Optomechanical Generation of Coherent GHz Vibrations in a Phononic Waveguide.

Nanophononics has the potential for information transfer, in an analogous manner to its photonic and electronic counterparts. The adoption of phononic systems has been limited, due to difficulties associated with the generation, manipulation, and detection of phonons, especially at GHz frequencies. Existing techniques often require piezoelectric materials with an external radiofrequency excitation that are not readily integrated into existing CMOS infrastructures, while nonpiezoelectric demonstrations have been inefficient. In this Letter, we explore the optomechanical generation of coherent phonons in a suspended 2D silicon phononic crystal cavity with a guided mode around 6.8 GHz. By incorporating an air-slot into this cavity, we turn the phononic waveguide into an optomechanical platform that exploits localized photonic modes resulting from inherent fabrication imperfections for the transduction of mechanics. Such a platform exhibits very fine control of phonons using light, and is capable of coherent self-sustained phonon generation around 6.8 GHz, operating at room temperature. The ability to generate high frequency coherent mechanical vibrations within such a simple 2D CMOS-compatible system could be a first step towards the development of sources in phononic circuitry and the coherent manipulation of other solid-state properties.

Dispersion Mapping in 3-Dimensional Core-Shell Photonic Crystal Lattices Capable of Negative Refraction in the Mid-Infrared.

Engineering of the dispersion properties of a photonic crystal (PhC) opens a new paradigm for the design and function of PhC devices. Exploiting the dispersion properties of PhCs allows control over wave propagation within a PhC. We describe the design, fabrication, and experimental observation of photonic bands for 3D PhCs capable of negative refraction in the mid-infrared. Band structure and equifrequency contours were calculated to inform the design of 3D polymer-germanium core-shell PhCs, which were fabricated using two-photon lithography direct laser writing and sputtering. We successfully characterized a polymer-Ge core-shell lattice and mapped its band structure, which we then used to calculate the PhC refraction behavior. An analysis of wave propagation revealed that this 3D core-shell PhC refracts light negatively and possesses an effective negative index of refraction in the experimentally observed region. These results suggest that architected nanolattices have the potential to serve as new optical components and devices across infrared frequencies.

Additive Manufacturing of High-Refractive-Index, Nanoarchitected Titanium Dioxide for 3D Dielectric Photonic Crystals.

Additive manufacturing at small scales enables advances in micro- and nanoelectromechanical systems, micro-optics, and medical devices. Materials that lend themselves to AM at the nanoscale, especially for optical applications, are limited. State-of-the-art AM processes for high-refractive-index materials typically suffer from high porosity and poor repeatability and require complex experimental procedures. We developed an AM process to fabricate complex 3D architectures out of fully dense titanium dioxide (TiO2) with a refractive index of 2.3 and nanosized critical dimensions. Transmission electron microscopy (TEM) analysis proves this material to be rutile phase of nanocrystalline TiO2, with an average grain size of 110 nm and <1% porosity. Proof-of-concept woodpile architectures with 300-600 nm beam dimensions exhibit a full photonic band gap centered at 1.8-2.9 µm, as revealed by Fourier-transform infrared spectroscopy (FTIR) and supported by plane wave expansion simulations. The developed AM process enables advances in 3D MEMS, micro-optics, and prototyping of 3D dielectric PhCs.

The impact of hospital harm on length of stay, costs of care and length of person-centred episodes of care: a retrospective cohort study.

BACKGROUND: There is a lack of data in Canada on the longitudinal effects of adverse events that occur in hospital, specifically in the period after discharge. Our objective was to quantify the impact of adverse events on hospital length of stay, length of person-centred episodes of care (PCEs) and costs of PCEs, as well as their impact on the total health system. METHODS: We conducted a population-based, retrospective cohort study using linked health administrative databases. We included adults in Ontario who had an acute hospital admission between Apr. 1, 2015, and Mar. 31, 2016. We grouped hospital admissions into 1 of 9 episode types and used the Canadian Institute for Health Information methodology for hospital harm to measure adverse events. We specified generalized linear models to estimate the impact of hospital harm on the following: incremental length of index acute hospital admission, incremental length of the PCE, and incremental costs of the PCE. RESULTS: Out of 610 979 hospital admissions, 36 004 (5.9%) involved an occurrence of harm. The impact of harm on the incremental length of hospital stay ranged from 0.4 to 24.2 days (p < 0.001); the incremental length of the PCE ranged from 0.3 to 30.2 days (p < 0.001); and the incremental costs of the PCE ranged from $800 to $51 067 (p < 0.001). Total hospital days attributable to hospital harm amounted to 407 696, and the total attributable cost to the Ontario health system amounted to $1 088 330 376. INTERPRETATION: We found that experiencing harm in hospital significantly affects both in-hospital and post-discharge use of health services and costs of care, and constitutes an enormous expense to Ontario's publicly funded health system.

