swiss Alps at an elevation of 2339 m a.s.l. were correlated according to their organic matter content. The sediments are characterized by organic silts and show in their uppermost part a surprisingly high amount of organic matter (30-35%). Synchronous changes, occurring in pollen from snow-bed vegetation, the alga Pediastrum, chironomids, and grain-size composition, point to a climatic change interpreted as cooler or shorter summers that led to prolonged ice-cover on the lake. According to palynological results the sediments date back to at least the early 15th century A.D., with the cooling phase encompassing the period between late 16th and the mid-19th century thus coinciding with the Little Ice Age. Low concentrations of both chironomid head capsules and cladoceran remains in combination with results from fossil pigment analyses point to longer periods of bottom-water anoxia as a result of long-lasting ice-cover that prevented mixing of the water column. According to our results aquatic biota in Hagelseewli are mainly indirectly influenced by climate change. The duration of ice-cover on the lake controls the mixing of the water column as well as light-availability for phytoplankton blooms.