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The WEST (Tungsten Environment for Steady State Tokamak) platform aims at testing ITER like divertor targets in an integrated tokamak environment, to minimize risks for procurement and operation. After 4 years of construction, WEST is now operational, with the first plasma breakdown achieved in December 2016. To operate long plasma discharge in WEST, infrared thermography is a key device, which enables a safe operation by means of a real time surface temperature monitoring, while providing essential data for various physics studies. For WEST, the IR thermography system has been deeply renewed, to match with the new tokamak configuration, and to fulfil the new measurement requirements. It consists of a set of 5 different diagnostics: 1) 7 endoscopes located in upper ports viewing the whole lower divertor and the 5 heating devices 2) a tangential endoscope located in a median port, providing a wide angle view of the vacuum vessel, and in particular of the upper divertor and first wall protections 3) a submillimetre resolution view on the divertor strike points from an upper port endoscope 4) 2 additional views of the divertor and of the heating devices. The paper describes the new IR diagnostics configuration (spatial covering, IR cameras, optics, data processing hardware and software), the main design options, manufacturing and installation issues, and some measurement performances.

Five endoscopes equipped with infrared cameras working in the medium infrared range (3–5 μ m) are installed on the controlled thermonuclear fusion research device Tore-Supra. These endoscopes aim at monitoring the plasma facing components surface temperature to prevent their overheating. Signals delivered by infrared cameras through endoscopes are analysed and used on the one hand through a real time feedback control loop acting on the heating systems of the plasma to decrease plasma facing components surface temperatures when necessary, on the other hand for physics studies such as determination of the incoming heat flux . To ensure these two roles a very accurate knowledge of the absolute surface temperatures is mandatory. Consequently the infrared endoscopes must be calibrated through a very careful procedure. This means determining their transmission coefficients which is a delicate operation. Methods to calibrate infrared endoscopes during the shutdown period of the Tore-Supra machine will be presented. As they do not allow determining the possible transmittances evolution during operation an in-situ method is presented. It permits the validation of the calibration performed in laboratory as well as the monitoring of their evolution during machine operation. This is possible by the use of the endoscope shutter and a dedicated plasma scenario developed to heat it. Possible improvements of this method are briefly evoked.

For the long-pulse high-confinement discharges in tokamaks, the equilibrium of plasma requires a contact with the first wall materials. The heat flux resulting from this interaction is of the order of 10 MW/m 2 for steady state conditions and up to 20 MW/m 2 for transient phases. The monitoring on surface temperatures of the plasma facing components (PFCs) is a major concern to ensure safe operation and to optimize performances of experimental operations on large fusion facilities. Furthermore, this measurement is also required to study the physics associated to the plasma material interactions and the heat flux deposition process. In tokamaks, infrared (IR) thermography systems are routinely used to monitor the surface temperature of the PFCs. This measurement requires an accurate knowledge of the surface emissivity. However, and particularly for metallic materials such as tungsten, this emissivity value can vary over a wide range with both the surface condition and the temperature itself, which makes instantaneous measurement challenging. In this context, the multi-spectral infrared method appears as a very promising alternative solution. Indeed, the system has the advantage to carry out a non-intrusive measurement on thermal radiation while evaluating surface temperature without requiring a mandatory surface emissivity measurement. In this paper, a conceptual design for the multi-spectral infrared thermography is proposed. The numerical study of the multi-channel system based on the Levenberg-Marquardt (LM) nonlinear curve fitting is applied. The numerical results presented in this paper demonstrate the design allows for measurements over a large temperature range with a relative error of less than 10%. Furthermore, laboratory experiments have been performed from 200 °C to 740 °C to confirm the feasibility for temperature measurements on stainless steel and tungsten. In these experiments, the unfolding results from the multi-channel detection provide good performance on temperature measurement, which supports our numerical evaluation and demonstrates the potential feasibility for metallic surface high temperature measurement with this method.

Summary Background In 2013, the interim analysis of the Protocol for Herceptin as Adjuvant therapy with Reduced Exposure (PHARE) trial could not show that 6 months of adjuvant trastuzumab was non-inferior to 12 months. Here, we report the planned final analysis based on the prespecified number of occurring events. Methods PHARE is an open-label, phase 3, non-inferiority randomised trial of patients with HER2-positive early breast cancer comparing 6 months versus 12 months of trastuzumab treatment concomitant with or following standard neoadjuvant or adjuvant chemotherapy. The study was undertaken in 156 centres in France. Eligible patients were women aged 18 years or older with non-metastatic, operable, histologically confirmed adenocarcinoma of the breast and either positive axillary nodes or negative axillary nodes but a tumour of at least 10 mm. Participants must have received at least four cycles of a chemotherapy for this breast cancer and have started receiving adjuvant trastuzumab-treatment. Eligible patients were randomly assigned to either 6 months or 12 months of trastuzumab therapy duration between the third and sixth months of adjuvant trastuzumab. The randomisation was stratified by concomitant or sequential treatment with chemotherapy, oestrogen receptor status, and centre. The primary objective was non-inferiority in the intention-to-treat population in the 6-month group in terms of disease-free survival with a prespecified hazard margin of 1·15. This trial is registered with ClinicalTrials.gov, number NCT00381901. Findings 3384 patients were enrolled and randomly assigned to either 12 months (n=1691) or 6 months (n=1693) of adjuvant trastuzumab. One patient in the 12-month group and three patients in the 6-month group were excluded, so 1690 patients in each group were included in the intention-to-treat analysis. At a median follow-up of 7·5 years (IQR 5·3–8·8), 704 events relevant to disease-free survival were observed (345 [20·4%] in the 12-month group and 359 [21·2%] in the 6-month group). The adjusted hazard ratio for disease-free survival in the 12-month group versus the 6-month group was 1·08 (95% CI 0·93–1·25; p=0·39). The non-inferiority margin was included in the 95% CI. No differences in effects pertaining to trastuzumab duration were found in any of the subgroups. After the completion of trastuzumab treatment, rare adverse events occurred over time and the safety analysis remained similar to the previously published report. In particular, we found no change in the cardiac safety comparison, and only three additional cases in which the left ventricular ejection fraction decreased to less than 50% have been reported in the 12-month group. Interpretation The PHARE study did not show the non-inferiority of 6 months versus 12 months of adjuvant trastuzumab. Hence, adjuvant trastuzumab standard duration should remain 12 months. Funding The French National Cancer Institute.