Preoperative Laboratory Investigations: Rates and Variability Prior to Low-risk Surgical Procedures.

BACKGROUND: Increasing attention has been focused on low-value healthcare services. Through Choosing Wisely campaigns, routine laboratory testing before low-risk surgery has been discouraged in the absence of clinical indications. The authors investigated rates, determinants, and institutional variation in laboratory testing before low-risk procedures. METHODS: Patients who underwent ophthalmologic surgeries or predefined low-risk surgeries in Ontario, Canada, between April 1, 2008, and March 31, 2013, were identified from population-based administrative databases. Preoperative blood work was defined as a complete blood count, prothrombin time, partial thromboplastin, or basic metabolic panel within 60 days before an index procedure. Adjusted associations between patient and institutional factors and preoperative testing were assessed with hierarchical multivariable logistic regression. Institutional variation was characterized using the median odds ratio. RESULTS: The cohort included 906,902 patients who underwent 1,330,466 procedures (57.1% ophthalmologic and 42.9% low-risk surgery) at 119 institutions. Preoperative blood work preceded 400,058 (30.1%) procedures. The unadjusted institutional rate of preoperative blood work varied widely (0.0 to 98.1%). In regression modeling, significant predictors of preoperative testing included atrial fibrillation (adjusted odds ratio [AOR], 2.58; 95% CI, 2.51 to 2.66), preoperative medical consultation (AOR, 1.68; 95% CI, 1.65 to 1.71), previous mitral valve replacement (AOR, 2.33; 95% CI, 2.10 to 2.58), and liver disease (AOR, 1.69; 95% CI, 1.55 to 1.84). The median odds ratio for interinstitutional variation was 2.43. CONCLUSIONS: Results of this study suggest that testing is associated with a range of clinical covariates. However, an association was similarly identified with preoperative consultation, and significant variation between institutions exists across the jurisdiction.

Triclosan is a mitochondrial uncoupler in live zebrafish.

Triclosan (TCS) is a synthetic antimicrobial agent used in many consumer goods at millimolar concentrations. As a result of exposure, TCS has been detected widely in humans. We have recently discovered that TCS is a proton ionophore mitochondrial uncoupler in multiple types of living cells. Here, we present novel data indicating that TCS is also a mitochondrial uncoupler in a living organism: 24-hour post-fertilization (hpf) zebrafish embryos. These experiments were conducted using a Seahorse Bioscience XFe 96 Extracellular Flux Analyzer modified for bidirectional temperature control, using the XF96 spheroid plate to position and measure one zebrafish embryo per well. Using this method, after acute exposure to TCS, the basal oxygen consumption rate (OCR) increases, without a decrease in survival or heartbeat rate. TCS also decreases ATP-linked respiration and spare respiratory capacity and increases proton leak: all indicators of mitochondrial uncoupling. Our data indicate, that TCS is a mitochondrial uncoupler in vivo, which should be taken into consideration when assessing the toxicity and/or pharmaceutical uses of TCS. This is the first example of usage of a Seahorse Extracellular Flux Analyzer to measure bioenergetic flux of a single zebrafish embryo per well in a 96-well assay format. The method developed in this study provides a high-throughput tool to identify previously unknown mitochondrial uncouplers in a living organism. Copyright © 2016 John Wiley & Sons, Ltd.

Increased risk of mycobacterial infections associated with anti-rheumatic medications.

