Increased length-dependent activation of human engineered heart tissue after chronic α1A-adrenergic agonist treatment: testing a novel heart failure therapy.

Chronic stimulation of cardiac α1A-adrenergic receptors (α1A-ARs) improves symptoms in multiple preclinical models of heart failure. However, the translational significance remains unclear. Human engineered heart tissues (EHTs) provide a means of quantifying the effects of chronic α1A-AR stimulation on human cardiomyocyte physiology. EHTs were created from thin slices of decellularized pig myocardium seeded with human induced pluripotent stem cell (iPSC)-derived cardiomyocytes and fibroblasts. With a paired experimental design, EHTs were cultured for 3 wk, mechanically tested, cultured again for 2 wk with α1A-AR agonist A61603 (10 nM) or vehicle control, and retested after drug washout for 24 h. Separate control experiments determined the effects of EHT age (3-5 wk) or repeat mechanical testing. We found that chronic A61603 treatment caused a 25% increase of length-dependent activation (LDA) of contraction compared with vehicle treatment (n = 7/group, P = 0.035). EHT force was not increased after chronic A61603 treatment. However, after vehicle treatment, EHT force was increased by 35% relative to baseline testing (n = 7/group, P = 0.022), suggesting EHT maturation. Control experiments suggested that increased EHT force resulted from repeat mechanical testing, not from EHT aging. RNA-seq analysis confirmed that the α1A-AR is expressed in human EHTs and found chronic A61603 treatment affected gene expression in biological pathways known to be activated by α1A-ARs, including the MAP kinase signaling pathway. In conclusion, increased LDA in human EHT after chronic A61603 treatment raises the possibility that chronic stimulation of the α1A-AR might be beneficial for increasing LDA in human myocardium and might be beneficial for treating human heart failure by restoring LDA.NEW & NOTEWORTHY Chronic stimulation of α1A-adrenergic receptors (α1A-ARs) is known to mediate therapeutic effects in animal heart failure models. To investigate the effects of chronic α1A-AR stimulation in human cardiomyocytes, we tested engineered heart tissue (EHT) created with iPSC-derived cardiomyocytes. RNA-seq analysis confirmed human EHT expressed α1A-ARs. Chronic (2 wk) α1A-AR stimulation with A61603 (10 nM) increased length-dependent activation (LDA) of contraction. Chronic α1A-AR stimulation might be beneficial for treating human heart failure by restoring LDA.

18F-FDG PET/CT in cardiovascular infection and inflammation.

The diagnosis of cardiovascular infection and inflammation by [18F]FDG PET/CT in Nuclear Cardiology is of growing interest, because with respect to echocardiography this technique has improved the certainty in the diagnosis of infective endocarditis in patients with prosthetic valves, the increasing number of patients with implantable cardiac devices because of the progressive ageing of the population, as well as in patients with suspected large vessel vasculitis. All are serious clinical situations which require correct diagnosis and appropriate treatment as soon as possible, because they can cause severe complications, high mortality and also increased health care costs. We review the use of [18F]FDG PET/CT in cardiovascular infection and inflammation, including the clinical point of view and the contribution of other image modalities. We focus on the appropriate methodology for this exploration, patient preparation, image acquisition and correct interpretation and the quantification possibilities, defining the specific characteristics of the diagnosis in patients with prosthetic valves, implantable cardiac devices and large vessel vasculitis in the initial diagnosis as well as during follow-up to assess treatment response. We analyze the possible causes of false positive and false negative results and emphasize the special value of a multidisciplinary team for optimal management of these patients.

Multi-wavelength high-energy gas-filled fiber Raman laser spanning from 1.53 µm to 2.4 µm.

In this work, we present a high-pulse-energy multi-wavelength Raman laser spanning from 1.53 µm up to 2.4 µm by employing the cascaded rotational stimulated Raman scattering effect in a 5 m hydrogen (H2)-filled nested anti-resonant fiber, pumped by a linearly polarized Er/Yb fiber laser with a peak power of ∼13kW and pulse duration of ∼7ns in the C-band. The developed Raman laser has distinct lines at 1683 nm, 1868 nm, 2100 nm, and 2400 nm, with pulse energies as high as 18.25 µJ, 14.4 µJ, 14.1 µJ, and 8.2 µJ, respectively. We demonstrate how the energy in the Raman lines can be controlled by tuning the H2 pressure from 1 bar to 20 bar.

