Coupling in silico and in vitro analysis of peptide-MHC binding:a bioinformatic approach enabling prediction of superbinding peptides and anchorless epitopes

The ability to define and manipulate the interaction of peptides with MHC molecules has immense immunological utility, with applications in epitope identification, vaccine design, and immunomodulation. However, the methods currently available for prediction of peptide-MHC binding are far from ideal. We recently described the application of a bioinformatic prediction method based on quantitative structure-affinity relationship methods to peptide-MHC binding. In this study we demonstrate the predictivity and utility of this approach. We determined the binding affinities of a set of 90 nonamer peptides for the MHC class I allele HLA-A*0201 using an in-house, FACS-based, MHC stabilization assay, and from these data we derived an additive quantitative structure-affinity relationship model for peptide interaction with the HLA-A*0201 molecule. Using this model we then designed a series of high affinity HLA-A2-binding peptides. Experimental analysis revealed that all these peptides showed high binding affinities to the HLA-A*0201 molecule, significantly higher than the highest previously recorded. In addition, by the use of systematic substitution at principal anchor positions 2 and 9, we showed that high binding peptides are tolerant to a wide range of nonpreferred amino acids. Our results support a model in which the affinity of peptide binding to MHC is determined by the interactions of amino acids at multiple positions with the MHC molecule and may be enhanced by enthalpic cooperativity between these component interactions.

Application of the Artificial Intelligence Algorithms for System Analysis of Multi Dimension Physiological Data for Developing Polyparametric Information System of Public Health Diagnostics

The polyparametric intelligence information system for diagnostics human functional state in medicine and public health is developed. The essence of the system consists in polyparametric describing of human functional state with the unified set of physiological parameters and using the polyparametric cognitive model developed as the tool for a system analysis of multitude data and diagnostics of a human functional state. The model is developed on the basis of general principles geometry and symmetry by algorithms of artificial intelligence systems. The architecture of the system is represented. The model allows analyzing traditional signs - absolute values of electrophysiological parameters and new signs generated by the model – relationships of ones. The classification of physiological multidimensional data is made with a transformer of the model. The results are presented to a physician in a form of visual graph – a pattern individual functional state. This graph allows performing clinical syndrome analysis. A level of human functional state is defined in the case of the developed standard (“ideal”) functional state. The complete formalization of results makes it possible to accumulate physiological data and to analyze them by mathematics methods.

An analysis and comparison of commonly available United Kingdom prescribing resources

Background and objective: Safe prescribing requires accurate and practical information about drugs. Our objective was to measure the utility of current sources of prescribing guidance when used to inform practical prescribing decisions, and to compare current sources of prescribing guidance in the UK with idealized prescribing guidance. Methods: We developed 25 clinical scenarios. Two independent assessors rated and ranked the performance of five common sources of prescribing guidance in the UK when used to answer the clinical scenarios. A third adjudicator facilitated review of any disparities. An idealized list of contents for prescribing guidance was developed and sent for comments to academics and users of prescribing guidance. Following consultation an operational check was used to assess compliance with the idealized criteria. The main outcome measures were relative utility in answering the clinical scenarios and compliance with the idealized prescribing guidance. Results: Current sources of prescribing guidance used in the UK differ in their utility, when measured using clinical scenarios. The British National Formulary (BNF) and EMIS LV were the best performing sources in terms of both ranking [mean rank 1·24 and 2·20] and rating [%excellent or adequate 100% and 72%]. Current sources differed in the extent to which they fulfilled criteria for ideal prescribing guidance, but the BNF, and EMIS LV to a lesser extent, closely matched the criteria. Discussion: We have demonstrated how clinical scenarios can be used to assess prescribing guidance resources. Producers of prescribing guidance documents should consider our idealized template. Prescribers require high-quality information to support their practice. Conclusion: Our test was helpful in distinguishing between prescribing resources. Producers of prescribing guidance should consider the utility of their products to end-users, particularly in those more complex areas where prescribers may need most support. Existing UK prescribing guidance resources differ in their ability to provide assistance to prescribers. © 2010 Blackwell Publishing Ltd.

