Mechanically controllable nonlinear dielectrics.

Strain-sensitive Ba x Sr1-x TiO3 perovskite systems are widely used because of their superior nonlinear dielectric behaviors. In this research, new heterostructures including paraelectric Ba0.5Sr0.5TiO3 (BSTO) and ferroelectric BaTiO3 (BTO) materials were epitaxially fabricated on flexible muscovite substrate. Through simple bending, the application of mechanical force can regulate the dielectric constant of BSTO from -77 to 36% and the channel current of BTO-based ferroelectric field effect transistor by two orders. The detailed mechanism was studied through the exploration of phase transition and determination of band structure. In addition, the phase-field simulations were implemented to provide theoretical support. This research opens a new avenue for mechanically controllable components based on high-quality oxide heteroepitaxy.

Author Correction: Sculpting nanoparticle dynamics for single-bacteria-level screening and direct binding-efficiency measurement.

The original version of this Article omitted the author Kuan Wang, who is from the 'College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan' and 'Nanyang Environment & Water Research Institute, Nanyang Technological University, Singapore 637141, Singapore.'Also, the author S.H. Lim was incorrectly given as L.S. Hoi and A. Larsson was incorrectly given as A. Larson.The "Author contributions" was amended to reflect the authorship changes. It previously read 'Y.Z.S., C.-W.Q., and A.Q.L. jointly conceived the idea. Y.Z.S., S.X., Y.Z., J.B.Z., W.S., J.H.W., T.N.C., Z.C.Y., Y.L.H., B.L., P.H.Y., D.P.T., and C.-W.Q. performed the numerical simulations and theoretical analysis. Y.Z.S., S.X., and L.K.C. did the fabrication and experiments of particle hopping, biomolecule binding and flow cytometry. A.L. and L.S.H. did the SPR experiments. S.X., Y.Z.S., Y.Z., C.-W.Q., Y.-Y.C., L.K.C., T.H.Z., and A.Q.L. prepared the manuscript. S.X., Y.Z., C.-W.Q., and A.Q.L. supervised and coordinated all the work. All authors commented on the manuscript.' The correct version states 'B.L., K. W., P.H.Y.' instead of 'B.L., P.H.Y.' and 'S.H.L.' in place of 'L.S.H.'This has been corrected in both the PDF and HTML versions of the Article.

Optimised dosing of vancomycin in critically ill Indigenous Australian patients with severe sepsis.

Vancomycin is a commonly used antibiotic due to the high burden of methicillin-resistant Staphylococcus aureus infections. This study aimed to describe the pharmacokinetics (PK) of vancomycin in Australian Indigenous patients with severe sepsis, and advise an optimal dosing strategy. A population PK study was conducted in a remote Australian intensive care unit (ICU). Serial plasma samples were collected over one to two dosing intervals and assayed by validated chromatography. Concentration-time data collected were analysed using Pmetrics® software. The final population PK model was then used for Monte Carlo dosing simulations to determine optimal loading and intermittent maintenance doses. Fifteen Indigenous subjects were included for analysis with a median (interquartile range, IQR) age, weight and creatinine clearance (CrCL) of 43 (34-46) years, 73 (66-104) kg and 99 (56-139) ml/minute respectively. A two-compartment model described the data adequately. Vancomycin clearance (CL) and volume of distribution of the central compartment (Vc) were described by CrCL and patient weight respectively. Median (IQR) CL, Vc, distribution rate constants from central to peripheral, and from peripheral to central compartments were 4.6 (3.8-5.6) litres per hour, 25.4 (16.1-31.3) litres, 0.46 (0.28-0.52)/hour and 0.25 (0.12-0.37)/hour respectively. No significant interethnic PK differences were observed in comparison to published data. Therapeutic loading doses were significantly dependent on both weight and CrCL, whereas maintenance doses were dependent on CrCL. In the absence of severe renal impairment, initiation of maintenance dose eight hours post-loading dose achieved higher probability of target attainment at 24 hours. This is the first report of vancomycin PK in this patient group.

A facile method to functionalize gold nano-tripods with high suspension stability in an aqueous environment.

