The Nexus approach for water utilities: A case study from South West UK

This is the author accepted manuscript.South West Water (SWW)European Union Horizon 202

A phase II study of a 5T4 oncofoetal antigen tumour-targeted superantigen (ABR-214936) therapy in patients with advanced renal cell carcinoma

In a phase II study, 43 renal cell carcinoma patients were treated with individualised doses of ABR-214936; a fusion of a Fab recognising the antigen 5T4, and Staphylococcal enterotoxin A. Drug was given intravenously on 4 consecutive days, treatment was repeated 1 month later. Treatment was associated with moderate fever and nausea, but well tolerated. Of 40 evaluable patients, 28 had disease control at 2 months, and at 4 months, one patient showed partial response (PR) and 16 patients stable disease. Median survival, with minimum follow-up of 26 months was 19.7 months with 13 patients alive to date. Stratification by the Motzer's prognostic criteria highlights prolonged survival compared to published expectation. Patients receiving higher drug exposure had greater disease control and lived almost twice as long as expected, whereas the low-exposure patients survived as expected. Sustained interleukin-2 (IL-2) production after a repeated injection appears to be a biomarker for clinical effect, as the induced-IL-2 level on the day 2 of treatment correlated with survival. The high degree of disease control and the prolonged survival suggest that this treatment can be effective. These findings will be used in the trial design for the next generation of drug, with reduced antigenicity and toxicity

Prolonged Visual Experience in Adulthood Modulates Holistic Face Perception

Background: Using the well-known composite illusion as a marker of the holistic perception of faces, we tested how prolonged visual experience with a specific population of faces (4- to 6-year-old children) modulates the face perception system in adulthood. Methodology/Principal Findings: We report a face composite effect that is larger for adult than children faces in a group of adults without experience with children faces (‘‘children-face novices’’), while it is of equal magnitude for adults and children faces in a population of preschool teachers (‘‘children-face experts’’). When considering preschool teachers only, we observed a significant correlation between the number of years of experience with children faces and the differential face composite effect between children and adults faces. Participants with at least 10 years of qualitative experience with children faces had a larger composite face effect for children than adult faces. Conclusions/Significance: Overall, these observations indicate that even in adulthood face processes can be reshaped qualitatively, presumably to facilitate efficient processing of the differential morphological features of the frequently encountered population of faces

Holistic Processing of Words Modulated by Reading Experience

Perceptual expertise has been studied intensively with faces and object categories involving detailed individuation. A common finding is that experience in fulfilling the task demand of fine, subordinate-level discrimination between highly similar instances is associated with the development of holistic processing. This study examines whether holistic processing is also engaged by expert word recognition, which is thought to involve coarser, basic-level processing that is more part-based. We adopted a paradigm widely used for faces – the composite task, and found clear evidence of holistic processing for English words. A second experiment further showed that holistic processing for words was sensitive to the amount of experience with the language concerned (native vs. second-language readers) and with the specific stimuli (words vs. pseudowords). The adoption of a paradigm from the face perception literature to the study of expert word perception is important for further comparison between perceptual expertise with words and face-like expertise

Therapy of human non-small-cell lung carcinoma using antibody targeting of a modified superantigen

Superantigens activate T-cells by linking the T-cell receptor to MHC class II on antigen-presenting cells, and novel reactivity can be introduced by fusing the superantigen to a targeting molecule. Thus, an antibody-targeted superantigen, which activates T cells to destroy tumour cells, might be used as cancer therapy. A suitable target is the 5T4 oncofetal antigen, which is expressed on many carcinomas. We constructed a fusion protein from a Fab of a monoclonal antibody recognizing the 5T4 antigen, and an engineered superantigen. The recombinant product 5T4FabV13-SEAD227A bound the 5T4 antigen expressed on the human non-small-cell lung cancer cell line Calu-1 with a Kd of 1.2 nM while the substitution of Asp227 to Ala in the superantigen moiety reduced binding activity to MHC class II. 5T4FabV13-SEAD227A tumour reactivity was demonstrated in 7/7 NSCLC samples by immunohistochemistry, while normal tissue reactivity was low to moderate. 5T4FabV13-SEAD227A induced significant T-cell-dependent in vitro killing of sensitive 5T4 bearing Calu-1 cells, with maximum lysis at 10−10M, while the capacity to lyse MHC class II expressing cells was approximately 1000 times less effective. Immunotherapy of 5T4FabV13-SEAD227A against human NSCLC was investigated in SCID mice reconstituted with human peripheral blood mononuclear cells. Mice carrying intreperitoneally growing Calu-1 cells showed significant reduction in tumour mass and number after intravenous therapy with 5T4FabV13-SEAD227A. Thus, 5T4FabV13-SEAD227A has highly attractive properties for therapy of human NSCLC. © 2001 Cancer Research Campaign http://www.bjcancer.co

Degradation of metalaxyl and folpet by filamentous fungi isolated from Portuguese (Alentejo) vineyard soils