Több szempontú részvételi döntések a fenntarthatósági értékelésekben. A legnépszerűbb módszerek összehasonlítása = Participatory multi-criteria decision analysis. A comparison of methodologies

A fenntarthatóság értékelése definíciószerűen többdimenziós probléma. A megfelelő alternatíva, forgatókönyv, eljárás stb. kiválasztásakor ugyanis a döntéshozóknak egyszerre kell figyelembe venniük környezetvédelmi, gazdasági és társadalmi szempontokat. Az ilyen döntéseket alátámaszthatják a több szempontú döntéshozatali modellek. A tanulmány a több szempontú döntési eljárások közül a legfontosabb hétnek az alkalmazhatóságát vizsgálja részvételi körülmények között. Az utóbbi évek e témában publikált esettanulmányainak áttekintésével megállapítható, hogy egyik módszer sem uralja a többit, azok különböző feltételek mellett eltérő sikerrel használhatók. Ennek ellenére a különböző módszerek kombinációjával végrehajthatunk olyan eljárásokat, amelyekkel az egyes módszerek előnyeit még jobban kiaknázhatjuk. ________ Measuring and comparing the sustainability of certain actions, scenarios, technologies, etc. is by definition a multidimensional problem. Decision-makers must consider environmental, economic and social aspects when choosing an alternative course of action. Such decisions can be aided by multi-criteria decision analysis (MCDA). This paper investigates seven different MCDA methodologies: MAU, the Analytic Hierarchic Process (AHP), the ELECTRE, PROMETHEE, REGIME, and NAIADE methods, and "Ideal and reference point" approaches). It is based on a series of reports in which over 30 real-world case studies focusing on participatory MCDA were reviewed. It is stressed, however, that there is no "best" choice in the list of MCDA techniques. Some methods fit certain decision problems better than others. Nonetheless, some complementary benefits of the different techniques can be exploited by combining these methodologies.

Against small arms: An analysis of an international network

Small Arms and Light Weapons (SALW) proliferation was undertaken by the Non-Governmental Organizations (NGOs) as the next important issue in international relations after the success of the International Campaign to Ban Landmines (ICBL). This dissertation focuses on the reasons why the issue of SALW resulted in an Action Program rather than an international convention. Thus, this result was considered as unsuccessful by the advocates of regulating the illicit trade in SALW. The study provides a social movement theoretical approach, using framing, political opportunity and network analysis to explain why the advocates of regulating the illicit trade in SALW did no succeed in their goals. The UN is taken as the arena in which NGOs, States and International Governmental Organizations (IGOs) discussed the illicit trade in SALW. ^ The findings of the study indicate that the political opportunity for the issue of SALW was not ideal. The network of NGOs, States and IGOs was not strong. The NGOs advocating regulation of SALW were divided over the approach of the issue and were part of different coalitions with differing objectives. Despite initial widespread interest among States, only a couple of States were fully committed to the issue till the end. The regional IGOs approached the issue based on their regional priorities and were less interested in an international covenant. The advocates of regulating illicit trade in SALW attempted to frame SALW as a humanitarian issue rather than as a security issue. Thus they were not able to use frame alignment to convince states to treat SALW as a humanitarian issue. In conclusion it can be said that all three items, framing, political opportunity and the network, play a role in the lack of success of advocates for regulating the illicit trade in SALW. ^