RATIONALE: Anti-tumour necrosis factor (TNF) agents and other anti-rheumatic medications increase the risk of TB in rheumatoid arthritis (RA). Whether they increase the risk of infections with nontuberculous mycobacteria (NTM) is uncertain. OBJECTIVES: To determine the effect of anti-TNF therapy and other anti-rheumatic drugs on the risk of NTM disease and TB in older patients with RA. METHODS: Population-based nested case-control study among Ontario seniors aged ≥67 years with RA who were prescribed at least one anti-rheumatic medication between 2001 and 2011. We identified cases of TB and NTM disease microbiologically and identified drug exposures using linked prescription drug claims. We estimated ORs using conditional logistic regression, controlling for several potential confounders. MEASUREMENTS AND MAIN RESULTS: Among 56 269 older adults with RA, we identified 37 cases of TB and 211 cases of NTM disease; each case was matched to up to 10 controls. Individuals with TB or NTM disease were both more likely to be using anti-TNF therapy (compared with non-use); adjusted ORs (95% CIs) were 5.04 (1.27 to 20.0) and 2.19 (1.10 to 4.37), respectively. Exposure to leflunomide and other anti-rheumatic drugs with high immunosuppressing potential also were associated with both TB and NTM disease, while oral corticosteroids and hydroxychloroquine were associated with NTM disease. CONCLUSIONS: Anti-TNF use is associated with increased risk of both TB and NTM disease, but appears to be a relatively greater risk for TB. Several other anti-rheumatic drugs were also associated with mycobacterial infections.

Preoperative testing before low-risk surgical procedures.

BACKGROUND: There is concern about increasing utilization of low-value health care services, including preoperative testing for low-risk surgical procedures. We investigated temporal trends, explanatory factors, and institutional and regional variation in the utilization of testing before low-risk procedures. METHODS: For this retrospective cohort study, we accessed linked population-based administrative databases from Ontario, Canada. A cohort of 1 546 223 patients 18 years or older underwent a total of 2 224 070 low-risk procedures, including endoscopy and ophthalmologic surgery, from Apr. 1, 2008, to Mar. 31, 2013, at 137 institutions in 14 health regions. We used hierarchical logistic regression models to assess patient- and institution-level factors associated with electrocardiography (ECG), transthoracic echocardiography, cardiac stress test or chest radiography within 60 days before the procedure. RESULTS: Endoscopy, ophthalmologic surgery and other low-risk procedures accounted for 40.1%, 34.2% and 25.7% of procedures, respectively. ECG and chest radiography were conducted before 31.0% (95% confidence interval [CI] 30.9%-31.1%) and 10.8% (95% CI 10.8%-10.8%) of procedures, respectively, whereas the rates of preoperative echocardiography and stress testing were 2.9% (95% CI 2.9%-2.9%) and 2.1% (95% CI 2.1%-2.1%), respectively. Significant variation was present across institutions, with the frequency of preoperative ECG ranging from 3.4% to 88.8%. Receipt of preoperative ECG and radiography were associated with older age (among patients 66-75 years of age, for ECG, adjusted odds ratio [OR] 18.3, 95% CI 17.6-19.0; for radiography, adjusted OR 2.9, 95% CI 2.8-3.0), preoperative anesthesia consultation (for ECG, adjusted OR 8.7, 95% CI 8.5-8.8; for radiography, adjusted OR 2.2, 95% CI 2.1-2.2) and preoperative medical consultation (for ECG, adjusted OR 6.8, 95% CI 6.7-6.9; for radiography, adjusted OR 3.6, 95% CI 3.5-3.6). The median ORs for receipt of preoperative ECG and radiography were 2.3 and 1.6, respectively. INTERPRETATION: Despite guideline recommendations to limit testing before low-risk surgical procedures, preoperative ECG and chest radiography were performed frequently. Significant variation across institutions remained after adjustment for patient- and institution-level factors.

Adequacy of prenatal care among women living with human immunodeficiency virus: a population-based study.

BACKGROUND: Prenatal care reduces perinatal morbidity. However, there are no population-based studies examining the adequacy of prenatal care among women living with HIV. Accordingly, we compared the prevalence of adequate prenatal care among women living with and without HIV infection in Ontario, Canada. METHODS: Using administrative data in a universal single-payer setting, we determined the proportions of women initiating care in the first trimester and receiving adequate prenatal care according to the Revised-Graduated Prenatal Care Utilization Index . We also determined the proportion of women with HIV receiving adequate prenatal care by immigration status. We used generalized estimating equations with a logit link function to derive adjusted odds ratios (aORs) and 95% confidence intervals (CI) for all analyses. RESULTS: Between April 1, 2002 and March 31, 2011, a total of 1,132,135 pregnancies were available for analysis, of which 634 (0.06%) were among women living with HIV. Following multivariable adjustment, women living with HIV were less likely to receive adequate prenatal care (36.1% versus 43.3%; aOR 0.74, 95% CI 0.62 to 0.88) or initiate prenatal care in the first trimester (50.8% versus 70.0%; aOR 0.51, 95% CI 0.43 to 0.60) than women without HIV. Among women with HIV, recent (i.e. ≤ 5 years) immigrants from Africa and the Caribbean were less likely to receive adequate prenatal care (25.5% versus 38.5%; adjusted odds ratio 0.51; 95% CI, 0.32 to 0.81) than Canadian-born women. CONCLUSION: Despite universal health care, disparities exist in the receipt of adequate prenatal care between women living with and without HIV. Interventions are required to ensure that women with HIV receive timely and adequate prenatal care.

