Tunable optical differential operation based on graphene at a telecommunication wavelength.

Optical differential operation based on the photonic spin Hall effect(SHE) has attracted extensive attention in image processing of edge detection, which has advantages of high speed, parallelism, and low power consumption. Here, we theoretically demonstrate tunable optical differential operation in a four-layered nanostructure of prism-graphene-air gap-substrate. It is shown that the spatial differentiation arises inherently from the photonic SHE. Furthermore, we find that the transverse spin-Hall shift induced by the photonic SHE changes dramatically near the Brewster angle with the incident angle increases at a telecommunication wavelength. Meanwhile, the Fermi energy of graphene and the thickness of the air gap can affect the transverse spin shift. Interestingly, we can easily adjust the Fermi energy of graphene in real time through external electrostatic field biasing, enabling fast edge imaging switching at a telecommunication wavelength. This may provide a potential way for future tunable spin-photonic devices, and open up more possible applications for artificial intelligence, such as target recognition, biomedical imaging, and edge detection.

Optical bistability modulation based on graphene sandwich structure with topological interface modes.

In this paper, we have investigated optical bistability modulation of transmitted beam that can be achieved by graphene sandwich structure with topological interface modes at terahertz frequency. Graphene with strong nonlinear optical effect was combined with sandwich photonic crystal to form a new sandwich structure with topological interface modes. The light-limiting properties of the topological interface modes, as well as its high unidirectionality and high transmission efficiency, all contribute positively to the reduction of the optical bistability threshold. In addition, the topological interface modes can effectively ensure the stability of the two steady state switching in the case of external interference. Moreover, optical bistability is closely related to the incident angle, the Fermi energy, the relaxation time, and the number of layers of graphene. Through parameter optimization, optical bistability with threshold of 105 V/m can be obtained, which has reached or is close to the range of the weak field.

Optical bistability in a heterodimer composed of a quantum dot and a metallic nanoshell.

We theoretically explore the conditions for generating optical bistability (OB) in a heterodimer comprised of a semiconductor quantum dot (SQD) and a metallic nanoshell (MNS). The MNS is made of a metallic nanosphere as a core and a dielectric material as a shell. For the specific hybrid system considered, the bistable effect appears only if the frequency of the pump field is equal to (or slightly less than) the exciton frequency for a proper shell thickness. Bistability phase diagrams, when plotted, show that the dipole-induced bistable region can be greatly broadened by changing the shell thickness of the MNS in a strong exciton-plasmon coupling regime. In particular, we demonstrate that the multipole polarization not only narrows the bistable zone but also enlarges the corresponding thresholds for a given intermediate scaled pumping intensity. On the other hand, when the SQD couples strongly with the MNS, the multipole polarization can also significantly broaden the bistable region and induce a great suppression of the FWM (four-wave mixing) signal for a fixed shell thickness. These interesting findings offer a fresh understanding of the bistability conditions in an SQD/MNS heterodimer, and may be useful in the fabrication of high-performance and low-threshold optical bistable nanodevices.

Risk of malignant melanoma and non-melanoma skin cancer in rheumatoid arthritis patients initiating methotrexate versus hydroxychloroquine: a cohort study.

OBJECTIVES: To characterise the incidence rate of skin cancer associated with methotrexate and hydroxychloroquine in older adults with rheumatoid arthritis (RA). METHODS: RA patients aged ≥65 years who initiated methotrexate or hydroxychloroquine as their first disease modifying antirheumatic drugs (DMARDs). The primary outcome was new occurrence of any skin cancer (i.e. malignant melanoma or non-melanoma skin cancer; NMSC) based on validated algorithms (positive predictive value >83%). Secondary outcomes were malignant melanoma, NMSC, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). We estimated the incidence rates (IRs) and hazard ratios (HRs) for each outcome in the 1:1 propensity score (PS)-matched methotrexate and hydroxychloroquine groups. RESULTS: We included 24,577 PS-matched pairs of methotrexate and hydroxychloroquine initiators. Compared with hydroxychloroquine (IR 25.20/1,000 person-years), methotrexate initiators (IR 26.21/1,000 person-years) had a similar risk of any skin cancer [HR 1.03 -(95%CI 0.92, 1.14)] over a mean follow-up of 388 days. The HR (95%CI) associated with methotrexate was 1.39 (0.87, 2.21) for malignant melanoma, 1.01(0.90, 1.12) for NMSC, 1.37 (1.13, 1.66) for BCC, and 0.79 (0.63, 0.99) for SCC compared with hydroxychloroquine. CONCLUSIONS: In this large cohort of older RA patients initiating methotrexate or hydroxychloroquine as their first DMARD, we found no difference in the risk of skin cancer including malignant melanoma and NMSC. However, for specific components of NMSC, methotrexate initiators had higher risk of BCC but lower risk of SCC compared with hydroxychloroquine initiators.

