Lifetime Analysis Research Articles

Smart Wide-field Fluorescence Lifetime Imaging System with CMOS Single-photon Avalanche Diode Arrays.

Wide-field fluorescence lifetime imaging (FLIM) is a promising technique for biomedical and clinic applications. Integrating with CMOS single-photon avalanche diode (SPAD) sensor arrays can lead to cheaper and portable real-time FLIM systems. However, the FLIM data obtained by such sensor systems often have sophisticated noise features. There is still a lack of fast tools to recover lifetime parameters from highly noise-corrupted fluorescence signals efficiently. This paper proposes a smart wide-field FLIM system containing a 192×128 COMS SPAD sensor and a field-programmable gate array (FPGA) embedded deep learning (DL) FLIM processor. The processor adopts a hardware-friendly and light-weighted neural network for fluorescence lifetime analysis, showing the advantages of high accuracy against noise, fast speed, and low power consumption. Experimental results demonstrate the proposed system's superior and robust performances, promising for many FLIM applications such as FLIM-guided clinical surgeries, cancer diagnosis, and biomedical imaging.

Analysis of Performance Degradation and Durability of the Air Cathode in an Alkaline Fuel Cell

Degradation of the air cathodes is one of the key issues affecting the lifetime and durability of alkaline fuel cells and metal-air batteries. To prevent the ingress of electrolyte in the air cathode, modifying the hydrophobicity and thickness of the AL has been reported [1,2]. It was reported that increased hydrophobicity/thickness of the AL resulted in a decrease in the air cathode performance [1,2]. In this work, experimental in-situ and post-test analyses of the air cathode were applied to investigate the mechanism of performance degradation. In-situ methods including performance / lifetime analysis using a half-cell setup [3, 4], polarization studies, and electrochemical impedance spectroscopy (EIS) were used to investigate the electrochemical characteristics of the electrodes during operation. Post-mortem analysis methods included X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray computed tomography (X-ray CT), and Raman spectroscopy. The properties of pristine, conditioned, and failed air cathodes were characterized by these methods. Conditioning of air cathodes was performed by operating in half-cell utilizing 6 M KOH solution for 24 hours at 200 mA cm 2. The composition of the air cathode, operating conditions, and procedure for determining the performance and lifetime of the air cathode have been discussed in our previous work [3].Cross-sectional SEM-EDX analysis was conducted on the air cathode to determine the amount of flooding/penetration of the electrolyte inside the active layers for electrodes prepared with 15, 25, and 40 wt% PTFE in the AL. Air cathodes were operated in the half-cell battery at 200 mA cm -2. EDX maps of the air cathodes showed that increasing the PTFE content leads to increased hydrophobicity and decreased depth of KOH penetration inside the AL after 5 hours of operation. However, air cathodes with higher PTFE content of 40 wt% exhibited a lifetime of only 48 hours, compared to > 150 hours for those containing 15 wt% and 25 wt% (conducted in a limited test duration). This could be due to decreased electrolyte content in the AL or blocking of pore space and active reaction sites [5], leading to higher local current densities and more rapid degradation. Cross-sectional EDX analysis indicated that electrolyte penetration/flooding inside the macrostructure of the backing layer (BL) was not observed in any of the electrodes.XPS was performed to reveal further information of the chemical states of the conditioned and failed cathodes [6]. XPS analysis indicated changes in the surface functional groups, in particular increasing hydroxyl groups in the failed cathodes, which may be indicative of reduced hydrophobicity of the carbon support. XPS analysis also indicated other changes in the chemical states of the catalyst, oxygen, fluorine and carbon after conditioning and failure of the air cathode.In-situ galvanostatic EIS was conducted during long-duration and accelerated stress tests to determine ohmic resistance, charge transfer resistance, and mass transfer limitation. The EIS data indicates that mass transfer resistance increased significantly after failure of the air cathode, confirming that oxygen transport to the catalyst was the cause of the poor performance of failed cathodes. Raman spectra and mapping was carried out to obtain additional information about changes in the AL after degradation. X-ray CT were conducted on air cathodes to determine the changes of pore structure, distribution of catalyst, PTFE and potassium.

