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.

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.

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.

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.

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.

Pure angular momentum generator using a ring resonator.

This paper reports a pure angular momentum generator using a ring resonator surrounded by a group of nano-rods. The evanescent waves of the circulating light in the ring are scattered by the nano-rods and generate a rotating electromagnetic field, which has only angular momentum but no linear momentum along the axis of rotation. The angular order is determined by the difference between the order of Whispering Gallery mode and the number of the rods, the rotating frequency is equal to the light frequency divided by the angular order. The maximum amplitude of the rotating electromagnetic fields can be 10 times higher than the amplitude of the input field when there are 36 rods (R(rod) = 120 nm, nr = 1.6). The pure angular momentum generator provides a new platform for trapping and rotation of small particles.

Spectral collapse in ensembles of metamolecules.

We report on the first direct experimental demonstration of a collective phenomenon in metamaterials: spectral line collapse with an increasing number of unit cell resonators (metamolecules). This effect, which is crucial for achieving a lasing spaser, a coherent source of optical radiation fuelled by coherent plasmonic oscillations in metamaterials, is linked to the suppression of radiation losses in periodic arrays. We experimentally demonstrate spectral line collapse at microwave, terahertz and optical frequencies.

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.

Towards the lasing spaser: controlling metamaterial optical response with semiconductor quantum dots.

We report the first experimental demonstration of compensating Joule losses in metallic photonic metamaterial using optically pumped PbS semiconductor quantum dots.

Dynamic modifications of polarizability for large metallic spheroidal nanoshells.

We present an approach alternative to the hybridization model for the treatment of the coupled interfacial plasmon modes in spheroidal metallic nanoshells. Rather than formulating the problem from the Lagrangian dynamics of the free electronic fluid, we adopt an effective medium approach together with the uniqueness of the solutions to electromagnetic boundary value problem, from which the polarizability of the shells can then be systematically and efficiently derived; and the resonance frequencies for the coupled modes can be obtained from the poles in the polarizability. This approach can treat confocal nanoshells with different geometries for the spheroidal cavity and external surface and allow for a natural extension to incorporate corrections from the finiteness of the optical wavelength which are important for nanoparticles of larger sizes. This thus surpasses the hybridization model which is limited to incorporate only the electrostatic Coulomb interaction between the uncoupled plasmons. Numerical results will be provided for different nanoshell systems, and for the illustration of the various geometric and dynamic effects from our model.

Exploring molecular diversity with combinatorial shape libraries.

Surface technologies based upon selection of ligands from combinatorial libraries herald a revolution in molecular research and drug discovery. Molecular diversity is generated by random combinations of monomeric building blocks to form polymeric conformers that constitute 'shape libraries'. The media for exploring surfaces of target molecules include synthetic or biological polymers consisting of natural or modified amino acids, nucleotides, carbohydrates and other organic materials. Targets can be any biological surface, including enzymes, antibodies, receptors and other regulatory molecules. The power of combinatorial selection is in finding conceptual leads for designing high-affinity ligands and effector molecules for the analysis and manipulation of biochemical interactions.

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.

EBV PCR in the diagnosis and monitoring of posttransplant lymphoproliferative disorder: results of a two-arm prospective trial.

While EBV PCR is used in the management of PTLD, the optimal primer set, relative importance of intracellular versus free plasma EBV, and the baseline profile in an organ transplant population remains unclear. We performed a prospective 2-arm trial utilizing an EBV PCR panel measuring LMP-1, EBER-1 and EBNA-1 in both free plasma as well as intracellular whole blood. Control Arm A consisted of 31 lung transplant patients and Arm B consisted of 35 transplant patients being evaluated for possible PTLD. In Arm A, 1/31 (3%) patients developed a transient plasma EBV load. Thirteen of 31 (42%) had detectable intracellular EBV. In Arm B, 17 (49%) patients were diagnosed with PTLD. Thirteen (76%) had EBV-positive PTLD with 12/13 (92%) having detectable EBV by PCR. The EBV PCR panel had a high sensitivity (92%), specificity (72%), positive predictive value (PPV) (71%) and negative predictive value (NPV) (93%) for diagnosing EBV-positive PTLD and followed patients' clinical course well (p < 0.001). Comparing the individual PCR assays, plasma EBNA PCR was superior with high sensitivity (77%), specificity (100%), PPV (100%) and NPV (86%). We conclude that EBV PCR is a useful test for managing PTLD patients. While plasma EBNA PCR is the best single assay for diagnosing and monitoring PTLD, the complete PCR panel is superior for ruling out its presence.

Variability in the biological response to anti-CD20 B cell depletion in systemic lupus erythaematosus.

