965 resultados para knowledge gaps


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Currently no pharmacogenomics-based criteria exist to guide clinicians in identifying individuals who are at risk of hearing loss from cisplatin-based chemotherapy. This review summarizes findings from pharmacogenomic studies that report genetic polymorphisms associated with cisplatin-induced hearing loss and aims to (1) provide up-to-date information on new developments in the field; (2) provide recommendations for the use of pharmacogenetic testing in the prevention, assessment and management of cisplatin-induced hearing loss in children and adults; and (3) identify knowledge gaps to direct and prioritize future research. These practice recommendations for pharmacogenetic testing in the context of cisplatin-induced hearing loss reflect a review and evaluation of recent literature and are designed to assist clinicians in providing optimal clinical care for patients receiving cisplatin based chemotherapy.

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The β-catenin/Lef/Tcf-mediated Wnt pathway is central to the developmental of all animals, stem cell renewal, and cancer progression. Prior studies in frogs and mice have indicated that the ligand Wnt-4 is essential for the mesenchyme to epithelial transition that generates tubules in the context of kidney organogenesis. More recently, Wnt-9b in mice, was likewise found to be required. Yet despite the importance of Wnt signals in renal development, the corresponding Frizzled receptor(s) and downstream signaling mechanim(s) are unclear. My work addresses these knowledge gaps using in vitro (Madin-Darby Canine Kidney cells) and in vivo (Xenopus laevis and zebrafish pronephros) tubulogenic kidney model systems. Employing established reporter constructs of Wnt/β-catenin pathway activity, I have determined that MDCK cells are highly responsive to Wnt-4, -1, and -3A, but not to Wnt-5A and control conditions. I have confirmed that Wnt-4's canonical signaling activity in MDCK cells is mediated by downstream effectors of the Wnt/β-catenin pathway using β-Engrailed and dnTCF-4, constructs that suppress this pathway. I have further found that MDCK cells express the Frizzled-6 receptor, and that Wnt-4 forms a biochemical complex with Frizzled-6, yet does not appear to transduce Wnt-4's canonical signal. Additionally, I demonstrate that standard Hepatocyte Growth Factor (HGF)-mediated (non-physiologic) induction of MDCK tubulogenesis in collagen matrices is not altered by activation or suppression of β-catenin signaling activity; however, β-catenin signaling maintains cell survival in this in vitro system. Using a Wnt/β-catenin signaling reporter in Xenopus laevis, I detect β-catenin signaling activity in the early pronephric epithelial kidney tubules. By inhibiting the Wnt/β-catenin signaling pathway in both zebrafish and Xenopus , a significant loss of kidney tubulogenesis is observed with little or no effect on adjoining axis or somite development. This inhibition also leads to the appearance of severe edema that phenocopies embryos depleted for Wnt-4. Tubulogenic loss does not appear to be caused by increased cell death in the Xenopus pronephric field, but rather by lessened expression of tubule epithelium genes associated with cellular differentiation. Together, my results show that Wnt/β-catenin signaling is required for renal tubule development and that Wnt-4 is a strong candidate for activating this pathway. ^

