Titanium:sapphire-on-insulator integrated lasers and amplifiers.

Titanium:sapphire (Ti:sapphire) lasers have been essential for advancing fundamental research and technological applications, including the development of the optical frequency comb1, two-photon microscopy2 and experimental quantum optics3,4. Ti:sapphire lasers are unmatched in bandwidth and tuning range, yet their use is restricted because of their large size, cost and need for high optical pump powers5. Here we demonstrate a monocrystalline titanium:sapphire-on-insulator (Ti:SaOI) photonics platform that enables dramatic miniaturization, cost reduction and scalability of Ti:sapphire technology. First, through the fabrication of low-loss whispering-gallery-mode resonators, we realize a Ti:sapphire laser operating with an ultralow, sub-milliwatt lasing threshold. Then, through orders-of-magnitude improvement in mode confinement in Ti:SaOI waveguides, we realize an integrated solid-state (that is, non-semiconductor) optical amplifier operating below 1 µm. We demonstrate unprecedented distortion-free amplification of picosecond pulses to peak powers reaching 1.0 kW. Finally, we demonstrate a tunable integrated Ti:sapphire laser, which can be pumped with low-cost, miniature, off-the-shelf green laser diodes. This opens the doors to new modalities of Ti:sapphire lasers, such as massively scalable Ti:sapphire laser-array systems for several applications. As a proof-of-concept demonstration, we use a Ti:SaOI laser array as the sole optical control for a cavity quantum electrodynamics experiment with artificial atoms in silicon carbide6. This work is a key step towards the democratization of Ti:sapphire technology through a three-orders-of-magnitude reduction in cost and footprint and introduces solid-state broadband amplification of sub-micron wavelength light.

Smart mandibular advancement devices for obstructive sleep apnea: a systematic literature review.

PURPOSE: The goal of this review is to provide sleep physicians, dentists, and researchers with an evidence-based overview of the literature on smart mandibular advancement devices (MADs) for the treatment of obstructive sleep apnea. METHODS: A systematic literature search was conducted by two blinded reviewers and an information specialist. A smart MAD was defined as any MAD with additional functionality besides mandibular protrusion. The bibliographic databases Medline, Embase, and Scopus were used to identify relevant publications. Studies were included if they described any stage of development of smart MADs. A total of 3162 titles and abstracts were screened for their relevance. In total, 58 articles were selected for full-text screening, 26 of which were included in this review. RESULTS: The overall quality of the available literature was low. Most of the studies were observational, clinical or applied-research articles. The authors classified MADs into two main groups: passive and active. Passive MADs measured patient data, most commonly patient compliance. Active MADs adjusted protrusion of the mandible in response to patient data and were found in various phases of technological readiness (in development, demonstration, or deployment). CONCLUSION: Innovations in smart mandibular advancement devices most frequently track patient compliance. Devices measuring other health parameters and active, feedback-controlled, devices are increasingly reported on. However, studies demonstrating their added benefit over traditional methods remain sparse. With further study, smart mandibular advancement devices have the potential to improve the efficiency of obstructive sleep apnea treatment and provide new treatment possibilities.

Digital technologies used in clinical trial recruitment and enrollment including application to trial diversity and inclusion: A systematic review.