Orbit Propagation and Lifetime Analysis of NARSSCUBE-2 Using High Precision Numerical Approach

Due to their short mission lifetime, Cube satellites launched in the last decades have increased the number of objects in Low Earth Orbits and the number of space debris. As a result, it is important to obtain accurate measurements of CubeSats trajectories in order to determine their decay and orbital lifetime and to avoid collisions with debris. In this paper, a special perturbation technique has been used as an orbit propagator in order to model orbital motion and predict the behavior of Cube satellites subjected to perturbations. This technique is a high-precision numerical approach via Cowell's formulation with adaptive step size Runge-Kutta-Fehlberg (RKF78) for numerical integration. The technique used is named SPC (Special Perturbation using Cowell's method). Orbit propagation and orbital decay evolution of NARSSCUBE-2 have been analyzed using appropriate orbital parameters derived from historic NORAD Two Line Element sets. The results from the SPC technique have been compared with the SGP4 analytical orbit propagator and then verified with the HPOP numerical orbit propagator from FreeFlyer® astrodynamics software. The accuracy of each propagator has been verified with the observation data. The SPC orbit propagator gives a higher accuracy of orbit prediction compared to SGP4 and closely matches with HPOP.

Rational control on the morphology of WS2 nanomaterials by altering hydrothermal reaction conditions

Here, we present the synthesis of nanomaterials based on WS2, using a simple and green hydrothermal route. The synthesis was accomplished by the high-temperature hydrothermal reaction of WS2 powder in aqueous NaOH. Upon changing the mole ratio of WS2 to NaOH, different types of nanomaterials such as quantum dots (QDs), nanosheets and hybrid QDs-nanosheets were obtained. We systematically characterized the optical properties of these materials. All exhibited high photoluminescence spanning a large portion of the UV and visible region of the electromagnetic spectrum. The morphological and other structural aspects were unraveled by transmission electron microscopy (TEM) and Raman spectroscopy. Size-dependent photophysical properties of various WS2 nanomaterials were investigated using UV–visible absorption spectroscopy, fluorescent spectroscopy and fluorescence lifetime analysis. We envisage that these materials can be promising candidates for various biological and optoelectronic applications due to their extraordinary temporal and photostability.

Development of a microstructured tissue phantom with adaptable optical properties for use with microscopes and fluorescence lifetime imaging systems

For the development and validation of diagnostic procedures based on microscopic methods, knowledge about the imaging depth and achievable resolution in tissue is crucial. This poses the challenge to develop a microscopic artificial phantom focused on the microscopic instead of the macroscopic optical tissue characteristics. As existing artificial tissue phantoms designed for image forming systems are primarily targeted at wide field applications, they are unsuited for reaching the formulated objective. Therefore, a microscopy- and microendoscopy-suited artificial tissue phantom was developed and characterized. It is based on a microstructured glass surface coated with fluorescent beads at known depths covered by a scattering agent with modifiable optical properties. The phantom was examined with different kinds of microscopy systems in order to characterize its quality and stability and to demonstrate its usefulness for instrument comparison, for example, regarding structural as well as fluorescence lifetime analysis. The analysis of the manufactured microstructured glass surfaces showed high regularity in their physical dimensions in accordance with the specifications. Measurements of the optical parameters of the scattering medium were consistent with simulations. The fluorescent beads coating proved to be stable for a respectable period of time (about a week). The developed artificial tissue phantom was successfully used to detect differences in image quality between a research microscope and an endoscopy based system. Plausible causes for the observed differences could be derived based on the well known microstructure of the phantom. The artificial tissue phantom is well suited for the intended use with microscopic and microendoscopic systems. Due to its configurable design, it can be adapted to a wide range of applications. It is especially targeted at the characterization and calibration of clinical imaging systems that often lack extensive positioning capabilities such as an intrinsic z-stage.

Experimental and theoretical investigations on chalcones containing pyrene

Three chalcone derivatives featuring pyrene chromophore are designed, synthesised and studied for their thermal, photophysical and electrochemical properties. They exhibited a maximum absorption peak ranging from 414 nm to 421 nm and emission in cyan region. A chalcone containing nitro substituent displayed intramolecular charge transfer than a similar compound containing methoxy group. Excited lifetime analysis reveals the biexponential decay with two lifetime components. Solvatochromism of the chalcones revealed the effect of auxochrome in the intramolecular charge transfer. All the chalcones exhibited aggregation induced blue-shifted emission due to the restricted rotation and H-aggregation. The density functional theoretical calculation results further confirmed the charge transfer characteristic of the compounds.

