In this paper, we investigate the slip effects on the boundary layer flow and heat transfer characteristics of a power-law fluid past a porous flat plate embedded in the Darcy type porous medium. The nonlinear coupled system of partial differential equations governing the flow and heat transfer of a power-law fluid is transformed into a system of nonlinear coupled ordinary differential equations by applying a suitable similarity transformation. The resulting system of ordinary differential equations is solved numerically using Matlab bvp4c solver. Numerical results are presented in the form of graphs and the effects of the power-law index, velocity and thermal slip parameters, permeability parameter, suction/injection parameter on the velocity and temperature profiles are examined. The boundary layer flow play a vital role in many aspects of fluid mechanics and has been studied extensively for decades. A comprehensive literature survey on boundary layer theory and related topics can be found in the studies of –5. RecenIt is revealed from the available literature on boundary layer models including heat transfer analysis that these are limited to Newtonian and some non-Newtonian fluids flow with traditional no-slip flow boundary conditions. Researchers extensively studied flow models for different geometries influenced by a number of factors including fluid viscosity, bounding surface characteristics, and external forces, to name a few. Limited attention was given to the slip boundary condition. Beavers and Joseph  first prThere are many models proposed for the non-Newtonian fluids. The theory of boundary layer for each proposed model is also available in the literature. It is beyond the scope of this work to revisit the vast amount of literature on the boundary layer flow of different non-Newtonian fluid models. Limited work on the topic can be referred as examples in –31. Non-In the present paper, we extend the work of  and invex = 0. The plate coincides with the plane y = 0. The corresponding velocity components in the x and y directions are u and v respectively. The temperature of the plate is Tw. The flow far away from the plate is uniform and in the direction parallel to the plate. The velocity and temperature far away from the plate are U∞ and T∞ respectively. The geometry of the flow model is given in ρ is the fluid density, τxy is the shear stress, T is temperature, Cp is the specific heat at constant pressure and k is the thermal conductivity of the fluid. The boundary conditions for the velocity and temperature fields are:L and D are the initial values of velocity and thermal slip factors and have dimensions of length. Here vw defines suction or blowing through the porous plate.We consider the steady, two-dimensional flow and heat transfer of a power-law fluid over a semi-infinite porous plate in a porous medium. The surface of the plate is insulated and admits partial slip conditions. The leading edge of the plate is at τxy in K is the consistency coefficient and n is the power-law index. In the above constitutive equation n = 1 corresponds to Newtonian fluid behavior. On the other hand, when n < 1 we observe the shear-thinning behavior of the fluid and for n > 1 shear-thickening behavior is observed.The shear stress component L is the characteristic length and f(η) and dimensionless temperature θ(η) are defined asψ in k* = 1/(DaxRex) represents the permeability of porous medium, Dax = k0/x is the local Darcy number, k0 is a constant and vw < 0 and vw > 0, respectively. Moreover, Substitution of m of Eqs  and 7),,u∂u∂x+v∂L)1n+1yL,where L ,v=-∂ψ∂x.Introducions Eqs  and 5)  u∂u∂x+v∂The nonlinear coupled ordinary differential Eqs  and 12)12) togetq(η) and z(η) at η = 0, and uses these initial values to generate solutions using a collocation method. In order to make an appropriate guess we start with a set of parameter values for which solution was known and progress until we obtain the solution of our problem. We verify the correctness of these solutions by comparing them with those obtained using the shooting method. We find the results to be in good agreement with the previous published results of [n = 1 and k* = δ = 0  and  = 0 see .η. The computations are performed for several values of the power-law index n, the velocity slip parameter δ, the thermal slip parameter β, the permeability parameter k* and the Prandtl number Pr and are depicted in Figs In the next section, the numerical results are presented for the velocity and temperature functions of the coordinate n < 1 rises faster than the shear-thickening fluid n > 1. This general observation is consistent with the recognition that at early times, when the strain rates are the largest, the shear-thinning fluid will have the smallest effective viscosity while the shear-thickening fluid will have the largest effective viscosity. Similarly, at later times, the strain rates get smaller and the effective viscosity of the shear thinning fluid will increase. k* on the velocity profile with slip boundary conditions. It is observed that the velocity along the plate increases with increase in the permeability. This in turn decreases the thickness of the momentum boundary layer. This observation is consistent with recognition that an increase in the porosity of the medium decreases the magnitude of the Darcian body force which enhances the motion of the fluid in the boundary layer and ultimately decelerates the fluid particles in the porous medium.k* = 0.3 gives variation of velocity profiles with slip and no-slip boundary conditions for the Newtonian and non-Newtonian fluids. Increase in velocity slip parameter increases the fluid velocity at the given distance from the plate. This in turn decreases the boundary layer thickness.Figs θ(η) for both the Newtonian and non-Newtonian fluids are presented in f approaches zero quickly). However, if n = 1.4, the boundary layer is relatively thick.The slip and permeability effect on the temperature profile S > 0) and the injection (S < 0) parameter on the velocity and temperature profiles in the presence of slip conditions on the boundary of flat plate sandwiched in porous medium. In the case of suction, the momentum boundary layer decreases because at the wall fluid particles are drawn out. This eventually causes the increase in the velocity gradient as well as skin friction. This behavior is observed for both Newtonian and non-Newtonian fluids. Again we observe the velocity of the shear thinning fluid is faster in the beginning due to the above mentioned reason. For the case of injection an opposite trend is observed. θ(η) when suction parameter is increased. This causes a decrease in thermal boundary layer thickness by bringing the fluid closer to wall which in turn increases the rate of heat transfer. For the case of injection the increase in temperature profile is observed. Note that the decrease (S > 0) and increase (S < 0) in temperature profile is slower for shear thickening n > 1 compared to a Newtonian fluid and faster for shear thinning fluid n < 1.Figs θ(η) is plotted for different value of thermal slip parameter δ. The increase in temperature slip parameter reduces the temperature of power law fluid for a given distance from the porous plate. The temperature profile for shear-thickening fluid decreases slower than the Newtonian fluid. The opposite trend is observed for the shear-thinning fluid for increase in the slip parameter. In each case increase in velocity due to slip parameter is responsible for the increase in heat transfer.Below we show the influence of the velocity slip parameter on the velocity and temperature profiles. In β. It is noted that increase in thermal slip parameter decreases the temperature as less amount of heat is transferred from the embedded plate to the fluid. Again this decrease in temperature profile for the n > 1 case is slower and faster for n < 1 case as compared to the Newtonian case. The velocity profile is independent of this effect because the velocity equations are independent of the thermal slip parameter β.Pr number causes a decrease in temperature of a power law fluid at a specified distance from the porous plate. On the other hand an increase in Pr causes an increase in the fluid viscosity. Again this trend is slower for the shear-thickening fluid and faster for the shear-thinning fluid, as compared to a Newtonian fluid. This implies that an increase in Prandtl number is accompanied by a decrease in thermal conductivity which means that the fluid transfers more heat effectively through convection. Thereby the thickness of the thermal boundary layer gets reduced.In n.In the present study we have conducted the study of forced convective boundary layer flow of power-law fluid along with heat transfer over a porous plate in a porous medium. The governing boundary layer equations along with the boundary conditions were first transformed to a set of coupled nonlinear ordinary differential equations using similarity transformation. The resulting system of differential equations was solved numerically. We have summarized our results based on the key parameters such as, the permeability parameter, velocity and thermal slip parameters, injection and suction parameters and Prandtl number along with variation of the power law index The basic feature of our model could be incorporated in further studies on a variety of flow situations in complex media. The anticipation is to incorporate the additional features such as temperature dependent thermal conductivity and heat flux boundary conditions . The


