Description: We present a case of multiple metastatic epithelioid sarcoma stabilized for 32 months under third line Sunitinib Malate treatment. A 34-year old male patient, native of Cameroon, presented with a 5 years history of multi-resected lesions of the right palm, which had spread on the forearm. The histopathological aspect consisted in a dermal and subcutaneous sarcomatous proliferation of atypical epithelioid and spindle cells, with foci of necrosis, and mitotic activity (9 mitoses per mm²) (Fig. 1A).

Description: The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC)-TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumor staging summarizes data on tumor burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can significantly vary among patients within the same stage. The current classification provides limited prognostic information, and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status, and gene expression-based stratification. These parameters rely on tumor-cell characteristics. Extensive literature investigated the host-immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumors. A methodology named “Immunoscore” has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM-classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).

Description: Purpose To introduce a direct method for estimating relaxation and kinetic parameter values from rapid dissolution dynamic nuclear polarization (RD-DNP) NMR time courses. Theory and Methods The analysis relied on a kinetic model that is often used to analyze data in these studies—a unidirectional (bio)chemical reaction with rate constant k 1 , coupled to longitudinal relaxation of the magnetization of substrate and product that is characterized by the time constant T 1 . The latter value was estimated from the width of the product curve (peak) at the height α relative to the maximum height. We showed α ∼ 0.8 under most conditions, so we measured the interval between the falling and rising parts of the curve at the relative height 0.8. We called this the “fall-minus-rise time at height α ,” or FmR α , and found that FmR 0.8 ∼ T 1 . The ratio β = (substrate signal/product signal) when the product is maximal was shown to be equal to k 1 T 1 . Therefore, k 1  =  β/FmR 0.8 . Results FmR α analysis was demonstrated with 13 C NMR RD-DNP data recorded from hemolysates and from previously published data. Conclusion FmR α analysis enables immediate estimates of kinetic and relaxation parameters from 13 C NMR RD-DNP data. The values can be used as initial estimates in more extensive computer-based data-regression analysis. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

Description: This paper presents two digital transmission techniques for long haul ionospheric links. Since 2003 we have studied the HF link between the Antarctic Spanish Base, Juan Carlos I, and Spain and we have described the link in terms of availability, signal to noise ratio (SNR) and delay and Doppler power profile. Based on these previous studies we have developed a test bed to investigate two digital transmission techniques, i.e. Direct Sequence Spread Spectrum and Orthogonal Frequency Division Multiplexing, which can provide a low power, low rate ionospheric data link from Antarctica. Symbol length, bandwidth and constellation are some of the features that are analyzed in this work. Data gathered from the link throughout the 2010/2011 and 2011/2012 Antarctic surveys show that spread spectrum techniques can be used to transmit data at low rate when the channel forecast is poor but when the channel forecast is good multicarrier techniques can be used to transmit sporadic bursts of data at higher rate.

Description: Thermal stress affects organism performance differently depending on the ambient temperature to which they are acclimatized, which varies along latitudinal gradients. This study investigated whether differences in physiological responses to temperature are consistent with regional differences in temperature regimes for the stony coral Oculina patagonica . To resolve this question we experimentally assessed how colonies originating from four different locations characterized by 〉3°C variation in mean maximum annual temperature responded to warming from 20 to 32°C. We assessed plasticity in symbiont identity, density, and photosynthetic properties, together with changes in host tissue biomass. Results show that, without changes in the type of symbiont hosted by coral colonies, O. patagonica has limited capacity to acclimatize to future warming. We found little evidence of variation in overall thermal tolerance, or in thermal optima, in response to spatial variation in ambient temperature. Given that the invader O. patagonica is a relatively new member of the Mediterranean coral fauna our results also suggest that coral populations may need to remain isolated for a long period of time for thermal adaptation to potentially take place. Our study indicates that for O. patagonica , mortality associated with thermal stress manifests primarily through tissue breakdown under moderate but prolonged warming (which does not impair symbiont photosynthesis and, therefore, does not lead to bleaching). Consequently, projected global warming is likely to causes repeat incidents of partial and whole colony mortality and might drive a gradual range contraction of Mediterranean corals. This article is protected by copyright. All rights reserved.

