Nozaki-Bekki solitons in semiconductor lasers.

Optical frequency-comb sources, which emit perfectly periodic and coherent waveforms of light1, have recently rapidly progressed towards chip-scale integrated solutions. Among them, two classes are particularly significant-semiconductor Fabry-Perót lasers2-6 and passive ring Kerr microresonators7-9. Here we merge the two technologies in a ring semiconductor laser10,11 and demonstrate a paradigm for the formation of free-running solitons, called Nozaki-Bekki solitons. These dissipative waveforms emerge in a family of travelling localized dark pulses, known within the complex Ginzburg-Landau equation12-14. We show that Nozaki-Bekki solitons are structurally stable in a ring laser and form spontaneously with tuning of the laser bias, eliminating the need for an external optical pump. By combining conclusive experimental findings and a complementary elaborate theoretical model, we reveal the salient characteristics of these solitons and provide guidelines for their generation. Beyond the fundamental soliton circulating inside the ring laser, we demonstrate multisoliton states as well, verifying their localized nature and offering an insight into formation of soliton crystals15. Our results consolidate a monolithic electrically driven platform for direct soliton generation and open the door for a research field at the junction of laser multimode dynamics and Kerr parametric processes.

Frequency combs induced by phase turbulence.

Wave instability-the process that gives rise to turbulence in hydrodynamics1-represents the mechanism by which a small disturbance in a wave grows in amplitude owing to nonlinear interactions. In photonics, wave instabilities result in modulated light waveforms that can become periodic in the presence of coherent locking mechanisms. These periodic optical waveforms are known as optical frequency combs2-4. In ring microresonator combs5,6, an injected monochromatic wave becomes destabilized by the interplay between the resonator dispersion and the Kerr nonlinearity of the constituent crystal. By contrast, in ring lasers instabilities are considered to occur only under extreme pumping conditions7,8. Here we show that, despite this notion, semiconductor ring lasers with ultrafast gain recovery9,10 can enter frequency comb regimes at low pumping levels owing to phase turbulence11-an instability known to occur in hydrodynamics, superconductors and Bose-Einstein condensates. This instability arises from the phase-amplitude coupling of the laser field provided by linewidth enhancement12, which produces the needed interplay of dispersive and nonlinear effects. We formulate the instability condition in the framework of the Ginzburg-Landau formalism11. The localized structures that we observe share several properties with dissipative Kerr solitons, providing a first step towards connecting semiconductor ring lasers and microresonator frequency combs13.

Opposing effects of genetic variation in MTCH2 for obesity versus heart failure.

Genetic variation in genes regulating metabolism may be advantageous in some settings but not others. The non-failing adult heart relies heavily on fatty acids as a fuel substrate and source of ATP. In contrast, the failing heart favors glucose as a fuel source. A bootstrap analysis for genes with deviant allele frequencies in cardiomyopathy cases versus controls identified the MTCH2 gene as having unusual variation. MTCH2 encodes an outer mitochondrial membrane protein, and prior genome-wide studies associated MTCH2 variants with body mass index, consistent with its role in metabolism. We identified the referent allele of rs1064608 (p.Pro290) as being overrepresented in cardiomyopathy cases compared to controls, and linkage disequilibrium analysis associated this variant with the MTCH2 cis eQTL rs10838738 and lower MTCH2 expression. To evaluate MTCH2, we knocked down Mtch in Drosophila heart tubes which produced a dilated and poorly functioning heart tube, reduced adiposity and shortened life span. Cardiac Mtch mutants generated more lactate at baseline, and they displayed impaired oxygen consumption in the presence of glucose but not palmitate. Treatment of cardiac Mtch mutants with dichloroacetate, a pyruvate dehydrogenase kinase inhibitor, reduced lactate and rescued lifespan. Deletion of MTCH2 in human cells similarly impaired oxygen consumption in the presence of glucose but not fatty acids. These data support a model in which MTCH2 reduction may be favorable when fatty acids are the major fuel source, favoring lean body mass. However, in settings like heart failure, where the heart shifts toward using more glucose, reduction of MTCH2 is maladaptive.

