Detuning-dependent Properties and Dispersion-induced Instabilities of Temporal Dissipative Kerr Solitons in Optical Microresonators

Temporal-dissipative Kerr solitons are self-localized light pulses sustained in driven nonlinear optical resonators. Their realization in microresonators has enabled compact sources of coherent optical frequency combs as well as the study of dissipative solitons. A key parameter of their dynamics is the effective-detuning of the pump laser to the thermally- and Kerr-shifted cavity resonance. Together with the free spectral range and dispersion, it governs the soliton-pulse duration, as predicted by an approximate analytical solution of the Lugiato-Lefever equation. Yet, a precise experimental verification of this relation was lacking so far. Here, by measuring and controlling the effective-detuning, we establish a new way of stabilizing solitons in microresonators and demonstrate that the measured relation linking soliton width and detuning deviates by less than 1 % from the approximate expression, validating its excellent predictive power. Furthermore, a detuning-dependent enhancement of specific comb lines is revealed, due to linear couplings between mode-families. They cause deviations from the predicted comb power evolution, and induce a detuning-dependent soliton recoil that modifies the pulse repetition-rate, explaining its unexpected dependence on laser-detuning. Finally, we observe that detuning-dependent mode-crossings can destabilize the soliton, leading to an unpredicted soliton breathing regime (oscillations of the pulse) that occurs in a normally-stable regime. Our results test the approximate analytical solutions with an unprecedented degree of accuracy and provide new insights into dissipative-soliton dynamics.Comment: Updated funding acknowledgement

Left ventricular ejection fraction and cardiac biomarkers for dynamic prediction of cardiotoxicity in early breast cancer

BACKGROUND/PURPOSE: This study aims to quantify the utility of monitoring LVEF, hs-cTnT, and NT-proBNP for dynamic cardiotoxicity risk assessment in women with HER2+ early breast cancer undergoing neoadjuvant/adjuvant trastuzumab-based therapy. MATERIALS AND METHODS: We used joint models of longitudinal and time-to-event data to analyze 1,136 echocardiography reports and 326 hs-cTnT and NT-proBNP measurements from 185 women. Cardiotoxicity was defined as a 10% decline in LVEF below 50% and/or clinically overt heart failure. RESULTS: Median pre-treatment LVEF was 64%, and 19 patients (10%) experienced cardiotoxicity (asymptomatic n = 12, during treatment n = 19). The pre-treatment LVEF strongly predicted for cardiotoxicity (subdistribution hazard ratio per 5% increase in pre-treatment LVEF = 0.68, 95%CI: 0.48–0.95, p = 0.026). In contrast, pre-treatment hs-cTnT and NT-proBNP were not consistently associated with cardiotoxicity. During treatment, the longitudinal LVEF trajectory dynamically identified women at high risk of developing cardiotoxicity (hazard ratio per 5% LVEF increase at any time of follow-up = 0.36, 95% CI: 0.2–0.65, p = 0.005). Thirty-four patients (18%) developed an LVEF decline ≥ 5% from pre-treatment to first follow-up (“early LVEF decline”). One-year cardiotoxicity risk was 6.8% in those without early LVEF decline and pre-treatment LVEF ≥ 60% (n = 117), 15.9% in those with early LVEF decline or pre-treatment LVEF 5% during trastuzumab-based therapy. The longitudinal LVEF trajectory but not hs-cTnT or NT-proBNP allows for a dynamic assessment of cardiotoxicity risk in this setting