The Warburg effect is a widespread metabolic phenotype of cancer, where glycolysis is favoured despite the presence of oxygen. Dichloroacetate (DCA) is a pyruvate dehydrogenase kinase (PDK) inhibitor in clinical use that can reverse the Warburg effect, inhibiting growth and enhancing apoptosis in a range of cancers. We have investigated its effectiveness against sarcoma cells in vitro , alone and in combination with doxorubicin. In vivo, K7M2 cells were injected s.c. into Rag1-/- mice  and established tumours were treated with DCA in the drinking water . Tumour growth was monitored with callipers. Plasma was collected on d1 and d15 for measurement of DCA levels (LC-MS).Three cell lines  were examined for cell viability after DCA treatment In vivo, 1.0 and 1.5 g/L DCA significantly reduced tumour growth . Plasma DCA was undetectable on d1 of treatment, but by d15, 1.0 and 1.5 g/L DCA delivered 2-44 uM. Tumour DCA concentrations were also measured and found to be in the range of 25-470 uM, much lower than those typically used in in vitro studies.DCA significantly reduced the total viable cell number after 48 h of treatment in the mouse sarcoma lines , however HT1080-luc2 cells showed only a 10% reduction in cell number with 5 mM DCA. There was no morphological indication of apoptosis, suggesting DCA was decreasing proliferation. Chronic treatment of the mouse cells (5 mM DCA for 2 weeks) resulted in significantly slower growth rates as measured over 48 h . DCA did not synergise with doxorubicin but was additive at lower concentrations of doxorubicin. in vivo sarcoma model, with tumour DCA concentrations in the micromolar range. These concentrations are achievable clinically, thus DCA warrants further investigation for sarcoma treatment.DCA was effective against an


To assess the tumour dimensions in uveal melanoma patients using 7-T ocular MRI and compare these values with conventional ultrasound imaging to provide improved information for treatment options.Ten uveal melanoma patients were examined on a 7-T MRI system using a custom-built eye coil and dedicated 3D scan sequences to minimise eye-motion-induced image artefacts. The maximum tumour prominence was estimated from the three-dimensional images and compared with the standard clinical evaluation from 2D ultrasound images.The MRI protocols resulted in high-resolution motion-free images of the eye in which the tumour and surrounding tissues could clearly be discriminated. For eight of the ten patients the MR images showed a slightly different value of tumour prominence (average 1.0 mm difference) compared to the ultrasound measurements, which can be attributed to the oblique cuts through the tumour made by the ultrasound. For two of these patients the more accurate results from the MR images changed the treatment plan, with the smaller tumour dimensions making them eligible for eye-preserving therapy.High-field ocular MRI can yield a more accurate measurement of the tumour dimensions than conventional ultrasound, which can result in significant changes in the prescribed treatment. T1 relaxation times and decreased T1-tissue contrast, the  decreased T2 relaxation times, and the increased sensitivity to differences in magnetic susceptibility. This means that clinical scanning protocols from lower fields must be re-optimised in terms of the different relaxation times. A recent paper provided a comprehensive overview of the current clinical applications of ultra-high-field MRI [The advantages of ultra-high-field human MRI compared to lower clinical fields primarily revolve around the increased signal-to-noise ratio (SNR), which can be used to increase the spatial resolution in a given imaging time. One of the aims of translating ultra-high-field MRI into true clinical applications is to determine which types of application require a higher spatial resolution than is currently achieved at clinical field strengths of 1.5 and 3 T. The major challenges include the increase in tissue One topic that was not specifically covered in this particular review was ophthalmic MRI. The potential advantages for clinical use revolve directly around the increased spatial resolution achievable within acceptable scan times (since short scans must be used to minimise eye-motion-induced image artefacts): this increased spatial resolution is key for identifying small pathologies within the eye. In recent years, MRI has become a promising new diagnostic imaging modality in ophthalmology, a discipline that relies mainly on optical imaging techniques –9. HowevUveal melanoma is the most common primary intraocular malignant tumour in adults –20. In tFor a patient to be eligible for ruthenium plaque brachytherapy the maximum distance between the outside of the sclera, where the plaque is located, and the tumour is 7 mm . ClinicaThe patients were admitted to the Department of Ophthalmology at the LUMC, and all data were acquired according to the Declaration of Helsinki. After the standard clinical evaluations , an additional 7-T ocular MRI examination was performed. For the ultrasound a probe  was used with a transducer frequency of 10 MHz, an exploration angle of 50°, focus of 24–26 mm, axial resolution of 200 µm and lateral resolution of 600 µm (data supplied by the manufacturer). Ultrasound images from three representative patients are shown in Fig. The MRI measurements were performed on a Philips  Achieva 7-T whole-body magnet . A custoTo reduce susceptibility artefacts, the affected eye was closed with a piece of tape and covered with a piece of wet gauze . The pat3 and a field of view (FOV) of 40 × 46 × 38 mm3. Two orthogonal reconstructions were made from this scan, from which additional two-dimensional scans were planned with different types of contrast. A turbo spin-echo sequence was used to acquire four slices of 1 mm thickness with a TR of 2500 ms and an echo train length of 10. The scan was performed both with and without spectral inversion recovery (SPIR) fat suppression and had an in-plane resolution of 0.3 × 0.3 mm2. The slice gap was adjusted for every patient in order to cover the complete tumour, and the scan took slightly more than 1 min. Then a 3D spoiled gradient echo with a TR/TE/tip angle of 10 ms/2.9 ms/6°, a spatial resolution of 0.5 × 0.5 × 1.0 mm3 and an FOV of 40 × 46 × 38 mm3 was acquired in 1 min and 16 s. Finally a multi-slice inversion recovery with SPIR fat suppression was acquired with an echo-train length of 16, a resolution of 0.3 × 03 mm2 and a total acquisition time of 3.5 min.MR images were acquired using a 3D inversion recovery turbo gradient echo technique (MP-RAGE) with an inversion time of 1280 ms, a shot interval of 3 s, and a turbo field echo factor of 92. The TR/TE/tip angle was: 6.7 ms/3.4 ms/16°. The scan time was 3 min and resulted in a spatial resolution of 0.4 × 0.4 × 0.9 mmT2-weighted multi-slice spin-echo images, shown in Figs. For all patients the MRI scans resulted in motion-free images in which the tumour could clearly be delineated, representative images are shown in Figs. The maximal prominence of the tumour for each patient was assessed on the 3D inversion recovery scan using a thee-dimensional viewer. Figure For 80 % of the patients the MRI-based 3D evaluation of the tumour prominence resulted in a different tumour prominence compared to the ultrasound. For some of the large tumours, which consisted of multiple lobes, the MRI showed an up to 1.6 mm larger tumour. As the eyes of these patients were not eligible for eye-preserving therapy, this did not have any influence on the proposed treatment. In five of the ten patients, however, the MRI revealed an up to 1.5 mm smaller tumour. For two of these patients (including patient 1 from Figs. As small millimetre-size differences in tumour prominence can result in significant changes in the treatment, accurate length measurements are essential to assess the optimal treatment. Although higher field MRI enables an increased spatial resolution, magnetic susceptibility effects are greater, which could potentially distort the images. The application of wet gauze to the imaged eye effectively shifts the air/tissue interface much further away from the eye. Small air bubbles can sometimes be present below the eyelid and can produce very local distortions in the image, but as the tumours are located posteriorly the image of the tumour itself is not affected. Further evidence that high-field MRI gives accurate ocular length measurements was provided in previous work that showed a high degree of agreement, <1 % difference, compared to the gold standard of optical biometry . OverallTo assess the reproducibility of the measurements, both the ultrasound and MR images were retrospectively evaluated by two additional independent observers. The MRI showed a slightly lower difference between the measurements compared to the ultrasound, an average SD of 0.22 and 0.32 mm respectively. Clinically, the variability of the ultrasound evaluation will be significantly higher as the measurement is very dependent on the orientation of the ultrasound transducer. A comprehensive study by Char et al.  showed aIn addition to the described diagnostic value of the additional MRI scans, the evaluation of these patients revealed two other potential benefits of MRI compared to ultrasound. First, the full three-dimensional data on the tumour geometry can be used for more precise planning for the different forms of external beam radiotherapy of uveal melanoma: this is currently based on two-dimensional fundus photography and ultrasound images. Second, the high intra-tumour contrast compared to ultrasound potentially enables a better determination of the tumour response to therapy. Currently, only changes in the outer tumour dimensions can be monitored, which are known to change after the full course of therapy is finished. The higher contrast of MRI could show tumour response at an earlier stage, enabling a more patient-specific treatment.This work has shown the diagnostic potential of ultra-high-field ocular MRI for uveal melanoma. In eight of the ten patients presented, the three-dimensional MR images provided a better measurement of the tumour dimensions compared to conventional ultrasound. For two of these patients this resulted in a significant change in treatment. The ultrasound suggested the tumour was too large for ruthenium plaque brachytherapy, in which case removal of the eye would have been considered. The three-dimensional MRI data, however, enabled a more precise measurement of the tumour dimensions, resulting in a slightly lower tumour prominence, which is still feasible for brachytherapy. This resulted in the preservation of these particular patient’s eye.


