Demonstration of Three-Dimensional Indoor Visible Light Positioning with Multiple Photodiodes and Reinforcement Learning.

To provide high-quality location-based services in the era of the Internet of Things, visible light positioning (VLP) is considered a promising technology for indoor positioning. In this paper, we study a multi-photodiodes (multi-PDs) three-dimensional (3D) indoor VLP system enhanced by reinforcement learning (RL), which can realize accurate positioning in the 3D space without any off-line training. The basic 3D positioning model is introduced, where without height information of the receiver, the initial height value is first estimated by exploring its relationship with the received signal strength (RSS), and then, the coordinates of the other two dimensions (i.e., X and Y in the horizontal plane) are calculated via trilateration based on the RSS. Two different RL processes, namely RL1 and RL2, are devised to form two methods that further improve horizontal and vertical positioning accuracy, respectively. A combination of RL1 and RL2 as the third proposed method enhances the overall 3D positioning accuracy. The positioning performance of the four presented 3D positioning methods, including the basic model without RL (i.e., Benchmark) and three RL based methods that run on top of the basic model, is evaluated experimentally. Experimental results verify that obviously higher 3D positioning accuracy is achieved by implementing any proposed RL based methods compared with the benchmark. The best performance is obtained when using the third RL based method that runs RL2 and RL1 sequentially. For the testbed that emulates a typical office environment with a height difference between the receiver and the transmitter ranging from 140 cm to 200 cm, an average 3D positioning error of 2.6 cm is reached by the best RL method, demonstrating at least 20% improvement compared to the basic model without performing RL.

Iterative point-wise reinforcement learning for highly accurate indoor visible light positioning.

Iterative point-wise reinforcement learning (IPWRL) is proposed for highly accurate indoor visible light positioning (VLP). By properly updating the height information in an iterative fashion, the IPWRL not only effectively mitigates the impact of non-deterministic noise but also exhibits excellent tolerance to deterministic errors caused by the inaccurate a priori height information. The principle of the IPWRL is explained, and the performance of the IPWRL is experimentally evaluated in a received signal strength (RSS) based VLP system and compared with other positioning algorithms, including the conventional RSS algorithm, the k-nearest neighbors (KNN) algorithm and the PWRL algorithm where iterations exclude. Unlike the supervised machine learning method, e.g., the KNN, whose performance is highly dependent on the training process, the proposed IPWRL does not require training and demonstrates robust positioning performance for the entire tested area. Experimental results also show that when a large height information mismatch occurs, the IPWRL is able to first correct the height information and then offers robust positioning results with a rather low positioning error, while the positioning errors caused by the other algorithms are significantly higher.

Multi-channel collision-free reception for optical interconnects.

A multi-channel reception scheme that allows each node to receive an arbitrary set of wavelengths simultaneously (i.e., collision-free) is proposed for optical interconnects. The proposed scheme only needs to use a few receivers and fixed-wavelength filters that are designed based on error-control coding theory. Experiments with up to four channel collision-free reception units are carried out to demonstrate the feasibility of the proposed scheme.

Nonlinearity-aware 200 Gbit/s DMT transmission for C-band short-reach optical interconnects with a single packaged electro-absorption modulated laser.

We experimentally demonstrate the transmission of a 200 Gbit/s discrete multitone (DMT) at the soft forward error correction limit in an intensity-modulation direct-detection system with a single C-band packaged distributed feedback laser and traveling-wave electro absorption modulator (DFB-TWEAM), digital-to-analog converter and photodiode. The bit-power loaded DMT signal is transmitted over 1.6 km standard single-mode fiber with a net rate of 166.7 Gbit/s, achieving an effective electrical spectrum efficiency of 4.93 bit/s/Hz. Meanwhile, net rates of 174.2 Gbit/s and 179.5 Gbit/s are also demonstrated over 0.8 km SSMF and in an optical back-to-back case, respectively. The feature of the packaged DFB-TWEAM is presented. The nonlinearity-aware digital signal processing algorithm for channel equalization is mathematically described, which improves the signal-to-noise ratio up to 3.5 dB.

China's Health Reform Update.