Description: Hyperpolarized [1, 13 C]pyruvate was injected rapidly into haemolysates in which hydrolysis of nicotinamide adenine dinucleotide (phosphate) (NAD(P))/NAD(P)H had been inhibited with nicotinamide. Haemolysates provide a stable glycolytic system in which membrane permeability is not a flux-controlling step, and they enable the concentration of NADH to be adjusted experimentally while keeping the rest of the sample with the same composition as that of the cytoplasm of the cell (albeit diluted twofold at the time of injection of the [1, 13 C]pyruvate). We showed that the maximum amplitude of the 13 C NMR signal from the [1, 13 C] L -lactate, produced from [1, 13 C]pyruvate, and the time at which it occurred was dependent on NADH concentration, as predicted by enzyme-kinetic analysis. The main feature of such curves was dictated by the immediacy of the supply of the co-substrate of lactate dehydrogenase (LDH, EC 1.1.1.27), and we posit that this also pertains in vivo in various tissues including neoplasms. By constructing an appropriate mathematical model and by using a Markov-chain Monte Carlo approach, we fitted experimental data to estimate LDH and NADH concentrations. Experiments carried out with only endogenous NADH present enabled the estimation of its effective concentration in human RBCs; the ability to make this estimate is a special feature of the rapid-dissolution dynamic nuclear polarization method. We found an endogenous NADH concentration in human RBCs two to four times higher than previously reported. Copyright © 2014 John Wiley & Sons, Ltd. We measured lactate dehydrogenase and NADH concentrations in human erythrocytes by using 13 C NMR rapid-dissolution dynamic nuclear polarization. A detailed enzyme kinetic model was used in the description of the experimental system, and a Markov-chain Monte Carlo procedure yielded estimates of parameter values. We report new estimates of concentrations of LDH and NADH in human erythrocytes; the former was about three times lower than previously reported while the latter was about three times higher.

Description: Idiopathic CD4 + lymphocytopenia (ICL) is a rare immunodeficiency syndrome of unknown origin for which the increased risks of opportunistic infections and of malignancies have been well established but skin dysimmune diseases, including psoriasis, have been scarcely reported to now. We report herein the severe course of psoriasis in 4 patients with ICL, and show evidence for a defect in the skin recruitment of regulatory CD4 + FoxP3 + T cells. These data raise the apparent paradigm of the occurrence of a severe immunomediated disease together with a profound T-cell defect, a model which might also apply to other immune deficiencies associated with psoriasis. This article is protected by copyright. All rights reserved.

Description: Background:  Even though efficacy of biologics has been extensively studied in psoriasis vulgaris, studies in erythrodermic psoriasis, the most severe form of the disease, have beenscarcelyreported. Objectives:  To address the efficacy and safety of biologics in patients with erythrodermic psoriasis. Methods:  A multicentre national retrospective study was performed using the French Psoriasis Group network. Patients showing psoriasis involving at least 90% of body surface area (BSA), and in whom severity of the disease had been evaluated before and after 3 and/or 6 months of treatment with biologics, were enrolled in the study. Results were expressed using intention to treat analysis. Results:  We included 28 patients, representing 42 flares of erythrodermic psoriasis treated with infliximab (n=24), adalimumab (7), etanercept (6), ustekinumab (3) or efalizumab (2). A 75% improvement of BSA or PASI index 12 to 14 weeks after treatment onset was reached in 48% of flares treated with infliximab, in 50% of those treated with adalimumab and in 40% of those treated with etanercept. Twelve serious adverse events consisting of bacterial infection in 7 of them were observed. Biological treatment was discontinued for safety concern in 19% of cases. A given biologic was pursued up to 48 weeks in 34% of flares. Conclusion:  Biologics show overall good short-term efficacy, but treatment switch due to lack of efficacy or side effects is frequently observed on a longer term, with one third of patients still receiving the drug after one year. The most significant safety concern consists of severe infections.

Description: Background:  Even though efficacy of biologics has been extensively studied in psoriasis vulgaris, studies in erythrodermic psoriasis, the most severe form of the disease, have beenscarcelyreported. Objectives:  To address the efficacy and safety of biologics in patients with erythrodermic psoriasis. Methods:  A multicentre national retrospective study was performed using the French Psoriasis Group network. Patients showing psoriasis involving at least 90% of body surface area (BSA), and in whom severity of the disease had been evaluated before and after 3 and/or 6 months of treatment with biologics, were enrolled in the study. Results were expressed using intention to treat analysis. Results:  We included 28 patients, representing 42 flares of erythrodermic psoriasis treated with infliximab (n=24), adalimumab (7), etanercept (6), ustekinumab (3) or efalizumab (2). A 75% improvement of BSA or PASI index 12 to 14 weeks after treatment onset was reached in 48% of flares treated with infliximab, in 50% of those treated with adalimumab and in 40% of those treated with etanercept. Twelve serious adverse events consisting of bacterial infection in 7 of them were observed. Biological treatment was discontinued for safety concern in 19% of cases. A given biologic was pursued up to 48 weeks in 34% of flares. Conclusion:  Biologics show overall good short-term efficacy, but treatment switch due to lack of efficacy or side effects is frequently observed on a longer term, with one third of patients still receiving the drug after one year. The most significant safety concern consists of severe infections.