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The presence of residual undifferentiated pluripotent stem cells (PSCs) in PSC-derived cell therapy products (CTPs) is a major safety issue for their clinical application, due to the potential risk of PSC-derived tumor formation. An international multidisciplinary multisite study to evaluate a droplet digital PCR (ddPCR) approach to detect residual undifferentiated PSCs in PSC-derived CTPs was conducted as part of the Health and Environmental Sciences Institute Cell Therapy-TRAcking, Circulation & Safety Technical Committee. To evaluate the use of ddPCR in quantifying residual iPSCs in a cell sample, different quantities of induced pluripotent stem cells (iPSCs) were spiked into a background of iPSC-derived cardiomyocytes (CMs) to mimic different concentrations of residual iPSCs. A one step reverse transcription ddPCR (RT-ddPCR) was performed to measure mRNA levels of several iPSC-specific markers and to evaluate the assay performance (precision, sensitivity, and specificity) between and within laboratories. The RT-ddPCR assay variability was initially assessed by measuring the same RNA samples across all participating facilities. Subsequently, each facility independently conducted the entire process, incorporating the spiking step, to discern the parameters influencing potential variability. Our results show that a RT-ddPCR assay targeting ESRG, LINC00678, and LIN28A genes offers a highly sensitive and robust detection of impurities of iPSC-derived CMs and that the main contribution to variability between laboratories is the iPSC-spiking procedure, and not the RT-ddPCR. The RT-ddPCR assay would be generally applicable for tumorigenicity evaluation of PSC-derived CTPs with appropriate marker genes suitable for each CTP.
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BACKGROUND AND OBJECTIVES: Assessing suicide risk in primary care settings has become standard practice; however, the emotional toll on medical providers remains understudied. This qualitative study examines the emotional impact of suicide assessments among family medicine residents. METHODS: We conducted one-on-one, semistructured, in-depth interviews with a convenience sample of residents enrolled in a family medicine residency program at a US military installation. Employing an exploratory, qualitative research approach, we iteratively coded transcribed interviews for content and themes. RESULTS: For this study, we interviewed 15 family medicine residents spanning all three postgraduate year groups. The primary objective of the comprehensive study was to evaluate the confidence levels of family medicine residents in suicide risk screening, with the intent to identify educational gaps for improvement. However, unexpectedly, participants revealed their profound negative emotional responses during these assessments. The emotional impact of suicide risk assessment was the most frequently coded theme in the study, with participants noting six main emotional reactions to assessing suicide risk among their patients: fear, weariness, anxiety, shock, overwhelm, and inadequacy. CONCLUSIONS: Despite claims of emotional detachment, participants often expressed surprise and vulnerability when faced with suicidal patients. With suicide screening becoming increasingly vital in primary care, understanding and mitigating the emotional impact on physicians is essential. Future research should explore strategies to support medical providers in navigating these challenging interactions effectively for both the patients and themselves.
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On-chip integration of 2D materials with unique structures and properties endow integrated devices with new functionalities and improved performance. With high flexibility in ways to modify its properties and compatibility with integrated platforms, graphene oxide (GO) is an exceptionally attractive 2D material for hybrid integrated photonic chips. Here, by harnessing unique property changes induced by photothermal effects in 2D GO films, novel functionalities beyond the capability of photonic integrated circuits are demonstrated. These include all-optical control and tuning, optical power limiting, and nonreciprocal light transmission. The 2D layered GO films are integrated onto photonic chips with precise control of their thickness and size. Benefitting from the broadband optical response of 2D GO films, all three functionalities feature a very wide operational optical bandwidth. By fitting the experimental results with theory, the changes in GO film properties induced by the photothermal effects are analyzed, revealing interesting insights about the physics of 2D GO films. These results highlight the versatility of 2D GO films in implementing new functions for integrated photonic devices for a wide range of applications.
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We study the interaction of a laser cavity-soliton microcomb with an externally coupled, co-propagating tunable CW pump, observing parametric Kerr interactions which lead to the formation of both a cross-phase modulation and a four-wave mixing replica of the laser cavity-soliton. We compare and explain the dependence of the microcomb spectra from both the cavity-soliton and pump parameters, demonstrating the ability to adjust the microcomb externally without breaking or interfering with the soliton state. The parametric nature of the process agrees with numerical simulations. The parametric extended state maintains the typical robustness of laser-cavity solitons.