All the probes were synthesized using Rhodamine B as the fluorophore, conjugated to various differently substituted cinnamyl aldehyde with C=N Schiff base structural motif as their core moiety. The structure-property relationships of these probes have been investigated. The change of optical properties, caused by different electronic effect and steric effect of the recognition group, has been analyzed systematically. DFT calculation simulation of the Ring-Close and Ring-Open form of all the probes have been employed to illuminate, summarize and confirm these correlations between optical properties and molecular structures. In addition, biological experiment demonstrated that all the probes have a high potential for both sensitive and selective detection, mapping of adsorbed Cu2+ both in vivo and environmental microbial systems. This approach provides a significant strategy for studying structure-property relationships and guiding the synthesis of probes with various optical properties.A series of Cu Selective recognition and detection of cations by receptors have attracted a significant amount of attention in chemistry, biology, and environmental science12356810111314152+ with chemo sensors is well known to induce intrinsic fluorescence quenching due to the paramagnetic nature of Cu2+ 25262+ fluorescent probes. Evermore, selection of an adequate probe for CLSM studies in bio-, geo-, and environmental sciences became more and more challengingCopper, as the third most abundant essential trace element in human body, plays a crucial role for a broad range of biological processes17181921222+ probe which contains 9 probes1a-1i based on our previous work  through a two-step reaction via Rhodamine B with substituted cinnamyl aldehyde. To our surprise, all probes showed different absorption and fluorescence responsive intensity to Cu2+.In order to investigate the effect of structure on performance for a probe, we synthesized and established a series of Cuous work 29. Each In this work, we focused on the structure-property relationships of this probe model, investigated the change of optical properties caused by different electronic effect and steric effect of the recognition group, and also employed DFT calculation simulate the Ring-Close and Ring-Open form of all the probes . Compreh+, Na+, K+, Ba2+, Ca2+, Cd2+, Mg2+, Co2+, Mn2+, Zn2+, Pb2+, Ni2+, Fe2+, Hg2+, Fe3+, Al3+, Cr3+, Cu2+ and the nitrate salt of Ag+ were evaluated by UV-vis spectroscopy. Upon addition of the respective metal ions, the absorption spectrum of the individual probes changed in different manners as shown in 2+ showed only minor spectral or color changes. Similar responses were observed when Cu2+ ions were added to the probe solutions in the presence of other metal ions. The absorption spectrum of probe 1a-1i exhibited a broad band at 556 nm at room temperature in the PBS buffer solution  ethanol). Since the closed form of rhodamine did not show an intense absorption band in the visible region2+ complexes were not present in the form of closed spirolactone, but in a opened quinoid configuration at neutral pH. Furthermore, the absorption response all individual probes toward Cu2+ showed linear relationships in the range 0–50.0 μM of Cu2+ . In addition, the absorbance of the probe + Cu2+ complexes were reduced gradually (1g > 1h > 1i), when methyl was introduced into different positions of benzene ring, whereas in ortho-, meta-, para-position it had scarcely any effect on the UV absorbance response in this series of probes.More importantly, the UV absorbance of these probes were shown to be adjusted by the different substituent groups. As shown in , the com2+ was evaluated in ethanol-PBS  solution. The remarkable orange fluorescence emission of our probes increase that is induced by Cu2+ can interpreted as the opening of the spiral ring at appropriate pH; the emission band of this probe series appeared at 576 nm. The changes of 1a-1i (10 μM) upon addition of Cu2+ (0–5.0 equiv.) have been studied  enhanced the fluorescence response significantly. For comparison, we have synthetized a congeneric probe 1j which is substituted by Cl at the same position of Br and exhibited a lower fluorescence intensity than that of 1d. Similarly, we introduced -NO2 and -OCH3 substituents to the recognition unit of the molecule to analyze the relationship between fluorescence intensity and electronic effects. The result suggested that electron-drawing groups promote fluorescence enhancement to a higher extent as compared to electron-donating groups. Substitutions in the ortho-position of the benzene ring increased the fluorescence intensity, whereas this effect was not observed when the substitution was inserted in meta- or para-position.As show in , fluores** for C, H elements and 6-31+G* for N, O, Br elements on Gaussian 09 ProgramTo better understand the structure-property relationships of these 9 probes, the mode of ring-close and ring-open were studied by DFT1a-1c show gradualness energy increase, which may be attributed to the block transition process by the growing steric hindrance. Extraordinary for probe 1d, the exist of heavy atom Br could promote the equalization of electronic cloud distribution and reduce energy accordingly, and the energy required for the formation of Ring-Open structure is less than any other probe, which indicated that probe 1d may show a better optical property because of its easy changed structure. The molecule energy seems to be insensitive to the Push-pull electronic effect and spatial effect on the benzene ring of recognition group.As show in 1e. The LUMO energy of probe 1e showed an abnormal reduction from other probes, which may due to the evenly distributed electron density caused by the strong electrophilic effect of NO2.The HOMO-LUMO orbital energies and the spatial distributions for these probes were determined; the spatial distributions HOMO and LUMO were displayed in The results of NBO analysisf−(r) has been successfully used to describe the reactivity concerning electrophilic attack2 attack in this model of probe. The condensed Fukui function of individual atom is obtained from NBO analysis. As show in f−(r) clearly demonstrates that the region around carbonyl O atom and hydrazide N atom possesses higher reactivity than other parts of the Ring-Open form and there is no obvious electrophilic site in the recognized moiety of Ring-Close form. These data illustrate that all the probes have the tendency to be opened rather than closed under the entrainment and coordination of Cu2+.On the other hand, 2+-localization studies in microbial cell-extracellular polymeric substances (EPS)-mineral aggregates. The photosynthetic Fe(II)-oxidizing Rhodobacter sp. strain SW2 was selected as an model organism because SW2 is known to form such aggregates2 for 30 min. Probe 1a-1i (50 μM), SYTO 9 green fluorescent nucleic acid stain (1:500) and polysaccharide-specific Wheat germ agglutinin, ALEXA FLUOR 633 conjugate (1:200)282+, bacterial cells and EPS respectively. The CLSM images show that probe 1a-1i was able to detect Cu2+ in the aqueous microbial cell-EPS-mineral aggregates. The results furthermore indicate that Cu2+ is collocated with the bacterial cells and with the free, cloud-like EPS, suggesting that the organic surfaces provide binding sites for Cu2+, even though the detailed spatial distribution of Cu2+ on subcellular level and microbial sorption mechanism still remain unclear and need to be analyzed by higher resolution analytical microscopy approaches  were prepared to be 200 μmol/L with ethanol and solubilized by little acetone (0.1 ml). The solutions of metal ions were prepared in ethanol for the selectivity and competitive study with chloride salts of Li+, Na+, K+, Ba2+, Ca2+, Cd2+, Mg2+, Co2+, Mn2+, Zn2+, Pb2+, Ni2+, Fe2+, Hg2+, Fe3+, Al3+, Cr3+, Cu2+ and the nitrate salt of Ag+.All the reagent grade chemicals consumed in this work were procured from commercial sources and used as received. Cu2+, 5.0 mL PBS and 0.50 mL of 200 μM probes were added. The mixtures were diluted to 10 mL with ethanol. Then, 3.0 mL of each solution were transferred to a 1 cm cuvette. The absorbance was recorded at 556 nm and the fluorescence intensity was recorded at 576 nm. The excitation and emission wavelength bandpasses were both set as 5.0 nm and the excitation wavelength was set at 550 nm.To a 10 mL volumetric tube, different concentration of Cu2+ sorption to cell-mineral aggregates of Fe(II)-oxidizing bacteria were prepared under anoxic conditions in a glovebox under N2 atmosphere. The samples were analyzed using an upright confocal laser scanning microscope , equipped with 4 lasers  and a 63x water immersion objective .A Beijing TAIKE XT-4 microscopy melting point apparatus was used to measure the melting points of the compounds. Mass spectrometry was performed on a BRUKER micrOTOF-Q II ESI-Q-TOF LC/MS/MS Spectroscopy. NMR spectra were recorded on a VARIAN INOVA-400 spectrometer, using TMS (TMS trimethylsilyl) as an internal standard. The absorbance spectra were recorded on a SHIMADZU UV-1700 spectrophotometer. A HITACHI F-4500 FL spectrophotometer employed to record the fluorescence spectra. A VARIO EL III analyzer was used for performing the elemental analyses. Samples for mapping Cu2+ probe which contains 9 probes, all the probes are based on the core segment of C=N Schiff base structural motif. This study revealed the relation between the structure and the optical properties of nine probes focusing on the influence of various substituents and provided a significant strategy for studying structure-property relationships which were illuminated, summarized and confirmed by DFT calculation simulation on the Ring-Close and Ring-Open form of this modular Schiff base Cu2+ fluorescent probes. We expect that these results of our research would help to guide the synthesis of high performance metal fluorescence probes with various properties. On the other hand, all the probes could permeate cellular membrane to investigating the effects of Cu2+ in living cells. Furthermore, CLSM experiments suggested that all the probes would be a powerful tool for sensitive and selective detection and mapping of Cu2+ adsorbed in environmental microbial systems.In summary, we have synthesized and evaluated a series of CuHow to cite this article: She, M. et al. A novel approach to study the structure-property relationships and applications in living systems of modular Cu2+ fluorescent probes. Sci. Rep.6, 28972; doi: 10.1038/srep28972 (2016).


