The First 1 1/2 Years of TOTEM Roman Pot Operation at LHC

Since the LHC running season 2010, the TOTEM Roman Pots (RPs) are fully operational and serve for collecting elastic and diffractive proton-proton scattering data. Like for other moveable devices approaching the high intensity LHC beams, a reliable and precise control of the RP position is critical to machine protection. After a review of the RP movement control and position interlock system, the crucial task of alignment will be discussed.Comment: 3 pages, 6 figures; 2nd International Particle Accelerator Conference (IPAC 2011), San Sebastian, Spain; contribution MOPO01

Staphylococcal entertotoxins of the enterotoxin gene cluster (egcSEs) induce nitrous oxide- and cytokine dependent tumor cell apoptosis in a broad panel of human tumor cells

International audienceThe egcSEs comprise five genetically linked staphylococcal enterotoxins, SEG, SEI, SElM, SElN, and SElO and two pseudotoxins which constitute an operon present in up to 80% of Staphylococcus aureus isolates. A preparation containing these proteins was recently used to treat advanced lung cancer with pleural effusion. We investigated the hypothesis that egcSEs induce nitrous oxide (NO) and associated cytokine production and that these agents may be involved in tumoricidal effects against a broad panel of clinically relevant human tumor cells. Preliminary studies showed that egcSEs and SEA activated T cells (range: 11-25%) in a concentration dependent manner. Peripheral blood mononuclear cells (PBMCs) stimulated with equimolar quantities of egcSEs expressed NO synthase and generated robust levels of nitrite (range: 200-250 μM), a breakdown product of NO; this reaction was inhibited by NG-monomethyl-L-arginine (L-NMMA) (0.3 mM), an NO synthase antagonist. Cell free supernatants (CSFs) of all egcSE-stimulated PBMCs were also equally effective in inducing concentration dependent tumor cell apoptosis in a broad panel of human tumor cells. The latter effect was due in part to the generation of NO and TNF-α since it was significantly abolished by L-NMMA, anti-TNF-α antibodies, respectively, and a combination thereof. A hierarchy of tumor cell sensitivity to these CFSs was as follows: lung carcinoma > osteogenic sarcoma > melanoma > breast carcinoma >neuroblastoma. Notably, SEG induced robust activation of NO/TNFα-dependent tumor cell apoptosis comparable to the other egcSEs and SEA despite TNF-α and IFN-γ levels that were 2 and 8 fold lower, respectively, than the other egcSEs and SEA. Thus, egcSEs produced by S. aureus induce NO synthase and the increased NO formation together with TNF-α appear to contribute to egcSE-mediated apoptosis against a broad panel of human tumor cells

In Vitro and In Vivo Antitumor Effect of Anti-CD33 Chimeric Receptor-Expressing EBV-CTL against CD33+ Acute Myeloid Leukemia

Genetic engineering of T cells with chimeric T-cell receptors (CARs) is an attractive strategy to treat malignancies. It extends the range of antigens for adoptive T-cell immunotherapy, and major mechanisms of tumor escape are bypassed. With this strategy we redirected immune responses towards the CD33 antigen to target acute myeloid leukemia. To improve in vivo T-cell persistence, we modified human Epstein Barr Virus-(EBV-) specific cytotoxic T cells with an anti-CD33.CAR. Genetically modified T cells displayed EBV and HLA-unrestricted CD33 bispecificity in vitro. In addition, though showing a myeloablative activity, they did not irreversibly impair the clonogenic potential of normal CD34+ hematopoietic progenitors. Moreover, after intravenous administration into CD33+ human acute myeloid leukemia-bearing NOD-SCID mice, anti-CD33-EBV-specific T cells reached the tumor sites exerting antitumor activity in vivo. In conclusion, targeting CD33 by CAR-modified EBV-specific T cells may provide additional therapeutic benefit to AML patients as compared to conventional chemotherapy or transplantation regimens alone

Estimation du sexe fœtal à partir de l’ilium

La détermination du sexe est une des problématiques les plus fréquemment rencontrées en anthropologie médico-légale. Chez l’adulte, cette détermination est essentiellement basée sur l’os iliaque et autorise un très fort taux de classification correcte, tandis que chez le fœtus, les études sont beaucoup moins nombreuses et conduisent à des résultats souvent contradictoires.Nous avons recherché sur 83 paires d’ilia fœtaux de la collection ostéologique hongroise de Fazekas et Kosa quels étaient les critères métriques qui décrivaient le mieux le dimorphisme sexuel, en évaluant les différentes méthodes proposées sur l’ilium fœtal et en adaptant certaines de celles proposées chez l’adulte. Nous avons pour cela établi et validé un protocole de prise de clichés photographiques et une méthode de mesure sur image numérisée à partir du logiciel Adobe Photoshop 6‚.Certains des paramètres retenus dans l’étude – principalement ceux qui ont été relevés sur l’échancrure ischiatique – présentant de fortes corrélations avec le sexe, nous avons établi une régression logistique estimant la probabilité d’appartenir à l’un ou l’autre des deux sexes. Le faible pourcentage de discrimination sexuelle obtenu avec cette formule nous a amené à tenir compte de l’âge : nous avons donc structuré notre échantillon en différents groupes d’âge et avons établi une formule permettant de déterminer correctement le sexe dans plus de 85 % des cas (sur l’échantillon qui a servi à l’établir) pour les fœtus dont l’âge est inférieur à 26 semaines d’aménorrhée.Sex estimation is one of the most frequently encountered issues in forensic medicine. While in the case of adults this determination is essentially based on iliac bones and provides a rather reliable classification, there are fewer studies conducted on fetuses and the results are often contradictory.Therefore, we examinated 83 pairs of fetal iliac bones in the Hungarian collection of Fazekas and Kosa and searched for metric criteria that can the best be applied for determining sexual dimorphism. During this research, we tested the different methods proposed for fetal iliac bones and adapted some others used particularly in the case of adults.For this reason, we set up and validated a protocol of taking photographs, as well as a measurement technique developed for numeric pictures with the help of a software program, Adobe Photoshop 6‚.During this study, we selected certain parameters, principally the ones taken on the great sciatic notch, which showed a strong correlation with sex, and we established a logistic regression for estimating the probability of belonging to one sex or the other.The weak percentage of sexual differentiation obtained by this formula led us to take into account age: we organised our sample in different age groups and established a formula that permits correct sex determination in more than 85% of cases (in our sample) for fetuses that are less than 24 gestational weeks old

