Early Iron Age Pottery: A Quantitative Approach. Proceedings of the International Round Table organized by the Swiss School of Archaeology in Greece (Athens, Novembre 28-30, 2008).

Quantitative approaches in ceramology are gaining ground in excavation reports, archaeological publications and thematic studies. Hence, a wide variety of methods are being used depending on the researchers' theoretical premise, the type of material which is examined, the context of discovery and the questions that are addressed. The round table that took place in Athens on November 2008 was intended to offer the participants the opportunity to present a selection of case studies on the basis of which methodological approaches were discussed. The aim was to define a set of guidelines for quantification that would prove to be of use to all researchers. Contents: 1) Introduction (Samuel Verdan); 2) Isthmia and beyond. How can quantification help the analysis of EIA sanctuary deposits? (Catherine Morgan); 3) Approaching aspects of cult practice and ethnicity in Early Iron Age Ephesos using quantitative analysis of a Protogeometric deposit from the Artemision (Michael Kerschner); 4) Development of a ceramic cultic assemblage: Analyzing pottery from Late Helladic IIIC through Late Geometric Kalapodi (Ivonne Kaiser, Laura-Concetta Rizzotto, Sara Strack); 5) 'Erfahrungsbericht' of application of different quantitative methods at Kalapodi (Sara Strack); 6) The Early Iron Age sanctuary at Olympia: counting sherds from the Pelopion excavations (1987-1996) (Birgitta Eder); 7) L'aire du pilier des Rhodiens à Delphes: Essai de quantification du mobilier (Jean-Marc Luce); 8) A new approach in ceramic statistical analyses: Pit 13 on Xeropolis at Lefkandi (David A. Mitchell, Irene S. Lemos); 9) Households and workshops at Early Iron Age Oropos: A quantitative approach of the fine, wheel-made pottery (Vicky Vlachou); 10) Counting sherds at Sindos: Pottery consumption and construction of identities in the Iron Age (Stefanos Gimatzidis); 11) Analyse quantitative du mobilier céramique des fouilles de Xombourgo à Ténos et le cas des supports de caisson (Jean-Sébastien Gros); 12) Defining a typology of pottery from Gortyn: The material from a pottery workshop pit, (Emanuela Santaniello); 13) Quantification of ceramics from Early Iron Age tombs (Antonis Kotsonas); 14) Quantitative analysis of the pottery from the Early Iron Age necropolis of Tsikalario on Naxos (Xenia Charalambidou); 15) Finding the Early Iron Age in field survey: Two case studies from Boeotia and Magnesia (Vladimir Stissi); 16) Pottery quantification: Some guidelines (Samuel Verdan).

Extending the planting period of dormant and growing Norway spruce container seedlings to early summer

Abstract

Sward and milk production response to early turnout of dairy cows to pasture in Finland

Selostus: Laiduntamisen aloitusajankohdan vaikutus laitumen tuottoon

Comparison of quality of life after stereotactic body radiotherapy and surgery for early-stage prostate cancer

Background: As the long-term efficacy of stereotactic body radiation therapy (SBRT) becomes established and other prostate cancer treatment approaches are refined and improved, examination of quality of life (QOL) following prostate cancer treatment is critical in driving both patient and clinical treatment decisions. We present the first study to compare QOL after SBRT and radical prostatectomy, with QOL assessed at approximately the same times pre- and post-treatment and using the same validated QOL instrument. Methods: Patients with clinically localized prostate cancer were treated with either radical prostatectomy (n = 123 Spanish patients) or SBRT (n = 216 American patients). QOL was assessed using the Expanded Prostate Cancer Index Composite (EPIC) grouped into urinary, sexual, and bowel domains. For comparison purposes, SBRT EPIC data at baseline, 3 weeks, 5, 11, 24, and 36 months were compared to surgery data at baseline, 1, 6, 12, 24,and 36 months. Differences in patient characteristics between the two groups were assessed using Chi-squared tests for categorical variables and t-tests for continuous variables. Generalized estimating equation (GEE) models were constructed for each EPIC scale to account for correlation among repeated measures and used to assess the effect of treatment on QOL. Results: The largest differences in QOL occurred in the first 16 months after treatment, with larger declines following surgery in urinary and sexual QOL as compared to SBRT, and a larger decline in bowel QOL following SBRT as compared to surgery. Long-term urinary and sexual QOL declines remained clinically significantly lower for surgery patients but not for SBRT patients. Conclusions: Overall, these results may have implications for patient and physician clinical decision making which are often influenced by QOL. These differences in sexual, urinary and bowel QOL should be closely considered in selecting the right treatment, especially in evaluating the value of non-invasive treatments, such as SBRT.