China experienced both economic and epistemological transitions within the past few decades, greatly increasing demand for accessible and affordable health care. These shifts put significant pressure on the existing outdated, highly centralized bureaucratic system. Adjusting to growing demands, the government has pursued a new round of health reforms since the late 2000s; the main goals are to reform health care financing, essential drug policies, and public hospitals. Health care financing reform led to universal basic medical insurance, whereas the public hospital reform required more complex measures ranging from changes in regulatory, operational, and service delivery settings to personnel management. This article reviews these major policy changes and the literature-based evidence of the effects of reforms on cost, access, and quality of care. It then highlights the outlook for future reforms. We argue that a better understanding of the unintended consequences of reform policies and of how practitioners' and patients' interests can be better aligned is essential for reforms to succeed.

Low-complexity frequency domain nonlinear compensation for OFDM based high-speed visible light communication systems with light emitting diodes.

A novel frequency domain nonlinear compensation method, FD-NC, is proposed for orthogonal frequency division multiplexing (OFDM) based visible light communication (VLC) system. By tackling the memory nonlinear impairments from light emitting diodes (LEDs) in the frequency domain rather than in the time domain, the proposed method has much lower computational complexity than the conventional time domain Volterra nonlinear compensation method (TD-NC). Both theoretical derivation and experimental investigation of the proposed method in OFDM based VLC systems with four types of commercial LEDs are presented. The results of experiments show that the proposed low-complexity FD-NC method with a moderate truncation factor achieves a performance comparable to that of the TD-NC. The application of FD-NC method in the bit-power loading OFDM VLC system is also experimentally demonstrated. Compared with the linear equalization case, at a bit error rate (BER) of 3.8 × 10-3 (a), the transmission distance of a 960 Mbps VLC system can be extended from 0.7 m to 1.8 m by the FD-NC, and (b) the achievable system capacity can be enhanced by 18.7%~36.5% for transmission distance in the range of 0.5 m~2 m with the FD-NC. The complexity analysis shows that the required number of real-valued multiplications (RNRM) of the FD-NC is independent of linear or nonlinear memory length. The reduction of RNRM achieved by the FD-NC over the TD-NC becomes more profound for a larger nonlinear memory length or a smaller truncation factor.

Integrated wavelength conversion for adaptively modulated WDM-OFDM signals in a silicon waveguide.

All-optical wavelength conversion for 2×11.64 GBaud adaptively-modulated orthogonal frequency division multiplexing (AM-OFDM) signals with QPSK/16QAM formats is experimentally demonstrated in a silicon waveguide. The AM-OFDM signal with partly higher- (and lower-) order formats on lower- (and higher-) frequency subcarriers has better overall conversion performance in receiving optical signal-to-noise ratio and power penalty. In comparison with the OFDM-QPSK signal, at the BER of 3.8×10-3, the bit rate increases 11.64 Gbit/s per channel almost without conversion power penalty increased by replacing the QPSK sequence with the 16QAM sequence on half subcarriers.

Changes of regulatory T cells, transforming growth factor-beta and interleukin-10 in patients with type 1 diabetes mellitus: A systematic review and meta-analysis.

Regulatory T lymphocyte cells (Treg) associated with interleukin-10 (IL-10) and transforming growth factor-ß (TGF-ß) have implicated in the development of type 1 diabetes mellitus (T1DM), yet the existing evidence remains unclear. Hereby we performed a systematic review and meta-analysis to characterize the changes in T1DM patients. A total of 1407 T1DM patients and 1373 healthy controls from 40 case-control studies were eventually included in the pooling analysis. Compared with the controls, T1DM patients had decreased frequency of CD4(+)CD25(+)Treg (p=0.0003), CD4(+)CD25(+)Foxp3(+)Treg (p=0.020), and the level of TGF-ß (p=0.030). Decrease in IL-10 (p=0.14) was not significant. All the changes remained significant when the studies with low NOS scores and publication bias were excluded. In conclusion, peripheral Treg and serum TGF-ß are reduced in type 1 diabetes mellitus whereas changes in serum IL-10 are not significant.

Low-complexity linewidth-tolerant time domain sub-symbol optical phase noise suppression in CO-OFDM systems.