Here we aim to develop a facile emulsion-based method to prepare tripod gold nanoparticles (AuNPs) with high suspension stability in an aqueous environment. A gyroid-structured polymer template formed by the hydrolysis of a degradable block copolymer, polystyrene (PS)-b-poly(l-lactide), is used for the fabrication of AuNPs. Also, a successful emulsification of dichloromethane (DCM) in the aqueous phase is developed by using thiolated polyethylene glycol (PEG-SH) as the stabilizer. Subsequently, the nanohybrids of PS/Au can be fabricated by templated electroless plating, and then selectively dissolving in the DCM dispersive phase. Most interestingly, a dedicated process for the simultaneous release of the tripod AuNPs from the dissolution of PS associated with PEG-SH at the interface of the emulsion is achieved, giving PEG-SH-functionalized tripod AuNPs dispersed in the aqueous phase, which significantly improves the suspension stabilization of tripod AuNPs. The in situ temperature-programmed electrospray-differential mobility analysis provides a quantitative, statistical analysis of mobility diameter, dynamic shape factor, polydispersity, and colloidal stability.

Sculpting nanoparticle dynamics for single-bacteria-level screening and direct binding-efficiency measurement.

Particle trapping and binding in optical potential wells provide a versatile platform for various biomedical applications. However, implementation systems to study multi-particle contact interactions in an optical lattice remain rare. By configuring an optofluidic lattice, we demonstrate the precise control of particle interactions and functions such as controlling aggregation and multi-hopping. The mean residence time of a single particle is found considerably reduced from 7 s, as predicted by Kramer's theory, to 0.6 s, owing to the mechanical interactions among aggregated particles. The optofluidic lattice also enables single-bacteria-level screening of biological binding agents such as antibodies through particle-enabled bacteria hopping. The binding efficiency of antibodies could be determined directly, selectively, quantitatively and efficiently. This work enriches the fundamental mechanisms of particle kinetics and offers new possibilities for probing and utilising unprecedented biomolecule interactions at single-bacteria level.

Prevalence of augmented renal clearance and performance of glomerular filtration estimates in Indigenous Australian patients requiring intensive care admission.

Augmented renal clearance (ARC) refers to the enhanced renal excretion of circulating solute commonly demonstrated in numerous critically ill subgroups. This study aimed to describe the prevalence of ARC in critically ill Indigenous Australian patients and explore the accuracy of commonly employed mathematical estimates of glomerular filtration. We completed a single-centre, prospective, observational study in the intensive care unit (ICU), Alice Springs Hospital, Central Australia. Participants were critically ill adult Indigenous and non-Indigenous Australian patients with a urinary catheter in situ. Exclusion criteria were anuria, pregnancy or the requirement for renal replacement therapy. Daily eight-hour measured creatinine clearances (CrCLm) were collected throughout the ICU stay. ARC was defined by a CrCLm ≥130 ml/min/1.73 m2. The Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration equations were also used to calculate mathematical estimates for comparison. In total, 131 patients were recruited (97 Indigenous, 34 non-Indigenous) and 445 samples were collected. The median (range) CrCLm was 93.0 (5.14 to 205.2) and 90.4 (18.7 to 206.8) ml/min/1.73 m2 in Indigenous and non-Indigenous patients, respectively. Thirty-one of 97 (32%) Indigenous patients manifested ARC, compared to 7 of 34 (21%) non-Indigenous patients (P=0.21). Younger age, major surgery, higher baseline renal function and an absence of diabetes were all associated with ARC. Both mathematical estimates manifest limited accuracy. ARC was prevalent in critically ill Indigenous patients, which places them at significant risk of underdosing with renally excreted drugs. CrCLm should be obtained wherever possible to ensure accurate dosing.

OC-14 - Baseline D-dimer levels are predictive of recurrent venous thromboembolism (VTE) at 6 months in cancer patients with VTE treated with tinzaparin.

