Studies on exploiting semiochemicals for pest management in organic farming systems OF0188

This study addresses the extent to which pest management systems can exploit semiochemicals (defined below) in ways acceptable to organic farming, and determines where the science base needs to be expanded to accommodate specific problems arising in an increasing organic farming sector. It considers whether current knowledge of semiochemical release from particular crop plants, herbs and wild plant species could be investigated further in relation to organic farming practice and identifies how strategies of multiple cropping, that exploit known semiochemical interactions, could be applied to key pest problems in organic production. Where such exploitation is not feasible, other strategies using semiochemicals including traps, extracts of natural products and nature-identical synthetic products are considered. Finally, general and specific directions in which research and development could facilitate greater penetration of the use of semiochemicals in crop protection for organic farming are identified. Semiochemicals are natural products that, by acting as signals, regulate interactions between organisms e.g. plants and insects. Once the semiochemical interactions between a pest and its host plant have been elucidated they can be exploited to regulate the pest population, providing an alternative control strategy to conventional toxicants. The choice of approach by which the semiochemicals are deployed relates to three options, i.e. from a natural plant source, from an extract or as a nature identical synthetic product. However, even where the most natural situations of mixed cropping are used, the scientific basis of the interaction must be established for robustness and sustainability of the approach. A complete understanding of the process allows a risk assessment to be made of any problems that might ensue when exploiting natural systems in different configurations from those encountered naturally. A major approach to using semiochemical based pest control is to exploit ways of repelling pests from crop plants and attracting them towards trap plantations. Deploying semiochemicals generated naturally by plants is consistent with organic farming practice, where a range of mixed cropping techniques are employed already, which ‘unconsciously’ utilise semiochemical effects. Thus, the acceptance and use of systems exploiting aspects of semiochemical deployment demonstrate an emerging role in organic farming practices. However, as emphasised before, a comprehensive knowledge of the semiochemical interactions that underpin these techniques is vital if they are to be exploited fully. Other pest control approaches compatible with organic farming, such as encouragement of beneficial species and the use of reflective surfaces in mulches, may not involve semiochemical effects, but could be exploited more beneficially by integration with semiochemical practices. Semiochemicals generated naturally by plants can be used to influence beneficial organisms as well as invertebrate pests. For example, plant defence chemicals, induced by pest or pathogen infestation, can affect the behaviour of pests and their natural enemies. Semiochemicals can be employed to maximise the impact of parasitic organisms that attack pest populations, for example in the management of refugia for maintaining and increasing populations of these beneficial organisms. In addition, the approach can be applied against other organisms antagonistic to agriculture besides invertebrate pests, for example in weed control, where signals interfering with weed germination can be exploited. Extracts of natural products provide semiochemicals in a form that is familiar and acceptable to organic farming practice, where plant extracts are already used as toxicants or as semiochemical antifeedants and repellents. However, often the scientific basis for use of these materials is limited, and therefore, exploitation is also limited and can be unreliable. By understanding the composition and the mechanism of activity of semiochemicals, natural product extracts can be improved by selection of the best sources of natural materials and appropriate processes of extraction and formulation. Many natural products, particularly pheromones (semiochemicals acting between members of the same species), can be synthesised as nature-identical and the synthetic forms are often indistinguishable from the natural form. Synthesis can be expensive, but where possible, starting materials should be obtained from natural renewable resources. Nature-identical synthetic pheromones are used widely in parts of the world, either deployed in traps for monitoring, mass trapping and lure and kill strategies or for direct pest control approaches such as mating disruption. In addition, manipulation of beneficial species with pheromones is being investigated and synthetic food-related attractants and oviposition attractants have also been developed for pests where pheromones are not available. Already some nature-identical synthetic semiochemicals have been accepted as compatible with organic farming practice. The registration of many sex and aggregation pheromones has been possible because they are nature-identical and are deployed away from the crop or on crop areas that are not consumed. In most cases, semiochemicals, deployed alone, are not sufficiently robust to control pest populations directly. They are most effective when incorporated into strategies, such as the ‘push-pull’ strategy, that are integrated with other forms of pest control, e.g. pathogens, parasitoids and predators, mechanical barriers and resistant plant varieties. The integration of semiochemical approaches with other methods of pest population reduction will help prevent the development of pest resistance to the overall strategy. Since the integrated strategy comprises a number of components that affect different aspects of pest behaviour and development each component can be relatively ineffective when compared to conventional pesticides. However, this has the advantage of not selecting efficiently for resistance to any component of the strategy and thus contributes to the sustainability of the approach. Recommendations 1) Develop a priority list of specific and general problems in organic production to be targeted by semiochemical methodologies in addition to known problems such as in carrot and lettuce production, aphids on a range of vegetable crops and for fruit pests. 2) Develop semiochemical based control methods suitable for 1) and for the targets already known. 3) Provide scientific input, where lacking, for 1 and 2. 4) Encourage greater diversification in organic cropping systems, including agroforestry, so as to exploit current knowledge of semiochemical based control and to pave the way for new interventions as the science develops. 5) Consider semiochemical attributes of non-crop plant inputs including mulches, weeds and multifunctional beneficial plants and the roles that they might play in organic systems. 6) Initiate organic plant breeding programmes, specifically to exploit natural semiochemical release where understood, for crop and companion plants

Assessing a sustainable manufacturing route to lapatinib

A synthetic route to an anti-cancer drug, lapatinib, was devised to support the development of a sustainable manufacturing process in South Africa. Quantitative metrics were employed to evaluate the sustainability of the key steps of the reaction

