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The intent of this article is to provide a comprehensive, educational review of adult-type diffuse gliomas, bringing together the role of the multidisciplinary team and giving the reader biologic, surgical, radiologic, and oncologic insight into these tumors. The reader will be guided through subsections that explain the molecular pathophysiology, diagnosis, treatment, prognosis and natural history of the disease. The 2021 World Health Organization Classification will be explained through a combination of concise historic review of glioma diagnosis and contemporary knowledge of the molecular pathways. Accompanying illustrations will act as powerful tools for comprehension. These concepts will be underpinned by frequent reference to neuroradiology and a grounding of normal brain composition.Learning Objective: To understand the pathophysiologic concepts that underly the World Health Organization Classification and natural history of adult-type diffuse gliomas and how these relate to imaging and treatment strategies

A disconnect between scientific research and environmental management communities can be a detriment to both. In the case of Great Lakes coastal ecosystems, which are inherently complex and subject to uncertain effects of future climatic, environmental, and anthropogenic drivers, greater collaboration could be beneficial to their sustainability. We capture the challenges and opportunities identified by a scientist/decision-maker co-production workshop focused on the future environmental quality of Great Lakes coastal wetlands. We explain our path through the stakeholder workshop process, our challenges in translating meeting outcomes into actionable items, and lessons learned to bridge gaps between scientists and decision-makers. Additionally, we determine topics and directions identified by decision-makers that can be modeled with existing technologies and others that require further research. These topics may be incorporated into future research efforts and could serve as a shortlist of research priorities that were identified by decision-makers working with coastal wetland issues. Based on lessons learned during and after the workshop, we provide suggestions for bridging the gap between researchers and decision-makers, including sustained engagement between these groups and improved interaction through the beginning, duration, and end of research and/or management efforts.

To better understand zooplankton dynamics in Lake Ontario’s Toronto Harbour and adjacent coastal area (CA), we sampled zooplankton, phytoplankton, nutrients and physical parameters on six dates in 2016. Despite higher levels of nutrients, chlorophyll and primary production in the inner harbor (IH), the areas supported similar May to November zooplankton biomass (IH = 32 ± 7 and CA = 42 ± 10 mg/m3). IH values were much lower than other nutrient-enriched embayments in Lake Ontario, yet CA biomass was twice that of nearshore sites away from Toronto. Small zooplankton such as rotifers and Bosmina dominated IH; and large taxa (Daphnia, calanoids and predatory cladocerans) were more important in the CA. Daphnia, Bosmina, cyclopoids and calanoids were larger in the CA, and adult cyclopoids had higher egg ratios. This led to low annual IH production estimates for both cyclopoid and calanoid copepods. Total phosphorus and chlorophyll did not appear to regulate zooplankton biomass, but positive relationships were found with bacterial biomass in the IH and with temperature in the cool season. Atypically high fish planktivory rates likely suppressed larger IH zooplankton in 2016, allowing small, resilient Bosmina to flourish and contribute 84% of total production in the IH. Comparing 2016 data to previous zooplankton surveys revealed considerable inter-annual variation in proportions of Daphnia, Bosmina and predatory cladocerans over the 1994 to 2016 period, and the strong top-down controls observed in 2016 were not typical. Elevated microbial production may serve as an important alternate trophic pathway supporting cladoceran populations in Toronto Harbour.

A population of Palmer amaranth (Amaranthus palmeri S. Watson) in Kansas (KSR) was found to have evolved resistance to three commonly used herbicides, i.e., chlorsulfuron, atrazine, and mesotrione....

Received 12th May 2021. Accepted 17th May 2021. Published online 28th May 2021. Issue published 1st August 2021.