Comprehensive forensic toxicological analysis of designer drugs

New designer drugs are constantly emerging onto the illicit drug market and it is often difficult to validate and maintaincomprehensive analytical methods for accurate detection of these compounds. Generally, toxicology laboratories utilize a screening method, such as immunoassay, for the presumptive identification of drugs of abuse. When a positive result occurs, confirmatory methods, such as gas chromatography (GC) or liquid chromatography (LC) coupled with mass spectrometry (MS), are required for more sensitive and specific analyses. In recent years, the need to study the activities of these compounds in screening assays as well as to develop confirmatory techniques to detect them in biological specimens has been recognized. Severe intoxications and fatalities have been encountered with emerging designer drugs, presenting analytical challenges for detection and identification of such novel compounds. The first major task of this research was to evaluate the performance of commercially available immunoassays to determine if designer drugs were cross-reactive. The second major task was to develop and validate a confirmatory method, using LC-MS, to identify and quantify these designer drugs in biological specimens.^ Cross-reactivity towards the cathinone derivatives was found to be minimal. Several other phenethylamines demonstrated cross-reactivity at low concentrations, but results were consistent with those published by the assay manufacturer or as reported in the literature. Current immunoassay-based screening methods may not be ideal for presumptively identifying most designer drugs, including the "bath salts." For this reason, an LC-MS based confirmatory method was developed for 32 compounds, including eight cathinone derivatives, with limits of quantification in the range of 1-10 ng/mL. The method was fully validated for selectivity, matrix effects, stability, recovery, precision, and accuracy. In order to compare the screening and confirmatory techniques, several human specimens were analyzed to demonstrate the importance of using a specific analytical method, such as LC-MS, to detect designer drugs in serum as immunoassays lack cross-reactivity with the novel compounds. Overall, minimal cross-reactivity was observed, highlighting the conclusion that these presumptive screens cannot detect many of the designer drugs and that a confirmatory technique, such as the LC-MS, is required for the comprehensive forensic toxicological analysis of designer drugs.^

Heavily obscured AGN: an ideal laboratory to study the early co-evolution of galaxies and black holes

Obscured AGN are a crucial ingredient to understand the full growth history of super massive black holes and the coevolution with their host galaxies, since they constitute the bulk of the BH accretion. In the distant Universe, many of them are hosted by submillimeter galaxies (SMGs), characterized by a high production of stars and a very fast consumption of gas. Therefore, the analysis of this class of objects is fundamental to investigate the role of the ISM in the early coevolution of galaxies and black holes. We present a multiwavelength study of a sample of six obscured X-ray selected AGN at z>2.5 in the CDF-S, detected in the far-IR/submm bands. We performed the X-ray spectral analysis based on the 7Ms Chandra dataset, which provides the best X-ray spectral information currently available for distant AGN. We were able to place constraints on the obscuring column densities and the intrinsic luminosities of our targets. Moreover, we built up the UV to FIR spectral energy distributions (SEDs) by combining the broad-band photometry from CANDELS and the Herschel catalogs, and analyzed them by means of an SED decomposition technique. Therefore, we derived important physical parameters of both the host galaxy and the AGN. In addition, we obtained, through an empirical calibration, the gas mass in the host galaxy and assessed the galaxy sizes in order to estimate the column density associated with the host ISM. The comparison of the ISM column densities with the values measured from the X-ray spectral analysis pointed out that the contribution of the host ISM to the obscuration of the AGN emission can be substantial, ranging from ~10% up to ~100% of the value derived from the X-ray spectra. The absorption may occur at different physical scales in these sources and, in particular, the medium in the host galaxy is an ingredient that should be taken into account, since it may have a relevant role in driving the early co-evolution of galaxies with their black holes.

