Optical amplification-free deep reservoir computing-assisted high-baudrate short-reach communication.

An optical amplification-free deep reservoir computing (RC)-assisted high-baudrate intensity modulation direct detection (IM/DD) system is experimentally demonstrated using a 100G externally modulated laser operated in C-band. We transmit 112 Gbaud 4-level pulse amplitude modulation (PAM4) and 100 Gbaud 6-level PAM (PAM6) signals over a 200-m single-mode fiber (SMF) link without any optical amplification. The decision feedback equalizer (DFE), shallow RC, and deep RC are adopted in the IM/DD system to mitigate impairment and improve transmission performance. Both PAM transmissions over a 200-m SMF with bit error rate (BER) performance below 6.25% overhead hard-decision forward error correction (HD-FEC) threshold are achieved. In addition, the BER of the PAM4 signal is below the KP4-FEC limit after 200-m SMF transmission enabled by the RC schemes. Thanks to the use of a multiple-layer structure, the number of weights in deep RC has been reduced by approximately 50% compared with the shallow RC, whereas the performance is comparable. We believe that the optical amplification-free deep RC-assisted high-baudrate link has a promising application in intra-data center communications.

High bitrate data transmission in the 8-14 µm atmospheric window using an external Stark-effect modulator with digital equalization.

High bitrate mid-infrared links using simple (NRZ) and multi-level (PAM-4) data coding schemes have been realized in the 8 µm to 14 µm atmospheric transparency window. The free space optics system is composed of unipolar quantum optoelectronic devices, namely a continuous wave quantum cascade laser, an external Stark-effect modulator and a quantum cascade detector, all operating at room-temperature. Pre- and post-processing are implemented to get enhanced bitrates, especially for PAM-4 where inter-symbol interference and noise are particularly detrimental to symbol demodulation. By exploiting these equalization procedures, our system, with a full frequency cutoff of 2 GHz, has reached transmission bitrates of 12 Gbit/s NRZ and 11 Gbit/s PAM-4 fulfilling the 6.25 % overhead hard-decision forward error correction threshold, limited only by the low signal-to-noise ratio of our detector.

Simultaneous modulation format identification and OSNR monitoring based on optoelectronic reservoir computing.

An approach for simultaneous modulation format identification (MFI) and optical signal-to-noise ratio (OSNR) monitoring in digital coherent optical communications is proposed based on optoelectronic reservoir computing (RC) and the signal's amplitude histograms (AHs) obtained after the adaptive post-equalization. The optoelectronic RC is implemented using a Mach-Zehnder modulator and optoelectronic delay feedback loop. We investigate the performance of the proposed model with the number of symbols, bins of AHs and the hyperparameters of optoelectronic RC. The results show that 100% MFI accuracy can be achieved simultaneously with accurate OSNR estimation for different modulation formats under study. The lowest achievable OSNR estimation mean absolute errors for the dual-polarization (DP)-quadrature phase-shift keying signal, the DP-16-ary quadrature amplitude modulation (16QAM) signal, and the DP-64QAM signal are 0.2 dB, 0.32 dB and 0.53 dB, respectively. The robustness of the proposed scheme is also evaluated when the optoelectronic RC is in presence of additive white Gaussian noises. Then, a proof of concept experiment is demonstrated to further verify our proposed method. The proposed approach offers a potential solution for next-generation intelligent optical performance monitoring in the physical layer.

Effect of cardiosphere-derived cells on segmental myocardial function after myocardial infarction: ALLSTAR randomised clinical trial.

BACKGROUND: Most cell therapy trials failed to show an improvement in global left ventricular (LV) function measures after myocardial infarction (MI). Myocardial segments are heterogeneously impacted by MI. Global LV function indices are not able to detect the small treatment effects on segmental myocardial function which may have prognostic implications for cardiac events. We aimed to test the efficacy of allogeneic cardiosphere-derived cells (CDCs) for improving regional myocardial function and contractility. METHODS: In this exploratory analysis of a randomised clinical trial, 142 patients with post-MI with LVEF <45% and 15% or greater LV scar size were randomised in 2:1 ratio to receive intracoronary infusion of allogenic CDCs or placebo, respectively. Change in segmental myocardial circumferential strain (Ecc) by MRI from baseline to 6 months was compared between CDCs and placebo groups. RESULTS: In total, 124 patients completed the 6-month follow-up (mean (SD) age 54.3 (10.8) and 108 (87.1%) men). Segmental Ecc improvement was significantly greater in patients receiving CDC (-0.5% (4.0)) compared with placebo (0.2% (3.7), p=0.05). The greatest benefit for improvement in segmental Ecc was observed in segments containing scar tissue (change in segmental Ecc of -0.7% (3.5) in patients receiving CDC vs 0.04% (3.7) in the placebo group, p=0.04). CONCLUSIONS: In patients with post-MI LV dysfunction, CDC administration resulted in improved segmental myocardial function. Our findings highlight the importance of segmental myocardial function indices as an endpoint in future clinical trials of patients with post-MI. TRIAL REGISTRATION NUMBER: NCT01458405.