openaire: EC/H2020/633053/EU//EUROfusion In JET with ITER-like wall (JET-ILW), the first wall was changed to metallic materials (tungsten and beryllium) [1] which require a reliable protection system to avoid damage of the plasma-facing components (PFCs) due to beryllium melting or cracking of tungsten owing to thermal fatigue. To address this issue, a protection system with real time control, based on imaging diagnostics, has been implemented on JET-ILW in 2011. This paper describes the design, implementation, and operation of the near infrared imaging diagnostic system of the JET-ILW plasma experiment and its integration into the existing JET-ILW protection architecture. The imaging system comprises eleven analogue CCD cameras which demonstrate a high robustness against changes of system parameters like the emissivity. The system covers about two thirds of the main chamber wall and almost half of the divertor. A real-time imaging processing unit is used to convert the raw data into surface temperatures taking into account the different emissivity for the various materials and correcting for artefacts resulting e.g. from neutron impact. Regions of interest (ROI) on the selected PFCs are analysed in real time and the maximum temperature measured for each ROI is sent to other real time systems to trigger an appropriate response of the plasma control system, depending on the location of a hot spot. A hot spot validation algorithm was successfully integrated into the real-time system and is now used to avoid false alarms caused by neutrons and dust. The design choices made for the video imaging system, the implications for the hardware components and the calibration procedure are discussed. It will be demonstrated that the video imaging protection system can work properly under harsh electromagnetic conditions as well as under neutron and gamma radiation. Examples will be shown of instances of hot spot detection that abort the plasma discharge. The limits of the protection system and the associated constraints on plasma operation are also presented. The real-time protection system has been operating routinely since 2011. During this period, less than 0.5% of the terminated discharges were aborted by a malfunction of the system. About 2%-3% of the discharges were terminated due to the detection of actual hot spots.

To operate long plasma discharge in tokamak equipped with actively cooled plasma facing components (PFC), infrared (IR) thermography is a key diagnostic. Indeed IR data are used for both PFC safety monitoring, to avoid material degradation and water leak, and various physics studies on plasma-wall interaction. The IR monitoring is becoming even more crucial with today metallic PFCs. This is the case for the WEST project (Tungsten (W) Environment for Steady State Tokamak), which aims at installing a W divertor in Tore Supra (TS), in order to operate the 1st tokamak with a full W actively cooled divertor in long plasma discharges. The IR thermography system for the WEST project described in this paper will consist of a set of 3 different diagnostics: (1) Six cameras located in upper ports viewing the full W divertor, which reuse a part of the existing diagnostic of TS. (2) Five novel views located behind the inner protection panels for the antennas monitoring, based on an innovative imaging fibers bundle technology. (3) A tangential wide angle view located in a median port, for the upper divertor and first wall monitoring.

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In order to reduce the risks for ITER Plasma Facing Components (PFCs), it is proposed to equip Tore Supra with a full tungsten divertor, benefitting from the unique long pulse capabilities, the high installed RF power and the long experience with actively cooled high heat flux components of the Tore Supra platform. The transformation from the current circular limiter geometry to the required X-point configuration will be achieved by installing a set of copper poloidal coils inside the vacuum vessel. The new configuration will allow for H-mode access, providing relevant plasma conditions for PFC technology validation. Furthermore, attractive steady-state regimes are expected to be achievable. The lower divertor target design will be closely based on that currently envisaged for ITER (W monoblocks), while the upper divertor region will be used to qualify the main first wall heat sink technology adopted for the ITER blanket modules (CuCrZr copper/stainless steel) with a tungsten coating (in place of the Be tiles which ITER will use). Extended plasma exposure will provide access to ITER critical issues such as PFC lifetime (melting, cracking, etc.), tokamak operation on damaged metallic surfaces, real time heat flux control through PFC monitoring, fuel retention and dust production.

Using the Tore Supra infrared thermography diagnostics, a new real time feedback control has been successfully implemented to maximize additional RF power while preventing plasma facing components (PFCs) from overheating and damage. As a first step, a thermography feedback control has been used to detect and extinguish electric arcs on lower hybrid current drive (LHCD) launchers. Secondly, heating sources on PFCs have been identified highlighting the role of the power from each ion cyclotron resonance heating (ICRH) antenna and LHCD launcher and the interactions between them. A new feedback control algorithm was developed to control the additional power. The real time feedback control of PFC temperatures which makes part of an integrated feedback controller, is a reliable tool routinely used as a basic protection system. Furthermore, it has proven its capability to operate in parallel with other control schemes such as the current profile control.

The aim of this study was to define the characteristics of patients with idiopathic thrombocytopenic purpura (ITP) and breast cancer and discuss the relationship between these two diseases. Ten patients treated for breast cancer and presenting with ITP were screened for this study. The diagnosis of breast cancer was confirmed by biopsy or surgical sample. The diagnosis of ITP was defined by 1) platelet count less than 140.10(9)/l with normal or increased number of megakaryocytes on bone marrow aspirate, 2) after exclusion of thrombocytopenia-induced medication or disorders, and 3) absence of splenomegaly. ITP was diagnosed before breast cancer in three cases, concomitantly in three, and after the diagnosis of breast cancer in four cases. Platelet count and breast cancer showed an independent course in seven cases, and appeared to be correlated in the other three patients. No correlation was found between the development of ITP and tumor characteristics. In contrast, the median platelet count was 15.10(9)/l (range 3-26) for the 3 patients with a correlation between the course of ITP and breast cancer evolution and 70.10(9)/l (range 20-90) for the other cases (p = 0.05, Mann-Whitney U test). Breast cancers are associated with ITP, with a parallel course of the two diseases in one third of cases. This may suggest tumor-induced immunologic thrombocytopenia.

The cell proliferation rate has been correlated to the response of breast carcinomas to preoperative chemotherapy (CT) and to disease outcome. However, this parameter is not yet used to select which tumours should be treated with preoperative CT. Furthermore, there is no consensus in the method used to evaluate cell proliferation. In poor prognosis breast carcinomas (PPBCs) treated by intensive preoperative CT, we compared the predictive value of S phase fraction (SPF), mitotic index (MI) and Ki67. We also evaluated the prognostic significance of the variation of the MI after CT. A series of 55 T2-T4N0N1M0 breast carcinomas were treated with 4 cycles of cyclophosphamide, 5-fluorouracil (5-FU) and doxorubicin. SPF was determined by flow cytometry on pretherapeutic needle aspiration products. NU and Ki67 were evaluated on pre-therapeutic biopsy samples and on the tumours after CT. Fifteen patients (27%) had a pathological complete response (pCR), whereas 40 (73%) had residual disease. All three proliferative markers were found to have predictive value, but this value was higher for MI than for SPF (P = 0.04) and Ki67 (P = 0.03): the rate of pCR was 50% in cases with MI > 17/3.3 mm(2), but was only 70% in cases with MI under this threshold (P = 0.0003). A significant decrease of MI (mean 10.97) was observed after CT (P 0.001). Furthermore, we observed that even for patients with residual tumour, the variation of MI after CT was a prognostic parameter and overall survival. The sequential analysis of MI in breast cancers treated by preoperative CT thus provides a surrogate for predicting long-term outcome. (C) 2004 Elsevier Ltd. All rights reserved.

