Use of forensic investigations in anti-doping.

The fight against doping is mainly focused on direct detection, using analytical methods for the detection of doping agents in biological samples. However, the World Anti-Doping Code also defines doping as possession, administration or attempted administration of prohibited substances or methods, trafficking or attempted trafficking in any prohibited substance or methods. As these issues correspond to criminal investigation, a forensic approach can help assessing potential violation of these rules. In the context of a rowing competition, genetic analyses were conducted on biological samples collected in infusion apparatus, bags and tubing in order to obtain DNA profiles. As no database of athletes' DNA profiles was available, the use of information from the location detection as well as contextual information were key to determine a population of suspected athletes and to obtain reference DNA profiles for comparison. Analysis of samples from infusion systems provided 8 different DNA profiles. The comparison between these profiles and 8 reference profiles from suspected athletes could not be distinguished. This case-study is one of the first where a forensic approach was applied for anti-doping purposes. Based on this investigation, the International Rowing Federation authorities decided to ban not only the incriminated athletes, but also the coaches and officials for 2 years.

Audit report on the Shelby County Area Solid Waste Agency for the year ended June 30, 2007

Audit report on the Shelby County Area Solid Waste Agency for the year ended June 30, 2007

Jackson County Sanitary Disposal Agency independent auditor's reports, basic financial statements and required supplementary information, schedule of findings, June 30, 2007

Audit report on the Jackson County Sanitary Disposal Agency for the year ended June 30, 2007

Audit report on the Heart of Iowa Regional Transit Agency, Des Moines, for the year ended June 30, 2007

Audit report on the Heart of Iowa Regional Transit Agency, Des Moines, for the year ended June 30, 2007

Audit report on the Westory Fire Agency for the year ended June 30, 2007

Audit report on the Westory Fire Agency for the year ended June 30, 2007

In vivo targeting of an anti-tumor antibody coupled to antigenic MHC class I complexes induces specific growth inhibition and regression of established syngeneic tumor grafts.

The concept of antibody-mediated targeting of antigenic MHC/peptide complexes on tumor cells in order to sensitize them to T-lymphocyte cytotoxicity represents an attractive new immunotherapy strategy. In vitro experiments have shown that an antibody chemically conjugated or fused to monomeric MHC/peptide can be oligomerized on the surface of tumor cells, rendering them susceptible to efficient lysis by MHC-peptide restricted specific T-cell clones. However, this strategy has not yet been tested entirely in vivo in immunocompetent animals. To this aim, we took advantage of OT-1 mice which have a transgenic T-cell receptor specific for the ovalbumin (ova) immunodominant peptide (257-264) expressed in the context of the MHC class I H-2K(b). We prepared and characterized conjugates between the Fab' fragment from a high-affinity monoclonal antibody to carcinoembryonic antigen (CEA) and the H-2K(b) /ova peptide complex. First, we showed in OT-1 mice that the grafting and growth of a syngeneic colon carcinoma line transfected with CEA could be specifically inhibited by systemic injections of the conjugate. Next, using CEA transgenic C57BL/6 mice adoptively transferred with OT-1 spleen cells and immunized with ovalbumin, we demonstrated that systemic injections of the anti-CEA-H-2K(b) /ova conjugate could induce specific growth inhibition and regression of well-established, palpable subcutaneous grafts from the syngeneic CEA-transfected colon carcinoma line. These results, obtained in a well-characterized syngeneic carcinoma model, demonstrate that the antibody-MHC/peptide strategy can function in vivo. Further preclinical experimental studies, using an anti-viral T-cell response, will be performed before this new form of immunotherapy can be considered for clinical use.

Corruption and the Hadleyburg effect

We study the dynamics of corruption relying on two fundamental observations:(a) Given agents detected as corrupt are typically fired and replaced, the historical levels of corruption have an impact on current corruption throughthe distribution of corruption costs of old agents; (b) Institutions negatively affected by their agents' corrupt activities are likely to respond optimally to it thereby decreasing the payoff from being corrupt. We model this situation by considering an agent who is supposed to monitor acontractor's delivery of a product or service and can manipulate hisreports thus allowing the contractor to deliver lower quality in exchange for a bribe. Given the two generations of agents overlapping at any particular date, the administration sets an optimal level of quality in eachperiod. We find that (i) A unique steady state level of corruption exists;(ii) Regardless of the initial distribution, apart from an initial period,equilibrium sequences are decreasing and converge to the steady state, aresult we term the "Hadleyburg effect". We use these findings to study thedynamic response of corruption to both temporary and permanent shocks to theprofitability of corruption and we find that the "Hadleyburg effect" hasimportant positive and normative implications.

Iodine-131-labeled MAb F(ab')2 fragments are more efficient and less toxic than intact anti-CEA antibodies in radioimmunotherapy of large human colon carcinoma grafted in nude mice.