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Environmental problems related to the use of synthetic fertilizers and to organic waste management have led to increased interest in the use of organic materials as an alternative source of nutrients for crops, but this is also associated with N2O emissions. There has been an increasing amount of research into the effects of using different types of fertilization on N2O emissions under Mediterranean climatic conditions, but the findings have sometimes been rather contradictory. Available information also suggests that water management could exert a high influence on N2O emissions. In this context, we have reviewed the current scientific knowledge, including an analysis of the effect of fertilizer type and water management on direct N2O emissions. A meta-analysis of compliant reviewed experiments revealed significantly lower N2O emissions for organic as opposed to synthetic fertilizers (23% reduction). When organic materials were segregated in solid and liquid, only solid organic fertilizer emissions were significantly lower than those of synthetic fertilizers (28% reduction in cumulative emissions). The EF is similar to the IPCC factor in conventionally irrigated systems (0.98% N2O-N N applied−1), but one order of magnitude lower in rainfed systems (0.08%). Drip irrigation produces intermediate emission levels (0.66%). Differences are driven by Mediterranean agro-climatic characteristics, which include low soil organic matter (SOM) content and a distinctive rainfall and temperature pattern. Interactions between environmental and management factors and the microbial processes involved in N2O emissions are discussed in detail. Indirect emissions have not been fully accounted for, but when organic fertilizers are applied at similar N rates to synthetic fertilizers, they generally make smaller contributions to the leached NO3− pool. The most promising practices for reducing N2O through organic fertilization include: (i) minimizing water applications; (ii) minimizing bare soil; (iii) improving waste management; and (iv) tightening N cycling through N immobilization. The mitigation potential may be limited by: (i) residual effect; (ii) the long-term effects of fertilizers on SOM; (iii) lower yield-scaled performance; and (iv) total N availability from organic sources. Knowledge gaps identified in the review included: (i) insufficient sampling periods; (ii) high background emissions; (iii) the need to provide N2O EF and yield-scaled EF; (iv) the need for more research on specific cropping systems; and (v) the need for full GHG balances. In conclusion, the available information suggests a potential of organic fertilizers and water-saving practices to mitigate N2O emissions under Mediterranean climatic conditions, although further research is needed before it can be regarded as fully proven, understood and developed.

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Esta Tesis Doctoral tiene como principal objetivo el obtener una cadena de tratamientos seguros de aguas seriados que nos permita asegurar la calidad de las aguas para consumo humano en caso de emergencias, de tal forma que se minimicen los efectos de acciones hostiles, como sabotajes o actos terroristas, desastres naturales, etc y buscar soluciones adecuadas para garantizar en este caso la salud. Las plantas de tratamientos de aguas existentes comercialmente no aseguran dicha calidad y la documentación sobre el tema presenta vacíos de conocimiento, contradicciones entre resultados de investigaciones o insostenibilidad de conclusiones de las mismas. Estas carencias nos permiten determinar los aspectos a tratar durante la investigación. Por ello, este objetivo se concretó en tres acciones: Investigar sobre rendimientos de plantas convencionales en eliminación de microorganismos y productos tóxicos y peligrosos. Introducir mejoras que garanticen el rendimiento de las plantas convencionales. Investigar sobre la conveniencia de complementar las instalaciones existentes buscando seguridad y garantía sanitaria. Y se desarrollaron tres líneas de investigación: LI 1 “Inorgánicos”: Investigación sobre la eliminación de los metales boro, cobre y molibdeno mediante procesos de intercambio iónico y de coagulaciónfloculación- decantación. LI 2 “Compuestos Orgánicos Volátiles”: Investigación sobre la eliminación de los compuestos orgánicos 1,1 dicloroetano, 1,2 dicloroetano, clorobenceno, 1,3 dicloropropeno y hexacloro 1,3 butadieno mediante procesos de carbón activo granular y de oxidación avanzada. LI 3 “Plantas portátiles”: Investigación sobre plantas existentes portátiles para verificar su rendimiento teórico y proponer mejoras. Estas líneas de investigación se desarrollaron tanto en el nivel teórico como en el empírico, bien sea en laboratorio como en campo. A lo largo del documento se demuestra que las principales fuentes de contaminación, salvo la degradación de yacimientos naturales, proceden de la actividad humana (efluentes industriales y agrícolas, aguas residuales y actividades beligerantes) que provocan un amplio espectro de enfermedades por lo que dificultan tanto la definición de la fuente como la anticipada detección de la enfermedad. Las principales conclusiones que se obtuvieron están relacionadas con el rendimiento de eliminación de los parámetros tras la aplicación de los procesos y plantas de tratamiento de aguas anteriormente reseñadas. Sin embargo, el verdadero elemento designador de originalidad de esta Tesis Doctoral, tal como se ha reseñado arriba, radica en la definición de un sistema seriado de procesos de tratamiento de aguas que asegura la calidad en caso de emergencia. Éste se define en el siguiente orden: pretratamiento, oxidación, coagulación-floculación-decantación, filtración por arena, intercambio iónico, carbón activo granular, microfiltración, radiación UV, ósmosis inversa, radiación UV y cloración final. The main objective of this Thesis is to obtain a chain of stepwise safe water treatments that allow us to ensure the quality of water for human consumption in case of emergencies, so that the effects of hostile actions, such as sabotage or terrorism, natural disasters, etc. and seek appropriate solutions in this case to ensure health. The existing commercial water treatment plants do not ensure quality, and the documentation on the subject presents knowledge gaps or contradictions. These gaps allow us to determine the issues to be discussed during the investigation. Therefore, this objective was manifested in three actions: Researching yields in commercial plants and microorganisms, or toxic and dangerous products removal. Improvements to ensure the performance of conventional plants. Inquire about the advisability of implementing existing facilities for safety and health guarantee. And three lines of research are developed: LI 1 “Inorganic elements”: Research removing metals iron, copper and molybdenum by ion exchange processes and coagulation-flocculation-decantation. LI 2 “Volatile Organic Compounds”: Research removing organic compounds 1,1 dichloroethane, 1,2 dichloroethane, chlorobenzene, 1,3-dichloropropene and 1,3-butadiene hexachloro through processes of granular activated carbon and advanced oxidation. LI 3 “Compact Water Treatment Plants”: Research on existing packaged plants to verify theoretical performance and suggest improvements. These lines of research are developed both theoretically and empirically, both in the laboratory and in the field. Throughout the document, it is evident that the main sources of pollution, other than the degradation of natural deposits, come from human activity (industrial and agricultural effluents, sewage and belligerent activities) which cause a broad spectrum of diseases which hamper both the definition of the source and the early detection of the disease. The main conclusions drawn are related to both the removal efficiency parameters after application of processes and treatment plants outlined above water. However, the real designator of originality of this thesis, such as outlined above, lies in the definition of a serial system water treatment processes assuring quality in case of emergency. This is defined in the following order: pretreatment, oxidation, coagulation-flocculation-sedimentation, sand filtration, ion exchange, granular activated carbon, microfiltration, UV radiation, reverse osmosis, UV radiation and final chlorination.

