Study design for a three-arm equivalence clinical trial with binomially distributed outcomes.

Equivalence in a clinical trial may be assessed through a three-arm trial (test drug, reference drug, and placebo). A three-arm equivalence trial consists of three hypothesis tests in practice, with two hypothesis tests demonstrating the superiority of the test and reference drugs against placebo, and the other one demonstrating the equivalence of the test and reference drugs. When designing a three-arm equivalence clinical trial, the practitioner should minimize the chances that a test drug will be found to be equivalent to the reference drug but non-superior to the placebo. One way to minimize these chances at the design stage, for a three-arm equivalence trial with a binary primary outcome, is to test the equivalence through hypotheses based upon the ratio of the differences of the proportions. In this article, we derived the test statistics and the power functions based on maximum likelihood estimate (MLE) and restricted MLE for the proposed hypotheses. The required sample size for achieving the desired power at the given significance level can be obtained by solving the power function. We illustrated the proposed design through an example and investigated the required sample sizes for various conditions.

Flexible light valves using polymer-dispersed liquid crystals and TiO2/Ag/TiO2 multilayers.

The era of flexible optoelectronics demands development of wearable and bendable structures, foldable touch screens, paper-like displays, and curved and flexible solid-state lighting devices. Here, we demonstrate the fabrication of highly flexible light valves using polymer-dispersed liquid crystal (PDLC) and TiO2/Ag/TiO2 transparent conductive films. TiO2/Ag/TiO2 multilayers were prepared by magnetron sputtering technique on polyethylene terephthalate (PET) substrates at room temperature. By keeping the equivalent TiO2 layers and varying the deposition time of the Ag layer, proper metal nanograins on TiO2 planar plane were formed, providing the best tradeoff between the transmittance, sheet resistance and bending ability. The results are validated by numerical simulations that suggest the best match between the deposition time and individual layer thickness. Based on the performed characteristics of TiO2/Ag/TiO2/PET structures, several flexible light valves are fabricated and characterized. The sheet resistance values of TiO2/Ag/TiO2/PET remain unchanged over 1000 bending cycles. The measured driving voltage and response time values open great potential of TiO2/Ag/TiO2/PET for integration into next-generation ITO-free flexible and stretchable devices.

A useful design utilizing the information fraction in a group sequential clinical trial with censored survival data.

Lan and DeMets (1983) proposed the alpha spending function for group sequential trials to permit the use of unspecified frequencies and timings of interim analyses in the trial design. Regarding a trial with censored time to endpoint, Lan and DeMets (1989) later defined information time at an interim analysis in a maximum duration trial. To compare two survival curves utilizing such a design, information times for group sequential logrank and Wilcoxon-type statistics have been developed by assuming that the survival time follows an exponential distribution or a Weibull distribution without considering the censoring distribution. To better address the practical concerns inherent in clinical trials with survival endpoints, we present a new approach to adequately design a group sequential trial using the Harrington-Fleming (1982) test based on our proposed information fractions by assuming the censoring distribution depends on the patient's accrual time according to various entry distributions and by extending the underlying survival distribution to the generalized gamma distribution. We also determine associated sample sizes, expected number of events and expected stopping time. Two phase III trials of non-small-cell lung cancer originally designed using fixed-sample tests are utilized to illustrate the potential advantages of using a group sequential design with the proposed approach. This enhanced method facilitates the design and analysis of group sequential clinical trials studying survival endpoints by increasing implemental flexibility.

Prism-hologram-prism sandwiched recording method for polarization-selective substrate-mode volume holograms with a large diffraction angle.

We propose a prism-hologram-prism sandwiched recording method for the fabrication of polarization-selective substrate-mode volume holograms with a large diffraction angle. In fabrication, the C-RT20 photopolymer is sandwiched between two 45°-90°-45° prisms and the interference fringes can be easily recorded in the recording material. The experimental results are in good agreement with the theoretical predictions. The proposed method features of a reflection-type recording setup for a transmission element and belongs to a technique of longer-wavelength construction for shorter-wavelength reconstruction. In addition, the method is much easier than the traditional recording method of two incident beam interference and has application potential in holographic photonics.

Exploiting the image of the surface reflectivity to measure refractive index profiling for various optical fibers.