Two linewidth-tolerant optical phase noise suppression algorithms, non-decision aided sub-symbol optical phase noise suppression (NDA-SPS) and partial-decision aided sub-symbol optical phase noise suppression (PDA-SPS), based on low-complexity time domain sub-symbol processing are proposed for coherent optical orthogonal frequency division multiplexing (CO-OFDM) systems. High accuracy carrier phase estimation is achieved in the NDA-SPS algorithm without decision error propagation. Compared with NDA-SPS, partial-decision aided estimation is introduced in PDA-SPS to reduce the pilot-overhead by half, yet only a small performance degradation is induced. The principles and computational complexities of the proposed algorithms are theoretically analyzed. By adopting specially designed comb-type pilot subcarriers, multiplier-free observation-based matrix generation is realized in the proposed algorithms. Computationally intensive discrete Fourier transform (DFT) or inverse DFT (IDFT) operations, which are usually carried out in other high-performance inter-carrier-interference (ICI) mitigation algorithms multiple times, are completely avoided. Compared with several other sub-symbol algorithms, the proposed algorithms with lower complexities offer considerably larger laser linewidth tolerances as demonstrated by Monte-Carlo simulations. Numerical analysis verifies that the optimal performance of PDA-SPS can be achieved with moderate numbers of sub-symbols.

Low-complexity optical phase noise suppression in CO-OFDM system using recursive principal components elimination.

A low-complexity optical phase noise suppression approach based on recursive principal components elimination, R-PCE, is proposed and theoretically derived for CO-OFDM systems. Through frequency domain principal components estimation and elimination, signal distortion caused by optical phase noise is mitigated by R-PCE. Since matrix inversion and domain transformation are completely avoided, compared with the case of the orthogonal basis expansion algorithm (L = 3) that offers a similar laser linewidth tolerance, the computational complexities of multiple principal components estimation are drastically reduced in the R-PCE by factors of about 7 and 5 for q = 3 and 4, respectively. The feasibility of optical phase noise suppression with the R-PCE and its decision-aided version (DA-R-PCE) in the QPSK/16QAM CO-OFDM system are demonstrated by Monte-Carlo simulations, which verify that R-PCE with only a few number of principal components q ( = 3) provides a significantly larger laser linewidth tolerance than conventional algorithms, including the common phase error compensation algorithm and linear interpolation algorithm. Numerical results show that the optimal performance of R-PCE and DA-R-PCE can be achieved with a moderate q, which is beneficial for low-complexity hardware implementation.

Linearly interpolated sub-symbol optical phase noise suppression in CO-OFDM system.

An optical phase noise suppression algorithm, LI-SCPEC, based on phase linear interpolation and sub-symbol processing is proposed for CO-OFDM system. By increasing the temporal resolution of carrier phase tracking through dividing one symbol into several sub-blocks, i.e., sub-symbols, inter-carrier-interference (ICI) mitigation is achieved in the proposed algorithm. Linear interpolation is employed to obtain a reliable temporal reference for sub-symbol phase estimation. The new algorithm, with only a few number of sub-symbols (N(B) = 4), can provide a considerably larger laser linewidth tolerance than several other ICI mitigation algorithms as demonstrated by Monte-Carlo simulations. Numerical analysis verifies that the best performance is achieved with an optimal and moderate number of sub-symbols. Complexity analysis shows that the required number of complex-valued multiplications is independent of the number of sub-symbols used in the proposed algorithm.

Passive optical interconnects at top of the rack: offering high energy efficiency for datacenters.

This paper introduces a new concept, namely passive optical interconnect at top of the rack in the datacenter networks, and investigates several architectures, which use only passive optical components to interconnect different servers. In such a manner, the proposed schemes are able to offer higher bandwidth and significantly improve energy efficiency compared to their electronic counterpart that is based on commodity switches. The proposed passive optical interconnect schemes are experimentally demonstrated in order to validate the transmission performance. Besides, an assessment in terms of energy consumption and cost has also been carried out, which shows our proposed concept can significantly outperform the conventional commodity switches on energy efficiency while keeping the cost in the similar level.

The economic effect of financial compensation in China's healthcare system: comprehensive insights regarding supply and demand factors.