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Carbon nanotubes exhibit the structure and chemical properties that make them apt substrates for many adsorption applications. Of particular interest are carbon nanotube bundles, whose unique geometry is conducive to the formation of pseudo-one-dimensional phases of matter, and graphite, whose simple planar structure allows ordered phases to form in the absence of surface effects. Although both of these structures have been the focus of many research studies, knowledge gaps still remain. Much of the work with carbon nanotubes has used simple adsorbates1-43, and there is little kinetic data available. On the other hand, there are many studies of complex molecules adsorbing on graphite; however, there is almost no kinetic data reported for this substrate. We seek to close these knowledge gaps by performing a kinetic study of linear molecules of increasing length adsorbing on carbon nanotube bundles and on graphite. We elucidated the process of adsorption of complex admolecules on carbon nanotube bundles, while at the same time producing some of the first equilibrium results of the films formed by large adsorbates on these structures. We also extended the current knowledge of adsorption on graphite to include the kinetics of adsorption. The kinetic data that we have produced enables a more complete understanding of the process of adsorption of large admolecules on carbon nanotube bundles and graphite. We studied the adsorption of particles on carbon nanotube bundles and graphite using analytical and computational techniques. By employing these methods separately but in parallel, we were able to constantly compare and verify our results. We calculated and simulated the behavior of a given system throughout its evolution and then analyzed our results to determine which system parameters have the greatest effect on the kinetics of adsorption. Our analytical and computational results show good agreement with each other and with the experimental isotherm data provided by our collaborators. As a result of this project, we have gained a better understanding of the kinetics of adsorption. We have learned about the equilibration process of dimers on carbon nanotube bundles, identifying the “filling effect”, which increases the rate of total uptake, and explaining the cause of the transient “overshoot” in the coverage of the surface. We also measured the kinetic effect of particle-particle interactions between neighboring adsorbates on the lattice. For our simulations of monomers adsorbing on graphite, we succeeded in developing an analytical equation to predict the characteristic time as a function of chemical potential and of the adsorption and interaction energies of the system. We were able to further explore the processes of adsorption of dimers and trimers on graphite (again observing the filling effect and the overshoot). Finally, we were able to show that the kinetic behaviors of monomers, dimers, and trimers that have been reported in experimental results also arise organically from our model and simulations.