Adverse Neonatal Outcomes Among Women Living With HIV: A Population-Based Study.

BACKGROUND: There have been few population-based studies describing the risk of adverse neonatal outcomes among women living with HIV in Canada. Accordingly, we compared the risk of preterm birth (PTB), low birth weight (LBW) and small for gestational age births among Ontario women aged 18 to 49 years living with and without HIV infection. METHODS: We conducted a population-based study using Ontario health administrative data. Generalized estimating equations with a logit link function were used to derive adjusted odds ratios (aORs) and 95% confidence intervals for the association of HIV infection with adverse neonatal outcomes. RESULTS: Between 2002-2003 and 2010-2011, a total of 1 113 874 singleton live births were available for analysis, of which 615 (0.06%) were to women living with HIV. The proportion of singleton births that were SGA (14.6% vs. 10.3%; P < 0.001), PTB (14.6% vs. 6.3%; P < 0.001), and LBW (12.5% vs. 4.6%; P < 0.001) were higher among women living with HIV than among women without HIV. Following multivariable adjustment, the risks of PTB (aOR 1.76; 95% CI 1.38 to 2.24), SGA (aOR 1.43; 95% CI 1.12 to 1.81), and LBW (aOR 1.90; 95% CI 1.47 to 2.45) were higher for women living with HIV than for women without HIV. CONCLUSION: Women with HIV are at higher risk of adverse neonatal outcomes than HIV-negative women. Further research is required to develop preconception and prenatal interventions that could reduce the excess burden of poor pregnancy outcomes among women living with HIV.

Contexte : Peu d'études en population générale ont décrit le risque d'issues néonatales indésirables chez les femmes vivant avec le VIH au Canada. Par conséquent, nous avons comparé les risques d'accouchement préterme (APT), de faible poids de naissance (FPN) et d'hypotrophie fœtale (HF) chez des Ontariennes de 18-49 ans vivant ou non avec le VIH. Méthodes : Nous avons mené une étude en population générale au moyen de données administratives sur la santé en Ontario. Des équations d'estimation généralisées comptant une fonction Logit ont été utilisées pour en venir à des rapports de cotes corrigés (RCc) et à des intervalles de confiance à 95 % en ce qui concerne l'association entre l'infection au VIH et des issues néonatales indésirables. Résultats : Entre 2002­2003 et 2010­2011, 1 113 874 naissances vivantes issues de grossesses monofœtales étaient disponibles aux fins de l'analyse, 615 (0,06 %) desquelles mettaient en jeu des femmes vivant avec le VIH. La proportion de naissances issues de grossesses monofœtales qui présentaient une HF (14,6 % vs 10,3 %; P < 0,001), un APT (14,6 % vs 6,3 %; P < 0,001) et un FPN (12,5 % vs 4,6 %; P < 0,001) était plus élevée chez les femmes vivant avec le VIH que chez les femmes n'étant pas infectées par ce dernier. À la suite d'une correction multivariée, les risques d'APT (RCc, 1,76; IC à 95 %, 1,38 - 2,24), d'HF (RCc, 1,43; IC à 95 %, 1,12 - 1,81) et de FPN (RCc, 1,90; IC à 95 %, 1,47 - 2,45) étaient plus élevés chez les femmes vivant avec le VIH que chez les femmes n'étant pas infectées par ce dernier. Conclusion : Les femmes vivant avec le VIH sont exposées à des risques d'issues néonatales indésirables plus élevés que les femmes séronégatives pour le VIH. La tenue d'autres recherches s'avère requise pour que l'on puisse élaborer des interventions préconceptionnelles et prénatales qui pourraient atténuer le fardeau supplémentaire que doivent assumer les femmes vivant avec le VIH en matière de piètres issues de grossesse.