Background: Many clinical trials fail because of poor recruitment and enrollment which can directly impact the success of biomedical and clinical research outcomes. Options to leverage digital technology for improving clinical trial management are expansive, with potential benefits for improving access to clinical trials, encouraging trial diversity and inclusion, and potential cost-savings through enhanced efficiency. Objectives: This systematic review has two key aims: (1) identify and describe the digital technologies applied in clinical trial recruitment and enrollment and (2) evaluate evidence of these technologies addressing the recruitment and enrollment of racial and ethnic minority groups. Methods: We conducted a cross-disciplinary review of articles from PubMed, IEEE Xplore, and ACM Digital Library, published in English between January 2012 and July 2022, using MeSH terms and keywords for digital health, clinical trials, and recruitment and enrollment. Articles unrelated to technology in the recruitment/enrollment process or those discussing recruitment/enrollment without technology aspects were excluded. Results: The review returned 614 results, with 21 articles (four reviews and 17 original research articles) deemed suitable for inclusion after screening and full-text review. To address the first objective, various digital technologies were identified and characterized, which included articles with more than one technology subcategory including (a) multimedia presentations (19%, n = 4); (b) mobile applications (14%, n = 3); (c) social media platforms (29%, n = 6); (d) machine learning and computer algorithms (19%, n = 4); (e) e-consenting (24%, n = 5); (f) blockchain (5%, n = 1); (g) web-based programs (24%, n = 5); and (h) virtual messaging (24%, n = 5). Additionally, subthemes, including specific diseases or conditions addressed, privacy and regulatory concerns, cost/benefit analyses, and ethnic and minority recruitment considerations, were identified and discussed. Limited research was found to support a particular technology's effectiveness in racial and ethnic minority recruitment and enrollment. Conclusion: Results from this review illustrate that several types of technology are currently being explored and utilized in clinical trial recruitment and enrollment stages. However, evidence supporting the use of digital technologies is varied and requires further research and evaluation to identify the most valuable opportunities for encouraging diversity in clinical trial recruitment and enrollment practices.

Non-sleep related outcomes of maxillomandibular advancement, a systematic review.

Maxillomandibular advancement has been shown to be an effective treatment for obstructive sleep apnea; however, the literature focuses mainly on sleep-related parameters such as apnea-hypopnea index, respiratory disturbance index and Epworth sleepiness scale. Other factors that may be important to patients, such as esthetics, patient satisfaction, nasality, swallowing problems and so forth have been reported in the literature but have not been systematically studied. Together with an information specialist, an extensive search in Medline, Embase and Scopus yielded 1592 unique articles. Titles and abstracts were screened by two blinded reviewers. In total, 75 articles were deemed eligible for full-text screening and 38 articles were included for qualitative synthesis. The most common categories of non-sleep related outcomes found were surgical accuracy, facial esthetics, functional outcomes, quality of life, patient satisfaction, and emotional health. All categories were reported using heterogenous methods, such that meta-analysis could not be performed. There was lack of consistent methods to assess these outcomes. This work is the first to systematically review non-sleep related outcomes of maxillomandibular advancement. Despite growing interest in evaluating surgical outcomes through patient subjective experiences, this review points to the need of standardized, validated methods to report these outcomes.

Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer's disease mice.

BACKGROUND: Biologic TNF-α inhibitors (bTNFIs) can block cerebral TNF-α in Alzheimer's disease (AD) if these macromolecules can cross the blood-brain barrier (BBB). Thus, a model bTNFI, the extracellular domain of type II TNF-α receptor (TNFR), which can bind to and sequester TNF-α, was fused with a mouse transferrin receptor antibody (TfRMAb) to enable brain delivery via BBB TfR-mediated transcytosis. Previously, we found TfRMAb-TNFR to be protective in a mouse model of amyloidosis (APP/PS1) and tauopathy (PS19), and herein we investigated its effects in mice that combine both amyloidosis and tauopathy (3xTg-AD). METHODS: Eight-month-old female 3xTg-AD mice were injected intraperitoneally with saline (n = 11) or TfRMAb-TNFR (3 mg/kg; n = 11) three days per week for 12 weeks. Age-matched wild-type (WT) mice (n = 9) were treated similarly with saline. Brains were processed for immunostaining and high-resolution multiplex NanoString GeoMx spatial proteomics. RESULTS: We observed regional differences in proteins relevant to Aß, tau, and neuroinflammation in the hippocampus of 3xTg-AD mice compared with WT mice. From 64 target proteins studied using spatial proteomics, a comparison of the Aß-plaque bearing vs. plaque-free regions in the 3xTg-AD mice yielded 39 differentially expressed proteins (DEP) largely related to neuroinflammation (39% of DEP) and Aß and tau pathology combined (31% of DEP). Hippocampal spatial proteomics revealed that the majority of the proteins modulated by TfRMAb-TNFR in the 3xTg-AD mice were relevant to microglial function (⁓ 33%). TfRMAb-TNFR significantly reduced mature Aß plaques and increased Aß-associated microglia around larger Aß deposits in the 3xTg-AD mice. Further, TfRMAb-TNFR increased mature Aß plaque-associated microglial TREM2 in 3xTg-AD mice. CONCLUSION: Overall, despite the low visual Aß load in the 11-month-old female 3xTg-AD mice, our results highlight region-specific AD-relevant DEP in the hippocampus of these mice. Chronic TfRMAb-TNFR dosing modulated several DEP involved in AD pathology and showed a largely microglia-centric mechanism of action in the 3xTg-AD mice.