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A evasão estudantil afeta as universidades, privadas e públicas, no Brasil, trazendo-lhes prejuízos financeiros proporcionais à incidência, respectivamente, de 12% e de 26% no âmbito nacional e de 23% na Universidade de São Paulo (USP), razão pela qual se deve compreender as variáveis que governam o comportamento. Neste contexto, a pesquisa apresenta os prejuízos causados pela evasão e a importância de pesquisá-la na Escola Politécnica da USP (EPUSP): seção 1, desenvolve revisão bibliográfica sobre as causas da evasão (seção 2) e propõe métodos para obter as taxas de evasão a partir dos bancos de dados do Governo Federal e da USP (seção 3). Os resultados estão na seção 4. Para inferir sobre as causas da evasão na EPUSP, analisaram-se bancos de dados que, descritos e tratados na seção 5.1, contêm informações (P. Ex.: tipo de ingresso e egresso, tempo de permanência e histórico escolar) de 16.664 alunos ingressantes entre 1.970 e 2.000, bem como se propuseram modelos estatísticos e se detalharam os conceitos dos testes de hipóteses 2 e t-student (seção 5.2) utilizados na pesquisa. As estatísticas descritivas mostram que a EPUSP sofre 15% de evasão (com maior incidência no 2º ano: 24,65%), que os evadidos permanecem matriculados por 3,8 anos, que a probabilidade de evadir cresce após 6º ano e que as álgebras e os cálculos são disciplinas reprovadoras no 1º ano (seção 5.3). As estatísticas inferenciais demonstraram relação entre a evasão - modo de ingresso na EPUSP e evasão - reprovação nas disciplinas do 1º ano da EPUSP, resultados que, combinados com as estatísticas descritivas, permitiram apontar o déficit vocacional, a falta de persistência, a falta de ambientação à EPUSP e as deficiências na formação predecessora como variáveis responsáveis pela evasão (seção 5.4).

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One of the most relevant subjects for the intellectual formation of elementary school students is Mathematics where its importance goes back to ancient civilizations and which its importance is underestimated nowadays. This phenomenon occurs in Mexico, where 63.1% of the total population of elementary school students between the third and sixth grade have insufficient/elemental level of mathematics knowledge. This has resulted in the need to use a new mechanism to complement student’s classroom learning. With the rapid growth of wireless and mobile technologies, the mobile learning has been gradually considered as a novel and effective form of learning due to it inherits all the advantages of e-learning as well as breaks the limitations of learning time and space occurring in the traditional classroom teaching. This project proposes the use of a Mathematics Game e-Library integrated by a set of games for mobile devices and a distribution/management tool. The games are developed for running on mobile devices and for cover the six competencies related with the mathematics learning approach established in Mexico. The distribution/management tool allows students to reach contents according to their needs; this is achieved through a core engine that infers, from an initial profile, the games that cover the user’s knowledge gaps.

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Forest plantations have been extensively used to combat desertification. In drylands, harsh climate conditions and unfertile soils often preclude seedling establishment. The improvement in seedling quality by manipulating nutrient availability could contribute to increase planting success. However, morpho-functional traits defining optimum seedling quality in drylands, and the fertilization schemes to achieve them, are still under discussion. Several studies suggest that well fertilized seedlings may perform better than nutrient limited seedlings in these environments. However, recent works have shown opposite results. In this review, we discuss the concept of seedling quality in drylands based on an evaluation of the effects of nutrient manipulation on seedling morpho-functional traits and field performance. According to existing data, we hypothesize that nutrient-limited small seedlings may be better adapted to arid environments and unfavorable microsites, where access to water is uncertain and a conservative water use strategy may be advantageous. In contrast, in dry sub-humid areas, areas with deep soils, protected from excess radiation, and areas where irrigation is feasible, well-fertilized big seedlings with high root growth potential may have more chances of success. We discuss this theory in the context of the multiple objectives of dryland restoration and the environmental constrains posed by these areas, and identify knowledge gaps that should be targeted to test our hypothesis.