A direct image method of surface reflectivities on a cleaved fiber end with a filtered halogen lamp and a TE-cooled CCD with high dynamic range is proposed to measure the multi-wavelength refractive index profiling (RIP). A polished black glass is used to be a reference standard for measuring the absolute reflectivity of the fiber end. With the developed calibration procedures, both the spatially dependent sensitivity and spectral responsivity of the CCD pixels can be eliminated to achieve the high spatial accuracy. Tested fiber is connected with a fiber terminator to prevent errors from the backside return light. With the present method, the RIP can be precisely measured for not only multi-mode fibers but also single-mode fibers.

Developing a microspectrophotometer to measure the dependence of broadband refractive indices on Ge-doped concentrations in GRIN rods.

A confocal microspectrophotometer is utilized to scan the surface reflectivities of a polished gradient-index (GRIN) rod in the range of 400 to 900 nm. The pure fused silica is used to be a reference standard for deducing the absolute reflectivities of the Ge-doped core. Then, multi-wavelength refractive index profiles of the Ge-doped core can be further determined based on the Fresnel equation. Moreover, this work shows a connection between the material dispersion of the GRIN rod and the Ge-doped concentrations measured by an energy dispersive spectrometer. Finally, the dependence of the refractive index of the Ge-doped core on the doping concentrations at a certain wavelength can be easily expressed as a linear form.

Heterodyne moiré surface profilometry.

In this study, a novel moiré fringe analysis technique is proposed for measuring the surface profile of an object. After applying a relative displacement between two gratings at a constant velocity, every pixel of CMOS camera can capture a heterodyne moiré signal. The precise phase distribution of the moiré fringes can be extracted using a one-dimensional fast Fourier transform (FFT) analysis on every pixel, simultaneously filtering the harmonic noise of the moiré fringes. Finally, the surface profile of the tested objected can be generated by substituting the phase distribution into the relevant equation. The findings demonstrate the feasibility of this measuring method, and the measurement error was approximately 4.3 µm. The proposed method exhibits the merits of the Talbot effect, projection moiré method, FFT analysis, and heterodyne interferometry.

Volume polarization holographic recording in thick photopolymer for optical memory.

Based on a vector wave theory of volume holograms, dependence of holographic reconstruction on the polarization states of the writing and reading beams is discussed. It is found that under paraxial approximation the circular polarization holograms provide a better distinction of the reading beams. Characteristics of recording polarization holograms in thick phenanthrenequinone-doped poly(methyl methacrylate) (PQ/PMMA) photopolymer are experimentally investigated. It is found that the circular polarization holographic recording possesses better dynamic range and material sensitivity, and a uniform spatial frequency response over a wide range. The performance is comparable to that of the intensity holographic recording in PQ/PMMA. Based on theoretical analyses and the material properties, a polarization multiplexing holographic memory using circularly polarization recording configuration for increasing storage capacity has been designed and experimentally demonstrated.

Near-infrared sensitive photorefractive device using polymer dispersed liquid crystal and BSO:Ru hybrid structure.

A near-infrared sensitive hybrid device, based on a Ru-doped BSO photorefractive substrate and polymer dispersed liquid crystal (PDLC) layer, is reported. It is found that the photoexcited charge carriers generated in the BSO:Ru substrate create an optically induced space charge field, sufficient to penetrate into the PDLC layer and to re-orient the LC molecules inside the droplets. Beam-coupling measurements at the Bragg regime are performed showing prospective amplification values and high spatial resolution. The proposed structure does not require indium tin oxide (ITO) contacts and alignment layers. Such a device allows all the processes to be controlled by light, thus opening further potential for real-time image processing at the near-infrared range.