Role of neutrophils in the early shaping of the Leishmania major specific immune response in experimental murine cutaneous Leishmaniasis

The development of a protective immune response to microorganisms involves complex interactions between the host and the pathogen. The murine model of infection with Leishmania major (L. major) allows the study of the factors leading to the development of a protective immune response. Following infection with the protozoan parasite L. major, most strains of mice heal their lesions, while a few fail to control infection, both processes linked to the development of specific T helper subsets. The early events occurring during the first days following parasite inoculation are thought to be critical in the development of the Leishmania-specific immune response. Neutrophils are the first cells arriving massively to the site of infection, and recent evidence points to their role as organizers of the immune response, yet their specific role in this process remains elusive. Through interactions with cells present at the parasite inoculation site, and possibly within the draining lymph nodes, neutrophils could have an impact not only on the recruitment of inflammatory cells but also on the activation of local as well as newly migrated cells that will be crucial in shaping the Leishmania-specific immune response.

Early Jurassic to Early late Cretaceous radiolarians from the Santa Rosa accretionary complex (Northwestern Costa Rica)

In the circum-Pacific ophiolitic belts, when no other biogenic constituents are found, radiolarians have the potential to provide significant biostratigraph- ic information. The Santa Rosa Accretionary Complex, which crops out in several half-windows (Carrizal, Sitio Santa Rosa, Bahia Nancite, Playa Naranjo) along the south shores of the Santa Elena Peninsula in northwestern Costa Rica, is one of these little-known ophiolitic mélanges. It contains various oceanic assemblages of alkaline basalt, radiolarite and polymictic breccias. The radiolarian biochronology presented in this work is mainly based by correlation on the biozonations of Carter et al. (2010), Baumgartner et al. (1995b), and O'Dogherty (1994) and indicate an Early Jurassic to early Late Cretaceous (early Pliensbachian to earliest Turonian) age for the sediments associated with oceanic basalts or recovered from blocks in breccias or megabreccias. The 19 illus- trated assemblages from the Carrizal tectonic window and Sitio Santa Rosa contain in total 162 species belonging to 65 genera. The nomenclature of tecton- ic units is the one presented by (Baumgartner and Denyer, 2006). This study brings to light the Early Jurassic age of a succession of radiolarite, which was previously thought to be of Cretaceous age, intruded by alkaline basalts sills (Unit 3). The presence of Early Jurassic large reworked blocks in a polymictic megabreccia, firstly reported by De Wever et al. (1985) is confirmed (Unit 4). Therefore, the alkaline basalt associated with the radiolarites of these two units (and maybe also Units 5 and 8) could be of Jurassic age. In the Carrizal tectonic window, Middle to early Late Jurassic radiolarian chert blocks associ- ated with massive tholeitic basalts and Early Cretaceous brick-red ribbon cherts overlying pillow basalts are interpreted as fragments of a Middle Jurassic oceanic basement accreted to an Early Cretaceous oceanic Plate, in an intra-oceanic subduction context. Whereas, the knobby radiolarites and black shales of Playa Carrizal are indicative of a shallower middle Cretaceous paleoenvironment. Other remnants of this oceanic basin are found in Units 2, 6, and 7, which documented the rapid approach of the depocentre to a subduction trench during the late Early Cretaceous (Albian-Cenomanian), to possibly early Late Cretaceous (Turonian).

Role of MT1-MMP in cancer dissemination : insights from the real time imaging of tumors

