Identification and visualization of multidimensional antigen-specific T-cell populations in polychromatic cytometry data.

An important aspect of immune monitoring for vaccine development, clinical trials, and research is the detection, measurement, and comparison of antigen-specific T-cells from subject samples under different conditions. Antigen-specific T-cells compose a very small fraction of total T-cells. Developments in cytometry technology over the past five years have enabled the measurement of single-cells in a multivariate and high-throughput manner. This growth in both dimensionality and quantity of data continues to pose a challenge for effective identification and visualization of rare cell subsets, such as antigen-specific T-cells. Dimension reduction and feature extraction play pivotal role in both identifying and visualizing cell populations of interest in large, multi-dimensional cytometry datasets. However, the automated identification and visualization of rare, high-dimensional cell subsets remains challenging. Here we demonstrate how a systematic and integrated approach combining targeted feature extraction with dimension reduction can be used to identify and visualize biological differences in rare, antigen-specific cell populations. By using OpenCyto to perform semi-automated gating and features extraction of flow cytometry data, followed by dimensionality reduction with t-SNE we are able to identify polyfunctional subpopulations of antigen-specific T-cells and visualize treatment-specific differences between them.

Le burnout de l'��l��ve : validation du School Burnout Inventory, identification de facteurs de risque et de protection et exploration des liens avec la consomation de substances

Syndrome de stress scolaire chronique, le bumout de l'��l��ve ou bumout scolaire suscite un int��r��t grandissant mais ses d��terminants sont encore peu connus. De plus, ce ph��nom��ne est rarement ��tudi�� chez les adolescents francophones et aucune recherche n'a encore ��t�� men��e en Suisse. Par cons��quent, au travers de ce travail de th��se, nous proposons d'��tendre la recherche sur le bumout scolaire aux adolescents de Suisse francophone et d'apporter des pr��cisions sur ses facteurs de risque ou de protection. Pour ce faire, nous avons men�� deux recherches empiriques impliquant 861 adolescents ��g��s de 14 �� 18 ans et scolaris��s en Suisse francophone. Ces adolescents ont r��pondu �� une s��rie d'��chelles ��valuant notamment le burnout scolaire, le stress scolaire, le soutien social, la consommation de substances et le parcours scolaire. Les r��sultats montrent tout d'abord que l'inventaire de Burnout Scolaire, version fran��aise du School Burnout lnventory, est un outil fiable et valide. Ensuite, il appara��t que le burnout scolaire touche jusqu'�� 24% des adolescents de Suisse francophone et que ce dernier se caract��rise par une perte d'int��r��t pour l'��cole, une grande remise en question du sens du travail scolaire ainsi qu'un sentiment ��lev�� d'insuffisance �� l'��cole. Il appara��t ��galement que le stress scolaire li�� au succ��s et �� l'avenir scolaire augmente le risque de bumout alors que le soutien des parents et des enseignants le diminue. Par ailleurs, nous mettons en ��vidence que l'effet du soutien social sur le burnout scolaire est m��diatis�� par le stress scolaire, ce qui souligne d'autant plus le r��le protecteur du soutien social. Nos r��sultats montrent ��galement que les niveaux de bumout scolaire varient en fonction, d'une part de certaines caract��ristiques du contexte scolaire et d'autre part en fonction de la s��v��rit�� de la consommation de substances des adolescents. Enfin, les connaissances accumul��es dans ce travail et leur mise en perspective dans un mod��le d'intervention pr��coce permettent d'insister sur le r��le de l'��cole et des professionnels de l'��cole dans la pr��vention du burnout scolaire. -- Syndrome of chronic school stress, pupil 's bumout or school bumout is of growing interest. However, little is known about its determinants. Moreover, this phenomenon is rarely studied in French speaking adolescents and no research has yet been conducted in Switzerland. Therefore, through this thesis, we propose to extend the research on school bumout to Swiss French speaking adolescents and to clarify its risk and protective factors. To achieve this, we conducted two empirical research involving 861 adolescents aged 14 to 18 and enrolled in the French part of Switzerland. These adolescents were asked to answer a questionnaire about school bumout, academic stress, social support, substance use and schooling. Results first show, that the French version of the School Bumout Inventory is a reliable and valid tool. lt then appears that school bumout affects up to 24% of adolescents in the French speaking part of Switzerland and that this phenomenon is characterized by a loss of interest in school, a great challenge to the sense of school work and a high sense of insufissance school. lt also appears that stress related to school success and academic future increases the risk of bumout while parents and teachers support decreases it. Moreover, we highlight that the effect of social support on school bumout is mediated by school stress, which further underscores the protective role of social support. Our results also show that school bumout levels vary depending on characteristics of the school context and on the severity of substance use of adolecents. Finally, the knowledge accumulated in this work and putting it onto perspective within early intervention model enable to insist on the role of school and school professionals in the prevention of school bumout

Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes.

Background Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes. Methods To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up. Results Three COPD groups were identified: group 1 (n �� 126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV 1 ) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n �� 125, 69 years) showed milder airflow limitation (FEV 1 63% predicted); and group 3 (n �� 91, 67 years) combined a similarly milder airflow limitation (FEV 1 58% predicted) with a high proportion of obesity, cardiovascular disorders, iabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p < 0.001) and higher all-cause mortality (HR 2.36, p �� 0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p �� 0.014). Conclusions In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated:"severe respiratory COPD","moderate respiratory COPD", and"systemic COPD'

Identification of the regions involved in phonological assembly using a novel paradigm.

Here we adopt a novel strategy to investigate phonological assembly. Participants performed a visual lexical decision task in English in which the letters in words and letterstrings were delivered either sequentially (promoting phonological assembly) or simultaneously (not promoting phonological assembly). A region of interest analysis confirmed that regions previously associated with phonological assembly, in studies contrasting different word types (e.g. words versus pseudowords), were also identified using our novel task that controls for a number of confounding variables. Specifically, the left pars opercularis, the superior part of the ventral precentral gyrus and the supramarginal gyrus were all recruited more during sequential delivery than simultaneous delivery, even when various psycholinguistic characteristics of the stimuli were controlled. This suggests that sequential delivery of orthographic stimuli is a useful tool to explore how readers, with various levels of proficiency, use sublexical phonological processing during visual word recognition.

Identification of Propionibacterium avidum from a breast abscess: an overlooked etiology of clinically significant infections.

We report the case of a 37-year-old previously healthy woman diagnosed with a breast abscess due to Propionibacterium avidum after breast reduction surgery. This case emphasizes the potential pathogenicity and morbidity associated with this commensal skin organism.

Identification of new transformation products during enzymatic treatment of tetracycline and erythromycin antibiotics at laboratory scale by an on-line turbulent flow liquid-chromatography coupled to a high resolution mass spectrometer LTQ-Orbitrap

This work describes the formation of transformation products (TPs) by the enzymatic degradation at laboratory scale of two highly consumed antibiotics: tetracycline (Tc) and erythromycin (ERY). The analysis of the samples was carried out by a fast and simple method based on the novel configuration of the on-line turbulent flow system coupled to a hybrid linear ion trap ��� high resolution mass spectrometer. The method was optimized and validated for the complete analysis of ERY, Tc and their transformation products within 10 min without any other sample manipulation. Furthermore, the applicability of the on-line procedure was evaluated for 25 additional antibiotics, covering a wide range of chemical classes in different environmental waters with satisfactory quality parameters. Degradation rates obtained for Tc by laccase enzyme and ERY by EreB esterase enzyme without the presence of mediators were ���78% and ���50%, respectively. Concerning the identification of TPs, three suspected compounds for Tc and five of ERY have been proposed. In the case of Tc, the tentative molecular formulas with errors mass within 2 ppm have been based on the hypothesis of dehydroxylation, (bi)demethylation and oxidation of the rings A and C as major reactions. In contrast, the major TP detected for ERY has been identified as the ���dehydration ERY-A���, with the same molecular formula of its parent compound. In addition, the evaluation of the antibiotic activity of the samples along the enzymatic treatments showed a decrease around 100% in both cases

Identification of imaging selection patterns in acute ischemic stroke patients and the influence on treatment and clinical trial enrollment decision making.