OBJECTIVES: We aim to analyse the effects of government subsidies on residents' health and healthcare expenditure from the perspectives of supply and demand. DATA AND METHODS: According to the regional division adopted in the data query system of the National Bureau of Statistics, this study divides 31 provinces and cities into three regions: eastern, central, and western. The data used are from public databases, such as the "China Statistical Yearbook," "China Health Statistical Yearbook," and "Government Final Account Report". In this study, mathematical model derivation is used to construct a fixed effects model, and an empirical study based on cross-sectional data and general linear regression is conducted. To prevent endogeneity issues, this study introduces instrumental variables and uses 2SLS regression to further analyse the output results. RESULTS: For every 1% increase in supplementary funding on the supply side, the perinatal mortality rate decreases by 1.765%, while for every 1% increase in financial compensation on the demand side, per capita outpatient expenses increase by 0.225% and per capita hospitalization expenses increase by 0.196%. Regarding medical resources, for every 1% increase in the number of beds per 1,000 people, per capita hospitalization expenses decrease by 0.099%. In the central and eastern regions, where economic levels are higher, supply-side government funding is more effective than demand-side funding. In contrast, demand-side funding is more effective in the western region. CONCLUSIONS: The roles of multiple influencing factors and significant regional heterogeneity are clarified. Increasing financial compensation to providers positively impacts perinatal mortality but leads to higher per capita outpatient and hospital expenditures. Finally, this study provides targeted policy recommendations and solid theoretical support for policymakers.

Attenuation of fibroblast activation and fibrosis by adropin in systemic sclerosis.

Fibrotic diseases impose a major socioeconomic challenge on modern societies and have limited treatment options. Adropin, a peptide hormone encoded by the energy homeostasis-associated (ENHO) gene, is implicated in metabolism and vascular homeostasis, but its role in the pathogenesis of fibrosis remains enigmatic. Here, we used machine learning approaches in combination with functional in vitro and in vivo experiments to characterize adropin as a potential regulator involved in fibroblast activation and tissue fibrosis in systemic sclerosis (SSc). We demonstrated consistent down-regulation of adropin/ENHO in skin across multiple cohorts of patients with SSc. The prototypical profibrotic cytokine TGFß reduced adropin/ENHO expression in a JNK-dependent manner. Restoration of adropin signaling by therapeutic application of bioactive adropin34-76 peptides in turn inhibited TGFß-induced fibroblast activation and fibrotic tissue remodeling in primary human dermal fibroblasts, three-dimensional full-thickness skin equivalents, mouse models of bleomycin-induced pulmonary fibrosis and sclerodermatous chronic graft-versus-host-disease (sclGvHD), and precision-cut human skin slices. Knockdown of GPR19, an adropin receptor, abrogated the antifibrotic effects of adropin in fibroblasts. RNA-seq demonstrated that the antifibrotic effects of adropin34-76 were functionally linked to deactivation of GLI1-dependent profibrotic transcriptional networks, which was experimentally confirmed in vitro, in vivo, and ex vivo using cultured human dermal fibroblasts, a sclGvHD mouse model, and precision-cut human skin slices. ChIP-seq confirmed adropin34-76-induced changes in TGFß/GLI1 signaling. Our study characterizes the TGFß-induced down-regulation of adropin/ENHO expression as a potential pathomechanism of SSc as a prototypical systemic fibrotic disease that unleashes uncontrolled activation of profibrotic GLI1 signaling.

Risk of hepatitis B reactivation in HBsAg-/HBcAb+ patients after biologic or JAK inhibitor therapy for rheumatoid arthritis: A meta-analysis.