OBJECTIVE: To study the effects in systemic lupus erythaematosus (SLE) of B cell directed therapy with rituximab, a chimeric monoclonal antibody directed at CD20+ B cells, without concomitant immunosuppressive therapy in mild to moderate SLE. METHODS: Patients (n=24) with active SLE and failure of >or=1 immunosuppressive were recruited from three university centres into this phase I/II prospective open-label study. Patients were followed for 1 year to assess safety, efficacy and biological effects. RESULTS: In total, 18 of the patients scheduled to receive the full lymphoma dose of rituximab were evaluable for B cell levels in peripheral blood. Of these, 17 had effective CD19+ B cell depletion (<5 cells/microl). However, six of the depleted patients showed B cell return before 24 weeks. A total of 70% of patients improved by week 55, as defined by an SLE Disease Activity Index (SLEDAI) score improvement of >or=2 units from baseline. The degree of CD19+ B cell depletion was correlated with SLEDAI improvement at week 15 (r=0.84). In general, rituximab infusions were well tolerated. Approximately a third of the patients developed human anti-chimeric antibody (HACA) titres, which correlated with poor B cell depletion. Most patients (9 of 14) did not respond to immunisations with Pneumovax and tetanus toxoid. CONCLUSIONS: Rituximab is a promising new therapy for SLE. The variability of responses in patients with SLE may be related to HACA formation. The failure to respond to immunisations is surprising, in view of the apparently low risk of infections. Better biological markers are necessary to follow these patients during treatment.

Evanescent field enhancement due to plasmonic resonances of a metamaterial slab.

The characteristics of plasmonic resonance in a dielectric-sandwiched metamaterial film at visible wavelengths of 650 and 568 nm have been investigated (for both p- and s-polarized light). Our calculated results demonstrate that each mode of plasmonic resonance has maximum resonance strength at a particular film thickness of the metamaterial. We also demonstrated that the effect of evanescent field enhancement is due to plasmonic resonances of the sandwiched metamaterial system. And the stronger the plasmonic resonance strength the larger the evanescent field is enhanced at the interfaces of the metamaterial film. Also we see that the plasmonic resonances in a sandwiched metamaterial are influenced not only by the materials that constitute the interfaces but also by the thickness of surrounding dielectrics or distance between evanescent light source and metamaterial film. Finally, our results show that there might be an effective light propagation length that will let the coupling efficiency between evanescent light source and SPs resonance become a maximum. These properties of plasmonic resonances to structure parameters of metamaterial film and its surrounding dielectrics provide a useful way to control the optical responses of an optoelectronic device when the wavelength of light source is fixed. That is, by suitably choosing light polarizations, thickness of the metamaterial thin film or the surrounding dielectrics and the position of evanescent light source, it is possible to modulate the plasmonic resonance wavenumber or resonance strength of the system. Therefore, the optical responses of the system can be modulated. Our results will be helpful for the structure design to control the behaviours of coupled plasmonic resonances and consequently the optical properties of the dielectric-sandwiched metamaterial film.

Study of the optical response of phase-change recording layer with zinc oxide nanostructured thin film.

Recently, use of nanostructured materials as a near-field optical active layer has attracted a lot of interest. The non-linear optical properties and strong enhancements of metallic oxide nanostructured thin films are key functions in applications of promising nanophotonics. For the importance of ultra-high density optical data storage, we continue investigating the ultra-high density recording property of near-field optical disk consisting of zinc oxide (ZnO(x)) nanostructured thin film. A carrier-to-noise ratio above 38 dB at a recording mark size of 100 nm can be obtained in the ZnO(x) near-field optical disk by a DVD driver tester directly. In this article, we use an optical pump-probe system (static media tester) to measure the optical response of a phase-change recording layer (Ge(2)Sb(2)Te(5)) and demonstrate the high contrast of optical recording with a ZnO(x) nanostructured thin film in short pulse durations. Also, we investigate the dependence of writing power and the optical response in conventional re-writable recording layers and the phase-change material with ZnO(x) nanostructured thin film.

Removal of gadolinium by peritoneal dialysis.

An association between gadolinium-containing contrast and the development of nephrogenic systemic fibrosis (NSF) has been increasingly recognized. For patients receiving hemodialysis (HD) who are exposed to gadolinium, the Federal Drug Administration (FDA) recommends HD to remove this contrast agent in order to minimize the risk of NSF. This study examines if gadolinium can be removed by frequent exchanges by peritoneal dialysis (PD). Following administration of 0.1 mmol/kg of gadodiamide to a patient with end-stage renal disease, the serum clearance of this contrast agent by automated PD was examined. 10 and 15 exchanges of PD using an automated cycler were respectively performed during the first and second 24-hour periods after gadolinium exposure. Serum gadolinium levels were measured 1 hour after the gadolinium administration, then at 24 and 48 hours after PD was initiated. 90% of the gadolinium was removed from the circulation in 2 days with a regimen of 10-15 exchanges per day of PD. For patients on chronic maintenance PD who receive gadolinium, our case suggests that a temporary intensive automated PD regimen, aimed at maximizing clearance of this contrast agent immediately after exposure, could be an effective alternative when institution of HD is problematic.