Mid-infrared photoacoustic gas monitoring driven by a gas-filled hollow-core fiber laser.

Development of novel mid-infrared (MIR) lasers could ultimately boost emerging detection technologies towards innovative spectroscopic and imaging solutions. Photoacoustic (PA) modality has been heralded for years as one of the most powerful detection tools enabling high signal-to-noise ratio analysis. Here, we demonstrate a novel, compact and sensitive MIR-PA system for carbon dioxide (CO2) monitoring at its strongest absorption band by combining a gas-filled fiber laser and PA technology. Specifically, the PA signals were excited by a custom-made hydrogen (H2) based MIR Raman fiber laser source with a pulse energy of ⁓ 18 µJ, quantum efficiency of ⁓ 80% and peak power of ⁓ 3.9 kW. A CO2 detection limit of 605 ppbv was attained from the Allan deviation. This work constitutes an alternative method for advanced high-sensitivity gas detection.

Bright, high-repetition-rate water window soft X-ray source enabled by nonlinear pulse self-compression in an antiresonant hollow-core fibre.

Bright, coherent soft X-ray radiation is essential to a variety of applications in fundamental research and life sciences. To date, a high photon flux in this spectral region can only be delivered by synchrotrons, free-electron lasers or high-order harmonic generation sources, which are driven by kHz-class repetition rate lasers with very high peak powers. Here, we establish a novel route toward powerful and easy-to-use SXR sources by presenting a compact experiment in which nonlinear pulse self-compression to the few-cycle regime is combined with phase-matched high-order harmonic generation in a single, helium-filled antiresonant hollow-core fibre. This enables the first 100 kHz-class repetition rate, table-top soft X-ray source that delivers an application-relevant flux of 2.8 × 106 photon s-1 eV-1 around 300 eV. The fibre integration of temporal pulse self-compression (leading to the formation of the necessary strong-field waveforms) and pressure-controlled phase matching will allow compact, high-repetition-rate laser technology, including commercially available systems, to drive simple and cost-effective, coherent high-flux soft X-ray sources.

Observation on temperature and strain dependency of Brillouin dynamic grating in a few-mode fiber with a ring-cavity configuration.

We experimentally conduct Brillouin dynamic grating (BDG) operation using a 1-km-long four-mode fiber. By employing a simplified ring-cavity configuration with single-end pumping, the BDG is effectively generated in $ {{\rm LP}_{01}} $LP01 mode within a range of 250 m, and three higher-order modes, namely, $ {{\rm LP}_{11b}} $LP11b, $ {{\rm LP}_{21a}} $LP21a, and $ {{\rm LP}_{02}} $LP02, are chosen as probes to analyze the BDG with a spatial resolution of 1 m. To the best of our knowledge, this is the first time to characterize the responses of BDG frequency to temperature and strain for different modes in a conventional few-mode fiber. By employing the pump-probe pair of $ {{\rm LP}_{01}}{{\rm - LP}_{02}} $LP01-LP02 mode, the highest temperature and strain sensitivities of 3.21 MHz/°C and $ - 0.0384\;{\rm MHz}/{\unicode{x00B5}}{\unicode{x03B5}} $-0.0384MHz/µÎµ have been achieved. Also, the performance of simultaneously distributed temperature and strain sensing based on BDG is evaluated.

Mode-selective few-mode Brillouin fiber lasers based on intramodal and intermodal SBS.

Mode-selective fiber lasers have advantages in a number of applications. Here we propose and experimentally demonstrate a transverse mode-selective few-mode Brillouin fiber laser using the mode-selective photonic lantern. We generated the lowest three orders of linearly polarized (LP) modes based on both intramodal and intermodal stimulated Brillouin scattering (SBS). Their slope efficiencies, optical spectra, mode profiles, and linewidths were measured.

High pulse energy and quantum efficiency mid-infrared gas Raman fiber laser targeting CO2 absorption at 4.2 µm.

