Docetaxel and gemcitabine combination in 133 advanced soft-tissue sarcomas: a retrospective analysis.

Advanced soft-tissue sarcomas are usually resistant to cytotoxic agents such as doxorubicin and ifosfamide. Antitumor activity has been observed for gemcitabine and docetaxel combination. We conducted a retrospective study on 133 patients (58 males/75 females) with unresectable or metastatic soft-tissue sarcoma. The median age at diagnosis was 51.7 (18-82), with 76 patients with leiomoyosarcoma and 57 patients with other histological subtypes. The initial localizations were limb (44), uterine (32), retroperitoneal (23) and organs or bone (34). Patients received 900 mg/m2 of gemcitabine (days 1 and 8) over 90 min plus 100 mg/m2 of docetaxel (day 8), intravenously every 21 days. Gemcitabine/docetaxel combination was well tolerated with an overall response of 18.4% and with no clear statistical difference between leiomyosarcomas and other histological subtypes (24.2% versus 10.4% (p=0.06)). No difference was found between uterine soft-tissue sarcomas versus others. The median overall survival was 12.1 months (1-28). Better overall survival was correlated with leiomyosarcoma (p=0.01) and with the quality of the response, even for patients with stable disease (p<10(-4)). No statistical difference was found for the initial localization. Response to treatment and overall survival were better for patients in World Health Organization (WHO) performance status classification (PS) 0 at baseline versus patients in WHO PS-1, 2 or 3 (p=0.023 and p<10(-4), respectively). Gemcitabine/docetaxel combination was tolerable and demonstrated better response and survival for leiomyosarcoma, especially for patients in WHO PS-0 at baseline. For the other histological subtypes, the response was not encouraging, but the survival for patients in response or stable suggests further investigation.

The Europeanisation of the measurement of diversity in education: a soft instrument of public policy

Faced with an increasing number of data and rankings, the author questions the roles of the different groups of actors who were originally involved in questioning the use of statistical indicators as a means of addressing issues of access to higher education. The comparison and nature of these international (UNESCO, OECD, EUROSTAT) and national (Germany, England, France, Switzerland) indicators in matters of inequalities of access to higher education question the tension between the discourses and the indicators they generate, and their recording at the national level. Who says what and with what consequences? What range of actors are involved in this process? What kind of power relations forms them? The author discusses how the issue of inequalities of access to higher education got on to the agendas of European organisations, identifies the policies that were defined, and sets them against an array of indicators, showing the discrepancy between the discourses and what the indicators reveal, the gap between the recommendations and the available tools. Why is there such a contrast? What are the mechanisms at work? Is it a technical or a political problem? What does this discrepancy reveal as far as national specificities within the construction of social inequalities are concerned?

Feasibility of direct mapping of cerebral fluorodeoxy-D-glucose metabolism in situ at subcellular resolution using soft X-ray fluorescence.

Glucose metabolism is difficult to image with cellular resolution in mammalian brain tissue, particularly with (18) fluorodeoxy-D-glucose (FDG) positron emission tomography (PET). To this end, we explored the potential of synchrotron-based low-energy X-ray fluorescence (LEXRF) to image the stable isotope of fluorine (F) in phosphorylated FDG (DG-6P) at 1 μm(2) spatial resolution in 3-μm-thick brain slices. The excitation-dependent fluorescence F signal at 676 eV varied linearly with FDG concentration between 0.5 and 10 mM, whereas the endogenous background F signal was undetectable in brain. To validate LEXRF mapping of fluorine, FDG was administered in vitro and in vivo, and the fluorine LEXRF signal from intracellular trapped FDG-6P over selected brain areas rich in radial glia was spectrally quantitated at 1 μm(2) resolution. The subsequent generation of spatial LEXRF maps of F reproduced the expected localization and gradients of glucose metabolism in retinal Müller glia. In addition, FDG uptake was localized to periventricular hypothalamic tanycytes, whose morphological features were imaged simultaneously by X-ray absorption. We conclude that the high specificity of photon emission from F and its spatial mapping at ≤1 μm resolution demonstrates the ability to identify glucose uptake at subcellular resolution and holds remarkable potential for imaging glucose metabolism in biological tissue. © 2012 Wiley Periodicals, Inc.