Developing an improved optical biosensing system based on gold nanoparticles acting as interferometric enhancers in Lactoferrin detection.

We report for the first time the whole development of a biosensing system based on the Interferometric Optical Detection Method (IODM) enriched with gold nanoparticles (AuNPs), acting as interferometric enhancers for improving the performance of immunoassays. For this purpose, the Lactoferrin sandwich immunoassay model was employed. We describe in detail the entire value chain from the AuNPs production, its functionalization, and characterization with anti-Lactoferrin (anti-LF), the biosensing response of these conjugates as well as their corresponding calculation of the kinetic constants, performance comparison of the readout interferometric signals versus Scanning Electron Microscopy (SEM) and the percentage of the sensing surface covered. Finally, a Lactoferrin sandwich immunoassay was carried out and correlated with Enzyme-Linked ImmunoSorbent Assay (ELISA), and the Limit of Detection and sensitivity figures were obtained. As a result, we demonstrate how the AuNPs act as interferometric amplifiers of the IODM for improving the biosensing response, opening the possibility of being applied in multiple biological detection applications.

Bacterial Superinfection Pneumonia in Patients Mechanically Ventilated for COVID-19 Pneumonia.

Rationale: Current guidelines recommend patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia receive empirical antibiotics for suspected bacterial superinfection on the basis of weak evidence. Rates of ventilator-associated pneumonia (VAP) in clinical trials of patients with SARS-CoV-2 pneumonia are unexpectedly low. Objectives: We conducted an observational single-center study to determine the prevalence and etiology of bacterial superinfection at the time of initial intubation and the incidence and etiology of subsequent bacterial VAP in patients with severe SARS-CoV-2 pneumonia. Methods: Bronchoscopic BAL fluid samples from all patients with SARS-CoV-2 pneumonia requiring mechanical ventilation were analyzed using quantitative cultures and a multiplex PCR panel. Actual antibiotic use was compared with guideline-recommended therapy. Measurements and Main Results: We analyzed 386 BAL samples from 179 patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. Bacterial superinfection within 48 hours of intubation was detected in 21% of patients. Seventy-two patients (44.4%) developed at least one VAP episode (VAP incidence rate = 45.2/1,000 ventilator days); 15 (20.8%) initial VAPs were caused by difficult-to-treat pathogens. The clinical criteria did not distinguish between patients with or without bacterial superinfection. BAL-based management was associated with significantly reduced antibiotic use compared with guideline recommendations. Conclusions: In patients with SARS-CoV-2 pneumonia requiring mechanical ventilation, bacterial superinfection at the time of intubation occurs in <25% of patients. Guideline-based empirical antibiotic management at the time of intubation results in antibiotic overuse. Bacterial VAP developed in 44% of patients and could not be accurately identified in the absence of microbiologic analysis of BAL fluid.

Comparison of conventional ligatures and a vessel sealing device for haemostasis during open ovariohysterectomy in rabbits.