BACKGROUND: The risk of hepatitis B virus (HBV) reactivation after biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) therapy in patients with rheumatoid arthritis (RA) combined with HBsAg-/HBcAb+ is still inconsistent. METHODS: We conducted a systematic review of existing databases from 1977 to August 22, 2021. Studies of RA patients combined with HBsAg-/HBcAb +, treated with b/tsDMARDs and the reported number of HBV reactivation were included. RESULTS: We included 26 studies of 2252 HBsAg-/HBcAb+ RA patients treated with b/tsDMARDs. The pooled HBV reactivation rate was 2.0% (95% confidence interval [CI]: 0.01-0.04; I2 = 66%, p < .01). In the subgroup analysis, the HBV reactivation rate of rituximab (RTX), abatacept, and inhibitors of Janus kinase (JAK), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were 9.0% (95% CI: 0.04-0.15; I2 = 61%, p = .03), 6.0% (95% CI: 0.01-0.13; I2 = 40%, p = .19), 1.0% (95% CI: 0.00-0.03; I2 = 41%, p = .19), 0.0% (95% CI: 0.00-0.02; I2 = 0%, p = .43), 0.0% (95% CI: 0.00-0.01; I2 = 0%, p = .87), respectively. While HBsAb- patients have a significant risk of reactivation (odds ratio [OR] = 4.56, 95% CI = 2.45-8.48; I2 = 7%, p = .37), low HBsAb+ group also display a significant risk of reactivation (OR = 5.45, 95% CI: 1.35-21.94; I2 = 0%, p = .46). CONCLUSIONS: This meta-analysis demonstrates the highest potential risk of HBV reactivation in HBsAg-/HBcAb+ RA patients receiving RTX treatment, especially HBsAb- patients. Our study furthers the understanding of the prophylactic use of anti-HBV drugs in such patients. However, it is relative safety to use the inhibitors of IL-6, TNF-α, and JAK in these patients.

Elevated serum creatinine levels and risk of cognitive impairment in older adults with diabetes: a NHANES study from 2011-2014.

Background: The brain and kidney have similar microvascular structure, which makes them susceptible to certain common pathophysiological processes. In this study, we examined several indicators of kidney injury/function associated with cognitive function in older diabetic patients in the hope of finding effective markers for detecting cognitive impairment (CI). Methods: A total of 2209 older participants (aged ≥60 years) from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) were analyzed for the association between diabetes and CI using a multiple linear regression analysis model. Using the same approach, we also analyzed the relationship between indicators of kidney injury/function and cognitive function (Animal Fluency Test, Digit Symbol Substitution Test) in the diabetic population. Results: Diabetes was associated with CI. In age-adjusted model, older diabetics performed significantly poorer on tests of cognitive function compared to normoglycaemic individuals (1.145 points lower on the Animal Fluency Test (P = 0.005) and 7.868 points reduced on the Digit Symbol Substitution Test (P < 0.001)). In diabetics, we found elevated serum creatinine (SCr) (especially at SCr≥300uM) was associated with lower scores on cognitive function tests after strict adjustment for potential influences on cognitive function. While, albumin/creatinine ratio (ACR) was only associated with Digit Symbol Substitution score (DSS) not Animal Fluency score (AFS), and estimated glomerular filtration rate (eGFR) was only associated with CI (AFS and DSS) at the end-stage renal disease. Conclusion: SCr, as a sensitive indicator of kidney injury, was significantly associated with CI and can potentially be used as an effective marker for screening CI in older diabetics.

Identification of a Distinct Monocyte-Driven Signature in Systemic Sclerosis Using Biophysical Phenotyping of Circulating Immune Cells.

OBJECTIVE: Pathologically activated circulating immune cells, including monocytes, play major roles in systemic sclerosis (SSc). Their functional characterization can provide crucial information with direct clinical relevance. However, tools for the evaluation of pathologic immune cell activation and, in general, of clinical outcomes in SSc are scarce. Biophysical phenotyping (including characterization of cell mechanics and morphology) provides access to a novel, mostly unexplored layer of information regarding pathophysiologic immune cell activation. We hypothesized that the biophysical phenotyping of circulating immune cells, reflecting their pathologic activation, can be used as a clinical tool for the evaluation and risk stratification of patients with SSc. METHODS: We performed biophysical phenotyping of circulating immune cells by real-time fluorescence and deformability cytometry (RT-FDC) in 63 SSc patients, 59 rheumatoid arthritis (RA) patients, 28 antineutrophil cytoplasmic antibody-associated vasculitis (AAV) patients, and 22 age- and sex-matched healthy donors. RESULTS: We identified a specific signature of biophysical properties of circulating immune cells in SSc patients that was mainly driven by monocytes. Since it is absent in RA and AAV, this signature reflects an SSc-specific monocyte activation rather than general inflammation. The biophysical properties of monocytes indicate current disease activity, the extent of skin or lung fibrosis, and the severity of manifestations of microvascular damage, as well as the risk of disease progression in SSc patients. CONCLUSION: Changes in the biophysical properties of circulating immune cells reflect their pathologic activation in SSc patients and are associated with clinical outcomes. As a high-throughput approach that requires minimal preparations, RT-FDC-based biophysical phenotyping of monocytes can serve as a tool for the evaluation and risk stratification of patients with SSc.