There is an error in the grant number associated with the National Science Council grant in the financial disclosure statement. The correct financial disclosure statement is:“This work was funded with support from a grant # NSC 102-2410-H-006-019 from National Science Council  and with a grant # BCS 07-46586 CAR from National Science Foundation . The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”


The present set of studies aimed to explore the effect of self-esteem on corrupt intention and the mediating role of materialism in generating this effect. In Study 1, we used questionnaires to investigate the correlation among self-esteem, materialism, and corrupt intention. In Study 2, we manipulated self-esteem to explore the causal effect of self-esteem on materialism and corrupt intention. In Study 3, we manipulated materialism to examine whether inducing materialism can reduce the relationship between self-esteem and corrupt intention. The three studies converged to show that increased self-esteem caused a low level of materialism, which in turn decreased corrupt intention. The theoretical and practical implications of the results are discussed. Corruption refers to the misuse of public power for private gain , 2000. ICorruption has recently received greater attention from psychologists. The subsequent research has identified important antecedents of corruption such as socio-economic status , culturaSelf-esteem refers to the overall self-evaluation of one’s worth, and it is a universal and fundamental human need . Most inhigh self-esteem decreases corrupt intention (Hypothesis 1).Achieving rewards and status could facilitate self-affirmation and likewise enhance self-esteem for individuals lacking it . Many unIf one is increasingly driven by extrinsic goals such as wealth, possessions, image, and status to affirm the self and to seek compensation for poor self-esteem, one might be mired by materialism. Materialism refers to the elevated importance placed by a person on possessions and their acquisition as a necessary or a desirable means of attaining desired end states, including happiness . ResearcIndeed, the earliest sophisticated attempt to measure materialism  conceiveIt has been shown that self-esteem is negatively associated with materialism . Self-esExisting literature indicates that materialism is positively associated with unethical behaviors . Simply materialism mediates the negative effect of self-esteem on corrupt intention (Hypothesis 2).Based on the above arguments, we hypothesize that In current research, we conducted three studies with correlated and experimental designs to test whether high self-esteem decreases corrupt intention and whether materialism plays a mediating role in the relationship between self-esteem and corrupt intention. In Study 1, we used questionnaires to investigate the correlated relationship among self-esteem, materialism, and corrupt intention. In Study 2, we manipulated self-esteem to explore its causal effect on materialism and corrupt intention. In Study 3, we manipulated materialism to further explore its mediating role. This study adopted a moderation-of-process design , wherebyIn Study 1, we aimed to identify direct associative evidence for the possible relationship among self-esteem, materialism, and corrupt intention. We predicted that self-esteem would be negatively correlated with corrupt intention and that materialism would mediate this correlation.The study was reviewed and approved by the Committee of Protection of Subjects at Beijing Normal University. All participants provided written informed consent before the study and were debriefed at the end of the research according to the established committee guidelines. This procedure was also followed in Studies 2 and 3.M = 18.73 years, SD = 1.11). To ensure the diversity of the sample, we included participants from different majors such as biology, accounting, information technology, education, and the arts.We recruited 462 participants  from two universities in China. The participants were between the ages of 17 and 22 (Cronbach’s α = 0.824).The widely recognized Chinese version of the 10-item Rosenberg Self-Esteem Scale  was usedCronbach’s α = 0.802).The widely recognized Chinese version of the 18-item Material Values Scale MVS;  was usedCronbach’s α = 0.773).A 14-item corrupt intention measure  was adapAfter providing informed consent, the participants completed an online survey, including several questionnaires, in a computer room. These questionnaires included the self-esteem scale, the materialism measure, the corrupt intention measure, and other unrelated measures to prevent the participants from guessing the purposes of the research. After the participants completed the questionnaires, they were asked to provide their demographic information, including their sex, age, major, and birthplace. Finally, the participants were debriefed.Table  The results demonstrated that self-esteem was negatively associated with corrupt intention , which supported Hypothesis 1.The correlations between the three variables, the means, and the standard deviations are shown in Additionally, we observed that each participant’s gender and age had nearly significant correlations with corrupt intention, which was consistent with previous research indicating that demographic variables, such as age and gender, are related to moral reasoning  and corrSE = 0.056, t = –4.127, p < 0.001). The variations in materialism predicted by self-esteem  and the variations in corrupt intention predicted by materialism  were both significant. After controlling for the effect of materialism, the direct effect of self-esteem on corrupt intention became non-significant . A bootstrapping procedure comprising 5,000 samples provided additional evidence that the 95% confidence interval for the direct effect of self-esteem was , including zero, whereas the indirect effect was , not including zero . These results support Hypothesis 2 that materialism accounts completely for the association between self-esteem and corrupt intention.We then tested our prediction that materialism mediates the association between self-esteem and corrupt intention using bootstrapping procedures . The anaAlthough Study 1 confirmed a negative association between self-esteem and corrupt intention, as well as the mediating role of materialism, it inadequately established a rigorous causal relationship. Potentially, high self-esteem decreases corrupt intention, but the opposite could also be plausible. To overcome this limitation, in Study 2, self-esteem was manipulated by random feedback on a personality test, thus placing participants into either a high or a control condition. We also extended the previous results by expanding on responses to a business scenario, which consisted of a behavior with real consequences. We expected that when self-esteem increased, individuals would exhibit lower materialism and a lower corrupt intention.M = 19.09 years, SD = 0.84). To ensure the diversity of the sample, participants from different majors were included. They were randomly assigned to one of two experimental conditions: the high self-esteem condition (n = 44) or the control condition (n = 56).One hundred participants  were recruited at a Chinese university through the campus network. The participants spanned the ages of 17 to 21 .To check the effectiveness of the manipulation, the participants were presented with a 10-item Rosenberg Self-Esteem Scale , as usedCronbach’s α = 0.821).We administered the same materialism scale as used in Study 1 to measure participants’ level of materialism (Cronbach’s α = 0.791).A business corruption scenario  was adapAll participants entered the laboratory and were informed that they were participating in a study concerned with the correlation between personality test scores and social behavior. The participants initially completed the CPI to evaluate their personalities and received random feedback, which randomly divided them into two conditions: the high self-esteem condition or the control condition. After receiving the random feedback  regarding their personalities, the participants were instructed to complete the next questionnaire. At the end of the study, the participants were thanked with stationery gifts and debriefed.M = 4.76, SD = 0.59) than those in the control condition did , t(98) = 2.18, p < 0.05, Cohen’s D = 0.28. This finding suggests that the manipulation was effective.As expected, participants in the high self-esteem condition had significantly higher self-esteem scores  and corrupt intention . Furthermore, the mean materialism score of participants in the high self-esteem condition  was significantly lower than that of the control condition , t(98) = –2.85, p < 0.01, Cohen’s D = –0.57. The mean corrupt intention score of the high self-esteem condition  was significantly lower than that of the control condition , t(98) = –2.39, p < 0.05, Cohen’s D = –0.49. These results suggest that increased self-esteem had a negative effect on materialism and corrupt intention.As expected, the manipulated self-esteem was significantly correlated with materialism . The variations in materialism predicted by the self-esteem condition  and the variations in corrupt intention predicted by materialism  were both significant. After controlling for the effect of materialism, the direct effect of the self-esteem condition on corrupt intention became non-significant . A bootstrapping procedure with 5,000 samples provided additional evidence that the 95% CI for an indirect effect of self-esteem on corrupt intention through materialism was , not including zero. The direct effect was , including zero, which implies that materialism completely mediated the effect of self-esteem on corrupt intention.We then coded the high self-esteem and control conditions as +1 and 0, respectively, and further explored the mediating effect of materialism through bootstrapping procedures . The anaFigure 2). The analyses showed that the self-esteem condition