62 research outputs found
Resonant Visible Light Modulation with Graphene
Fast modulation and switching of light at visible and near-infrared (vis-NIR)
frequencies is of utmost importance for optical signal processing and sensing
technologies. No fundamental limit appears to prevent us from designing
wavelength-sized devices capable of controlling the light phase and intensity
at gigaherts (and even terahertz) speeds in those spectral ranges. However,
this problem remains largely unsolved, despite recent advances in the use of
quantum wells and phase-change materials for that purpose. Here, we explore an
alternative solution based upon the remarkable electro-optical properties of
graphene. In particular, we predict unity-order changes in the transmission and
absorption of vis-NIR light produced upon electrical doping of graphene sheets
coupled to realistically engineered optical cavities. The light intensity is
enhanced at the graphene plane, and so is its absorption, which can be switched
and modulated via Pauli blocking through varying the level of doping.
Specifically, we explore dielectric planar cavities operating under either
tunneling or Fabry-Perot resonant transmission conditions, as well as Mie modes
in silicon nanospheres and lattice resonances in metal particle arrays. Our
simulations reveal absolute variations in transmission exceeding 90% as well as
an extinction ratio >15 dB with small insertion losses using feasible material
parameters, thus supporting the application of graphene in fast electro-optics
at vis-NIR frequencies.Comment: 17 pages, 13 figures, 54 reference
Gate-tunable Topological Valley Transport in Bilayer Graphene
Valley pseudospin, the quantum degree of freedom characterizing the
degenerate valleys in energy bands, is a distinct feature of two-dimensional
Dirac materials. Similar to spin, the valley pseudospin is spanned by a time
reversal pair of states, though the two valley pseudospin states transform to
each other under spatial inversion. The breaking of inversion symmetry induces
various valley-contrasted physical properties; for instance, valley-dependent
topological transport is of both scientific and technological interests.
Bilayer graphene (BLG) is a unique system whose intrinsic inversion symmetry
can be controllably broken by a perpendicular electric field, offering a rare
possibility for continuously tunable valley-topological transport. Here, we
used a perpendicular gate electric field to break the inversion symmetry in
BLG, and a giant nonlocal response was observed as a result of the topological
transport of the valley pseudospin. We further showed that the valley transport
is fully tunable by external gates, and that the nonlocal signal persists up to
room temperature and over long distances. These observations challenge
contemporary understanding of topological transport in a gapped system, and the
robust topological transport may lead to future valleytronic applications
Population pharmacokinetics of Amisulpride in Chinese patients with schizophrenia with external validation: the impact of renal function
Introduction: Amisulpride is primarily eliminated via the kidneys. Given the clear influence of renal clearance on plasma concentration, we aimed to explicitly examine the impact of renal function on amisulpride pharmacokinetics (PK) via population PK modelling and Monte Carlo simulations.Method: Plasma concentrations from 921 patients (776 in development and 145 in validation) were utilized.Results: Amisulpride PK could be described by a one-compartment model with linear elimination where estimated glomerular filtration rate, eGFR, had a significant influence on clearance. All PK parameters (estimate, RSE%) were precisely estimated: apparent volume of distribution (645 L, 18%), apparent clearance (60.5 L/h, 2%), absorption rate constant (0.106 h−1, 12%) and coefficient of renal function on clearance (0.817, 10%). No other significant covariate was found. The predictive performance of the model was externally validated. Covariate analysis showed an inverse relationship between eGFR and exposure, where subjects with eGFR= 30 mL/min/1.73 m2 had more than 2-fold increase in AUC, trough and peak concentration. Simulation results further illustrated that, given a dose of 800 mg, plasma concentrations of all patients with renal impairment would exceed 640 ng/mL.Discussion: Our work demonstrated the importance of renal function in amisulpride dose adjustment and provided a quantitative framework to guide individualized dosing for Chinese patients with schizophrenia
Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study
Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030
Targeted gene sanger sequencing should remain the first-tier genetic test for children suspected to have the five common X-linked inborn errors of immunity
DATA AVAILABILITY STATEMENT : The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited
regions, our centre developed and offered free genetic testing for the most common IEI by
Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary
Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of
IEI were further improved with collaboration among centres caring for IEI patients from
East and Southeast Asia. We also started to use whole exome sequencing (WES) for
undiagnosed cases and further extended our collaboration with centres from South Asia
and Africa. With the increased use of Next Generation Sequencing (NGS), we have shifted
our diagnostic practice from SS to WES. However, SS was still one of the key diagnostic
tools for IEI for the past two decades. Our centre has performed 2,024 IEI SS genetic
tests, with in-house protocol designed specifically for 84 genes, in 1,376 patients with 744
identified to have disease-causing mutations (54.1%). The high diagnostic rate after just
one round of targeted gene SS for each of the 5 common IEI (X-linked