In this Letter, we demonstrate a high pulse energy and linearly polarized mid-infrared Raman fiber laser targeting the strongest absorption line of ${\rm CO}_2$CO2 at $\sim{4.2}\;\unicode {x00B5} {\rm m}$∼4.2µm. This laser was generated from a hydrogen (${\rm H}_2$H2)-filled antiresonant hollow-core fiber, pumped by a custom-made 1532.8 nm Er-doped fiber laser delivering 6.9 ns pulses and 11.6 kW peak power. A quantum efficiency as high as 74% was achieved, to yield 17.6 µJ pulse energy at 4.22 µm. Less than 20 bar ${\rm H}_2$H2 pressure was required to maximize the pulse energy since the transient Raman regime was efficiently suppressed by the long pump pulses.

ADHD Endophenotypes in Caribbean Families.

Objective: The aim of this study is to contrast the genetics of neuropsychological tasks in individuals from nuclear families clustering ADHD in a Caribbean community. Method: We recruited and clinically characterized 408 individuals using an extensive battery of neuropsychological tasks. The genetic variance underpinning these tasks was estimated by heritability. A predictive framework for ADHD diagnosis was derived using these tasks. Results: We found that individuals with ADHD differed from controls in tasks of mental control, visuospatial ability, visuoverbal memory, phonological and verbal fluency, verbal and semantic fluency, cognitive flexibility, and cognitive ability. Among them, tasks of mental control, visuoverbal memory, phonological fluency, semantic verbal fluency, and intelligence had a significant heritability. A predictive model of ADHD diagnosis using these endophenotypes yields remarkable classification rate, sensitivity, specificity, and precision values (above 80%). Conclusion: We have dissected new cognitive endophenotypes in ADHD that can be suitable to assess the neurobiological and genetic basis of ADHD.

Low-crosstalk few-mode EDFAs using retro-reflection for single-mode fiber trunk lines and networks.

Few-mode EDFAs with low channel crosstalk can replace multiple parallel single-mode EDFAs in single-mode fiber trunk lines and networks. Here we proposed a low-crosstalk few-mode EDFA by exploiting the unitary property of the coupling matrix of a symmetric photonic lantern. We experimentally demonstrated a 3-channel few-mode EDFA using retro-reflection of a 3-mode symmetric photonic lantern. The small signal gain for all three channels are measured to be larger than 25 dB over the entire C-band and the crosstalks are below -10 dB.

Control over the transverse structure and long-distance fiber propagation of light at the single-photon level.

Quantum entanglement is arguably the cornerstone which differentiates the quantum realm from its classical counterpart. While entanglement can reside in any photonic degree of freedom, polarization permits perhaps the most straightforward manipulation due to the widespread availability of standard optical elements such as waveplates and polarizers. As a step towards a fuller exploitation of entanglement in other degrees of freedom, in this work we demonstrate control over the transverse spatial structure of light at the single-photon level. In particular we integrate in our setup all the technologies required for: (i) fibre-based photon pair generation, (ii) deterministic and broadband single-photon spatial conversion relying on a passive optical device, and (iii) single-photon transmission, while retaining transverse structure, over 400 m of few-mode fibre. In our experiment, we employ a mode selective photonic lantern multiplexer with the help of which we can convert the transverse profile of a single photon from the fundamental mode into any of the supported higher-order modes. We also achieve conversion to an incoherent or coherent addition of two user-selected higher order modes by addressing different combinations of inputs in the photonic lantern multiplexer. The coherent nature of the addition, and extraction of usable orbital angular momentum at the single-photon level, is further demonstrated by far-field diffraction through a triangular aperture. Our work could enable studies of photonic entanglement in the transverse modes of a fibre and could constitute a key resource quantum for key distribution with an alphabet of scalable dimension.

Multioctave supercontinuum from visible to mid-infrared and bend effects on ultrafast nonlinear dynamics in gas-filled hollow-core fiber.

Broadband supercontinuum generation is numerically investigated in a Xe-filled nested hollow-core antiresonant (HC-AR) fiber pumped at 3 µm with pulses of 100 fs duration and 15 µJ energy. For a 25 cm long fiber, under 7 bar pressure, the supercontinuum spectrum spans multiple octaves from 400 nm to 5000 nm. Furthermore, the influence of bending on ultrafast nonlinear pulse propagation dynamics is investigated for two types of HC-AR fibers (nested and non-nested capillaries). Our results predict similar nonlinear dynamics for both fiber types and a significant reduction of the spectral broadening under tight bending conditions.

