Polarization of the third harmonic emission from the filamentation of femtosecond cylindrical vector beams.

We experimentally generate a third harmonic (TH) vector optical field in deep ultraviolet wavelength range using femtosecond vector laser beams. The generated TH beams are characterized by analyzing the Stokes parameters with different input laser energies. The results show that the TH predominantly preserves the vector polarization distribution of the fundamental frequency beam. Moreover, the intensity profile of the TH exhibits a multiple-ring structure. A hybrid polarization pattern is observed in the TH, where the ellipticity is influenced by the input laser energy. Our work provides an effective and straightforward method for producing TH vector optical fields, which may facilitate potential applications such as micro/nanofabrication and super-resolution microscopy.

A unified Bayesian framework for bias adjustment in multiple comparisons from clinical trials.

In clinical trials, multiple comparisons arising from various treatments/doses, subgroups, or endpoints are common. Typically, trial teams focus on the comparison showing the largest observed treatment effect, often involving a specific treatment pair and endpoint within a subgroup. These findings frequently lead to follow-up pivotal studies, many of which do not confirm the initial positive results. Selection bias occurs when the most promising treatment, subgroup, or endpoint is chosen for further development, potentially skewing subsequent investigations. Such bias can be defined as the deviation in the observed treatment effects from the underlying truth. In this article, we propose a general and unified Bayesian framework to address selection bias in clinical trials with multiple comparisons. Our approach does not require a priori specification of a parametric distribution for the prior, offering a more flexible and generalized solution. The proposed method facilitates a more accurate interpretation of clinical trial results by adjusting for such selection bias. Through simulation studies, we compared several methods and demonstrated their superior performance over the normal shrinkage estimator. We recommended the use of Bayesian Model Averaging estimator averaging over Gaussian Mixture Models as the prior distribution based on its performance and flexibility. We applied the method to a multicenter, randomized, double-blind, placebo-controlled study investigating the cardiovascular effects of dulaglutide.

Research on predicting hematoma expansion in spontaneous intracerebral hemorrhage based on deep features of the VGG-19 network.

PURPOSE: To construct a clinical noncontrastive computed tomography (NCCT) deep learning joint model for predicting early hematoma expansion (HE) after cerebral hemorrhage (sICH) and evaluate its predictive performance. METHODS: All 254 patients with primary cerebral hemorrhage from January 2017 to December 2022 in the General Hospital of the Western Theater Command were included. According to the criteria of hematoma enlargement exceeding 33% or the volume exceeding 6 ml, the patients were divided into the HE group and the hematoma non-enlargement (NHE) group. Multiple models and the 10-fold cross-validation method were used to screen the most valuable features and model the probability of predicting HE. The area under the curve (AUC) was used to analyze the prediction efficiency of each model for HE. RESULTS: They were randomly divided into a training set of 204 cases in an 8:2 ratio and 50 cases of the test set. The clinical imaging deep feature joint model (22 features) predicted the area under the curve of HE as follows: clinical Navie Bayes model AUC 0.779, traditional radiology logistic regression (LR) model AUC 0.818, deep learning LR model AUC 0.873, and clinical NCCT deep learning multilayer perceptron model AUC 0.921. CONCLUSION: The combined clinical imaging deep learning model has a high predictive effect for early HE in sICH patients, which is helpful for clinical individualized assessment of the risk of early HE in sICH patients.

High-precision clock date recovery for optical wireless communications using orbital-angular-momentum-based mode division multiplexing.

In this Letter, we explore the potential of the application of clock data recovery for the implementation of real-time optical wireless communications (OWCs) employing orbital angular momentum (OAM)-based mode division multiplexing (MDM). We experimentally demonstrate a 3-mode multiplexed optical wireless link with a sum rate of 60 Gbps, in which the time synchronization of different channels is realized by the proposed modified digital feedback clock recovery based on the Gardner algorithm. The experimental results show that high-precision channel synchronization with a low timing error can be achieved, and the bit-error rate of all channels can drop below 7% of the hard-decision forward error correction (HD-FEC) limit of 3.8 × 10-3, which indicates that clock data recovery can potentially provide the implementation of real-time OWCs using OAM-based MDM.