Kochia accessions (designated as KS-4A and KS-4H) collected from a corn field near Garden City, KS, have previously shown multiple resistance to glyphosate, dicamba, and fluroxypyr. These accessions were also suspected as being resistant to photosystem II (PS II) inhibitors. The main objectives of this research were to 1) confirm the coexistence of cross-resistance to PS II inhibitors (atrazine and metribuzin) applied PRE and POST, 2) investigate the underlying mechanism of PS II-inhibitor resistance, and 3) determine the effectiveness of alternative POST herbicides for control of these multiple herbicide–resistant (MHR) kochia accessions. Results from dose-response experiments revealed that the KS-4A and KS-4H kochia accessions were 23-fold to 48-fold resistant to PRE- and POST-applied atrazine and 13-fold to 18-fold resistant to POST-applied metribuzin compared to a known susceptible kochia accession (KS-SUS). Both accessions also showed putative resistance to PRE-applied metribuzin that needs to be confirmed. Sequence analyses of the psbA gene further revealed that all samples from the KS-4A and KS-4H kochia accessions had a Ser264Gly point mutation. A pretreatment with malathion followed by a POST application of atrazine at 1,120 g ha−1 or metribuzin at 630 g ha−1 did not reverse the resistance phenotypes of these MHR accessions. In a separate greenhouse study, alternative POST herbicides, including bicyclopyrone + bromoxynil; bromoxynil + pyrasulfotole; paraquat alone or in combination with atrazine, metribuzin, 2,4-D, or saflufenacil; and saflufenacil alone or in combination with 2,4-D effectively controlled the KS-4H accession (≥97% injury). To our knowledge, this research reports the first case of kochia accessions with cross-resistance to PRE-applied atrazine and POST-applied metribuzin. Growers should adopt diversified weed control strategies, including the use of competitive crops, cover crops, targeted tillage, and harvest weed seed control along with effective alternative PRE and POST herbicides with multiple sites of action to control MHR kochia seedbanks on their production fields.

In this paper we model a graphene nano-ribbon structure by analysing an infinite 3-regular hexagonal grid which is transformed to a rectangular coordinate system or “wall”. Our goal is to solve the inverse problem of identifying the position of a single vacancy break using the lengths of the closed paths along the edges of the underlying graph. We provide an algorithm to determine the exact position of the defect by using data from at most three reference points.

Injection-induced seismicity became an important issue over the past decade, and although much of the rise in seismicity is attributed to wastewater disposal, a growing number of cases have identified hydraulic fracturing (HF) as the cause. A recent study identified regions in Oklahoma where ≥75% of seismicity from 2010 to 2016 correlated with nearly 300 HF wells. To identify factors associated with increased probability of induced seismicity, we gathered publicly available information about the HF operations in these regions including: injected volume, number of wells on a pad, injected fluid (gel vs. slickwater), vertical depth of the well, proximity of the well to basement rock, and the formation into which the injection occurred. To determine the statistical strength of the trends, we applied logistic regression, bootstrapping, and odds ratios. We see no trend with total injected volume in our Oklahoma dataset, in contrast to strong trends observed in Alberta and Texas, but we note those regions have many more multiwell pads leading to larger cumulative volumes within a localized area. We found a ∼50% lower probability of seismicity with the use of gel compared to slickwater. We found that HF wells targeting older formations had a higher probability of seismicity; however, these wells also tend to be deeper, and we found the trend with well depth to be stronger than the trend with age of formation. When isolated to the Woodford formation, well depth produced the strongest relationship, increasing from ∼5% to ∼50% probability from 1.5 to 5.5 km. However, no trend was seen in the proximity to basement parameter. Based on previously measured pore pressure gradients, we interpret the strong absolute depth relationship to be a result of the increasing formation overpressure measured in deeper portions of the basin that lower the stress change needed to induce seismicity.