Evaporation maps for ternary non-ideal liquid mixtures

This thesis deals with the evaporation of non-ideal liquid mixtures using a multicomponent mass transfer approach. It develops the concept of evaporation maps as a convenient way of representing the dynamic composition changes of ternary mixtures during an evaporation process. Evaporation maps represent the residual composition of evaporating ternary non-ideal mixtures over the full range of composition, and are analogous to the commonly-used residue curve maps of simple distillation processes. The evaporation process initially considered in this work involves gas-phase limited evaporation from a liquid or wetted-solid surface, over which a gas flows at known conditions. Evaporation may occur into a pure inert gas, or into one pre-loaded with a known fraction of one of the ternary components. To explore multicomponent masstransfer effects, a model is developed that uses an exact solution to the Maxwell-Stefan equations for mass transfer in the gas film, with a lumped approach applied to the liquid phase. Solutions to the evaporation model take the form of trajectories in temperaturecomposition space, which are then projected onto a ternary diagram to form the map. Novel algorithms are developed for computation of pseudo-azeotropes in the evaporating mixture, and for calculation of the multicomponent wet-bulb temperature at a given liquid composition. A numerical continuation method is used to track the bifurcations which occur in the evaporation maps, where the composition of one component of the pre-loaded gas is the bifurcation parameter. The bifurcation diagrams can in principle be used to determine the required gas composition to produce a specific terminal composition in the liquid. A simple homotopy method is developed to track the locations of the various possible pseudo-azeotropes in the mixture. The stability of pseudo-azeotropes in the gas-phase limited case is examined using a linearized analysis of the governing equations. Algorithms for the calculation of separation boundaries in the evaporation maps are developed using an optimization-based method, as well as a method employing eigenvectors derived from the linearized analysis. The flexure of the wet-bulb temperature surface is explored, and it is shown how evaporation trajectories cross ridges and valleys, so that ridges and valleys of the surface do not coincide with separation boundaries. Finally, the assumption of gas-phase limited mass transfer is relaxed, by employing a model that includes diffusion in the liquid phase. A finite-volume method is used to solve the system of partial differential equations that results. The evaporation trajectories for the distributed model reduce to those of the lumped (gas-phase limited) model as the diffusivity in the liquid increases; under the same gas-phase conditions the permissible terminal compositions of the distributed and lumped models are the same.

A tight-binding analysis of the electronic properties of III-nitride semiconductors

This thesis divides into two distinct parts, both of which are underpinned by the tight-binding model. The first part covers our implementation of the tight-binding model in conjunction with the Berry phase theory of electronic polarisation to probe the atomistic origins of spontaneous polarisation and piezoelectricity as well as attempting to accurately calculate the values and coefficients associated with these phenomena. We first develop an analytic model for the polarisation of a one-dimensional linear chain of atoms. We compare the zincblende and ideal wurtzite structures in terms of effective charges, spontaneous polarisation and piezoelectric coefficients, within a first nearest neighbour tight-binding model. We further compare these to real wurtzite structures and conclude that accurate quantitative results are beyond the scope of this model but qualitative trends can still be described. The second part of this thesis deals with implementing the tight-binding model to investigate the effect of local alloy fluctuations in bulk AlGaN alloys and InGaN quantum wells. We calculate the band gap evolution of Al1_xGaxN across the full composition range and compare it to experiment as well as fitting bowing parameters to the band gap as well as to the conduction band and valence band edges. We also investigate the wavefunction character of the valence band edge to determine the composition at which the optical polarisation switches in Al1_xGaxN alloys. Finally, we examine electron and hole localisation in InGaN quantum wells. We show how the built-in field localises the carriers along the c-axis and how local alloy fluctuations strongly localise the highest hole states in the c-plane, while the electrons remain delocalised in the c-plane. We show how this localisation affects the charge density overlap and also investigate the effect of well width fluctuations on the localisation of the electrons.

Series-L/parallel-tuned Class-E power amplifier analysis

An analysis of the operation of a new series-L/parallel-tuned Class-E amplifier and its equivalence to the classic shunt-C/series-tuned Class-E amplifier are presented. The first reported closed form design equations for the series-L/parallel-tuned topology operating under ideal switching conditions are given, including the switch current and voltage in steady state, the circuit component values, the peak values of switch current and voltage and the power-output capability. Theoretical analysis is confirmed by numerical simulation for a 500 mW (27 dBm), 10% bandwidth, 5 V series-L/parallel-tuned, then, shunt-C/series-tuned Class-E power amplifier, operating at 2.5 GHz. Excellent agreement between theory and simulation results is achieved.