Amelioration of Fibrotic Remodeling of Human 3-Dimensional Full-Thickness Skin by Transglutamase 2 Inhibition.

OBJECTIVE: Fibrotic tissues are characterized by excessive crosslinking between extracellular matrix (ECM) proteins, rendering them more resistant to degradation. Although increased crosslinking of ECM is thought to play an important role for progression of tissue fibrosis, enhanced ECM crosslinking has not yet been targeted therapeutically in systemic sclerosis (SSc). Here, we investigated the role of transglutaminase 2 (TG2), a central crosslinking enzyme, in the activation of SSc fibroblasts. METHODS: We assessed TG2 expression and activity using TG2 staining, Western blotting, and TG2 activity assays. We inhibited TG2 in fibroblasts cultured under standard 2-dimensional conditions and in a 3-dimensional full-thickness equivalent skin model using monoclonal inhibitory anti-TG2 antibodies. RESULTS: TG2 expression was increased in the skin of patients with SSc compared with healthy controls, with levels particularly high in patients with SSc-associated interstitial lung disease. TG2 expression and TG2 activity were also increased in SSc dermal fibroblasts. Moreover, the levels of circulating TG2 in the plasma samples from SSc patients were increased versus samples from healthy controls. Anti-TG2 antibodies did not show consistent antifibrotic effects across different fibroblast cell lines under 2-dimensional culture conditions; however, anti-TG2 antibodies effectively reduced transforming growth factor ß-induced dermal thickening, myofibroblast differentiation, and collagen accumulation in the 3-dimensional full-thickness model of human skin. CONCLUSION: We provide the first evidence, to our knowledge, that inhibition of TG2 might be a potential antifibrotic approach in SSc. Our findings have translational potential as anti-TG2 antibodies are currently evaluated in a phase II clinical trial in chronic allograft injury and would thus be available for clinical studies in SSc (ClinicalTrials.gov identifier: NCT04335578).

Engrailed 1 coordinates cytoskeletal reorganization to induce myofibroblast differentiation.

Transforming growth factor-ß (TGFß) is a key mediator of fibroblast activation in fibrotic diseases, including systemic sclerosis. Here we show that Engrailed 1 (EN1) is reexpressed in multiple fibroblast subpopulations in the skin of SSc patients. We characterize EN1 as a molecular amplifier of TGFß signaling in myofibroblast differentiation: TGFß induces EN1 expression in a SMAD3-dependent manner, and in turn, EN1 mediates the profibrotic effects of TGFß. RNA sequencing demonstrates that EN1 induces a profibrotic gene expression profile functionally related to cytoskeleton organization and ROCK activation. EN1 regulates gene expression by modulating the activity of SP1 and other SP transcription factors, as confirmed by ChIP-seq experiments for EN1 and SP1. Functional experiments confirm the coordinating role of EN1 on ROCK activity and the reorganization of cytoskeleton during myofibroblast differentiation, in both standard fibroblast culture systems and in vitro skin models. Consistently, mice with fibroblast-specific knockout of En1 demonstrate impaired fibroblast-to-myofibroblast transition and are partially protected from experimental skin fibrosis.

Demonstration of optical steganography transmission using temporal phase coded optical signals with spectral notch filtering.

A novel approach is proposed and experimentally demonstrated for optical steganography transmission in WDM networks using temporal phase coded optical signals with spectral notch filtering. A temporal phase coded stealth channel is temporally and spectrally overlaid onto a public WDM channel. Direct detection of the public channel is achieved in the presence of the stealth channel. The interference from the public channel is suppressed by spectral notching before the detection of the optical stealth signal. The approach is shown to have good compatibility and robustness to the existing WDM network for optical steganography transmission.