Chip-to-chip ODDM network with optically enabled equalization

We propose and model an optical communication scheme for short distance datacom links based on the distribution of information across a wide comb spectrum. This modulation format, orthogonal delay division multiplexing, allows the multiplexing of data streams from multiple modulators, as well as the deserialization and equalization of the data in the optical domain. A concrete communication system, that allows the transport of 400 Gb/s across a single CWDM channel with a single 80 GHz cutoff lithium niobate on insulator modulator, is modeled under consideration of all noise sources present in the system and its sensitivity to group velocity dispersion is analyzed. Data is deserialized and equalized at the receiver with a 5-tap optical equalizer. This communication architecture may provide a path forward to implement high-baud-rate signaling in short-reach optical links without requiring high-speed ADCs and electronic deserializers at the receiver, thus maintaining the in-package power consumption at manageable levels

Distribution of different HBV DNA forms in plasma and peripheral blood mononuclear cells (PBMCs) of chronically infected patients with low or undetectable HBV plasma viremia

Few studies have documented hepatitis B virus (HBV) DNA in peripheral blood mononuclear cells (PBMCs). We developed real-time PCR methods for differential amplification of covalently closed circular (cccDNA) and total HBV DNA (tDNA). The different distribution of cccDNA and tDNA in plasma and PBMCs was evaluated in 37 patients with low or undetectable viremia. Plasma tDNA measured by the Abbott reference system and the in-house assay correlated well (Spearman rho = 0.804; P<0.0001). tDNA was detected in four PBMC samples, all from patients with detectable plasma viremia (range 633-6,406 IU/ml), cccDNA was not detected in any sample. The reasons for apparently discrepant results need further investigation but possibly include the high diversification of HBV status and plasma viremia levels

Semiconductor laser mode locking stabilization with optical feedback from a silicon PIC

Semiconductor mode-locked lasers can be used in a variety of applications ranging from multi-carrier sources for WDM communication systems to time base references for metrology. Their packaging in compact chip- or module-level systems remains however burdened by their strong sensitivity to back-reflections, quickly destroying the coherence of the mode-locking. Here, we investigate the stabilization of mode-locked lasers directly edge coupled to a silicon photonic integrated circuit, with the objective of moving isolators downstream to the output of the photonic circuit. A 2.77 kHz 3 dB RF linewidth, substantially improved compared to the 15.01 kHz of the free running laser, is obtained in the best case. Even in presence of detrimental reflections from the photonic circuit, substantial linewidth reductions from 20 kHz to 8.82 kHz, from 572 kHz to 14.8 kHz, and from 1.5 MHz to 40 kHz are realized

Stability of unfrozen whole blood DNA for remote genotypic analysis of HIV-1 coreceptor tropism

Maraviroc is an HIV-1 coreceptor antagonist that has shown good efficacy and tolerability in treatment-naive and treatment-experienced patients harboring CCR5-tropic virus. The use of Maraviroc in treatment simplification in patients with suppressed plasma HIV-1 RNA requires analysis of HIV-1 DNA. Coreceptor tropism testing is often performed remotely at reference laboratories. In this study paired whole blood stored at + 4 °C and at-20°C were compared as a source for genotypic coreceptor tropism testing

Mode-locked laser timing jitter limitation in optically enabled, spectrally sliced ADCs

Novel analog-to-digital converter (ADC) architectures are motivated by the demand for rising sampling rates and effective number of bits (ENOB). The main limitation on ENOB in purely electrical ADCs lies in the relatively high jitter of oscillators, in the order of a few tens of fs for state-of-the-art components. When compared to the extremely low jitter obtained with best-in-class Ti:sapphire mode-locked lasers (MLL), in the attosecond range, it is apparent that a mixed electrical-optical architecture could significantly improve the converters' ENOB. We model and analyze the ENOB limitations arising from optical sources in optically enabled, spectrally sliced ADCs, after discussing the system architecture and implementation details. The phase noise of the optical carrier, serving for electro-optic signal transduction, is shown not to propagate to the reconstructed digitized signal and therefore not to represent a fundamental limit. The optical phase noise of the MLL used to generate reference tones for individual slices also does not fundamentally impact the converted signal, so long as it remains correlated among all the comb lines. On the other hand, the timing jitter of the MLL, as also reflected in its RF linewidth, is fundamentally limiting the ADC performance, since it is directly mapped as jitter to the converted signal. The hybrid nature of a photonically enabled, spectrally sliced ADC implies the utilization of a number of reduced bandwidth electrical ADCs to convert parallel slices, resulting in the propagation of jitter from the electrical oscillator supplying their clock. Due to the reduced sampling rate of the electrical ADCs, as compared to the overall system, the overall noise performance of the presented architecture is substantially improved with respect to a fully electrical ADC

Evaluation of HIV-1 integrase resistance emergence and evolution in patients treated with integrase inhibitors.