Abstract 2461: Integrated lifetime and spectral phasor imaging of biomarker expression and metabolism in hormone receptor positive breast cancer models

Abstract In HR+ (hormone receptor positive) breast cancer, endocrine therapies that directly antagonize estrogen receptor or reduce synthesis of its ligand can be highly effective, but endocrine-resistance occurs frequently. Metabolic dysregulation is a mechanistic driver of endocrine-resistant HR+ breast cancer, but most existing methods cannot be multiplexed with assays for biomarker expression. Spectral phasor imaging of multiplex immunofluorescence (mIF) staining for expression of hormone receptors and other biomarkers combined with phasor lifetime analysis of NADH to quantify metabolic state will provide integrated spatial maps of metabolism and biomarker expression in endocrine-resistant HR breast cancer. We used the HCI-013 (013) and HCI-013EI (013EI) patient-derived xenograft (PDX) system, derived from a HR+, invasive lobular metastatic breast cancer which harbors the Y537S ESR1 mutation. Tumors were stained with a multiplex immunofluorescence (mIF) panel for pan-cytokeratin, ER, PR, HER2, and Ki67, detected by spectrally separate OPAL dyes. Hyperspectral phasor fluorescence spectra were obtained using successive single photon excitation at 488 nm, 561 nm and 640 nm and using multiphoton excitation at 1024 nm. Single photon excitation excites specific dyes, and multiphoton excites the entire panel of dyes simultaneously. The emission was collected using a Zeiss 880 laser scanning microscope equipped with a 32 channel spectral detector. Phasor coordinates of each component were resolved into fractional intensities of the five genes. In the same tissues and sections, phasor fluorescence lifetime imaging (FLIM) of NADH was used to quantify metabolic heterogeneity. NADH is present in two forms: free and protein-bound NADH. They have different fluorescence lifetimes and the ratio of these two species are correlated with NAD+/NADH ratio. Free NADH is associated with increased glycolysis. We observed greater metabolic heterogeneity in 013EI PDX samples, with similar levels of free NADH (glycolysis) at the tumor border, but significantly increased bound NADH (oxidative phosphorylation) in the tumor core. Spectral phasor data show differential expression of PR and PanCK (for 640 nm excitation), and HER2 and ERalpha (for 561 nm excitation) in the edge and center of cancer in 013 and 013EI variants. Our results show how a combination of spectral phasor and phasor-FLIM can be used to define metabolic changes in endocrine-resistant, HR+ PDX models and correlate them with biomarker expression. Ongoing work is quantitatively mapping these measurements at single-pixel resolution, and applying this imaging workflow to RNAscope in situ hybridization assays for gene expression. Combining multiphoton spectral (RNAscope) and FLIM (NADH) will allow pixelwise correlation of the gene expression and metabolic changes. Citation Format: Belen Torrado, Alexander Vallmitjana, Ayodeji Olukoya, Shaymaa Bahnassy, Hillary Stires, Aaron Rozeboom, Rebecca B. Riggins, Suman Ranjit. Integrated lifetime and spectral phasor imaging of biomarker expression and metabolism in hormone receptor positive breast cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2461.

Broadband NIR-II phosphors with Cr4+ single activated centers based on special crystal structure for nondestructive analysis

Due to the widespread applications of near-infrared (NIR) light in medical diagnosis, food inspection and biological detection, the need for NIR phosphors with longer wavelengths has become more urgent. Herein, a series of Cr-doped Li2ZnGeO4 (LZGO) phosphors were successfully synthesized. Excited by 470 or 675 nm, the LZGO: Cr phosphor emits a broadband NIR-II spectrum from 1000 to 1600 nm centered at 1230 nm with a full width at half-maximum up to 213 nm. The broadband emission is attributed to the 3T2→3A2 spin-allowing transition of Cr4+. The phosphor can be excited by an efficient blue LED chip, and the emitted NIR light can be detected by a cheap In-GaAs detector. The analysis of XPS, EPR, fluorescence lifetime and excitation spectra at different wavelengths show that both Cr3+ and Cr4+ exist in the samples with a content ratio of approximately 3:1, and Cr4+ ions are the sole luminescent center. The reasons for the production of Cr4+ were summarized. Furthermore, transmission experiments of several solutions show that LZGO: Cr4+ phosphors have potential applications in physical property identification, quantitative and non-destructive analysis. This work provides a new direction for the development of broadband NIR-Ⅱ phosphors.