Ultra-strong optical four-wave mixing signal induced by strong exciton-phonon and exciton-plasmon couplings.

We propose a scheme to generate ultra-strong four-wave mixing (FWM) signal based on a suspended monolayer graphene nanoribbon nanomechanical resonator (NR) coupled to an Au nanoparticle (NP). It is shown that, the FWM spectrum can switch among two-peaked, three-peaked, four-peaked or five-peaked via the modulation of exciton-phonon and exciton-plasmon couplings. This is mainly attributed to the vibrational properties of NR related to the exciton-phonon coupling, and the energy-level splitting of the localized exciton correlated to three classes of resonances consisting of three-photon resonance, Rayleigh Resonance, and AC-Stark atomic resonance. Especially, in a dual-strong coupling regime, the gains for these peaks can be as high as nine orders of magnitude (∼ 109) around the lower bistable threshold due to a combined effect of two couplings. Our findings not only offer an efficient way to measure the vibrational frequency of NR and the exciton-phonon coupling strength but also provide a possibility to fabricate high-performance optoelectronic nanodevices.

Validation of claims-based algorithms to identify patients with psoriasis.

PURPOSE: Accurately identifying patients with psoriasis (PsO) is crucial for generating real-world evidence on PsO disease course and treatment utilization. METHODS: We developed nine claims-based algorithms for PsO using a combination of the International Classification of Diseases (ICD)-9 codes, specialist visit, and medication dispensing using Medicare linked to electronic health records data (2013-2014) in two healthcare provider networks in Boston, Massachusetts. We calculated positive predictive value (PPV) and 95% confidence interval (CI) for each algorithm using the treating physician's diagnosis of PsO via chart review as the gold standard. Among the confirmed PsO cases, we assessed their PsO disease activity. RESULTS: The nine claims-based algorithms identified 990 unique patient records. Of those, 918 (92.7%) with adequate information were reviewed. The PPV of the algorithms ranged from 65.1 to 82.9%. An algorithm defined as ≥1 ICD-9 diagnosis code for PsO and ≥1 prescription claim for topical vitamin D agents showed the highest PPV (82.9%). The PPV of the algorithm requiring ≥2 ICD-9 diagnosis codes and ≥1 prescription claim for PsO treatment excluding topical steroids was 81.1% but higher (82.5%) when ≥1 diagnosis was from a dermatologist. Among 411 PsO patients with adequate information on PsO disease activity in EHRs, 1.5-5.8% had no disease activity, 31.3-36.8% mild, and 26.9-35.1% moderate-to-severe across the algorithms. CONCLUSIONS: Claims-based algorithms based on a combination of PsO diagnosis codes and dispensing for PsO-specific treatments had a moderate-to-high PPV. These algorithms can serve as a useful tool to identify patients with PsO in future real-world data pharmacoepidemiologic studies.

Dual-channel bistable switch based on a monolayer graphene nanoribbon nanoresonator coupled to a metal nanoparticle.

