No abstract

Glioblastoma (GBM), the most common primary malignant brain tumor in adults, is associated with significant morbidity and mortality despite maximal safe resection followed by chemo- and radiotherapy. GBMs contain self-renewing, tumorigenic glioma stem cells that contribute to tumor initiation, heterogeneity, therapeutic resistance, and recurrence. Intratumoral heterogeneity (ITH) of GBMs is also a major contributing factor to poor clinical outcomes associated with these high-grade glial tumors. Herein, the authors summarize recent discoveries and advances in the molecular and phenotypic characterization of GBMs with particular focus on ITH. In so doing, they attempt to highlight recent advances in molecular signatures/properties and metabolic alterations in an effort to clarify translational implications that may ultimately improve clinical outcomes.

Models are key tools in our quest to better understand the impacts of soil waterlogging on plant growth and crop production. Here, we reviewed the state of the art of modeling approaches and compared the conceptual design of these models with recent experimental findings. We show that many models adopt an aeration stress (AS) principle where surplus water reduces air-filled porosity, with implications for root growth. However, subsequent effects of AS within each model vary considerably. In some cases, AS inhibits biomass accumulation (e.g. AquaCrop), altering processes prior to biomass accumulation such as light interception (e.g. APSIM), or photosynthesis and carbohydrate accumulation (e.g. SWAGMAN Destiny). While many models account for stage-dependent waterlogging effects, few models account for experimentally observed delays in phenology caused by waterlogging. A model intercomparison specifically designed for long-term waterlogged conditions (APSIM-Oryza) with models developed for dryland conditions with transient waterlogging would advance our understanding of the current fitness for purpose of exsiting frameworks for simulating transient waterlogging in dryland cropping systems. Of the point-based dynamic models examined here, APSIM-Soybean and APSIM-Oryza simulations most closely matched with the observed data, while GLAM-WOFOST achieved the highest performance of the spatial-regional models examined. We conclude that future models should incorporate waterlogging effects on genetic tolerance parameters such as (1) phenology of stress onset, (2) aerenchyma, (3) root hydraulic conductance, (4) nutrient-use efficiency, and (5) plant ion (e.g. Fe/Mn) tolerance. Incorporating these traits/effects into models, together with a more systematic model intercomparison using consistent initialization data, will significantly improve our understanding of the relative importance of such factors in a systems context, including feedbacks between biological factors, emergent properties, and sensitive variables responsible for yield losses under waterlogging.

Climate change will drive increased frequencies of extreme climatic events. Despite this, there is little scholarly information on the extent to which waterlogging caused by extreme rainfall events will impact on crop physiological behaviour. To improve the ability to reliably model crop growth and development under soil waterlogging stress, we advanced the process-basis of waterlogging in the farming systems model Agricultural Systems Production Systems sIMulator. Our new mathematical description of waterlogging adequately represented waterlogging stress effects on the development, biomass and grain yield of many commercial Australian barley genotypes. We then used the improved model to examine how optimal flowering periods (OFPs, the point at which long-term abiotic stresses are minimal) change under historical and future climates in waterlogging-prone environments, and found that climate change will reduce waterlogging stress and shift forward OFP (26 d earlier on average across locations). For the emissions scenario representative concentration pathway 8.5 at 2090, waterlogging stresses diminished but this was not enough to prevent substantial yield reduction due to increasingly severe high temperature stress (−35% average reduction in yield across locations, genotypes and sowing dates). It was shown that seasonal waterlogging stress patterns under future conditions will be similar to those occurring historically. Yield reduction caused by waterlogging stress was 6% and 4% on average across sites under historical and future climates. To adapt, both genotypic and management adaptations will be required: earlier sowing and planting waterlogging tolerant genotypes mitigate yield penalty caused by waterlogging by up to 26% and 24% under historical and future climates. We conclude that even though the prevalence of waterlogging in future will diminish, climate change and extreme climatic events will have substantial and perverse effects on the productivity and sustainability of Australian farms.

Background:Preclinical and clinical data suggest the possibility of neurotoxicity following exposure of young children to general anesthetics with subsequent behavioral disturbances. The aim of the study was to determine the overall effect of repeated general anesthesia on behavior and emotions of young children aged 1½-5 years old, compared to healthy children.Materials and Methods:Thirty-five children underwent repeated anesthesia and surgery were matched with the same number of healthy children who attended vaccination clinic, as a control group. Both groups were administered the child behavior checklist (CBCL) 1½-5 years and Diagnostic and Statistical Manual of Mental Disorders (DSM) oriented scale. Behavior data were collected through a semi-structured questionnaire.Results:The CBCL score revealed that children with repeated anesthesia were at risk to become anxious or depressed (relative risk [RR]; 95% confidence interval [CI] = 11 [1.5-80.7]), to have sleep (RR; 95% CI = 4.5 [1.1-19.4]), and attention problems (RR; 95% CI = 8 [1.1-60.6]). There was no difference in the risk between the two groups regarding emotionally reactive, somatic complaints, withdrawn problems, aggressive behavior, internalizing or externalizing problems. On DSM scale, children with repeated anesthesia were at risk to develop anxiety problems (RR; 95% CI = 3.7 [1.1-12.0]), and attention deficit/hyperactivity problems (RR; 95% CI = 3 [1.1-8.4]). There was no difference in the risk between the two groups regarding affective, pervasive developmental and oppositional defiant problems.Conclusion:Young children who undergone repeated surgical procedures under general anesthesia were at risk for subsequent behavioral and emotional disturbances. Proper perioperative pain management, social support, and avoidance of unpleasant surgical experiences could minimize these untoward consequences.