Far-Field Radiative Thermal Rectification Based on Asymmetric Emissivity.

This experimental study investigates thermal rectification via asymmetric far-field thermal radiation on a fused silica slab. An asymmetrical distribution of surface emissivity is created over the device by partially covering the fused silica with a 100 nm thick aluminum film. The slab is subjected to a thermal bias, and when this bias is reversed, a small temperature difference is observed between the different configurations. This temperature difference arises from the difference in emissivity between the aluminum layer and fused silica, resulting in the transfer of thermal energy to the surrounding environment through radiation. Experimental findings are supported by finite element simulations, which not only confirm the measured values but also provide valuable insights into the rectification efficiency of the system. The rectification efficiency is found to be approximately 50% at room temperature for a thermal bias of 140 K. Simulations, which are performed by considering different environmental conditions experienced by the radiation and free convection processes, provide further insight into the underlying thermal rectification mechanism. These simulations consider an environmental temperature of 4 K for thermal radiation and an ambient temperature of 294 K for free convection and reveal an enhanced rectification effect with a rectification efficiency up to 600% when a thermal bias of 195 K is applied. This result emphasizes the significance of considering both convection and radiation in the thermal management and rectification of asymmetric systems. The outcomes of this study further our understanding of the thermal rectification phenomenon. They also show the importance of system asymmetry, emissivity disparities, environmental conditions, and the interplay between convection and radiation. Furthermore, the findings have implications for heat transfer and rectification in asymmetric systems, offering potential applications in areas such as energy harvesting, thermal management, and heat transfer optimization in electronic devices.

MoS2 phononic crystals for advanced thermal management.

Effective thermal management of electronic devices encounters substantial challenges owing to the notable power densities involved. Here, we propose layered MoS2 phononic crystals (PnCs) that can effectively reduce thermal conductivity (κ) with relatively small disruption of electrical conductivity (σ), offering a potential thermal management solution for nanoelectronics. These layered PnCs exhibit remarkable efficiency in reducing κ, surpassing that of Si and SiC PnCs with similar periodicity by ~100-fold. Specifically, in suspended MoS2 PnCs, we measure an exceptionally low κ down to 0.1 watts per meter kelvin, below the amorphous limit while preserving the crystalline structure. These findings are supported by molecular dynamics simulations that account for the film thickness, porosity, and temperature. We demonstrate the approach efficiency by fabricating suspended heat-routing structures that effectively confine and guide heat flow in prespecified directions. This study underpins the immense potential of layered materials as directional heat spreaders, thermal insulators, and active components for thermoelectric devices.

No consistent bioenergetic defects in presynaptic nerve terminals isolated from mouse models of Alzheimer's disease.

Depressed cortical energy supply and impaired synaptic function are predominant associations of Alzheimer's disease (AD). To test the hypothesis that presynaptic bioenergetic deficits are associated with the progression of AD pathogenesis, we compared bioenergetic variables of cortical and hippocampal presynaptic nerve terminals (synaptosomes) from commonly used mouse models with AD-like phenotypes (J20 age 6 months, Tg2576 age 16 months, and APP/PS age 9 and 14 months) to age-matched controls. No consistent bioenergetic deficiencies were detected in synaptosomes from the three models; only APP/PS cortical synaptosomes from 14-month-old mice showed an increase in respiration associated with proton leak. J20 mice were chosen for a highly stringent investigation of mitochondrial function and content. There were no significant differences in the quality of the synaptosomal preparations or the mitochondrial volume fraction. Furthermore, respiratory variables, calcium handling, and membrane potentials of synaptosomes from symptomatic J20 mice under calcium-imposed stress were not consistently impaired. The recovery of marker proteins during synaptosome preparation was the same, ruling out the possibility that the lack of functional bioenergetic defects in synaptosomes from J20 mice was due to the selective loss of damaged synaptosomes during sample preparation. Our results support the conclusion that the intrinsic bioenergetic capacities of presynaptic nerve terminals are maintained in these symptomatic AD mouse models.

Estimating the Burden of Illness of Relapsed Follicular Lymphoma and Marginal Zone Lymphoma in Ontario, Canada.

