LES FACTEURS OBJECTIFS DE LA COMPLEXITÉ DE LA TÂCHE EN AUDIT LÉGAL

Les recherches sur les erreurs de jugement en audit légal se sont surtout concentrées sur les causes provenant du manque d'indépendance de l'auditeur. Mais les travaux actuels s'accordent à avancer que ces erreurs sont également liées à la complexité de la tâche en audit (task complexity), cette complexité résultant des caractéristiques de l'auditeur (les facteurs subjectifs) ou de paramètres liés à la mission ellemême (les facteurs objectifs). Aussi, cette communication propose-t-elle de démontrer que les facteurs objectifs expliquant la complexité de la tâche en audit légal ne sont pas à négliger, car ils provoquent aussi des erreurs de certification inévitables du fait de risques difficiles à évaluer, de l'instabilité du droit, de l'absence, de l'abondance ou de l'imprécision de règles comptables ou fiscales.audit légal, complexité, complexité de la tâche, facteurs subjectifs, facteurs objectifs

Modulation de la réponse immunitaire dans le cerveau par la barrière hémato-encéphalique : implication en sclérose en plaques

La sclérose en plaques (SEP) est une maladie inflammatoire du système nerveux central (SNC) caractérisée par une infiltration périvasculaire de cellules mononucléaires, telles que les lymphocytes T CD4+ et CD8+, les lymphocytes B ainsi que les cellules myéloïdes qui comprend les monocytes, les macrophages et les cellules dendritiques (DCs). Ce phénomène d’infiltration est dû à une fragilisation de la barrière hémato-encéphalique (BHE). L’entrée des cellules immunitaires au SNC va mener à la destruction de la gaine de myéline et donc à l’apparition de plaques de démyélinisation. Ainsi, nous avons émis l’hypothèse que la migration des divers sous-types de cellules immunitaires du sang périphérique à travers la BHE est contrôlée par des mécanismes moléculaires distincts et spécifiques à chaque type cellulaire. Afin de répondre à cette hypothèse, quatre différentes études ont été mises sur pieds. En premier lieu, nous démontrons un effet bénéfique des statines sur la BHE en SEP, en diminuant la migration des lymphocytes T et des monocytes, et en diminuant la diffusion de marqueurs moléculaire soluble. Ce phénomène s’opère via la suppression du processus d’isoprenylation, et en empêchant probablement la contraction des cellules endothéliales de la BHE. De plus, nous démontrons que les monocytes qui migrent au SNC en condition inflammé sont en mesures de se différencier en DCs et d’induire une réponse inflammatoire de la part des lymphocytes T CD4+. La migration des monocytes à travers la BHE est contrôlée par une nouvelle molécule d’adhérence nommée Ninjurin-1. Le blocage de Ninjurin-1 conduit à une inhibition spécifique de la migration des monocytes in vitro, ainsi qu’à une amélioration des signes cliniques du modèle animal de la SEP, soit l’encéphalomyélite auto-immune expérimentale (EAE). Finalement, nous démontrons que la migration des lymphocytes T CD8+ au SNC s’effectue via l’intégrine alpha-4. De plus, la majorité des lymphocytes T CD8+ que l’on retrouve dans le liquide céphalo-rachidien de patients SEP, dans le SNC de souris EAE ainsi que dans le SNC de souris infectée au virus de l’hépatite murine portent un phénotype effecteur mémoire. Ces données pourraient expliquer l’émergence de leucoencéphalopathie multifocale progressive observée chez certains patients SEP traités au natalizumab, un anticorps dirigé contre l’intégrine alpha-4. En conclusion, notre étude a permis de démontrer l’importance des monocytes provenant de la périphérie dans le processus inflammatoire prenant part au SNC en SEP. L’inhibition d’entrée de ces cellules pourrait s’avérer bénéfique en SEP tout en permettant l’immuno-surveillance du cerveau, ce que l’anti-alpha-4 intégrine ne permet pas. Les statines pourraient s’avérer une autre option intéressante puisqu’elles agissent sur les processus inflammatoires impliqués dans la SEP.Multiple sclerosis (MS) is an immune-mediated disorder of the central nervous system (CNS) characterized by multifocal areas of leukocyte infiltration and demyelination associated with a breakdown of the blood-brain barrier (BBB). Typically, demyelination is centered around perivascular accumulation of CD4+ and CD8+ T lymphocytes, monocytes, macrophages and dendritic cells (DCs) that arise from migration of peripheral blood immune cells across the CNS microvascular endothelium. We have thus suggested that the migration across the BBB of immune cells subsets from the blood is controlled by molecular mechanism specific for each cell type. To answer this hypothesize, we have performed four different studies. We first show a beneficial effect of statins on the BBB, restricting the migration of lymphocytes and monocytes as well as the diffusion of soluble molecular tracers. This phenomenon is mediated through abrogation of isoprenylation processes that is probably inhibiting the ability of endothelial cells of the BBB to contract. We also show that CD14+ monocytes migrate across the inflamed human blood BBB and differentiate into DCs in response to BBB-secreted TGF-beta and GM-CSF. These DCs then promote the proliferation and expansion of inflammatory CD4+ T lymphocytes. We demonstrate that the migration of monocytes is controlled by a new adhesion molecule called Ninjurin-1. Ninjurin-1 neutralization specifically abrogated the adhesion and migration of human monocytes across endothelial cells of the BBB, without affecting lymphocyte recruitment. Moreover, Ninjurin-1 blockade reduced clinical disease activity and histopathological indices of experimental allergic encephalomyelitis (EAE). Finally we show that migration of CD8+ T lymphocytes across BBB is dependent on alpha-4 integrin. Also, the majority of CD8+ T lymphocytes found in the cerebrospinal fluid of MS patients, and in the CNS of EAE mice as well as the CNS of mouse infected with hepatitis virus are showing an effector memory phenotype. These data could explain the numerous cases of progressive multifocal leukoencephalopathy seen in natalizumab treated MS patients. In conclusion, our study unveils an important role of peripheral monocytes in MS. The inhibition of migration of these cells to the CNS could be a beneficial therapy since it would allow immune surveillance of the brain. The statins could also be a very interesting option since these molecules would reduce the inflammatory processes involved in MS