Abstract : Matrix metalloproteinases (MMPs) are thought to play a major role in the tumor dissemination process as they degrade all components of the extracellular matrix. However, failure of clinical trials testing broad MMP inhibitors in cancer led to the consensus that a better understanding of the MMP biology was required. Using intravital multiphoton laser scanning microscopy, we developed an in vivo model to observe tumor dissemination and extracellular matrix remodeling in real time. We show that the matrix-modifying hormone relaxin increases tumor associated fibroblast interaction with collagen fibers by inducing integrin beta-1 expression. This causes changes in the collagen network that are mediated by MMP-8 and MT1-MMP. Also, we show that MMP-mediated collagen remodeling in vivo requires a direct contact between stationary tumor associated fibroblasts (TAFs) and collagen fibers. As MMPs are expressed in the tumor and stromal compartment of breast cancers we determined the importance of Membrane-type 1 MMP (MT1-MMP) from each compartment for cancer progression. We find that tumor-MT1-MMP promotes the invasion of the blood vasculature and blood-borne metastasis in vivo by enhancing tumor cell migration and endothelial basement membrane degradation. Interestingly, stromal-MT1-MMP cannot compensate for the lack of tumor-MT1-MMP but promotes peritumor collagen I remodeling. Thus, the function of MT1-MMP is context dependent and we identify the different but complementary roles of tumor and stromal MT1-MMP for tumor dissemination. Finally, we translate our preclinical findings in to human breast cancer samples. We show that tumor-MT1-MMP expression correlates with tumor invasion of the blood vasculature in ER-PR-HER2- breast cancers and that MT1-MMP expression increases with cancer progression. MT1-MMP could thus represent an interesting therapeutic target for the prevention of blood vasculature invasion in these tumors. Resumé : Les matrix metalloproteinases (MMPs) semblent jouer un rôle majeur pour la dissémination tumorale en raison de leur capacité à dégrader l'ensemble des composants de la matrice extracellulaire (MEC). Néanmoins, les résultats décevants des études cliniques testant les inhibiteurs des MMP ont conduit à la notion qu'une compréhension plus précise de la biologie des MMP était requise. Dans ce travail de thèse, nous avons développé un modèle murin qui permet d'observer simultanément la dissémination tumorale ainsi que les modifications de la MEC en temps réel. Nous démontrons que le traitement de tumeurs par l'hormone relaxin augmente l'interaction des fibroblastes tumoraux avec les fibres de collagène via l'intégrine beta-1. Nous montrons que cette interaction favorise et est nécessaire à la dégradation des fibres de collagène par MMP-8 et MT1-MMP. Ensuite, étant donné que les MMPs sont exprimées dans les cellules tumorales et stromales des cancers du sein, nous nous sommes intéressés au rôle de la MMP membranaire type 1 (MT1-MMP) exprimée dans chacun de ces compartiments. Nous démontrons que MT1-MMP dérivant des cellules tumorales favorise leur invasion dans les vaisseaux sanguins par la dégradation de la membrane basale vasculaire. De manière inattendue, nous montrons que l'expression de MT1-MMP par le compartiment stromal ne peut compenser le manque de MT1-MMP dans le compartiment tumoral. Néanmoins, nos résultats prouvent que MT1-MMP dérivant du compartiment stromal est impliqué dans la dégradation de collagène peritumorale. La fonction de la protéine MT1-MMP varie donc selon le compartiment tumoral d'origine. Finalement, nous avons testé nos résultats pré cliniques chez l'humain. Dans des biopsies de cancer du sein nous montrons une corrélation entre l'expression de MT1-MMP dans les cellules tumorales et l'invasion de vaisseaux sanguins par des tumeurs ER-PR-HER2-. MT1-MMP pourrait donc être une cible intéressante pour la prévention de dissémination vasculaire de ces tumeurs

A new early and automated MRI-based predictor of motor improvement after stroke.

OBJECTIVES: In this study, we investigated the structural plasticity of the contralesional motor network in ischemic stroke patients using diffusion magnetic resonance imaging (MRI) and explored a model that combines a MRI-based metric of contralesional network integrity and clinical data to predict functional outcome at 6 months after stroke. METHODS: MRI and clinical examinations were performed in 12 patients in the acute phase, at 1 and 6 months after stroke. Twelve age- and gender-matched controls underwent 2 MRIs 1 month apart. Structural remodeling after stroke was assessed using diffusion MRI with an automated measurement of generalized fractional anisotropy (GFA), which was calculated along connections between contralesional cortical motor areas. The predictive model of poststroke functional outcome was computed using a linear regression of acute GFA measures and the clinical assessment. RESULTS: GFA changes in the contralesional motor tracts were found in all patients and differed significantly from controls (0.001 ≤ p < 0.05). GFA changes in intrahemispheric and interhemispheric motor tracts correlated with age (p ≤ 0.01); those in intrahemispheric motor tracts correlated strongly with clinical scores and stroke sizes (p ≤ 0.001). GFA measured in the acute phase together with a routine motor score and age were a strong predictor of motor outcome at 6 months (r(2) = 0.96, p = 0.0002). CONCLUSION: These findings represent a proof of principle that contralesional diffusion MRI measures may provide reliable information for personalized rehabilitation planning after ischemic motor stroke. Neurology® 2012;79:39-46.

Functional plasticity of the LACK-reactive Vbeta4-Valpha8 CD4(+) T cells normally producing the early IL-4 instructing Th2 cell development and susceptibility to Leishmania major in BALB / c mice.