agammaglobulinemia (XLA) 77.4%, Wiskott–Aldrich syndrome (WAS) 69.2%, X-linked chronic granulomatous disease (XCGD) 59.5%, X-linked severe combined
immunodeficiency (XSCID) 51.1%, and X-linked hyper-IgM syndrome (HIGM1) 58.1%)
demonstrated targeted gene SS should remain the first-tier genetic test for the 5 common
X-linked IEI.The Hong Kong Society for Relief of Disabled Children and Jeffrey Modell Foundation.http://www.frontiersin.org/Immunologyam2023Paediatrics and Child Healt
Assessment of the nlmixr R package for population pharmacokinetic modeling: A metformin case study
AIM: nlmixr offers first-order conditional estimation with or without interaction (FOCE or FOCEi) and stochastic approximation estimation-maximisation (SAEM) to fit nonlinear mixed-effect models (NLMEM). We modelled metformin's pharmacokinetic data using nlmixr and investigated SAEM and FOCEi's performance with respect to bias and precision of parameter estimates, and robustness to initial estimates. METHOD: Compartmental models were fitted. The final model was determined based on the objective function value and inspection of goodness-of-fit plots. The bias and precision of parameter estimates were compared between SAEM and FOCEi using stochastic simulations and estimations. For robustness, parameters were re-estimated as the initial estimates were perturbed 100-times and resultant changes evaluated. RESULTS: Absorption kinetics of metformin depends significantly on food status. Under the fasted state, the first-order absorption into the central compartment was preceded by zero-order infusion into the depot compartment, whereas for the fed state, the absorption into the depot was instantaneous followed by first-order absorption from depot into the central compartment. The mean of relative mean estimation error (rMEE) ( ME E SAEM ME E FOCEi ) and rRMSE ( RMS E SAEM RMS E FOCEi ) was 0.48 and 0.35 respectively. All parameter estimates given by SAEM appeared to be narrowly distributed and were close to the true value used for simulation. In contrast, the distribution of estimates from FOCEi were skewed and more biased . When initial estimates were perturbed, FOCEi estimates were more biased and imprecise. DISCUSSION: nlmixr is reliable for NLMEM. SAEM was superior to FOCEi in terms of bias and precision, and more robust against initial estimate perturbations
Assessment of the nlmixr R package for population pharmacokinetic modeling: a metformin case study
Aimnlmixr offers first-order conditional estimation (FOCE), FOCE with interaction (FOCEi) and stochastic approximation estimation-maximisation (SAEM) to fit nonlinear mixed-effect models (NLMEM). We modelled metformin's pharmacokinetic data using nlmixr and investigated SAEM and FOCEi's performance with respect to bias and precision of parameter estimates, and robustness to initial estimates.
MethodCompartmental models were fitted. The final model was determined based on the objective function value and inspection of goodness-of-fit plots. The bias and precision of parameter estimates were compared between SAEM and FOCEi using stochastic simulations and estimations. For robustness, parameters were re-estimated as the initial estimates were perturbed 100 times and resultant changes evaluated.
ResultsThe absorption kinetics of metformin depend significantly on food status. Under the fasted state, the first-order absorption into the central compartment was preceded by zero-order infusion into the depot compartment, whereas for the fed state, the absorption into the depot was instantaneous followed by first-order absorption from depot into the central compartment. The means of relative mean estimation error (rMEE) ( MEESAEMMEEFOCEi ) and rRMSE ( RMSESAEMRMSEFOCEi ) were 0.48 and 0.35, respectively. All parameter estimates given by SAEM appeared to be narrowly distributed and were close to the true value used for simulation. In contrast, the distribution of estimates from FOCEi were skewed and more biased. When initial estimates were perturbed, FOCEi estimates were more biased and imprecise.
Discussionnlmixr is reliable for NLMEM. SAEM was superior to FOCEi in terms of bias and precision, and more robust against initial estimate perturbations
Examination of the Impact of CYP3A4/5 on Drug–Drug Interaction between Schizandrol A/Schizandrol B and Tacrolimus (FK-506): A Physiologically Based Pharmacokinetic Modeling Approach
Schizandrol A (SZA) and schizandrol B (SZB) are two active ingredients of Wuzhi capsule (WZC), a Chinese proprietary medicine commonly prescribed to alleviate tacrolimus (FK-506)-induced hepatoxicity in China. Due to their inhibitory effects on cytochrome P450 (CYP) 3A enzymes, SZA/SZB may display drug–drug interaction (DDI) with tacrolimus. To identify the extent of this DDI, the enzymes’ inhibitory profiles, including a 50% inhibitory concentration (IC50) shift, reversible inhibition (RI) and time-dependent inhibition (TDI) were examined with pooled human-liver microsomes (HLMs) and CYP3A5-genotyped HLMs. Subsequently, the acquired parameters were integrated into a physiologically based pharmacokinetic (PBPK) model to quantify the interactions between the SZA/SZB and the tacrolimus. The metabolic studies indicated that the SZB displayed both RI and TDI on CYP3A4 and CYP3A5, while the SZA only exhibited TDI on CYP3A4 to a limited extent. Moreover, our PBPK model predicted that multiple doses of SZB would increase tacrolimus exposure by 26% and 57% in CYP3A5 expressers and non-expressers, respectively. Clearly, PBPK modeling has emerged as a powerful approach to examine herb-involved DDI, and special attention should be paid to the combined use of WZC and tacrolimus in clinical practice
High-temperature driven inter-valley carrier transfer and significant fluorescence enhancement in multilayer WS 2
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