An Integrated-Photonics Optical-Frequency Synthesizer

Integrated-photonics microchips now enable a range of advanced functionalities for high-coherence applications such as data transmission, highly optimized physical sensors, and harnessing quantum states, but with cost, efficiency, and portability much beyond tabletop experiments. Through high-volume semiconductor processing built around advanced materials there exists an opportunity for integrated devices to impact applications cutting across disciplines of basic science and technology. Here we show how to synthesize the absolute frequency of a lightwave signal, using integrated photonics to implement lasers, system interconnects, and nonlinear frequency comb generation. The laser frequency output of our synthesizer is programmed by a microwave clock across 4 THz near 1550 nm with 1 Hz resolution and traceability to the SI second. This is accomplished with a heterogeneously integrated III/V-Si tunable laser, which is guided by dual dissipative-Kerr-soliton frequency combs fabricated on silicon chips. Through out-of-loop measurements of the phase-coherent, microwave-to-optical link, we verify that the fractional-frequency instability of the integrated photonics synthesizer matches the $7.0*10^{-13}$ reference-clock instability for a 1 second acquisition, and constrain any synthesis error to $7.7*10^{-15}$ while stepping the synthesizer across the telecommunication C band. Any application of an optical frequency source would be enabled by the precision optical synthesis presented here. Building on the ubiquitous capability in the microwave domain, our results demonstrate a first path to synthesis with integrated photonics, leveraging low-cost, low-power, and compact features that will be critical for its widespread use.Comment: 10 pages, 6 figure

Patterns of peripheral blood B-cell subtypes are associated with treatment response in patients treated with immune checkpoint inhibitors: a prospective longitudinal pan-cancer study

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized systemic anti-tumor treatments across different types of cancer. Nevertheless, predictive biomarkers regarding treatment response are not routinely established yet. Apart from T-lymphocytes, the humoral immunity of B-lymphocytes is studied to a substantially lesser extent in the respective setting. Thus, the aim of this study was to evaluate peripheral blood B-cell subtypes as potential predictors of ICI treatment response. METHODS: Thirty-nine cancer patients receiving ICI therapy were included into this prospective single-center cohort study. All had a first blood draw at the date before treatment initiation and a second at the time of first response evaluation (after 8-12 weeks). Seven different B-cell subtypes were quantified by fluorescence-activated cell sorting (FACS). Disease control- (DCR) and objective response rate (ORR) were co-primary study endpoints. RESULTS: Overall, DCR was 48.7% and ORR was 25.6%, respectively. At baseline, there was no significant association of any B-cell subtype with neither DCR nor ORR. At the first response evaluation, an increase in the frequency of CD21(-) B-cells was a statistically significant negative predictor of response, both regarding DCR (OR=0.05, 95%CI=0.00-0.67, p=0.024) and ORR (OR=0.09, 95%CI=0.01-0.96, p=0.046). An increase of the frequency of switched memory B-cells was significantly associated with reduced odds for DCR (OR=0.06, 95%CI=0.01-0.70, p=0.025). Patients with an increased frequency of naïve B-cells were more likely to benefit from ICI therapy as indicated by an improved DCR (OR=12.31, 95%CI=1.13-134.22, p=0.039). CONCLUSION: In this study, certain B-cell subpopulations were associated with ICI treatment response in various human cancer types

The relationship between negative life events and cortical structural connectivity in adolescents

Adolescence is a crucial period for physical and psychological development. The impact of negative life events represents a risk factor for the onset of neuropsychiatric disorders. This study aims to investigate the relationship between negative life events and structural brain connectivity, considering both graph theory and connectivity strength. A group (n = 487) of adolescents from the IMAGEN Consortium was divided into Low and High Stress groups. Brain networks were extracted at an individual level, based on morphological similarity between grey matter regions with regions defined using an atlas-based region of interest (ROI) approach. Between-group comparisons were performed with global and local graph theory measures in a range of sparsity levels. The analysis was also performed in a larger sample of adolescents (n = 976) to examine linear correlations between stress level and network measures. Connectivity strength differences were investigated with network-based statistics. Negative life events were not found to be a factor influencing global network measures at any sparsity level. At local network level, between-group differences were found in centrality measures of the left somato-motor network (a decrease of betweenness centrality was seen at sparsity 5%), of the bilateral central visual and the left dorsal attention network (increase of degree at sparsity 10% at sparsity 30% respectively). Network-based statistics analysis showed an increase in connectivity strength in the High stress group in edges connecting the dorsal attention, limbic and salience networks. This study suggests negative life events alone do not alter structural connectivity globally, but they are associated to connectivity properties in areas involved in emotion and attention.</p

Evaluation of intracranial stenting in a simulated training and assessment environment for neuroendovascular procedures