The elevation history of the Tibetan Plateau promises insight into the mechanisms and dynamics that develop and sustain high topography over tens of millions of years, as well as the contribution of uplift-related erosive flux to Cenozoic global cooling. The elevation history of the center and northern margin of the plateau have been historically less well-constrained than the southern margin. A diverse suite of techniques, each with their own biases and uncertainties, yield discrepant mid-Cenozoic elevation estimates (0–5 km). We reconstruct Paleogene to Miocene elevations of the Lunpola basin on the northern Lhasa terrane, the southernmost crustal block of the Tibetan Plateau, using stable isotope paleoaltimetry and clumped-isotope paleothermometry on lacustrine and pedogenic carbonates, integrated with previously published compound-specific n-alkane-derived hydrogen isotopes. Paleo-elevation estimates for the Lunpola basin (∼3.1–4.7 km) demonstrate that the northern edge of the Lhasa Block attained high elevation prior to ∼24 Ma and potentially by the Early Eocene (

The evolution of resistance to multiple herbicides in Palmer amaranth is a major challenge for its management. In this study, a Palmer amaranth population from Hutchinson, Kansas (HMR), was characterized for resistance to inhibitors of photosystem II (PSII) (e.g., atrazine), acetolactate synthase (ALS) (e.g., chlorsulfuron), and EPSP synthase (EPSPS) (e.g., glyphosate), and this resistance was investigated. About 100 HMR plants were treated with field-recommended doses (1×) of atrazine, chlorsulfuron, and glyphosate, separately along with Hutchinson multiple-herbicide (atrazine, chlorsulfuron, and glyphosate)–susceptible (HMS) Palmer amaranth as control. The mechanism of resistance to these herbicides was investigated by sequencing or amplifying the psbA, ALS, and EPSPS genes, the molecular targets of atrazine, chlorsulfuron, and glyphosate, respectively. Fifty-two percent of plants survived a 1× (2,240 g ai ha−1) atrazine application with no known psbA gene mutation, indicating the predominance of a non–target site resistance mechanism to this herbicide. Forty-two percent of plants survived a 1× (18 g ai ha−1) dose of chlorsulfuron with proline197serine, proline197threonine, proline197alanine, and proline197asparagine, or tryptophan574leucine mutations in the ALS gene. About 40% of the plants survived a 1× (840 g ae ha−1) dose of glyphosate with no known mutations in the EPSPS gene. Quantitative PCR results revealed increased EPSPS copy number (50 to 140) as the mechanism of glyphosate resistance in the survivors. The most important finding of this study was the evolution of resistance to at least two sites of action (SOAs) (~50% of plants) and to all three herbicides due to target site as well as non–target site mechanisms. The high incidence of individual plants with resistance to multiple SOAs poses a challenge for effective management of this weed.

Human appropriation of net primary productivity (HANPP) is employed as a measure of human pressures on biodiversity, though largely at global and national scales rather than landscape to regional scales where many conservation decisions take place. Though gaining in familiarity, HANPP is not widely utilized by conservation professionals. This study, encompassing the US side of the Great Lakes basin, examines how regional distributions of HANPP relate to landscape-based biodiversity proxy metrics used by conservation professionals. Our objectives were (1) to quantify the HANPP of managed lands at the county scale; and (2) to assess spatial patterns of HANPP in comparison to landscape diversity and local habitat connectedness to determine if the metric can provide useful information to conservation professionals. We aggregated forest and cropland NPP data between 2005 and 2015 and coupled it with previously published potential vegetation maps to quantify the HANPP of each county in the study region. We mapped the outputs at 500 m resolution to analyze spatial relationships between HANPP and landscape metrics of biodiversity potential. Area-weighted HANPP across our study region averaged 45% of NPP, down to 4.9% in forest-dominated counties. Greater HANPP correlated with reduced landscape diversity (p