significantly predicted corrupt intention . The variations in materialism predicted by the self-esteem condition  and the variations in corrupt intention predicted by materialism  were both significant. After controlling for the effect of materialism, the direct effect of the self-esteem condition on corrupt intention became non-significant . A bootstrapping procedure indicated that the 95% CI for an indirect association between the self-esteem condition and corrupt intention operating through materialism with the controlled variables was , not including zero. The direct effect was , including zero, which implies materialism completely mediated the effect of self-esteem on corrupt intention.The results were identical to the findings of the analysis with controlled variables including age and gender . They were randomly assigned to one of two experimental conditions: the materialism-induction condition (n = 63) or the control condition (n = 64).A total of 127 participants  were recruited at a Chinese university. The participants spanned the ages of 18 to 27 (Cronbach’s α = 0.817).A 10-item Rosenberg Self-Esteem Scale was used, as in Study 1, to measure the participants’ self-esteem levels . For example, participants in this condition were asked to construct sentences out of such strings as “expensive, his, was, everybody, watch.” In the control condition, highly similar word sets were created except that in each instance, materialistic concepts were replaced with mundane, non-materialistic ones . Correspondingly, participants in this condition were presented with such neutral strings as “accurate, his, was, everybody, watch.”To prime materialism, we relied on and adapted from a common experimental procedure, the scrambled-sentences task . The parCronbach’s α = 0.770).To check the effectiveness of the manipulation, the participants were asked to complete the identical materialism scale as in Study 1. We only changed prolonged words such as “always” in the original scale into present tense words such as “now” (Cronbach’s α = 0.867).A business corruption scenario was used, as in Study 2, and five questions were asked to measure the participants’ corrupt intention  than the participants did in the control condition , t(125) = 2.06, p < 0.05, Cohen’s D = 0.37. This result suggests that the manipulation of materialism was effective. However, there was no difference in self-esteem between the materialism-induction  and the control condition , t(125) = 0.10, p = 0.92, suggesting that materialism did not influence self-esteem.As expected, the participants in the materialism-induction condition exhibited a higher materialistic tendency , and the interaction of self-esteem and the experimental condition. To interpret the results, we centered self-esteem prior to the analysis because it is a continuous variable .Table  After controlling for gender and age, self-esteem was negatively associated with corrupt intention. This association was qualified by a significant interaction between self-esteem and experimental condition (p = 0.043), displayed in Figure 3. To interpret the interaction, we tested the simple slopes using the procedures described by simple slope = –1.092, SE = 0.294, t(120) = –3.716, p < 0.001, a finding consistent with Studies 1 and 2. By contrast, and consistent with our prediction, in the materialism-induction condition: simple slope = –0.268, SE = 0.296, t(120) = –0.906, p = 0.367. When primed to a materialistic mindset, the corrupt intention of participants with higher self-esteem was comparable to participants with lower self-esteem. This finding suggests that lower self-esteem individuals tended to favor corrupt behavior, at least partly because they experience a higher level of materialism than individuals with higher self-esteem do.The results are presented in In Study 3, we adopted the moderation-of-process design and observed that the negative effect of self-esteem on corrupt intention observed in Studies 1 and 2 was reduced when materialism was experimentally induced. The results suggest that one reason that individuals with high self-esteem tend to have lower corrupt intentions is that they tend to have a lower passion for materialism. Further, corruption might serve as a coping pattern accompanied with high materialism to satisfy the needs of individuals lacking self-esteem. In sum, the results imply that increased self-esteem decreases corrupt intention through a lower level of materialism.The present three studies showed that high self-esteem decreased individuals’ tendencies toward corruption and that materialism mediated this relationship based on a sample of Chinese university students. We confirmed our hypotheses in three studies using different measures of corrupt intention and different strategies to examine the process. The results of Study 1 suggest that self-esteem was negatively associated with the corrupt intention and that materialism mediated this relationship. In Study 2, we manipulated self-esteem, and the results indicated that increased self-esteem caused a low level of materialism and corrupt intention. In Study 3, we used a different strategy to examine the underlying psychological process, determining that the differences in the degree of materialism explain why individuals with varying self-esteem levels differ in their corrupt intention. These studies converged to show that increased self-esteem caused a low level of materialism, which in turn decreased corrupt intention.The findings from the present research make a significant contribution to the literature of self-esteem. Previous research has shown that high self-esteem tends to be associated with, albeit might not cause, positive outcomes, such as better performance , interpeFurthermore, the present research also contributes to the effects of self-esteem on unethical behaviors like corruption, by identifying materialism as an underlying psychological process. The mediating role of materialism explains why individuals endorse less corruption after self-esteem is enhanced. On the one hand, the increasing self-esteem depresses materialism and corrupt intention. Material possessions are important for maintaining a self-concept  and are The present research adds to the current debate on whether material possession amounts to self-worth. Previous research has found that an individual’s self-esteem is negatively associated with materialism , and thaThe results from the current research have practical implications for anti-corruption. For China, rapid economic growth has introduced multiple pressures and temptations, including status, riches, and fame. Some limitations of the current research should be mentioned. First, it seems that receiving a positive feedback could potentially boost positive mood, and mood and emotion have been shown to be linked to ethics in some ways . HoweverYL contributed to all aspects of work for this article. LL contributed to conception, design, and revising the article critically. XT contributed to data collection, design, and interpretation. ZH and JD contributed to data analysis, interpretation, and revising the article critically. WZ contributed to interpretation and revising the article carefully.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Major surgery and critical illnesses such as sepsis and trauma all disturb normal physiological fluid handling. Intravenous fluid therapy for resuscitation and fluid maintenance is a central part of medical care during these conditions, yet the evidence base supporting practice in this area lacks answers to a number of important questions. Recent research developments include a refinement of our knowledge of the endothelial barrier structure and function and a focus on the potential harm that may be associated with intravenous fluid therapy. Here, we briefly describe the contemporary view of fluid physiology and how this may be disrupted by pathological processes. The important themes in critical illness fluid research are discussed, with a particular focus on two emerging ideas: firstly, that individualising fluid treatment to the patient, their underlying disease state and the phase of that illness may be key to improving clinical outcomes using fluid interventions and, secondly, that fluids should be considered to be drugs, with specific indications and contraindications, dose ranges and potential toxicities. Disturbances of body fluid homeostasis are common in major surgery and a range of critical illnesses including sepsis and trauma. Administering appropriate intravenous fluid is a core part of medical care during these episodes. Despite years of research, there is still widespread debate about the best dosing strategy for these fluids and the optimum fluid composition for a given clinical situation. These are still important research questions, as there are clear signs from the current literature that fluid administration strategies have the power to affect clinical outcomes in a variety of areas.Our study of fluid therapy is being refined by recent advances in basic physiology research. In particular, our knowledge of the structure of the vascular endothelium and the way in which fluid is handled at a capillary level has recently been redeveloped. There has also been progress in pharmacokinetic modelling of the movement of exogenous fluids between the body's fluid compartments. At the other end of the research spectrum, clinical fluid trials are becoming ever larger in an effort to address the limitations of the preceding literature, which is based predominantly on relatively small, single-centre studies.Some key themes have emerged from this body of research. Firstly, it is increasingly clear that clinical context is key to the success or failure of a given fluid strategy. A fluid strategy which appears to reduce morbidity in one clinical population (e.g. patients undergoing major surgery) may actually be harmful to another (patients with established sepsis). Fluid therapies are being increasingly tailored to very tightly