Field recovery via simplified carrier-assisted differential detection with interleaved subcarrier loading scheme at low CSPR condition.

In this Letter, we propose a simplified carrier-assisted differential detection (CADD) receiver with interleaved subcarrier loading scheme to further reduce the system hardware complexity while preserving the capability of field recovery of double sideband (DSB) complex-valued signals at the low carrier to signal power ratio (CSPR) condition. The numerical results show that the simplified CADD receiver requires less gap subcarriers to achieve a bit-error-rate (BER) below the 7% hard-decision forward error correction (HD-FEC) limit of 3.8 × 10-3 as compared with a conventional CADD receiver. Despite the robustness to the time delay fluctuation decreases, which can be avoided using time-independent components in place of time delay line, more than a 3.2-dB optical signal-to-noise ratio (OSNR) gain can be obtained regardless of CSPR.

Effects of initial invasive vs. initial conservative treatment strategies on recurrent and total cardiovascular events in the ISCHEMIA trial.

AIMS: The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial prespecified an analysis to determine whether accounting for recurrent cardiovascular events in addition to first events modified understanding of the treatment effects. METHODS AND RESULTS: Patients with stable coronary artery disease (CAD) and moderate or severe ischaemia on stress testing were randomized to either initial invasive (INV) or initial conservative (CON) management. The primary outcome was a composite of cardiovascular death, myocardial infarction (MI), and hospitalization for unstable angina, heart failure, or cardiac arrest. The Ghosh-Lin method was used to estimate mean cumulative incidence of total events with death as a competing risk. The 5179 ISCHEMIA patients experienced 670 index events (318 INV, 352 CON) and 203 recurrent events (102 INV, 101 CON). A single primary event was observed in 9.8% of INV and 10.8% of CON patients while ≥2 primary events were observed in 2.5% and 2.8%, respectively. Patients with recurrent events were older; had more frequent hypertension, diabetes, prior MI, or cerebrovascular disease; and had more multivessel CAD. The average number of primary endpoint events per 100 patients over 4 years was 18.2 in INV [95% confidence interval (CI) 15.8-20.9] and 19.7 in CON (95% CI 17.5-22.2), difference -1.5 (95% CI -5.0 to 2.0, P = 0.398). Comparable results were obtained when all-cause death was substituted for cardiovascular death and when stroke was added as an event. CONCLUSIONS: In stable CAD patients with moderate or severe myocardial ischaemia enrolled in ISCHEMIA, an initial INV treatment strategy did not prevent either net recurrent events or net total events more effectively than an initial CON strategy. CLINICAL TRIAL REGISTRATION: ISCHEMIA ClinicalTrials.gov number, NCT01471522, https://clinicaltrials.gov/ct2/show/NCT01471522.

Investigation on repetition-coding and space-time-block-coding for indoor optical wireless communications employing beam shaping based on orbital angular momentum modes.

In this paper, we propose a novel beam shaping technique based on orbital angular momentum (OAM) modes for indoor optical wireless communications (OWC). Furthermore, we investigate two spatial diversity techniques, namely repetition-coding (RC) and Alamouti-type orthogonal space-time-block-coding (STBC) for indoor OWC employing the new beam shaping technique. The performance of both diversity schemes is systematically analyzed and compared under different beam shaping techniques using different OAM modes with different power ratios of the modes. It is shown that both RC and STBC can improve the system performance and effective coverage and RC outperforms STBC in all the beam shaping techniques regardless of the power ratios of the different modes. In addition, to further understand the performance of RC and STBC schemes against the signal delays induced during OAM mode conversion, the system tolerance of the two schemes to the delay interval is investigated with different OAM mode-based beam shaping techniques. Numerical results show that higher resistance to the delay interval can be achieved in STBC scheme. The advantage is more obvious when employing OAM0 and OAM1 based beam shaping technique.

