thereby establishing the full impact of odonate predation on prey communities. © 2020 British Ecological Society.Sphingolipid metabolism is increasingly recognised as a therapeutic target in cancer due to its regulation of cell proliferation and apoptosis. The sphingolipid rheostat is proposed to control cell fate through maintaining balance between pro-apoptotic and pro-survival sphingolipids. This balance is regulated by metabolising enzymes involved in sphingolipid production. One such enzyme, sphingosine kinase-2 (SPHK2), produces pro-survival sphingosine 1-phosphate (S1P) by phosphorylation of pro-apoptotic sphingosine. Elevated SPHK2 has been found in multiple cancer types and contributes to cell survival, chemotherapeutic resistance and apoptosis resistance. We have previously shown elevation of S1P in large granular lymphocyte (LGL) leukaemia serum and cells isolated from patients. Here, we examined SPHK2 expression in LGL leukaemia and found SPHK2 mRNA and protein upregulation in a majority of LGL leukaemia patient samples. Knockdown of SPHK2 with siRNA in LGL leukaemia cell lines decreased proliferation. Additionally, the use of ABC294640 or K145, both SPHK2-specific inhibitors, decreased viability of LGL leukaemia cell lines. ABC294640 selectively induced apoptosis in LGL cell lines and freshly isolated LGL leukaemia patient cells compared to normal controls. Mechanistically, SPHK2 inhibition downregulated pro-survival myeloid cell leukaemia-1 (Mcl-1) protein through proteasomal degradation. Targeting of SPHK2 therefore provides a novel therapeutic approach for the treatment of LGL leukaemia. © 2020 British Society for Haematology and John Wiley & Sons Ltd.BACKGROUND Composite outcomes may more accurately reflect patient and provider expectations around optimal care. We sought to determine the impact of achieving a so-called "textbook oncologic outcome" (TOO) among patients undergoing resection of pancreatic adenocarcinoma (PDAC). METHODS Patients undergoing pancreaticoduodenectomy (PD) for PDAC between 2006 and 2016 were identified in the National Cancer Database (NCDB). TOO was defined by margin negative resection, compliant lymph node evaluation, no prolonged length-of-stay, no 30-day readmission/mortality, and receipt of adjuvant chemotherapy. Factors associated with TOO and overall survival (OS) were evaluated using multivariable logistic and Cox regression models, respectively. RESULTS Among 18 608 patients who underwent PD at 782 hospitals, many patients successfully achieved certain TOO factors such as R0 margin (77.9%) and no 30-day mortality (96.9%), while other TOO criteria such as receipt of adjuvant therapy (48.2%) were achieved less frequently. Overall, only 3124 (16.8%) patients achieved a TOO. Factors associated with lower odds of TOO included older age, Black race, Medicaid insurance, Community facility, and low PD facility ( less then 20 PD/y) (all P  less then  .05). Achievement of a TOO was associated with lower risk of mortality (HR 0.74; 95% CI, 0.70-0.77). CONCLUSIONS While TOO was associated with improved long-term survival, TOO was only achieved in 16.8% of patients undergoing PD. © 2020 Wiley Periodicals, Inc.AIM To compare anterior and posterior standing balance reactions, as measured by single-stepping thresholds, in children with and without spastic cerebral palsy (CP).  https://www.selleckchem.com/products/Docetaxel(Taxotere).html  METHOD Seventeen ambulatory children with spastic CP (eight males, nine females) and 28 typically developing children (13 males, 15 females; age range 5-12y, mean [SD] 9y 2mo [2y 3mo]), were included in this cross-sectional, observational study. Balance reaction skill was quantified as anterior and posterior single-stepping thresholds, or the treadmill-induced perturbations that consistently elicited a step in that direction. In order to understand the underlying mechanisms of between-group differences in stepping thresholds, dynamic stability was quantified using the minimum margin of stability. Ankle muscle activation latency, magnitude, and co-contraction were assessed with surface electromyography. RESULTS We observed an age and group interaction for anterior thresholds (p=0.001, partial η2 =0.24). At older (≈11y; p less then 0.001, partial η2 =0.48), but not younger (≈7y; p=0.33, partial η2 =0.02) ages, typically developing children had larger anterior thresholds than those with CP. In response to near-threshold anterior perturbations, older typically developing children recovered from more instability than their peers with CP (p=0.004, partial η2 =0.18). Older children had no between-group differences in ankle muscle activity. No between-group differences were observed in posterior thresholds. INTERPRETATION The effects of CP on balance reactions are age- and direction-specific. Older typically developing children are more able or willing to withhold a step when unstable. © 2020 Mac Keith Press.Transplant-associated thrombotic microangiopathy (TA-TMA) is a complication of allogeneic transplantation (allo-HCT). The incidence and risk factors associated with TA-TMA are not well known. A retrospective analysis from the Center for International Blood and Marrow Transplant Research (CIBMTR) was conducted including patients receiving allo-HCT between 2008 and 2016, with the primary objective of evaluating the incidence of TA-TMA. Secondary objectives included identification of risk factors associated with TA-TMA, and the impact of TA-TMA on overall survival and the need for renal replacement therapy (RRT). Among 23,665 allo-HCT recipients, the 3-year cumulative incidence of TA-TMA was 3%. Variables independently-associated with increased incidence of TA-TMA included female sex, prior autologous transplant, primary disease (acute lymphoblastic leukaemia and severe aplastic anaemia), donor type (mismatched or unrelated donor), conditioning intensity (myeloablative), GVHD prophylaxis (sirolimus + calcineurin inhibitor), pre-transplant kidney dysfunction and acute GVHD (time-varying effect). TA-TMA was associated with higher mortality (HR = 3·1, 95% Confidence Interval [CI] = 2·8-16·3) and RRT requirement (HR = 7·1, 95% CI = 5·7-311·6). This study provides epidemiologic data on TA-TMA and its impact on transplant outcomes. Increased awareness of the risk factors will enable providers to be vigilant of this uncommon but serious transplant complication. The results will also provide benchmarking for future study designs and comparisons. © 2020 British Society for Haematology and John Wiley & Sons Ltd.