Differential disturbance severity effects on forest vegetation structure, species diversity, and net primary production (NPP) have been long theorized and observed. Here, we examined these factors concurrently to explore the potential for a mechanistic pathway linking disturbance severity, changes in light environment, leaf functional response, and wood NPP in a temperate hardwood forest.Using a suite of measurements spanning an experimental gradient of tree mortality, we evaluated the direction and magnitude of change in vegetation structural and diversity indexes in relation to wood NPP. Informed by prior observations, we hypothesized that forest structural and species diversity changes and wood NPP would exhibit either a linear, unimodal, or threshold response in relation to disturbance severity. We expected increasing disturbance severity would progressively shift subcanopy light availability and leaf traits, thereby coupling structural and species diversity changes with primary production.Linear or unimodal changes in three of four vegetation structural indexes were observed across the gradient in disturbance severity. However, disturbance‐related changes in vegetation structure were not consistently correlated with shifts in light environment, leaf traits, and wood NPP. Species diversity indexes did not change in response to rising disturbance severity.We conclude that, in our study system, the sensitivity of wood NPP to rising disturbance severity is generally tied to changing vegetation structure but not species diversity. Changes in vegetation structure are inconsistently coupled with light environment and leaf traits, resulting in mixed support for our hypothesized cascade linking disturbance severity to wood NPP., We examined multiple metrics of vegetation structural and biological diversity concurrently to explore the potential for a mechanistic pathway linking disturbance severity, changes in light environment, leaf functional response, and wood NPP in a temperate hardwood forest. Significant linear or unimodal changes in three of four vegetation structural indexes were observed across the gradient in disturbance severity, although disturbance‐related changes in vegetation structure were not consistently correlated with shifts in light environment, leaf traits, and wood NPP. We conclude that, in our study system, the sensitivity of wood NPP to rising disturbance severity is generally tied to changing vegetation structure but not species diversity.

Normothermic Regional Perfusion (NRP) has shown encouraging clinical results. However, translation from an experimental to routine procedure poses several challenges. Herein we describe a model that led to the implementation of NRP into standard clinical practice in our centre following an iterative process of refinement incorporating training, staffing and operative techniques. Using this approach we achieved a four-fold increase in trained surgical staff and a 6-fold increase in competent senior organ preservation practitioners in 12 months, covering 93% of the retrieval calls. We now routinely provide NRP throughout the UK and attended 186 NRP retrievals from which 225 kidneys, 26 pancreases and 61 livers have been transplanted, including 5 that were initially declined by all UK transplant centres. The 61 DCD(NRP) liver transplants undertaken exhibited no primary non-function or ischaemic cholangiopathy with up to 8 years of follow-up. This approach also enabled successful implementation of ex situ normothermic liver perfusion which together with NRP contributed 37.5% of liver transplant activity in 2021. Perfusion technologies (in situ and ex situ) are now supported by a team of Advanced Perfusion and Organ Preservation Specialists. The introduction of novel perfusion technologies into routine clinical practice presents significant challenges but can be greatly facilitated by developing a specific role of Advanced Perfusion and Organ Preservation Specialist supported by a robust education, training and recruitment programme.

Monitoring of cyanobacterial bloom biomass in large lakes at high resolution is made possible by remote sensing. However, monitoring cyanobacterial toxins is only feasible with grab samples, which, with only sporadic sampling, results in uncertainties in the spatial distribution of toxins. To address this issue, we conducted two intensive “HABs Grabs” of microcystin (MC)-producing Microcystis blooms in the western basin of Lake Erie. These were one-day sampling events during August of 2018 and 2019 in which 100 and 172 grab samples were collected, respectively, within a six-hour window covering up to 2,270 km2 and analyzed using consistent methods to estimate the total mass of MC. The samples were analyzed for 57 parameters, including toxins, nutrients, chlorophyll, and genomics. There were an estimated 11,513 kg and 30,691 kg of MCs in the western basin during the 2018 and 2019 HABs Grabs, respectively. The bloom boundary poses substantial issues for spatial assessments because MC concentration varied by nearly two orders of magnitude over very short distances. The MC to chlorophyll ratio (MC:chl) varied by a factor up to 5.3 throughout the basin, which creates challenges for using MC:chl to predict MC concentrations. Many of the biomass metrics strongly correlated (r > 0.70) with each other except chlorophyll fluorescence and phycocyanin concentration. While MC and chlorophyll correlated well with total phosphorus and nitrogen concentrations, MC:chl correlated with dissolved inorganic nitrogen. More frequent MC data collection can overcome these issues, and models need to account for the MC:chl spatial heterogeneity when forecasting MCs.