defined clinical subgroups and indeed to individual patients and the stage of their clinical course. A further theme is the emergence of toxicities related to fluid composition which have only become apparent through large clinical trials. Fluids are therefore increasingly being seen as drugs, with specific indications, contraindications and dose ranges .In this review, we will outline the contemporary model of normal physiological fluid handling. The effects of a range of extreme physiological situations will be described, including acute haemorrhage and systemic inflammation. We will then review the latest literature in relation to clinical fluid strategies in a number of clinical settings Table Water makes up approximately 60% of total body weight in the average adult. Due to the low water content of adipose tissue, this proportion varies widely with obesity (as low as 45%), age  and sex . Body water occupies functional and anatomical compartments. Fluid within cells—the intracellular compartment—is separated from the extracellular compartment by the cell membrane. This is impermeable to large hydrophilic molecules and charged particles, although these may cross it by specific transport mechanisms.A proportion of extracellular water is contained within the bone and dense connective tissue, although due to slow kinetics this is viewed as non-functional. The extracellular compartment is further divided into interstitial fluid between cells and in lymphatics, intravascular fluid within blood vessels, and transcellular fluid including gastrointestinal secretions, joint fluid, cerebrospinal fluid and pleural, peritoneal and pericardial fluid.The vascular endothelium is the key barrier between the intravascular and interstitial spaces. It is particularly relevant clinically as it can be damaged during pathophysiological states such as inflammation, allowing potentially harmful fluid accumulation in the interstitial space. The vascular endothelium in a typical capillary is composed of a single layer of endothelial cells with intercellular clefts closed by tight junctions. The cells sit on a continuous basement membrane. On the vascular aspect of the endothelial cells lies a continuous layer of glycosaminoglycan chains, membrane-bound proteoglycans and glycoproteins. These form the endothelial glycocalyx layer (EGL), which is approximately 1 μm thick.Water and electrolytes can pass freely across the glycocalyx and then beyond the endothelial cells via the intercellular clefts. Proteins and other large molecules however are unable to pass through an intact glycocalyx and are transported in relatively small quantities across the endothelial cells by active processes. The EGL is therefore still part of the intravascular space but contains up to 700–1,000 ml of almost protein-free fluid with the same electrolyte composition as plasma. This creates a large protein concentration gradient—and oncotic pressure gradient—between the plasma and the space immediately below the EGL. This opposes the hydrostatic pressure gradient at the arteriolar end of capillaries, reducing the volume of water and electrolytes filtered out of the capillary. Net filtration across a capillary is expressed by the modified Starling equation , gastrointestinal tract  or kidneys  without adequate replacement.Acute blood loss causes a sudden reduction in intravascular volume, cardiac filling and cardiac output. The transient reduction in arterial pressure is rapidly sensed by the high-pressure baroreceptors in the aortic arch and carotid sinus. The resultant sympathetic activation results in vasoconstriction, increased cardiac inotropy and increased heart rate. A range of other neurohumoral mechanisms are activated, including the renin-angiotensin-aldosterone axis and antidiuretic hormone release. These further contribute to vasoconstriction, reduction in glomerular filtration rate and renal retention of salt and water to compensate for the acute volume loss.These early mechanisms may initially result in apparently normal haemodynamic observations. However, these responses divert blood away from ‘non-essential’ organs  and towards essential organs . Healthy volunteer experiments have demonstrated signs of critical organ hypoperfusion, measured by a reduction in gut pH, despite normal-range blood pressure and heart rate after up to 30% blood volume loss ,5.Acutely reduced capillary pressure, seen in blood loss or due to widespread vasodilatation due to sepsis or anaesthesia, alters fluid movement at the capillary level also. In the initial phase, there may be an ‘autotransfusion’ of interstitial fluid into the intravascular space, although this is limited to approximately 500 ml . OngoingFluid homeostasis becomes even more disturbed if the endothelium becomes damaged and loses its barrier function. A range of insults has been associated with degradation of the glycocalyx, including inflammatory mediators  or even The clinical management of intravenous fluid administration therefore has the potential to influence organ function, morbidity and mortality in pathophysiological settings. If fluid replacement is inadequate during critical illness, inadequate organ blood flow and therefore inadequate delivery of oxygen and energy substrates may occur. This results in inefficient anaerobic cellular metabolism and in severe cases cell death and organ failure. Conversely, excessive salt and water administration, particularly in the setting of endothelial dysfunction, may worsen organ oxygenation and function through oedema formation.Again, the capillary handling of administered intravenous fluids is critical and has recently been re-examined. Free water contained in hypotonic solutions distributes evenly throughout all fluid compartments, leaving only a small proportion within the intravascular space. Traditionally, isotonic electrolyte solutions were thought to distribute evenly through the extracellular  space only, leaving approximately 20%–25% of their volume in the intravascular space. Colloids, due to their superior oncotic pressure, were thought to initially remain almost completely within the intravascular space and were seen as the best fluid for acute plasma volume expansion.It is now proposed that the ‘context’ of capillary pressure is important . At low For both fluid types, in the setting of normal or supra-normal capillary pressure, net filtration will occur, with loss of fluid from the intravascular space and the potential for oedema formation. Although in health the maintained oncotic pressure associated with colloids helps to limit this filtration, this effect is reduced in the presence of endothelial dysfunction. Here, there is the potential for large colloid molecules to pass freely into the interstitial space. However, as more crystalloid volume is needed to achieve similar resuscitation endpoints to colloids, patients resuscitated with crystalloid do ultimately gain a more positive fluid balance  Table 1.As a core part of medical treatment during acute illness and trauma, it is not surprising that a number of fluid administration strategies have been trialled in various clinical settings over the years. This evidence base has shown that fluid strategies have the potential to influence morbidity and possibly mortality outcomes after critical illness and major surgery. However, clear-cut answers which can be confidently translated to widespread clinical practice are rare. A summary of some of the critical illness fluid research areas is contained in Table There are a number of challenges which have hampered evidence-based practice in this area. Firstly, fluid therapy is a prime example of what the Medical Research Council terms a ‘complex intervention’ . This coOne example of this complexity leading to ongoing uncertainty is in fluid strategies around the time of major surgery. An approach to haemodynamic therapy, based on targeting supra-normal global oxygen delivery—monitored using the pulmonary artery catheter—was initially investigated in the 1970s ,40. DespEven at a basic physiological, pathological and pharmacological level, there is considerable complexity which may be important in fluid therapy. The mechanisms of action of fluid strategies at an organ and cellular level have been relatively under-explored in relevant human clinical settings. This gap in the knowledge base may help to explain the variable success of many fluid clinical trials. The ultimate goals of fluid therapy are to provide enough circulating volume and blood flow to organs, so that the quantities of oxygen and nutrients delivered are sufficient to meet their metabolic requirements, while avoiding iatrogenic harm through excess dosing of water, electrolytes or exogenous compounds. Yet this apparent simplicity belies the biological complexity of achieving these goals in diverse disease settings. The clinical benefit or harm brought by administering fluids may result from fluid composition, dose, physiological target, timing during the illness, or complex interactions between these factors, the patient's pre-morbid phenotype and the acute but ever-changing pathophysiological processes.Developing the evidence base behind critical illness fluid practices further therefore needs a combination of basic science, translational trials and clinical trials. Controlled trials with large sample sizes are necessary to definitively detect differences in outcome which may be small but important when applied to the huge number of patients undergoing major surgery or critical illness. But achieving this size often requires pragmatic trial design and heterogeneous groups  which potentially obscure the nuances of which individual patients might get benefit or harm and when. More mechanistic studies are needed to explore what aspect(s) of the intervention strategy brought the benefit or harm and to address apparently basic but as-yet unanswered questions, such as how the body handles the currently available range of exogenously administered anions.It is implausible that one