Background: We evaluated vorasidenib (VOR), a dual inhibitor of mIDH1/2, in patients with mIDH1/2 glioma (Phase 3; NCT04164901). Methods: Patients with residual/recurrent grade 2 mIDH1/2 oligodendroglioma or astrocytoma were enrolled (age ≥12; Karnofsky Performance Score ≥80; measurable non-enhancing disease; surgery as only prior treatment; not in immediate need of chemoradiotherapy). Patients were stratified by 1p19q status and baseline tumor size and randomized 1:1 to VOR 40 mg or placebo (PBO) daily in 28-day cycles. Endpoints included imaging-based progression-free survival (PFS), time to next intervention (TTNI), tumor growth rate (TGR), health-related quality of life (HRQoL), neurocognition and seizure activity. Results: 331 patients were randomized (VOR, 168; PBO, 163). The median age was 40.0 years. 172 and 159 patients had histologically confirmed oligodendroglioma and astrocytoma, respectively. Treatment with VOR significantly improved PFS and TTNI. Median PFS: VOR, 27.7 mos; PBO, 11.1 mos (P=0.000000067). Median TTNI: VOR, not reached; PBO, 17.8 mos (P=0.000000019). Treatment with VOR resulted in shrinkage of tumor volume. Post-treatment TGR: VOR, -2.5% (95% CI: -4.7, -0.2); PBO, 13.9% (95% CI: 11.1, 16.8). HRQoL and neurocognition were preserved and seizure control was maintained. VOR had a manageable safety profile. Conclusions: VOR was effective in mIDH1/2 diffuse glioma not in immediate need of chemoradiotherapy.

The main aim of the current study was to present the abilities of widely used crop models to simulate four different field crops (winter wheat, spring barley, silage maize and winter oilseed rape). The 13 models were tested under Central European conditions represented by three locations in the Czech Republic, selected using temperature and precipitation gradients for the target crops in this region. Based on observed crop phenology and yield from 1991 to 2010, performances of individual models and their ensemble were analyzed. Modelling of anthesis and maturity was generally best simulated by the ensemble median (EnsMED) compared to the ensemble mean and individual models. The yield was better simulated by the best models than estimated by an ensemble. Higher accuracy was achieved for spring crops, with the best results for silage maize, while the lowest accuracy was for winter oilseed rape according to the index of agreement (IA). Based on EnsMED, the root mean square errors (RMSEs) for yield was 1365 kg/ha for winter wheat, 1105 kg/ha for spring barley, 1861 kg/ha for silage maize and 969 kg/ha for winter oilseed rape. The AQUACROP and EPIC models performed best in terms of spread around the line of best fit (RMSE, IA). In some cases, the individual models failed. For crop rotation simulations, only models with reasonable accuracy (i.e. without failures) across all included crops within the target environment should be selected. Application crop models ensemble is one way to increase the accuracy of predictions, but lower variability of ensemble outputs was confirmed.

Neurotrophins are central to several aspects of central nervous system function, and emerging evidence links these growth factors to mood disorders. The purpose of this study was to investigate serum neurotrophin-4/5 (NT-4/5) levels in patients with bipolar disorder, both within mood episodes and in euthymia. Patients with bipolar I disorder (n=154) and controls (n=30) had their NT-4/5 serum levels assayed using an ELISA. Levels of NT-4/5 levels were significantly higher in bipolar disorder patients than in controls; NT-4/5 levels were increased in mania, depression and euthymia, but not significantly different between BD mood states. As far as are aware, this is the first study showing NT-4/5 immunocontent alterations in bipolar disorder. A tentative explanation would be that NT-4/5 increases is compensating for ongoing oxidative damage in dopaminergic neurons.

In the current regional-scale study, the model DSSAT CROPGRO was applied in order to simulate the cultivation of industrial tomato and to estimate the green water (GW), blue water (BW), blue water requirement (BWR) and water footprint (WFP) through a dual-step approach (with and without full irrigation). Simulation covered a period of 30 years for three climate scenarios including a reference period and two future scenarios based on forecast global average temperature increases of 2 and 5 °C. The spatial patterns of indicators relating to the whole territory of Puglia region (Southern Italy), characterized by the high evaporative demand of the atmosphere, are discussed and analysed. Considering the climatic pattern, the analysis was developed for three areas (Northern, Central and Southern). Future scenarios affected all indicators significantly, particularly the Northern area, characterized by higher temperature and rainfall anomalies. Under the A5 scenario, compared with the baseline, this area was forecast to have a large increase of BW (+30%) and reduction in yield (−20%). As a consequence, the BWR and WFP were predicted to increase dramatically, up to 40 and >65%, respectively. On the other hand, Central and Southern areas, with lower anomalies of temperature and rainfall, were forecast to be less vulnerable to climate change. The distributed analysis performed could be important for water policy, allowing most efficient allocation of scarce water resources and concentrating them where the WFP is lowest, or in other words, water use efficiency is highest.

