Understanding the factors influencing fall armyworm (Spodoptera frugiperda J.E. Smith) damage in African smallholder maize fields and quantifying its impact on yield: a case study in eastern Zimbabwe

Open Access Article; Published online: 26 Jan 2019Fall armyworm (FAW, Spodoptera frugiperda J.E. Smith) is an invasive lepidopteran pest established in most of sub-Saharan Africa since 2016. Although the immediate reaction of governments has been to invest in chemical pesticides, control methods based on agronomic management would be more affordable to resource-constrained smallholders and minimize risks for health and the environment. However, little is known about the most effective agronomic practices that could control FAW under typical African smallholder conditions. In addition, the impact of FAW damage on yield in Africa has been reported as very large, but these estimates are mainly based on farmers' perceptions, and not on rigorous field scouting methods. Thus, the objectives of this study were to understand the factors influencing FAW damage in African smallholder maize fields and quantify its impact on yield, using two districts of Eastern Zimbabwe as cases. A total of 791 smallholder maize plots were scouted for FAW damage and the head of the corresponding farming household interviewed. Grain yield was later determined in about 20% of these fields. FAW damage was found to be significantly reduced by frequent weeding operations and by minimum- and zero-tillage. Conversely, pumpkin intercropping was found to significantly increase FAW damage. FAW damage was also found to be higher for some maize varieties, although these varieties may not be the lowest yielding. If the incidence of plants with FAW damage symptoms recorded in this research (32–48%, depending on the estimate used) is commensurate with what other studies conducted on the continent found, our best estimate of the impact of FAW damage on yield (11.57%) is much lower than what these studies reported. Although our study presents limitations, losses due to FAW damage in Africa could have been over-estimated. The threat that FAW represents for African smallholders, although very real, should not divert attention away from other pressing challenges they face

Yield potentiality of maize as relay crop with T. Aman rice under different agronomic management

The experiment was conducted at the Regional Agricultural Research Station, BARI, Ishwardi, Pabna, Bangladesh, during 2013-2014 and 2014- 2015 to introduce maize as relay crop with T. Aman rice under different agronomic practices for determine the production potentials. The experiment was design split plot with three replications. The agronomic management practices included four plant spacing viz. S1=75 cm×20 cm (66666 plants/ha), S2=60 cm×20 cm (83333 plants/ha), S3=50 cm×20 cm (100000 plants/ha) and S4=40 cm×20 cm (125000 plants/ha) and four soil management practices viz. M1=soil mulching at 25 DAE, M2=earthing up at 25 DAE, M3=straw mulching at 25 DAE and M4= without earthing up and mulching (control). Seeds were relayed by dibbling manually in 10 days before the harvest of T. Aman rice. Results showed that an increasing plant spacing increased leaf area Index (LAI), total dry matter (TDM), crop growth rate (CGR) and light energy interception (LEI). Grain yield was higher in S3 spacing (8.44 t/ha) than others (S4 8.11 t/ha, S2 7.34 t/ha and S1 6.89 t/ha). Among the soil management practices, M2 increased LAI, TDM, CGR, LEI as well as grain yield. Moreover, M2 and M1 gave similar grain yield (8.22 t/ha and 8.02 t/ha), that were significantly greater than other two soil management practices (M3 7.55 t/ha and M4 6.98 t/ha). From the economic point of view, combination of S3M1 gave better performance with gross margin of Tk. 95000/ha and BCR of 2.17. On the basis of results, S3M1 combination was suitable for growing maize under relay sowing with T. Aman rice

Conservation agriculture with optimum fertilizer nitrogen rate reduces GWP for rice cultivation in floodplain soils

Wetland rice cultivation contributes significantly to global warming potential (GWP), an effect which is largely attributed to emissions of methane (CH4). Emerging technologies for wetland rice production such as conservation agriculture (CA) may mitigate greenhouse gas (GHG) emissions, but the effects are not well defined. Investigations were carried out in an irrigated rice (Boro rice) field in the fifth crop after conversion of conventional tillage (CT) to strip tillage (ST). Two crop residue levels (low versus high, LR versus HR) and three nitrogen (N) application rates (N1 = 108, N2 = 144, and N3 = 180 kg N ha−1) were laid out in a split-plot experiment with three replicates. Yield-scaled GHG emissions and GWP were estimated to evaluate the impacts of CA on mitigating CH4 and N2O emissions in the rice paddy field. There was a 55% higher N2O emission in ST with HR coupled with N3 than that in CT with LR coupled with N1. The N2O emission factors ranged from 0.43 to 0.75% in ST and 0.45 to 0.59% in CT, irrespective of the residue level and N rate. By contrast, CH4 emissions were significantly lower in CA than in the conventional practices (CT plus LR). The ST with LR in N2 reduced the GWP by 39% over the GWP in CT with HR in N1 and 16% over the conventional practices. Based on our investigation of the combination of tillage, residue, and N rate treatments, the adoption of CA with high and low residue levels reduced the GWP by 10 and 16%, respectively, because of lower CH4 and N2O emissions than the current management practices. The relatively high N2O emission factors suggest that mitigation of this GHG in wetland rice systems needs greater attention

