We have performed a systematic experimental and simulation analysis of the optical frequency combs generated by gain-switching single mode laser diodes, either free-running or subjected to optical ...injection. The simulations have been produced with a dynamical model consisting of three rate equations that include stochastic noise terms. The model parameters have been extracted from experiments. An exhaustive comparison between the simulated and the experimental temporal profiles and optical spectra generated under a wide range of switching and optical injection conditions has been performed. The excellent quantitative agreement found in the entire range of the explored operating conditions supports the validity of the model for the analysis of the comb generation mechanisms. The detailed maps generated provide guidelines for selecting suitable operating conditions for specific comb characteristics.
Abstract In this paper we address the use of Neural Networks (NNs) for the assessment of the quality and hence safety of several Random Number Generators (RNGs), focusing both on the vulnerability of ...classical Pseudo Random Number Generators (PRNGs), such as Linear Congruential Generators (LCGs) and the RC4 algorithm, and extending our analysis to non-conventional data sources, such as Quantum Random Number Generators (QRNGs) based on Vertical-Cavity Surface-Emitting Laser (VCSEL). Among the results found, we have classified the generators based on the capability of the NN to distinguish between the RNG and a Golden Standard RNG (GSRNG). We show that sequences from simple PRNGs like LCGs and RC4 can be distinguished from the GSRNG. We also show that sequences from LCG on elliptic curves and VCSEL-based QRNG can not be distinguished from the GSRNG even with the biggest long-short term memory or convolutional neural networks (CNNs) that we have considered. We underline the fundamental role of design decisions in enhancing the safety of RNGs. The influence of network architecture design and associated hyper-parameters variations was also explored. We show that longer sequence lengths and CNNs are more effective for discriminating RNGs against the GSRNG. Moreover, in the prediction domain, the proposed model is able to deftly distinguish between the raw data of our QRNG and data from the GSRNG exhibiting a cross-entropy error of 0.52 on the test data-set used. All these findings reveal the potential of NNs to enhance the security of RNGs, while highlighting the robustness of certain QRNGs, in particular the VCSEL-based variants, for high-quality random number generation applications.
We report an experimental study of the excitation of the linearly polarized modes of a gain-switched VCSEL in order to obtain random bits. The generated bit strings pass all tests in the standard ...test suite for random number generators provided by NIST.
We experimentally study a quantum random number generator based on the random excitation of the linearly polarized modes of a gain-switched vertical-cavity surface-emitting laser (VCSEL). Our device ...is characterized by having polarization switching under continuous wave operation. By measuring the linear polarization mode that is excited in each pulse we collect a sufficient number of bits to evaluate if a standard statistical test suite is passed. We consider linear and Von Neumann post-processing methods in order to reduce the bias with different levels of bits rejection. The post-processed bit strings pass all tests in the standard test suite for random number generators provided by the National Institute of Standards and Technology (NIST). We finally compare the results obtained with different post-processing functions, including several n , k , d linear BCH codes. We show that large values of n and k are the best choice to obtain simultaneously improved throughput and randomness.
Semiconductor lasers are normally used as single-photon sources in most commercial and research quantum key distribution (QKD) systems 1. These lasers are also used for quantum random number ...generation (QRNG) that is a necessary security requirement for QKD. In device-dependent QRNGs unpredictability is guaranteed by comparing experimental measurements with simulation data obtained from a model of the physical entropy source 2. The characterization of phase fluctuations in a gain-switched edge-emitting semiconductor laser for QRNG has been recently performed 2. Very recently a QRNG based on the random excitation of the linearly polarized modes of a gain-switched vertical-cavity surface-emitting laser (VCSEL) has also been proposed 3. In this work we characterize the polarization fluctuations found in this system by comparing experimental measurements with the results obtained from the simulation of a VCSEL's model that incorporates the device intrinsic parameters found using state-of-the-art experimental techniques 4.
Background
Echocardiography‐ and cardiovascular magnetic resonance (CMR)‐based studies have revealed a wide range of phenotypic manifestations in hypertrophic cardiomyopathy (HCM) apart from ...hypertrophy. This study sought to comprehensively describe a number of structural abnormalities in HCM beyond hypertrophy, by multimodality imaging.
Methods
A total of 100 HCM patients were prospectively enrolled, undergoing standard and contrast echocardiography, and CMR. Morphological characteristics involving mitral valve leaflets (MVL), subvalvular apparatus, and left ventricular cavity and wall were investigated. Seventy healthy volunteers served as control population.
Results
As assessed by echo, MVLs were longer in HCM patients than in controls (anterior method 1: 2422,28 vs 1918,20 mm, P < 0.01; anterior method 2: 2724, 29 vs 2119, 23 mm, P < 0.01; posterior: 1512,19 vs 1413,15 mm, P < 0.01). Abnormal chordal attachment to anterior MVL, anterior papillary muscle displacement, and accessory apical‐basal muscle bundle were present in 42 (42%), 61 (61%), and 35 (35%) patients, respectively (P values vs controls <0.01); direct papillary muscle insertion into MVL and hypertrabeculation were found in two and five patients, respectively. Contrast echocardiography (n = 94) detected myocardial crypts in 15 patients (16%). Overall, 83% of HCM subjects had at least one of these phenotypic manifestations. Echocardiography and CMR agreement for MVL length was poor, while for structural characteristics was moderate to substantial (Cohen's Kappa: 0.53‐1.00). Except for posterior MVL length and hypertrabeculation, the phenotypic characteristics studied had acceptable reproducibility by echocardiography and CMR.