Novel intracoronary supersaturated oxygen treatment for anterior myocardial infarction.

Primary percutaneous coronary intervention (PCI) is now the recommended reperfusion technique for patients with acute ST-segment elevation myocardial infarction. However, despite early reperfusion in the majority of patients, PCI does not achieve effective myocardial reperfusion in a significant proportion of patients due to the prevalence of coronary microvascular obstruction. The amount of infarcted myocardium has been considered to be a reliable indicator of major adverse cardiovascular events and resultant adverse left ventricular remodeling. The purpose of this paper is to review the clinical benefits of supersaturated oxygen therapy following PCI for ST-segment elevation myocardial infarction.

Rare survival of left ventricular free wall rupture following myocardial infarction.

Myocardial free wall rupture is a rare but usually fatal complication of acute myocardial infarction (MI) especially if it occurs out of hospital and occurs in 2-4% of patients who suffer from acute MI. Rapid diagnosis is essential but not always easy as diagnostic tests may be inconclusive. In this case report authors examine a rare and unique patient survival after left ventricular free wall rupture following MI. The patient developed chest pain and hypotension in the hospital and was taken directly to the catheterization laboratory where a diagnostic angiogram showed a high-grade occlusion of a very small marginal branch, fluoroscopy demonstrated a large pericardial effusion, which was drained then auto transfused back to the patient using a femoral vein sheath. Rapid diagnostic testing including transesophageal echocardiography with Definity, transthoracic echocardiography, aortography and left ventriculography were all negative for dissection and rupture. Despite the negative diagnostic test, a high index of suspicion for rupture led to urgent surgical exploration where a large 4-cm hole was found in the lateral wall. Repair was successful and the patient left the hospital about several weeks later.

"Protocol for a phase 2, randomized, double-blind, placebo-controlled, safety and efficacy study of dutogliptin in combination with filgrastim in early recovery post-myocardial infarction": study protocol for a randomized controlled trial.

BACKGROUND: Regenerative therapies offer new approaches to improve cardiac function after acute ST-elevation myocardial infarction (STEMI). Previous trials using bone marrow cells, selected stem cell populations, or cardiac stem cell progenitors require invasive procedures and had so far inconclusive results. A less invasive approach utilizes granulocyte-colony stimulating factor (G-CSF) to mobilize stem cells to circulating blood and induce neovascularization and differentiation into endothelial cells and cardiomyocytes. Stromal cell-derived factor 1 alpha (SDF-1α) is an important chemokine for initiating stem cell migration and homing to ischemic myocardium. SDF-1α concentrations can be increased by inhibition of CD26/DPP4. Dutogliptin, a novel DPP4 inhibitor, combined with stem cell mobilization using G-CSF significantly improved survival and reduced infarct size in a murine model. METHODS: We test the safety and tolerability and efficacy of dutogliptin in combination with filgrastim (G-CSF) in patients with STEMI (EF < 45%) following percutaneous coronary intervention (PCI). Preliminary efficacy will be analyzed using cardiac magnetic resonance imaging (cMRI) to detect > 3.8% improvement in left ventricular ejection fraction (LV-EF) compared to placebo. One hundred forty subjects will be randomized to filgrastim plus dutogliptin or matching placebos. DISCUSSION: The REC-DUT-002 trial is the first to evaluate dutogliptin in combination with G-CSF in patients with STEMI. Results will lay the foundation for an appropriately powered cardiovascular outcome trial to test the efficacy of this combined pharmacological strategy. TRIAL REGISTRATION: EudraCT no.: 2018-000916-75 . Registered on 7 June 2018. IND number: 123717.

Intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR): a randomized, placebo-controlled, double-blinded trial.