905-P: Simulation Model Estimating Lifetime Health and Economic Outcomes of Prediabetes Screening by One-Hour Plasma Glucose

Background: One of the current methods to diagnose prediabetes and predict diabetes incidence is based on 2-h plasma glucose (2-hPG) value following 75-g oral glucose tolerance test. Evidence demonstrates that 1-hour post-load plasma glucose (1-hPG) ≥ 155 mg/dl (8.6 mmol/L) in those with normal glucose tolerance at 2-hPG is highly predictive for T2D incidence. We conducted a health economic analysis to estimate long-term cost-effectiveness of using 1-hPG as compared to 2-hPG to screen and assess diabetes risk. Methods: The main outcome of the study was cost per quality-adjusted life-year (QALY) gained. We used a Monte Carlo-based Markov simulation model to simulate long-term effects of the two screening strategies on clinical and cost-effectiveness outcomes. The base case model included 20.000 simulated patients over 35-years. Transition probabilities were retrieved from landmark studies. Direct medical costs were sourced from the literature and inflated to 20Euros. Results: In the lifetime analysis, 1-hPG was projected to increase the number of years free from disease (2yr/patient) ; to delay the onset of T2D (1yr/patient) ; to reduce the incidence of T2D complications (0.6 Relative Risk/patient) and to increase the QALY gained (0.58/patient) . Though testing the 1-hPG resulted in higher initial costs owing to a larger number of preventive treatments, long-term diabetes and complications costs were reduced leading to -31,225,719.82€ saving over a lifetime as compared to 2-hPG. The incremental cost-effectiveness ratio was -8,214.7€ per each QALY gained for the overall population. Conclusions: Screening prediabetes by using 1h-PG is feasible and cost-effective resulting in QALYs gained and reduced costs. Notwithstanding the higher initial costs of 1-hPG compared to 2-hPG, due to the incremental number of preventive treatments, long-term diabetes and complications costs were reduced expecting an overall cost saving of -8,214.7€ per each QALY gained. Disclosure M.Andellini: None. M.Manco: None. M.Esposito: None. A.Tozzi: None. M.Bergman: None. M.Ritrovato: None.

Influence of rare earth doping and calcination temperature on temperature sensitivity of gadolinium molybdate nanoparticle

NaGd(MoO4)2: Er3+/Yb3+ up-conversion fluorescence materials was prepared by a sol-gel method. And the effects of activator ion doping concentration, sensitizer ion doping concentration and calcination temperature on the temperature sensitivity of NaGd(MoO4)2: Er3+/Yb3+ materials were studied. The samples were characterized by XRD, SEM and fluorescence spectra. The temperature sensitivity of different powder was calculated by using the temperature measurement formula of fluorescence intensity ratio. At this time, the results show that the temperature sensitivity is the highest when the concentration of Er3+ is 0.5% in the range of 0.3–2.0% and when the concentration of Yb3+ is 28% in the range of 16–32%. Under the condition of 0.5% Er3+/ 28% Yb3+, a higher value of 0.0268 K−1 can be obtained. Then, the change of temperature sensitivity with doping concentration was analyzed based on the theory of energy transition and the analysis of fluorescence lifetime. In addition, with the calcination temperature increasing from 700 ℃ to 1100 ℃, it is found that the fluorescence intensity and temperature sensitivity of the calcination temperature at 800 ℃ are both great. At the same time, the influence of doping concentration of Er3+， doping concentration of Yb3+ and calcination temperature on the sensitivity was compared. It was found that the influence of Er3+ ion doping concentration was more significant. These results indicate that Er3+ and Yb3+ co-doped NaGd(MoO4)2 powder has a great application prospect in temperature sensing.