The aim of this study was to determine whether the metastatic potential of breast cancer could be related to phenotypic characteristics of the tumour. Therefore, we compared the metastatic patterns of invasive lobular (ILC) and ductal (IDC) carcinomas. In ILC, we also analysed this pattern according to the histological subtype of the primary and the E-cadherin (EC) expression level. Metastatic ILC cases (n=96) were retrospectively analysed and classified into classical, alveolar, solid, tubulo-lobular, signet ring cells or pleomorphic subtypes. Anatomical distribution of metastases was detailed for every patient and compared with that registered for IDC (n=2749). Immunostaining of EC (HECD1 antibody) was performed in 82 cases. Histologically, 78 of the 96 cases (81%) corresponded to classical ILC. The pleomorphic subtype was observed in 14 cases (15%), a rate that was higher than that expected. Others corresponded to alveolar (2 cases), signet ring cell (1 case) and solid (1 case) subtypes. EC was undetectable in 72/82 cases (88%). The rate of multiple metastases was higher in ILC (25.0%) than in IDC (15.8%) (P=0.016). Metastases were found more frequently in ILC than in IDC in the bone (P=0.02) and/or in various other sites (peritoneum, ovary, digestive tract, skin em leader ) (P

The data acquisition for the infrared measurement system on Tore-Supra is a key element in ensuring the supervision of the new actively-cooled plasma facing components of the CIEL project. It will allow us to follow the thermal evolution of components of Tore-Supra, in particular the toroidal pumped limiter (LPT) (360°–15 m long) and the five additional heating launchers. When fully installed, the infrared measurement system will be composed of 12 digital 16-bit infrared cameras. They cover a 100–1200 °C temperature range and each picture has a definition of 320×240 pixels with a 20 ms time resolution. The objectives of the data acquisition system is real-time recording and analysis of each view element for further post-pulse analysis in order to understand the physics phenomenon and ensure the supervision of the plasma facing components and also to be part of the global feedback control system of Tore Supra.

A short review of diagnostics and techniques for active power exhaust control is given from the point of view of experiences gained at Tore Supra. The physical and technological aspects are presented with the aim of illustrating strengths, difficulties and potential for future long pulse and steady state fusion devices such as W7X and ITER-FEAT. One of the main features of the Tore Supra approach to power exhaust control is the reliance on infrared (IR) thermography to survey nearly 100% of the high flux target zones. This is applied to the largest elements, the toroidal pump limiter and the heating antennae, by a number of IR endoscopes. For high flux target areas inaccessible to direct view, optical fibres in the IR and the near-IR range are used. The large wall panels, which evacuate the rest of the power, are controlled by calorimetry. Bolometry is used to achieve a complete power balance. These measurements can be inserted in control loops acting typically on the injected heating power or the radiation cooling.

The aim of this retrospective study was to assess predictive factors for clinical response to preoperative chemotherapy and prognostic factors for survival. From 1981 to 1992, 936 patients with T2-T3, N0-N1 breast cancer who received 2–6 months (median 4) of preoperative chemotherapy were selected from the Institute Curie database. Preoperative treatment was followed by surgery and/or radiotherapy. Median follow-up was 8.5 years (range 7–211 months). The objective response rate before surgery and/or radiotherapy was 58.3%. In stepwise multivariate analysis (Cox model), favourable prognostic factors for survival were the absence of pathological axillary lymph node involvement (Relative Risk (RR) 1.54; P=0.0004), low histological tumour grade (RR=1.54; P=0.0017), clinical response to preoperative chemotherapy (RR=1.45, P=0.0013), positive progesterone receptor (PR) status (RR=1.56; P=0.0001), smaller tumour size (RR=1.37; P=0.005) and lack of clinical lymph node involvement (RR=1.42; P=0.007). The association of clinical tumour response with survival is independent of the baseline characteristics of the tumour. Clinical response could be used as a surrogate marker for evaluation of the efficacy of neoadjuvant chemotherapy before assessment of the pathological response.

Tore Supra has chosen to protect the most heavily solicited and actively cooled target plates by thermography using optical fibres. In consequence to previous experience [J. Nucl. Mater. 290–293 (2001) 701], the prototype periscope for the 2001 experimental campaign was equipped not only with silica fibres but also with a ZrF 4 fibre, transparent up to 4 μm. As then, the measurements in the mid infrared range give lower temperatures than the ones in the near infrared range. The silica fibres are more robust and easier to calibrate, which may justify to use both types side by side using a cross calibration formula. Measurements with an silica fibre embedded in the interior of the target plate exhibited only during discharges with LHCD heating sufficient signal levels to be spectrally analysed. Under these conditions the same kind of additional near infrared radiation as on the silica fibres looking at the exterior of the target plates was observed.

BACKGROUND The objective of this study was to determine whether HER2 expression levels in breast carcinomas were modified by chemotherapy or during the metastatic process. METHODS HER2 expression was analyzed on sequential tissue specimens taken from the primary tumor before patients received preoperative chemotherapy (CT) and from post-CT residual breast tumor or at a metastatic site. The first group of patients included 59 women who presented with T2–T4,N1–N2 breast carcinoma and were treated by preoperative anthracycline-based CT and then underwent surgery. The second group included 44 patients with metastatic breast carcinoma localized to the lung (27 patients) or to the liver (17 patients). HER2 status was determined by immunohistochemistry using an anti-p185HER/neu monoclonal antibody and was classified as overexpressed or not overexpressed. RESULTS Among the patients who received preoperative CT, HER2 overexpression was observed in 15 of 59 patients (25%). A complete pathologic response was observed in 2 of these 15 patients. HER2 still was overexpressed in 11 of 13 remaining residual tumors and was no longer detectable in 2 tumors. In addition, the 29 tumors with no HER2 overexpression before CT remained negative after treatment. In patients with metastatic breast carcinoma, HER2 was overexpressed in 11 of 44 primary tumors (25%). In 9 of these 11 tumors, HER2 overexpression was maintained in the metastases (9 pulmonary metastases and 4 hepatic metastases). In two patients who had low levels of HER2 overexpression in their primary tumors, no staining was observed in the secondary tumor (one pulmonary tumor and one liver tumor). There were no tumors in which the overexpression of HER2 was found only in the metastasis. CONCLUSIONS The current study showed that, in most patients, HER2 overexpression was unchanged after CT and in metastatic sites. No HER2 negative primary tumors became HER2 positive after patients received CT or during the metastatic process. In a few patients, a diminution in the level of HER2 expression was observed after CT or in secondary tumors. This may have been due to a transitory state of altered tumor cells or to the selection of HER2 negative tumor cells clones. Cancer 2002;94:2169–73. © 2002 American Cancer Society. DOI 10.1002/cncr.10456

The data acquisition for the infrared measurement system on Tore-Supra is a key element to ensure the supervision of the new actively cooled plasma-facing components of CIEL (Inner Components and Limiter), which is a major upgrade of Tore Supra. It will allow us to follow the thermal evolution of components of Tore-Supra, in particular the toroidal pumped limiter (LPT) (360/spl deg/-15 m long) and the five additional heating launchers. When fully installed, the infrared measurement system will be composed of 12 digital 14-bit infrared cameras. They cover a 100-1200/spl deg/C temperature range, and each picture has a definition of 320 /spl times/ 240 pixels with a 20 ms time resolution. The objectives of the data acquisition system are real-time recording and analysis of each view element for further postpulse analysis in order to understand the physics phenomenon and ensure the supervision of the plasma facing components, and also to be part of the global feedback control system of Tore Supra.