Group sequential testing for cluster randomized trials with time-to-event endpoint.

We propose group sequential methods for cluster randomized trials (CRTs) with time-to-event endpoint. The alpha spending function approach is used for sequential data monitoring. The key to this approach is determining the joint distribution of test statistics and the information fraction at the time of interim analysis. We prove that the sequentially computed log-rank statistics in CRTs do not have independent increment property. We also propose an information fraction for group sequential trials with clustered survival data and a corresponding sample size determination approach. Extensive simulation studies are conducted to evaluate the performance of our proposed testing procedure using some existing alpha spending functions in terms of expected sample size and maximal sample size. Real study examples are taken to demonstrate our method.

VOCs characteristics and their ozone and SOA formation potentials in autumn and winter at Weinan, China.

Frequent ozone and fine particulate matter (PM2.5) pollution have been occurring in the Guanzhong Plain in China. To effectively control the tropospheric ozone and PM2.5 pollution, this study performed measurements of 102 VOCs species from Sep.19-25 (autumn) and Nov.27-Dec. 8, 2017 (winter) at Weinan in the central Guanzhong Plain. The total volatile organic compounds (TVOCs) concentrations were 95.8 ± 30.6 ppbv in autumn and 74.4 ± 37.1 ppbv in winter. Alkanes were the most abundant group in both of autumn and winter, accounting for 33.5% and 39.6% of TVOCs concentrations, respectively. The levels of aromatics and oxygenated VOCs were higher in autumn than in winter, mainly due to changes in industrial activities and combustion strength. Photochemical reactivities and ozone formation potentials (OFPs) of VOCs were calculated by applying the OH radical loss rate (LOH) and maximum incremental reactivity (MIR) method, respectively. Results showed that Alkenes and aromatics were the key VOCs in term ozone formation in Weinan, which together contributed 59.6% ̶ 65.3% to the total LOH and OFP. Secondary organic aerosol formation potentials (SOAFP) of the measured VOCs were investigated by employing the fractional aerosol coefficient (FAC) method. Aromatics contributed 94.9% and 96.2% to the total SOAFP in autumn and winter, respectively. The regional transport effects on VOCs and ozone formation were investigated by using trajectory analysis and potential source contribution function (PSCF). Results showed that regional anthropogenic sources from industrial cities (Tongchuan, Xi'an city) and biogenic sources from Qinling Mountain influenced VOCs levels and OFP at Weinan. Future studies need to emphasize on meteorological factors and sources that impact on VOCs concentrations in Weinan.

Spatial characteristics of VOCs and their ozone and secondary organic aerosol formation potentials in autumn and winter in the Guanzhong Plain, China.

As critical precursors of tropospheric ozone (O3) and secondary organic aerosol (SOA), volatile organic compounds (VOCs) largely influence air quality in urban environments. In this study, measurements of 102 VOCs at all five major cities in the Guanzhong Plain (GZP) were conducted during Sep.09-Oct. 13, 2017 (autumn) and Nov. 14, 2017-Jan. 19, 2018 (winter) to investigate the characteristics of VOCs and their roles in O3 and SOA formation. The average concentrations of total VOCs (TVOCs) at Xi'an (XA), Weinan (WN), Xianyang (XY), Tongchuan (TC), and Baoji (BJ) sites were in the range of 55.2-110.2 ppbv in autumn and 42.4-74.3 ppbv in winter. TVOCs concentrations were reduced by 22.4%-43.5% from autumn to winter at XA, WN and BJ. Comparatively low concentrations of TVOCs were observed in XY and TC, ranging from 53.5 to 62.7 ppbv across the sampling period. Alkanes were the major components at all sites, accounting for 26.4%-48.9% of the TVOCs during the sampling campaign, followed by aromatics (4.2%-26.4%). The average concentration of acetylene increased by a factor of up to 4.8 from autumn to winter, indicating the fuel combustion in winter heating period significantly impacted on VOCs composition in the GZP. The OH radical loss rate and maximum incremental reactivity method were employed to determine photochemical reactivities and ozone formation potentials (OFPs) of VOCs, respectively. The VOCs in XA and WN exhibited the highest reactivities in O3 formation, with the OFP of 168-273 ppbv and the OH loss rates of 19.3-40.8 s-1. Alkenes and aromatics primarily related to on-road and industrial emissions contributed 57.8%-76.3% to the total OFP. The contribution of aromatics to the SOA formation at all sites reached 94.1%-98.6%. Considering the potential source-area of VOCs, regional transport of VOCs occurred within the GZP cities.