Purpose: Randomized data assessing the longitudinal quality of life (QoL) impact of stereotactic ablative radiation therapy (SABR) in the oligometastatic setting are lacking. Methods and Materials: We enrolled patients who had a controlled primary malignancy with 1 to 5 metastatic lesions, with good performance status and life expectancy >6 months. We randomized in a 1:2 ratio between standard of care (SOC) treatment (SOC arm) and SOC plus SABR to all metastatic lesions (SABR arm). QoL was measured using the Functional Assessment of Cancer Therapy–General. QoL changes over time and between groups were assessed with linear mixed modeling. Results: Ninety-nine patients were randomized. Median age was 68 years (range, 43-89), and 60% were male. The most common primary tumor types were breast (n = 18), lung (n = 18), colorectal (n = 18), and prostate (n = 16). Most patients (n = 92) had 1 to 3 metastases. Median follow-up was 26 months. Because of the previously reported inferior survival of the SOC arm, the time for attrition in QoL respondents to

Rapid growth of Palmer amaranth (Amaranthus palmeri S. Watson) poses a challenge for timely management of this weed. Dose response studies were conducted in 2017 and 2018 under field and greenhouse conditions near Garden City and Manhattan, KS, respectively, to evaluate the efficacy of dicamba to control ≤10 cm, 15 cm, and 30 cm tall-Palmer amaranth that mimics three herbicide application timing: on time application (Day 0), and 1 (Day 1) and 4 days (Day 4) delay. Visual injury rating and reduction in shoot biomass (% of non-treated), and mortality were assessed at four weeks after treatment using a three- and four-parameter log-logistic model, in R software program. Increasing dicamba doses increased A. palmeri control regardless of plant height both in the field and greenhouse studies. The results suggest that delaying application one (15 cm) and four days (30 cm), resulted in a two- and 27-fold increase in the effective dose of dicamba on A. palmeri, respectively, under field conditions. However, in the greenhouse, for the same level of A. palmeri control, more than one- and two-fold increase in dicamba dose, respectively was required. Similarly, the effective dose of dicamba required for 50% reduction in A. palmeri shoot biomass (GR50) increased more than four- and eight-fold or more than one- and two-fold when dicamba application was delayed by one (15 cm) and four days (30 cm), in the field or in the greenhouse, respectively. To understand the basis of increased efficacy of dicamba in controlling early growth stage of A. palmeri, dicamba absorption and translocation studies were conducted. Results indicate a significant reduction in dicamba absorption (7%) and translocation (15%) with increase in A. palmeri height. Therefore, increased absorption and translocation of dicamba results in increased efficacy in improving A. palmeri control at early growth stage.

Remote sensing can advance the work of the Circumpolar Biodiversity Monitoring Program through monitoring of satellite-derived terrestrial and marine physical and ecological variables. Standardized data facilitate an unbiased comparison across variables and environments. Using MODIS standard products of land surface temperature, percent snow covered area, NDVI, EVI, phenology, burned area, marine chlorophyll, CDOM, sea surface temperature, and marine primary productivity, significant trends were observed in almost all variables between 2000 and 2017. Analysis of seasonal data revealed significant breakpoints in temporal trends. Within the terrestrial environment, data showed significant increasing trends in land surface temperature and NDVI. In the marine environment, significant increasing trends were detected in primary productivity. Significantly earlier onset of green up date was observed in bioclimate subzones C&E and longer end of growing season in B&E. Terrestrial and marine parameters showed similar rates of change with unidirectional change in terrestrial and significant directional and magnitude shifts in marine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13280-019-01249-z) contains supplementary material, which is available to authorized users.