Magnetic resonance imaging, computed tomography, and 68Ga-DOTATOC positron emission tomography for imaging skull base meningiomas with infracranial extension treated with stereotactic radiotherapy - a case series

<p>Abstract</p> <p>Introduction</p> <p>Magnetic resonance imaging (MRI) and computed tomography (CT) with ⁶⁸Ga-DOTATOC positron emission tomography (⁶⁸Ga-DOTATOC-PET) were compared retrospectively for their ability to delineate infracranial extension of skull base (SB) meningiomas treated with fractionated stereotactic radiotherapy.</p> <p>Methods</p> <p>Fifty patients with 56 meningiomas of the SB underwent MRI, CT, and ⁶⁸Ga-DOTATOC PET/CT prior to fractionated stereotactic radiotherapy. The study group consisted of 16 patients who had infracranial meningioma extension, visible on MRI ± CT (MRI/CT) <it>or </it>PET, and were evaluated further. The respective findings were reviewed independently, analyzed with respect to correlations, and compared with each other.</p> <p>Results</p> <p>Within the study group, SB transgression was associated with bony changes visible by CT in 14 patients (81%). Tumorous changes of the foramen ovale and rotundum were evident in 13 and 8 cases, respectively, which were accompanied by skeletal muscular invasion in 8 lesions. We analysed six designated anatomical sites of the SB in each of the 16 patients. Of the 96 sites, 42 had infiltration that was delineable by MRI/CT and PET in 35 cases and by PET only in 7 cases. The mean infracranial volume that was delineable in PET was 10.1 ± 10.6 cm³, which was somewhat larger than the volume detectable in MRI/CT (8.4 ± 7.9 cm³).</p> <p>Conclusions</p> <p>⁶⁸Ga-DOTATOC-PET allows detection and assessment of the extent of infracranial meningioma invasion. This method seems to be useful for planning fractionated stereotactic radiation when used in addition to conventional imaging modalities that are often inconclusive in the SB region.</p

Inhibition of Chondrosarcoma Growth by mTOR Inhibitor in an In Vivo Syngeneic Rat Model

BACKGROUND: Chondrosarcomas are the second most frequent primary malignant type of bone tumor. No effective systemic treatment has been identified in advanced or adjuvant phases for chondrosarcoma. The aim of the present study was to determine the antitumor effects of doxorubicin and everolimus, an mTOR inhibitor on chondrosarcoma progression. METHODS AND FINDINGS: Doxorubin and/or everolimus were tested in vivo as single agent or in combination in the rat orthotopic Schwarm chondrosarcoma model, in macroscopic phase, as well as with microscopic residual disease. Response to everolimus and/or doxorubicin was evaluated using chondrosarcoma volume evolution (MRI). Histological response was evaluated with % of tumor necrosis, tumor proliferation index, metabolism quantification analysis between the treated and control groups. Statistical analyses were performed using chi square, Fishers exact test. Doxorubicin single agent has no effect of tumor growth as compared to no treatment; conversely, everolimus single agent significantly inhibited tumor progression in macroscopic tumors with no synergistic additive effect with doxorubicin. Everolimus inhibited chondrosarcoma proliferation as evaluated by Ki67 expression did not induce the apoptosis of tumor cells; everolimus reduced Glut1 and 4EBP1 expression. Importantly when given in rats with microscopic residual diseases, in a pseudo neoadjuvant setting, following R1 resection of the implanted tumor, everolimus significantly delayed or prevented tumor recurrence. CONCLUSIONS: MTOR inhibitor everolimus blocks cell proliferation, Glut1 expression and HIF1a expression, and prevents in vivo chondrosarcoma tumor progression in both macroscopic and in adjuvant phase post R1 resection. Taken together, our preclinical data indicate that mTOR inhibitor may be effective as a single agent in treating chondrosarcoma patients. A clinical trial evaluating mTOr inhibitor as neo-adjuvant and adjuvant therapy in chondrosarcoma patients is being constructed

New perspectives on evolutionary medicine: the relevance of microevolution for human health and disease

Evolutionary medicine (EM) is a growing field focusing on the evolutionary basis of human diseases and their changes through time. To date, the majority of EM studies have used pure theories of hominin macroevolution to explain the present-day state of human health. Here, we propose a different approach by addressing more empirical and health-oriented research concerning past, current and future microevolutionary changes of human structure, functions and pathologies. Studying generation-to-generation changes of human morphology that occurred in historical times, and still occur in present-day populations under the forces of evolution, helps to explain medical conditions and warns clinicians that their current practices may influence future humans. Also, analyzing historic tissue specimens such as mummies is crucial in order to address the molecular evolution of pathogens, of the human genome, and their coadaptations.Frank Jakobus Rühli and Maciej Henneber