Abstract Objectives We evaluated the emergence of mutations associated to integrase strand transfer inhibitors (INSTI) resistance (INSTI-RMs) and the integrase evolution in HIV-1 infected patients treated with this drug class. Methods Emergence of INSTI-RMs and integrase evolution (estimated as genetic distance between integrase sequences under-INSTI and before-INSTI treatment) were evaluated in 107 INSTI-naive patients (19 drug-naive and 88 drug-experienced) with two plasma genotypic resistance tests available: one before and one under INSTI treatment. A logistic regression analysis was performed to evaluate factors associated with the integrase evolution under INSTI treatment. Results Patients were mainly infected by B subtype (72.0%). 87 patients were treated with raltegravir, 13 with dolutegravir and 7 with elvitegravir. Before INSTI treatment, one patient harboured the major INSTI-RM R263 K, and three patients the accessory INSTI-RMs T97A. Under INSTI treatment, the emergence of ≥1 INSTI-RM was found in 39 (36.4%) patients. The major INSTI-RMs which emerged more frequently were: N155H (17.8%), G140S (8.4%), Y143R (7.5%), Q148H (6.5%), Y143C (4.7%). Concerning integrase evolution, a higher genetic distance was found in patients with ≥1 INSTI-RM compared to those without emergence of resistance (0.024 [0.012-0.036] vs. 0.015 [0.009-0.024], p = 0.018). This higher integrase evolution was significantly associated with a longer duration of HIV-1 infection, a higher number of past regimens and non-B subtypes. Conclusions Our findings confirmed that in INSTI-naive patients, major INSTI-RMs occur very rarely. Under INSTI treatment, selection of drug-resistance follows the typical drug-resistance pathways; a higher evolution characterizes integrase sequences developing drug-resistance compared to those without any resistance

Switch to maraviroc with darunavir/r, both QD, in patients with suppressed HIV-1 was well tolerated but virologically inferior to standard antiretroviral therapy: 48-Week results of a randomized trial

Objectives Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption) per protocol at week 48. Methods Patients on 3-drug ART with stable HIV-1 RNA <50 copies/mL and CCR5-tropic virus were randomized 1:1 to maraviroc with darunavir/ritonavir qd (study arm) or continue current ART (continuation arm).Results In June 2015, 115 patients were evaluable for the primary outcome (56 study, 59 continuation arm). The study was discontinued due to excess of VF in the study arm (7 cases, 12.5%, vs 0 in the continuation arm, p = 0.005). The proportion free of treatment failure was 73.2% in the study and 59.3% in the continuation arm. Two participants in the study and 10 in the continuation arm discontinued therapy due to adverse events (p = 0.030). At VF, no emergent drug resistance was detected. Co-receptor tropism switched to non-R5 in one patient. Patients with VF reported lower adherence and had lower plasma drug levels. Femoral bone mineral density was significantly improved in the study arm. Conclusion Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therap

Optically Enabled ADCs and Application to Optical Communications

Electrical-optical signal processing has been shown to be a promising path to overcome the limitations of state-of-the-art all-electrical data converters. In addition to ultra-broadband signal processing, it allows leveraging ultra-low jitter mode-locked lasers and thus increasing the aperture jitter limited effective number of bits at high analog signal frequencies. In this paper, we review our recent progress towards optically enabled time- and frequency-interleaved analog-to-digital converters, as well as their monolithic integration in electronic-photonic integrated circuits. For signal frequencies up to 65 GHz, an optoelectronic track-and-hold amplifier based on the source-emitter-follower architecture is shown as a power efficient approach in optically enabled BiCMOS technology. At higher signal frequencies, integrated photonic filters enable signal slicing in the frequency domain and further scaling of the conversion bandwidth, with the reconstruction of a 140 GHz optical signal being shown. We further show how such optically enabled data converter architectures can be applied to a nonlinear Fourier transform based integrated transceiver in particular and discuss their applicability to broadband optical links in general

Early versus delayed antiretroviral therapy based on genotypic resistance test: Results from a large retrospective cohort study

Rapid start of antiretroviral therapy (ART) pending genotypic resistance test (GRT) has been recently proposed, but the effectiveness of this strategy is still debated. The rate of virological success (VS), defined as HIV-RNA\u2009<\u200950 copies/ml, with and without GRT was compared in drug-na\uefve individuals enrolled in the Italian ARCA cohort who started ART between 2015 and 2018. 521 individuals started ART: 397 without GRT (pre-GRT group) and 124 following GRT (post-GRT group). Overall, 398 (76%) were males and 30 (6%) were diagnosed with AIDS. In the pre-GRT group, baseline CD4+\u2009cell counts were lower (p\u2009<\u20090.001), and viral load was higher (p\u2009<\u20090.001) than in the post-GRT group. The estimated probability of VS in pre-GRT versus post-GRT group was 72.54% (CI95 : 67.78-76.60) versus 66.94% (CI95 : 57.53-74.26) at Week 24 and 92.40% (CI95 : 89.26-94.62) versus 92.92% (CI95 : 86.35-96.33) at Week 48, respectively (p\u2009=\u20090.434). At Week 48, VS was less frequent among individuals with baseline CD4+\u2009cell counts <200 versus >500 (90.33% vs. 97.33%), log viral load <5.00 versus >5.70 log10 cps/ml (97.17% vs 78.16%; p\u2009<\u20090.001), and those treated with protease inhibitors or non-nucleoside reverse transcriptase inhibitors versus those treated with integrase strand transfer inhibitors (p\u2009<\u20090.001). The rate of VS does not seem to be affected by an early ART initiation pending GRT results, but it could be influenced by the composition of the ART regimen, as well as immuno-virological parameters