Evaluation of the AGDISP ground boom spray drift model

AGDISP is a well-established spray drift model that has been validated for aerial spraying of forests. Recently a prototypical ground boom option has been added to AGDISP. This was evaluated in the current study by collecting data from spray trials over a grass sward using a ground boom sprayer and representative application parameters. Spray solutions were made up of water, sticker adjuvant and a metal cation, which was changed for each spray application. Deposition from spray drift was measured by analyses of the cation deposits on artificial targets (plastic tapes) placed on the grass surface. Measured deposition was compared with profiles calculated using AGDISP. AGDISP overpredicted deposition from spray drift by a factor of 3.5-100 outside the spray block. Possible reasons for these discrepancies are given. Options are to improve measured deposition and the algorithms for the deposition on the downwind swath of the spray block and evaporation of droplets

The HSP90 inhibitor ganetespib: a potential effective agent for Acute Myeloid Leukemia in combination with cytarabine

HSP90 is a multi-client chaperone involved in regulating a large array of cellular processes and is commonly overexpressed in many different cancer types including hematological malignancies. Inhibition of HSP90 holds promise for targeting multiple molecular abnormalities and is therefore an attractive target for heterogeneous malignancies such as Acute Myeloid Leukemia (AML). Ganetespib is a highly potent second generation HSP90 inhibitor which we show is significantly more effective against primary AML blasts at nanomolar concentrations when compared with cytarabine (p < 0.001). Dose dependant cytotoxicity was observed with an apoptotic response coordinate with the loss of pro-survival signaling through the client protein AKT. Combination treatment of primary blasts with ganetespib and cytarabine showed good synergistic interaction (combination index (CI): 0.47) across a range of drug effects with associated reduction in HSP70 feedback and AKT signaling levels. In summary, we show ganetespib to have high activity in primary AMLs as a monotherapy and a synergistic relationship with cytarabine when combined. The combination of cytotoxic cell death, suppression of cytoprotective/drug resistance mechanisms such as AKT and reduced clinical toxicity compared to other HSP90 inhibitors provide strong rationale for the clinical assessment of ganetespib in AML

Lkb1 Deficiency Alters Goblet and Paneth Cell Differentiation in the Small Intestine

The Lkb1 tumour suppressor is a multitasking kinase participating in a range of physiological processes. We have determined the impact of Lkb1 deficiency on intestinal homeostasis, particularly focussing on secretory cell differentiation and development since we observe strong expression of Lkb1 in normal small intestine Paneth and goblet cells. We crossed mice bearing an Lkb1 allele flanked with LoxP sites with those carrying a Cyp1a1-specific inducible Cre recombinase. Lkb1 was efficiently deleted from the epithelial cells of the mouse intestine after intraperitoneal injection of the inducing agent β-naphthoflavone. Bi-allelic loss of Lkb1 led to the perturbed development of Paneth and goblet cell lineages. These changes were characterised by the lack of Delta ligand expression in Lkb1-deficient secretory cells and a significant increase in the levels of the downstream Notch signalling effector Hes5 but not Hes1. Our data show that Lkb1 is required for the normal differentiation of secretory cell lineages within the intestine, and that Lkb1 deficiency modulates Notch signalling modulation in post-mitotic cells

Proteins that bind methylated DNA and human cancer: reading the wrong words

DNA methylation and the machinery involved in epigenetic regulation are key elements in the maintenance of cellular homeostasis. Epigenetic mechanisms are involved in embryonic development and the establishment of tissue-specific expression, X-chromosome inactivation and imprinting patterns, and maintenance of chromosome stability. The balance between all the enzymes and factors involved in DNA methylation and its interpretation by different groups of nuclear factors is crucial for normal cell behaviour. In cancer and other diseases, misregulation of epigenetic marks is a common feature, also including DNA methylation and histone post-translational modifications. In this scenario, it is worth mentioning a family of proteins characterized by the presence of a methyl-CpG-binding domain (MBDs) that are involved in interpreting the information encoded by DNA methylation and the recruitment of the enzymes responsible for establishing a silenced state of the chromatin. The generation of novel aberrantly hypermethylated regions during cancer development and progression makes MBD proteins interesting targets for their biological and clinical implications

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Characterization of synthetic and commercial trisiloxane surfactant materials

The organosilicone surfactant Silwet L-77® (L-77), used as an agrochemical adjuvant, is a mixture comprised predominantly of [(CH₃)₃SiO]₂ (CH₃)Si (CH₂)₃ (OCH₂CH₂)n OCH₃ oligomers (n = 3-16, average n 7.5). The commercially available L-77 mixture was purified by reversed-phase high-performance liquid chromatography (HPLC) to obtain individual trisiloxane surfactant components. Pure oligomers (n = 3, 6 and 9) were also synthesized. Synthesis was achieved by hydrosilylation of monomeric ethoxylate monomethyl ether starting reagents. Pure hexa- and nona-ethylene glycols were produced by condensation of smaller oligomers. Atmospheric-pressure ionization mass spectrometry (MS) methods were used to characterize fully the commercial L-77 product and synthesized or isolated components. The application of Fourier-transform ion cyclotron resonance MS and online HPLC-electrospray ionization MS techniques to the analysis of this surfactant are described here. The application of these analytical techniques also enabled elucidation of the synthetic by-products present in the commercial formulation