Geometric Semantic Grammatical Evolution

This is the author accepted manuscript. The final version is available from Springer via the DOI in this record.Geometric Semantic Genetic Programming (GSGP) is a novel form of Genetic Programming (GP), based on a geometric theory of evolutionary algorithms, which directly searches the semantic space of programs. In this chapter, we extend this framework to Grammatical Evolution (GE) and refer to the new method as Geometric Semantic Grammatical Evolution (GSGE). We formally derive new mutation and crossover operators for GE which are guaranteed to see a simple unimodal fitness landscape. This surprising result shows that the GE genotypephenotype mapping does not necessarily imply low genotype-fitness locality. To complement the theory, we present extensive experimental results on three standard domains (Boolean, Arithmetic and Classifier)

Outbreak of influenza in highly vaccinated crew of U.S. Navy ship.

An outbreak of influenza A (H3N2) occurred aboard a U.S. Navy ship in February 1996, despite 95% of the crew's having been appropriately vaccinated. Virus isolated from ill crew members was antigenically distinct from the vaccination strain. With an attack rate of 42%, this outbreak demonstrates the potential for rapid spread of influenza in a confined population and the impact subsequent illness may have upon the workplace

Time series prediction via aggregation : an oracle bound including numerical cost

We address the problem of forecasting a time series meeting the Causal Bernoulli Shift model, using a parametric set of predictors. The aggregation technique provides a predictor with well established and quite satisfying theoretical properties expressed by an oracle inequality for the prediction risk. The numerical computation of the aggregated predictor usually relies on a Markov chain Monte Carlo method whose convergence should be evaluated. In particular, it is crucial to bound the number of simulations needed to achieve a numerical precision of the same order as the prediction risk. In this direction we present a fairly general result which can be seen as an oracle inequality including the numerical cost of the predictor computation. The numerical cost appears by letting the oracle inequality depend on the number of simulations required in the Monte Carlo approximation. Some numerical experiments are then carried out to support our findings

Managerial Work in a Practice-Embodying Institution - The role of calling, the virtue of constancy

What can be learned from a small scale study of managerial work in a highly marginal and under-researched working community? This paper uses the ‘goods-virtues-practices-institutions’ framework to examine the managerial work of owner-directors of traditional circuses. Inspired by MacIntyre’s arguments for the necessity of a narrative understanding of the virtues, interviews explored how British and Irish circus directors accounted for their working lives. A purposive sample was used to select subjects who had owned and managed traditional touring circuses for at least 15 years, a period in which the economic and reputational fortunes of traditional circuses have suffered badly. This sample enabled the research to examine the self-understanding of people who had, at least on the face of it, exhibited the virtue of constancy. The research contributes to our understanding of the role of the virtues in organizations by presenting evidence of an intimate relationship between the virtue of constancy and a ‘calling’ work orientation. This enhances our understanding of the virtues that are required if management is exercised as a domain-related practice

Unravelling the molecular determinants of bee sensitivity to neonicotinoid insecticides

This is the final version of the article. Available from the publisher via the DOI in this record.The impact of neonicotinoid insecticides on the health of bee pollinators is a topic of intensive research and considerable current debate [1]. As insecticides, certain neonicotinoids, i.e., N-nitroguanidine compounds such as imidacloprid and thiamethoxam, are as intrinsically toxic to bees as to the insect pests they target. However, this is not the case for all neonicotinoids, with honeybees orders of magnitude less sensitive to N-cyanoamidine compounds such as thiacloprid [2]. Although previous work has suggested that this is due to rapid metabolism of these compounds [2, 3, 4, 5], the specific gene(s) or enzyme(s) involved remain unknown. Here, we show that the sensitivity of the two most economically important bee species to neonicotinoids is determined by cytochrome P450s of the CYP9Q subfamily. Radioligand binding and inhibitor assays showed that variation in honeybee sensitivity to N-nitroguanidine and N-cyanoamidine neonicotinoids does not reside in differences in their affinity for the receptor but rather in divergent metabolism by P450s. Functional expression of the entire CYP3 clade of P450s from honeybees identified a single P450, CYP9Q3, that metabolizes thiacloprid with high efficiency but has little activity against imidacloprid. We demonstrate that bumble bees also exhibit profound differences in their sensitivity to different neonicotinoids, and we identify CYP9Q4 as a functional ortholog of honeybee CYP9Q3 and a key metabolic determinant of neonicotinoid sensitivity in this species. Our results demonstrate that bee pollinators are equipped with biochemical defense systems that define their sensitivity to insecticides and this knowledge can be leveraged to safeguard bee health.his study received funding from Bayer AG. C.B. received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 646625 ). C.B. and K.B. received funding from Biotechnology and Biological Sciences Research Council (BBSRC, award number 15076182 ). The work at Rothamsted forms part of the Smart Crop Protection (SCP) strategic programme ( BBS/OS/CP/000001 ) funded through the Biotechnology and Biological Sciences Research Council’s Industrial Strategy Challenge Fund