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We report a dual-polarization radio frequency (RF) channelizer based on microcombs. Two high-Q micro-ring resonators (MRRs) with slightly different free spectral ranges (FSRs) are used: one MRR is pumped to yield soliton crystal microcombs ("active"), and the other MRR is used as a "passive" periodic optical filter supporting dual-polarization operation to slice the RF spectrum. With the tailored mismatch between the FSRs of the active and passive MRRs, wideband RF spectra can be channelized into multiple segments featuring digital-compatible bandwidths via the Vernier effect. Due to the use of dual-polarization states, the number of channelized spectral segments, and thus the RF instantaneous bandwidth (with a certain spectral resolution), can be doubled. In our experiments, we used 20 microcomb lines with â¼ 49â GHz FSR to achieve 20 channels for each polarization, with high RF spectra slicing resolutions at 144â MHz (TE) and 163â MHz (TM), respectively; achieving an instantaneous RF operation bandwidth of 3.1â GHz (TE) and 2.2â GHz (TM). Our approach paves the path towards monolithically integrated photonic RF receivers (the key components - active and passive MRRs are all fabricated on the same platform) with reduced complexity, size, and unprecedented performance, which is important for wide RF applications with digital-compatible signal detection.
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OBJECTIVES: Dementia caregivers (CGs) are at heightened risk for developing problems with anxiety and depression. Much attention has been directed toward developing and deploying interventions designed to protect CG health, but few have been supported by rigorous empirical evidence. Technology-based interventions that are effective, scalable, and do not add greatly to the CG burden are of particular interest. METHODS: We conducted a nine-month randomized controlled trial in 63 homes evaluating People Power Caregiver (PPCg), a system of sensors in the home connected to cloud-based software that alerts CGs about worrisome deviations from normal patterns (e.g., falls, wandering). RESULTS: CGs in the active condition had significantly less anxiety than those in the control condition at the six-month assessment. Greater anxiety reduction in the active condition at the six-month assessment was associated with greater interaction with PPCg via SMS text messages. There were no differences in anxiety at the three-month or nine-month assessments or in depression at any assessment. CONCLUSIONS: PPCg shows promise for reducing anxiety associated with caring for a =person with dementia. CLINICAL IMPLICATIONS: Technology-based interventions can help reduce CG anxiety, a major adverse consequence of caregiving that may be difficult to treat due to other demands on caregiver time and energy.
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Demencia , Dispositivos de Autoayuda , Humanos , Cuidadores , Demencia/terapia , Ansiedad/terapia , Trastornos de AnsiedadRESUMEN
The engineering of thermo-optic effects has found broad applications in integrated photonic devices, facilitating efficient light manipulation to achieve various functionalities. Here, we perform both an experimental characterization and a theoretical analysis of these effects in integrated microring resonators made from high-index doped silica, which have had many applications in integrated photonics and nonlinear optics. By fitting the experimental results with theory, we obtain fundamental parameters that characterize their thermo-optic performance, including the thermo-optic coefficient, the efficiency of the optically induced thermo-optic process, and the thermal conductivity. The characteristics of these parameters are compared to those of other materials commonly used for integrated photonic platforms, such as silicon, silicon nitride, and silica. These results offer a comprehensive insight into the thermo-optic properties of doped silica-based devices. Understanding these properties is essential for efficiently controlling and engineering them in many practical applications.
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Soliton crystals are a novel form of microcomb, with relatively high conversion efficiency, good thermal robustness, and simple initiation among the methods to generate them. Soliton crystals can be easily generated in microring resonators with an appropriate mode-crossing. However, fabrication defects can significantly affect the mode-crossing placement and strength in devices. To enable soliton crystal states to be harnessed for a broader range of microcomb applications, we need a better understanding of the link between mode-crossing properties and the desired soliton crystal properties. Here, we investigate how to generate the same soliton crystal state in two different microrings, how changes in microring temperature change the mode-crossing properties, and how mode-crossing properties affect the generation of our desired soliton crystal state. We find that temperature affects the mode-crossing position in these rings but without major changes in the mode-crossing strength. We find that our wanted state can be generated over a device temperature range of 25 ∘C, with different mode-crossing properties, and is insensitive to the precise mode-crossing position between resonances.