BACKGROUND: Many patients with advanced follicular lymphoma (FL) and marginal zone lymphoma (MZL) relapse after first-line chemotherapy. OBJECTIVE: To examine healthcare resource utilization (HCRU) and cost, treatment patterns, progression, and survival of patients with FL and MZL who relapse after first-line treatment, in Ontario, Canada. METHODS: A retrospective, administrative data study identified patients with relapsed FL and MZL (1 January 2005-31 December 2018). Patients were followed for up to three years post relapse to assess HCRU, healthcare costs, time to next treatment (TTNT), and overall survival (OS), stratified by first- and second-line treatment. RESULTS: The study identified 285 FL and 68 MZL cases who relapsed after first-line treatment. Average duration of first-line treatment was 12.4 and 13.4 months for FL and MZL patients, respectively. Drug (35.9%) and cancer clinic costs (28.1%) were major contributors to higher costs in year 1. Three-year OS was 83.9% after FL and 74.2% after MZL relapse. No statistically significant differences were observed in TTNT and OS between patients with FL who received R-CHOP/R-CVP/BR in the first line only versus both the first- and second- line. A total of 31% of FL and 34% of MZL patients progressed to third-line treatment within three years of initial relapse. CONCLUSION: Relapsing and remitting nature of FL and MZL in a subset of patients results in substantial burden to patients and the healthcare system.

Application of Synchrotron Radiation-Based Fourier-Transform Infrared Microspectroscopy for Thermal Imaging of Polymer Thin Films.

The thermal imaging of surfaces with microscale spatial resolution over micro-sized areas remains a challenging and time-consuming task. Surface thermal imaging is a very important characterization tool in mechanical engineering, microelectronics, chemical process engineering, optics, microfluidics, and biochemistry processing, among others. Within the realm of electronic circuits, this technique has significant potential for investigating hot spots, power densities, and monitoring heat distributions in complementary metal-oxide-semiconductor (CMOS) platforms. We present a new technique for remote non-invasive, contactless thermal field mapping using synchrotron radiation-based Fourier-transform infrared microspectroscopy. We demonstrate a spatial resolution better than 10 um over areas on the order of 12,000 um2 measured in a polymeric thin film on top of CaF2 substrates. Thermal images were obtained from infrared spectra of poly(methyl methacrylate) thin films heated with a wire. The temperature dependence of the collected infrared spectra was analyzed via linear regression and machine learning algorithms, namely random forest and k-nearest neighbor algorithms. This approach speeds up signal analysis and allows for the generation of hyperspectral temperature maps. The results here highlight the potential of infrared absorbance to serve as a remote method for the quantitative determination of heat distribution, thermal properties, and the existence of hot spots, with implications in CMOS technologies and other electronic devices.

Lorlatinib Effectiveness and Quality-of-Life in Patients with ALK-Positive NSCLC Who Had Failed Second-Generation ALK Inhibitors: Canadian Real-World Experience.

Lorlatinib is the only targeted therapy approved in Canada to treat patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) whose tumor has progressed despite treatment with second-generation ALK tyrosine kinase inhibitor (TKI), a patient population with high unmet need and lack of publicly reimbursed targeted treatments in Canada. We prospectively examined the real-world effectiveness and impact of lorlatinib on quality-of-life in 59 lorlatinib-treated patients, characterized as: median age of 62.0 years; 47.5% were female; 32.2% had central nervous system metastases; 50.8% had 2+ prior ALK TKI lines; and alectinib was the most common ALK TKI (72.9%) administered before lorlatinib, including 44.1% who received first-line alectinib. With a median follow-up of 15.3 months (IQR: 6.2-19.2), median time-to-treatment discontinuation of lorlatinib was 15.3 months (95% CI: 7.9-not reached), with 54.2% (95% CI: 40.8-65.9%) of patients without treatment discontinuation at 12 months. At baseline, the mean health utility score (HUS) was 0.744 (SD: 0.200). At 3 months, patients receiving lorlatinib demonstrated a 0.069 (95% CI: 0.020-0.118; p = 0.007) average HUS increase over baseline; HUS was maintained at 6 and 12 months. Thus, patients with ALK-positive NSCLC post second-generation ALK TKI remained on lorlatinib for a meaningful duration of time while their quality-of-life was preserved.

Spectroscopic and Thermal Characterization of Extra Virgin Olive Oil Adulterated with Edible Oils.