Conclusions
Structural abnormalities in HCM beyond hypertrophy are significantly common. Multimodality imaging approach to these HCM facets by echocardiography and CMR is feasible and desirable.
Introduction
Headache is one of the most frequent neurologic manifestations in COVID-19. We aimed to analyze which symptoms and laboratory abnormalities were associated with the presence of headache ...and to evaluate if patients with headache had a higher adjusted in-hospital risk of mortality.
Methods
Retrospective cohort study. We included all consecutive patients admitted to the Hospital with confirmed SARS-CoV-2 infection between March 8th and April 11th, 2020. We collected demographic data, clinical variables and laboratory abnormalities. We used multivariate regression analysis.
Results
During the study period, 576 patients were included, aged 67.2 (SD: 14.7), and 250/576 (43.3%) being female. Presence of headache was described by 137 (23.7%) patients. The all-cause in-hospital mortality rate was 127/576 (20.0%). In the multivariate analysis, patients with headache had a lower risk of mortality (OR: 0.39, 95% CI: 0.17–0.88,
p
= 0.007). After adjusting for multiple comparisons in a multivariate analysis, variables that were independently associated with a higher odds of having headache in COVID-19 patients were anosmia, myalgia, female sex and fever; variables that were associated with a lower odds of having headache were younger age, lower score on modified Rankin scale, and, regarding laboratory variables on admission, increased C-reactive protein, abnormal platelet values, lymphopenia and increased D-dimer.
Conclusion
Headache is a frequent symptom in COVID-19 patients and its presence is an independent predictor of lower risk of mortality in COVID-19 hospitalized patients.
Multigene panels provide a powerful tool for analyzing several genes simultaneously. We evaluated the frequency of pathogenic variants (PV) in customized predefined panels according to clinical ...suspicion by phenotype and compared it to the yield obtained in the analysis of our clinical research gene panel. We also investigated mutational yield of opportunistic testing of BRCA1/2 and mismatch repair (MMR) genes in all patients. A total of 1,205 unrelated probands with clinical suspicion of hereditary cancer were screened for germline mutations using panel testing. Overall, 1,048 females and 157 males were analyzed, mean age at cancer diagnosis was 48; 883 had hereditary breast/ovarian cancer‐suspicion, 205 hereditary nonpolyposis colorectal cancer (HNPCC)‐suspicion, 73 adenomatous‐polyposis‐suspicion and 44 with other/multiple clinical criteria. At least one PV was found in 150 probands (12%) analyzed by our customized phenotype‐driven panel. Tumoral MMR deficiency predicted for the presence of germline MMR gene mutations in patients with HNPCC‐suspicion (46/136 vs. 0/56 in patients with and without MMR deficiency, respectively). Opportunistic testing additionally identified five MSH6, one BRCA1 and one BRCA2 carriers (0.6%). The analysis of the extended 24‐gene panel provided 25 additional PVs (2%), including in 4 out of 51 individuals harboring MMR‐proficient colorectal tumors (2 CHEK2 and 2 ATM). Phenotype‐based panels provide a notable rate of PVs with clinical actionability. Opportunistic testing of MMR and BRCA genes leads to a significant straightforward identification of MSH6, BRCA1 and BRCA2 mutation carriers, and endorses the model of opportunistic testing of genes with clinical utility within a standard genetic counseling framework.
What's new?
Multigene panels offer a powerful tool for analyzing several cancer‐related genes with a single test. But which genes are actually useful in guiding medical decisions in the clinic? In this study, the authors analyzed several customized, phenotype‐driven diagnostic gene panels. These yielded a notable rate of pathogenic variants with clear clinical actionability. The study also found that opportunistic testing of MMR and BRCA genes leads to a significant, straightforward identification of MSH6, BRCA1 and BRCA2 mutation carriers. This approach could be applied within a standard genetic counseling framework.
Abstract Macrophage migration inhibitory factor (MIF) is an upstream immunoregulatory cytokine associated with the pathogenesis of autoimmune inflammatory diseases. There is evidence that MIF ...functions in a positive feedback loop with TNF-α that could perpetuate the inflammatory process in systemic lupus erythematosus (SLE). In this case–control study we investigated whether commonly occurring functional MIF polymorphisms are associated with SLE as well as with MIF and TNF-α serum levels in a Mexican-Mestizo population. Genotyping of the −794 CATT5–8 (rs5844572) and −173 G>C (rs755622) MIF polymorphisms was performed by PCR and PCR–RFLP, respectively in 186 SLE patients and 200 healthy subjects. MIF and TNF-α serum levels were determined by ELISA. A significant increase of MIF and TNF-α levels was found in SLE patients. According to a genetic model, we found a significant association of genotypes carrying the −794 CATT7 and −173∗ C risk alleles with susceptibility to SLE and with a significant increase of TNF-α. In conclusion, MIF gene polymorphisms are associated with SLE susceptibility and with an increase of TNF-α serum levels in a Mexican-Mestizo population.
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