preoperative c reactive protein and thrombocyte count as potential markers for longterm survival in ovarian cancer

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Toward sustainable environmental quality : priority research questions for Europe

The United Nations' Sustainable Development Goals have been established to end poverty, protect the planet, and ensure prosperity for all. Delivery of the Sustainable Development Goals will require a healthy and productive environment. An understanding of the impacts of chemicals which can negatively impact environmental health is therefore essential to the delivery of the Sustainable Development Goals. However, current research on and regulation of chemicals in the environment tend to take a simplistic view and do not account for the complexity of the real world, which inhibits the way we manage chemicals. There is therefore an urgent need for a step change in the way we study and communicate the impacts and control of chemicals in the natural environment. To do this requires the major research questions to be identified so that resources are focused on questions that really matter. We present the findings of a horizon-scanning exercise to identify research priorities of the European environmental science community around chemicals in the environment. Using the key questions approach, we identified 22 questions of priority. These questions covered overarching questions about which chemicals we should be most concerned about and where, impacts of global megatrends, protection goals, and sustainability of chemicals; the development and parameterization of assessment and management frameworks; and mechanisms to maximize the impact of the research. The research questions identified provide a first-step in the path forward for the research, regulatory, and business communities to better assess and manage chemicals in the natural environment. Environ Toxicol Chem 2018;9999:1-15

Simplified dynamic energy budget model for analysing ecotoxicity data.

Models based on Dynamic Energy Budget (DEB) theory offer important advantages in the interpretation of toxicant effects on life-history traits. In contrast to descriptive approaches, they make use of all of the data (all time points, and all endpoints) in one framework, and yield time-independent parameters. In 1996, a suite of simplified DEB models for the analysis of standard toxicity tests was presented under the name 'DEBtox'. Unfortunately, the original equations contained a few errors and inconsistencies. In this paper, we revisit DEBtox, presenting a new and consistent set of simplified DEB equations. The full derivation is presented in the supplementary material to facilitate critical examination of our work. The simplification is appropriate for situations where body size at the start of investment in reproduction remains constant, as well as the egg costs (and thus hatchling size). These conditions are probably met in many ecotoxicological tests, allowing this framework to be used, at least as a first approach. Additionally, we present a statistical framework for fitting the model to experimental data sets, and to calculate intervals on parameter estimates, model curves and model predictions. As an illustration, we provide a case study for the effects of fluoranthene on Daphnia magna, although the framework is by no means limited to this species or toxicant. © 2011 Elsevier B.V

Debkiss or the quest for the simplest generic model of animal life history.

Understanding the life cycle of individual animals, and how it responds to stress, requires a model that causally links life-history traits (feeding, growth, development and reproduction). Dynamic Energy Budget (DEB) theory offers a powerful and formalised framework for building process-based models for organism life cycles. However, it takes some serious investment to understand the resulting equations and to implement them into software, and a substantial amount of data to parameterise. For many practical applications, there is therefore a need for further simplification. Here, we present a simple and transparent model that fully specifies the life cycle of an (invertebrate) animal, applies a strict mass balance, and has direct access to the primary parameters that determine the metabolic processes. We derive our 'DEBkiss' in a formalised manner, starting from an explicit formulation of the simplifying assumptions. The presented model can serve as a teaching tool and a smooth introduction into the much richer world of DEB theory. Furthermore, the model may prove useful as a building block for individual-based population modelling (where simplicity of the blocks is essential), and for the analysis of toxicity data (where ease of model verification and parameterisation is crucial). The model is illustrated using a fit on growth and reproduction data for the pond snail (Lymnaea stagnalis) at three food levels, and subsequent predictions for embryonic growth and respiration (oxygen use), and weight loss on starvation, for the same species. © 2013 Elsevier Ltd

Metabolic acceleration in the pond snail Lymnaea stagnalis?

Under constant environmental conditions, most animals tend to grow following the von Bertalanffy growth curve. Deviations from this curve can point to changes in the environment that the animals experience, such as food limitation when the available food is not sufficient or suitable. However, such deviations can also point to a phenomenon called metabolic acceleration, which is receiving increasing attention in the field of Dynamic Energy Budget (DEB) modeling. Reasons for such an acceleration are usually changes in shape during ontogeny, which cause changes in the surface area to volume ratio of the organism. Those changes, in turn, lead to changes in some of the model parameters that have length in their dimension. The life-history consequences of metabolic acceleration as implemented in the DEB theory are an s-shaped growth curve (when body size is expressed as a length measure) and a prolongation of the hatching time. The great pond snail Lymnaea stagnalis was earlier found to be food limited during the juvenile phase in laboratory experiments conducted under classical ecotoxicity test protocols. The pond snail has isomorphic shell growth but yet does not exhibit the expected von Bertalanffy growth curve under food limitation. When applying the standard DEB model to data from such life-cycle experiments, we also found that the hatching time is consistently underestimated, which could be a sign of metabolic acceleration. We here present an application of the DEB model including metabolic acceleration to the great pond snail. We account for the simultaneous hermaphroditism of the snail by including a model extension that describes the relative investment into the male and female function. This model allowed us to adequately predict the life history of the snail over the entire life cycle. However, the pond snail does not change in shape substantially after birth, so the original explanation for the metabolic acceleration does not hold. Since the change in shape is not the only explanation for metabolic acceleration in animals, we discuss the possible other explanations for this pattern in L stagnalis

Steady-state Spin Contrast Created by Dynamic Nuclear Polarisation

URL: http://www-spht.cea.fr/articles/S03/010Rapport PSI. Scientific Report p. 191 (march 2003)

Chemotherapy after immune checkpoint inhibitor failure in metastatic melanoma: a retrospective multicentre analysis.

Despite remarkably improved outcomes with immune checkpoint inhibition, many patients with metastatic melanoma will eventually require further therapy. Chemotherapy has limited activity when used first-line but can alter the tumour microenvironment and does improve efficacy when used in combination with immunotherapy in lung cancer. Whether chemotherapy after checkpoint inhibitor failure has relevant activity in patients with metastatic melanoma is unknown. Patients with metastatic melanoma treated with chemotherapy after progression on immunotherapy with checkpoint inhibitors were identified retrospectively from 24 melanoma centres. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety were examined. In total, 463 patients were treated between 2007 and 2017. Fifty-six per cent had received PD-1-based therapy before chemotherapy. Chemotherapy regimens included carboplatin + paclitaxel (32%), dacarbazine (25%), temozolomide (15%), taxanes (9%, nab-paclitaxel 4%), fotemustine (6%) and others (13%). Median duration of therapy was 7.9 weeks (0-108). Responses included 0.4% complete response (CR), 12% partial response (PR), 21% stable disease (SD) and 67% progressive disease (PD). Median PFS was 2.6 months (2.2, 3.0), and median PFS in responders was 8.7 months (6.3, 16.3), respectively. Twelve-month PFS was 12% (95% CI 2-15%). In patients who had received anti-PD-1 before chemotherapy, the ORR was 11%, and median PFS was 2.5 months (2.1, 2.8). The highest activity was achieved with single-agent taxanes (N = 40), with ORR 25% and median PFS 3.9 months (2.1, 6.2). Median OS from chemotherapy start was 7.1 months (6.5, 8.0). Subsequent treatment with checkpoint inhibitors achieved a response rate of 16% with a median PFS of 19.1 months (2.0-43.1 months). No unexpected toxicities were observed. Chemotherapy has a low response rate and short PFS in patients with metastatic melanoma who have failed checkpoint inhibitor therapy, although activity varied between regimens. Chemotherapy has a limited role in the management of metastatic melanoma