Comprehensive analysis and optimal design of top-emitting organic light-emitting devices

We present an accurate analysis of light emission in top-emitting organic light-emitting devices (TOLEDs) by explicitly considering the Purcell effect. TOLEDs are optimized separately for maximum zero-degree luminance, maximum electroluminescence (EL) efficiency, and wide viewing angle with high EL efficiency. For fluorescent material with an internal quantum efficiency ( int 0) of 0.25, the maximum zero-degree luminance and EL efficiency can be achieved by locating the emitters around the first antinode of the microcavity while for phosphorescent material with int 0 =1.0, the maximum zero-degree luminance and EL efficiency are around the second antinode. Through relaxing the efficiency by 10%-20%, the angular intensity distribution can be even better than the Lambertian distribution; meanwhile, the color shows only a small variation over an angle range of 150°. Our results, which are in good agreement with experiments, show that the Purcell effect on TOLED performances is significant and should be carefully examined in studying TOLEDs. © 2007 American Institute of Physics.published_or_final_versio

Highly efficient fluorescence of a fluorescing nanoparticle with a silver shell

Spontaneous emission (SE) rate and the fluorescence efficiency of a bare fluorescing nanoparticle and the nanoparticle with a silver nanoshell are analyzed rigorously by using a classical electromagnetic approach with the consideration of the nonlocal effect of the silver nanoshell. The dependences of the SE rate and the fluorescence efficiency on the core-shell structure are carefully studied and the physical interpretations of the results are addressed. The results show that the SE rate of a bare nanoparticle is much slower than that in the infinite medium by almost an order of magnitude and consequently the fluorescence efficiency is usually low. However, by encapsulating the nanoparticle with a silver shell, highly efficient fluorescence can be achieved as a result of a large Purcell enhancement and high out-coupling efficiency for a well-designed core-shell structure. We also show that a higher SE rate may not offer a larger fluorescence efficiency since the fluorescence efficiency not only depends on the internal quantum yield but also the out-coupling efficiency. © 2007 Optical Society of America.published_or_final_versio

The Purcell effect of silver nanoshell on the fluorescence of nanoparticles

Proceedings of the Asia Optical Fiber Communication and Optoelectronics Conference, 2007, p. 81-83The Purcell effect on the spontaneously emission rate and fluorescence efficiency of nanoparticles with and without a silver nanoshell will be investigated which are important for nanoparticle applications in biomedical diagnostics, information storage and optoelectronics.published_or_final_versio

Improving the efficiency of organic light emitting devices by using co-host electron transport layer

By engineering a new cohosting system of tris(8-hydroxyquinoline) and 4,7-diphenyl-1,10-phenanthroline in the electron transport layer, the current efficiency of the organic light emitting diode is improved by 34% to 4.3 cd/A as compared to the device with a single host of Alq 3 as the electron transport layer. The maximum luminance is over 16,000 cd/m 2 at the bias of 22 V and the current of 475 mA/cm 2, which is ∼ 73% higher than the single host Alq 3 device without optimizing the layer thickness. The reasons for the improvement will be investigated. The results strongly indicate that the knowledge of bulk conductivity engineering of organic n-type transporters shows practical significance in OLED applications. © 2005 Elsevier B.V. All rights reserved.postprin

Optical properties of organic materials for optical communication devices

2005 International Symposium on Intelligent Signal Processing and Communication Systems (ISPACS 2005), Hong Kong, 13-16 December 2005Recently, organic materials have been considered as a potential candidate for making optoelectronic devices. In order to optimize the performance of the optoelectronic devices, the absolute refractive index and absorption coefficient of the organic materials have to be determined. In this article, the absolute optical properties of two novel bipolar organic materials will be investigated through ellipsometry and modeling using Lorentz Oscillator model and stimulated annealing algorithm. © 2005 IEEE.published_or_final_versio

Synovial tissue signatures enhance clinical classification and prognostic/treatment response algorithms in early inflammatory arthritis and predict requirement for subsequent biological therapy: results from the pathobiology of early arthritis cohort (PEAC)

Funding for PEAC MRC: Grant code 36661. Funding Infrastructure support to EMR, Arthritis Research UK Experimental Treatment Centre: Grant code 20022