Hegel on the Absolute, with a Blumenbergian Twist

This article does not seek to settle the question of the meaning and significance of Hegel’s notion of the Absolute. Rather, it seeks to shed new light on the possibility of a relationship with the Absolute, that is, the possibility that the Absolute is something – some entity that we, as subjects, can have a real relation to. To make my case for the plausibility of my reading of the Absolute, I begin by offering an interpretation of Hegel’s “System Fragment.” I then attempt to add substance to the idea of such a relationship by adducing the thought of Hans Blumenberg, a strikingly ‘non-Hegelian’ thinker. After showing that Blumenberg, too, struggled with the question of our relation to the absolute, albeit in a completely different context, I argue that Blumenberg’s reading of the absolute, as a backdrop against which humankind persistently positions itself, suggests a meaningful new direction in the ongoing efforts to interpret the Hegelian Absolute.Este artículo no busca solucionar la cuestión del sentido y de la relevancia del concepto hegeliano de Absoluto. Más bien, busca arrojar nueva luz sobre la posibilidad de una relación con el Absoluto, que es, la posibilidad de que el Absoluto sea algo -una entidad con la que nosotros, en tanto que sujetos, podemos tener una relación real. Para la plausibiilidad de mi lectura del Absoluto, comienzo ofreciendo una interpretación del «Fragmento de sistema» de Hegel. Intento, entonces, dar sustancia a la idea de tal relación trayendo a colación el pensamiento de Hans Blumenberg, sorprendentemente, un pensador no hegeliano. Tras mostrar que también Blumengerg, pugna con la cuestión de nuestra relación con el absoluto,  aunque en un contexto completamente diferente, arguyo que la lectura de Blumenberg del absoluto, como un transformdo contra el que la humanidad se posiciona persistentemente, sugiere una nueva dirección, plena de sentido, en los esfuerzos actuales para interpretar el Absoluto hegeliano. &nbsp