Are all Cages Created Equal? Analysis of Cervical Cage Malfunctions Using FDA MAUDE Database.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To characterize failure rates of cervical cages based on manufacturer and design characteristics using the nationwide database of reported malfunctions. BACKGROUND: The Food and Drug Administration (FDA) aims to ensure the safety and efficacy of cervical interbody implants postimplantation; however, intraoperative malfunctions may be overlooked. MATERIALS AND METHODS: The FDA's Manufacturer and User Facility Device Experience database was queried for reports of cervical cage device malfunctions from 2012 to 2021. Each report was categorized based on the failure type, implant design, and manufacturer. Two market analyses were performed. First, "failure-to-market share indices" were generated by dividing the number of failures per year for each implant material by its yearly US market share in cervical spine fusion. Second, "failure-to-revenue indices" were calculated by dividing the total number of failures per year for each manufacturer by their approximate yearly revenue from spinal implants in the US. Outlier analysis was performed to generate a threshold value above which failure rates were defined as greater than the normal index. RESULTS: In total, 1336 entries were identified, and 1225 met the inclusion criteria. Of these, 354 (28.9%) were cage breakages, 54 (4.4%) were cage migrations, 321 (26.2%) were instrumentation-related failures, 301 (24.6%) were assembly failures, and 195 (15.9%) were screw failures. Poly-ether-ether-ketone implants had higher failure by market share indices for both migration and breakage compared with titanium. Upon manufacturer market analysis, Seaspine, Zimmer-Biomet, K2M, and LDR exceeded the failure threshold. CONCLUSION: The most common cause of implant malfunction was breakage. Poly-ether-ether-ketone cages were more likely to break and migrate compared with titanium ones. Many of these implant failures occurred intraoperatively during instrumentation, which underscores the need for FDA evaluation of these implants and their accompanying instrumentation under the appropriate loading conditions before commercial approval.

The prognostic value of lymph node to primary tumor standardized uptake value ratio in cancer patients: a meta-analysis.

OBJECTIVE: The lymph node to primary tumor standardized uptake value ratio (NTR) is an innovative parameter derived from positron emission tomography/computed tomography (PET/CT) scans that captures the intricate relationship between primary tumors and associated lymph nodes. This meta-analysis aimed to investigate the prognostic value of NTR in cancer patients. METHODS: A systematic search of PubMed, Cochrane, and Embase databases was conducted to identify studies investigating the association between NTR and survival outcomes in cancer patients. The pooled adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Twelve studies comprising a total of 2037 patients were included in the meta-analysis. Elevated NTR was significantly associated with worse overall survival aHR (2.21, 95% CI 1.63 to 2.99), disease-free survival aHR (3.27, 95% CI 2.12 to 5.05), and distant metastasis-free survival aHR (2.07, 95% CI 1.55 to 2.78) in cancer patients. Subgroup analyses by cancer type showed consistent results across various malignancies, including head and neck squamous cell carcinoma, endometrial carcinoma, lung cancer, breast cancer, and nasopharyngeal carcinoma. CONCLUSIONS: This meta-analysis provides evidence for a significant association between elevated NTR and worse survival outcomes in cancer patients. Elevated NTR may serve as a useful prognostic biomarker for cancer patients and could potentially be used to guide treatment decisions and monitor disease progression. Future studies should aim to validate these findings in larger and more diverse patient populations and investigate the underlying mechanisms for the observed association between NTR and survival outcomes.

PQ:DMNA/PMMA photopolymer having amazing volume holographic recording at wavelength of insignificant absorption.

N, N-dimethyl-4-nitroaniline doping enables red-light holographic recording that was originally insensitive in thick phenanthrenequinone/poly(methyl methacrylate) photopolymer to have reasonable sensitivity. A volume hologram was recorded by a 647 nm laser with maximum diffraction efficiency of about 43% in a 2-mm-thick sample. A Bragg selectivity curve and an image hologram reconstruction are also demonstrated. These experimental results support recording material for volume holographic applications in an extended red spectral range.

Near-infrared properties of Rh-doped Bi12TiO20 crystals for photonic applications.

The effect of Rh doping in Bi(12)TiO(20) (BTO) crystals on the photosensitivity and recording speed at 1064 nm is reported. Response time of 0.1 s is measured during real-time holographic recording without any preliminary treatments. Once the crystal is pre-excited with a green light, the detected response time becomes 0.02 s. A possibility to implement BTO:Rh crystal plate with liquid crystals into a hybrid organic/inorganic device is demonstrated, which opens perspectives for further near-infrared applications.

Treatment of facet cysts associated with neurogenic intermittent claudication with x-stop.