INTRODUCTION: VTE is a major complication in cancer patients. Despite treatment with low molecular weight heparin (LMWH), 9% will have recurrent VTE within 6 months. Measurement of plasma biomarkers in cancer patients receiving LMWH may be predictive of recurrent VTE or overall survival (OS). AIM: We conducted a single arm phase 2 study to evaluate the efficacy and safety of once daily tinzaparin for the initial treatment and extended prophylaxis of VTE in cancer patients. The study included a prospective analysis of plasma biomarkers D-dimer and IL-6 to assess whether these were predictive of recurrent VTE or OS. MATERIALS AND METHODS: Consecutive patients with active cancer diagnosed with a pulmonary embolism (PE) and/or proximal deep venous thrombosis (DVT) at the University of Southern California Norris Comprehensive Cancer Center, Los Angeles County Medical Center, or New York Presbyterian - Weill Cornell Medical Center were invited to participate in this study with a target enrollment of 100 patients. Key eligibility criteria included: age ≥18, ECOG score ≤2, adequate organ function, and ≥6 month estimated survival. Patients were treated with daily subcutaneously tinzaparin 175 U/kg for 6 months on study. Tinzaparin could be continued ≤1 year at the discretion of the treating physician. All patients who received ≥1 dose were evaluable for efficacy and safety. Primary study endpoints were recurrent VTE or major bleeding. Secondary outcome measures included OS and plasma biomarkers. Biomarkers were measured at baseline, 7 days, 1 month and 6 months after tinzaparin initiation. Patients who had baseline and 1 week or 1 month samples collected were included in the biomarker analysis. RESULTS: 97 patients were enrolled. 2 patients were ineligible. 8 patients did not have baseline or follow-up biomarkers completed. 87 patients were included in the analysis. 28 (32%) of patients completed≥6 months of tinzaparin. Major bleeding occurred in 2 patients. 11 patients had recurrent VTE at 6 months (3 PE, 7 DVT, 1 central venous thrombosis not associated with a catheter). Median baseline D-dimer level was 2759 ng/mL (range: 375-37,591). Median baseline IL-6 level was 9.4 pg/mL (range: 0.8-20.9). Baseline D-dimer>median was predictive of VTE recurrence at 6 months (p=.006). Baseline IL-6>median was not predictive of VTE recurrence at 6 months. Neither 1 month D-dimer or IL-6 levels were predictive of VTE recurrence at 6 months. D-dimer and IL-6 at baseline and at 1 month were not predictive of OS. CONCLUSIONS: In patients with active cancer and VTE treated with tinzaparin, baseline D-dimer levels above the median value were predictive of VTE recurrence at 6 months.

The Impact of EBV Status on Characteristics and Outcomes of Posttransplantation Lymphoproliferative Disorder.

We examined the associations of Epstein-Barr virus (EBV) status with characteristics and outcomes of posttransplantation lymphoproliferative disorder (PTLD) by studying 176 adult solid organ transplant recipients diagnosed with PTLD between 1990 and 2013 (58 [33%] EBV-negative; 118 [67%] EBV-positive). The proportion of EBV-negative cases increased over time from 10% (1990-1995) to 48% (2008-2013) (p < 0.001). EBV-negative PTLD had distinct characteristics (monomorphic histology, longer latency) though high-risk features (advanced stage, older age, high lactate dehydrogenase, central nervous system involvement) were not more common compared to EBV-positive PTLD. In multivariable analysis, EBV negativity was not significantly associated with worse response to initial therapy (adjusted odds ratio, 0.84; p = 0.75). The likelihood of achieving a complete remission (CR) was not significantly different for EBV-negative versus EBV-positive PTLD including when therapy was reduction of immunosuppression alone (35% vs. 43%, respectively, p = 0.60) or rituximab (43% vs. 47%, p = 1.0). EBV negativity was also not associated with worse overall survival (adjusted hazard ratio, 0.91; p = 0.71). Our findings indicate that EBV status is not prognostic or predictive of treatment response in adults with PTLD. The high proportion of EBV-negative disease diagnosed in recent years highlights the need for new strategies for prevention and management of EBV-negative PTLD.

Effects of gain medium on the plasmonic enhancement of Forster resonance energy transfer in the vicinity of a metallic particle or cavity.

We perform theoretical studies on the plasmonic enhancement for the Forster resonance energy transfer (FRET) between a donor and an acceptor molecule in the vicinity of a metallic particle or cavity, with focus on the possible role of the addition of a clad layer of gain material can play in such a process. The results show that while the plasmonic resonances can be shifted with higher order plasmonic enhancements emerged in the presence of such a layer of gain material, optimal enhancement of the FRET rate can be achieved when gain just balances with the loss in the metal. This then leads to the existence of an optimal thickness for the gain material layer, for both particle and cavity enhancement. In addition, it is observed that the FRET efficiency can always be increased with the coating of the gain material even at the dipole plasmonic resonance when nonradiative transfer from the donor to the metal is high, provided that the gain level is not beyond a certain critical value.

Molecular fluorescence in the vicinity of a charged metallic nanoparticle.

The modified fluorescence properties of a molecule in the vicinity of a metallic nanoparticle are further studied accounting for the possible existence of extraneous charges on the particle surface. This is achieved via a generalization of the previous theory of Bohren and Hunt for light scattering from a charged sphere, with the results applied to the calculation of the various decay rates and fluorescence yield of the admolecule. Numerical results show that while charge effects will in general blue-shift all the plasmonic resonances of the metal particle, both the quantum yield and the fluorescence yield can be increased at emission frequencies close to that of the surface plasmon resonance of the particle due to the suppression of the nonradiative decay rate. This provides a possibility of further enhancing the particle-induced molecular fluorescence via the addition of surface charge to the metal particle.