Rates of adverse events and related risk factors following e-cigarette use.

BACKGROUND: E-cigarettes have emerged as popular products, especially for younger populations. However, concerns regarding health effects exist and there is a notable gap in understanding the prevalence and nature of adverse events. This study aims to examine the rate of adverse events in individuals who use e-cigarettes in a large sample. METHODS: A cross-sectional survey was conducted with a sample of 4695 current and former e-cigarette users with a median age of 34 years. The survey collected data on e-cigarette use, adverse events experienced, product characteristics, related behaviors, sociodemographic factors and presence of medical comorbidities. Statistical analyses were conducted using Pearson's chi-squared tests and logistic regression. RESULTS: A total of 78.9% of respondents reported experiencing an adverse event within 6 h of using a vaping device, with the most common events being headache, anxiety and coughing. Product characteristics and related behaviors significantly influenced the risk of adverse events. There were also sociodemographic disparities, with Hispanic respondents and those with at least college-level education reporting higher rates of adverse events. CONCLUSIONS: Our study found a high rate of adverse events among e-cigarette users. We identified that certain e-cigarette product characteristics, behaviors and medical comorbidities significantly increased the risk of these events.

Identification and Characterization of Illegal Sales of Cannabis and Nicotine Delivery Products on Telegram Messaging Platform.

INTRODUCTION: Unregulated and potentially illegal sales of tobacco, nicotine, and cannabis products have been detected on various social media platforms, e-commerce sites, online retailers, and the dark web. New end-to-end encrypted messaging services are popular among online users and present opportunities for marketing, trading, and selling of these products. The purpose of this study was to identify and characterize tobacco, nicotine, and cannabis selling activity on the messaging platform Telegram. METHODS: The study was conducted in three phases: (1) identifying keywords related to tobacco, nicotine, and cannabis products for purposes of detecting Telegram groups and channel messages; (2) automated data collection from public Telegram groups; and (3) manual annotation and classification of messages engaged in marketing and selling products to consumers. RESULTS: Four keywords were identified ("Nicotine," "Vape," "Cannabis," and "Smoke") that yielded 20 Telegram groups with 262 506 active subscribers. Total volume of channel messages was 43 963 unique messages that included 3094 (7.04%) marketing/selling messages. The most commonly sold products in these groups were cannabis-derived products (83.25%, n = 2576), followed by tobacco/nicotine-derived products (6.46%, n = 200), and other illicit drugs (0.77%, n = 24). A variety of marketing tactics and a mix of seller accounts were observed, though most appeared to be individual suppliers. CONCLUSIONS: Telegram is an online messaging application that allows for custom group creation and global connectivity, but also includes unregulated activities associated with the sale of cannabis and nicotine delivery products. Greater attention is needed to conduct monitoring and enforcement on these emerging platforms for unregulated and potentially illegal cannabis and nicotine product sales direct-to-consumer. IMPLICATIONS: Based on study results, Telegram represents an emerging platform that enables a robust cannabis and nicotine-selling marketplace. As local, state, and national tobacco control regulations continue to advance sales restrictions and bans at the retail level, easily accessible and unregulated Internet-based channels must be further assessed to ensure that they do not act as conduits for exposure and access to unregulated or illegal cannabis and nicotine products.

Tobacco Product Marketing Orders and Online Marketing and Sale of Unauthorized ENDS Products.

This study characterizes online marketing of unauthorized electronic nicotine delivery systems (ENDS).

Dataset on mesoplastics and microplastics abundances and characteristics from sandy beaches before and after typhoon events in northern Taiwan.