Purpose Incidence of anal squamous cell carcinoma (ASCC) is increasing, with curative chemoradiotherapy (CRT) as the primary treatment of non-metastatic disease. A significant proportion of patients have locoregional treatment failure (LRF), but distant relapse is uncommon. Accurate prognostication of progression-free survival (PFS) would help personalisation of CRT regimens. The study aim was to evaluate novel imaging pre-treatment features, to prognosticate for PFS in ASCC. Methods Consecutive patients with ASCC treated with curative intent at a large tertiary referral centre who underwent pre-treatment FDG-PET/CT were included. Radiomic feature extraction was performed using LIFEx software on baseline FDG-PET/CT. Outcome data (PFS) was collated from electronic patient records. Elastic net regularisation and feature selection were used for logistic regression model generation on a randomly selected training cohort and applied to a validation cohort using TRIPOD guidelines. ROC-AUC analysis was used to compare performance of a regression model encompassing standard clinical prognostic factors (age, sex, tumour and nodal stage—model A), a radiomic feature model (model B) and a combined radiomic/clinical model (model C). Results A total of 189 patients were included in the study, with 145 in the training cohort and 44 in the validation cohort. Median follow-up was 35.1 and 37. 9 months, respectively for each cohort, with 70.3% and 68.2% reaching this time-point with PFS. GLCM entropy (a measure of randomness of distribution of co-occurring pixel grey-levels), NGLDM busyness (a measure of spatial frequency of changes in intensity between nearby voxels of different grey-level), minimum CT value (lowest HU within the lesion) and SMTV (a standardized version of MTV) were selected for inclusion in the prognostic model, alongside tumour and nodal stage. AUCs for performance of model A (clinical), B (radiomic) and C (radiomic/clinical) were 0.6355, 0.7403, 0.7412 in the training cohort and 0.6024, 0.6595, 0.7381 in the validation cohort. Conclusion Radiomic features extracted from pre-treatment FDG-PET/CT in patients with ASCC may provide better PFS prognosis than conventional staging parameters. With external validation, this might be useful to help personalise CRT regimens in the future. Electronic supplementary material The online version of this article (10.1007/s00259-019-04495-1) contains supplementary material, which is available to authorized users.

Inflammatory bowel disease (IBD) is a chronic, debilitating condition with a significant impact on quality of life. In spite of recent advances with antibody therapies, there remains a significant unmet medical need in IBD. Ongoing research and development efforts aim to identify new therapies that will increase remission rates beyond those achieved with current standard-of-care, while maintaining a high safety margin. This review will provide an overview of the small-molecule agents that are being explored in this regard.

The oxygen isotopic composition of lacustrine carbonate deposits has been frequently used to reconstruct paleoaltimetry of orogenic belts. However, the primary oxygen isotopic composition of lacustrine carbonate can be partially or wholly altered by post-depositional diagenetic processes, such as deep burial recrystallization and the interaction with geologically younger meteoric waters. To better understand how ancient lacustrine carbonates are diagenetically modified by meteoric waters, we present detailed mineralogy, petrography, stable carbon and oxygen isotopic compositions, and major and minor element geochemistry of lacustrine carbonates from the Miocene Wudaoliang Group, which underwent only shallow burial (

Background: The oligometastatic paradigm suggests that some patients with a limited number of metastases might be cured if all lesions are eradicated. Evidence from randomised controlled trials to support this paradigm is scarce. We aimed to assess the effect of stereotactic ablative radiotherapy (SABR) on survival, oncological outcomes, toxicity, and quality of life in patients with a controlled primary tumour and one to five oligometastatic lesions. Methods: This randomised, open-label phase 2 study was done at 10 hospitals in Canada, the Netherlands, Scotland, and Australia. Patients aged 18 or older with a controlled primary tumour and one to five metastatic lesions, Eastern Cooperative Oncology Group score of 0–1, and a life expectancy of at least 6 months were eligible. After stratifying by the number of metastases (1–3 vs 4–5), we randomly assigned patients (1:2) to receive either palliative standard of care treatments alone (control group), or standard of care plus SABR to all metastatic lesions (SABR group), using a computer-generated randomisation list with permuted blocks of nine. Neither patients nor physicians were masked to treatment allocation. The primary endpoint was overall survival. We used a randomised phase 2 screening design with a two-sided α of 0·20 (wherein p