We theoretically propose a dual-channel bistable switch based on a monolayer Z-shaped graphene nanoribbon nanoresonator (NR) coupled to a metal nanoparticle (MNP). We show that the bistable nonlinear absorption response can be realized due to a competition and combination of the exciton-plasmon and exciton-phonon interactions. We map out two-dimensional and three-dimensional bistability phase diagrams, which reveal clearly the dynamical evolution of the roles played by these two interactions in managing optical bistability (OB) at all stages. Specifically, the bistable switch proposed can be controlled via a single channel or dual channels by only adjusting the intensity or frequency of the pump field. In/outside these channels, the switch will be turned on/off. The results obtained here not only can be employed to measure precisely the distance between the MNP and the NR but also provide promising applications in optical switching and optical storage.

Mapping from the International Classification of Diseases (ICD) 9th to 10th Revision for Research in Biologics and Biosimilars Using Administrative Healthcare Data.

PURPOSE: The Centers for Medicare and Medicaid Services (CMS) mandated the transition from ICD-9 to ICD-10 codes on October 1, 2015. Postmarketing surveillance of newly marketed drugs, including novel biologics and biosimilars, requires a robust approach to convert ICD-9 to ICD-10 codes for study variables. We examined three mapping methods for health conditions (HCs) of interest to the Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) and compared their prevalence. METHODS: Using CMS General Equivalence Mappings, we applied forward-backward mapping (FBM) to 108 HCs and secondary mapping (SM) and tertiary mapping (TM) to seven preselected HCs. A physician reviewed the mapped ICD-10 codes. The prevalence of the 108 HCs defined by ICD-9 versus ICD-10 codes was examined in BBCIC's distributed research network (September 1, 2012 to March 31, 2018). We visually assessed prevalence trends of these HCs and applied a threshold of 20% level change in ICD-9 versus ICD-10 prevalence. RESULTS: Nearly four times more ICD-10 codes were mapped by SM and TM than FBM, but most were irrelevant or nonspecific. For conditions like myocardial infarction, SM or TM did not generate additional ICD-10 codes. Through visual inspection, one-fifth of the HCs had inconsistent ICD-9 versus ICD-10 prevalence trends. 13% of HCs had a level change greater than +/-20%. CONCLUSION: FBM is generally the most efficient way to convert ICD-9 to ICD-10 codes, yet manual review of converted ICD-10 codes is recommended even for FBM. The lack of existing guidance to compare the performance of ICD-9 with ICD-10 codes led to challenges in empirically determining the quality of conversions.

Validation of algorithms to identify adverse perinatal outcomes in the Medicaid Analytic Extract database.

BACKGROUND: The Medicaid Analytic eXtract (MAX) is a health care utilization database from publicly insured individuals that has been used for studies of drug safety in pregnancy. Claims-based algorithms for defining many important maternal and neonatal outcomes have not been validated. OBJECTIVE: To validate claims-based algorithms for identifying selected pregnancy outcomes in MAX using hospital medical records. METHODS: The medical records of mothers who delivered between 2000 and 2010 within a single large healthcare system were linked to their claims in MAX. Claims-based algorithms for placental abruption, preeclampsia, postpartum hemorrhage, small for gestational age, and noncardiac congenital malformation were defined. Fifty randomly sampled cases for each outcome identified using these algorithms were selected, and their medical records were independently reviewed by two physicians to confirm the presence of the diagnosis of interest; disagreements were resolved by a third physician reviewer. Positive predictive values (PPVs) and 95% confidence intervals (CIs) of the claims-based algorithms were calculated using medical records as the gold standard. RESULTS: The linked cohort included 10,899 live-birth pregnancies. The PPV was 92% (95% CI, 82%-97%) for placental abruption, 82% (95% CI, 70%-91%) for preeclampsia, 74% (95% CI, 61%-85%) for postpartum hemorrhage, 92% (95% CI, 82%-97%) for small for gestational age, and 86% (95% CI, 74%-94%) for noncardiac congenital malformation. CONCLUSIONS: Across the perinatal outcomes considered, PPVs ranged between 74% and 92%. These PPVs can inform bias analyses that correct for outcome misclassification.

Glucose-lowering medications and the risk of cancer: A methodological review of studies based on real-world data.