Accelerated Lifetime Testing and Analysis of Delta-Doped Silicon Test Structures

As transistor features shrink beyond the 2 nm node, studying and designing for atomic scale effects become essential. Being able to combine conventional CMOS with new atomic scale fabrication routes capable of creating 2D patterns of highly doped phosphorus layers with atomic precision has implications for the future of digital electronics. This work establishes the accelerated lifetime tests of such doped layers, showing that these materials survive high current (>3.0 MA/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ) and 300°C for greater than 70 days and are still electrically conductive. The doped layers compare well to failures in traditional metal layers like aluminum and copper where mean time to failure at these temperatures and current densities would occur within hours. It also establishes that these materials are more stable than metal features, paving the way toward their integration with operational CMOS.

Generalized Estimation for Two-Parameter Life Time Distributions Based on Fuzzy Life Times

Ongoing developments of the measurement sciences say that measurements based on continuous phenomena are no more precise observations but more or less fuzzy. Therefore, it is necessary to utilize this imprecision of observations to obtain such estimators, which are based on all the available information that is given in the form of randomness and fuzziness. Objective of this research was to get such parameter estimation procedure that utilizes all the available information for some well-known two-parameter life time distributions. Therefore, the estimators need to be generalized in such a way to cover both uncertainties. For this purpose, based on δ -cuts of the life time observations, the generalized estimators are developed in such manner to cover stochastic variation in addition to fuzziness. The proposed generalized estimators are much preferred over classical estimators for life time analysis as these are based on all the available information present in the form of fuzziness of single observations and random variation among the observations to make suitable inferences.

Temperature-dependent photoluminescence spectra mechanism analysis of N–B co-doped 4H–SiC

The temperature dependence of photoluminescence (PL) spectra of heavily N–B co-doped fluorescent SiC grown by the PVT method has been investigated. With fixed N and different B doping concentration, the luminescence intensity and position as a function of temperature were analyzed. With higher B doping concentration, it is the higher PL intensity from 40 K to 300 K and weaker blue-shift. The broad peak with energy separations show that three kinds of bands, which are free-electron-to-acceptor (e-A), donor-acceptor pair (DAP) and Band 3, are recognized from 40 K to 160 K. And only e-A and DAP emission exist from 160 K to 300 K. The luminous mechanism of the above three emission components was discussed. It is confirmed that Band 3 originated from the recombination of deep level introduced by C vacancies with conduction band electrons by EPR results, which occurs only below 160 K. Moreover, the fluorescence lifetime analyses of N–B co-doped fluorescent SiC were performed. At low temperatures, many holes are trapped in the shallow B level, resulting in a long fluorescence lifetime.

Stable Zinc(II) Coordination Polymer as a Rapid and Highly Sensitive Fluorescence Sensor for the Discriminative Sensing of Biomarker 2-(2-Methoxyethoxy) Acetic Acid.

A novel two-dimensional bilayer Zn-based luminescent coordination polymer (LCP) [Zn2(μ2-OH)(4-dptp)(3,4',5-bpt)] (LCP 1) [4-dptp = N3,N4-bis(pyridin-4-ylmethyl)thiophene-3,4-dicarboxamide and 3,4',5-H3bpt = biphenyl-3,4',5-tricarboxylic acid] was successfully prepared under hydrothermal conditions and characterized by single-crystal X-ray diffraction, IR spectroscopy, powder X-ray diffraction, and luminescence spectroscopy. LCP 1 displayed excellent fluorescence-quenching efficiency toward a biomarker 2-(2-methoxyethoxy) acetic acid (MEAA) with a high Ksv (5.153 × 104 M-1), a low limit of detection (0.244 μM), and a rapid response time (28 s). Additionally, LCP 1 can repeatedly detect MEAA at least eight times with excellent stability. The sensing mechanism was also carefully investigated through UV-vis absorption spectroscopy, density functional theory calculations, and fluorescence lifetime analysis.

Fluorescence Lifetime Phasor Analysis of the Decamer-Dimer Equilibrium of Human Peroxiredoxin 1.