The STRATAA study protocol: a programme to assess the burden of enteric fever in Bangladesh, Malawi and Nepal using prospective population census, passive surveillance, serological studies and healthcare utilisation surveys.

Introduction Invasive infections caused by Salmonella enterica serovar Typhi and Paratyphi A are estimated to account for 12–27 million febrile illness episodes worldwide annually. Determining the true burden of typhoidal Salmonellae infections is hindered by lack of population-based studies and adequate laboratory diagnostics. The Strategic Typhoid alliance across Africa and Asia study takes a systematic approach to measuring the age-stratified burden of clinical and subclinical disease caused by typhoidal Salmonellae infections at three high-incidence urban sites in Africa and Asia. We aim to explore the natural history of Salmonella transmission in endemic settings, addressing key uncertainties relating to the epidemiology of enteric fever identified through mathematical models, and enabling optimisation of vaccine strategies. Methods/design Using census-defined denominator populations of ≥100 000 individuals at sites in Malawi, Bangladesh and Nepal, the primary outcome is to characterise the burden of enteric fever in these populations over a 24-month period. During passive surveillance, clinical and household data, and laboratory samples will be collected from febrile individuals. In parallel, healthcare utilisation and water, sanitation and hygiene surveys will be performed to characterise healthcare-seeking behaviour and assess potential routes of transmission. The rates of both undiagnosed and subclinical exposure to typhoidal Salmonellae (seroincidence), identification of chronic carriage and population seroprevalence of typhoid infection will be assessed through age-stratified serosurveys performed at each site. Secondary attack rates will be estimated among household contacts of acute enteric fever cases and possible chronic carriers. Ethics and dissemination This protocol has been ethically approved by the Oxford Tropical Research Ethics Committee, the icddr,b Institutional Review Board, the Malawian National Health Sciences Research Committee and College of Medicine Research Ethics Committee and Nepal Health Research Council. The study is being conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Informed consent was obtained before study enrolment. Results will be submitted to international peer-reviewed journals and presented at international conferences. Trial registration number ISRCTN 12131979. Ethics references Oxford (Oxford Tropical Research Ethics Committee 39-15). Bangladesh (icddr,b Institutional Review Board PR-15119). Malawi (National Health Sciences Research Committee 15/5/1599). Nepal (Nepal Health Research Council 306/2015)

Single coronary artery from the right sinus of Valsalva

We describe a case of a single coronary artery originating from the right coronary sinus and bifurcating into the left coronary artery (LCA) and right coronary artery (RCA) in a 74-year old woman, with a non-ST elevation acute myocardial infarction (NSTEMI). Diagnosis was made by coronary angiography which ruled out stenosis, and showed normal LCA and RCA branching. The connection path of LCA, with the opposite cusp, was defined retroaortic by multislice computed tomography (CT). The variants of this coronary anomaly, together with their clinical implications and pathophysiology of acute myocardial infarction (AMI) are discussed. Multislice CT is fundamental for clinical decision making

IL-7 Receptor Mutations and Steroid Resistance in Pediatric T cell Acute Lymphoblastic Leukemia: A Genome Sequencing Study