BACKGROUND AND PURPOSE: For the STroke Imaging Research (STIR) and VISTA-Imaging Investigators The purpose of this study was to collect precise information on the typical imaging decisions given specific clinical acute stroke scenarios. Stroke centers worldwide were surveyed regarding typical imaging used to work up representative acute stroke patients, make treatment decisions, and willingness to enroll in clinical trials. METHODS: STroke Imaging Research and Virtual International Stroke Trials Archive-Imaging circulated an online survey of clinical case vignettes through its website, the websites of national professional societies from multiple countries as well as through email distribution lists from STroke Imaging Research and participating societies. Survey responders were asked to select the typical imaging work-up for each clinical vignette presented. Actual images were not presented to the survey responders. Instead, the survey then displayed several types of imaging findings offered by the imaging strategy, and the responders selected the appropriate therapy and whether to enroll into a clinical trial considering time from onset, clinical presentation, and imaging findings. A follow-up survey focusing on 6&#8201;h from onset was conducted after the release of the positive endovascular trials. RESULTS: We received 548 responses from 35 countries including 282 individual centers; 78% of the centers originating from Australia, Brazil, France, Germany, Spain, United Kingdom, and United States. The specific onset windows presented influenced the type of imaging work-up selected more than the clinical scenario. Magnetic Resonance Imaging usage (27-28%) was substantial, in particular for wake-up stroke. Following the release of the positive trials, selection of perfusion imaging significantly increased for imaging strategy. CONCLUSIONS: Usage of vascular or perfusion imaging by Computed Tomography or Magnetic Resonance Imaging beyond just parenchymal imaging was the primary work-up (62-87%) across all clinical vignettes and time windows. Perfusion imaging with Computed Tomography or Magnetic Resonance Imaging was associated with increased probability of enrollment into clinical trials for 0-3 h. Following the release of the positive endovascular trials, selection of endovascular only treatment for 6&#8201;h increased across all clinical vignettes.

Identification of Low-Risk Patients with Acute Symptomatic Pulmonary Embolism for Outpatient Therapy.

RATIONALE: Patients with acute symptomatic pulmonary embolism (PE) deemed to be at low risk for early complications might be candidates for partial or complete outpatient treatment. OBJECTIVES: To develop and validate a clinical prediction rule that accurately identifies patients with PE and low risk of short-term complications and to compare its prognostic ability with two previously validated models (i.e., the Pulmonary Embolism Severity Index [PESI] and the Simplified PESI [sPESI]) METHODS: Multivariable logistic regression of a large international cohort of patients with PE prospectively enrolled in the RIETE (Registro Informatizado de la Enfermedad TromboEmb��lica) registry. MEASUREMENTS AND MAIN RESULTS: All-cause mortality, recurrent PE, and major bleeding up to 10 days after PE diagnosis were determined. Of 18,707 eligible patients with acute symptomatic PE, 46 (0.25%) developed recurrent PE, 203 (1.09%) bled, and 471 (2.51%) died. Predictors included in the final model were chronic heart failure, recent immobilization, recent major bleeding, cancer, hypotension, tachycardia, hypoxemia, renal insufficiency, and abnormal platelet count. The area under receiver-operating characteristic curve was 0.77 (95% confidence interval [CI], 0.75-0.78) for the RIETE score, 0.72 (95% CI, 0.70-0.73) for PESI (P&#8201;<&#8201;0.05), and 0.71 (95% CI, 0.69-0.73) for sPESI (P&#8201;<&#8201;0.05). Our RIETE score outperformed the prognostic value of PESI in terms of net reclassification improvement (P&#8201;<&#8201;0.001), integrated discrimination improvement (P&#8201;<&#8201;0.001), and sPESI (net reclassification improvement, P&#8201;<&#8201;0.001; integrated discrimination improvement, P&#8201;<&#8201;0.001). CONCLUSIONS: We built a new score, based on widely available variables, that can be used to identify patients with PE at low risk of short-term complications, assisting in triage and potentially shortening duration of hospital stay.