Early production of IL-4 by LACK-reactive Vbeta4-Valpha8 CD4(+) T cells instructs aberrant Th2 cell development and susceptibility to Leishmania major in BALB / c mice. This was demonstrated using Vbeta4(+)-deficient BALB / c mice as a result of chronic infection with MMTV (SIM), a mouse mammary tumor virus expressing a Vbeta4-specific superantigen. The early IL-4 response was absent in these mice which develop a Th1 response to L. major. Here, we studied the functional plasticity of LACK-reactive Vbeta4-Valpha8 CD4(+) T cells using BALB/ c mice inoculated with L. major shortly after infection with MMTV (SIM), i. e. before deletion of Vbeta4(+) cells. These mice fail to produce the early IL-4 response to L. major and instead exhibit an IFN-gamma response that occurs within LACK-reactive Vbeta4-Valpha8 CD4(+) T cells. Neutralization of IFN-gamma restores the production of IL-4 by these cells. These data suggest that the functional properties of LACK-reactive Vbeta4-Valpha8 CD4(+) T cells are not irreversibly fixed.

Concurrent or sequential adjuvant letrozole and radiotherapy after conservative surgery for early-stage breast cancer (CO-HO-RT): a phase 2 randomised trial.

BACKGROUND: Letrozole radiosensitises breast cancer cells in vitro. In clinical settings, no data exist for the combination of letrozole and radiotherapy. We assessed concurrent and sequential radiotherapy and letrozole in the adjuvant setting. METHODS: This phase 2 randomised trial was undertaken in two centres in France and one in Switzerland between Jan 12, 2005, and Feb 21, 2007. 150 postmenopausal women with early-stage breast cancer were randomly assigned after conserving surgery to either concurrent radiotherapy and letrozole (n=75) or sequential radiotherapy and letrozole (n=75). Randomisation was open label with a minimisation technique, stratified by investigational centres, chemotherapy (yes vs no), radiation boost (yes vs no), and value of radiation-induced lymphocyte apoptosis (< or = 16% vs >16%). Whole breast was irradiated to a total dose of 50 Gy in 25 fractions over 5 weeks. In the case of supraclavicular and internal mammary node irradiation, the dose was 44-50 Gy. Letrozole was administered orally once daily at a dose of 2.5 mg for 5 years (beginning 3 weeks pre-radiotherapy in the concomitant group, and 3 weeks post-radiotherapy in the sequential group). The primary endpoint was the occurrence of acute (during and within 6 weeks of radiotherapy) and late (within 2 years) radiation-induced grade 2 or worse toxic effects of the skin. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00208273. FINDINGS: All patients were analysed apart from one in the concurrent group who withdrew consent before any treatment. During radiotherapy and within the first 12 weeks after radiotherapy, 31 patients in the concurrent group and 31 in the sequential group had any grade 2 or worse skin-related toxicity. The most common skin-related adverse event was dermatitis: four patients in the concurrent group and six in the sequential group had grade 3 acute skin dermatitis during radiotherapy. At a median follow-up of 26 months (range 3-40), two patients in each group had grade 2 or worse late effects (both radiation-induced subcutaneous fibrosis). INTERPRETATION: Letrozole can be safely delivered shortly after surgery and concomitantly with radiotherapy. Long-term follow-up is needed to investigate cardiac side-effects and cancer-specific outcomes. FUNDING: Novartis Oncology France.