Neoadjuvant chemotherapy is able to reduce the size of the majority of breast tumours and down-stage axillary-node status. The aim of this study was to assess the prognostic value of persistent node involvement after neoadjuvant chemotherapy. A total of 488 patients with T2–T3, N0–N1 breast cancer treated by neoadjuvant chemotherapy followed by tumour excision and axillary lymph-node dissection between 1981 and 1992 were selected from the Institut Curie database. Median follow-up was 7 years. Overall objective response rate before local treatment was 52% and breast tumour size was reduced in 83% of patients. No pathologic nodal involvement was observed in 46.5% of patients. Patients with ≥ eight positive nodes had a very poor median disease-free survival of only 20 months. Their 10-year disease-free survival rate was 7%, while the 10-year disease-free survival rate for patients with no node involvement was 64%. Median survival for patients with ≥ eight nodes positive was 48 months and the 10-year survival rate was 26% (P < 0.0001). On multivariate analysis, outcome was strongly correlated with pathological nodal status, tumour grade, hormonal receptor status and clinical response of the tumour. In conclusion, patients with extensive nodal involvement after neoadjuvant chemotherapy have a very poor outcome. Second-line treatment should be considered in this population. © 2000 Cancer Research Campaign http://www.bjcancer.com

Tore-Supra is an actively cooled machine aiming at long pulse operation. Surface temperature measurements are necessary in this context to achieve a real time feed-back control on plasma parameters, as well as auxiliary heating systems. Safety interlock is also mandatory when using such actively cooled elements to prevent any damage due to overheating by the plasma, or a loss of active cooling. As an example, it will be shown how the actively cooled pump limiters test campaign has been conducted. The CIEL project for Tore-Supra is aimed at replacing the old generation of plasma facing components designed in 1984, by new ones with a full coverage of the inside vessel. A set of dedicated infrared systems will be used to measure the surface temperatures. They will be included in the real time feed-back loop control and the safety system.

We have previously reported an overall response rate of 41% and a median survival duration of 14 months in a series of 49 patients with metastatic or recurrent endometrial carcinoma treated by a combination of etoposide, 5-fluorouracil, and cisplatin. In order to increase response rate and survival duration, doxorubicin was added to this combination. From August 1992 to January 1996, 20 consecutive patients were treated with a monthly combination chemotherapy consisting of doxorubicin 30 mg/m 2 iv Day 1, 5-fluorouracil 600 mg/m 2 iv Days 1 to 3, etoposide 80 mg/m 2 iv Days 1 to 3, and cisplatin 35 mg/m 2 iv Days 1 to 3 (AFEP). All patients were evaluable for response and toxicity. Median age was 62 years (range 45–72). Two to eight cycles were delivered (median 5). Two of 20 patients had complete response and 7 of 20 had partial response. The objective response rate was 45% (CI 95%: 23–68%). The median survival duration was 17 months. The median progression-free survival was 8 months. Major toxic effect was myelosuppression: 75% of grade 3 and 4 leukopenia and 20% of grade 3 and 4 thrombocytopenia. Seven patients (35%) developed infection and 4 (20%) were hospitalized once or more for toxicity. These results indicate that AFEP is an effective combination therapy in metastatic endometrial carcinoma but its toxicity is unacceptable.

BACKGROUND The clinicopathologic features of infiltrating lobular carcinoma (ILC), which represents 5% to 15% of all breast cancers, are still controversial. In particular, the high frequency of multicentric lesions has led to questioning of the effectiveness of conservative treatment for this type of cancer. By studying a large number of cases, we aimed to compare the clinicopathological features of ILC with those of nonlobular infiltrating carcinoma (NLIC) and to assess the advisability of conservative therapy in the management of ILC. METHODS The population analyzed included 726 cases of ILC, 249 cases of mixed ILC/invasive ductal carcinoma (ILC/IDC), and 10,061 cases of NLIC. The age of patients, TNM status, estrogen- and progesterone-receptor status (ER, PR), and histologic grades of the 3 groups were compared. The follow-up was carried out on a subgroup of 5846 cases. RESULTS At diagnosis, ILC tumors were found to be larger on average and were detected in patients older than those with NLIC, but the degree of lymph node involvement was lower in patients with ILC than in NLIC. In ILC, tumors are more frequently grade I and ER-positive than in NLIC. Multicentric lesions were not significantly more frequent in ILC than in NLIC. The overall survival, locoregional control, disease free interval, and metastatic spread rates were not different among the three groups neither by univariate nor multivariate analysis, but the pattern of metastatic dissemination was different. In 480 cases of ILC considered for conservation therapy, the local recurrence and overall survival rates were similar to those observed for IDC. CONCLUSIONS Our analysis specifies the clinicopathological features of ILC and confirms that conservation therapy may be an appropriate treatment for this type of cancer. Cancer 1996;77:113-20.

PURPOSE The study investigated the therapeutic effects of a combination of Navelbine (vinorelbine or 5'noranhydrovinblastine; Pierre Fabre Médicament, Boulogne, France) and doxorubicin in women who had received no prior chemotherapy for locally advanced or metastatic breast cancer. PATIENTS AND METHODS Ninety-seven patients with progressive and assessable advanced or metastatic breast cancer who had received no prior chemotherapy except in an adjuvant setting were entered onto the study. Eighty-nine patients were assessable for toxicity and response by World Health Organization (WHO) criteria; the other eight patients were excluded because they did not meet entry criteria or because of protocol violations. Navelbine was administered at 25 mg/m2 by 30-minute intravenous (IV) infusion on days 1 and 8, and doxorubicin at 50 mg/m2 by slow IV infusion on day 1, with each course repeated at 3-week intervals. Patients were treated for a maximum of 11 cycles or until progression or major toxicity. RESULTS Objective responses were observed in 66 of 89 assessable patients (74%; 95% confidence interval, 63% to 85%). There were nineteen (21%) complete responses (CRs) and 47 (53%) partial responses (PRs). In addition, 20 patients (22.5%) had stable disease and three (3.5%) progressed while on treatment. Responses were observed at all sites of metastatic disease. Forty-one of 58 patients with visceral disease responded (71%) and 25 of 31 with soft tissue and bone disease experienced an objective response (81%). The median duration of response was 12 months (range, 2.4 to 40.5), and the median overall survival was 27.5 months (range, 4 to 46). Neutropenia was dose-limiting, with 36 patients (41%) experiencing grade 3 or 4 toxicity. Of 727 cycles administered, there were 20 admissions (3%) for treatment of febrile neutropenia, involving 14 of 89 patients (16%). Treatment-related cardiotoxicity at grade 2 to 4 was experienced by 10% of patients and necessitated the interruption of treatment in 1.5% of cycles. Other side effects were uncommon or manageable by conventional means. CONCLUSION The encouraging response rates and duration achieved with this combination of Navelbine/doxorubicin under the conditions of this study deserve further randomized comparative trials with standard regimens.