Genomic insights into neonicotinoid sensitivity in the solitary bee Osmia bicornis

This is the final version. Available from the publisher via the DOI in this record.The Osmia bicornis whole genome shotgun project has been deposited at DDBJ/ENA/GenBank under the accession MPJT00000000. The RNAseq data generated in this study has been deposited in the Sequence Read Archive (SRA) under accession SRP065762. Accession numbers of the bee P450 genes manually curated in this study are shown in S5 Table. All other relevant data are within the paper and its Supporting Information files.The impact of pesticides on the health of bee pollinators is determined in part by the capacity of bee detoxification systems to convert these compounds to less toxic forms. For example, recent work has shown that cytochrome P450s of the CYP9Q subfamily are critically important in defining the sensitivity of honey bees and bumblebees to pesticides, including neonicotinoid insecticides. However, it is currently unclear if solitary bees have functional equivalents of these enzymes with potentially serious implications in relation to their capacity to metabolise certain insecticides. To address this question, we sequenced the genome of the red mason bee, Osmia bicornis, the most abundant and economically important solitary bee species in Central Europe. We show that O. bicornis lacks the CYP9Q subfamily of P450s but, despite this, exhibits low acute toxicity to the N-cyanoamidine neonicotinoid thiacloprid. Functional studies revealed that variation in the sensitivity of O. bicornis to N-cyanoamidine and N-nitroguanidine neonicotinoids does not reside in differences in their affinity for the nicotinic acetylcholine receptor or speed of cuticular penetration. Rather, a P450 within the CYP9BU subfamily, with recent shared ancestry to the Apidae CYP9Q subfamily, metabolises thiacloprid in vitro and confers tolerance in vivo. Our data reveal conserved detoxification pathways in model solitary and eusocial bees despite key differences in the evolution of specific pesticide-metabolising enzymes in the two species groups. The discovery that P450 enzymes of solitary bees can act as metabolic defence systems against certain pesticides can be leveraged to avoid negative pesticide impacts on these important pollinators.Biotechnology and Biological Science Research Council (BBSRC)Bayer AGEuropean Research Council (ERC

Comparison of different methods for delayed post-mortem diagnosis of falciparum malaria

<p>Abstract</p> <p>Background</p> <p>Between 10,000 and 12,000 cases of imported malaria are notified in the European Union each year. Despite an excellent health care system, fatalities do occur. In case of advanced autolysis, the post-mortem diagnostic is impaired. Quicker diagnosis could be achieved by using rapid diagnostic malaria tests.</p> <p>Methods</p> <p>In order to evaluate different methods for the post-mortem diagnosis of <it>Plasmodium falciparum </it>malaria in non-immunes, a study was performed on the basis of forensic autopsies of corpses examined at variable intervals after death in five cases of fatal malaria (with an interval of four hours to five days), and in 20 cases of deaths unrelated to malaria. Detection of parasite DNA by PCR and an immunochromatographic test (ICT) based upon the detection of <it>P. falciparum </it>histidine-rich protein 2 (PfHRP2) were compared with the results of microscopic examination of smears from cadaveric blood, histopathological findings, and autopsy results.</p> <p>Results</p> <p>In all cases of fatal malaria, post-mortem findings were unsuspicious for the final diagnosis, and autoptic investigations, including histopathology, were only performed because of additional information by police officers and neighbours. Macroscopic findings during autopsy were unspecific. Histopathology confirmed sequestration of erythrocytes and pigment in macrophages in most organs in four patients (not evaluable in one patient due to autolysis). Microscopy of cadaveric blood smears revealed remnants of intraerythrocytic parasites, and was compromised or impossible due to autolysis in two cases. PCR and ICT performed with cadaveric blood were positive in all malaria patients and negative in all controls.</p> <p>Conclusion</p> <p>In non-immune fatalities with unclear anamnesis, ICT can be recommended as a sensitive and specific tool for post-mortem malaria diagnosis, which is easier and faster than microscopy, and also applicable when microscopic examination is impossible due to autolysis. PCR is more expensive and time-consuming, but may be used as confirmatory test. In highly endemic areas where asymptomatic parasitaemia is common, confirmation of the diagnosis of malaria as the cause of death has to rely on histopathological findings.</p