Protein self-assembly is a common feature in biology and is often required for a myriad of fundamental processes, such as enzyme activity, signal transduction, and transport of solutes across membranes, among others. There are several techniques to find and assess homo-oligomer formation in proteins. Naturally, all these methods have their limitations, meaning that at least two or more different approaches are needed to characterize a case study. Herein, we present a new method to study protein associations using intrinsic fluorescence lifetime with phasors. In this case, the method is applied to determine the equilibrium dissociation constant (KD) of human peroxiredoxin 1 (hPrx1), an efficient cysteine-dependent peroxidase, that has a quaternary structure comprised of five head-to-tail homodimers non-covalently arranged in a decamer. The hPrx1 oligomeric state not only affects its activity but also its association with other proteins. The excited state lifetime of hPrx1 has distinct values at high and low concentrations, suggesting the presence of two different species. Phasor analysis of hPrx1 emission lifetime allowed for the identification and quantification of hPrx1 decamers, dimers, and their mixture at diverse protein concentrations. Using phasor algebra, we calculated the fraction of hPrx1 decamers at different concentrations and obtained KD (1.1 × 10−24 M4) and C0.5 (1.36 μM) values for the decamer–dimer equilibrium. The results were validated and compared with size exclusion chromatography. In addition, spectral phasors provided similar results despite the small differences in emission spectra as a function of hPrx1 concentration. The phasor approach was shown to be a highly sensitive and quantitative method to assess protein oligomerization and an attractive addition to the biophysicist’s toolkit.

Investigation of Eu3+ Doped Oxy-Fluoride Phosphate Glass for Red Laser Gain Medium Application

The oxyfluoride phosphate glass doped with europium oxide was synthesized by melt quenching technique. The structural and spectroscopic analysis has been carried out by Raman, absorption, photoluminescence, phonon side band and lifetime analysis. The absorption spectrum revealed the characteristic transitions between the 7F0 ground state and 7F1 first excited state to the upper-lying electronic states. The several J-O parameters: oscillator strength, radiative transition probability, stimulated emission cross-section and branching ratio. The local structure around the Eu3+ ions and the phonon energy of oxyfluoride phosphate glass have been confirmed on the basis of PSB associated with the 7F0→5D2 transition. The highest excitation spectrum showed at 395 nm for transition 7F0→5L6. The emission spectrum showed two major peaks corresponding to 591 nm orang emission (5D0→7F1) and 613 nm red emission (5D0→7F2). This work confirmed that 1 mol% Eu2O3 doped oxyfluoride phosphate glass performs a high potential for using as efficient luminescence materials for solid-state lighting application, especially for reddish-orange light-emitting glass.

Abstract 170: Cost-effectiveness Of Icosapent Ethyl In Reduce-it USA: Results From Patients Randomized In The United States

Background: The Reduction of Cardiovascular Events with Icosapent Ethyl (IE)-Intervention Trial (REDUCE-IT) demonstrated the efficacy of IE among patients with elevated triglyceride levels despite the use of statins. This study aimed to examine the cost-effectiveness (CE) of IE among US adults using both in-trial and lifetime time horizons. Methods: US patients in REDUCE-IT were included in the in-trial analysis. We included all cardiovascular and serious adverse events from the REDUCE-IT database where rates differed between the study arms; we used patient-level data from REDUCE-IT USA based on 2019 US costs and $4.16/day for IE. The lifetime analysis used a microsimulation Markov model. Both analyses considered value from a US health sector perspective. The primary result is the incremental CE ratio (ICER), measured as incremental costs divided by incremental quality-adjusted life-years (QALY) of IE compared with placebo. We performed univariate and probabilistic sensitivity analyses (PSA) to capture the uncertainties involved in the estimation of costs and QALYs. Results: Based on 3146 REDUCE-IT USA participants, there was an incremental gain in QALYs with IE compared with placebo using in-trial (3.28 vs. 3.13) and lifetime (10.36 vs. 9.83) time horizons. Total healthcare costs were lower with IE compared with placebo for both in-trial ($20,221 vs. $20,357) and lifetime ($201,842 vs. $204,701). IE was a dominant strategy compared to placebo using a lifetime time horizon with a 74.8% probability of being more effective and costing less and had a 99.6% probability of costing below $50,000 per QALY. The lifetime PSA showed that IE was a dominant strategy in 65.6% of simulations and cost-effective in 98.8%, 99.6%, and 99.9% of simulations at the $50,000, $100,000, and $150,000 per QALY gained thresholds, respectively. Conclusions: The REDUCE-IT USA cost-effectiveness analysis has shown that IE provides better outcomes with lower costs, dominant both in-trial and lifetime as well in the majority of sensitivity analyses and subgroups, both in primary and secondary prevention. These results, with the clinical evidence of efficacy, suggest that at $4.16 per day, IE therapy should be strongly considered in patients similar to those enrolled in REDUCE-IT USA.