El concepto de ciudadanía en la obra de Dominique Schnapper: entre el tipo ideal sociológico y el ideal de sociedad democrática

Este artículo analiza la evolución del concepto de ciudadanía en la obra de Dominique Schnapper como uno de los ejemplos más destacados en la sociología contemporánea de una aproximación completa a la cuestión. A través de un recorrido exhaustivo por su obra, el objetivo es profundizar en la comprensión de la tensión entre la dinámica democrática y la idea de ciudadanía en cuanto que tipo ideal del vínculo social y como principio regulador de las sociedades democráticas. La autora propone en sus primeros trabajos una noción de ciudadanía vinculada al proceso político de construcción de la nación que no distingue entre la definición de un tipo ideal sociológico y la construcción de un ideal de sociedad. Esta confusión se corrige al introducir posteriormente en el análisis la incidencia de la democracia sobre las experiencias individuales de la ciudadanía, aportando una perspectiva de análisis de gran utilidad tanto para la comprensión de la dinámica contemporánea de las sociedades democráticas como para la necesaria defensa de la ciudadanía como vínculo social fundamental y como principio fundador de la legitimidad política.

Distribution, occurrence and biotoxin composition of the main shellfish toxin producing microalgae within European waters: A comparison of methods of analysis.

Harmful algal blooms (HABs) are a natural global phenomena emerging in severity and extent. Incidents have many economic, ecological and human health impacts. Monitoring and providing early warning of toxic HABs are critical for protecting public health. Current monitoring programmes include measuring the number of toxic phytoplankton cells in the water and biotoxin levels in shellfish tissue. As these efforts are demanding and labour intensive, methods which improve the efficiency are essential. This study compares the utilisation of a multitoxin surface plasmon resonance (multitoxin SPR) biosensor with enzyme-linked immunosorbent assay (ELISA) and analytical methods such as high performance liquid chromatography with fluorescence detection (HPLC-FLD) and liquid chromatography–tandem mass spectrometry (LC–MS/MS) for toxic HAB monitoring efforts in Europe. Seawater samples (n = 256) from European waters, collected 2009–2011, were analysed for biotoxins: saxitoxin and analogues, okadaic acid and dinophysistoxins 1/2 (DTX1/DTX2) and domoic acid responsible for paralytic shellfish poisoning (PSP), diarrheic shellfish poisoning (DSP) and amnesic shellfish poisoning (ASP), respectively. Biotoxins were detected mainly in samples from Spain and Ireland. France and Norway appeared to have the lowest number of toxic samples. Both the multitoxin SPR biosensor and the RNA microarray were more sensitive at detecting toxic HABs than standard light microscopy phytoplankton monitoring. Correlations between each of the detection methods were performed with the overall agreement, based on statistical 2 × 2 comparison tables, between each testing platform ranging between 32% and 74% for all three toxin families illustrating that one individual testing method may not be an ideal solution. An efficient early warning monitoring system for the detection of toxic HABs could therefore be achieved by combining both the multitoxin SPR biosensor and RNA microarray.

Distribution, occurrence and biotoxin composition of the main shellfish toxin producing microalgae within European waters: A comparison of methods of analysis.