The aim of this study was to assess a potential advantage in survival by neoadjuvant as compared to adjuvant chemotherapy. 414 premenopausal patients with T2-T3 N0-N1 M0 breast cancer were randomised to receive either four cycles of neoadjuvant chemotherapy (cyclophosphamide, doxorubicin, 5-fluorouracil), followed by local-regional treatment (group I) or four cycles of adjuvant chemotherapy after primary irradiation +/- surgery (group II). Surgery was limited to those patients with a persisting mass after irradiation, and aimed to be as conservative as possible. 390 patients were evaluable. With a median follow-up of 54 months, we observed a statistically significant difference (P = 0.039) in survival in favour of the neoadjuvant chemotherapy group. A similar trend was seen when the time to metastatic recurrence was evaluated (P = 0.09). At this stage, no difference in disease-free interval or local recurrence between these two groups could be observed. The mean total dose of chemotherapy administered was similar in both groups. On average, group I had more intensive chemotherapy regimes (doxorubicin P = 0.02) but fewer treatment courses (P = 0.008) as compared to the treated patients in group II. Haematological tolerance was reduced when chemotherapy succeeded to exclusive irradiation. Breast conservation was identical for both groups at the end of primary treatment (82 and 77% for groups I and II, respectively). Of the 191 evaluable patients in the neoadjuvant treatment arm, 65% had an objective response (> 50% regression) following four cycles of chemotherapy. The objective response rate to primary irradiation (55 Gy) was 85%. Improved survival figures in the neoadjuvant treatment arm could be the result of the early initiation of chemotherapy, but we cannot exclude that this difference might be attributable to a slightly more aggressive treatment. So far, the trend in favour of decreased metastases was not statistically significant. The local control appeared similar in both subgroups.

19th International Conference on Plasma-Surface Interactions in Controlled Fusion Devices (PSI), Univ Calif, Gen Atom, San Diego, CA, MAY 24-28, 2010; International audience; Understanding heat flux deposition processes is essential for the design of the plasma facing components allowing reliable high power steady state plasma operations. Due to the magnetic configuration of Tore Supra, the deposited heat flux is found to be particularly sensitive to tile misalignment in a region where magnetic field lines graze the surface (incident angle typically

The ITER tokamak is the next generation fusion device which will allow studying burning plasma obtained by a Deuterium-Tritium (D-T) fusion reaction during hundreds of seconds. ITER vacuum vessel real-time protection will be mandatory during plasma operation to avoid water leaks and critical plasma facing components degradation. The protection system will be based on a wide angle viewing system (WAVS) composed with 18 visible (VIS) and 18 infrared (IR) cameras covering 80 % of the vacuum vessel which will be one of the major imaging systems of ITER. Compared to protection systems routinely used on current tokamaks and based on imaging (VIS and/or IR), new constraints must be taken into account because of their influence on the system performance: the harsh environment (high neutron flux) and the metallic plasma facing components (both first wall and divertor). In this new demanding context, we have achieved three mandatory R&D studies starting from the understanding of the source of signals by using realistic photonic simulation up to real-time processing strategy taken into account first order optical design constraints to define what type of performance could be reached for ITER vacuum vessel protection.

1. Séminaire FONCIMED sur les Modes de Régulation des Echanges Fonciers et de l'Occupation du Sol, 2008/10/08-12, Antalya (Turquie); International audience; Les terres agricoles subissent une pression croissante à la suite de l'étalement urbain et résidentiel, du développement du tourisme et de la modification des formes d'usage des espaces ruraux, et ce, quel que soit le niveau de développement des pays. C'est dans la perspective d'apporter des connaissances utiles aux décideurs publics du bassin méditerranéen souhaitant mettre en oeuvre des mesures de protection des espaces agricoles, qu'un réseau méditerranéen pluridisciplinaire d'échanges et de comparaison d'expériences sur la question foncière s'est constitué à l'initiative du CIHEAM-IAMM et de l'INRA en 2007 : le réseau FONCIMED. Son premier séminaire s'est tenu à Antalya en Turquie (8-12 octobre 2008) sur le thème des "modes de régulation des échanges fonciers et de l'occupation du sol". Le présent numéro d'Options méditerranéennes rassemble les contributions présentées à cette occasion. Ces recherches visent en premier lieu à connaître la nature des outils utilisés ou mobilisables par l'action publique. En second lieu, elles tendent à comprendre la relation qui s'instaure entre l'action publique et les comportements sociaux ou économiques sur lesquels elle est censée influer afin d'identifier les liens entre le niveau d'efficience et la nature des mesures mises en oeuvre et de dégager des enseignements transférables.

Breast cancer cells from 92 patients were obtained by repeated fine needle sampling and analysed by flow cytometry for cell cycle modifications during neoadjuvant chemotherapy. Modifications of the histograms were observed for 47 of the 71 informative cases (66%), the most frequent concerning S-phase (increase or decrease) and G2M accumulation. These modifications correlated well with the efficacy of cytotoxic chemotherapy (P0.0001). A significant relationship between clinical regression and pretreatment proliferative activity was also observed, with 31/35 (89%) responders in the high proliferation group (S-phase fraction5% or BrdU labelling index3.3%) compared to 20/36 (56%) in the low proliferation group (P0.002). For patients undergoing chemotherapy including doxorubicin, a high incidence of G2M accumulation was observed (33%), a modification which was rare (4.5%) for a regimen with no anthracycline, for which S-phase was the most frequently modified cell cycle compartment (64%). The measurement of the pretreatment tumour proliferative activity as well as the early kinetic modifications, as indicators of response, may prove interesting parameters for the future management of neoadjuvant chemotherapy.

The conceptual and technological development of ITER divertor thermography approaches the aim to provide measurements for machine protection and physics studies even for the case of an eventual change to metallic targets. This requires not only the use of spectrally resolved imaging thermography but also the use of various additional calibration and precision measurement tools such as pyroreflectometry and the use of the photothermal effect. The question of the optical transport through the divertor port is resolved in a compromise with justification for both conventional and fibre elements. The remote handling sequence for such a device is demonstrated. The next steps to take are outlined.