AIMS: To compare surgical times and rates of intra-operative and post-operative complications for open ovariohysterectomy (OVH) in female rabbits using conventional ligatures or a vessel sealing device (VSD) for haemostasis. METHODS: Female pet rabbits (n = 23) presented for OVH for either desexing or treatment of reproductive disorders were randomly assigned to a conventional ligatures (CL) group (n = 12) or a LigaSure 5-mm (LS5) group (n = 11). In the CL group, the ovarian pedicles were ligated with a single surgeon's knot. After transection of the ovarian pedicles, the broad ligament was manually broken down along the uterine horns to their respective cervices. In the LS5 group, both ovarian pedicles and the broad ligaments were sealed with a LigaSure Dolphin Tip VSD with 5-mm forceps. All the rabbits were hospitalised for 24 hours after surgery. Two weeks after discharge, a clinical recheck examination was performed. Incision length, overall surgical time (from initial incision to completion of intradermal suturing), OVH time (from identification of the first ovary to transection of the vaginal vault), and intra- and post-operative complications were recorded and compared between groups, using the Student's t-test for normally distributed continuous data, the Wilcoxon-Mann-Whitney test for non-normally distributed continuous data and Pearson's χ2 test for categorical data. RESULTS: The mean overall surgical time was 14.1 (SD 4.4) minutes. The surgery took 15.0 (SD 4.9) minutes in the CL group and 13.1 (SD 3.8) minutes in the LS5 group (p=0.10). The OVH time was shorter in the LS5 group (mean 4.2 (SD 0.9) minutes) than in the CL group (mean 6.3 (SD 1.7) minutes; p = 0.005). No intra-operative complications were encountered in the LS5 group. Haemorrhage occurred in three rabbits in the CL group. One rabbit in the LS5 group developed steatonecrosis post-operatively. There was no evidence of a difference in the proportion of rabbits that experienced intra- and post-operative complications (p = 0.25 and p = 0.94 respectively) between groups. CONCLUSIONS: The use of a LigaSure 5-mm VSD and conventional ligatures during open OVH were both associated with similar overall surgical times and complication rates. The OVH times were shorter in the LS5 group compared to the CL group. CLINICAL RELEVANCE: Use of the LigaSure 5-mm VSD allows efficient haemostasis while performing open OVH in female pet rabbits.

Comparative Effectiveness of Surgical Approaches for Lung Cancer.

BACKGROUND: The magnitude of association and quality of evidence comparing surgical approaches for lung cancer resection has not been analyzed. This has resulted in conflicting information regarding the relative superiority of the different approaches and disparate opinions on the optimal surgical treatment. We reviewed and systematically analyzed all published data comparing near- (30-d) and long-term mortality for minimally invasive to open surgical approaches for lung cancer. METHODS: Comprehensive search of EMBASE, MEDLINE, and the Cochrane Library, from January 2009 to August 2019, was performed to identify the studies and those that passed bias assessment were included in the analysis utilizing propensity score matching techniques. Meta-analysis was performed using random-effects and fixed-effects models. Risk of bias was assessed via the Newcastle-Ottawa Scale and the ROBINS-I tool. The study was registered in PROSPERO (CRD42020150923) prior to analysis. RESULTS: Overall, 1382 publications were identified but 19 studies were included encompassing 47,054 patients after matching. Minimally invasive techniques were found to be superior with respect to near-term mortality in early and advanced-stage lung cancer (risk ratio 0.45, 95% confidence interval [CI] 0.21-0.95, I2 = 0%) as well as for elderly patients (odds ratio 0.45, 95% CI 0.31-0.65, I2 = 30%), but did not demonstrate benefit for high-risk patients (odds ratio 0.74, 95% CI 0.06-8.73, I2 = 78%). However, no difference was found in long-term survival. CONCLUSIONS: We performed the first systematic review and meta-analysis to compare surgical approaches for lung cancer which indicated that minimally invasive techniques may be superior to thoracotomy in near-term mortality, but there is no difference in long-term outcomes.

Measuring the Kinetics of Neutral Pair Evaporation from Cluster Ions of Ionic Liquid in the Drift Region of a Differential Mobility Analyzer.