Harmful algal blooms (HABs) are a natural global phenomena emerging in severity and extent. Incidents have many economic, ecological and human health impacts. Monitoring and providing early warning of toxic HABs are critical for protecting public health. Current monitoring programmes include measuring the number of toxic phytoplankton cells in the water and biotoxin levels in shellfish tissue. As these efforts are demanding and labour intensive, methods which improve the efficiency are essential. This study compares the utilisation of a multitoxin surface plasmon resonance (multitoxin SPR) biosensor with enzyme-linked immunosorbent assay (ELISA) and analytical methods such as high performance liquid chromatography with fluorescence detection (HPLC-FLD) and liquid chromatography–tandem mass spectrometry (LC–MS/MS) for toxic HAB monitoring efforts in Europe. Seawater samples (n = 256) from European waters, collected 2009–2011, were analysed for biotoxins: saxitoxin and analogues, okadaic acid and dinophysistoxins 1/2 (DTX1/DTX2) and domoic acid responsible for paralytic shellfish poisoning (PSP), diarrheic shellfish poisoning (DSP) and amnesic shellfish poisoning (ASP), respectively. Biotoxins were detected mainly in samples from Spain and Ireland. France and Norway appeared to have the lowest number of toxic samples. Both the multitoxin SPR biosensor and the RNA microarray were more sensitive at detecting toxic HABs than standard light microscopy phytoplankton monitoring. Correlations between each of the detection methods were performed with the overall agreement, based on statistical 2 × 2 comparison tables, between each testing platform ranging between 32% and 74% for all three toxin families illustrating that one individual testing method may not be an ideal solution. An efficient early warning monitoring system for the detection of toxic HABs could therefore be achieved by combining both the multitoxin SPR biosensor and RNA microarray.

SYSTEMATIC REVIEW AND META-ANALYSIS: EFFECTS OF WALKING EXERCISE IN CHRONIC MUSCULOSKELETAL PAIN

SYSTEMATIC REVIEW AND META-ANALYSIS: EFFECTS OF WALKING EXERCISE IN CHRONIC MUSCULOSKELETAL PAIN O'Connor S.R.1, Tully M.A.2, Ryan B.3, Baxter D.G.3, Bradley J.M.1, McDonough S.M.11University of Ulster, Health & Rehabilitation Sciences Research Institute, Newtownabbey, United Kingdom, 2Queen's University, UKCRC Centre of Excellence for Public Health (NI), Belfast, United Kingdom, 3University of Otago, Centre for Physiotherapy Research, Dunedin, New ZealandPurpose: To examine the effects of walking exercise on pain and self-reported function in adults with chronic musculoskeletal pain.Relevance: Chronic musculoskeletal pain is a major cause of morbidity, exerting a substantial influence on long-term health status and overall quality of life. Current treatment recommendations advocate various aerobic exercise interventions for such conditions. Walking may represent an ideal form of exercise due to its relatively low impact. However, there is currently limited evidence for its effectiveness.Participants: Not applicable.Methods: A comprehensive search strategy was undertaken by two independent reviewers according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) and the recommendations of the Cochrane Musculoskeletal Review Group. Six electronic databases (Medline, CINAHL, PsychINFO, PEDro, Sport DISCUS and the Cochrane Central Register of Controlled Trials) were searched for relevant papers published up to January 2010 using MeSH terms. All randomised or non-randomised studies published in full were considered for inclusion. Studies were required to include adults aged 18 years or over with a diagnosis of chronic low back pain, osteoarthritis or fibromyalgia. Studies were excluded if they involved peri-operative or post-operative interventions or did not include a comparative, non exercise or non-walking exercise control group. The U.S. Preventative Services Task Force system was used to assess methodological quality. Data for pain and self-reported function were extracted and converted to a score out of 100.Analysis: Data were pooled and analyzed using RevMan (v.5.0.24). Statistical heterogeneity was assessed using the X2 and I2 test statistics. A random effects model was used to calculate the mean differences and 95% CIs. Data were analyzed by length of final follow-up which was categorized as short (≤8 weeks post randomisation), mid (2-12 months) or long-term (>12 months).Results: A total of 4324 articles were identified and twenty studies (1852 participants) meeting the inclusion criteria were included in the review. Overall, studies were judged to be of at least fair methodological quality. The most common sources of likely bias were identified as lack of concealed allocation and failure to adequately address incomplete data. Data from 12 studies were suitable for meta-analysis. Walking led to reductions in pain at short (<8 weeks post randomisation) (-8.44 [-14.54, -2.33]) and mid-term (>8 weeks - 12 month) follow-up (-9.28 [-16.34, -2.22]). No effect was observed for long-term (>12 month) data (-2.49 [-7.62, 2.65]). For function, between group differences were observed for short (-11.57 [-16.06, -7.08]) and mid-term data (-13.26 [-16.91, -9.62]). A smaller effect was also observed at long-term follow-up (-5.60 [-7.70, -3.50]).Conclusions: Walking interventions were associated with statistically significant improvements in pain and function at short and mid-term follow-up. Long-term data were limited but indicated that these effects do not appear to be maintained beyond twelve months.Implications: Walking may be an effective form of exercise for individuals with chronic musculoskeletal pain. However, further research is required which examines longer term follow-up and dose-response issues in this population.Key-words: 1. Walking exercise 2. Musculoskeletal pain 3. Systematic reviewFunding acknowledgements: Department of Employment and Learning, Northern Ireland.Ethics approval: Not applicable.