Identification of novel factors during the establishment of the Casparian strip in the endodermis

Multicellular organisms rely on specialized tissues that allow for the controlled exchange of matter with their surrounding. In order to function properly, these tissues need to establish a tight connection between the individual cells to prevent uncontrolled passive diffusion across the extracellular space. In animals, these connections are called tight and adherens junctions and are a critical feature of epithelia. These connections, however, rely on direct protein-protein interaction of plasma membrane proteins of adjacent cells. Such a mechanism is not possible in plants due to the cell wall, which encases the individual cells. In order to absorb nutrients, while simultaneously preventing uncontrolled diffusion between cells, land plants have evolved the root endodermis, which is functionally equivalent to animal epithelia. Its cells are surrounded by a precisely localized and aligned, ring-like lignin deposition, called the Casparian strip, and therefore tightly connected between each other. Very little was known about the development of the endodermis and the Casparian strip until recently. In the meantime, however, we have identified a family of endodermis- specific proteins, the CASPs, which recruits extracellular proteins the specific Casparian strip membrane domain (CSD) to locally synthesize lignin in the cell wall. Yet, we hardly knew any specifics on how the CSD is initially defined and how the critically important CASPs are being recruited to it. We therefore conducted a forward genetic screen on the localization of CASPI-GFP in order to identify novel mutants, which lack a defined CSD. We identified 48 mutants, which fell into 15 different complementation groups. While some of the isolated genes had previously been identified through different approaches, nine novel genes, which had never been implicated in CSD development and maintenance, were identified. One of them, LORD OF THE RINGS 2 (.LOTR2) is described to greater detail in this work. LOTR2 encodes for EX070A1, a protein of the evolutionary conserved exocyst complex. This complex has frequently been implicated in various secretory processes across kingdoms. In Arabidopsis, it transiently defines the positioning of CASPI-GFP. We have performed a detailed analysis of the dynamics of EX070A1 and CASPI-GFP, including studies with other markers and propose a mechanism, by which the cytosolic EX070A1 transiently defines a plasma membrane domain to recruit transmembrane proteins, which then recruit extracellular enzymes for localized cell wall modification. Considering the ubiquitous expression of EX070A1, we think that this mechanism is potentially of importance not only for the endodermis and the Casparian strip but also for many other tissues, in which the cell wall becomes locally modified. In fact, many other tissues with secondary cell wall modifications contain proteins very similar to the CASPs. It will be interesting to see to which degree this mechanism is employed in other tissues. As for the endodermis, we have now identified the first gene, which is not specific to the endodermis but shows endodermis-specific dynamics. This might give us a better insight on how the plant modulates this ubiquitously present factor in a cell- or tissue-type specific manner. Considering the knowledge, mutants and tools, which are available to us for investigating the endodermis, the Casparian strip, the exocyst complex and EX070A1 might be just the right experimental system to address these questions. -- Les organismes multicellulaires d��pendent des tissues sp��cialis�� pour l'��change contr��l�� entre eux et leur environnement. Pour leur bon fonctionnement, les cellules de ces tissus ont besoin d'��tre tr��s ��troitement assembl��s afin de pr��venir la diffusion non-contr��l��e �� travers l'espace extracellulaire. Chez les animaux, ces connexions sont appel��es jonctions serr��es et jonctions adh��rentes. Ces jonctions d��pendent des interactions directes entre les prot��ines des cellules voisines. Ceci n'est pas possible chez les plantes �� cause de la paroi cellulaire qui recouvre chaque cellule individuellement. Pour absorber les nutriments et en m��me temps emp��cher la diffusion non-contr��l�� entre cellules, les plantes ont ��volu�� 1'endoderme dans la racine, qui est fonctionnellement ��quivalent aux ��pith��liums des animaux. Les cellules de l'endoderme sont ceintur��es par une d��position de lignine tr��s pr��cis��ment localis��es comme un anneau et align��es entre les cellules, et qui, donc, connecte ��troitement les cellules avoisinante: Le cadre de Caspary. Peu ��tait connu sur le d��veloppement de l'endoderme et le cadre de Caspaiy jusqu'�� il y a quelques ann��es. R��cemment, pourtant, nous avons identifi�� une famille de prot��ines sp��cifiques �� l'endoderme, les CASPs, qui d��finissent le domaine membranaire du cadre de Caspaiy (CSD). Les CASPs recrutent les prot��ines extracellulaires n��cessaire �� la synth��se du cadre de Caspary vers une r��gion limit�� dans la paroi cellulaire. Pourtant, on conna��t tr��s peu les processus sp��cifiques concernant la d��finition initiale du CSD et comment les CASPs, qui ont une importance cruciale, sont recrut��es vers ce domaine. Par cons��quent nous avons men�� un crible g��n��tique sur la localisation du CASPI- GFP, qui sert comme marqueur pour le CSD. Notre but ��tant d'isoler de nouveaux mutants affect��s dans l'��tablissement du CSD. Nous avons identifi�� 48 mutants, en 15 groupes de compl��mentation. Bien que certains des g��nes isol��s ��taient d��j�� impliqu�� dans la formation du cadre de Caspary, neuf nouveaux g��nes n'ayant jamais ��t�� impliqu��s dans le d��veloppement ou la maintenance du CSD ont pu ��tre identifi��s. Un de ces g��nes, LORD OF THE RINGS2 (LOTR2) sera d��crit plus en d��tail dans cette ��tude. LOTR2 code pour EX070A1, qui est une prot��ine, du complexe exocyste. Ce complexe de prot��ines a tr��s bien ��t�� conserv�� au cours de l'��volution. Il ��tait souvent impliqu�� dans plusieurs processus de s��cr��tion dans toutes les branches de la vie. Chez Arabidopsis, EX070A1 d��finit la position du CSD d'une fa��on transitoire et recrute CASP1- GFP. Nous avons men�� une analyse d��taill��e des dynamiques d'EX070Al et CASPI-GFP ainsi que, des ��tudes avec des autres mutants. Nous proposons un m��canisme, d'apr��s lequel EX070A1, recrut�� du cytosol, d��finit un domaine dans la membrane plasmique pour localiser des prot��ines transmembranaires, ces derni��res ensuite recruteront des enzymes extracellulaires pour la modification locale de la paroi cellulaire. Vu qu'EX070A1 est exprim�� dans toute dans la plante, nous pensons que ce m��canisme est potentiellement important non seulement pour l'endoderme et le cadre de Caspary, mais aussi pour les autres tissus o�� la paroi cellulaire doit ��tre localement modifi��e. En effet, plusieurs autres tissus contiennent des prot��ines tr��s similaires aux CASPs. Il serait int��ressant de voir �� quelle d��gr��e ce m��canisme est ��galement utilis�� dans ces tissues. En ce qui concerne l'endoderme, nous avons maintenant identifi�� le premier g��ne qui n'est pas exprim�� sp��cifiquement dans l'endoderme, mais qui montre tout de m��me une dynamique caract��ristique dans ce tissu. Il serait int��ressant de voir comment la plante peut moduler ce facteur omnipr��sent d'une fa��on sp��cifique. Vu les connaissances, les mutants et les outils qu'on a maintenant �� notre disposition, l'endoderme et son cadre de Caspary, le complexe exocyste et EX070A1 sont probablement des bons syst��mes exp��rimentaux pour ��tudier ces questions. -- Identification des nouveaux facteurs pendant l'��tablissement du cadre de Caspary dans l'endoderme. Lothar Kalmbach, D��partement de Biologie Mol��culaire V��g��tale (DBMV), Universit�� de Lausanne. Comme tous les autres organismes multicellulaires, les plantes terrestres d��pendent de tissus sp��cialis��s pour l'��change contr��l�� avec leur environnement. Ces tissus sont importants pour l'absorption des nutriments mais ��galement pour ��viter l'influx de compos��s toxiques. Chez les plantes, ce tissu se trouve dans la racine. C'est l'endoderme. Gr��ce au cadre de Caspary, qui permet une forte connexion entre les cellules au niveau de leur paroi, l'endoderme emp��che les ��l��ments toxiques d'entrer dans le syst��me vasculaire. Depuis quelques ann��es, nous comprenons de plus en plus la nature et la biosynth��se, ainsi que les prot��ines impliqu��es dans l'ancrage des enzymes �� la membrane plasmique. Nous n'avons eu, par contre, aucune id��e sur le m��canisme qui d'abord d��finit cet endroit dans la membrane plasmique. Nous avons men�� un crible g��n��tique sur la localisation de CASPI-GFP, une prot��ine, qui recrute les enzymes extracellulaires pour la synth��se du cadre de Caspary. Nous avons identifi�� plusieurs nouveaux g��nes qui sont impliqu��s dans l'int��grit�� du cadre de Caspary. L'un de ces g��nes est EX070A1, qui est un facteur ayant un r��le important lors de la s��cr��tion des prot��ines dans tous les organismes eukaryotes. Ces mutants sont gravement affect��s au niveau du cadre de Caspary, mais surtout ils ne sont plus capables de localiser CASPI-GFP. Nous avons suivi la dynamique d'EX070Al et de CASP1-GFP en combinaison avec d'autres marqueurs. Nous avons pu montrer que l'accumulation d'EX070Al est sp��cifique pour l'endoderme et essentielle pour bien localiser CASPI-GFP et donc, le cadre de Caspary. Ces r��sultats nous aident �� mieux comprendre le d��veloppement de l'endoderme mais peuvent potentiellement aussi ��tre utilis��s pour ��tudier les modifications de la paroi cellulaire dans d'autres cellules de la plante.