AIMS: Cardiosphere-derived cells (CDCs) are cardiac progenitor cells that exhibit disease-modifying bioactivity in various models of cardiomyopathy and in previous clinical studies of acute myocardial infarction (MI), dilated cardiomyopathy, and Duchenne muscular dystrophy. The aim of the study was to assess the safety and efficacy of intracoronary administration of allogeneic CDCs in the multicentre, randomized, double-blinded, placebo-controlled, intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR) trial. METHODS AND RESULTS: We enrolled patients 4 weeks to 12 months after MI, with left ventricular ejection fraction (LVEF) ≤45% and LV scar size ≥15% of LV mass by magnetic resonance imaging (MRI). A pre-specified interim analysis was performed when 6-month MRI data were available. The trial was subsequently stopped due to the low probability of detecting a significant treatment effect of CDCs based on the primary endpoint. Patients were randomly allocated in a 2:1 ratio to receive CDCs or placebo in the infarct-related artery by stop-flow technique. The primary safety endpoint was the occurrence, during 1-month post-intracoronary infusion, of acute myocarditis attributable to allogeneic CDCs, ventricular tachycardia- or ventricular fibrillation-related death, sudden unexpected death, or a major adverse cardiac event (death or hospitalization for heart failure or non-fatal MI or need for left ventricular assist device or heart transplant). The primary efficacy endpoint was the relative percentage change in infarct size at 12 months post-infusion as assessed by contrast-enhanced cardiac MRI. We randomly allocated 142 eligible patients of whom 134 were treated (90 to the CDC group and 44 to the placebo group). The mean baseline LVEF was 40% and the mean scar size was 22% of LV mass. No primary safety endpoint events occurred. There was no difference in the percentage change from baseline in scar size (P = 0.51) between CDCs and placebo groups at 6 months. Compared with placebo, there were significant reductions in LV end-diastolic volume (P = 0.02), LV end-systolic volume (P = 0.02), and N-terminal pro b-type natriuretic peptide (NT-proBNP) (P = 0.02) at 6 months in CDC-treated patients. CONCLUSION: Intracoronary infusion of allogeneic CDCs in patients with post-MI LV dysfunction was safe but did not reduce scar size relative to placebo at 6 months. Nevertheless, the reductions in LV volumes and NT-proBNP reveal disease-modifying bioactivity of CDCs. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01458405.

400-Gb/s direct modulation using a DFB+R laser.

We demonstrate a direct-modulation and direct-detection system with a back-to-back line rate of 411.6 (net bit rate of 337.5) Gb/s using a 65 GHz DFB+R laser. The O-band laser with a chirp parameter of 0.6 supports dispersion-tolerant transmissions up to 15 km without an optical amplifier.

The Clinical Course and Management of Severe Esophagitis Dissecans Superficialis: A Case Report.

Esophagitis dissecans superficialis is a rare clinical endoscopic finding with poorly understood pathogenesis and ill-defined management. A 71-year-old man is admitted with progressively worsening dysphagia and odynophagia with endoscopic features most consistent with severe esophagitis dissecans superficialis. Extensive workup did not reveal an etiology, and he was subsequently treated with steroids, resulting in rapid, almost complete clinical and endoscopic recovery.

Real-time 100 Gbps/λ/core NRZ and EDB IM/DD transmission over multicore fiber for intra-datacenter communication networks.

A BiCMOS chip-based real-time intensity modulation/direct detection spatial division multiplexing system is experimentally demonstrated for both optical interconnects. 100 Gbps/λ/core electrical duobinary (EDB) transmission over 1 km 7-core multicore fiber (MCF) is carried out, achieving KP4 forward error correction (FEC) limit (BER < 2E-4). Using optical dispersion compensation, 7 × 100 Gbps/λ/core transmission of both non-return-to-zero (NRZ) and EDB signals over 10 km MCF transmission is achieved with BER lower than 7% overhead hard-decision FEC limit (BER < 3.8E-3). The integrated low complexity transceiver IC and analog signal processing approach make such a system highly attractive for the high-speed intra-datacenter interconnects.

Autologous CD34+ cell therapy improves exercise capacity, angina frequency and reduces mortality in no-option refractory angina: a patient-level pooled analysis of randomized double-blinded trials.