fluid administration strategy will ever be beneficial to all patients in all clinical settings at all time points in their critical illness or physiological insult. There is an increasing realisation that trial findings in one group cannot be readily extrapolated to other groups. The theme of ‘individualisation’—tailoring fluid interventions to each patient and each setting—is gaining momentum and is seen in the following areas.Goal-directed haemodynamic therapy in patients undergoing major surgery is a longstanding example of adapting fluid dosing to a patient's baseline physiology. This is also true of contemporary algorithms aimed at optimising cardiac stroke volume. These involve a physiological ‘test’ in the form of a fluid bolus with ongoing monitoring of stroke volume. If the patient is fluid replete—or cardiac performance is beyond the optimum point of the Starling curve—there will be no further increase in stroke volume and fluid bolus administration can stop. This is in contrast to other dosing strategies based on patient weight or physiological signs which are poor at predicting a response to fluid.There is growing evidence that the timing of plasma volume expansion is important in its potential success. This may be seen even within the relatively short time frame of a surgical operation. One study showed that despite only modest differences in the overall volume of fluid given to patients undergoing surgery, the use of cardiac output monitoring to guide fluid input led to fluid being given earlier in the operation, which led to sustained increases in cardiac output not seen in the control group . This waThe differing physiological requirements from fluid therapy during the developing stages of critical illness and circulatory shock have been recognised in a new proposed treatment approach :• Salvage phase—the immediate phase where fluid resuscitation is used as a lifesaving measure, guided by immediately available information such as clinical assessment, blood pressure and heart rate• Optimisation phase—guided by more in-depth monitoring, and aiming to optimise global oxygen delivery, with resultant improvements in arterial lactate and mixed venous blood desaturation• Stabilisation phase—a more cautious approach to fluid administration, aiming to minimise iatrogenic harm caused by fluid overload and institute more general organ support where required• De-escalation phase—appropriate during the start of resolution of critical illness, aiming to reduce vasoactive treatments and achieve a negative fluid balanceA number of clinical syndromes  appear to have common features which may be addressed by similar fluid approaches. Yet the underlying disease process seems to be critical to the benefit or harm brought by these fluid strategies. In mixed critical care populations, including severe sepsis, there is growing evidence that starch-based colloids are associated with an increased requirement for renal replacement therapy ,18. This−1), which may have contributed to intracranial hypertension [Another example of this is the Saline vs. Albumin Fluid Evaluation (SAFE) study, a large multicentre trial comparing albumin with isotonic saline for fluid resuscitation in a mixed critical illness population . Overallrtension . Conversrtension . No diffLastly, the most basic example of matching fluid input to the pathophysiological situation has been summarised in the UK national guidance on intravenous fluid use . Here, c−1 but avoiding starches)• Resuscitation • Routine maintenance (25–30 ml.kg• Replacement due to ongoing losses and redistribution (fluid composition tailored to match the estimated water and electrolyte loss)A further layer of complexity in fluid treatments may come from the health-care setting in which they are used. Fascinating insights have come from the FEAST study, which took the principle of fluid bolus therapy early in the presentation of patients with sepsis but applied it in the setting of children presenting to hospital in Africa . In contAbnormal fluid handling is a central part of many critical illnesses, and exogenous fluid administration has become a core part of medical care in these settings. Despite apparently rational physiological goals, the reality of successful fluid intervention is extremely complex at a basic biological, clinical and health-care system level. As a result, many of the key research questions in this field have not yet been definitively answered despite years of research. Large trials and meta-analyses have raised the possibility of fluid-related toxicities long after these fluids have been brought to market. Intravenous fluids must be re-framed as drugs, with indications, contraindications, side effects and dose ranges. Lastly, the emergence of the theme of individualisation—to timing, patient, disease state and health-care setting—is an important step forward, but a combination of robust basic science, translational trials and large clinical trials will be required to progress this area further.Jv: net transcapillary flow; Pi: interstitial hydrostatic pressure; Pv: vascular lumen hydrostatic pressure; S: subglycocalyx layer.EG: endothelial glycocalyx; EGL: endothelial glycocalyx layer; ESL: endothelial surface layer; IIs: subglycocalyx oncotic pressure; IIv: intravascular oncotic pressure; MRE declares that he has no competing interests. MGM has received honoraria for speaking, or consultation and/or travel expenses from Baxter, B. Braun, Covidien, Fresenius Kabi, Hospira and LiDCO. He is the National Clinical Advisor for the Department of Health Enhanced Recovery Partnership, is a Smiths Medical Professor of Anaesthesia and Critical Care at UCL, has consulted AQIX , is the Director of Medical Defence Technologies LLC (‘Gastrostim’ patented) and is a co-inventor of ‘QUENCH’ (pump) IP being exploited by UCL Business. Professor Mythen's institution has also received charitable donations and grants from Smiths Medical Endowment and Deltex Medical. Professor Mythen is also a co-author of the GIFTASUP guidelines on peri-operative fluid management, the Chair of the National Institute of Academic Anaesthesia, a Board member of the Faculty of Intensive Care Medicine, a Council member of the Royal College of Anaesthetists of Great Britain and Ireland, the Editor in Chief of Peri-operative Medicine, on the Editorial Board of the BJA and Critical Care, a member of the Improving Surgical Outcomes Group, a member of the NICE IV Fluids Guideline Development Group (now an expert advisor) and the Co-Director of Xtreme Everest.MRE and MGM both conceived and planned this review. MRE drafted the manuscript. MGM helped to draft the manuscript and revised it critically. Both authors read and approved the final manuscript.


He) instead of traditionally used geopotential height, especially in climate change studies.The Western North Pacific Subtropical High (WNPSH) regulates East Asian climate in summer. Anomalous WNPSH causes floods, droughts and heat waves in China, Japan and Korea. The potential change of the WNPSH under global warming is concerned by Asian people, but whether the WNPSH would be enhanced or weakened remains inconclusive. Based on the multi-model climate change projection from the 5th phase of Coupled Model Intercomparison Project (CMIP5), we show evidences that the WNPSH tends to weaken and retreat eastward in the mid-troposphere in response to global warming, accompanied by an eastward expansion of East Asian rain belt along the northwestern flank of WNPSH. Weakened meridional temperature gradient on the northern flank of WNPSH and the associated thermal wind account for the weakened WNPSH in the mid troposphere. We recommend the WNPSH be measured by eddy geopotential height ( In summer, the subtropical western North Pacific (WNP) is controlled by a high pressure system associated with anticyclone circulation in the mid and lower troposphere. This high pressure system is called Western North Pacific Subtropical High (WNPSH), also named Bonin High or Ogasawara High by Korean and Japanese scientists132346310The decadal change of the WNPSH in the late 1970s has caused a regime shift of East Asian climate12131216H) over the WNP. Higher (lower) H over WNP is regarded as a stronger (weaker) WNPSH. The 5880 m contour of H at 500 hPa is widely used as a benchmark to measure the WNPSH by meteorologists from China, Korea and Japan11715The WNPSH is usually measured by geopotential height  as the deviation of H from the regional average over 0˚–40N˚, 180˚W–180˚E, following the definition in previous studies12He = 0 m contour, instead of the H = 5880 m contour. Since some previous studies also measure the subtropical highs using stream function related variables, we also validate our results based on the eddy stream function (Se) defined as the deviation of stream function from the regional average of 0˚–40˚N, 180˚W-180˚E.The nature of the WNPSH is planetary wave2122He = 0 m and the Se = 0 m2 s−1 contours, and the anticyclone wind field is also well captured. But the H values is systematically underestimated and the H = 5880 m contour cannot be found in Historical run, as noted by previous studyH rather than the absolute magnitude of H according to the momentum equation of atmosphere, the systematic underestimation of H does not affect the simulation of WPNSH. This explains why the simulated He, Se and wind field resembles the observation but the H does not.In Historical run , the MMEHe = 0 m and the Se = 0 m2 s−1 contours both contract in RCP8.5 run, and their western edge retreats eastward  are seen in more than 75% of the individual models. The MME projected decrease of He is 3.7 m, and the MME projected decrease of Se is 3.0 × 106 m2 s−1  contour of the Historical run  should be systematically increasing due to increasing H may mislead people to conclude an intensification and westward extension of the WNPSH, which is inconsistent with the changes in circulation and rainfall. In fact, the increase of H over WNP is smaller than the zonal mean increase .