Background: Pediatric acute lymphoblastic leukemia (ALL) is the most common childhood cancer and the leading cause of cancer-related mortality in children. T cell ALL (T-ALL) represents about 15% of pediatric ALL cases and is considered a high-risk disease. T-ALL is often associated with resistance to treatment, including steroids, which are currently the cornerstone for treating ALL; moreover, initial steroid response strongly predicts survival and cure. However, the cellular mechanisms underlying steroid resistance in T-ALL patients are poorly understood. In this study, we combined various genomic datasets in order to identify candidate genetic mechanisms underlying steroid resistance in children undergoing T-ALL treatment. Methods and Findings: We performed whole genome sequencing on paired pre-treatment (diagnostic) and post-treatment (remission) samples from 13 patients, and targeted exome sequencing of pre-treatment samples from 69 additional T-ALL patients. We then integrated mutation data with copy number data for 151 mutated genes, and this integrated dataset was tested for associations of mutations with clinical outcomes and in vitro drug response. Our analysis revealed that mutations in JAK1 and KRAS, two genes encoding components of the interleukin 7 receptor (IL7R) signaling pathway, were associated with steroid resistance and poor outcome. We then sequenced JAK1, KRAS, and other genes in this pathway, including IL7R, JAK3, NF1, NRAS, and AKT, in these 69 T-ALL patients and a further 77 T-ALL patients. We identified mutations in 32% (47/146) of patients, the majority of whom had a specific T-ALL subtype (early thymic progenitor ALL or TLX). Based on the outcomes of these patients and their prednisolone responsiveness measured in vitro, we then confirmed that these mutations were associated with both steroid resistance and poor outcome. To explore how these mutations in IL7R signaling pathway genes cause steroid resistance and subsequent poor outcome, we expressed wild-type and mutant IL7R signaling molecules in two steroid-sensitive T-ALL cell lines (SUPT1 and P12 Ichikawa cells) using inducible lentiviral expression constructs. We found that expressing mutant IL7R, JAK1, or NRAS, or wild-type NRAS or AKT, specifically induced steroid resistance without affecting sensitivity to vincristine or L-asparaginase. In contrast, wild-type IL7R, JAK1, and JAK3, as well as mutant JAK3 and mutant AKT, had no effect. We then performed a functional study to examine the mechanisms underlying steroid resistance and found that, rather than changing the steroid receptor’s ability to activate downstream targets, steroid resistance was associated with strong activation of MEK-ERK and AKT, downstream components of the IL7R signaling pathway, thereby inducing a robust antiapoptotic response by upregulating MCL1 and BCLXL expression. Both the MEK-ERK and AKT pathways also inactivate BIM, an essential molecule for steroid-induced cell death, and inhibit GSK3B, an important regulator of proapoptotic BIM. Importantly, treating our cell lines with IL7R signaling inhibitors restored steroid sensitivity. To address clinical relevance, we treated primary T-ALL cells obtained from 11 patients with steroids either alone or in combination with IL7R signaling inhibitors; we found that including a MEK, AKT, mTOR, or dual PI3K/mTOR inhibitor strongly increased steroid-induced cell death. Therefore, combining these inhibitors with steroid treatment may enhance steroid sensitivity in pat

Antitumor activity of lurbinectedin in second-line small cell lung cancer patients who are candidates for re-challenge with the first-line treatment

Introduction: The National Comprehensive Cancer Network guidelines recommend re-challenge with the first-line treatment for relapsed small cell lung cancer (SCLC) with chemotherapy-free interval (CTFI)=180 days. A phase II study (NCT02454972) showed remarkable antitumor activity in SCLC patients treated with lurbinectedin 3.2 mg/m2 1 -h intravenous infusion every 3 weeks as second-line therapy. We report results for the pre-planned subset of patients with CTFI = 180 days. Material and Methods: Twenty patients aged =18 years with pathologically proven SCLC diagnosis, pretreated with only one prior platinum-containing line, no CNS metastases, and with CTFI = 180 days were evaluated. The primary efficacy endpoint was the overall response rate (ORR) assessed by the Investigators according to RECIST v1.1. Results: ORR was 60.0 % (95 %CI, 36.1-86.9), with a median duration of response of 5.5 months (95 %CI, 2.9-11.2) and disease control rate of 95.0 % (95 %CI, 75.1-99.9). Median progression-free survival was 4.6 months (95 %CI, 2.6-7.3). With a censoring of 55.0 %, the median overall survival was 16.2 months (95 %CI, 9.6-upper level not reached). Of note, 60.9 % and 27.1 % of patients were alive at 1 and 2 years, respectively. The most common grade 3/4 adverse events and laboratory abnormalities were hematological disorders (neutropenia, 55.0 %; anemia; 10.0 % thrombocytopenia, 10.0 %), fatigue (10.0 %) and increased liver function tests (GGT, 10 %; ALT and AP, 5.0 % each). No febrile neutropenia was reported. Conclusion: Lurbinectedin is an effective treatment for platinum-sensitive relapsed SCLC, especially in patients with CTFI = 180 days, with acceptable safety and tolerability. These encouraging results suggest that lurbinectedin can be another valuable therapeutic option rather than platinum re-challenge