Rituximab versus tocilizumab and B-cell status in TNF-alpha inadequate-responder rheumatoid arthritis patients: the R4-RA RCT

BackgroundAlthough biological therapies have transformed the outlook for those with rheumatoid arthritis, there is a lack of any meaningful response in approximately 40% of patients. The role of B cells in rheumatoid arthritis pathogenesis is well recognised and is supported by the clinical efficacy of the B-cell-depleting agent rituximab (MabThera, F. Hoffman La-Roche Ltd, Basel, Switzerland). Rituximab is licensed for use in rheumatoid arthritis following failure of conventional synthetic disease-modifying antirheumatic drugs and tumour necrosis factor inhibitor therapy. However, over 50% of patients show low/absent synovial B-cell infiltration, suggesting that, in these patients, inflammation is driven by alternative cell types. This prompted us to test the hypothesis that, in synovial biopsy B-cell-poor patients, tocilizumab (RoActemra, F. Hoffman La-Roche Ltd, Basel, Switzerland) (targeting interleukin 6) is superior to rituximab (targeting CD20+/B cells).DesignThe R4–RA (A Randomised, open-labelled study in anti-TNFalpha inadequate responders to investigate the mechanisms for Response, Resistance to Rituximab versus Tocilizumab in Rheumatoid Arthritis patients) trial is a 48-week Phase IV, open-label, randomised controlled trial conducted in 19 European centres that recruited patients failing on or intolerant to conventional synthetic disease-modifying antirheumatic drug therapy and at least one tumour necrosis factor inhibitor.ParticipantsSynovial tissue was obtained at trial entry and classified histologically as B-cell rich or B-cell poor to inform balanced stratification. Patients were randomised on a 1 : 1 basis to receive standard therapy with rituximab or tocilizumab. B-cell-poor/-rich molecular classification was also carried out. The study was powered to test the superiority of tocilizumab over rituximab at 16 weeks in the B-cell-poor population.Main outcome measuresThe primary end point was defined as an improvement in the Clinical Disease Activity Index (CDAI) score of ≥ 50% from baseline. In addition, patients were considered to be non-responders if they did not reach an improvement in CDAI score of ≥ 50% and a CDAI score of ResultsIn total, 164 patients were randomised: 83 patients received rituximab and 81 received tocilizumab. Eighty-one out of 83 rituximab patients and 73 out of 81 tocilizumab patients completed treatment up to week 16 (primary end point). Baseline characteristics were comparable between the treatment groups. In the histologically classified B-cell-poor population (n = 79), no significant difference was observed in the primary outcome, an improvement in CDAI score of ≥ 50% from baseline (risk ratio 1.25, 95% confidence interval 0.80 to 1.96). A supplementary analysis of the CDAI-MTR, however, did reach statistical significance (risk ratio 1.96, 95% confidence interval 1.01 to 3.78). In addition, when B-cell-poor classification was determined molecularly, both the primary end point and the CDAI-MTR were statistically significant (risk ratio 1.72, 95% confidence interval 1.02 to 2.91, and risk ratio 4.12, 95% confidence interval 1.55 to 11.01, respectively). Moreover, a larger number of secondary end points achieved significance when classified molecularly than when classified histologically. In the B-cell-rich population, there was no significant difference between treatments in the majority of both primary and secondary end points. There were more adverse events and serious adverse events, such as infections, in the tocilizumab group than in the rituximab group.ConclusionTo our knowledge, this is the first biopsy-based, multicentre, randomised controlled trial of rheumatoid arthritis. We were unable to demonstrate that tocilizumab was more effective than rituximab in patients with a B-cell-poor pathotype in our primary analysis. However, superiority was shown in most of the supplementary and secondary analyses using a molecular classification. These analyses overcame possible unavoidable weaknesses in our original study plan, in which the histological method of determining B-cell status may have misclassified some participants and our chosen primary outcome was insufficiently sensitive. Given the significant results observed using the molecular classification, future research will focus on refining this stratification method and evaluating its clinical utility.Trial registrationCurrent Controlled Trials ISRCTN97443826.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health and Care Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 9, No. 7. See the NIHR Journals Library website for further project information

A systematic molecular and pharmacologic evaluation of AKT inhibitors reveals new insight into their biological activity.