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RF photonic transversal signal processors, which combine reconfigurable electrical digital signal processing and high-bandwidth photonic processing, provide a powerful solution for achieving adaptive high-speed information processing. Recent progress in optical microcomb technology provides compelling multi-wavelength sources with a compact footprint, yielding a variety of microcomb-based RF photonic transversal signal processors with either discrete or integrated components. Although they operate based on the same principle, the processors in these two forms exhibit distinct performances. This paper presents a comparative investigation of their performances. First, we compare the performances of state-of-the-art processors, focusing on the processing accuracy. Next, we analyze various factors that contribute to the performance differences, including the tap number and imperfect response of experimental components. Finally, we discuss the potential for future improvement. These results provide a comprehensive comparison of microcomb-based RF photonic transversal signal processors implemented using discrete and integrated components and provide insights for their future development.
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Graphene oxide (GO) was initially developed to emulate graphene, but it was soon recognized as a functional material in its own right, addressing an application space that is not accessible to graphene and other carbon materials. Over the past decade, research on GO has made tremendous advances in material synthesis and property tailoring. These, in turn, have led to rapid progress in GO-based photonics, electronics and optoelectronics, paving the way for technological breakthroughs with exceptional performance. In this Review, we provide an overview of the optical, electrical and optoelectronic properties of GO and reduced GO on the basis of their chemical structures and fabrication approaches, together with their applications in key technologies such as solar energy harvesting, energy storage, medical diagnosis, image display and optical communications. We also discuss the challenges of this field, together with exciting opportunities for future technological advances.
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All-optical signal processing based on nonlinear optical devices is promising for ultrafast information processing in optical communication systems. Recent advances in two-dimensional (2D) layered materials with unique structures and distinctive properties have opened up new avenues for nonlinear optics and the fabrication of related devices with high performance. This paper reviews the recent advances in research on third-order optical nonlinearities of 2D materials, focusing on all-optical processing applications in the optical telecommunications band near 1550 nm. First, we provide an overview of the material properties of different 2D materials. Next, we review different methods for characterizing the third-order optical nonlinearities of 2D materials, including the Z-scan technique, third-harmonic generation (THG) measurement, and hybrid device characterization, together with a summary of the measured n2 values in the telecommunications band. Finally, the current challenges and future perspectives are discussed.
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BACKGROUND: Shoulder pathology can occur concurrently with a distal radius fracture (DRF) but few studies have examined this population. PURPOSE: The purpose of this study was to expand the understanding of the impact of shoulder pathology on individuals with DRF. STUDY DESIGN: Mixed Methods Design. METHODS: A total of 45 participants with a DRF were categorized into a DRF only (n = 29) and shoulder pathology concurrent with DRF (SPCDRF) (n = 16) groups. Quantitative data gathered included demographics, Quick Disabilities of the Arm, Shoulder, and Hand, Tampa Scale of Kinesiophobia-11, Visual Analog Scale, and Compensatory Mechanism Checklist. Qualitative interviews were performed with 7 participants in the SPCDRF group. Within group correlations were analyzed via the Spearman Rank. The Mann Whitney U test was used to compare the two groups. Qualitative analysis was performed to describe the experience of participants in the SPCDRF group. A mixed methods analysis compared quantitative and qualitative data. RESULTS: Sixteen participants (35.6%) in the sample presented with shoulder pathology; 6 participants (37.5%) presented at initial evaluation due to the fall; 10 participants (62.5%) developed shoulder pathology due to compensation or disuse. Average number of days to develop shoulder pathology after the DRF was 43 days. SPCDRF participants had significantly greater pain levels (p = .02) and more activity avoidance (p = .03) than the DRF only group. Four qualitative themes emerged: It's difficult to perform occupations and changes had to be made; There is fear and uncertainty; The impact of pain; Tried to be normal but could not Mixed methods analysis found that qualitative data further illuminated quantitative findings. CONCLUSIONS: Individuals with shoulder pathology concurrent with a DRF may present with higher pain levels and avoid activity more. In addition, they may describe fearfulness in using their injured upper extremity especially if they have high levels of pain. STUDY DESIGN: Mixed Methods Design.