Accelerated nonlinear interactions in graded-index multimode fibers.

Multimode optical fibers have recently reemerged as a viable platform for addressing a number of long-standing issues associated with information bandwidth requirements and power-handling capabilities. As shown in recent studies, the complex nature of such heavily multimoded systems can be effectively exploited to observe altogether novel physical effects arising from spatiotemporal and intermodal linear and nonlinear processes. Here, we study for the first time, accelerated nonlinear intermodal interactions in core-diameter decreasing multimode fibers. We demonstrate that in the anomalous dispersion region, this spatiotemporal acceleration can lead to relatively blue-shifted multimode solitons and blue-drifting dispersive wave combs, while in the normal domain, to a notably flat and uniform supercontinuum, extending over 2.5 octaves. Our results pave the way towards a deeper understanding of the physics and complexity of nonlinear, heavily multimoded optical systems, and could lead to highly tunable optical sources with very high spectral densities.

Single-mode, low loss hollow-core anti-resonant fiber designs.

In this paper, we numerically investigate various hollow-core anti-resonant (HC-AR) fibers towards low propagation and bend loss with effectively single-mode operation in the telecommunications window. We demonstrate how the propagation loss and higher-order mode modal contents are strongly influenced by the geometrical structure and the number of the anti-resonant cladding tubes. We found that 5-tube nested HC-AR fiber has a wider anti-resonant band, lower loss, and larger higher-order mode extinction ratio than designs with 6 or more anti-resonant tubes. A loss ratio between the higher-order modes and fundamental mode, as high as 12,000, is obtained in a 5-tube nested HC-AR fiber. To the best of our knowledge, this is the largest higher-order mode extinction ratio demonstrated in a hollow-core fiber at 1.55 µm. In addition, we propose a modified 5-tube nested HC-AR fiber, with propagation loss below 1 dB/km from 1330 to 1660 nm. This fiber also has a small bend loss of ~15 dB/km for a bend radius of 1 cm.

Direct quantification of inorganic iodine in seawater by mixed-mode liquid chromatography-electrospray ionization-mass spectrometry.

Atmospheric iodine plays a relevant role in climate change. Bearing in mind that most of this iodine comes from the oceans, analytical methods capable of determining iodine in a challenging matrix as seawater are necessary. In this work, the first method capable of direct determination of total inorganic iodine in seawater at subnanomolar level based on mixed-mode liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) without any sample treatment is presented. Analytical characteristics of the developed method were studied in terms of linear range, limits of detection and quantification, precision, trueness, matrix effect, and robustness. The detection limit for iodide was as low as 0.16 nM, injecting 5 µL of seawater without any sample treatment and the working linear range of four orders of magnitude was wide enough to cover the broad concentration range observed in seawater samples. Average values for repeatability and intermediate precision were 4.1% and 8.1%, respectively. The suitability of the method was demonstrated through its application to the analysis of several types of samples, including seawater samples taken at different locations along the Spanish Mediterranean coast and some domestic iodized salts. According to the results obtained, the method developed is rapid, easy to apply and to be automated, avoids sample treatment and requires only few microliters of sample. Furthermore, it has a low detection limit and allows the quantification of inorganic iodine over a wide concentration range.

Psychometric assessment of the cultural capacity scale Spanish version in Chilean nursing students.