Interprétativisme et complexité des normes d'audit françaises

Dans une décision de la commission des sanctions de l'AMF de décembre 2009, l'interprétativisme de la NEP 320 a été retenu pour justifier l'absence de sanction d'auditeurs ayant commis une erreur de jugement. Cet article a pour but de démontrer que le processus des normes d'audit françaises au cours de la tâche d'audit n'est pas positiviste. Ainsi, l'interprétativisme et le constructivisme des normes d'audit sont des facteurs de complexité de la tâche qui influencent la performance du jugement d'audit. L'audit n'est pas une théorie positive.Normes d'audit ; complexité ; interprétativisme ; constructivisme ; positivisme

Autotransplante dentário assistido por computador e réplicas de dentes 3D-impressos: revisão sistemática

Introdução: O autotransplante dentário (TAT) é um procedimento cirúrgico que consiste no reposicionamento de um dente exodonciado para um local recetor no mesmo individuo. A preservação das células do ligamento periodontal (CLP) é o critério mais importante para o sucesso do TAT. Atualmente, novas tecnologias de rapid prototyping (CARP) são utilizadas a partir de imagens do cone beam computed tomography (CBCT), e réplicas de dente são impressas em 3D. Objetivos: Descrever o procedimento do TAT através do uso do CBCT, CARP e modelo 3D e, concomitantemente, demostrar os seus efeitos positivos. Materiais e métodos: foi realizada uma pesquisa bibliográfica na Pubmed com as palavras chaves «tooth autotransplantation», «cone-beam computed tomography», «3D tooth replica», «rapid prototyping». Inclui os artigos com menos de 10 anos, em inglês, efetuados em população humana. Foram encontrados 104 artigos, tendo sido selecionados 14. Resultados: Após verificação da compatibilidade do dente doador com o local recetor através de medidas nas imagens do CBCT, o planeamento virtual é realizado com a conceção da réplica do dente e posteriormente sua impressão em 3D. A utilização do modelo 3D do dente doador permite reduzir o tempo extra-alveolar do transplante e diminuir o número de tentativas de adaptabilidade ao alvéolo recetor. Deste modo, torna-se possível maior preservação do ligamento periodontal o que conduzirá a um aumento da taxa de sucesso do TAT com este protocolo. Conclusão: O TAT assistido por computador tem revelado ser uma alternativa com taxa de sucesso aumentada, proporcionando tempo extra-alveolar diminuído e preservação das CLP do doador graças ao modelo CARP impresso em 3D. No entanto, são necessários mais estudos clínicos para confirmar os benefícios do TAT.Introduction: Dental autotransplantation (TAT) is a surgical procedure that consists of repositioning an exodonted tooth to a recipient site in the same individual. The preservation of periodontal ligament cells (PLC) is the most important criterion for the success of TAT. Currently, new technologies like rapid prototyping (CARP) are used from cone beam computed tomography (CBCT) images, and tooth replicas are 3D printed. Objectives: To describe the TAT procedure by using CBCT, CARP and 3D model; and to demonstrate its positive effects. Materials and methods: a bibliographic search was performed on Pubmed with the keywords " tooth autotransplantation ", " cone-beam computed tomography ", " 3D tooth replica ", " rapid prototyping ". It included articles less than 10 years old, in English and in the human population. 104 artciles were found, and 14 were selected. Results: After checking the compatibility of the donor tooth with the recipient site through measurements on CBCT images, virtual planning is performed with the design of the tooth replica and subsequently its 3D printing. The use of the 3D model of the donor tooth enables the extra-alveolar time of the transplant to be reduced and the number of attempts to adapt to the recipient alveolus to be reduced. Thus, greater preservation of the periodontal ligament is possible, which will lead to an increase in the success rate of TAT with this protocol. Conclusion: Computer-assisted TAT is a good alternative with an increased success rate, providing decreased extra-alveolar time and the preservation of donor PLCs thanks to the 3D printed CARP model. However, clinical studies are needed to confirm the benefits of TAT

Herpes Viral Origin of the Parsonage-Turner Syndrome: Highlighting of Serological Immune Anti-Herpes Deficiency Cured by Anti-Herpes Therapy.