BACKGROUND: Facet degeneration often leads to the formation of synovial facet cysts. As facet cysts invade the spinal canal, they become a contributing factor to spinal stenosis. Previous studies have demonstrated successful treatment of neurogenic intermittent claudication (NIC), a major symptom of spinal stenosis, with an interspinous process device. PURPOSE: To compare clinical outcomes of patients with and without synovial facet cysts treated with an interspinous process device. STUDY DESIGN: Retrospective review of prospective data of consecutive patients undergoing the X-Stop procedure at an institution. OUTCOME MEASURES: Visual Analog Scale; Oswestry Disability Index; sitting, standing, and walking tolerances; and satisfaction survey. METHODS: Review of all patients from 2006 to 2010 undergoing X-Stop procedure at an institution. Imaging studies were used to identify the presence and measure the size of the facet cysts in 285 patients with a minimum of 6-month follow-up. Comparative clinical outcomes determined if X-Stop is a successful treatment option for patients with NIC in conjunction with synovial facet cysts (<3 mm, ≥3 mm). RESULTS: Fifty-eight of 285 patients (20.4%) were determined to have a synovial cyst as a contributing component of spinal stenosis. Twelve of 58 patients were noted to have a cyst ≥3 mm. The mean follow-up time for patients with and without a facet cyst was 21 months (6-55±12 mo) and 22 months (6-61±12 mo), respectively. The age of the patient at the time of the operation with and without facet cysts was 73 (±10 y). Patients without synovial cysts, with synovial cysts, and cysts ≥3 mm had an average change in Oswestry Disability Index of 15.6, 15.8, and 16.2, respectively. Visual Analog Scale scores were 2.3, 1.8, and 2.3, respectively. In addition, on satisfaction surveys 72.4%, 82.0%, and 77.8% were either very or somewhat satisfied, respectively. Overall complications included 4 spinous process fracture, 4 hematomas, 1 wound infection, and 1 implant migration. CONCLUSIONS: No statistical difference was noted in any of the outcome measures among patients with small facet cysts, large facet cysts, or without facet cysts when treated with an interspinous process device. We can thus conclude that X-Stop is an appropriate treatment consideration for NIC with or without the presence of synovial facet cysts.

An Analysis of a Decade of Lumbar Interbody Cage Failures in the United States: A MAUDE Database Study.

STUDY DESIGN: A retrospective case series. OBJECTIVE: This study aims to assess the rates of lumbar interbody cage failures based on their material and manufacturer. SUMMARY OF BACKGROUND DATA: Perioperative lumbar interbody cage malfunctions are underreported events in the spine literature and may result in complications. Although the Food and Drug Administration ensures the safety of these devices under physiological conditions after implantation, these devices may experience nonphysiological conditions during implantation, which may be overlooked. MATERIALS AND METHODS: The MAUDE database was examined for reports of lumbar cage device malfunctions from 2012 to 2021. Each report was categorized based on failure type and implant design. A market analysis was performed by dividing the total number of failures per year for each manufacturer by their approximate yearly revenue from spinal implants in the United States. Outlier analysis was performed to generate a threshold value above which failure rates were defined as greater than the normal index. RESULTS: Overall, 1875 lumbar cage malfunctions were identified. Of these, 1230 (65.6%) were cage breakages, 257 (13.7%) were instrument malfunctions, 177 (9.4%) were cage migrations, 143 (7.6%) were assembly failures, 70 (4.5%) were screw-related failures, and 21 (1.1%) were cage collapses. Of the breakages, 923 (74.9%) occurred during insertion or impaction and 97 entries detailed a medical complication or a retained foreign body. Of the migrations, 155 (88.6%) were identified postoperatively, of which 73 (47.1%) detailed complications and 52 (33.5%) required a revision procedure. Market analysis demonstrated that Medtronic, Zimmer Biomet, Stryker, Seaspine, and K2M exceeded the calculated threshold. CONCLUSIONS: Lumbar cages with polyether ether ketone core material failed more frequently by breakage, whereas titanium surface cages failed more frequently by migration. Failure rates varied depending on the manufacturer. Most cage breakages identified in the present study occurred intraoperatively during implantation. These findings call for a more detailed Food and Drug Administration evaluation of these intraoperative malfunctions before commercial approval. LEVEL OF EVIDENCE: Level 4.

Quasi-nonvolatile storage in Ru-doped Bi12SiO20 crystals by two-wavelength holography.

Prolonged read-out process of a hologram recorded at near infrared with simultaneous green light exposure is measured in Ru-doped Bi12SiO20 crystal. The experimental results are confirmed by numerical simulations, suggesting two different traps involved in the space-charge transport mechanism. In addition, quasi-permanent holographic recording of image with fast updating speed by using two-wavelength recording is demonstrated.

Thermally activated state transition technique for femto-Newton-level force measurement.