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Fracturas del Radio , Fracturas de la Muñeca , Humanos , Hombro , Mano , Dimensión del Dolor , Dolor , Fracturas del Radio/complicaciones , Fracturas del Radio/epidemiologíaRESUMEN
Laser cavity-soliton microcombs are robust optical pulsed sources, usually implemented with a microresonator-filtered fibre laser. In such a configuration, a nonlinear microcavity converts the narrowband pulse resulting from bandwidth-limited amplification to a background-free broadband microcomb. Here, we theoretically and experimentally study the soliton conversion efficiency between the narrowband input pulse and the two outputs of a four-port integrated microcavity, namely the 'Drop' and 'Through' ports. We simultaneously measure on-chip, single-soliton conversion efficiencies of 45% and 25% for the two broadband comb outputs at the 'Drop' and 'Through' ports of a 48.9 GHz free-spectral range micro-ring resonator, obtaining a total conversion efficiency of 72%.
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In many disciplines, states that emerge in open systems far from equilibrium are determined by a few global parameters1,2. These states can often mimic thermodynamic equilibrium, a classic example being the oscillation threshold of a laser3 that resembles a phase transition in condensed matter. However, many classes of states cannot form spontaneously in dissipative systems, and this is the case for cavity solitons2 that generally need to be induced by external perturbations, as in the case of optical memories4,5. In the past decade, these highly localized states have enabled important advancements in microresonator-based optical frequency combs6,7. However, the very advantages that make cavity solitons attractive for memories-their inability to form spontaneously from noise-have created fundamental challenges. As sources, microcombs require spontaneous and reliable initiation into a desired state that is intrinsically robust8-20. Here we show that the slow non-linearities of a free-running microresonator-filtered fibre laser21 can transform temporal cavity solitons into the system's dominant attractor. This phenomenon leads to reliable self-starting oscillation of microcavity solitons that are naturally robust to perturbations, recovering spontaneously even after complete disruption. These emerge repeatably and controllably into a large region of the global system parameter space in which specific states, highly stable over long timeframes, can be achieved.
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We experimentally investigate power-sensitive photo-thermal tuning (PTT) of two-dimensional (2D) graphene oxide (GO) films coated on integrated optical waveguides. We measure the light power thresholds for reversible and permanent GO reduction in silicon nitride (SiN) waveguides integrated with one and two layers of GO. For the device with one layer of GO, the power threshold for reversible and permanent GO reduction are ~20 and ~22 dBm, respectively. For the device with two layers of GO, the corresponding results are ~13 and ~18 dBm, respectively. Raman spectra at different positions of a hybrid waveguide with permanently reduced GO are characterized, verifying the inhomogeneous GO reduction along the direction of light propagation through the waveguide. The differences between the PTT induced by a continuous-wave laser and a pulsed laser are also compared, confirming that the PTT mainly depend on the average input power. These results reveal interesting features for 2D GO films coated on integrated optical waveguides, which are of fundamental importance for the control and engineering of GO's properties in hybrid integrated photonic devices.
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E1 and E2 (E1E2), the fusion proteins of Hepatitis C Virus (HCV), are unlike that of any other virus yet described, and the detailed molecular mechanisms of HCV entry/fusion remain unknown. Hypervariable region-1 (HVR-1) of E2 is a putative intrinsically disordered protein tail. Here, we demonstrate that HVR-1 has an autoinhibitory function that suppresses the activity of E1E2 on free virions; this is dependent on its conformational entropy. Thus, HVR-1 is akin to a safety catch that prevents premature triggering of E1E2 activity. Crucially, this mechanism is turned off by host receptor interactions at the cell surface to allow entry. Mutations that reduce conformational entropy in HVR-1, or genetic deletion of HVR-1, turn off the safety catch to generate hyper-reactive HCV that exhibits enhanced virus entry but is thermally unstable and acutely sensitive to neutralising antibodies. Therefore, the HVR-1 safety catch controls the efficiency of virus entry and maintains resistance to neutralising antibodies. This discovery provides an explanation for the ability of HCV to persist in the face of continual immune assault and represents a novel regulatory mechanism that is likely to be found in other viral fusion machinery.
