Distance measurement by delayed optical feedback in a ring laser

We numerically study the behavior of a semiconductor ring laser subject to bidirectional delayed optical feedback, when the isolated laser is in the quasi-unidirectional regime. The optical feedback, provided by two external refectors located in front of the ring output waveguides, can modify the laser regime produced by the cross-saturation between the clockwise and the counter-clockwise mode. Thus, the system exhibits new diferent regimes, most of which are asymmetric and bidirectional, with alternating dominant mode. Two of these regimes are of special interest in view of applications, because the laser switching period, between the clockwise and the counter-clockwise mode, is linearly related to the time of fight from the laser to one or both refectors. In these operating conditions, the laser is thus suitable to implement a telemeter. A convenient electrical output signal is obtained by a photodiode located behind one (partially refecting) fxed mirror, or by measuring the voltage drop across the laser junction. Simulations are performed by mathematical models based on rate-equations, assuming typical literature parameters for a 1 mW ring laser

Impact of resistance mutations on virological efficacy of DTG-based maintenance two-drug regimens: an ARCA cohort study

Background: Two-drug regimens (2DR) are largely prescribed as maintenance therapy, nowadays mainly based on DTG. While many data have been reported about PI-based 2DR, the impact of resistance mutations and duration of virological suppression on DTG-based 2DR remains to be clarified. The aim of this study was to evaluate the impact of resistance mutations on virological outcome of DTG-based 2DR maintenance ART. Material and methods: Virologically suppressed patients (pts) switching to DTG+3TC or DTG+RPV with pre-baseline (time of switch=baseline, BL) resistance genotype (at least PR/RT) were selected from the ARCA database. Primary endpoint was virological failure (VF: an HIV-RNA, VL, >200 cps/mL or 2 consecutive >50 cps/mL). The probability of VF was estimated by Kaplan-Meier analysis. Resistance to 2DR was defined as occurrence of at least Stanford HIVdb (v.8.5) low-level resistance (LLR) to at least one drug included in the current 2DR, based on cumulative genotype. CD4 changes were assessed using Student’s t- test for paired samples. A secondary analysis comparing 2DR with DTG-based 3D regimens was also performed. Results: A total of 318 2DR pts were analysed: 260 (82%) switching to DTG+3TC, 58 (18%) to DTG+RPV; 68% were males, median age was 51 (44-56) years, 12 (6-23) years of HIV infection, 5 (3-8) years of virological suppression, nadir CD4 231 (121-329), 5 (3-9) previous ARV lines, 59% previously exposed to INSTI, 11% with resistance to current 2DR. The integrase sequence was available in 14% of patients, none harbouring resistance to DTG. 20 VF were observed, of whom 4 (3/17 VF in DTG+3TC, 1/3 in DTG+RPV) in patients with at least LLR at BL (M184V+K219Q; D67N+K70R+K219Q; D67N+K70R+T215Y+219Q; E138A), in a median FU of 1.3 years (IQR 0.6-2). The 2-year estimated probability of VF was 8.7% (95% CI 4.4;13); 8.6% (4.1;13.1) in those without resistance and 9.7% (-4.4;23.8) in those with resistance (Log rank: p=ns, figure 1). No factor was significantly associated with VF at multivariate analysis, but in pts with <6 years of virological suppression, BL resistance was associated with a higher probability of VF (p=0.003). After 48 weeks, a statistically significant increase in CD4+ was detected (+56 cells/mmc, p<0.001), independently from baseline resistance. The 2-year estimated probability of VF in the reference 3DR group (n=564) was not different from that for the 2DR group: 8.8% (5.9;11.7) in the whole case file and 9.7% (6.6;12.8) in the presence of baseline resistance. Longer time of virological suppression was the only factor associated with a lower risk of VF in the 3DR dataset. Conclusions: DTG-based 2DRs show high virological efficacy, even in the context of predicted incomplete activity, at least within a short-term follow-up. A longer duration of virological suppression seems to decrease the impact of resistance on virological outcome, however further studies are warranted to confirm this hypothesis and possibly define a clinically useful threshold

Early Immunotherapy and Longer Corticosteroid Treatment Are Associated With Lower Risk of Relapsing Disease Course in Pediatric MOGAD

Background and Objectives We sought to identify early factors associated with relapse and outcome in paediatric-onset myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD). Methods In a multicenter retrospective cohort of pediatric MOGAD (≤18 years), onset features and treatment were compared in patients with monophasic vs relapsing disease (including cases with follow-up ≥12 months after onset or relapse at any time) and in patients with final Expanded Disability Status Scale (EDSS) 0 vs ≥1 at last follow-up (including cases with followup >3 months after last event or EDSS0 at any time). Multivariable logistic regression models were used to evaluate factors associated with relapsing disease course and EDSS ≥ 1 at final follow-up. Results Seventy-five children were included (median onset age 7 years; median 30 months of follow-up). Presentation with acute disseminated encephalomyelitis was more frequent in children aged 8 years or younger (66.7%, 28/42) than in older patients (30.3%, 10/33) (p = 0.002), whereas presentation with optic neuritis was more common in children older than 8 years (57.6%, 19/33) than in younger patients (21.4%, 9/42) (p = 0.001). 40.0% (26/65) of patients relapsed. Time to first relapse was longer in children aged 8 years or younger than in older patients (median 18 vs 4 months) (p = 0.013). Factors at first event independently associated with lower risk of relapsing disease course were immunotherapy <7 days from onset (6.7-fold reduced odds of relapsing course, OR 0.15, 95% CI 0.03–0.61, p = 0.009), corticosteroid treatment for ≥5 weeks (6.7-fold reduced odds of relapse, OR 0.15, 95% CI 0.03–0.80, p = 0.026), and abnormal optic nerves on onset MRI (12.5-fold reduced odds of relapse, OR 0.08, 95% CI 0.01–0.50, p = 0.007). 21.1% (15/71) had EDSS ≥ 1 at final follow-up. Patients with a relapsing course had a higher proportion of final EDSS ≥ 1 (37.5%, 9/24) than children with monophasic disease (12.8%, 5/39) (p = 0.022, univariate analysis). Each 1-point increment in worst EDSS at onset was independently associated with 6.7-fold increased odds of final EDSS ≥ 1 (OR 6.65, 95% CI 1.33–33.26, p = 0.021). Discussion At first attack of pediatric MOGAD, early immunotherapy, longer duration of corticosteroid treatment, and abnormal optic nerves on MRI seem associated with lower risk of relapse, whereas higher disease severity is associated with greater risk of final disability (EDSS ≥ 1)