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Contexte: Les approches de synthèse exploratoire (ou scoping studies) font actuellement l’objet de confusion dans leur appellation, définition et but. Elles continuent aussi de manquer de description méthodologique suffisante ou de détails sur le processus de l’analyse de données. Objectif : Cette synthèse exploratoire fait le point des connaissances sur les approches de synthèse exploratoire utilisées en santé. Plus spécifiquement, ses objectifs sont : 1) d’examiner le volume et l’étendue des synthèses exploratoires ainsi que les domaines d’étude dans lesquels elles ont été conduites; 2) de faire l’inventaire de leurs définitions, buts, forces et faiblesses; et 3) et de faire l’inventaire des approches méthodologiques existantes. Méthodes : Une recherche systématique des synthèses exploratoires a été entreprise jusqu’en avril 2014 dans les bases de données Medline, PubMed, ERIC, PsycINFO, CINAHL, EMBASE, EBM Reviews/Cochrane. Des critères d’inclusion et d’exclusion ont été appliqués afin de ne retenir que des études de langue française et anglaise présentant des définitions, méthodes et écarts de connaissances sur les synthèses exploratoires, ainsi que celles les comparant à d’autres types de revues de littérature. Deux reviseurs ont examiné de façon indépendante les références pertinentes. Une grille d’extraction des données a été conçue afin de recueillir pour chacune des études, les données contextuelles, les étapes méthodologiques ainsi que les définitions, buts et limites des synthèses exploratoires. Les données ont été répertoriées et classées afin de dresser un portrait global des approches de synthèses exploratoires dans un format narratif et tabulaire. Résultats : Sur deux cent cinquante-deux références identifiées, quatre-vingt-douze références pertinentes ont été retenues. Les synthèses exploratoires ont été publiées par 6 pays dans 10 domaines d’études et 73 journaux. Elles ont pour finalité d’être à la fois un support aux connaissances, une aide à la décision et un préalable à une revue systématique de littérature. Cinq auteurs ont été cités en référence et huit autres ont publié sur leur méthodologie. Elles ont 3 étapes importantes de réalisation dont la revue de littérature, la consultation des parties prenantes et la synthèse globale avec ou sans validation des résultats. Les synthèses exploratoires utilisent une méthode systématique, pas toujours exhaustive et sans évaluation formelle des études incluses Des notions claires portant sur leur définition, buts, forces et faiblesses ont été identifiées. Conclusion : Nous suggérons que de nouvelles études soient entreprises afin d’asseoir complètement cette méthode et dégager des lignes directrices pour les chercheurs qui s’y intéresseront.

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Marteilia sydneyi (Paramyxea) is the causative agent of QX disease in oysters. In spite of the economic impact of this disease, its origin and the precise reason(s) for its apparent spread in Australian waters are not yet known. Given such knowledge gaps, investigating the population genetic structure(s) of M. sydneyi populations could provide insights into the epidemiology and ecology of the parasite and could assist in its prevention and control. In this study, single strand conformation polymorphism (SSCP)-based analysis of a region (195 bp) of the first internal transcribed spacer (ITS-1) of ribosomal DNA was employed to investigate genetic variation within and among five populations of M. sydneyi from oysters from five different locations in eastern Australia. The analysis showed the existence of a genetic variant of M. sydneyi common to the Great Sandy Strait, and the Richmond and Georges Rivers, as distinct from variants at the Pimpama and Clarence Rivers. Together with historical and other information relating to the QX disease outbreaks in eastern Australia, the molecular findings support the proposal that the parasite originated in the Great Sandy Strait and/or Richmond River and then extended southward along the coast. From a technical perspective, the study demonstrated the usefulness of SSCP as a tool to study the population genetics and epidemiology of M. sydneyi. (C) 2003 Elsevier Ltd. All rights reserved.