Reducing nitrous oxide emissions by changing N fertiliser use from calcium ammonium nitrate (CAN) to urea based formulations

This research was financially supported under the National Development Plan, through the Research Stimulus Fund, administered by the Department of Agriculture, Food and the Marine (Grant numbers RSF10-/RD/SC/716 and RSF11S138) and from the Department of Agriculture and Rural Development (Ref: DARD Evidence and Innovation project 13/04/06) for Northern Ireland. The first author gratefully acknowledges funding received from the Teagasc Walsh Fellowship Scheme (Ref: 2012005).peer-reviewedThe accelerating use of synthetic nitrogen (N) fertilisers, to meet the world's growing food demand, is the primary driver for increased atmospheric concentrations of nitrous oxide (N2O). The IPCC default emission factor (EF) for N2O from soils is 1% of the N applied, irrespective of its form. However, N2O emissions tend to be higher from nitrate-containing fertilisers e.g. calcium ammonium nitrate (CAN) compared to urea, particularly in regions, which have mild, wet climates and high organic matter soils. Urea can be an inefficient N source due to NH3 volatilisation, but nitrogen stabilisers (urease and nitrification inhibitors) can improve its efficacy. This study evaluated the impact of switching fertiliser formulation from calcium ammonium nitrate (CAN) to urea-based products, as a potential mitigation strategy to reduce N2O emissions at six temperate grassland sites on the island of Ireland. The surface applied formulations included CAN, urea and urea with the urease inhibitor N-(n-butyl) thiophosphoric triamide (NBPT) and/or the nitrification inhibitor dicyandiamide (DCD). Results showed that N2O emissions were significantly affected by fertiliser formulation, soil type and climatic conditions. The direct N2O emission factor (EF) from CAN averaged 1.49% overall sites, but was highly variable, ranging from 0.58% to 3.81. Amending urea with NBPT, to reduce ammonia volatilisation, resulted in an average EF of 0.40% (ranging from 0.21 to 0.69%)-compared to an average EF of 0.25% for urea (ranging from 0.1 to 0.49%), with both fertilisers significantly lower and less variable than CAN. Cumulative N2O emissions from urea amended with both NBPT and DCD were not significantly different from background levels. Switching from CAN to stabilised urea formulations was found to be an effective strategy to reduce N2O emissions, particularly in wet, temperate grassland.Department of Agriculture and Rural Development for Northern IrelandTeagasc Walsh Fellowship ProgrammeDepartment of Agriculture, Food and the Marin

PGE2 inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function.

Expansion of antigen-experienced CD8+ T cells is critical for the success of tumour-infiltrating lymphocyte (TIL)-adoptive cell therapy (ACT) in patients with cancer1. Interleukin-2 (IL-2) acts as a key regulator of CD8+ cytotoxic T lymphocyte functions by promoting expansion and cytotoxic capability2,3. Therefore, it is essential to comprehend mechanistic barriers to IL-2 sensing in the tumour microenvironment to implement strategies to reinvigorate IL-2 responsiveness and T cell antitumour responses. Here we report that prostaglandin E2 (PGE2), a known negative regulator of immune response in the tumour microenvironment4,5, is present at high concentrations in tumour tissue from patients and leads to impaired IL-2 sensing in human CD8+ TILs via the PGE2 receptors EP2 and EP4. Mechanistically, PGE2 inhibits IL-2 sensing in TILs by downregulating the IL-2Rγc chain, resulting in defective assembly of IL-2Rβ-IL2Rγc membrane dimers. This results in impaired IL-2-mTOR adaptation and PGC1α transcriptional repression, causing oxidative stress and ferroptotic cell death in tumour-reactive TILs. Inhibition of PGE2 signalling to EP2 and EP4 during TIL expansion for ACT resulted in increased IL-2 sensing, leading to enhanced proliferation of tumour-reactive TILs and enhanced tumour control once the cells were transferred in vivo. Our study reveals fundamental features that underlie impairment of human TILs mediated by PGE2 in the tumour microenvironment. These findings have therapeutic implications for cancer immunotherapy and cell therapy, and enable the development of targeted strategies to enhance IL-2 sensing and amplify the IL-2 response in TILs, thereby promoting the expansion of effector T cells with enhanced therapeutic potential