The substitution of extra virgin olive oil with other edible oils is the primary method for fraud in the olive-oil industry. Developing inexpensive analytical methods for confirming the quality and authenticity of olive oils is a major strategy towards combatting food fraud. Current methods used to detect such adulterations require complicated time- and resource-intensive preparation steps. In this work, a comparative study incorporating Raman and infrared spectroscopies, photoluminescence, and thermal-conductivity measurements of different sets of adulterated olive oils is presented. The potential of each characterization technique to detect traces of adulteration in extra virgin olive oils is evaluated. Concentrations of adulterant on the order of 5% can be detected in the Raman, infrared, and photoluminescence spectra. Small changes in thermal conductivity were also found for varying amounts of adulterants. While each of these techniques may individually be unable to identify impurity adulterants, the combination of these techniques together provides a holistic approach to validate the purity and authenticity of olive oils.

Excitation and detection of acoustic phonons in nanoscale systems.

Phonons play a key role in the physical properties of materials, and have long been a topic of study in physics. While the effects of phonons had historically been considered to be a hindrance, modern research has shown that phonons can be exploited due to their ability to couple to other excitations and consequently affect the thermal, dielectric, and electronic properties of solid state systems, greatly motivating the engineering of phononic structures. Advances in nanofabrication have allowed for structuring and phonon confinement even down to the nanoscale, drastically changing material properties. Despite developments in fabricating such nanoscale devices, the proper manipulation and characterization of phonons continues to be challenging. However, a fundamental understanding of these processes could enable the realization of key applications in diverse fields such as topological phononics, information technologies, sensing, and quantum electrodynamics, especially when integrated with existing electronic and photonic devices. Here, we highlight seven of the available methods for the excitation and detection of acoustic phonons and vibrations in solid materials, as well as advantages, disadvantages, and additional considerations related to their application. We then provide perspectives towards open challenges in nanophononics and how the additional understanding granted by these techniques could serve to enable the next generation of phononic technological applications.

Elevated levels of mitochondrial CoQ10 induce ROS-mediated apoptosis in pancreatic cancer.

Reactive oxygen species (ROS) are implicated in triggering cell signalling events and pathways to promote and maintain tumorigenicity. Chemotherapy and radiation can induce ROS to elicit cell death allows for targeting ROS pathways for effective anti-cancer therapeutics. Coenzyme Q10 is a critical cofactor in the electron transport chain with complex biological functions that extend beyond mitochondrial respiration. This study demonstrates that delivery of oxidized Coenzyme Q10 (ubidecarenone) to increase mitochondrial Q-pool is associated with an increase in ROS generation, effectuating anti-cancer effects in a pancreatic cancer model. Consequent activation of cell death was observed in vitro in pancreatic cancer cells, and both human patient-derived organoids and tumour xenografts. The study is a first to demonstrate the effectiveness of oxidized ubidecarenone in targeting mitochondrial function resulting in an anti-cancer effect. Furthermore, these findings support the clinical development of proprietary formulation, BPM31510, for treatment of cancers with high ROS burden with potential sensitivity to ubidecarenone.

Smoking, drinking, diet and physical activity-modifiable lifestyle risk factors and their associations with age to first chronic disease.

BACKGROUND: This study examined the incidence of a person's first diagnosis of a selected chronic disease, and the relationships between modifiable lifestyle risk factors and age to first of six chronic diseases. METHODS: Ontario respondents from 2001 to 2010 of the Canadian Community Health Survey were followed up with administrative data until 2014 for congestive heart failure, chronic obstructive respiratory disease, diabetes, lung cancer, myocardial infarction and stroke. By sex, the cumulative incidence function of age to first chronic disease was calculated for the six chronic diseases individually and compositely. The associations between modifiable lifestyle risk factors (alcohol, body mass index, smoking, diet, physical inactivity) and age to first chronic disease were estimated using cause-specific Cox proportional hazards models and Fine-Gray competing risk models. RESULTS: Diabetes was the most common disease. By age 70.5 years (2015 world life expectancy), 50.9% of females and 58.1% of males had at least one disease and few had a death free of the selected diseases (3.4% females; 5.4% males). Of the lifestyle factors, heavy smoking had the strongest association with the risk of experiencing at least one chronic disease (cause-specific hazard ratio = 3.86; 95% confidence interval = 3.46, 4.31). The lifestyle factors were modelled for each disease separately, and the associations varied by chronic disease and sex. CONCLUSIONS: We found that most individuals will have at least one of the six chronic diseases before dying. This study provides a novel approach using competing risk methods to examine the incidence of chronic diseases relative to the life course and how their incidences are associated with lifestyle behaviours.