A comprehensive dataset is presented, which describes the abundance, shapes, and colors of meso- and microplastic particles collected from two sandy beaches situated on the north coast of Taiwan. The sampling of beach sand was conducted repetitively at fixed locations over a time period of 20 months, commencing from April 2018 to November 2019, with the aim of monitoring the variations in distribution and composition of plastic particles. A total of three adjacent transects perpendicular to the waterline were sampled, with bulk sand samples collected from 50 × 50 cm quadrats. The samples were subjected to drying, weighing, and sieving to obtain mesoplastic fractions (5-25 mm) and microplastic fractions (1-5 mm). Visual identification was employed to extract mesoplastic particles, while density separation using a saturated NaCl solution was utilized to extract microplastic particles. The particles were counted visually under a stereo microscope, and subsequently classified based on their shape and color. Any unknown particles were subjected to FTIR spectroscopy. Particle count data are presented as particles per unit area (0.25 m2) but can be converted to particles per kg d.w. by employing the weight of dry sand, as provided in the tables. The dataset encompasses a time series and delineates the changes in particle distribution and composition following extreme weather events. It can be utilized for further research by reanalyzing the data from different perspectives or by incorporating other factors.

Inverse-designed silicon carbide quantum and nonlinear photonics.

Inverse design has revolutionized the field of photonics, enabling automated development of complex structures and geometries with unique functionalities unmatched by classical design. However, the use of inverse design in nonlinear photonics has been limited. In this work, we demonstrate quantum and classical nonlinear light generation in silicon carbide nanophotonic inverse-designed Fabry-Pérot cavities. We achieve ultra-low reflector losses while targeting a pre-specified anomalous dispersion to reach optical parametric oscillation. By controlling dispersion through inverse design, we target a second-order phase-matching condition to realize second- and third-order nonlinear light generation in our devices, thereby extending stimulated parametric processes into the visible spectrum. This first realization of computational optimization for nonlinear light generation highlights the power of inverse design for nonlinear optics, in particular when combined with highly nonlinear materials such as silicon carbide.

Association between the Dietary Phytochemical Index and Lower Prevalence of Obesity in Korean Preschoolers.

Little is known regarding Korean preschooler dietary phytochemical index (DPIs). We used the 24 h recall data of 1196 participants aged 3-5 years from the Korea National Health and Nutrition Examination Survey to study the association between dietary food intake and obesity prevalence. The amount of dietary intake by food group was compared according to sex and DPI quartile. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression models. The average total DPI and energy from phytochemical food groups were not significantly different according to sex, although boys had a higher total daily food intake. Different inclinations between DPI quartiles and amount of intake were observed in the food groups; specifically, beans showed a higher intake difference between Q1 and Q4 for boys than in the other food groups. The highest DPI quartile had a significantly lower obesity prevalence than the lowest DPI quartile in all models for boys only when obesity prevalence by weight percentile was analyzed (Model 3, OR: 0.287, 95% CI: 0.095-0.868, p for trend < 0.05). Our results suggest a high DPI could help prevent obesity in preschoolers.

The Effects of a Blood-Brain Barrier Penetrating Erythropoietin in a Mouse Model of Tauopathy.