Resonant transparency and non-trivial non-radiating excitations in toroidal metamaterials.

Engaging strongly resonant interactions allows dramatic enhancement of functionalities of many electromagnetic devices. However, resonances can be dampened by Joule and radiation losses. While in many cases Joule losses may be minimized by the choice of constituting materials, controlling radiation losses is often a bigger problem. Recent solutions include the use of coupled radiant and sub-radiant modes yielding narrow asymmetric Fano resonances in a wide range of systems, from defect states in photonic crystals and optical waveguides with mesoscopic ring resonators to nanoscale plasmonic and metamaterial systems exhibiting interference effects akin to electromagnetically-induced transparency. Here we demonstrate theoretically and confirm experimentally a new mechanism of resonant electromagnetic transparency, which yields very narrow isolated symmetric Lorentzian transmission lines in toroidal metamaterials. It exploits the long sought non-trivial non-radiating charge-current excitation based on interfering electric and toroidal dipoles that was first proposed by Afanasiev and Stepanovsky in [J. Phys. A Math. Gen. 28, 4565 (1995)].

Effects of extraneous surface charges on the enhanced Raman scattering from metallic nanoparticles.

Motivating by recent experiments on surface enhanced Raman scattering (SERS) from colloidal solutions, we present here a simple model to elucidate the effects of extraneous surface charges on the enhanced Raman signal. The model is based on the well-established Gersten-Nitzan model coupled to the modified Mie scattering theory of Bohren and Hunt in the long wavelength approximation. We further introduce corrections from the modified long wavelength approximation to the Gersten-Nitzan model for the improvement of its accuracy. Our results show that the surface charge will generally lead to a blueshift in the resonance frequency and greater enhancements in the SERS spectrum. Possible correlations with the recent experiments are elaborated.

Microelectromechanical Maltese-cross metamaterial with tunable terahertz anisotropy.

Dichroic polarizers and waveplates exploiting anisotropic materials have vast applications in displays and numerous optical components, such as filters, beamsplitters and isolators. Artificial anisotropic media were recently suggested for the realization of negative refraction, cloaking, hyperlenses, and controlling luminescence. However, extending these applications into the terahertz domain is hampered by a lack of natural anisotropic media, while artificial metamaterials offer a strong engineered anisotropic response. Here we demonstrate a terahertz metamaterial with anisotropy tunable from positive to negative values. It is based on the Maltese-cross pattern, where anisotropy is induced by breaking the four-fold symmetry of the cross by displacing one of its beams. The symmetry breaking permits the excitation of a Fano mode active for one of the polarization eigenstates controlled by actuators using microelectromechanical systems. The metamaterial offers new opportunities for the development of terahertz variable waveplates, tunable filters and polarimetry.

Transformation optofluidics for large-angle light bending and tuning.

Transformation optics is a new art of light bending by designing materials with spatially variable parameters for developing wave-manipulation devices. Here, we introduce a transformation optofluidic Y-branch splitter with large-angle bending and tuning based on the design of a spatially variable index. Differing from traditional splitters, the optofluidic splitter is achieved in an inhomogeneous medium by coordinate transformation. The designed bidirectional gradient index (GRIN) distribution can be achieved practically by the convection-diffusion process of liquid flowing streams. The transformation optofluidic splitter can achieve a much larger split angle with little bend loss than the traditional ones. In the experiments, a large tunable split angle up to 30° is achieved by tuning the flow rates, allowing optical signals to be freely transferred to different channels. Besides the symmetrical branch splitting, asymmetrical Y-branch splitting with approximately equal power splitting is also demonstrated by changing the composition of the liquids. The optofluidic splitter has high potential applications in biological, chemical and biomedical solution measurement and detection.

Equivalence between the mechanical model and energy-transfer theory for the classical decay rates of molecules near a spherical particle.

In the classical modeling of decay rates for molecules interacting with a nontrivial environment, it is well known that two alternate approaches exist which include: (1) a mechanical model treating the system as a damped harmonic oscillator driven by the reflected fields from the environment; and (2) a model based on the radiative and nonradiative energy transfers from the excited molecular system to the environment. While the exact equivalence of the two methods is not trivial and has been explicitly demonstrated only for planar geometry, it has been widely taken for granted and applied to other geometries such as in the interaction of the molecule with a spherical particle. Here we provide a rigorous proof of such equivalence for the molecule-sphere problem via a direct calculation of the decay rates adopting each of the two different approaches.