Primary chemotherapy in localised breast cancer may prevent tumour spread during surgical treatment and reduce proliferation of micrometastases. A randomised clinical trial, in 196 premenopausal and postmenopausal patients with operable (T2-3, N0-1b) breast cancer, was started in November 1983 at the Institut Curie to compare neoadjuvant and adjuvant regimens of chemotherapy with radiotherapy with or without surgery. The patients have been followed up for 35-70 months (median 54). A neoadjuvant group received two monthly cycles of intravenous doxorubicin/cyclophosphamide/5-fluorouracil before locoregional therapy and four cycles subsequently. Six monthly cycles following locoregional therapy were administered to the adjuvant group. Because of inclusion of postmenopausal and/or node-negative patients, compliance was less than optimal in 39 patients who were analysed separately according to actual dose received. Tumour response, evaluated after two cycles of neoadjuvant chemotherapy, was significantly associated with dose (P = 0.003). Survival showed a slight non-significant advantage for the neoadjuvant group. Survival plotted by actual dose was also similar. Neoadjuvant chemotherapy was safe and at least as effective as the adjuvant regimen. Patients have been accrued to a subsequent larger trial of chemotherapy as first-line treatment.

We give here a short overview of the status of the development for ITER thermography as performed by the CEA‐Cadarache and some of its collaboration partners. The topics that have been included in this synthesis are the status of the optical design, the role of multi‐wavelength mesurements, multicolour pyroreflectometry, photothermal methods, and reflection simulations and measurements.

In the course of the development of a concept for a spectrally resolving infrared thermography diagnostic for the ITER divertor we have tested 3 types of infrared (IR) fibres in Co60 irradiation facilities under γ irradiation. The fibres were ZrF4 (and HfF4) fibres from different manufacturers, hollow fibres (silica capillaries with internal Ag/AgJ coating) and a sapphire fibre. For the IR range, only the latter fibre type encourages to go further for neutron tests in a reactor. If one restricted the interest onto the near infrared range, high purity core silica fibres could be used. This study might be seen as a typical example of the relation between diagnostic development for a nuclear environment and irradiation experiments.

Resume Les auteurs decrivent l'utilisation du trace d'electrophorese des extraits proteiques totaux sur gel polyacrylamide (SDS-PAGE) comme methode d'identification des especes de Clostridium presentant un interet clinique, en particulier C. difficile. 83 souches isolees a partir de toutes sortes de prelevements ont ete incluses. Toutes les souches provenaient de nos patients hospitalises, a l'exception de six, aimablement fournies par le Dr Sedallian (Annecy, France). Des souches de reference venant de l'Institut Pasteur ont ete utilisees. L'identification a ete effectuee par des techniques classiques comprenant l'etude du mode de fermentation, du contenu enzymatique et des produits de fermentation par electrophorese en phase gazeuse. Les extraits proteiques ont ete obtenus par un traitement assez brutal : 10 ml d'un bouillon de culture de 24 heures ont ete recoltes et centrifuges. Le culot a ete repris en tampon phosphate, puis porte a ebullition en presence de SDS et de β-mercapto-ethanol. La SDS-PAGE de cet extrait a ete effectuee selon Laemmli et coloree au bleu de Coomassie. Dans des conditions tres minutieusement standardisees, le trace proteique est tres constant pour la meme souche. Pour plusieurs especes, par exemple C.perfringens, le trace est tres constant et tres specifique, permettant d'utiliser cette methode comme procede d'identification. Au contraire, des especes comme C. difficile montrent des traces tres differents d'une souche a l'autre, en relation avec le serotype. Dans ces cas, l'utilite de la SDS-PAGE comme methode de typage intra-especes est a l'etude.

International audience; In the course of the development of a concept for a spectrally resolving thermography diagnostic for the ITER divertor using optical fibres experimental development work has been carried out in three different areas. Firstly ZrF4 fibres and hollow fibres (silica capillaries with internal AG/AgJ coating) were tested in a Co60 irradiation facility under c irradiation up to doses of 5 kGy and 27 kGy, respectively. The ZrF4 fibres suffered more radiation induced degradation (>1 db/m) then the hollow fibres (0–0.4 db/m). Secondly multi-colour pyroreflectometry is being developed towards tokamak applicability. The emissivity and temperature of tungsten samples were measured in the range of 700–1500 degC. The angular working range for off normal observation of the method was 20–30deg. The working distance of the method has been be increased from cm to the m range. Finally, encouraging preliminary results have been obtained concerning the application of pulsed and modulated active thermography.

During operation of present fusion devices, the plasma facing components (PFCs) are submitted to large heat fluxes within a range of 10-20 MW/m2. Understanding and preventing overheating of these components during long pulse discharges is a crucial issue. The surface temperature of the PFCs in the inner chamber of a tokamak is measured by infrared (IR) cameras interfaced with complex optical systems. Due to the complexity of the observed IR scenes and the large amount of data produced, a computer-aided analysis of infrared images will be a key point for ITER, the next fusion device for both real-time applications and deferred-time analysis. This paper describes the current state of IR image analysis based on region of interest (ROI) approach at Tore Supra with an extrapolation to the future ITER tokamak.

The Tore Supra tokamak is well adapted to sustain long duration non-inductive discharges using the lower hybrid (LH) heating and current drive as the main power source. In these conditions the LH power deposition profile is strongly linked to the current density profile and can be deducted from the hard X-rays (HXRs) measurements which are produced by the suprathermal electrons (SE) generated by the absorption of the LH wave. The powerful HXR diagnostics that is operating in Tore Supra has been connected to the real-time (RT) data network. The availability of the HXR measurements in RT has allowed the development of an ad hoc algorithm for the RT computation of the SE local emission profile. Since the SE local emission profile is well representative of the LH power deposition profile, this can be controlled in feedback (and so the current density profile as well). This article illustrates the main issues of the code developed to compute the SE local emission profile and its RT connections, together with an explanation of the underlying physics and a description of the HXR diagnostics

From 1981 to 1995, 1755 patients aged 70 years or over who had nonmetastatic unilateral breast carcinoma received curative local or regional treatment in our institute. Median follow-up was 8 years. The median age of these patients was 75 years (range: 70-94), and 86% were under 81 years of age. Tumors were classed as T3-4 in 24% of them; 18% had N1b/N2 tumors, and in 12% grade 3 disease was present. Only 19% were both ER and PR negative. The S phase fraction was5% in 79% of patients. In 1046 patients (60%) modified radical mastectomy was performed, while 20% underwent lumpectomy and in 20% radiotherapy was the only treatment administered. Adjuvant endocrine therapy was given in 463 (26%) cases, and only 3% of patients received chemotherapy. The median overall survival time was 121 months. The overall cancer-related death rate was 49%. The 10-year disease-free survival (DFS) rate was 64%, and the 10-year local relapse rate was 14%. Prognostic factors determined on univariate analysis were tumor size, clinical nodal status (ER and PR), and grade. No significant difference in outcome was observed between mastectomy and conservative treatment. Parameters for which correlations with DFS were found on multivariate analysis were clinical nodal status (P0.0001), tumor size (P0.0001), ER (P0.0001), and PR (P = 0.04). Breast cancer in elderly women is frequently hormone-dependent (81%) with a low proliferation index. Prognostic factors are the same as in younger postmenopausal patients. More than 50% of these patients died from a cause other than their breast cancer.