Eight sediment gravity cores, collected from the joides and Drygalski basins, were analysed in order to understand late Pleistocene-Holocene biogenic flux changes in the Ross Sea, driven by paleoenvironmental changes. Core lithologies and magnetic-susceptibility depth profiles were used for core logging and stratigraphic correlation. Nineteen AMS radiocarbon dates of bulk organic matter were used to set chronological constraints and calculate sediment accumulation rates. These rates, which vary from 1.4-38 cm ka−1. were used to obtain the burial fluxes of biogenic components. The highest fluxes occur in the deepest parts of the basins (TOC, 0.05-0.2 g cm −2 ka−1; biogenic silica, 1.5-5 g cm−1 ka−1), where as topographic highs show the lowest values (TOC, 0.01-0.1 g cm−2 ka−1 ; biogenic silica, 0.1-1.4 g cm−2 ka−1). Dramatic changes in both physical properties and fluxes record the establishment of open marine-sedimentation conditions which occurred first in the joides basin and then, with a delay of ca. 6000 years, in the Drygalski basin. Both TOC and biogenic-silica fluxes increase through the Holocene, though slightly differently. The high fluxes of both 10Be and biogenic Ba suggest that sediment accumulation at basin sites is strongly influenced by lateral transport.

Trapping experiments have been performed at the Idaho National Laboratory to assess the performance of AgX sorbent media in capturing volatile iodine during the oxidation of irradiated oxide fuel. The demonstration of iodine release and capture from the used fuel has been accomplished with laboratory-scale equipment in a hot cell environment. Iodine loadings as high as 6 ug/g media have been achieved via chemical adsorption with filter efficiencies in excess of 90%. In addition to iodine, significant quantities of tritium have also been collected on the AgX filter media. Filter media loaded with radioactive iodine has been sequestered in a tin matrix by hot isostatic pressing at 200°C. The placement and encapsulation of the sorbent media was examined by neutron radiography, thus confirming the sequestration of radioactive iodine.

A seroprevalence study was carried out on 1757 outpatients consecutively seen in a sexually transmitted disease (STD) clinic in order to evaluate the sexual transmission of hepatitis C virus (HCV). A total of 1442 consenting patients were tested for hepatitis C, hepatitis B and human immunodeficiency virus type 1 (HCV. HBV, HIV - 1) antibodies. The relations between anti-HCV, anti-HBc and anti-HIV - 1 were studied. Of 73 anti-HCV positive reactions, 45 (61.6%) were confirmed by the recombinant immunoblot assay (RIBA). The proportion of individuals with anti-HCV was higher in outpatients with a history of sexually transmitted disease than without. It was 2.8% in non drug user heterosexuals and 2.9% in non drug user homosexuals. Intravenous drug users (IDU) had higher anti-HCV prevalence when a history of STD was taken into account (42.3% in subjects with STD versus 36.7% in subjects without STD). Among non drug user heterosexuals an association was found between anti-HCV and anti-HBc. These data suggest that sexual transmission of HCV occurs, although it seems to be less efficient than other parenteral modes of transmission. When a more sensitive and specific marker of HCV infection become available, a more accurate estimate of the frequency and efficiency of the sexual transmission will be possible.

Flux data from moored sediment trap experiments and mass accumulation rates in sediments were obtained for three sites in the Ross Sea which are currently studied for the formation and transit of High Salinity Shelf Water and Ice Shelf Water. These two data sets were compared to obtain inferences on the coupling between water column processes and sedimentary records. The depth distribution of physical features and concentrations of organic carbon and biogenic silica in box cores and gravity cores were studied. Mass accumulation rates, established on the basis of two conventional 14C dates for each core, range between 7.64 and 19.46 g m−2 yr−1. Although these are productive areas, downward fluxes measured by sediment traps are low: 7.5–25.6, 2.4–17.9 and 0.5–0.9 g m−2 yr−1 for particles, biogenic silica and organic carbon, respectively. The concentrations of biogenic components in surficial sediments are correspondingly low. Simple mass balances were calculated assuming the conservative behaviour of the lithic fraction of sinking materials and sediment. Lateral advection of suspended particles is needed to balance the fluxes at the three sites. Furthermore, the model suggests that the preservation of biogenic components is lower than at other sites of the Ross Sea, probably due to the low accumulation rates that imply a high residence time of biogenic materials at the sediment-water interface.