We develop and test a thermally activated state transition technique for ultraweak force measurement. As a force sensor, the technique was demonstrated on a classical Brownian bead immersed in water and restrained by a bistable optical trap. A femto-Newton-level flow force imposed on this sensor was measured by monitoring changes in the transition rates of the bead hopping between two energy states. The treatment of thermal disturbances as a requirement instead of a limiting factor is the major feature of the technique, and provides a new strategy by which to measure other ultraweak forces beyond the thermal noise limit.

Identification of protein domains on major pilin MrkA that affects the mechanical properties of Klebsiella pneumoniae type 3 fimbriae.

The Klebsiella pneumoniae type 3 fimbriae are mainly composed of MrkA pilins that assemble into a helixlike filament. This study determined the biomechanical properties of the fimbriae and analyzed 11 site-directed MrkA mutants to identify domains that are critical for the properties. Escherichia coli strains expressing type 3 fimbriae with an Ala substitution at either F34, V45, C87, G189, T196, or Y197 resulted in a significant reduction in biofilm formation. The E. coli strain expressing MrkAG189A remained capable of producing a normal number of fimbriae. Although F34A, V45A, T196A, and Y197A substitutions expressed on E. coli strains produced sparse quantities of fimbriae, no fimbriae were observed on the cells expressing MrkAC87A. Further investigations of the mechanical properties of the MrkAG189A fimbriae with optical tweezers revealed that, unlike the wild-type fimbriae, the uncoiling force for MrkAG189A fimbriae was not constant. The MrkAG189A fimbriae also exhibited a lower enthalpy in the differential scanning calorimetry analysis. Together, these findings indicate that the mutant fimbriae are less stable than the wild-type. This study has demonstrated that the C-terminal ß strands of MrkA are required for the assembly and structural stability of fimbriae.

Sound Pressure Distribution in the Ear After Radical Mastoidectomy With Meatoplasty.

OBJECTIVE: We aimed to identify the sound pressure distribution along the external auditory canal after radical mastoidectomy with meatoplasty by combining real ear measurements and measurements obtained using a finite-element model. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care university hospital. PATIENTS: We evaluated 16 patients who had undergone radical mastoidectomy with meatoplasty in one ear and had intact nonoperated contralateral ears, which served as the control group. INTERVENTION DIAGNOSTIC: Real ear measurements testing at specific frequencies were performed postoperatively. MAIN OUTCOME MEASURE: Sound pressure gains were measured at five different depths along the external auditory canal, and a validated finite-element model was used to simulate the sound pressure distributions along the external auditory canals of the operated and nonoperated ears. RESULTS: The average peak resonant frequency near the tympanic membrane in operated ears was significantly lesser than that in nonoperated ears (2434.4 ± 616.4 versus 2935.9 ± 602.2 Hz; Wilcoxon signed-rank test, p < 0.05). The average peak resonant amplitude near the tympanic membrane showed no significant intergroup difference (paired-sample t test, p > 0.05). The peak resonant frequencies at different depths of the external auditory canal varied in the nonoperated ears (Kruskal-Wallis rank-sum test, 2880.9 ± 581.7 Hz, p = 0.02) but did not differ significantly in the operated ears (Kruskal-Wallis rank-sum test, 2464.4 ± 670.3 Hz, p = 0.75). In the finite-element model, the peak resonant frequencies along the depth of the external auditory canal varied in the normal ear and were homogeneous in the operated ear. CONCLUSION: Radical mastoidectomy with meatoplasty altered the sound distribution in the external auditory canal. Our finite-element model successfully simulated the postoperative sound distribution in the external auditory canal and will facilitate development of wearable equipment for these patients.

Structural and mechanical properties of Klebsiella pneumoniae type 3 Fimbriae.

This study investigated the structural and mechanical properties of Klebsiella pneumoniae type 3 fimbriae, which constitute a known virulence factor for the bacterium. Transmission electron microscopy and optical tweezers were used to understand the ability of the bacterium to survive flushes. An individual K. pneumoniae type 3 fimbria exhibited a helix-like structure with a pitch of 4.1 nm and a three-phase force-extension curve. The fimbria was first nonlinearly stretched with increasing force. Then, it started to uncoil and extended several micrometers at a fixed force of 66 ± 4 pN (n = 22). Finally, the extension of the fimbria shifted to the third phase, with a characteristic force of 102 ± 9 pN (n = 14) at the inflection point. Compared with the P fimbriae and type 1 fimbriae of uropathogenic Escherichia coli, K. pneumoniae type 3 fimbriae have a larger pitch in the helix-like structure and stronger uncoiling and characteristic forces.