The spatial variability of water chemistry and DOC in bog pools: the importance of slope position, diurnal turnover and pool type

We have previously shown that marine influence is an important factor controlling regional variability of pool water chemistry in blanket peatlands. Here we examine within-site controls on pool water chemistry. We surveyed natural and artificial (restoration sites) bog pools at blanket peatland sites in northern Scotland and Sweden. DOC, pH, conductivity, dissolved oxygen, temperature, cations, anions and absorbance spectra from 220-750nm were sampled. We sampled changes over time but also conducted intensive spatial surveys within individual pools and between pools on the same sampling days at individual study sites. Artificial pools had significantly greater DOC concentrations and different spectral absorbance characteristics when compared to natural pools at all sites studied. Within-pool variability in water chemistry tended to be small, even for very large pools (~400 m2), except where pools had a layer of loose, mobile detritus on their beds. In these instances rapid changes took place between the overlying water column and the mobile sediment layer wherein dissolved oxygen concentrations dropped from values of around 12-10 mg L-1 to values less than 0.5 mg L-1 over just 2-3 cm of the depth profile. Such strong contrasts were not observed for pools which had a hard peat floor and which lacked a significant detritus layer. Strong diurnal turnover occurred within the pools on summer days, including within small, shallow pools (e.g. < 30 cm deep, 1 m2 area). For many pools on these summer days there was an evening spike in dissolved oxygen concentrations which originated at the surface and was then cycled downwards as the pool surface waters cooled. Slope location was a significant control on several pool water chemistry variables including pH and DOC concentration with accumulation (higher concentrations) in pools that were located further downslope in both natural and artificial pool systems. These processes have important implications for our interpretation of water chemistry and gas flux data from pool systems, how we design our sampling strategies and how we upscale results

655MO Quality of life in patients with p16+ oropharyngeal cancer receiving accelerated radiotherapy (RT) with either cisplatin or cetuximab in NRG/RTOG 1016

Background: This phase 3 randomized non-inferiority de-escalation trial compared cetuximab (cetux) vs cisplatin (cis), concurrent with accelerated RT 70 Gy/6 weeks, in p16+ oropharyngeal cancer (OPC). Quality of life (QOL) was an important secondary endpoint. Methods: EORTC QLQ-C30/HN35 was completed at baseline, end of treatment, 3, 6, and 12 months post. The substudy aimed for 400 eligible patients. We report completion rates and compare by arm for change from baseline in each domain (0.05 two-sided alpha and MID of 10 points) using linear mixed models. Results: Consent was 91% (381/419 offered substudy); 6 protocol deviations excluded (n=375). No significant differences in patient/tumor characteristics were found by participation status. Completion rates (%) at the 5 times did not differ by arm (cis/cetux): 92/94, 74/77, 76/81, 76/81, and 73/74. The swallowing domain of HN35 (previously reported) did not differ significantly by arm. No significant difference was seen by arm for the 6-mo change from baseline on any domain. At end of RT (only), dry mouth was significantly worse for RT+cetux. At end of treatment, all domains showed statistically and clinically significant mean worsening across both arms except Emotional Functioning, Dyspnea, Diarrhea, and Teeth. Most domains returned within 10 points of baseline by 6 mo, with the following maintaining significant impairment: Senses (taste/smell), Social Eating, Opening Mouth, Dry Mouth, Sticky Saliva. At 12 mo post-treatment, worsening from baseline persisted for Senses, Dry Mouth, Sticky Saliva, and Weight Gain. Pain Killer use improved significantly from baseline to 3, 6, and 12 mo. Conclusions: Although replacing RT+cis with RT+cetux did not benefit QOL, this study has confirmed the responsiveness of EORTC QLQ-C30/HN35 to the effects of concurrent systemic/RT for OPC. Dry Mouth, Sticky Saliva, and Senses showed large, significant, and persistent impairments, and remain worthwhile targets for future de-escalation efforts. Domains related to eating (Swallowing, Appetite, Nutritional Supplements, Social Eating, Weight Loss) did not show sustained significant impairment on this instrument in this study. Clinical trial identification: NCT01302834