Perspectives de l'inactivation des pathogènes: quand la fiction dépasse la réalité [Back to the future: a fiction dealing with pathogen inactivation of blood products].

AIM OF THE PAPER: Arouse the reflection with a fiction having a scientific appearance, presenting a late and unexpected complication of the universal inactivation of pathogens. CONCLUSION: Such a fiction story opens the debate on a series of fundamental questions that could be addressed during the paradigm shift that is expected by introducing universal pathogen inactivation of blood products.

Photographic art and dealing with death

Recently, we were faced with a request from a student photographer who wanted to take pictures of bodies donated to our institute and used for dissection courses for medical students or for scientific purposes. Students are expressly forbidden to take pictures in the dissection hall; however, we allowed this student photographer to do her diploma work in our institute. The reason why she was proposing such a topic was that her brother died young and her parents donated his body to science. To overcome this loss of a loved one, she wanted to know what happens to the donated bodies. She followed the procedure of embalming and different dissections that took place during the summer semester and she took pictures throughout. The outcome of this work was a very nice photographic document, called 'dissection', a book with many pictures but no figure legends. The image document shows the different steps in the preparation and preservation of bodies and the work of an anatomist in the dissection hall. As we impose rules on our students, we had also to give directives in the use of the photographs taken, especially for a photographer who will use the most prominent pictures for exhibitions, i.e. that the pictures do not show names or are used for publication on the internet, or show identification numbers of cadavers, or give indication ofn the institution and are relatively anonymous. This story tells how one can deal with death and at the same time advance one's personal career. The author represents the Swiss Anatomical Society SGAHE and is supported by the Swiss Academy of Science, ScNat.

Dix erreurs a ne pas commettre lors de la prise en charge d'une prothèse articulaire infectée en orthopédie [Ten errors to avoid while dealing with infected total joint arthroplasties].

Infections after total joint arthroplasty are rare but come with severe consequences. Timely, adequate and standardized treatment beginning at the onset of symptoms will have a major impact on the handling of this dreaded complication. In absences of clear guidelines, errors are often committed, with occasionally severe consequences for the patient. In this article, the 10 most frequent errors starting with diagnostics till antibiotic and surgical treatment will be discussed.

Dealing with Errors in QCA

This paper discusses five strategies to deal with five types of errors in Qualitative Comparative Analysis (QCA): condition errors, systematic errors, random errors, calibration errors, and deviant case errors. These strategies are the comparative inspection of complex, intermediary, and parsimonious solutions; the use of an adjustment factor, the use of probabilistic criteria, the test of the robustness of calibration parameters, and the use of a frequency threshold for observed combinations of conditions. The strategies are systematically reviewed, assessed, and evaluated as regards their applicability, advantages, limitations, and complementarities.

Dealing with clients' diversity in test situations: Client categorisations in psychologists' accounts of their practices

Reducing a test administration to standardised procedures reflects the test designers' standpoint. However, from the practitioners' standpoint, each client is unique. How do psychologists deal with both standardised test administration and clients' diversity? To answer this question, we interviewed 17 psychologists working in three public services for children and adolescents about their assessment practices. We analysed the numerous "client categorisations" they produced in their accounts. We found that they had shared perceptions about their clients' diversity, and reported various non-standard practices that complemented standardised test administration, but also differed from them or were even forbidden. They seem to experience a dilemma between: (a) prescribed and situated practices; (b) scientific and situated reliability; (c) commutative and distributive justice. For practitioners, dealing with clients' diversity this is a practical problem, halfway between a problem-solving task and a moral dilemma.

Systematic and exclusive use of intravascular ultrasound for endovascular aneurysm repair - the Lausanne experience.

Five years of experience with endovascular infrarenal aneurysm repair at our institution is reviewed. Implantation of endoprostheses in 88 patients has been performed by surgeons using exclusively intravascular ultrasound (IVUS) and fluoroscopy. IVUS identified the target site of deployment in all cases. In-hospital morbidity was 22% (19/88). Two percent mortality (2/88) and 5% early conversion (4/88) as a consequence of type I endoleaks were noted only in the first 53 patients with early devices (NS). Early endoleaks were present in 36% (32/88) including twenty-two type I, five type II and five type III endoleaks. Proximal endoleaks were associated with early devices (P<0.001), and technical difficulties with deployment. Tube grafts used in the beginning, performed poorly with 54% (7/13) type I endoleaks. Endoleaks diminished to 10% (9/88) by spontaneous closure and secondary endovascular procedures that were necessary in 24% (21/88) and consisted of coil embolization/cuff extension (9), late conversion (6), and limb recanalization or femoral cross-over bypass (6). Endovascular aneurysm repair using IVUS is a valid alternative technique. Improved devices and systematic use of bifurcated endoprostheses for infrarenal aneurysms reduce the occurrence of type I endoleaks.