AIM: To review the methodology of observational studies examining the association between glucose-lowering medications and cancer to identify the most common methodological challenges and sources of bias. METHODS: We searched PubMed systematically to identify observational studies on glucose-lowering medications and cancer published between January 2000 and January 2016. We assessed the design and analytical methods used in each study, with a focus on their ability to achieve study validity, and further evaluated the prevalence of major methodological choices over time. RESULTS: Of 155 studies evaluated, only 26% implemented a new-user design, 41% used an active comparator, 33% implemented a lag or latency period, and 51% adjusted for diabetes duration. Potential for immortal person-time bias was identified in 63% of the studies; 55% of the studies adjusted for variables measured during the follow-up without appropriate statistical methods. Aside from a decreasing trend in adjusting for variables measured during the follow-up, we observed no trends in methodological choices over time. CONCLUSIONS: The prevalence of well-known design and analysis flaws that may lead to biased results remains high among observational studies on glucose-lowering medications and cancer, limiting the conclusions that can be drawn from these studies. Avoiding known pitfalls could substantially improve the quality and validity of real-world evidence in this field.

Relative Performance of Propensity Score Matching Strategies for Subgroup Analyses.

Postapproval drug safety studies often use propensity scores (PSs) to adjust for a large number of baseline confounders. These studies may involve examining whether treatment safety varies across subgroups. There are many ways a PS could be used to adjust for confounding in subgroup analyses. These methods have trade-offs that are not well understood. We conducted a plasmode simulation to compare relative performance of 5 methods involving PS matching for subgroup analysis, including methods frequently used in applied literature whose performance has not been previously directly compared. These methods varied as to whether the overall PS, subgroup-specific PS, or no rematching was used in subgroup analysis as well as whether subgroups were fully nested within the main analytical cohort. The evaluated PS subgroup matching methods performed similarly in terms of balance, bias, and precision in 12 simulated scenarios varying size of the cohort, prevalence of exposure and outcome, strength of relationships between baseline covariates and exposure, the true effect within subgroups, and the degree of confounding within subgroups. Each had strengths and limitations with respect to other performance metrics that could inform choice of method.

Plasmon-modulated bistable four-wave mixing signals from a metal nanoparticle-monolayer MoS2 nanoresonator hybrid system.

We present a study for the impact of exciton-phonon and exciton-plasmon interactions on bistable four-wave mixing (FWM) signals in a metal nanoparticle (MNP)-monolayer MoS2 nanoresonator hybrid system. Via tracing the FWM response we predict that, depending on the excitation conditions and the system parameters, such a system exhibits 'U-shaped' bistable FWM signals. We also map out bistability phase diagrams within the system's parameter space. Especially, we show that compared with the exciton-phonon interaction, a strong exciton-plasmon interaction plays a dominant role in the generation of optical bistability, and the bistable region will be greatly broadened by shortening the distance between the MNP and the monolayer MoS2 nanoresonator. In the weak exciton-plasmon coupling regime, the impact of exciton-phonon interaction on optical bistability will become obvious. The scheme proposed may be used for building optical switches and logic-gate devices for optical computing and quantum information processing.

Bistable four-wave mixing response in a semiconductor quantum dot coupled to a photonic crystal nanocavity.

We perform a theoretical study of the bistable four-wave mixing (FWM) response in a coupled system comprised of a semiconductor quantum dot (SQD) and a photonic crystal (PC) nanocavity in which the SQD is embedded. It is shown that the shape of the FWM spectrum can switch among single-peaked, double-peaked, triple-peaked, and four-peaked arising from the vacuum Rabi splitting and the exciton-nanocavity coupling. Especially, we map out bistability phase diagrams within a parameter subspace of the system, and find that it is easy to turn on or off the bistable FWM response by only adjusting the excitation frequency or the pumping intensity. Our results offer a feasible means for measuring the SQD-PC nanocavity coupling strength and open a new avenue to design optical switches and memories.

Switching freely between superluminal and subluminal light propagation in a monolayer MoS2 nanoresonator.