Identification and ethnic diversity underlie support for multicultural rights : a multilevel analysis in Bulgaria

Bulgaria is historically a multicultural society, composed of the Bulgarian (ethnic) majority and a number of ethnic minorities among which Bulgarian Turks and Roma are the largest. Both minority communities are stigmatized in contemporary Bulgaria, though to different degrees and for different reasons. Ethnic minorities' rights to preserve their culture, customs, and language are a topic of contentious debate. The purpose of this study was to examine individual- and context-level antecedents of the ethnic Bulgarian majority's support for multicultural rights of ethnic minorities. Multilevel regression analyses were conducted with International Social Survey Programme ISSP 2003 data (N = 920 in 28 Bulgarian districts). At the individual-level, an ethnic conception of the nation and anti-Roma symbolic prejudice were negatively related to support for multicultural rights, whereas national identification was positively related to the support of these rights. Over and above individual-level effects, and in line with recent extensions of intergroup contact theory, thepercentage ofBulgarianTurks withindistricts was positively related to support for multicultural rights. Importantly, support for multicultural rights was particularly high in districts characterized by ethnic diversity, that is, in districts with high proportions of both Bulgarian Turks and Roma. The beneficial effects of ethnic diversity and theoretical implications of findings are discussed.

A web-based tool to aid the identification of chemicals potentially posing a health risk through percutaneous exposure

Occupational hygiene practitioners typically assess the risk posed by occupational exposure by comparing exposure measurements to regulatory occupational exposure limits (OELs). In most jurisdictions, OELs are only available for exposure by the inhalation pathway. Skin notations are used to indicate substances for which dermal exposure may lead to health effects. However, these notations are either present or absent and provide no indication of acceptable levels of exposure. Furthermore, the methodology and framework for assigning skin notation differ widely across jurisdictions resulting in inconsistencies in the substances that carry notations. The UPERCUT tool was developed in response to these limitations. It helps occupational health stakeholders to assess the hazard associated with dermal exposure to chemicals. UPERCUT integrates dermal quantitative structure-activity relationships (QSARs) and toxicological data to provide users with a skin hazard index called the dermal hazard ratio (DHR) for the substance and scenario of interest. The DHR is the ratio between the estimated 'received' dose and the 'acceptable' dose. The 'received' dose is estimated using physico-chemical data and information on the exposure scenario provided by the user (body parts exposure and exposure duration), and the 'acceptable' dose is estimated using inhalation OELs and toxicological data. The uncertainty surrounding the DHR is estimated with Monte Carlo simulation. Additional information on the selected substances includes intrinsic skin permeation potential of the substance and the existence of skin notations. UPERCUT is the only available tool that estimates the absorbed dose and compares this to an acceptable dose. In the absence of dermal OELs it provides a systematic and simple approach for screening dermal exposure scenarios for 1686 substances.