AIM: To assess the psychometric properties of the Cultural Capacity Scale Spanish version in Chilean nursing students. BACKGROUND: The increased diversity in healthcare facilities and the current shortage of local nursing workforce in Chile present a significant challenge to the nursing education to train future competent local nurses. To facilitate cultural competence development among Chilean nursing students, it is necessary to regularly assess their cultural competence, which necessitates a culturally adapted valid and reliable tool. METHODS: A convenience sample of 502 Chilean nursing students was surveyed in this cross-sectional study using the culturally adapted scale. Reliability of the instrument was established by internal consistency and stability reliability, while validity was established by content and construct. RESULTS: The Cronbach's α value of the entire scale was 0.95, and the test-retest reliability was 0.85. The Corrected Item-Total Correlations ranged from 0.45 to 0.78. The tool manifested an excellent content and construct validity. The exploratory factor analysis confirmed a single factor of the scale. DISCUSSION: The tool demonstrated evidence of internal consistency, stability reliability, content validity and construct validity. The study provided cross-cultural evidence for the potential application of this scale in Chile and other Spanish-speaking countries. CONCLUSION: The Cultural Capacity Scale Spanish version demonstrated sound psychometric properties for assessing the cultural competence of Chilean nursing students. LIMITATIONS: The sample was restricted to one university, and the tool was only used in Chilean nursing students. IMPLICATIONS FOR NURSING POLICY: The establishment of the Spanish version of the tool will facilitate accurate and timely monitoring of the cultural competence among Chilean nursing students and other Spanish-speaking nursing students and nurses, which can inform the creation of nursing policies aimed at ensuring cultural competence development.

Instant and efficient second-harmonic generation and downconversion in unprepared graded-index multimode fibers.

We show that germanium-doped graded-index multimode silica fibers can exhibit relatively high conversion efficiencies (∼6.5%) for second-harmonic generation when excited at 1064 nm. This frequency-doubling behavior is also found to be accompanied by an effective downconversion. As opposed to previous experiments carried out in single- and few-mode fibers where hours of preparation were required, in our system, these χ(2) related processes occur almost instantaneously. The efficiencies observed in our experiments are, to the best of our knowledge, among the highest ever reported in unprepared fibers.

All-fiber few-mode multicore photonic lantern mode multiplexer.

The emergence of space division multiplexing (SDM) for ultrahigh capacity networks has heralded pioneering Petabit-class optical transmission systems. In parallel to novel SDM fibers, a new class of components to enable scalable, low-loss schemes for unlocking fiber capacity is being developed. In this work, an all-fiber mode selective photonic lantern mode multiplexer designed for launching into few-mode multicore fibers is demonstrated. This device is capable of selectively exciting LP01, LP11a and LP11b modes in a seven-core configuration, resulting in 21 spatial channels, with less than 38 dB core-to-core crosstalk and insertion loss below 0.4 dB. The multicore photonic lantern multiplexer is scalable to larger number of cores and modes per core, and can be easily integrated with emerging ultra-high bandwidth few-mode multicore optical communication systems.

Reduced-symmetry LMA rod-type fiber for enhanced higher-order mode delocalization.

We present a novel design of a micro-structured large-pitch, large-mode-area (LMA) asymmetric rod-type fiber. By reducing the cladding symmetry through six high-refractive index germanium-doped silica inclusions, the fiber features strong higher-order mode (HOM) delocalization, leading to a potentially enhanced preferential gain for the fundamental mode in active fibers. In addition, high resolution spatially and spectrally (S2) resolved mode analysis measurements confirm HOM contributions below 1% and LP1m-like HOM contributions below the detection limit. This proposed fiber design enables single-mode operation, with near-diffraction-limited beam quality of M2=1.3 and an effective mode area of 2560 µm2 at 1064 nm. This design opens new insights into improving the threshold-like onset of modal instabilities in high-power fiber lasers and fiber amplifiers by efficiently suppressing LP11 modes.

Tailoring frequency generation in uniform and concatenated multimode fibers.

We demonstrate that frequency generation in multimode parabolic-index fibers can be precisely engineered through appropriate fiber design. This is accomplished by exploiting the onset of a geometric parametric instability that arises from resonant spatiotemporal compression. By launching the output of an amplified Q-switched microchip laser delivering 400 ps pulses at 1064 nm, we observe a series of intense frequency sidebands that strongly depend on the fiber core size. The nonlinear frequency generation is analyzed in three fiber samples with 50 µm, 60 µm, and 80 µm core diameters. We further demonstrate that by cascading fibers of different core sizes, a desired frequency band can be generated from the frequency lines parametrically produced in each section. The observed frequency shifts are in good agreement with analytical predictions and numerical simulations. Our results suggest that core scaling and fiber concatenation can provide a viable avenue in designing optical sources with tailored output frequencies.