Standards and service offshoring in India: Moving beyond industry and institutional specificities

Résumé Cet article examine le rôle joué par les normes internationales techniques dans la mondialisation des activités de service. Différentes approches d'économie considèrent que les spécificités des activités de services sont un frein à leur délocalisation, à leur industrialisation et à leur normalisation. A l'opposé de ces approches centrées sur les spécificités des activités de services, les approches d'économie politique internationale mettent en avant l'existence de configurations conflictuelles de pouvoir à l'oeuvre dans l'internationalisation des activités de services et ce, au-delà des limites sectorielles et nationales. Cet article examine le cas du secteur des centres d'appels et, plus généralement, celui de la sous-traitance des services aux entreprises (BPO) en Inde. Nos résultats suggèrent que les normes techniques sont importantes dans le secteur étudié, alors même que ces types de services sont conventionnellement identifiés comme étant peu susceptibles d'être soumis à des normes. Une perspective d'économie politique sur la normalisation des activités de service souligne comment la problématique du pouvoir investit la normalisation technique d'une dimension plus progressive à travers les thématiques du "travailleur", du "consommateur", ou de "l'environnement". Abstract This paper explores the role of international standards in the much-debated globalisation of the service economy. Various strands of economic analyses consider that core attributes of services affect their ability to be reliably delocalised, industrialised, and standardised. In contrast, international political economy approaches draw attention to power configurations supporting conflicting use of standards across industries and nations. The paper examines the case of the rising Indian service industry in customer centres and business process outsourcing to probe these opposing views. Our findings suggest that standards matter in types of services that conventional economic analyses identify as unlikely to be standardised, and that the standards used in the Indian BPO industry are widely accepted. Despite little conflict in actual definitions of market requirements, an international political economy perspective on service standardisation highlights the importance of potential power issues related to workers', consumers', and environmental concerns likely to be included in more progressive forms of standardisation.

Role of trabectedin in the treatment of soft tissue sarcoma.

Interest in marine natural products has allowed the discovery of new drugs and trabectedin (ET-743, Yondelis), derived from the marine tunicate Ecteinascidia turbinata, was approved for clinical use in 2007. It binds to the DNA minor groove leading to interferences with the intracellular transcription pathways and DNA-repair proteins. In vitro antitumor activity was demonstrated against various cancer cell lines and soft tissue sarcoma cell lines. In phase I studies tumor responses were observed also in osteosarcomas and different soft tissue sarcoma subtypes. The most common toxicities were myelosuppression and transient elevation of liver function tests, which could be reduced by dexamethasone premedication. The efficacy of trabectedin was established in three phase II studies where it was administered at 1.5 mg/m2 as a 24 h intravenous infusion repeated every three weeks, in previously treated patients. The objective response rate was 3.7%-8.3% and the tumor control rate (which included complete response, partial response and stable disease) was obtained in half of patients for a median overall survival reaching 12 months. In nonpretreated patients the overall response rate was 17%. Twenty-four percent of patients were without progression at six months. The median overall survival was almost 16 months with 72% surviving at one year. Predictive factors of response are being explored to identify patients who are most likely to respond to trabectedin. Combination with other agents are currently studied with promising results. In summary trabectedin is an active new chemotherapeutic agents that has demonstrated its role in the armamentarium of treatments for patients with sarcomas.

Soft tissue artifact assessment during treadmill walking in subjects with total knee arthroplasty.

Accurate measurement of knee kinematics during functional activities suffers mainly from soft tissue artifact (STA): the combination of local surface deformations and rigid movement of markers relative to the underlying bone (also called rigid STA movement: RSTAM). This study proposes to assess RSTAM on the thigh, shank, and knee joint and to observe possible features between subjects. Nineteen subjects with knee arthroplasty were asked to walk on a treadmill while a biplane fluoroscopic system (X-rays) and a stereophotogrammetric system (skin markers) recorded their knee movement. The RSTAM was defined as the rigid movement of the cluster of skin markers relative to the prosthesis. The results showed that RSTAM amplitude represents approximately 80-100% of the STA. The vertical axis of the anatomical frame of the femur was influenced the most by RSTAM. Combined with tibial error, internal/external rotation angle and distraction-compression were the knee kinematics parameters most affected by RSTAM during the gait cycle, with average rms values of 3.8° and 11.1 mm. This study highlighted higher RSTAM during the swing phase particularly in the thigh segment and suggests new features for RSTAM such as the particular shape of some RSTAM waveforms and the absence of RSTAM in certain kinematics during the gait phases. The comparison of coefficient of multiple correlations showed some similarities of RSTAM between subjects, while some correlations were found with gait speed and BMI. These new insights could potentially allow the development of new methods of compensation to avoid STA.