P is P is topological; (2) P is P is topological.In this paper, we present one way to generalize  The theory of continuous domains, due to its strong background in computer science, general topology and logic has been extensively studied by people from various areas . We put A, respectively. A cut operator A has a join (supremum) then Let P, a subset U of P is called Scott open if (i) D is a directed set of P and P form a topology, which we shall call the Scotttopology, denoted by For a poset P be a poset. We order the collection of nonempty subsets of P by directed if given F in the family such that F and G of P, we say FapproximatesG if for every directed subset P is called a quasicontinuousdomain if for all F approximates F is finite. In particular, a poset P is called a continuous poset if for all y, where Let P be a poset.x is way below y, written For any P is called Erné  Let P beIndeed, we have Let us note that an Example 1.7 (1) in Erné  with value x. So by the definition x) must be eventually in U. This means U; whence First, suppose that D of eventual lower bounds of the net Conversely, suppose that LetPbe ancontinuous poset. Then for anyIt follows from Lemma LetPbe a poset andThenwheredenotes the interior ofwith respect to the weak Scott topologyD with Let LetPbe ancontinuous poset. Thenif and only if the netconverges to the elementxwith respect to the weak Scott topologyThat is, theconvergence is topological.x with respect to the weak Scott topology. For all P is The necessity follows from Lemma LetPbe a poset. If theconvergence is topological, thenPiscontinuous.x in the weak Scott topology. For any N(x) consists of all weak Scott open sets containing x, and define an order on J to be the lexicographic order on the first two coordinates, i.e., V is proper subset of U or x with respect to the weak Scott topology, and hence D of eventual lower bounds of the net P is By Lemma From Propositions LetPbe a poset. Then the following conditions are equivalent:Piscontinuous;Theconvergence inPis topological for the weak Scott topology, that is, for alland all netsinP, if and only ifconverges to the elementxwith respect to the weak Scott topology.LetPbe a dcpo. Then the following conditions are equivalent:Pis a domain;Theconvergence inPis topological for the Scott topology, that is, for alland all netsinP, if and only ifconverges to the elementxwith respect to the Scott topology. consists of all weak Scott open sets containing x, and define an order on J to be the lexicographic order on the first two coordinates. That is, V is proper subset of U or J is directed. Let x with respect to the weak Scott topology, and hence P such that F is a quasi-eventual lower bound of the net Let F is a quasi-eventual lower bound of the net We only need to show that For any From Propositions LetPbe a poset. Then the following conditions are equivalent:Pisquasicontinuous;Theconvergence inPis topological for the weak Scott topologythat is, for alland all netsinP, if and only ifconverges toxwith respect to the weak Scott topology.LetPbe a dcpo. Then the following conditions are equivalent:Pis a quasicontinuous domain;convergence inPis topological for the Scott topologythat is, for alland all netsinP, converges toxif and only ifconverges toxwith respect to the Scott topology. P is P is topological.In this paper, we present one way to generalize


Per definition, tumour and pseudo-tumours are lesions that look alike on ultrasound (US), computer tomography (CT) or magnetic resonance imaging (MRI) studies. Misinterpretation may lead to a significant delay of adequate treatment for malignant tumours or on the contrary may result in over-treatment of a tumour-like, benign lesion. The essential question is how does a radiologist reliably differentiate between both entities? Typically, he will use anatomical imaging studies like US, CT or MRI. A tumour is suspected when a focal density or signal alteration is seen displacing or infiltrating adjacent structures with or without a matching contrast enhancement and possibly surrounded by vasogenic edema. Unfortunately, many pseudo-tumours including abscesses, resolving hematomas, vascular malformations, benign cysts, and even metabolic disorders may have similar imaging features. In addition, a frequent, difficult question is the differentiation between postsurgical changes and residual tumour after recent tumour surgery or between radiation induced lesions and recurrent or residual tumour. The recent development of functional MRI sequences like diffusion tensor imaging (DTI), perfusion weighted imaging (PWI), It is impossible to present a complete list of pseudo-tumours, however the current presentation will discuss how a multidisciplinary, multi-imaging and multi-sequence approach may facilitate differentiation between tumors and pseudo-tumours.


Extraneural metastases (ENM) rarely occur in medulloblastoma (MBL) patients and only few cases of subcutaneous localizations have been described. ENM indicate an aggressive disease associated with a worse prognosis. The characterization of metastatic tumours might be useful to understand their pathogenesis and to identify the most appropriate therapeutic strategies.We present the case of a child with Large Cell Anaplastic (LC/A) MBL, who developed multiple subcutaneous metastases in the scalp area after a ventriculo-peritoneal shunting procedure. The disease rapidly progressed and the child died despite chemotherapy and primary tumour surgical debulking.We molecularly classified the tumour as a group 3 MBL; in addition, we derived stem-like cells (SLC) from a metastatic lesion. Primary tumour, metastases and SLC were further analysed, particularly focusing on features linked to the cutaneous dissemination. Indeed, molecules involved in angiogenesis, cell invasion and epidermal growth factor signalling resulted highly expressed.The present report describes a very rare case of subcutaneous metastatic MBL. The tumour, metastases and SLC have been clinically, pathologically and molecularly characterized. Our case is an example of multidisciplinary approach aiming to characterize MBL aggressive behaviour. MBL is the most common malignant brain tumour of childhood, accounting for approximately 15-20% of central nervous system (CNS) malignancies . Brain aIn recent years, high-throughput studies -14 allowHere we report the case of a child affected by LC/A MBL who developed subcutaneous metastases after a ventriculo-peritoneal shunting procedure. We performed histological and molecular analysis to characterize in details this aggressive tumour, particularly focusing on the stem-like cell population.Histology: Paraffin-embedded 3-μm-thick sections from MBL tumour sample were stained with haematoxylin and eosin (H&E). Histology was reviewed by 2 neuropathologists (F.G. and M.A.) and diagnosis was centralized to minimize inter-observer variability.Immunohistochemistry (IHC): Monoclonal antibody to p53 , and polyclonal anti-Beta catenin antibody  were used.Fluorescence in situ hybridization (FISH): Tumour tissue sections were deparaffinised and pre-treated with pepsin before hybridization with c-myc and control (centromere of chromosome 8) probes .Stem-like cells (SLC) culture: Cells were isolated as previously reported . BrieflyImmunofluorescence: Immunofluerescence was performed as previously described . PrimaryRNA extraction, reverse transcription and gene expression analysis: RNA extraction, reverse transcription and gene expression analysis were performed as previously described . RNA froCytofluorimetry: Samples were dissociated into single cells and incubated with APC-conjugated anti-CD133 or with isotype control  according to manufacturer’s instructions.Ethics Committee of Bambino Gesù Children Hospital approved the case study.A 5 years old male with a recent history of MBL was referred to Hematology/Oncology Department of the Bambino Gesù Children Hospital for obstructive hydrocephalus. A partial resection of MBL had been performed at another institution 20 days earlier. After surgery, MRI revealed a surgical residue associated with a diffuse supra- and infratentorial meningeal involvement Figure A and B aRNA was extracted and retro-transcribed from fresh primary tumour and subcutaneous metastases . cDNA was analysed on a custom microfluid card with a panel of genes specific for MBL molecular subgroups ,18. OverWe investigated molecular features linked to angiogenesis, cell invasion and epidermal growth factor receptors on the primary tumour (pMBL), metastases M1 and M2) and SLC  was also evaluated due to its reported correlation with aggressive MBL subgroups . Indeed,MBL is a heterogeneous disease with survival rates ranging from 85% for average risk patients to lower rates (<65%) in the presence of risk factors ,22. The Recently, Von Hoff suggested a better outcome for children with severe anaplastic histology without additional clinical and molecular risk factors  . AmplifiOur patient showed adverse prognostic markers: severe anaplastic histology, c-myc amplification and p53 immunoreactivity. According to the subgroup classification , our patSubcutaneous metastases have been reported in very few cases ,6. Our cPresence of VP shunt has been suggested as a risk factor for MBL metastases ; howeverInterestingly, stem cell signatures have been associated with a poor prognosis in tumours, raising the concept that the stem cell population may indeed contribute to the aggressive behaviour ,36. VeryThe opportunity to compare primary tumour with its metastases and SLC allowed us to highlight novel molecular findings. Our results are in agreement with the disease model based on different compartments: metastases were very similar among each other, while showing some differences versus the primary MBL. Differences were more evident between tumour samples and stem like cells.Neoangiogenesis and cell invasion molecules were highly expressed in tumour bulk and even more in SLC. The same pattern was observed for the expression levels of molecules involved in EGF signalling, that may be linked to the occurrence of subcutaneous seeding.In the era of molecular characterization of tumours, the identification of biological mechanisms of aggressiveness might well contribute to develop the most appropriate therapeutic strategies. In the present clinical case, we have shown that both primary tumour cells and SLC express ERBB family members, supporting a possible use of anti-ERBB specific therapies, which are already available ,39. In aIn conclusion, we report a rare case of subcutaneous metastatic LC/A MBL, which was analysed in details through a multidisciplinary approach. The molecular characterization of these aggressive tumours might improve the understanding of their pathogenesis and provide the rationale for targeted therapeutic strategies.Written informed consent was obtained from the patient’s parents for publication of this Case report and of any accompanying images.The authors declare that they have no competing interests.EM, AP, GPS, RF, AG and EF carried out molecular studies. AM, FdB, GSC, AC and FL clinically followed the patient. MA, FRB, FG carried out pathologic assessments. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/14/262/prepub