Erythropoietin (EPO), a hematopoietic neurotrophin, is a potential therapeutic for Alzheimer's disease (AD) but has limited blood-brain barrier (BBB) permeability. EPO fused to a chimeric transferrin receptor monoclonal antibody (cTfRMAb) enters the brain via TfR-mediated transcytosis across the BBB. We previously showed that cTfRMAb-EPO is protective in a mouse model of amyloidosis, but its effects on tauopathy are not known. Given that amyloid and tau pathology are characteristics of AD, the effects of cTfRMAb-EPO were studied in a tauopathy mouse model (PS19). Six-month-old PS19 mice were injected intraperitoneally with either saline (PS19-Saline; n = 9) or cTfRMAb-EPO (PS19-cTfRMAb-EPO, 10 mg/kg; n = 10); every two or three days on alternate weeks for 8 weeks. Age-matched, saline-treated, wildtype littermates (WT-Saline; n = 12) were injected using the same protocol. After 8 weeks, locomotion, hyperactivity, and anxiety were assessed via the open-field test, and brains were harvested and sectioned. Cerebral cortex, hippocampus, amygdala, and entorhinal cortex sections were analyzed for phospho-tau (AT8) and microgliosis (Iba1). Hippocampal cellular density (H&E) was also assessed. PS19-Saline mice were hyperactive and less anxious compared to WT-Saline mice, and these behavioral phenotypes were significantly reduced in the PS19-cTfRMAb-EPO mice compared to the PS19-Saline mice. cTfRMAb-EPO significantly reduced AT8 load by ≥50% in all of the brain regions analyzed and microgliosis in the entorhinal cortex and amygdala compared to the PS19-Saline mice. Hippocampal pyramidal and granule cell layer density did not differ significantly between the PS19-cTfRMAb-EPO and PS19-Saline mice. This proof-of-concept study demonstrates the therapeutic effects of the BBB-penetrating cTfRMAb-EPO in PS19 mice.

Human Capital Development Factors and Black Adolescent Tobacco and Cannabis Use.

INTRODUCTION: This study examined the association of four domains of human capital development (cognitive development, social and emotional development, physical health, and mental health) and exclusive and concurrent tobacco and cannabis use (TCU) among black youth. AIMS AND METHODS: Nationally representative annual cross-sectional data for black adolescents (12-17 years; N = 9017) in the National Survey on Drug Use and Health 2015-2019 were analyzed. Analyses examined the influence of human capital factors (cognitive development, social and emotional development, physical health, and mental health) on exclusive and concurrent TCU. RESULTS: In total, 50.4% were males; prevalence of 12-month tobacco use fluctuated insignificantly between 5.6% and 7.6% across survey years. Similarly, prevalence of 12-month cannabis use remained relatively stable around 13%, with no significant linear change. Prevalence of concurrent TCU also fluctuated insignificantly between 3.5% and 5.3%. Investment in cognitive development decreased the odds of tobacco (aOR = 0.58, p < .001), cannabis (aOR = 0.64, p < .001), and concurrent tobacco and cannabis (aOR = 0.58, p < .001) use. Similarly, investment in social and emotional development reduced the odds of tobacco (aOR = 086, p < .001), cannabis (aOR = 0.83, p < .001), and concurrent tobacco and cannabis (aOR = 0.81, p < .001) use. Good physical health reduced the odds of tobacco (aOR = 0.52, p < .1), cannabis (aOR = 0.63, p < .05), and concurrent TCU (aOR = 0.54, p < .05). Major depressive episodes increased the likelihood of cannabis use (aOR = 1.62, p < .001). CONCLUSIONS: Investment in cognitive, social, and emotional aspects of human capital development, and physical health among black youth is protective against TCU. Efforts to sustain human capital development among black adolescents may contribute to reducing TCU disparities. IMPLICATIONS: This is one of few studies to examine human capital development factors and their associations with TCU among black youth. Efforts to eliminate tobacco/cannabis-related disparities among black youth should also invest in social, emotional, cognitive, and physical health development opportunities.

Disparities in localized malignant lung cancer surgical treatment: A population-based cancer registry analysis.