We theoretically propose a feasible scheme to advance or slow the propagation of light in a monolayer MoS2 nanoresonator (NR). The scheme allows one to easily turn on or off the fast (superluminal) and slow (subluminal) light effects and switch freely between fast and slow light propagation by only adjusting the frequency or intensity of the pump field. As the exciton interacts strongly with the phonons in MoS2, the slow light effect will appear along with a large dispersion with a very steep negative slope and a sharp absorption peak. Especially, the maximal group velocity index of the slow light in the monolayer MoS2 NR can reach two orders of magnitude larger than that in a carbon nanotube resonator. These results provide a new way to measure the exciton-phonon coupling strength and may prove useful in device applications such as optical switching and optical signal processing.

A review of the performance of different methods for propensity score matched subgroup analyses and a summary of their application in peer-reviewed research studies.

PURPOSE: When evaluating safety signals, there is often interest in understanding safety in all patients for whom compared treatments are reasonable alternatives, as well as in specific subgroups of interest. There are numerous ways that propensity score (PS) matching can be implemented for subgroup analyses. METHODS: We conducted a systematic literature review of methods papers that compared the performance of alternative methods to implement PS matched subgroup analyses and examined how frequently different PS matching methods have been used for subgroup analyses in applied studies. RESULTS: We identified 5 methods papers reporting small improvements in covariate balance and bias with use of a subgroup-specific PS instead of a mis-specified overall PS within subgroups. Applied research papers frequently used PS for subgroups in ways not evaluated in methods papers. Thirty three percent used PS to match in the overall cohort and broke the matched sets for subgroup analysis without further adjustment. CONCLUSIONS: While the performance of several alternative ways to use PS matching in subgroup analyses has been evaluated in methods literature, these evaluations do not include the most commonly used methods to implement PS matched subgroup analyses in applied studies. There is a need to better understand the relative performance of commonly used methods for PS matching in subgroup analyses, particularly within settings encountered during active surveillance, where there may be low exposure, infrequent outcomes, and multiple subgroups of interest.

Four-wave mixing signal enhancement and optical bistability of a hybrid metal nanoparticle-quantum dot molecule in a nanomechanical resonator.

We investigate theoretically four-wave mixing (FWM) response and optical bistability (OB) in a hybrid nanosystem composed of a metal nanoparticle (MNP) and a semiconductor quantum dot (SQD) coupled to a nanomechanical resonator (NR). It is shown that the FWM signal is enhanced by more than three orders of magnitude as compared to that of the system without exciton-phonon interaction, and the FWM signal can also be suppressed significantly and broadened due to the exciton-plasmon interaction. As the MNP couples strongly with the SQD, the bistable FWM response can be achieved by adjusting the SQD-MNP distance and the pumping intensity. For a given pumping constant and a fixed SQD-MNP distance, the enhanced exciton-phonon interaction can promote the occurrence of bistability. Our findings not only present a feasible way to detect the spacing between two nanoparticles, but also hold promise for developing quantum switches and nanoscale rulers.

Four-wave parametric amplification in semiconductor quantum dot-metallic nanoparticle hybrid molecules.

We study theoretically four-wave parametric amplification arising from the nonlinear optical response of hybrid molecules composed of semiconductor quantum dots and metallic nanoparticles. It is shown that highly efficient four-wave parametric amplification can be achieved by adjusting the frequency and intensity of the pump field and the distance between the quantum dot and the metallic nanoparticle. Specifically, the induced probe-wave gain is tunable in a large range from 1 to 1.43 × 105. This gain reaches its maximum at the position of three-photon resonance. Our findings hold great promise for developing four-wave parametric oscillators.

Plasmon resonances in a stacked pair of graphene ribbon arrays with a lateral displacement.

We find that a stacked pair of graphene ribbon arrays with a lateral displacement can excite plasmon waveguide mode in the gap between ribbons, as well as surface plasmon mode on graphene ribbon surface. When the resonance wavelengthes of plasmon waveguide mode and surface plasmon mode are close to each other, there is a strong electromagnetic interaction between the two modes, and then they contribute together to transmission dip. The plasmon waveguide mode resonance can be manipulated by the lateral displacement and longitudinal interval between arrays due to their influence on the manner and strength of electromagnetic coupling between two arrays. The findings expand our understanding of electromagnetic resonances in graphene-ribbon array structure and may affect further engineering of nanoplasmonic devices and metamaterials.