Role of secretory immunoglobulin A and secretory component in the protection of mucosal surfaces.

The contribution of secretory immunoglobulin A (SIgA) antibodies in the defense of mucosal epithelia plays an important role in preventing pathogen adhesion to host cells, therefore blocking dissemination and further infection. This mechanism, referred to as immune exclusion, represents the dominant mode of action of the antibody. However, SIgA antibodies combine multiple facets, which together confer properties extending from intracellular and serosal neutralization of antigens, activation of non-inflammatory pathways and homeostatic control of the endogenous microbiota. The sum of these features suggests that future opportunities for translational application from research-based knowledge to clinics include the mucosal delivery of bioactive antibodies capable of preserving immunoreactivity in the lung, gastrointestinal tract, the genito-urinary tract for the treatment of infections. This article covers topics dealing with the structure of SIgA, the dissection of its mode of action in epithelia lining different mucosal surfaces and its potential in immunotherapy against infectious pathogens.

The management of brain metastases

Brain metastases occur in 20-50% of NSCLC and 50-80% of SCLC. In this review, we will look at evidence-based medicine data and give some perspectives on the management of BM. We will address the problems of multiple BM, single BM and prophylactic cranial irradiation. Recursive Partitioning Analysis (RPA) is a powerful prognostic tool to facilitate treatment decisions. Dealing with multiple BM, the use of corticosteroids was established more than 40 years ago by a unique randomized trial (RCT). Palliative effect is high (_80%) as well as side-effects. Whole brain radiotherapy (WBRT) was evaluated in many RCTs with a high (60-90%) response rate; several RT regimes are equivalent, but very high dose per fraction should be avoided. In multiple BM from SCLC, the effect of WBRT is comparable to that in NSCLC but chemotherapy (CXT) although advocated is probably less effective than RT. Single BM from NSCLC occurs in 30% of all BM cases; several prognostic classifications including RPA are very useful. Several options are available in single BM: WBRT, surgery (SX), radiosurgery (RS) or any combination of these. All were studied in RCTs and will be reviewed: the addition of WBRT to SX or RS gives a better neurological tumour control, has little or no impact on survival, and may be more toxic. However omitting WBRT after SX alone gives a higher risk of cerebro-spinal fluid dissemination. Prophylactic cranial irradiation (PCI) has a major role in SCLC. In limited disease, meta-analyses have shown a positive impact of PCI in the decrease of brain relapse and in survival improvement, especially for patients in complete remission. Surprisingly, this has been recently confirmed also in extensive disease. Experience with PCI for NSCLC is still limited, but RCT suggest a reduction of BM with no impact on survival. Toxicity of PCI is a matter of debate, as neurological or neuro-cognitive impairment is already present prior to PCI in almost half of patients. However RT toxicity is probably related to total dose and dose per fraction. Perspectives : Future research should concentrate on : 1) combined modalities in multiple BM. 2) Exploration of treatments in oligo-metastases. 3) Further exploration of PCI in NSCLC. 4) Exploration of new, toxicity-sparing radiotherapy techniques (IMRT, Tomotherapy etc).

Effort, reward and self-reported mental health: a simulation study on negative affectivity bias.

Background : In the present article, we propose an alternative method for dealing with negative affectivity (NA) biases in research, while investigating the association between a deleterious psychosocial environment at work and poor mental health. First, we investigated how strong NA must be to cause an observed correlation between the independent and dependent variables. Second, we subjectively assessed whether NA can have a large enough impact on a large enough number of subjects to invalidate the observed correlations between dependent and independent variables.Methods : We simulated 10,000 populations of 300 subjects each, using the marginal distribution of workers in an actual population that had answered the Siegrist's questionnaire on effort and reward imbalance (ERI) and the General Health Questionnaire (GHQ).Results : The results of the present study suggested that simulated NA has a minimal effect on the mean scores for effort and reward. However, the correlations between the effort and reward imbalance (ERI) ratio and the GHQ score might be important, even in simulated populations with a limited NA.Conclusions : When investigating the relationship between the ERI ratio and the GHQ score, we suggest the following rules for the interpretation of the results: correlations with an explained variance of 5% and below should be considered with caution; correlations with an explained variance between 5% and 10% may result from NA, although this effect does not seem likely; and correlations with an explained variance of 10% and above are not likely to be the result of NA biases. [Authors]

Sports practice among adolescents with chronic health conditions.