International audienceIn 2012, a 50 year-old athletic male presented with weakness, pain and unilateral phrenic paralysis, followed by bilateral phrenic paralysis with deep dyspnea. In 2013, the Parsonage-Turner syndrome was diagnosed. When the patient was seen in September 2014 for the first time, he was facing phrenic neuromuscular failure, which led to the hypothesis of neurotropic herpes viruses. A control of the global serological anti-Herpes immunity to analyze his antibody (Ab) levels confirmed herpes immune genetic deficiency. An appropriate herpes chemotherapy treatment was proposed. Immediately, a spectacular recovery of the patient was observed, and after a few weeks, the respiratory function tests showed normal values. The hypothesis of the inductive role of viruses of the herpes family in the Parsonage-Turner syndrome was thus substantiated. The patient's immune deficiency covers the HSV2, HHV3, HHV4, HHV5 and HHV6 Ab levels. This led to the control of herpes in the family lineage: indeed, his daughter presented alterations of her serological herpes Ab levels

Structure and Function of ABCG2-Rich Extracellular Vesicles Mediating Multidrug Resistance

Multidrug resistance (MDR) is a major impediment to curative cancer chemotherapy. The ATP-Binding Cassette transporters ABCG2, ABCB1 and ABCC2 form a unique defense network against multiple structurally and functionally distinct chemotherapeutics, thereby resulting in MDR. Thus, deciphering novel mechanisms of MDR and their overcoming is a major goal of cancer research. Recently we have shown that overexpression of ABCG2 in the membrane of novel extracellular vesicles (EVs) in breast cancer cells results in mitoxantrone resistance due to its dramatic sequestration in EVs. However, nothing is known about EVs structure, biogenesis and their ability to concentrate multiple antitumor agents. To this end, we here found that EVs are structural and functional homologues of bile canaliculi, are apically localized, sealed structures reinforced by an actin-based cytoskeleton and secluded from the extracellular milieu by the tight junction proteins occludin and ZO-1. Apart from ABCG2, ABCB1 and ABCC2 were also selectively targeted to the membrane of EVs. Moreover, Ezrin-Radixin-Moesin protein complex selectively localized to the border of the EVs membrane, suggesting a key role for the tethering of MDR pumps to the actin cytoskeleton. The ability of EVs to concentrate and sequester different antitumor drugs was also explored. Taking advantage of the endogenous fluorescence of anticancer drugs, we found that EVs-forming breast cancer cells display high level resistance to topotecan, imidazoacridinones and methotrexate via efficient intravesicular drug concentration hence sequestering them away from their cellular targets. Thus, we identified a new modality of anticancer drug compartmentalization and resistance in which multiple chemotherapeutics are actively pumped from the cytoplasm and highly concentrated within the lumen of EVs via a network of MDR transporters differentially targeted to the EVs membrane. We propose a composite model for the structure and function of MDR pump-rich EVs in cancer cells and their ability to confer multiple anticancer drug resistance

Overcoming Multidrug Resistance via Photodestruction of ABCG2-Rich Extracellular Vesicles Sequestering Photosensitive Chemotherapeutics