Singly charged clusters [C+A-]nC+ or [C+A-]nA- of two salts [C+A-] are produced by electrospray ionization of alcohol solutions of the ionic liquids 1-ethyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate (EMI-FAP) and 1,2-dimethyl-3-propylimidazolium-methide (DMPI-Me). The rate of neutral pair evaporation into [C+A-] + [C+A-]n-1C+ or [C+A-]n-1A- is studied in atmospheric pressure as a function of temperature T for the positive trimer ion (n = 2) of DMPI-Me and the negative trimer ion of EMI-FAP. The trimer is separated from all other electrosprayed ions in a first differential mobility analyzer (DMA1) and then transferred through a cooled tube to a second DMA whose drift gas is kept at a controlled temperature (25 °C < T < 100 °C). Singular characteristics of the DMA are a residence time τ of ∼0.1 to 1 ms, with essentially uniform temperature and τ. The decomposition occurring within DMA2 results in a complex mobility spectrum associated with dimer product ions, with apparent mobilities intermediate between those of the dimer and the trimer, depending on the product of the reaction rate k and τ. A theoretical expression yielding k from the shape of the collected mobility spectrum is obtained by accounting for the deterministic reactive, convective, and diffusive evolutions of the parent and product ions within DMA2. Observed and predicted mobility spectra agree well, yielding the reaction rate k with little ambiguity. Activation energies near 1 eV are determined for both trimer ions. Paradoxically, the evaporation process substantially heats up the cluster ion product. The theory developed enables measuring decay times much smaller and much larger than the residence time in the DMA.

Threshold behavior of optical frequency comb self-generation in an InAs/InGaAs quantum dot laser.

We report on a significant reduction of both the radio-frequency beat note line width at 40.7 GHz and the integrated relative intensity noise of a 1 mm long edge-emitting monolithic Fabry-Perot InAs/InGaAs quantum dot semiconductor laser emitting from the ground state at 1250 nm by injection current control. For increasing injection currents, first an unlocked multi-mode behavior is observed and then, at a certain current above lasing threshold, self-locking of the longitudinal modes due to the internal non-linear effects occurs yielding a beat line width of 20 kHz (-3 dB) in contrast to tens of megahertz for lower injection currents. These results are confirmed by simulations.

Merging Photocatalysis with Electrochemistry: The Dawn of a new Alliance in Organic Synthesis.

The merging of a homogeneous photocatalytic system with an electrochemical cell, having exchanged electrons as the only common point, has been recently demonstrated. This combination opens unexplored pathways in synthesis and allowed net-oxidative photocatalytic processes to be realized in the absence of a chemical oxidant, including: 1) the C-H alkylation of heteroarenes and 2) the coupling of azoles with arenes in the presence of an electrogenerated photocatalyst.

Experimental Modeling Supports a Role for MyBP-HL as a Novel Myofilament Component in Arrhythmia and Dilated Cardiomyopathy.

BACKGROUND: Cardiomyopathy and arrhythmias are under significant genetic influence. Here, we studied a family with dilated cardiomyopathy and associated conduction system disease in whom prior clinical cardiac gene panel testing was unrevealing. METHODS: Whole-genome sequencing and induced pluripotent stem cells were used to examine a family with dilated cardiomyopathy and atrial and ventricular arrhythmias. We also characterized a mouse model with heterozygous and homozygous deletion of Mybphl. RESULTS: Whole-genome sequencing identified a premature stop codon, R255X, in the MYBPHL gene encoding MyBP-HL (myosin-binding protein-H like), a novel member of the myosin-binding protein family. MYBPHL was found to have high atrial expression with low ventricular expression. We determined that MyBP-HL protein was myofilament associated in the atria, and truncated MyBP-HL protein failed to incorporate into the myofilament. Human cell modeling demonstrated reduced expression from the mutant MYBPHL allele. Echocardiography of Mybphl heterozygous and null mouse hearts exhibited a 36% reduction in fractional shortening and an increased diastolic ventricular chamber size. Atria weight normalized to total heart weight was significantly increased in Mybphl heterozygous and null mice. Using a reporter system, we detected robust expression of Mybphl in the atria, and in discrete puncta throughout the right ventricular wall and septum, as well. Telemetric electrocardiogram recordings in Mybphl mice revealed cardiac conduction system abnormalities with aberrant atrioventricular conduction and an increased rate of arrhythmia in heterozygous and null mice. CONCLUSIONS: The findings of reduced ventricular function and conduction system defects in Mybphl mice support that MYBPHL truncations may increase risk for human arrhythmias and cardiomyopathy.

Phase-resolved terahertz self-detection near-field microscopy.