Optofluidic waveguide as a transformation optics device for lightwave bending and manipulation.

Transformation optics represents a new paradigm for designing light-manipulating devices, such as cloaks and field concentrators, through the engineering of electromagnetic space using materials with spatially variable parameters. Here we analyse liquid flowing in an optofluidic waveguide as a new type of controllable transformation optics medium. We show that a laminar liquid flow in an optofluidic channel exhibits spatially variable dielectric properties that support novel wave-focussing and interference phenomena, which are distinctively different from the discrete diffraction observed in solid waveguide arrays. Our work provides new insight into the unique optical properties of optofluidic waveguides and their potential applications.

High-dose corticosteroids with or without etanercept for the treatment of idiopathic pneumonia syndrome after allo-SCT.

Idiopathic Pneumonia Syndrome (IPS) is a common complication after allo-SCT and results in high mortality rates. Conventional treatment for IPS typically includes supportive care and high-dose corticosteroids (CS). Data suggests that TNF-α is important in the pathogenesis of IPS and that the TNF-α inhibitor etanercept may be useful for IPS treatment. We performed a retrospective comparison of consecutive patients treated at our center for IPS with CS only from 1999 to 2003 (group 1, n=22) or CS plus etanercept from 2004 to 2007 (group 2, n=17). In all, 18% of patients in group 1 vs 53% in group 2 were successfully taken off respiratory support and discharged from the hospital (P=0.039). OS was significantly better for recipients of CS plus etanercept (P=0.003). The estimated survival at 28 days and 2 years after IPS was 36.4% (95% CI 17-56%) and 9.1% (95% CI 2-25%) for group 1 and 88.2% (95% CI 61-97%) and 18% (95% CI 4-38%) for group 2, respectively. Our retrospective comparison suggests that the addition of etanercept to CS for IPS improves response rates and OS. However, outcomes remain limited in both groups, highlighting the need for more effective interventions to treat early and late complications of IPS.

Preparation and characterization of iridium dioxide-carbon nanotube nanocomposites for supercapacitors.

A thin film of novel hierarchical structure, suitable for supercapacitor applications, has been developed through combining conductive multi-wall carbon nanotubes (MWCNTs) and square IrO(2) nanotubes (IrO(2)NT) of nanometer size. Synthesis of this hierarchical structure with open porosity is performed by depositing IrO(2) short tubes densely along the long wires of carbon nanotube on a substrate of stainless steel. A IrO(2) tube of rutile structure grows in the [001] direction, with an opening at its top, surrounded by very thin walls. The IrO(2) addition on the MWCNT template increases the capacitance of the CNT thin film effectively, because of pseudocapacitance of the IrO(2) surface. For this particular composite, featured with two tubular nanostructures, the specific capacitance increases from 15 F g(-1) (MWCNT) to 69 F g(-1) (IrO(2)NT/MWCNT), measured using the galvanostatic discharge experiment. Its property of fast retrieval of the stored charge is assured in the impedance measurement, showing that the internal resistance of the IrO(2)NT/MWCNT nanocomposite electrode is lower than that of the bare MWCNTs.

Reduction of immunosuppression as initial therapy for posttransplantation lymphoproliferative disorder(☠).

Reduction of immunosuppression (RI) is commonly used to treat posttransplant lymphoproliferative disorder (PTLD) in solid organ transplant recipients. We investigated the efficacy, safety and predictors of response to RI in adult patients with PTLD. Sixty-seven patients were managed with RI alone and 30 patients were treated with surgical excision followed by adjuvant RI. The response rate to RI alone was 45% (complete response-37%, partial response-8%). The relapse rate in complete responders was 17%. Adjuvant RI resulted in a 27% relapse rate. The acute rejection rate following RI-containing strategies was 32% and a second transplant was feasible without relapse of PTLD. The median survival was 44 months in patients treated with RI alone and 9.5 months in patients who remained on full immunosuppression (p = 0.07). Bulky disease, advanced stage and older age predicted lack of response to RI. Survival analysis demonstrated predictors of poor outcome-age, dyspnea, B symptoms, LDH level, hepatitis C, bone marrow and liver involvement. Patients with none or one of these factors had a 3-year overall survival of 100% and 79%, respectively. These findings support the use of RI alone in low-risk PTLD and suggest factors that predict response and survival.