Multidrug resistance (MDR) remains a dominant impediment to curative cancer chemotherapy. Efflux transporters of the ATP-binding cassette (ABC) superfamily including ABCG2, ABCB1 and ABCC1 mediate MDR to multiple structurally and functionally distinct antitumor agents. Recently we identified a novel mechanism of MDR in which ABCG2-rich extracellular vesicles (EVs) form in between attached neighbor breast cancer cells and highly concentrate various chemotherapeutics in an ABCG2-dependent manner, thereby sequestering them away from their intracellular targets. Hence, development of novel strategies to overcome MDR modalities is a major goal of cancer research. Towards this end, we here developed a novel approach to selectively target and kill MDR cancer cells. We show that illumination of EVs that accumulated photosensitive cytotoxic drugs including imidazoacridinones (IAs) and topotecan resulted in intravesicular formation of reactive oxygen species (ROS) and severe damage to the EVs membrane that is shared by EVs-forming cells, thereby leading to tumor cell lysis and the overcoming of MDR. Furthermore, consistent with the weak base nature of IAs, MDR cells that are devoid of EVs but contained an increased number of lysosomes, highly accumulated IAs in lysosomes and upon photosensitization were efficiently killed via ROS-dependent lysosomal rupture. Combining targeted lysis of IAs-loaded EVs and lysosomes elicited a synergistic cytotoxic effect resulting in MDR reversal. In contrast, topotecan, a bona fide transport substrate of ABCG2, accumulated exclusively in EVs of MDR cells but was neither detected in lysosomes of normal breast epithelial cells nor in non-MDR breast cancer cells. This exclusive accumulation in EVs enhanced the selectivity of the cytotoxic effect exerted by photodynamic therapy to MDR cells without harming normal cells. Moreover, lysosomal alkalinization with bafilomycin A1 abrogated lysosomal accumulation of IAs, consequently preventing lysosomal photodestruction of normal breast epithelial cells. Thus, MDR modalities including ABCG2-dependent drug sequestration within EVs can be rationally converted to a pharmacologically lethal Trojan horse to selectively eradicate MDR cancer cells

Serum levels of interleukin-6 and interleukin-8 as diagnostic markers of acute pyelonephritis in children

PurposeEarly diagnosis and treatment of acute pyelonephritis in children is of special importance in order to prevent serious complications. This study was conducted to determine the diagnostic value of serum interleukin (IL)-6 and IL-8 in children with acute pyelonephritis.MethodsEighty-seven patients between 1 month to 12 years old with urinary tract infection (UTI) were divided into 2 groups based on the result of 99m-technetium dimercapto-succinic acid renal scan: acute pyelonephritis (n=37) and lower UTI (n=50) groups. White blood cell (WBC) count, neutrophil (Neutl) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) concentration, platelet count, and serum IL-6 and IL-8 concentrations of both groups were measured and compared.ResultsThere was a significant difference between two groups regarding WBC count, Neutl count, ESR, and CRP concentration (P<0.05). In addition, the difference between the two groups regarding serum IL-6 and IL-8 concentrations was not significant (IL-6, 60 and 35.4 pg/mL and IL-8, 404 and 617 pg/mL, respectively). The sensitivity and specificity of serum IL-6 and IL-8 for diagnosis of acute pyelonephritis were 73%, 42% and 78%, 32%, respectively. Sensitivity, specificity, negative and positive predictive values of serum IL-6 and IL-8 were less than those of acute phase serum reactants such as CRP.ConclusionThis study showed that there was no significant difference between acute pyelonephritis and lower UTI groups regarding serum IL-6 and IL-8 levels. Therefore, despite confirming results of previous studies, it seems that IL-6 and IL-8 are not suitable markers for differentiating between acute pyelonephritis and lower UTI

Demonstration of the event identification capabilities of the NEXT-White detector

In experiments searching for neutrinoless double-beta decay, the possibility of identifying the two emitted electrons is a powerful tool in rejecting background events and therefore improving the overall sensitivity of the experiment. In this paper we present the first measurement of the efficiency of a cut based on the different event signatures of double and single electron tracks, using the data of the NEXT-White detector, the first detector of the NEXT experiment operating underground. Using a 228Th calibration source to produce signal-like and background-like events with energies near 1.6 MeV, a signal efficiency of 71.6 ± 1.5 stat± 0.3 sys% for a background acceptance of 20.6 ± 0.4 stat± 0.3 sys% is found, in good agreement with Monte Carlo simulations. An extrapolation to the energy region of the neutrinoless double beta decay by means of Monte Carlo simulations is also carried out, and the results obtained show an improvement in background rejection over those obtained at lower energies. [Figure not available: see fulltext.