Cardiovascular Risks of Hydroxychloroquine vs Methotrexate in Patients With Rheumatoid Arthritis.

BACKGROUND: Hydroxychloroquine is often used as a first-line treatment of rheumatoid arthritis despite limited evidence on its cardiovascular risk. OBJECTIVES: We conducted a cardiovascular safety evaluation comparing hydroxychloroquine to methotrexate among patients with rheumatoid arthritis. METHODS: Using Medicare data (2008-2016), we identified 54,462 propensity score-matched patients with rheumatoid arthritis, aged ≥65 years, who initiated hydroxychloroquine or methotrexate. Primary outcomes were sudden cardiac arrest or ventricular arrythmia (SCA/VA) and major adverse cardiovascular event (MACE). Secondary outcomes were cardiovascular mortality, all-cause mortality, myocardial infarction, stroke, and hospitalized heart failure (HF). We also examined treatment effect modification by history of HF. RESULTS: Hydroxychloroquine was not associated with risk of SCA/VA (HR: 1.03; 95% CI: 0.79-1.35) or MACE (HR: 1.07; 95% CI: 0.97-1.18) compared with methotrexate. In patients with history of HF, hydroxychloroquine initiators had a higher risk of MACE (HR: 1.30; 95% CI: 1.08-1.56), cardiovascular mortality (HR: 1.34; 95% CI: 1.06-1.70), all-cause mortality (HR: 1.22; 95% CI: 1.04-1.43), myocardial infarction (HR: 1.74; 95% CI: 1.25-2.42), and hospitalized HF (HR: 1.29; 95% CI: 1.07-1.54) compared to methotrexate initiators. Cardiovascular risks were not different in patients without history of HF except for an increased hospitalized HF risk (HR: 1.57; 95% CI: 1.30-1.90) among hydroxychloroquine initiators. CONCLUSIONS: In older patients with rheumatoid arthritis, hydroxychloroquine and methotrexate showed similar SCA/VA and MACE risks; however, hydroxychloroquine initiators with history of HF had higher risks of MACE, cardiovascular mortality, all-cause mortality, and myocardial infarction. An increased hospitalized HF risk was observed among hydroxychloroquine initiators regardless of an HF history.

Prevalence of Avoidable and Bias-Inflicting Methodological Pitfalls in Real-World Studies of Medication Safety and Effectiveness.

Many real-word evidence (RWE) studies that utilize existing healthcare data to evaluate treatment effects incur substantial but avoidable bias from methodologically flawed study design; however, the extent of preventable methodological pitfalls in current RWE is unknown. To characterize the prevalence of avoidable methodological pitfalls with potential for bias in published claims-based studies of medication safety or effectiveness, we conducted an English-language search of PubMed for articles published from January 1, 2010 to May 20, 2019 and randomly selected 75 studies (10 case-control and 65 cohort studies) that evaluated safety or effectiveness of cardiovascular, diabetes, or osteoporosis medications using US health insurance claims. General and methodological study characteristics were extracted independently by two reviewers, and potential for bias was assessed across nine bias domains. Nearly all studies (95%) had at least one avoidable methodological issue known to incur bias, and 81% had potentially at least one of the four issues considered major due to their potential to undermine study validity: time-related bias (57%), potential for depletion of outcome-susceptible individuals (44%), inappropriate adjustment for postbaseline variables (41%), or potential for reverse causation (39%). The median number of major issues per study was 2 (interquartile range (IQR), 1-3) and was lower in cohort studies with a new-user, active-comparator design (median 1, IQR 0-1) than in cohort studies of prevalent users with a nonuser comparator (median 3, IQR 3-4). Recognizing and avoiding known methodological study design pitfalls could substantially improve the utility of RWE and confidence in its validity.