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Hepacivirus , Hepatitis C , Anticuerpos Neutralizantes , Entropía , Hepacivirus/genética , Hepacivirus/metabolismo , Humanos , Proteínas del Envoltorio Viral/metabolismo , Internalización del VirusRESUMEN
BACKGROUND: Given negative publicity surrounding surgical mesh in the media, the aim of this study was to assess post-operative morbidity and quality of life (QoL) following laparoscopic inguinal hernia surgery with self-adhesive ProgripTM mesh. METHODS: This study is a retrospective analysis of ProgripTM mesh for laparoscopic inguinal hernia repairs by two experienced surgeons in the public and private sectors. Data were collected by screening electronic clinical records. A sample of participants were contacted directly for QoL assessment using the Carolinas Comfort Scale (CCS). Descriptive statistical analysis was performed in Microsoft Excel. RESULTS: Five hundred and fifty-two patients had 648 hernia repairs using ProgripTM mesh from 2013 to 2019. The rate of hernia recurrence was 0.2% (n = 1). The rate of reoperation was 0.5% (n = 3). There were no mesh explant procedures, no adhesion-related readmissions and no perioperative deaths. Haematoma was the most common post-operative complication, occurring in 3.1% of participants (n = 17). The CCS assessment had a response rate of 55.8%. A total of 93% of CCS questions were answered with no sensation of mesh, 92% with no pain and 98% with no movement limitation. No participants reported severe or disabling symptoms. CONCLUSION: In this cohort, laparoscopic inguinal hernia repair with ProgripTM has shown a low recurrence rate and excellent post-operative QoL. The QoL data shows that the public perception of mesh based on media reports of complications may not be relevant for this operation. The knowledge gained from this study reinforces the potential value of a national mesh registry such as those seen overseas.
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Hernia Inguinal , Laparoscopía , Cirujanos , Adhesivos , Hernia Inguinal/complicaciones , Hernia Inguinal/cirugía , Herniorrafia/efectos adversos , Herniorrafia/métodos , Humanos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Dolor Postoperatorio/etiología , Calidad de Vida , Recurrencia , Cementos de Resina , Estudios Retrospectivos , Mallas Quirúrgicas/efectos adversosRESUMEN
We experimentally demonstrate enhanced spectral broadening of femtosecond optical pulses after propagation through silicon-on-insulator (SOI) nanowire waveguides integrated with two-dimensional (2D) graphene oxide (GO) films. Owing to the strong mode overlap between the SOI nanowires and the GO films with a high Kerr nonlinearity, the self-phase modulation (SPM) process in the hybrid waveguides is significantly enhanced, resulting in greatly improved spectral broadening of the femtosecond optical pulses. A solution-based, transfer-free coating method is used to integrate GO films onto the SOI nanowires with precise control of the film thickness. Detailed SPM measurements using femtosecond optical pulses are carried out, achieving a broadening factor of up to ~4.3 for a device with 0.4-mm-long, 2 layers of GO. By fitting the experimental results with the theory, we obtain an improvement in the waveguide nonlinear parameter by a factor of ~3.5 and in the effective nonlinear figure of merit (FOM) by a factor of ~3.8, relative to the uncoated waveguide. Finally, we discuss the influence of GO film length on the spectral broadening and compare the nonlinear optical performance of different integrated waveguides coated with GO films. These results confirm the improved nonlinear optical performance of silicon devices integrated with 2D GO films.
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With compact footprint, low energy consumption, high scalability, and mass producibility, chip-scale integrated devices are an indispensable part of modern technological change and development. Recent advances in 2D layered materials with their unique structures and distinctive properties have motivated their on-chip integration, yielding a variety of functional devices with superior performance and new features. To realize integrated devices incorporating 2D materials, it requires a diverse range of device fabrication techniques, which are of fundamental importance to achieve good performance and high reproducibility. This paper reviews the state-of-art fabrication techniques for the on-chip integration of 2D materials. First, an overview of the material properties and on-chip applications of 2D materials is provided. Second, different approaches used for integrating 2D materials on chips are comprehensively reviewed, which are categorized into material synthesis, on-chip transfer, film patterning, and property tuning/modification. Third, the methods for integrating 2D van der Waals heterostructures are also discussed and summarized. Finally, the current challenges and future perspectives are highlighted.