National audience; Les auteurs décrivent les conflits entre les différents acteurs de la zone péri-urbaine. Celle-ci a beaucoup changé depuis 20 ans au détriment de l'activité agricole. Quatre stratégies principales ont été observées dans les zones péri-urbaines étudiées : le maintien du foncier, l'extension foncière, la rétention du foncier, la vente du foncier. Le droit de propriété discrimine fortement les stratégies des agriculteurs péri-urbains. Ils réagissent fortement aux contraintes et opportunités des villes et les systèmes de production observés autour de Montpellier ou d'Aix-en-Provence combinent trois stratégies principales : stratégies d'intensification, stratégies de spécialisation, stratégies de diversification et d'extensification. Les paysages en sont grandement transformés : mitage, extension des friches, regroupement de parcelles. Dans certains cas des actions de restauration patrimoniale d'espace agricole sont menées. Dans cette arène péri-urbaine, la gouvernance territoriale qui s'appuie sur la création des institutions territoriales, l'élaboration de politiques d'aménagement et l'application de ces programmes doit permettre d'effectuer des consultations et des réajustements entre les différents acteurs.

The aim of this retrospective study was to assess predictive factors for clinical response to preoperative chemotherapy and prognostic factors for survival. From 1981 to 1992, 936 patients with T2-T3, N0-N1 breast cancer who received 2-6 months (median 4) of preoperative chemotherapy were selected from the Institute Curie database. Preoperative treatment was followed by surgery and/or radiotherapy. Median follow-up was 8.5 years (range 7-211 months). The objective response rate before surgery and/or radiotherapy was 58.3%. In stepwise multivariate analysis (Cox model), favourable prognostic factors for survival were the absence of pathological axillary lymph node involvement (Relative Risk (RR) 1.54; P=0.0004), low histological tumour grade (RR=1.54; P=0.0017), clinical response to preoperative chemotherapy (RR=1.45, P=0.0013), positive progesterone receptor (PR) status (RR=1.56; P=0.0001), smaller tumour size (RR=1.37; P=0.005) and lack of clinical lymph node involvement (RR=1.42; P=0.007). The association of clinical tumour response with survival is independent of the baseline characteristics of the tumour. Clinical response could be used as a surrogate marker for evaluation of the efficacy of neoadjuvant chemotherapy before assessment of the pathological response.

Economie et développement; National audience; Le chapitre expose les choix auxquels sont confrontés les agriculteurs dans le cadre d'un processus d'agglomération. Celui-ci impose une concurrence importante à l'agriculture périurbaine. La première partie présente les outils normatifs de l'économie géographique susceptibles de donner un cadre d'analyse mettant en évidence le lien entre zone urbaine et périphérie. La deuxième partie, grâce aux outils de terrain, analyse le processus des stratégies des agriculteurs et leur adaptation aux contraintes nouvelles. Enfin, les stratégies des groupes sociaux ont été étudiées dans le cadre des politiques publiques locales en troisième partie : le lien a pu être ainsi fait entre cette politique et la place des agriculteurs sur le territoire communal.

National audience; In the perimeters under urban centre influence, the agriculture prevalence on its environment is called into question, in particular by the land market with new competitor land uses interference. Before urban growth, the landowners, including farmers, anticipate a land use change and the land prices increase, without relationship with the results of the agricultural activity. All exploitations do not disappear. There are in particular productive strategies incorporating land precariousness (on a annual cultures model which can be realized on one year pieces different on the other). In exchange of the acceptance of precariousness, owners have a less important land rent and compensate for the annual loss surfaces by other lots elsewhere. But these exploitations testify already to a strong urban growth anticipation and in the long term, buildings progresses without constraint. So, the suburbs agricultural landscapes is any more one agricultural problem, but an urban question. Only an institutional and social space regulation can currently counterbalance the space spreading phenomenon. Suburbs agriculture will be able to then become integral part of the urban aménagement plans, recognizing its specificity and its various contributions at the company (production, tallies of life).; Dans les périmètres sous influence d'un centre urbain, la prédominance de l'agriculture sur son environnement spatial immédiat est remise en cause, notamment par le marché foncier du fait de l'immixtion progressive de nouveaux usages du sol concurrents à l'agriculture. Avant même qu'une demande urbaine se formalise, les propriétaires fonciers, y compris les agriculteurs, anticipent un changement d'usage des sols et les prix des terres augmentent, sans rapport avec les résultats de l'activité agricole. Toutes les exploitations ne disparaissent pas. Il existe notamment des stratégies productives incorporant la précarité foncière (sur un modèle de cultures annuelles ne réclamant pas de grosses préparation du sol et pouvant être réalisées sur des parcelles différentes d'une année sur l'autre). En échange de l'acceptation de la précarité les exploitants ont une rente foncière moins importante et compensent la perte annuelle en surface par d'autres gains ailleurs. Mais ces exploitations témoignent déjà d'une anticipation forte de constructibilté et à terme la ville progresse sans contrainte. La préservation des paysages agricoles périurbains n'est donc plus un problème agricole, mais une question urbaine. Seule une volonté institutionnelle et sociale de régulation spatiale peut contrebalancer le phénomène d'étalement spatial de la ville à l'oeuvre actuellement. L'agriculture périurbaine pourra alors devenir partie intégrante des plans d'aménagement urbain, reconnaissant sa spécificité et ses divers apports à la société (production, cadre de vie ).

Summary Background In cancer patients, correlation between response to chemotherapy and gain in survival remains debated. We addressed this question in a multivariate analysis evaluating response to chemotherapy as a factor influencing survival of patients with metastatic breast cancer. Patients and methods From 1977 to 1992, 1430 patients included in eight consecutive prospective trials of anthracycline-based first-line chemotherapy in metastatic breast cancer, were available for assessment. Median follow-up was 155 months. Results Median survival from the date of randomisation was 24 months. Objective response rate was 63.6%. A complete response (CR) was achieved in 17% (249 patients). In a step-wise forward progression analysis objective response was the first independent prognostic factor for survival. Median survival time was 43 months for complete responders (CR), 29 months for partial responders (PR), 18 months for stable disease (SD), 5 months for progressive disease (PD). The probability of survival at 5 and 10 years was 35% and 15% for CR’s and decreased to 18% and 6% for PR’s. The timing of best response (at 4 or 8 months) was not related to outcome. Conclusions Response to an anthracycline-based chemotherapy is a major independent prognostic factor in metastatic breast cancer. The use of this factor to investigate new drugs seems to be pertinent. The good prognosis of complete responders justifies further evaluation of new treatment strategies for this patient population.