OBJECTIVES: To compare the level of sports practice between adolescents with chronic health conditions (CHCs) and control peers and to examine the reasons given by adolescents with CHCs for not practicing any sports in comparison with the control group. DESIGN: School survey. SETTING: Postmandatory schools. PARTICIPANTS: A total of 6790 students (3275 females) aged 16 to 20 years, grouped as adolescents with CHCs (355 females, 354 males) and control peers (2920 females, 3161 males). MAIN EXPOSURE: Chronic health condition was defined using a noncategorical approach including adolescents with a chronic disease and/or a physical handicap. MAIN OUTCOME MEASURES: Sports practice, barriers to sports practice among individuals not practicing any sports, and biological, psychological, socioeducative, and physical activity characteristics. RESULTS: Males with CHCs were less likely than control males to practice sports, whereas no significant difference was observed for females. Chronically ill youth were significantly more likely to report having a CHC as a barrier for not practicing sports. However, the most frequently reported barrier was preference for other activities for males with CHCs and lack of time for control males and for females with and without CHCs. CONCLUSIONS: Having a CHC seems to influence sports practice among males but not females. We recommend that practitioners dealing with adolescents remember to take into account sports practice as part of the care of young patients with CHCs.

Prise en charge des cancers du cavum (rhinopharynx) Nasopharyngeal cancers, an overview.

Les cancers du cavum ont une incidence d'environ 0,5 cas par an et par 100 000 habitants pour les hommes en France, mais sont endémiques dans des régions comme l'Asie du Sud-Est. La prise en charge thérapeutique par radiothérapie exclusive, qui a longtemps été le standard, permet d'obtenir des taux de contrôle local pour les stades T3-T4 de l'ordre de 50 à 75 % des cas. Les techniques d'irradiation en modulation d'intensité permettent une excellente couverture dosimétrique avec une meilleure protection des organes à risque et doivent être privilégiées. L'apport d'une chimiothérapie concomitante à l'IMRT améliore significativement les taux de survie globale qui sont supérieurs ou égaux à 75 % à cinq ans dans les stades avancés. Dans la pratique courante, une radiochimiothérapie concomitante à base de sels de platine est réalisée mais la place des cures néoadjuvantes et/ou adjuvantes est discutée dans le but principal de diminuer les rechutes à distance, des études sont en cours. Enfin, la surveillance doit être axée sur la détection précoce de rechutes locales potentiellement curables et sur la prise en charge des séquelles thérapeutiques à long terme. Cancer of the nasopharynx is an uncommon malignancy in France (incidence = 0.5/year/100,000 men) but is endemic in areas like in South-East Asia. Exclusive radiation therapy used to be the standard and results in local control rates for T3-T4 tumors around 50-75 %. Intensity-modulated radiotherapy (IMRT) improves tumor coverage with a sparing of organs at risk and has to be privileged. Concurrent chemotherapy with IMRT achieved significant survival benefice with 5-year overall survival above 75 %. Concurrent radiochemotherapy with platinium is the most frequent scheme but induction and adjuvant chemotherapies are discussed to reduce distant failure: studies are currently ongoing. Follow-up aims to detect early local failures with a chance of cure and to manage long-term toxicities.

Memory and effector CD8 T-cell responses after nanoparticle vaccination of melanoma patients.

Induction of cytotoxic CD8 T-cell responses is enhanced by the exclusive presentation of antigen through dendritic cells, and by innate stimuli, such as toll-like receptor ligands. On the basis of these 2 principles, we designed a vaccine against melanoma. Specifically, we linked the melanoma-specific Melan-A/Mart-1 peptide to virus-like nanoparticles loaded with A-type CpG, a ligand for toll-like receptor 9. Melan-A/Mart-1 peptide was cross-presented, as shown in vitro with human dendritic cells and in HLA-A2 transgenic mice. A phase I/II study in stage II-IV melanoma patients showed that the vaccine was well tolerated, and that 14/22 patients generated ex vivo detectable T-cell responses, with in part multifunctional T cells capable to degranulate and produce IFN-γ, TNF-α, and IL-2. No significant influence of the route of immunization (subcutaneous versus intradermal) nor dosing regimen (weekly versus daily clusters) could be observed. It is interesting to note that, relatively large fractions of responding specific T cells exhibited a central memory phenotype, more than what is achieved by other nonlive vaccines. We conclude that vaccination with CpG loaded virus-like nanoparticles is associated with a human CD8 T-cell response with properties of a potential long-term immune protection from the disease.