Sample size calculation for clustered survival data under subunit randomization.

Each cluster consists of multiple subunits from which outcome data are collected. In a subunit randomization trial, subunits are randomized into different intervention arms. Observations from subunits within each cluster tend to be positively correlated due to the shared common frailties, so that the outcome data from a subunit randomization trial have dependency between arms as well as within each arm. For subunit randomization trials with a survival endpoint, few methods have been proposed for sample size calculation showing the clear relationship between the joint survival distribution between subunits and the sample size, especially when the number of subunits from each cluster is variable. In this paper, we propose a closed form sample size formula for weighted rank test to compare the marginal survival distributions between intervention arms under subunit randomization, possibly with variable number of subunits among clusters. We conduct extensive simulations to evaluate the performance of our formula under various design settings, and demonstrate our sample size calculation method with some real clinical trials.

Survival outcomes in sinonasal carcinoma with neuroendocrine differentiation: A NCDB analysis.

BACKGROUND: Sinonasal carcinoma with neuroendocrine differentiation (SCND) is a rare group of tumors with poor prognosis. Treatment and sequence of therapies are still unclear. The goal of this study is to analyze treatment outcomes in SCND using a national database. METHODS: The National Cancer Database was queried for SCND from 2004 to 2014. Patient demographics, tumor characteristics and treatment paradigms were tabulated. Multivariable Cox proportional hazards regression was performed for statistical analysis of treatment regimen on overall survival (OS). RESULTS: A total of 415 patients were identified. Most patients were male (61.2%), with a median age of 58 years and the most common primary site was the nasal cavity (52.5%). T4 tumors were observed in 67.7% of cases. Unimodality (41.9%) and bimodality (43.9%) therapies were the most common treatment modalities. Radiation therapy was the only treatment administered in 30% of the patients, while 27.2% received definitive chemoradiation (CRT) and 11.6% had surgery with adjuvant CRT. In our Cox-PH model, age (HR = 1.04, p < 0.001), T4 (HR = 2.6, p = 0.004) and N2/N3 (HR = 2.18, p = 0.001) were associated with worse survival. Trimodality (HR = 0.49, p = 0.005) and bimodality (HR = 0.65, p = 0.009) therapies had a better OS compared to unimodality. Patients treated with definitive CRT or surgery with adjuvant CRT had a significant increase in OS (p = 0.01 and 0.002 respectively). CONCLUSION: SCND appears to be best treated using a multimodality approach with definitive CRT or surgery followed by CRT. Neoadjuvant chemotherapy could be helpful in selecting the best treatment strategy.

Emission characteristics and ozone formation potentials of gaseous pollutants from in-use methanol-, CNG- and gasoline-fueled vehicles.