New dosing schedules of dasatinib for CML and adverse event management

Resistance to imatinib in patients with chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) has emerged as a significant clinical issue. Dasatinib is a tyrosine kinase inhibitor that has 325-fold greater in vitro activity against native BCR-ABL (breakpoint cluster region-Abelson leukemia virus) compared with imatinib and can overcome primary (intrinsic) and secondary (acquired) imatinib resistance. Here, we review the clinical profile of dasatinib in imatinib-resistant and -intolerant patients and share clinical approaches for managing adverse events (AEs) to ensure maximum patient benefit. References were obtained through literature searches on PubMed as well as from the Proceedings of Annual Meetings of the American Society of Clinical Oncology, the American Society of Hematology, and European Hematology Association. Phase II and III studies of dasatinib in patients with imatinib-resistant or -intolerant CML in any phase or Ph+ ALL were selected for discussion. Dasatinib is currently indicated for the treatment of patients with imatinib-resistant or -intolerant CML or Ph+ ALL. AEs associated with dasatinib are typically mild to moderate, and are usually resolved with temporary treatment interruption and/or dose adjustments. A Phase III dose optimization study showed that in patients with chronic phase (CP) CML, 100 mg once-daily dasatinib improves the safety profile, particularly pleural effusion and thrombocytopenia, while maintaining efficacy compared with the previously recommended dose of 70 mg twice-daily. Dasatinib has a manageable safety profile. For patients with CP CML, a new recommended starting dose of 100 mg once daily has recently been approved. The recommended dose for patients with advanced CML or Ph+ ALL remains 70 mg twice daily

Local host-dependent persistence of the entomopathogenic nematode Steinernema carpocapsae used to control the large pine weevil Hylobius abietis

Entomopathogenic nematodes (EPN) applied inundatively to suppress insect pests are more likely to persist and establish in stable agroecosystems than in annual crops. We investigated a system of intermediate stability: three stumps harbouring the large pine weevil (Hylobius abietis L.; Coleoptera: Curculionidae), a major European forestry pest. We tested whether persistence of EPN Steinernema carpocapsae Weiser (Rhabditida: Steinernematidae) applied around stumps is maintained by recycling of EPN through pine weevils developing within stumps. Steinernema carpocapsae was detected in soil around and under the bark of treated tree stumps up to two years, but not 4–5 years after application. Differences in nematode presence between sites were better explained by tree species (pine or spruce) than soil type (mineral or peat). Presence of S. carpocapsae in soil was positively correlated with the number of H. abietis emerging from untreated stumps the previous year, which was greater for pine stumps than spruce stumps

Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model

Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo

Feasibility and reliability of frailty assessment in the critically ill: a systematic review

Background. For healthcare systems, an ageing population poses challenges in the delivery of equitable and effective care. Frailty assessment has the potential to improve care in the intensive care setting, but applying assessment tools in critical illness may be problematic. The aim of this systematic review was to evaluate evidence for the feasibility and reliability of frailty assessment in critical care. Methods. Our primary search was conducted in Medline, Medline In-process, EMBASE, CINAHL, PsycINFO, AMED, Cochrane Database of Systematic Reviews, and Web of Science (January 2001 to October 2017). We included observational studies reporting data on feasibility and reliability of frailty assessment in critical care setting in patients 16 years and older. Feasibility was assessed in terms of timing of evaluation, the background, training and expertise required for assessors, and reliance upon proxy input. Reliability was assessed in terms of inter-rater reliability. Results. Data from 11 study publications are included, representing eight study cohorts and 7761 patients. Proxy involvement in frailty assessment ranged from 58- 100%. Feasibility data were not well-reported overall, but the exclusion rate due to lack of proxy availability ranged from 0 to 45%, the highest rate observed where family involvement was mandatory and the assessment tool relatively complex (Frailty Index, FI). Conventional elements of Frailty Phenotype (FP) assessment required modification prior to use in two studies. Clinical staff tended to use a simple judgement-based tool, the Clinical Frailty Scale (CFS). Inter-rater reliability was reported in one study using the CFS and although a good level of agreement was observed between clinician assessments, this was a small and single centre study. Conclusion. Though of unproven reliability in the critically ill, CFS was the tool used most widely by critical care clinical staff. Conventional FP assessment required modification for general application in critical care, and a FI-based assessment may be difficult to deliver by the critical care team on a routine basis. There is a high reliance on proxies for frailty assessment, and the reliability of frailty assessment tools in critical care needs further evaluation. PROSPERO CRD42016052073

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

The Roots of Virtue: A Cross-Cultural Lexical Analysis

Although the notion of virtue is increasingly prominent in psychology, the way it has been studied and conceptualised has been relatively Western-centric, and does not fully account for variations in how it has been understood cross-culturally. As such, an enquiry was conducted into ideas relating to virtue found across the world’s cultures, focusing specifically on so-called untranslatable words. Through a quasi-systematic search of academic and grey literature, together with conceptual snowballing and crowd-sourced suggestions, over 200 relevant terms were located. An adapted grounded theory analysis identified five themes which together provide an insight into the “roots” of virtue (i.e., the main sources from which it appears to spring): virtue itself (the concept of it); considerateness (caring about it); wisdom (knowing what it consists of); agency (managing to be/do it); and skill (mastery of the preceding elements). The results help shed further light on the potential dynamics of this important phenomenon