PurposeGiven the inherent complexity of neurointerventional procedures and the associated risks of ionizing radiation exposure, it is crucial to prioritize ongoing training and improve safety protocols. The aim of this study is to assess a training and evaluation in-vitro environment using a vascular model of M1 stenosis, within a clinical angiography suite, without relying on animal models or X-ray radiation.Materials and methodsUsing a transparent model replicating M1 stenosis, we conducted intracranial stenting procedures with four different setups (Gateway &amp; Wingspan, Gateway &amp; Enterprise, Neurospeed &amp; Acclino, and Pharos Vitesse). A video camera was integrated with the angiography system’s monitor for real-time visualization, while a foot switch was employed to simulate live fluoroscopy. Three neuroradiologists with varying levels of expertise performed each procedure for three times. The total duration of fluoroscopy as well as the time from passing the stenosis with the wire to completion of the procedure were recorded using a dedicated software designed for this experimental setup.ResultsCompared to the Gateway &amp; Wingspan procedure, the total fluoroscopy time reduced significantly with the Gateway &amp; Enterprise, Neurospeed &amp; Acclino, and Pharos Vitesse procedures by 51.56 s, 111.33 s, and 144.89 s, respectively (p &lt; 0.001). Additionally, physicians with under 2 years and over 5 years of experience reduced FT by 62.83 s and 106.42 s, respectively, (p &lt; 0.001), compared to a novice physician. Similar trends were noted for the time of wire distal to stenosis, with significant reductions for Neurospeed &amp; Acclino and Pharos Vitesse compared to both Gateway &amp; Wingspan as well as Gateway &amp; Enterprise (all p &lt; 0.001).ConclusionProcedures requiring wire exchange maneuvers exhibited nearly twice the fluoroscopy time in comparison to balloon-mounted stenting or stent-placement via PTA balloon catheters. The more experienced neuroradiologist demonstrated significantly quicker performance in line with expectations in a real-life clinical setting, when compared to the less experienced interventionalist. This in-vitro setup allowed the evaluation of alternative technical approaches and differences in experience of operators without the use of animal models or X-ray. The setup combines advantages of simulators and silicone vessel models in a realistic working environment

Genetic and Evolutionary Analyses of the Human Bone Morphogenetic Protein Receptor 2 (BMPR2) in the Pathophysiology of Obesity

Human bone morphogenetic protein receptor 2 (BMPR2) is essential for BMP signalling and may be involved in the regulation of adipogenesis. The BMPR2 locus has been suggested as target of recent selection in human populations. We hypothesized that BMPR2 might have a role in the pathophysiology of obesity.Evolutionary analyses (dN/dS, Fst, iHS) were conducted in vertebrates and human populations. BMPR2 mRNA expression was measured in 190 paired samples of visceral and subcutaneous adipose tissue. The gene was sequenced in 48 DNA samples. Nine representative single nucleotide polymorphisms (SNPs) were genotyped for subsequent association studies on quantitative traits related to obesity in 1830 German Caucasians. An independent cohort of 925 Sorbs was used for replication. Finally, relation of genotypes to mRNA in fat was examined.The evolutionary analyses indicated signatures of selection on the BMPR2 locus. BMPR2 mRNA expression was significantly increased both in visceral and subcutaneous adipose tissue of 37 overweight (BMI>25 and <30 kg/m²) and 80 obese (BMI>30 kg/m²) compared with 44 lean subjects (BMI< 25 kg/m²) (P<0.001). In a case-control study including lean and obese subjects, two intronic SNPs (rs6717924, rs13426118) were associated with obesity (adjusted P<0.05). Combined analyses including the initial cohort and the Sorbs confirmed a consistent effect for rs6717924 (combined P = 0.01) on obesity. Moreover, rs6717924 was associated with higher BMPR2 mRNA expression in visceral adipose tissue.Combined BMPR2 genotype-phenotype-mRNA expression data as well as evolutionary aspects suggest a role of BMPR2 in the pathophysiology of obesity

Chinese characters reveal impacts of prior experience on very early stages of perception

Visual perception is strongly determined by accumulated experience with the world, which has been shown for shape, color, and position perception, in the field of visuomotor learning, and in neural computation. In addition, visual perception is tuned to statistics of natural scenes. Such prior experience is modulated by neuronal top-down control the temporal properties of which had been subject to recent studies. Here, we deal with these temporal properties and address the question how early in time accumulated past experience can modulate visual perception