Dicamba-resistant (DR) kochia is an increasing concern for growers in the US Great Plains, including Kansas. Greenhouse and field experiments (Garden City and Tribune, KS, in the 2014 to 2015 growing season) were conducted to characterize the dicamba resistance levels in two recently evolved DR kochia accessions collected from fallow fields (wheat–sorghum–fallow rotation) near Hays, KS, and to determine the effectiveness of various PRE herbicide tank mixtures applied in fall or spring prior to the fallow year. Dicamba dose–response studies indicated that the KS-110 and KS-113 accessions had 5- to 8-fold resistance to dicamba, respectively, relative to a dicamba-susceptible (DS) accession. In separate field studies, atrazine-based PRE herbicide tank mixtures, dicamba + pendimethalin + sulfentrazone, and metribuzin + sulfentrazone when applied in the spring had excellent kochia control (85% to 95%) for 3 to 4 mo at the Garden City and Tribune sites. In contrast, kochia control with those PRE herbicide tank mixtures when applied in the fall did not exceed 79% at the later evaluation dates. In conclusion, the tested kochia accessions from western Kansas had evolved moderate to high levels of resistance to dicamba. Growers should utilize these effective PRE herbicide tank mixtures (multiple sites of action) in early spring to manage kochia seed bank during the summer fallow phase of this 3-yr crop rotation (wheat–corn/sorghum–fallow) in the Central Great Plains.

Evolution and rapid spread of herbicide-resistant (HR) kochia has become a significant challenge for growers in the U.S. Great Plains. The main objectives of this research were to confirm and characterize the response of putative auxinic HR (Aux-HR) kochia accessions (designated as KS-4A, KS-4D, KS-4H, KS-10A, KS-10-G, and KS-10H) collected from two different corn fields near Garden City, KS, to dicamba and fluroxypyr and to determine the EPSPS gene copy number to detect whether those accessions were also resistant to glyphosate. Single-dose experiments indicated that putative Aux-HR kochia accessions had 78% to 100% and 85% to 100% survivors when treated with dicamba (560 g ae ha−1) and fluroxypyr (235 g ae ha−1), respectively. Whole-plant dicamba dose–response studies revealed that the selected Aux-HR accessions had 2.9- to 15.1- and 3.1- to 9.4-fold resistance to dicamba relative to two susceptible accessions (MT-SUS and KS-SUS). In a separate fluroxypyr dose–response experiment, the selected Aux-HR accessions also exhibited 3.8- to 7.3- and 3.0- to 8.6-fold resistance to fluroxypyr on the basis of shoot fresh and dry weight responses, respectively. The confirmed Aux-HR kochia accessions also had 3 to 13 EPSPS gene copies relative to MT-SUS and KS-SUS accessions (each with 1 EPSPS gene copy). These results suggest that the putative Aux-HR kochia accessions from Kansas had developed moderate to high levels of cross-resistance to dicamba and fluroxypyr and low to high levels of resistance to glyphosate. This is the first confirmation of kochia accessions with cross-resistance to dicamba and fluroxypyr in Kansas. Growers should use diverse kochia control programs, including the proper use of dicamba and fluroxypyr stewardship, use of cover crops, occasional tillage, diversified crop rotations, and alternative effective herbicides to prevent further evolution and spread of Aux-HR kochia on their fields.

The Central Andes of South America are one of the highest and broadest mountain ranges on earth and have a profound influence on climate in the Southern Hemisphere. Yet, the timing of Andean uplift and its subsequent impact on atmospheric circulation is not well known. Here we use fossil soils from along an 800-km transect (19–25°S) in the Atacama Desert of northern Chile to identify the initiation of extreme aridity along the west coast of South America and infer a minimum age for the development of the Central Andean rain-shadow. Paleosols record the onset of extreme aridity at the boundary between the middle and late Miocene (12–10 Ma). Lower Miocene (24–20 Ma) soils are chemically weathered and contain soil carbonate, indicative of a vegetated landscape and semi-arid climate. In contrast, gypsum dominates massive (2–5 m thick) upper middle Miocene soils that formed on a hyperarid landscape devoid of vegetation. The development of extreme hyperaridity is linked to the formation of the Central Andean rain-shadow through the divergence of oxygen isotope values. Oxygen isotope values of lower Miocene soil carbonates in the Atacama Desert ( − 5.0 ± 1.1 ‰ VPDB) and Central Andes ( − 7.8 ± 1 ‰ ) are similar, indicating no or a limited rain-shadow. By 15 Mya, however, δ 18 O values of soil carbonate differ by ∼8‰, with values of soil carbonate in Altiplano paleosols getting lower due to uplift while soil carbonate values in the Atacama Desert get higher due to aridity. Therefore, by 15 Mya there is clear evidence for a rain-shadow from the Central Andes. By the latest middle Miocene (ca. 12–10 Ma), paleosols in the Altiplano decreased to − 11.8 ± 1.0 ‰ while soils in the Atacama Desert increase to + 1.5 ± 4.5 ‰ . This almost 14‰ divergence in the δ 18 O values of soil carbonate for soils only ∼250 km apart is evidence of a strong Central Andes rain-shadow effect in place during the late middle Miocene (12–10 Ma).