BACKGROUND: Lung cancer (LC) continues to be the leading cause of cancer deaths in the United States. Surgical treatment has proven to offer a favorable prognosis and a better 5-year relative survival for patients with early or localized tumors. This novel study investigates the factors associated with the odds of receiving surgical treatment for localized malignant LC in Tennessee. METHODS: Population-based data of 9679 localized malignant LC patients from the Tennessee Cancer Registry (2005-2015) were utilized to examine the factors associated with receiving surgical treatment for localized malignant LC. Bivariate and multivariate logistic regression analyses, cross-tabulation, and Chi-Square ( χ 2 ) tests were conducted to assess these factors. RESULTS: Patients with localized malignant LC who initiated treatment after 2.7 weeks were 46% less likely to receive surgery (adjusted odds ratio [AOR] = 0.54; 95% confidence interval [CI] = 0.50-0.59; p < 0.0001). Females had a greater likelihood (AOR = 1.14; CI = 1.03-1.24) of receiving surgical treatment compared to men. Blacks had lower odds (AOR = 0.76; CI = 0.65-0.98) of receiving surgical treatment compared to Whites. All marital groups had higher odds of receiving surgical treatment compared to those who were single/never married. Patients living in Appalachian county had lower odds of receiving surgical treatment (AOR = 0.65; CI = 0.59-0.71) compared with those in the non-Appalachian county. Patients with private (AOR = 2.09; CI = 1.55-2.820) or public (AOR = 1.42; CI = 1.06-1.91) insurance coverage were more likely to receive surgical treatment compared to self-pay/uninsured patients. Overall, the likelihood of patients receiving surgical treatment for localized malignant LC decreases with age. CONCLUSION: Disparities exist in the receipt of surgical treatment among patients with localized malignant LC in Tennessee. Health policies should target reducing these disparities to improve the survival of these patients.

Multi-dimensional data transmission using inverse-designed silicon photonics and microcombs.

The use of optical interconnects has burgeoned as a promising technology that can address the limits of data transfer for future high-performance silicon chips. Recent pushes to enhance optical communication have focused on developing wavelength-division multiplexing technology, and new dimensions of data transfer will be paramount to fulfill the ever-growing need for speed. Here we demonstrate an integrated multi-dimensional communication scheme that combines wavelength- and mode- multiplexing on a silicon photonic circuit. Using foundry-compatible photonic inverse design and spectrally flattened microcombs, we demonstrate a 1.12-Tb/s natively error-free data transmission throughout a silicon nanophotonic waveguide. Furthermore, we implement inverse-designed surface-normal couplers to enable multimode optical transmission between separate silicon chips throughout a multimode-matched fibre. All the inverse-designed devices comply with the process design rules for standard silicon photonic foundries. Our approach is inherently scalable to a multiplicative enhancement over the state of the art silicon photonic transmitters.

Factors affecting tobacco, nicotine, and cannabis product use among California young adults during the COVID-19 pandemic: A qualitative study.

The effects of COVID-19 on tobacco and cannabis use have been variable, and it is unclear the extent to which factors affecting changes in tobacco and cannabis use differ. The purpose of this study was to identify the COVID-19-related factors that affect changes in tobacco and cannabis use during the pandemic. Focus groups with 114 young adults in California in April 2021 were held to discuss tobacco and cannabis use patterns, adverse events, and the effect of COVID-19 on tobacco and cannabis product use. Factors affecting changes in use were largely similar between tobacco products and cannabis products. Increases in product use were a result of changing social environment, coping with emotional and psychological distress, and product related factors. Decreases in product use were a result of social isolation, COVID-19-related health concerns, disruptions in daily patterns of living, and reduced access. Drivers of increased cannabis use distinct from tobacco or nicotine product use included feeling greater freedom to disengage and perceptions of less harm. Improved understanding of how the pandemic has affected tobacco and cannabis use can inform tailored interventions to both support those who have decreased or quit and assist those who have increased use during the pandemic to reduce or cease their consumption.

Engineered helicase replaces thermocycler in DNA amplification while retaining desired PCR characteristics.

Polymerase Chain Reaction (PCR) is an essential method in molecular diagnostics and life sciences. PCR requires thermal cycling for heating the DNA for strand separation and cooling it for replication. The process uses a specialized hardware and exposes biomolecules to temperatures above 95 °C. Here, we engineer a PcrA M6 helicase with enhanced speed and processivity to replace the heating step by enzymatic DNA unwinding while retaining desired PCR characteristics. We name this isothermal amplification method SHARP (SSB-Helicase Assisted Rapid PCR) because it uses the engineered helicase and single-stranded DNA binding protein (SSB) in addition to standard PCR reagents. SHARP can generate amplicons with lengths of up to 6000 base pairs. SHARP can produce functional DNA, a plasmid that imparts cells with antibiotic resistance, and can amplify specific fragments from genomic DNA of human cells. We further use SHARP to assess the outcome of CRISPR-Cas9 editing at endogenous genomic sites.