Alternative-fueled vehicles have been introduced to solve the problem of the energy crisis and address air pollution. However, typical pollutants (e.g., methane and methanol) are emitted through combustion of the alternative fuel. In this study, the concentrations of regulated pollutants (CO, NO) and unregulated pollutants (CH4, methanol, formaldehyde, and 8 NMHC species) in the exhaust from methanol, CNG, and gasoline-fueled vehicles (MV, NGV, and GV) were measured systematically on a chassis dynamometer during an in-use vehicle driving cycle. The emission factors of these gaseous pollutants were calculated, and the ozone formation potential (OFP) of each ozone precursor measured in this work was evaluated with the MIR scale. The results showed that NO and NMHC species exhausted from the MV and NGV decreased significantly than that from the GV. However, the unburned pollutants exhausted from MV and NGV warrant attention. For the OFPs, CO was the largest contributor for all tested vehicles. Formaldehyde was ranked the second for the MV and NGV. Among the tested vehicles, the OFPs of NGV were the lowest. The results are helpful in quantitating analysis of the vehicle emissions and evaluating the impacts of alternative-fueled vehicles on atmospheric environment.

Sample size calculation for cluster randomization trials with a time-to-event endpoint.

Cluster randomization trials randomize groups (called clusters) of subjects (called subunits) between intervention arms, and observations are collected from each subject. In this case, subunits within each cluster share common frailties, so that the observations from subunits of each cluster tend to be correlated. Oftentimes, the outcome of a cluster randomization trial is a time-to-event endpoint with censoring. In this article, we propose a closed form sample size formula for weighted rank tests to compare the marginal survival distributions between intervention arms under cluster randomization with possibly variable cluster sizes. Extensive simulation studies are conducted to evaluate the performance of our sample size formula under various design settings. Real study examples are taken to demonstrate our method.

Standing wave type localized surface plasmon resonance of multifold Ag nanorods.

Multifold Ag nanorods (AgNRs) have demonstrated great potentials in applications such as surface-enhanced Raman scattering technique due to their specially organized nanostructures. However, there is so far no systematic understanding of their localized surface plasmon resonance (LSPR) behaviors. This work comprehensively studied the plasmonic behaviors of AgNRs with 1, 2 and 3 folded arms. LSPR modes with charge oscillations resembling standing waves were excited in all nanostructures. As arm length increases, there were linear relationships between resonance wavelength and arm length, which applied to all LSPR modes studied. In addition, directly proportional relationships between the slopes of the linear functions and arm number were found for same order LSPR modes of AgNRs. For different modes of a specific AgNR, inversely proportional relationships between the slope and the resonance order N were discovered. These findings evidenced AgNR's standing wave type LSPR characteristics.

Upregulation of miR-1306-5p decreases cerebral ischemia/reperfusion injury in vitro by targeting BIK.

MiR-1306-5p is involved in the progression of acute heart failure, but its role in ischemic stroke remains unclear. Here, SH-SY5Y cells were exposed to oxygen-glucose deprivation (OGD) for 4, 8, and 12 h, respectively, and then reoxygenation for 12 h to construct OGD/R induced cell injury model. Cell viability, cell death, and cell apoptosis were assessed with CCK-8 assay, LDH assay, flow cytometry, and caspase-3 activity assay. The target gene of miR-1306-5p was confirmed by luciferase reporter assay. We found miR-1306-5p expression was significantly down-regulated in OGD/R-induced SH-SY5Y cell model. Moreover, miR-1306-5p protected SH-SY5Y cell against OGD/R-induced injury. Mechanistically, Bcl2-interacting killer (BIK) was the direct target gene of miR-1306-5p. Furthermore, BIK knockdown mimicked, while overexpression reversed the protective effects of miR-1306-5p against OGD/R induced injury. Our findings thus provide an experimental basis miR-1306-5p targeting BIK-based therapy for cerebral I/R injury.

Fabrication and simulation of V-shaped Ag nanorods as high-performance SERS substrates.