Background Positron emission tomography (PET) using anti-1-amino-3-18fluorine-fluorocyclobutane-1-carboxylic acid (18F-fluciclovine) shows preferential glioma cell uptake with low activity in normal brain. Dynamic contrast-enhanced (DCE) MRI may also be used to investigate regions of glioma that do not show gadolinium-enhancement on post-contrast T1-weighted MR sequences (Gd-T1) and may reflect tumour infiltration beyond the Gd-T1 enhancing margin. There is a paucity of data on how 18F-fluciclovine uptake correlates with Gd-T1 and DCE-MRI activity, how it correlates with tumour biology and whether significant changes in uptake occur during treatment. The aims of this pilot study were: 1 To compare 18F-fluciclovine PET, DCE-MRI and Gd-T1 in patients undergoing chemoradiotherapy for glioblastoma (GBM) 2 To investigate correlation between 18F-fluciclovine uptake, MRI findings, and tumour biology in a pre-clinical glioma model. Material and Methods 18F-fluciclovine-PET-CT and MRI including DCE-MRI were acquired before, during and after adjuvant chemoradiotherapy (60 Gy in 30 fractions with temozolomide) in GBM patients. DCE-MRI and Gd-T1 volumes were manually contoured, and PET volumes defined using semi-automatic thresholding. Gd-T1 was subtracted from PET and DCE-MRI volumes to identify areas beyond the Gd-T1 volume boundary and similarity of the PET and DCE-MRI volumes outside the Gd-T1 volume boundary were measured using the Dice similarity coefficient (DSC). CT-2A tumour cells were stereotactically injected into the right striatum of 8 to 10-week-old C57BL6J mice and they underwent MRI and 18F-fluciclovine PET-CT. Post-mortem mice brains underwent immunohistochemistry staining for ASCT2 (amino acid transporter), nestin (stemness) and Ki-67 (proliferation) to assess for biologically active tumour. Results 6 patients were recruited (GBM 1-6). For GBM 1-3: PET volumes were greater than DCE-MRI, in turn greater than Gd-T1. For GBM 4-6, Gd-T1 volumes were similar to DCE-MRI and both were greater than PET volumes. GBM 1-3 had lower overall survival than GBM 4-6: median 249 vs. 903 days. 18F-fluciclovine uptake and Gd uptake (on DCE-MRI) was seen beyond the margins of the standard Gd-T1 volume. Comparing these regions beyond the Gd-T1 margins, the PET and DCE-MRI had low DSC, suggesting distinct areas of fluciclovine and DCE-MRI uptake. Pre-clinical PET-CT demonstrated tumour-specific 18F-fluciclovine uptake which corresponded to biologically active tumour based on immunostaining for Ki-67, nestin and ASCT2. Conclusion Results from this joint pre-clinical and clinical pilot study suggest volumes of 18F-fluciclovine-PET activity beyond that depicted by MRI-DCE and Gd-T1 are associated with a poorer prognosis in patients undergoing chemoradiotherapy for GBM. The pre-clinical model confirmed 18F-fluciclovine uptake reflected biologically active tumour.