Direct mapping of 19F in 19FDG-6P in brain tissue at subcellular resolution using soft X-ray fluorescence

Low energy x-ray fluorescence (LEXRF) detection was optimized for imaging cerebral glucose metabolism by mapping the fluorine LEXRF signal of 19 F in 19 FDG, trapped as intracellular 19 F-deoxyglucose-6-phosphate ( 19 FDG-6P) at 1μm spatial resolution from 3μm thick brain slices. 19 FDG metabolism was evaluated in brain structures closely resembling the general cerebral cytoarchitecture following formalin fixation of brain slices and their inclusion in an epon matrix. 2-dimensional distribution maps of 19 FDG-6P were placed in a cytoarchitectural and morphological context by simultaneous LEXRF mapping of N and O, and scanning transmission x-ray (STXM) imaging. A disproportionately high uptake and metabolism of glucose was found in neuropil relative to intracellular domains of the cell body of hypothalamic neurons, showing directly that neurons, like glial cells, also metabolize glucose. As 19 F-deoxyglucose-6P is structurally identical to 18 F-deoxyglucose-6P, LEXRF of subcellular 19 F provides a link to in vivo 18 FDG PET, forming a novel basis for understanding the physiological mechanisms underlying the 18 FDG PET image, and the contribution of neurons and glia to the PET signal.

Network governance and the domestic adoption of soft rules

European regulatory networks (ERNs) are in charge of producing and disseminating non-bindings standards, guidelines and recommendations in a number of important domains, such as banking and finance, electricity and gas, telecommunications, and competition regulation. The goal of these soft rules is to promote 'best practices', achieve co-ordination among regulatory authorities and ensure the consistent application of harmonized pro-competition rules across Europe. This contribution examines the domestic adoption of the soft rules developed within the four main ERNs. Different factors are expected to influence the process of domestic adoption: the resources of regulators; the existence of a review panel; and the interdependence of the issues at stake. The empirical analysis supports hypotheses about the relevance of network-level factors: monitoring and public reporting procedures increase the final level of adoption, while soft rules concerning highly interdependent policy areas are adopted earlier.

Acute pulmonary toxicity following occupational exposure to a floor stain protector in the building industry in Switzerland.

BACKGROUND: Waterproofing agents are widely applied to leather and textile garments; they are also used as floor stain protectors by professionals. Acute respiratory injury is described in three cases of young healthy adults following occupational inhalation of a new waterproofing formulation containing an acrylate fluoropolymer. Within 1 or 2 h after exposure they developed a rapidly progressive dyspnoea; two of them had hypoxaemia and flu-like reactions. All patients improved with supportive treatment in a few days. The mechanism of toxicity is still under investigation, but experimental data suggest the role of this new acrylate fluoropolymer. CONCLUSION: Tilers should be warned against spraying floor stain repellents; there is also a need to make consumers aware that the spraying of waterproofing agents in a closed environment and concomitant smoking should be avoided.

Epithelioid soft tissue tumors.

Epithelioid neoplasms are generally carcinomas. As confirmation that every rule is meant to be broken, some sarcomas demonstrate epithelioid morphology, and can even express cytokeratins. These sarcomas have unique behavior, for example, a much higher rate of lymph node metastasis than other sarcomas. This group of sarcomas also presents diagnostic and therapeutic challenges to those clinicians who help patients contend with these difficult tumors. In this review, some of the major categories of epithelioid soft tissue tumors are described, with clinical data reported as available. Some of these tumors provide excellent opportunities to examine newer protein-targeted agents in investigational settings.

Spirometric alterations in workers in the chromium electroplating industry.

The spirometric values (VC, FeV1, FEF25-75%) were studied in 44 workers of 17 chromium electroplating plants. Urinary chromium was also measured. The dynamic values of spirometry are lower amongst the workers who have higher urinary chromium. The part that can be attributed to tobacco smoking is much lower than that of chromium. The workers dealing with chromium electroplating in poor conditions seem to be subjects at risk in developing obstructive respiratory syndrome. The hazard seems to be especially high in plants dealing with hard chromium plating.