Bending straight Ag nanorods (AgNRs) into V-shaped structures can generate a higher surface-enhanced Raman scattering (SERS) performance. Numerical simulations showed that V-shaped AgNRs with a total length between 300 nm and 800 nm were more sensitive than equal-length straight AgNRs under a 785 nm laser in most cases. It was found that at a laser wavelength between 500 nm and 1000 nm, the Raman enhancement factor (EF) of a V-shaped AgNR's 3rd plasmon mode was not only optimal among the other major plasmon modes, but also outperformed the plasmon modes of straight AgNRs. Besides, a linear relationship between the resonance wavelength of the V-shaped AgNR's 3rd mode and its length was observed both numerically and experimentally, which was beneficial for the optimization of SERS substrates. Under 785 nm laser excitation, V-shaped AgNR substrates with a single arm length between 330 nm and 340 nm possessed the highest SERS efficiency. This work took AgNR array substrates one step closer to practical applications.

Nanoparticle-on-mirror cavity modes for huge and/or tunable plasmonic field enhancement.

We present a careful numerical study of nanoparticle (NP) faceting, highlighting the great influence of small morphological changes of NP-mirror cavities on near-field enhancement in the nanoparticle-on-mirror (NPOM) system. Using a 3D finite element method (FEM) plasmon mapping method, the active transverse cavity modes can be confirmed. For the dominant mode, we have found that, by increasing the facet width, the resonance can be tuned linearly to the red with little decrease of the peak near-field intensity. It is further demonstrated that by increasing the NP size, the near-field intensity can be strongly enhanced. Understanding of such extreme optics benefits significantly both the optimized design of potential plasmonic devices and the fundamental understanding of nano-optics. Collaborative experimental considerations are expected with the rapid development of nanotechnology.

Statistical evaluation of the scaled criterion for drug interchangeability.

As more and more generic drug products become available in the marketplace, it is a concern whether these generic drug products can be used interchangeably in terms of their quality, safety, and efficacy. The United States Food and Drug Administration (FDA) indicates that an approved generic drug product can serve as a substitute for the innovative drug product. The FDA, however, does not indicate that approved generic drug products can be used interchangeably even if they are bioequivalent to the same innovative drug product. In the past decade, several criteria for assessing interchangeability were proposed in regulatory guidances and/or literature. Chow, Xu, and Endrenyi proposed a scaled criterion for drug interchangeability (SCDI), which takes both intra-subject variability and subject-by-drug variability into consideration. In this paper, the performance of this criterion is statistically evaluated by deriving the upper confidence limit of the test statistic and extrapolating expression of the power to facilitate sample size calculation. The performance of SCDI is also compared with that of the criterion for assessment of individual bioequivalence (IBE) for addressing drug switchability recommended by the FDA, which also takes into account the subject-by-drug variability, under various parameter specifications.

Ag Nanorods-Oxide Hybrid Array Substrates: Synthesis, Characterization, and Applications in Surface-Enhanced Raman Scattering.

Over the last few decades, benefitting from the sufficient sensitivity, high specificity, nondestructive, and rapid detection capability of the surface-enhanced Raman scattering (SERS) technique, numerous nanostructures have been elaborately designed and successfully synthesized as high-performance SERS substrates, which have been extensively exploited for the identification of chemical and biological analytes. Among these, Ag nanorods coated with thin metal oxide layers (AgNRs-oxide hybrid array substrates) featuring many outstanding advantages have been proposed as fascinating SERS substrates, and are of particular research interest. The present review provides a systematic overview towards the representative achievements of AgNRs-oxide hybrid array substrates for SERS applications from diverse perspectives, so as to promote the realization of real-world SERS sensors. First, various fabrication approaches of AgNRs-oxide nanostructures are introduced, which are followed by a discussion on the novel merits of AgNRs-oxide arrays, such as superior SERS sensitivity and reproducibility, high thermal stability, long-term activity in air, corrosion resistivity, and intense chemisorption of target molecules. Next, we present recent advances of AgNRs-oxide substrates in terms of practical applications. Intriguingly, the recyclability, qualitative and quantitative analyses, as well as vapor-phase molecule sensing have been achieved on these nanocomposites. We further discuss the major challenges and prospects of AgNRs-oxide substrates for future SERS developments, aiming to expand the versatility of SERS technique.