During one week, beginning 18 days after transplantation, nude mice bearing human colon carcinoma ranging from 115 to 943 mm3 (mean 335 mm3) were treated by repeated intravenous injections of either iodine-131-(131I) labeled intact antibodies or 131I-labeled corresponding F(ab')2 fragments of a pool of four monoclonal antibodies (MAbs) directed against distinct epitopes of carcinoembryonic antigen (CEA). Complete tumor remission was observed in 8 of 10 mice after therapy with F(ab')2 and 6 of the animals survived 10 mo in good health. In contrast, after treatment with intact MAbs, tumors relapsed in 7 of 8 mice after remission periods of 1 to 3.5 mo despite the fact that body weight loss and depression of peripheral white blood cells, symptoms of radiation toxicity, and the calculated radiation doses for liver, spleen, bone, and blood were increased or equal in these animals as compared to mice treated with F(ab')2.

Audit report on the Crawford County Area Solid Waste Agency Commission for the year ended June 30, 2007

Audit report on the Crawford County Area Solid Waste Agency Commission for the year ended June 30, 2007

Audit report on the ADLM Counties Environmental Public Health Agency for the year ended June 30, 2007

Audit report on the ADLM Counties Environmental Public Health Agency for the year ended June 30, 2007

Economic integration and corruption: The corrupt soul of the European Union

We study the link between corruption and economic integration. We show that if an economic union establishes a common regulation for public procurement, the country more prone to corruption benefits more from integration. However, if the propensities to corruption are too distinct, the less corrupt country will not be willing to join the union. This difference in corruption propensities can be offset by a difference in efficiency. We also show that corruption is lower if integration occurs. A panel data analysis for the European Union confirms that more corrupt countries are more favorable towards integration but less acceptable as potential new members.

Anti-60kDa heat shock protein antibodies in fetal serum : a biomarker for unexplained small for gestational age fetuses

Rapport de synthèseObjectifsLe retard de croissance intrautérin (RCIU) est un problème affectant 10% des grossesses et est associé à une morbidité périnatale importante. Dans environ 80% des cas, une étiologie ou un facteur de risque majeur peuvent être identifiés. Mais près de 20% des cas sont considérés comme inexpliqués. La heat shock protéine 60kDa (HSP60) est une protéine fortement immunogène dont la synthèse est considérablement augmentée lors de conditions non- physiologiques. Les HSP60 humaines et bactériennes partagent un haut degré d'homologie de séquence ce qui peut engendrer une maladie auto-immune à la suite d'une infection bactérienne. Nous avons supposé que les RCIU inexpliqués pourraient être la conséquence d'une sensibilisation à l'HSP60 humaine.MéthodesLes RCIU inexpliqués ont été identifiés par mesure échographique avec un doppler normal, sans anomalies décelables chez la mère ou le foetus. Les sera foetaux ont été obtenus par cordocentèse, effectuée lors d'analyse du caryotype en cas de RCIU inexpliqué (groupe d'étude) ou pour le dépistage d'une incompatibilité Rhésus (groupe témoin). Ils ont été testés pour l'antigène HSP60 et les IgG et IgM anti-HSP60 par ELISA ainsi que pour d'autres paramètres immunitaires et hématologiques.RésultatsLes paramètres maternels sont similaires entre les 12 cas du groupe d'étude et les 23 cas du groupe contrôle. L'âge gestationnel moyen lors de la cordocentèse est de 29 semaines. Les IgM anti-HSP60 sont détectés dans 12 cas d'étude (100%) mais dans aucun cas contrôle (p <0,00017), les IgG anti-HSP60 dans 7 cas d'étude (58%) et un seul dans le groupe contrôle (p <0,001). Trois des quatre cas avec les taux d'IgM les plus élevés sont décédés. Il n'y a pas de différences entre les deux groupes quant aux taux d'antigène HSP60 ou d'autres marqueurs immunologiques ou hématologiques.ConclusionLes foetus avec un RCIU inexpliqué expriment un taux élevé d'anticorps IgM et IgG contre l'HSP60 humaine et le taux d'IgM est un facteur prédictif de la mortalité foetale. La détection de ces anticorps indique qu'une perturbation placentaire et une réaction auto-immune foetale liée à l'HSP60 sont associées à ce retard de développement chez le foetus.

Combating corruption in international business transactions

We analyze the impact of different types of international conventions thatrequire signatory countries to penalize domestic firms that are found tohave bribed foreign public officials. We analyze enforcement of penaltiesunder a convention styled after the OECD's 'Convention on Combating Briberyof Foreign Public Officials in International Business Transactions', in whichsignatory countries commit to prosecuting firms that have bribed publicofficials of any foreign country. We compare the results with the case inwhich the convention requires signatory countries to commit to prosecutingfirms that have bribed public officials of signatory countries only.We argue that the second type of convention is more likely to ensureenforcement of penalties on firms found to have bribed foreign publicofficials.

Report on the Shelby County Area Solid Waste Agency for the year ended June 30, 2008

Report on the Shelby County Area Solid Waste Agency for the year ended June 30, 2008