Power relations and good governance: a social network analysis of the evolution of the integrity in public office act in the Commonwealth of Dominica

La Banque mondiale propose la bonne gouvernance comme la stratégie visant à corriger les maux de la mauvaise gouvernance et de faciliter le développement dans les pays en développement (Carayannis, Pirzadeh, Popescu & 2012; & Hilyard Wilks 1998; Leftwich 1993; Banque mondiale, 1989). Dans cette perspective, la réforme institutionnelle et une arène de la politique publique plus inclusive sont deux stratégies critiques qui visent à établir la bonne gouvernance, selon la Banque et d’autres institutions de Bretton Woods. Le problème, c’est que beaucoup de ces pays en voie de développement ne possèdent pas l’architecture institutionnelle préalable à ces nouvelles mesures. Cette thèse étudie et explique comment un état en voie de développement, le Commonwealth de la Dominique, s’est lancé dans un projet de loi visant l’intégrité dans la fonction publique. Cette loi, la Loi sur l’intégrité dans la fonction publique (IPO) a été adoptée en 2003 et mis en œuvre en 2008. Cette thèse analyse les relations de pouvoir entre les acteurs dominants autour de évolution de la loi et donc, elle emploie une combinaison de technique de l’analyse des réseaux sociaux et de la recherche qualitative pour répondre à la question principale: Pourquoi l’État a-t-il développé et mis en œuvre la conception actuelle de la IPO (2003)? Cette question est d’autant plus significative quand nous considérons que contrairement à la recherche existante sur le sujet, l’IPO dominiquaise diverge considérablement dans la structure du l’IPO type idéal. Nous affirmons que les acteurs "rationnels," conscients de leur position structurelle dans un réseau d’acteurs, ont utilisé leurs ressources de pouvoir pour façonner l’institution afin qu’elle serve leurs intérêts et ceux et leurs alliés. De plus, nous émettons l’hypothèse que: d’abord, le choix d’une agence spécialisée contre la corruption et la conception ultérieure de cette institution reflètent les préférences des acteurs dominants qui ont participé à la création de ladite institution et la seconde, notre hypothèse rivale, les caractéristiques des modèles alternatifs d’institutions de l’intégrité publique sont celles des acteurs non dominants. Nos résultats sont mitigés. Le jeu de pouvoir a été limité à un petit groupe d’acteurs dominants qui ont cherché à utiliser la création de la loi pour assurer leur légitimité et la survie politique. Sans surprise, aucun acteur n’a avancé un modèle alternatif. Nous avons conclu donc que la loi est la conséquence d’un jeu de pouvoir partisan. Cette recherche répond à la pénurie de recherche sur la conception des institutions de l’intégrité publique, qui semblent privilégier en grande partie un biais organisationnel et structurel. De plus, en étudiant le sujet du point de vue des relations de pouvoir (le pouvoir, lui-même, vu sous l’angle actanciel et structurel), la thèse apporte de la rigueur conceptuelle, méthodologique, et analytique au discours sur la création de ces institutions par l’étude de leur genèse des perspectives tant actancielles que structurelles. En outre, les résultats renforcent notre capacité de prédire quand et avec quelle intensité un acteur déploierait ses ressources de pouvoir.