Aims: Autologous CD34+ (auto-CD34+) cells represent an attractive option for the treatment of refractory angina. Three double-blinded randomized trials (n = 304) compared intramyocardial (IM) auto-CD34+ cells with IM placebo injections to affect total exercise time (TET), angina frequency (AF), and major adverse cardiac events (MACE). Patient-level data were pooled from the Phase I, Phase II ACT-34, ACT-34 extension, and Phase III RENEW trials to determine the efficacy and safety of auto-CD34+ cells. Methods and results: Treatment effects for TET were analysed using an analysis of covariance mixed-effects model and for AF using Poisson regression in a log linear model with repeated measures. The Kaplan-Meier rate estimates for MACE were compared using the log-rank test. Autologous CD34+ cell therapy improved TET by 46.6 s [3 months, 95% confidence interval (CI) 13.0 s-80.3 s; P = 0.007], 49.5 s (6 months, 95% CI 9.3-89.7; P = 0.016), and 44.7 s (12 months, 95% CI - 2.7 s-92.1 s; P = 0.065). The relative frequency of angina was 0.78 (95% CI 0.63-0.98; P = 0.032), 0.66 (0.48-0.91; P = 0.012), and 0.58 (0.38-0.88; P = 0.011) at 3-, 6- and 12-months in auto-CD34+ compared with placebo patients. Results remained concordant when analysed by treatment received and when confined to the Phase III dose of 1 × 105 cells/kg. Autologous CD34 + cell therapy significantly decreased mortality (12.1% vs. 2.5%; P = 0.0025) and numerically reduced MACE (38.9% vs. 30.0; P = 0.14) at 24 months. Conclusion: Treatment with auto-CD34+ cells resulted in clinically meaningful durable improvements in TET and AF at 3-, 6- and 12-months, as well as a reduction in 24-month mortality in this patient-level meta-analysis.

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.

Public unawareness of physician reimbursement.

OBJECTIVES: To assess subjects' perception of healthcare costs and physician reimbursement. BACKGROUND: The lack of transparency in healthcare reimbursement leaves patients and physicians unaware of the distribution of health care dollars. METHODS: Anonymous survey-based study by means of convenience sampling. Participants were asked to estimate the total hospital cost and physician fee for one of the six medical procedures (n = 250). RESULTS: On the average for all 6 procedures, patients estimated the total cost was $36,177, ∼1,540% more than the actual Medicare rate of $7,333. Similarly, patients estimated the physician fee was $7,694, 1,474% more the actual Medicare rate of $589. CONCLUSION: Patients' perception of the total cost and physician fee are significantly higher than Medicare rates for all 6 procedures. This lack of insight may have widespread negative implications on the patient-physician relationship, on political trends to reduce physician reimbursement, and on a physician's desire to continue practicing medicine.

Gastrointestinal and Hepatic Disease in Fibromyalgia.

Fibromyalgia (FM) has historically been associated with several diseases in gastroenterology and hepatology. The most substantiated evidence pertains to irritable bowel syndrome (IBS). The pathogeneses of FM and IBS remain unclear, but it is likely related to dysregulation within the brain-gut axis, resulting in a hyperalgesic state. IBS and FM share other similarities, including a female predominance, fatigue, insomnia, and susceptibility to psychiatric state. These common manifestations and pathogeneses serve as a foundation for overlapping, multidisciplinary treatment modalities.

Digital mobile fronthaul employing differential pulse code modulation with suppressed quantization noise.

A differential pulse code modulation (DPCM) based digital mobile fronthaul architecture is proposed and experimentally demonstrated. By using a linear predictor in the DPCM encoding process, the quantization noise can be effectively suppressed and a prediction gain of 7~8 dB can be obtained. Experimental validation is carried out with a 20 km 15-Gbaud/λ 4-level pulse amplitude modulation (PAM4) intensity modulation and direct detection system. The results verify the feasibility of supporting 163, 122, 98, 81 20-MHz 4, 16, 64, 256 QAM based antenna-carrier (AxC) containers with only 3, 4, 5, 6 quantization bits at a sampling rate of 30.72MSa/s in LTE-A environment. Further increasing the number of quantization bits to 8 and 9, 1024 quadrature amplitude modulation (1024 QAM) and 4096 QAM transmission can be realized with error vector magnitude (EVM) lower than 1% and 0.5%, respectively. The supported number of AxCs in the proposed DPCM-based fronthaul is increased and the EVM is greatly reduced compared to the common public radio interface (CPRI) based fronthaul that uses pulse code modulation. Besides, the DPCM-based fronthaul is also experimentally demonstrated to support universal filtered multicarrier signal that is one candidate waveform for the 5th generation mobile systems.

Gigabit free-space multi-level signal transmission with a mid-infrared quantum cascade laser operating at room temperature.

Gigabit free-space transmissions are experimentally demonstrated with a quantum cascaded laser (QCL) emitting at mid-wavelength infrared of 4.65 µm, and a commercial infrared photovoltaic detector. The QCL operating at room temperature is directly modulated using on-off keying and, for the first time, to the best of our knowledge, four- and eight-level pulse amplitude modulations (PAM-4, PAM-8). By applying pre- and post-digital equalizations, we achieve up to 3 Gbit/s line data rate in all three modulation configurations with a bit error rate performance of below the 7% overhead hard decision forward error correction limit of 3.8×10-3. The proposed transmission link also shows a stable operational performance in the lab environment.