Impact of the Femoral Head Position on Moment Arms in Total Hip Arthroplasty: A Parametric Finite Element Study.

BACKGROUND: Although the importance of accurate femoral reconstruction to achieve a good functional outcome is well documented, quantitative data on the effects of a displacement of the femoral center of rotation on moment arms are scarce. The purpose of this study was to calculate moment arms after nonanatomical femoral reconstruction. METHODS: Finite element models of 15 patients including the pelvis, the femur, and the gluteal muscles were developed. Moment arms were calculated within the native anatomy and compared to distinct displacement of the femoral center of rotation (leg lengthening of 10 mm, loss of femoral offset of 20%, anteversion ��10��, and fixed anteversion at 15��). Calculations were performed within the range of motion observed during a normal gait cycle. RESULTS: Although with all evaluated displacements of the femoral center of rotation, the abductor moment arm remained positive, some fibers initially contributing to extension became antagonists (flexors) and vice versa. A loss of 20% of femoral offset led to an average decrease of 15% of abductor moment. Femoral lengthening and changes in femoral anteversion (��10��, fixed at 15��) led to minimal changes in abductor moment arms (maximum change of 5%). Native femoral anteversion correlated with the changes in moment arms induced by the 5 variations of reconstruction. CONCLUSION: Accurate reconstruction of offset is important to maintaining abductor moment arms, while changes of femoral rotation had minimal effects. Patients with larger native femoral anteversion appear to be more susceptible to femoral head displacements.

Preparation of a blood culture pellet for rapid bacterial identification and antibiotic susceptibility testing.

Bloodstream infections and sepsis are a major cause of morbidity and mortality. The successful outcome of patients suffering from bacteremia depends on a rapid identification of the infectious agent to guide optimal antibiotic treatment. The analysis of Gram stains from positive blood culture can be rapidly conducted and already significantly impact the antibiotic regimen. However, the accurate identification of the infectious agent is still required to establish the optimal targeted treatment. We present here a simple and fast bacterial pellet preparation from a positive blood culture that can be used as a sample for several essential downstream applications such as identification by MALDI-TOF MS, antibiotic susceptibility testing (AST) by disc diffusion assay or automated AST systems and by automated PCR-based diagnostic testing. The performance of these different identification and AST systems applied directly on the blood culture bacterial pellets is very similar to the performance normally obtained from isolated colonies grown on agar plates. Compared to conventional approaches, the rapid acquisition of a bacterial pellet significantly reduces the time to report both identification and AST. Thus, following blood culture positivity, identification by MALDI-TOF can be reported within less than 1 hr whereas results of AST by automated AST systems or disc diffusion assays within 8 to 18 hr, respectively. Similarly, the results of a rapid PCR-based assay can be communicated to the clinicians less than 2 hr following the report of a bacteremia. Together, these results demonstrate that the rapid preparation of a blood culture bacterial pellet has a significant impact on the identification and AST turnaround time and thus on the successful outcome of patients suffering from bloodstream infections.