At terahertz (THz) frequencies, scattering-type scanning near-field optical microscopy (s-SNOM) based on continuous wave sources mostly relies on cryogenic and bulky detectors, which represents a major constraint for its practical application. Here, we devise a THz s-SNOM system that provides both amplitude and phase contrast and achieves nanoscale (60-70nm) in-plane spatial resolution. It features a quantum cascade laser that simultaneously emits THz frequency light and senses the backscattered optical field through a voltage modulation induced inherently through the self-mixing technique. We demonstrate its performance by probing a phonon-polariton-resonant CsBr crystal and doped black phosphorus flakes.

Bilateral testicular torsion in an adolescent: a case with challenging diagnosis.

Bilateral testicular torsion is a very uncommon emergency, with a challenging differential diagnosis. We describe the case of a 15-year-old patient with a left testicular torsion of 48 hours of duration and a sudden onset of right scrotum pain during his stay at the emergency area. Bilateral testicular torsion was diagnosed after repeat physical examination and doppler ultrasound, which had been normal for right testis in a first evaluation. Surgical exploration was performed with orchiectomy in left testis and fixation in right testis. In previous literature, there are reported bilateral torsion only in four adolescents and five adults. With this case, we demonstrate that bilateral spermatic cord torsion may be easily overlooked in a patient with acute scrotum and we emphasize the importance of bilateral exploration in testicular torsion.

Network burst activity in hippocampal neuronal cultures: the role of synaptic and intrinsic currents.

The goal of this work was to define the contributions of intrinsic and synaptic mechanisms toward spontaneous network-wide bursting activity, observed in dissociated rat hippocampal cell cultures. This network behavior is typically characterized by short-duration bursts, separated by order of magnitude longer interburst intervals. We hypothesize that while short-timescale synaptic processes modulate spectro-temporal intraburst properties and network-wide burst propagation, much longer timescales of intrinsic membrane properties such as persistent sodium (Nap) currents govern burst onset during interburst intervals. To test this, we used synaptic receptor antagonists picrotoxin, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and 3-(2-carboxypiperazine-4-yl)propyl-1-phosphonate (CPP) to selectively block GABAA, AMPA, and NMDA receptors and riluzole to selectively block Nap channels. We systematically compared intracellular activity (recorded with patch clamp) and network activity (recorded with multielectrode arrays) in eight different synaptic connectivity conditions: GABAA + NMDA + AMPA, NMDA + AMPA, GABAA + AMPA, GABAA + NMDA, AMPA, NMDA, GABAA, and all receptors blocked. Furthermore, we used mixed-effects modeling to quantify the aforementioned independent and interactive synaptic receptor contributions toward spectro-temporal burst properties including intraburst spike rate, burst activity index, burst duration, power in the local field potential, network connectivity, and transmission delays. We found that blocking intrinsic Nap currents completely abolished bursting activity, demonstrating their critical role in burst onset within the network. On the other hand, blocking different combinations of synaptic receptors revealed that spectro-temporal burst properties are uniquely associated with synaptic functionality and that excitatory connectivity is necessary for the presence of network-wide bursting. In addition to confirming the critical contribution of direct excitatory effects, mixed-effects modeling also revealed distinct combined (nonlinear) contributions of excitatory and inhibitory synaptic activity to network bursting properties.

Distribution of Silica-Coated Silver/Gold Nanostars in Soft- and Hardwood Applying SERS-Based Imaging.

Nanoparticles (NPs) in aqueous suspension have just begun to be exploited for the preservative treatment of wood. However, at present, there is very little information available on the distribution of NPs in wood after impregnation, due to associated analytical challenges. In this study, we present the detection of model NPs in softwood and hardwood by surface-enhanced Raman spectroscopy (SERS). SERS is a highly sensitive analytical method requiring no fluorescent labeling. The NP distribution after impregnation is evaluated with one representative species of the two wood types. To show the feasibility of the method, we prepared SERS-active Au/Ag nanostars coated with silica to act as a model NP system. We show herein that NPs can be imaged in very low quantities in both wood types without any matrix interactions. The presence of the NPs in the wood was confirmed by scanning electron microscopy (SEM) imaging and energy dispersive X-ray analysis (EDX). The fast detection of NPs in a complex matrix, without complicated sample preparation, marks a huge step forward in the development and application of nanotechnology for wood preservation and the quest to optimize the properties of one of the world's most important raw materials.