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CO2 Geosequestration is seen by many worldwide scientists and engineers as a leading prospective solution to the global warming problem arising from excessive CO2 and other greenhouse gas emissions. CO2 geosequestration in coal seams has two important strategic benefits: the process has an extremely low risk of leakage, due to the adsorbed state of the CO2 and the known reservoir context of essentially-zero leakage into which it is be injected; the second benefit arises from the valuable by-product, clean burning coalbed methane gas. This paper presents the authors’ experience, knowledge and perspective on what coal properties and engineering processes would favour implementing a demonstration or commercial CO2 storage-in-coal project, in Queensland, Australia. As such, it may be considered a template for screening studies to select the optimum coal seam reservoir, and for preliminary studies in designing the injection system and predicting production response to the technology. The paper concludes by examining the current knowledge gaps of CO2 geosequestration in coal, identifying further basic and applied research topics.

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Communication in Forensic Contexts provides in-depth coverage of the complex area of communication in forensic situations. Drawing on expertise from forensic psychology, linguistics and law enforcement worldwide, the text bridges the gap between these fields in a definitive guide to best practice. • Offers best practice for understanding and improving communication in forensic contexts, including interviewing of victims, witnesses and suspects, discourse in courtrooms, and discourse via interpreters • Bridges the knowledge gaps between forensic psychology, forensic linguistics and law enforcement, with chapters written by teams bringing together expertise from each field • Published in collaboration with the International Investigative Interviewing Research Group, dedicated to furthering evidence-based practice and practice-based research amongst researchers and practitioners • International, cross-disciplinary team includes contributors from North America, Europe and Asia Pacific, and from psychology, linguistics and forensic practice

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This study was concerned with the computer automation of land evaluation. This is a broad subject with many issues to be resolved, so the study concentrated on three key problems: knowledge based programming; the integration of spatial information from remote sensing and other sources; and the inclusion of socio-economic information into the land evaluation analysis. Land evaluation and land use planning were considered in the context of overseas projects in the developing world. Knowledge based systems were found to provide significant advantages over conventional programming techniques for some aspects of the land evaluation process. Declarative languages, in particular Prolog, were ideally suited to integration of social information which changes with every situation. Rule-based expert system shells were also found to be suitable for this role, including knowledge acquisition at the interview stage. All the expert system shells examined suffered from very limited constraints to problem size, but new products now overcome this. Inductive expert system shells were useful as a guide to knowledge gaps and possible relationships, but the number of examples required was unrealistic for typical land use planning situations. The accuracy of classified satellite imagery was significantly enhanced by integrating spatial information on soil distribution for Thailand data. Estimates of the rice producing area were substantially improved (30% change in area) by the addition of soil information. Image processing work on Mozambique showed that satellite remote sensing was a useful tool in stratifying vegetation cover at provincial level to identify key development areas, but its full utility could not be realised on typical planning projects, without treatment as part of a complete spatial information system.

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Background: Despite chronic pain being a feature of functional chest pain (FCP) its experience is variable. The factors responsible for this variability remain unresolved. We aimed to address these knowledge gaps, hypothesizing that the psychophysiological profiles of FCP patients will be distinct from healthy subjects. Methods: 20 Rome III defined FCP patients (nine males, mean age 38.7 years, range 28-59 years) and 20 healthy age-, sex-, and ethnicity-matched controls (nine males, mean 38.2 years, range 24-49) had anxiety, depression, and personality traits measured. Subjects had sympathetic and parasympathetic nervous system parameters measured at baseline and continuously thereafter. Subjects received standardized somatic (nail bed pressure) and visceral (esophageal balloon distension) stimuli to pain tolerance. Venous blood was sampled for cortisol at baseline, post somatic pain and post visceral pain. Key Results: Patients had higher neuroticism, state and trait anxiety, and depression scores but lower extroversion scores vs controls (all p < 0.005). Patients tolerated less somatic (p < 0.0001) and visceral stimulus (p = 0.009) and had a higher cortisol at baseline, and following pain (all p < 0.001). At baseline, patients had a higher sympathetic tone (p = 0.04), whereas in response to pain they increased their parasympathetic tone (p ≤ 0.008). The amalgamating the data, we identified two psychophysiologically distinct 'pain clusters'. Patients were overrepresented in the cluster characterized by high neuroticism, trait anxiety, baseline cortisol, pain hypersensitivity, and parasympathetic response to pain (all p < 0.03). Conclusions & Inferences: In future, such delineations in FCP populations may facilitate individualization of treatment based on psychophysiological profiling. © 2013 John Wiley & Sons Ltd.