Background AKT, a critical effector of the phosphoinositide 3-kinase (PI3K) signalling cascade, is an intensely pursued therapeutic target in oncology. Two distinct classes of AKT inhibitors have been in clinical development, ATP-competitive and allosteric. Class-specific differences in drug activity are likely the result of differential structural and conformational requirements governing efficient target binding, which ultimately determine isoform-specific potency, selectivity profiles and activity against clinically relevant AKT mutant variants.Methods We have carried out a systematic evaluation of clinical AKT inhibitors using in vitro pharmacology, molecular profiling and biochemical assays together with structural modelling to better understand the context of drug-specific and drug-class-specific cell-killing activity.Results Our data demonstrate clear differences between ATP-competitive and allosteric AKT inhibitors, including differential effects on non-catalytic activity as measured by a novel functional readout. Surprisingly, we found that some mutations can cause drug resistance in an isoform-selective manner despite high structural conservation across AKT isoforms. Finally, we have derived drug-class-specific phosphoproteomic signatures and used them to identify effective drug combinations.Conclusions These findings illustrate the utility of individual AKT inhibitors, both as drugs and as chemical probes, and the benefit of AKT inhibitor pharmacological diversity in providing a repertoire of context-specific therapeutic options

Comparison of single versus fractionated dose of stereotactic radiotherapy for salvaging local failures of nasopharyngeal carcinoma: a matched-cohort analysis

BACKGROUND: Local failure is an important cause of morbidity and mortality in nasopharyngeal carcinoma (NPC). Although surgery or brachytherapy may be feasible in selected cases, most patients with local failure require external beam re-irradiation. Stereotactic radiation using single or multiple fractions have been employed in re-irradiation of NPC, but the optimal fractionation scheme and dose are not clear. METHODS: Records of 125 NPC patients who received salvage stereotactic radiation were reviewed. A matched-pair design was used to select patients with similar prognostic factors who received stereotactic re-irradiation using single fraction (SRS) or multiple fractions (SRM). Eighty-six patients were selected with equal number in SRS and SRM groups. All patients were individually matched for failure type (persistent or recurrent), rT stage (rT1-2 or rT3-4), and tumor volume (5-10 cc, or >10 cc). Median dose was 12.5 Gy in single fraction by SRS, and 34 Gy in 2-6 fractions by SRM. RESULTS: Local control rate was better in SRM group although overall survival rates were similar. One- and 3-year local failure-free rates were 70% and 51% in SRS group compared with 91% and 83% in SRM group (p = 0.003). One- and 3-year overall survival rates were 98% and 66% in SRS group compared with 78% and 61% in SRM group (p = 0.31). The differences in local control were mainly observed in recurrent or rT2-4 disease. Incidence of severe late complications was 33% in SRS group vs. 21% in SRM group, including brain necrosis (16% vs. 12%) and hemorrhage (5% vs. 2%). CONCLUSION: Our study showed that SRM was superior to SRS in salvaging local failures of NPC, especially in the treatment of recurrent and rT2-4 disease. In patient with local failure of NPC suitable for stereotactic re-irradiation, use of fractionated treatment is preferred.link_to_subscribed_fulltex

Current treatment options for recurrent nasopharyngeal cancer

Loco-regional control rate of nasopharyngeal carcinoma (NPC) has improved significantly in the past decade. However, local recurrence still represents a major cause of mortality and morbidity in advanced stages, and management of local failure remains a challenging issue in NPC. The best salvage treatment for local recurrent NPC remains to be determined. The options include brachytherapy, external radiotherapy, stereotactic radiosurgery, and nasopharyngectomy, either alone or in different combinations. In this article we will discuss the different options for salvage of locally recurrent NPC. Retreatment of locally recurrent NPC using radiotherapy, alone or in combination with other treatment modalities, as well as surgery, can result in long-term local control and survival in a substantial proportion of patients. For small-volume recurrent tumors (T1–T2) treated with external radiotherapy, brachytherapy or stereotactic radiosurgery, comparable results to those obtained with surgery have been reported. In contrast, treatment results of advanced-stage locally recurrent NPC are generally more satisfactory with surgery (with or without postoperative radiotherapy) than with reirradiation