Early auditory processing

ABSTRACT (English)An accurate processing of the order between sensory events at the millisecond time scale is crucial for both sensori-motor and cognitive functions. Temporal order judgment (TOJ) tasks, is the ability of discriminating the order of presentation of several stimuli presented in a rapid succession. The aim of the present thesis is to further investigate the spatio-temporal brain mechanisms supporting TOJ. In three studies we focus on the dependency of TOJ accuracy on the brain states preceding the presentation of TOJ stimuli, the neural correlates of accurate vs. inaccurate TOJ and whether and how TOJ performance can be improved with training.In "Pre-stimulus beta oscillations within left posterior sylvian regions impact auditory temporal order judgment accuracy" (Bernasconi et al., 2011), we investigated if the brain activity immediately preceding the presentation of the stimuli modulates TOJ performance. By contrasting the electrophysiological activity before the stimulus presentation as a function of TOJ accuracy we observed a stronger pre-stimulus beta (20Hz) oscillatory activity within the left posterior sylvian region (PSR) before accurate than inaccurate TOJ trials.In "Interhemispheric coupling between the posterior sylvian regions impacts successful auditory temporal order judgment" (Bernasconi et al., 2010a), and "Plastic brain mechanisms for attaining auditory temporal order judgment proficiency" (Bernasconi et al., 2010b), we investigated the spatio-temporal brain dynamics underlying auditory TOJ. In both studies we observed a topographic modulation as a function of TOJ performance at ~40ms after the onset of the first sound, indicating the engagement of distinct configurations of intracranial generators. Source estimations in the first study revealed a bilateral PSR activity for both accurate and inaccurate TOJ trials. Moreover, activity within left, but not right, PSR correlated with TOJ performance. Source estimations in the second study revealed a training-induced left lateralization of the initial bilateral (i.e. PSR) brain response. Moreover, the activity within the left PSR region correlated with TOJ performance.Based on these results, we suggest that a "temporal stamp" is established within left PSR on the first sound within the pair at early stages (i.e. ~40ms) of cortical processes, but is critically modulated by inputs from right PSR (Bernasconi et al., 2010a; b). The "temporal stamp" on the first sound may be established via a sensory gating or prior entry mechanism.Behavioral and brain responses to identical stimuli can vary due to attention modulation, vary with experimental and task parameters or "internal noise". In a fourth experiment (Bernasconi et al., 2011b) we investigated where and when "neural noise" manifest during the stimulus processing. Contrasting the AEPs of identical sound perceived as High vs. Low pitch, a topographic modulation occurred at ca. 100ms after the onset of the sound. Source estimation revealed activity within regions compatible with pitch discrimination. Thus, we provided neurophysiological evidence for the variation in perception induced by "neural noise".ABSTRACT (French)Un traitement précis de l'ordre des événements sensoriels sur une échelle de temps de milliseconde est crucial pour les fonctions sensori-motrices et cognitives. Les tâches de jugement d'ordre temporel (JOT), consistant à présenter plusieurs stimuli en succession rapide, sont traditionnellement employées pour étudier les mécanismes neuronaux soutenant le traitement d'informations sensorielles qui varient rapidement. Le but de cette thèse est d'étudier le mécanisme cérébral soutenant JOT. Dans les trois études présentées nous nous sommes concentrés sur les états du cerveau précédant la présentation des stimuli de JOT, les bases neurales pour un JOT correct vs. incorrect et sur la possibilité et les moyens d'améliorer l'exécution du JOT grâce à un entraînement.Dans "Pre-stimulus beta oscillations within left posterior sylvian regions impact auditory temporal order judgment accuracy" (Bernasconi et al., 2011),, nous nous sommes intéressé à savoir si l'activité oscillatoire du cerveau au pré-stimulus modulait la performance du JOT. Nous avons contrasté l'activité électrophysiologique en fonction de la performance TOJ, mesurant une activité oscillatoire beta au pré-stimulus plus fort dans la région sylvian postérieure gauche (PSR) liée à un JOT correct.Dans "Interhemispheric coupling between the posterior sylvian regions impacts successful auditory temporal order judgment" (Bernasconi et al., 2010a), et "Plastic brain mechanisms for attaining auditory temporal order judgment proficiency" (Bernasconi et al., 2010b), nous avons étudié la dynamique spatio-temporelle dans le cerveau impliqué dans le traitement du JOT auditif. Dans ses deux études, nous avons observé une modulation topographique à ~40ms après le début du premier son, en fonction de la performance JOT, indiquant l'engagement des configurations de générateurs intra- crâniens distincts. La localisation de source dans la première étude indique une activité bilatérale de PSR pour des JOT corrects vs. incorrects. Par ailleurs, l'activité dans PSR gauche, mais pas dans le droit, est corrélée avec la performance du JOT. La localisation de source dans la deuxième étude indiquait une latéralisation gauche induite par l'entraînement d'une réponse initialement bilatérale du cerveau. D'ailleurs, l'activité dans la région PSR gauche corrèlait avec la performance de TOJ.Basé sur ces résultats, nous proposons qu'un « timbre-temporel » soit établi très tôt (c.-à-d. à ~40ms) sur le premier son par le PSR gauche, mais module par l'activité du PSR droite (Bernasconi et al., 2010a ; b). « Le timbre- temporel » sur le premier son peut être établi par le mécanisme neuronal de type « sensory gating » ou « prior entry ».Les réponses comportementales et du cerveau aux stimuli identiques peut varier du à des modulations d'attention ou à des variations dans les paramètres des tâches ou au bruit interne du cerveau. Dans une quatrième expérience (Bernasconi et al. 2011B), nous avons étudié où et quand le »bruit neuronal« se manifeste pendant le traitement des stimuli. En contrastant les AEPs de sons identiques perçus comme aigus vs. grave, nous avons mesuré une modulation topographique à env. 100ms après l'apparition du son. L'estimation de source a révélé une activité dans les régions compatibles avec la discrimination de fréquences. Ainsi, nous avons fourni des preuves neurophysiologiques de la variation de la perception induite par le «bruit neuronal».