Degradation of xenobiotics by microbial populations is a potential method to enhance the effectiveness of ex situ or in situ bioremediation. The purpose of this study was to evaluate the impact of repeated metalaxyl and folpet treatments on soil microbial communities and to select soil fungal strains able to degrade these fungicides. Results showed enhanced degradation of metalaxyl and folpet in vineyards soils submitted to repeated treatments with these fungicides. Indeed, the greatest degradation ability was observed in vineyard soil samples submitted to greater numbers of treatments. Respiration activities, as determined in the presence of selective antibiotics in soil suspensions amended with metalaxyl and folpet, showed that the fungal population was the microbiota community most active in the degradation process. Batch cultures performed with a progressive increase of fungicide concentrations allowed the selection of five tolerant fungal strains: Penicillium sp. 1 and Penicillium sp. 2, mycelia sterila 1 and 3, and Rhizopus stolonifer. Among these strains, mycelium sterila 3 and R. stolonifer presented only in vineyard soils treated with repeated application of these fungicides and showed tolerance >1,000 mg l−1 against commercial formulations of metalaxyl (10 %) plus folpet (40 %). Using specific methods for inducing sporulation, mycelium sterila 3 was identified as Gongronella sp. Because this fungus is rare, it was compared using csM13-polymerase chain reaction (PCR) with the two known species, Gongronella butleri and G. lacrispora. The high tolerance to metalaxyl and folpet shown by Gongronella sp. and R. stolonifer might be correlated with their degradation ability. Our results point out that selected strains have potential for the bioremediation of metalaxyl and folpet in polluted soil sites

Discrete Choice Experiments: A Guide to Model Specification, Estimation and Software

We provide a user guide on the analysis of data (including best–worst and best–best data) generated from discrete-choice experiments (DCEs), comprising a theoretical review of the main choice models followed by practical advice on estimation and post-estimation. We also provide a review of standard software. In providing this guide, we endeavour to not only provide guidance on choice modelling but to do so in a way that provides a ‘way in’ for researchers to the practicalities of data analysis. We argue that choice of modelling approach depends on the research questions, study design and constraints in terms of quality/quantity of data and that decisions made in relation to analysis of choice data are often interdependent rather than sequential. Given the core theory and estimation of choice models is common across settings, we expect the theoretical and practical content of this paper to be useful to researchers not only within but also beyond health economics

The Muslim headscarf and face perception: "they all look the same, don't they?"

YesThe headscarf conceals hair and other external features of a head (such as the ears). It therefore may have implications for the way in which such faces are perceived. Images of faces with hair (H) or alternatively, covered by a headscarf (HS) were used in three experiments. In Experiment 1 participants saw both H and HS faces in a yes/no recognition task in which the external features either remained the same between learning and test (Same) or switched (Switch). Performance was similar for H and HS faces in both the Same and Switch condition, but in the Switch condition it dropped substantially compared to the Same condition. This implies that the mere presence of the headscarf does not reduce performance, rather, the change between the type of external feature (hair or headscarf) causes the drop in performance. In Experiment 2, which used eye-tracking methodology, it was found that almost all fixations were to internal regions, and that there was no difference in the proportion of fixations to external features between the Same and Switch conditions, implying that the headscarf influenced processing by virtue of extrafoveal viewing. In Experiment 3, similarity ratings of the internal features of pairs of HS faces were higher than pairs of H faces, confirming that the internal and external features of a face are perceived as a whole rather than as separate components.The Educational Charity of the Federation of Ophthalmic and Dispensing Opticians

Blood pressure and site-specific cancer mortality: evidence from the original Whitehall study

Studies relating blood pressure to cancer risk have some shortcomings and have revealed inconsistent findings. In 17498 middle-aged London-based government employees we related systolic and diastolic blood pressure recorded at baseline examination (1967-1970) to the risk of cancer mortality risk at 13 anatomical sites 25 years later. Following adjustment for potential confounding and mediating factors, inverse associations between blood pressure and mortality due to leukaemia and cancer of the pancreas (diastolic only) were seen. Blood pressure was also positively related to cancer of the liver and rectum (diastolic only). The statistically significant blood pressure-cancer associations seen in this large-scale prospective investigation offering high power were scarce and of sufficiently small magnitude as to be attributable to chance or confounding

Seeing faces as objects: no face inversion effect with geometrical discrimination

Inversion dramatically impairs face perception, recognition, and discrimination. Yet it does not interfere with the ability to make precise estimates of facial feature distances. To investigate this discontinuity between facial feature distance estimation and general perception and recognition, we assessed the effect of inversion on the discrimination of differences in facial compression and elongation or expansion using geometrically distorted faces. The results clearly showed that geometrical face discrimination is not subject to the traditional face inversion effect and did not show a benefit for natural faces. Although discrimination thresholds were not affected by inversion, response times to the distance judgments were faster with inversion, especially when the inverted faces contained natural configurations. Based on these counterintuitive results, we suggest that participants used analytical processing to do the discrimination task. Moreover, we suggest that the depth with which a face is holistically encoded depends on the nature of the task, face orientation, and similarity between a face and the prototypical face template