Supercomputing for the parallelization of whole genome analysis.

MOTIVATION: The declining cost of generating DNA sequence is promoting an increase in whole genome sequencing, especially as applied to the human genome. Whole genome analysis requires the alignment and comparison of raw sequence data, and results in a computational bottleneck because of limited ability to analyze multiple genomes simultaneously. RESULTS: We now adapted a Cray XE6 supercomputer to achieve the parallelization required for concurrent multiple genome analysis. This approach not only markedly speeds computational time but also results in increased usable sequence per genome. Relying on publically available software, the Cray XE6 has the capacity to align and call variants on 240 whole genomes in ∼50 h. Multisample variant calling is also accelerated. AVAILABILITY AND IMPLEMENTATION: The MegaSeq workflow is designed to harness the size and memory of the Cray XE6, housed at Argonne National Laboratory, for whole genome analysis in a platform designed to better match current and emerging sequencing volume.

Tumefactive Primary Central Nervous System Vasculitis: Dynamic Susceptibility Contrast Perfusion-Weighted Magnetic Resonance Imaging Findings With Histological Correlation.

Purpose: Primary central nervous system vasculitis (PCNSV) is a rare inflammatory disease affecting the central nervous system. In some cases, it presents with large, solitary lesion with extensive mass effect that mimic intracranial neoplasms. This condition results in a diagnostic confusion for neuroradiologists because the differentiation is almost impossible on conventional MRI sequences. The aim of this study is to reveal the significance of dynamic susceptibility contrast (DSC) perfusion-weighted imaging in differentiating of tumefactive PCNSV (t-PCNSV) lesions from intracranial neoplasms such as glio-blastomas and metastasis. Methods: In this retrospective study, DSC of 8 patients with biopsy-proven t-PCNSV has been compared with DSC obtained in 10 patients with glioblastoma, 10 patients with metastasis, who underwent surgery and histopathological confirmation. The ratio of relative cerebral blood volume (rrCBV) was calculated by rCBV (lesion) / rCBV (controlateral normal-appearing white matter) in the gadolinium-enhancing solid areas. Results: The mean rrCBV was 0.86±0.7 (range: 0.76-0.98) in the patients with t-PCNSV, 5,16±0.79 in patients with glioblastoma (range: 3.9-6.3), and 4.27±0.73 (range: 2.8-5.3) in patients with metastases. Conclusion: DSC-PWI seems to be useful in the diagnostic work-up of t-PCSNVs. A low rrCBV, i.e. a rCBV similar or lower to that of the contralateral normal white matter, seems to be consistent with the possibility of t-PCSNV.

[Efficacy of high-intensity exercise in people with chronic low back pain: A systematic review]. / Eficacia del ejercicio de alta intensidad en personas con dolor lumbar crónico: una revisión sistemática.

Chronic low back pain causes disability and socioeconomic impact. High-intensity exercise shows positive results in other diseases, but there is no evidence on this pathology. The aim is to determine its efficacy on health-related quality of life, disability, pain intensity and adherence to treatment in people with chronic low back pain. A literature review is conducted in Pubmed, PEDro and Scopus, including randomized clinical trials, clinical practice guidelines and systematic reviews in Spanish, English or Portuguese (2012-2022). In addition, a snowball search is performed. Eight randomized clinical trials (n=379) are incorporated. Different high-intensity exercise modalities are analyzed, which seem to improve health-related quality of life and reduce disability and pain intensity. These data should be taken with caution given the small number of studies and the risk of bias presented.