BACKGROUND The objective of the current study was to analyze the impact of adjuvant chemotherapy in comparison with other prognostic parameters on the outcome of a series of patients with breast carcinoma at time of metastatic recurrence. METHODS Data from 1430 patients accrued in 8 prospective trials of anthracycline-based first-line chemotherapy conducted at the Institut Curie between 1977 and 1992 were reviewed. RESULTS Patients who had not received adjuvant chemotherapy had better response rates (66%) than pretreated patients (56%; P < 0.0001). Median overall survival rates after metastatic recurrence were 26 months compared with 19 months, respectively (P < 0.0001). Local and regional recurrences as well as the number of organ sites involved with metastatic disease were reduced in patients who had received adjuvant chemotherapy. In a multivariate analysis, the following parameters if present at the initiation of treatment were associated with poor outcome: elevated lactico dehydrogenase (LDH), low Karnofsky index, short disease free interval, more than two involved sites, liver involvement, and prior adjuvant chemotherapy. This adverse prognostic effect of prior adjuvant chemotherapy was independent of the type of drugs and of the duration of the treatment and was present even in the subgroup patients with prolonged disease free intervals longer than 48 months. CONCLUSIONS Adjuvant chemotherapy adversely affects overall response rates and overall survival rates in patients with metastatic breast carcinoma treated with first-line anthracycline based chemotherapy. Cancer 2001;91:1079–89. © 2001 American Cancer Society.

Since response to chemotherapy is a major determinant of survival in metastatic breast cancer, the purpose of our study was to analyse the predictive factors of response. 1426 patients enrolled into eight consecutive randomised trials of anthracycline-based first-line chemotherapy in metastatic breast cancer, between 1977 and 1992, were analysed. A forward stepwise logistic regression analysis was used. The objective response rate (ORR) to chemotherapy in the total population was 63.6% (95% confidence interval (CI): 61.5–67.7). The complete response rate was 17.5%. Multivariate analysis defined adjuvant chemotherapy, lactate dehydrogenase (LDH), Karnofsky index (KI), and pleural and lung metastases to be the five main variables correlated with ORR. A predictive score was calculated using the coefficient of these five variables. The score was established as follows: −1.32+0.54 (if prior adjuvant chemotherapy)+0.80 (low KI)+0.75 (raised LDH)+0.49 (lung metastases)+0.51 (pleural metastases). A low score (less than −0.78) was associated with an ORR greater than 70.0%, representing 41.2% of our population. An intermediate score (between −0.78 and 0) was associated with an ORR of 50 to 70%, representing 37.5% of our population and a positive score was associated with an ORR of less than 50%, representing 21.3% of our population. This score can be used to predict objective response rates to first-line anthracycline-based chemotherapy. This method now needs to be evaluated prospectively in phase II trials. Identification of various risk groups may also be useful for interpretation and design of clinical trials.

In the versatile single species of Escherichia coli, the diarrheagenic group displays a remarkable array of virulence traits. These comprise microbial attachment, production of secretory endotoxins or cell-destroying cytotoxins, direct epithelial cell invasion, and localized effacement of the epithelium. The knowledge of how enteric E. coli induce disease has become increasingly important in the world, because of new pathogen emergence, increasing threats of drug resistance, and growing awareness of their importance in malnutrition and diarrhea. Numerous research programs have demonstrated various mechanisms of pathogenesis. We point out how some pathogens are able to develop intercourse with their host through subversion of its cytoskeleton and signaling processes without toxin secretion or heavy invasiveness. In that domain, the cellular biology of infected cells owes fundamental data to the electron microscopic approach. Combined with advances in microbiology and molecular biology, this approach may provide answers to many unanswered questions.

The afa gene clusters, which encode proteins involved in adhesion to epithelial cells, from Escherichia coli strains associated with urinary and intestinal infections in humans have been characterized. Pathogenic isolates of bovine and porcine origin that possess afa-related sequences have recently been described. We report in this work the cloning and characterization of the afa-7 and afa-8 gene clusters from bovine isolates. Hybridization and sequencing experiments revealed that despite similarity in genetic organization, the afa-7 and afa-8 genes, and the well-characterized afa-3 operon expressed by human-pathogenic isolates, correspond to three different members of the afa family of gene clusters. However, like the afa-3 gene cluster, both the afa-7 and afa-8 gene clusters were found to encode an afimbrial adhesin (AfaE) and an invasin (AfaD). The AfaD peptides encoded by the three gene clusters were only 45% identical, but functional complementation experiments indicated that they belong to the same family of invasins. Hemagglutination and adhesion assays demonstrated that the AfaE-VII and AfaE-VIII adhesins bind to different receptors and that these receptors are not the human decay-accelerating factor recognized to be the receptor of all previously described AfaE adhesins. The AfaE-VIII adhesin is very similar to the M agglutinin of human-uropathogenic strains. We used PCR assays to screen 25 bovine strains for afaD and afaE genes of either the afa-7 or afa-8 gene cluster. The afa-8 gene cluster was highly prevalent in bovine isolates previously reported to carry afa-related sequences (23 of 24 strains), particularly in strains producing cytotoxic necrotizing factors (16 of 16 strains). The location of the afa-8 gene cluster on the plasmids or chromosome of these isolates suggests that it could be carried by a mobile element, facilitating its dissemination among bovine-pathogenic E. coli strains.

The aim of this analysis was to assess how the clinical response to chemotherapy corresponded to long-term prognosis in patients of less than 35 years of age. A retrospective analysis was made of response and survival data of 609 premenopausal patients who had been treated by four cycles of neoadjuvant chemotherapy followed by surgery and/or radiotherapy. Patients were stratified into three age groups (group 1, ≤35 years; group 2, 35–40 years; group 3, ≥41 years). Objective and complete clinical response rates were significantly higher in the youngest patients (below 35 yrs: P =0.005 and P =0.001, respectively) in stark contrast to a particularly poor outcome of this subpopulation. Five-year local recurrence rates were 31% in the youngest patients, compared with 26% and 16% in groups 2 and 3, respectively ( P =0.0007). Group 1 patients also had significantly higher 5-year metastatic relapse rates (41% versus 35% and 28%; P =0.007) and 5-year survival figures were 70%, 82% and 84% for groups 1, 2 and 3 respectively ( P =0.002). Finally, stratification by age and by response revealed that, whilst the outcome of the youngest patients was highly dependent on their response to primary chemotherapy, complete responders showed disease-free survival rates at 5 years that were lower than these of older patients, whatever their response. Despite a seemingly better control of the primary tumour by chemotherapy, the patients in the youngest age group remained at a high risk for local and metastatic relapse. This apparent paradox may be in part attributable to rapid disease progression of micrometastatic tumour subpopulations that are refractory to chemotherapy.