Cost-effectiveness analyses of biologic and targeted synthetic disease-modifying anti-rheumatic diseases in patients with rheumatoid arthritis: Three approaches with a cohort simulation and real-world data.

To assess the cost-effectiveness of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in rheumatoid arthritis. We conducted three analyses: a lifetime analysis with a cohort model (Study A) and two short-term analyses (Studies B and C). Study A evaluated the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained from costs of standard treatments. Study B evaluated yearly costs per person achieving American College of Rheumatology (ACR) response (ACR20, ACR50, and ACR70), and Study C evaluated costs per person achieving previously defined claims-based effectiveness (equivalent to 28-joint Disease Activity Score ≤ 3.2). The proportion of ACR responders to the drugs of interest were determined by mixed treatment comparisons. Studies B and C estimated costs using a claims database. In Study A, ICERs of all b/tsDMARDs were lower than 5.0 million Japanese yen (JPY) per QALY. In Study B, yearly costs per person with ACR50 response were lower for subcutaneous tocilizumab (TCZ-SC; 1.9 million JPY) and SC abatacept (2.3 million JPY). In Study C, costs per person were lower for TCZ-SC (1.3 million JPY) and intravenous TCZ (1.6 million JPY) and effectiveness rates were higher for intravenous TCZ (45.3%) and infliximab (43.0%). The b/tsDMARDs with lower prices showed higher cost-effectiveness.

Slow crack growth in multispectral zinc sulfide for use in aircraft window design

The slow crack growth rate and inert strength of multispectral zinc sulfide were measured for use in aircraft window lifetime analysis. Dynamic fatigue data for uncoated multispectral zinc sulfide were fit to a power law by linear regression and to an exponential law by computer-aided numerical integration to obtain best-fit slow crack growth rate parameters. For the power law slow crack growth equation, crack velocity ( v ) = A * (KI/KIc)n, we find A * = 0.00769 m / s and n = 14.65, where KI is the stress intensity factor, KIc = 0.72 MPam is the critical stress intensity factor, and we assign the value of the geometric factor to be Y = 2 / π. Parameters for the exponential law slow crack growth equation, crack velocity ( v ) = vo exp ( βKI ) are vo = 3.02 × 10 − 14 m / s and β = 43.64 (MPam) − 1. There were only small differences in the crack growth rate between uncoated and antireflection-coated material. The crack growth rate that we observe is 10 to 200 times faster than previously reported for a stress intensity factor KI = 0.25 MPam, which is a representative value of KI for an aircraft window in service. The faster crack growth rate predicts a correspondingly shorter window lifetime. The inert strength of uncoated biaxial flexure disks (38.1 mm diameter with 15.88 mm load diameter and 31.75 mm support diameter) measured in dry nitrogen exhibited a 50% Weibull failure probability at 115 MPa with an unbiased ASTM C1239 Weibull modulus of 4.68. Antireflection-coated material had a 50% Weibull failure probability at 100 MPa with a Weibull modulus of 5.25.

Two phase secure data collection technique for wireless sensor networks

Wireless &lt;span&gt;sensor networks (WSNs) are the sensors that are dispersed in a different location that can sense the accumulated data in real-time and send it to the central location for the process of data aggregation. During the transfer of the information using the data nodes from the WSNs to the central location, there may be chances that the data node could be compromised by sensor failure or by an attack from a malicious user. To overcome this problem, we propose a two-phase secure data collection (TPSDC) technique for wireless sensor networks which provides confidentiality and integrity for the data nodes that are being sent to the central location and also during the data aggregation in the central location. Various existing methods have been proposed to secure the data when sent from the WSNs to the internet of things (IoT) devices but they lack to provide both confidentiality and integrity at the same time. Hence our model provides both integrity and confidentiality by providing security to the data nodes. Experimental results show that our model TPSDC performs better in terms of misclassification rate, detection rate, throughput, network lifetime analysis of the node, and communication overhead of the node when compared with the existing methods.&lt;/span&gt;