Pressure-Compensated Fiber-Optic Photoacoustic Sensors for Trace SO2 Analysis in Gas Insulation Equipment.

A high-sensitivity fiber-optic photoacoustic sensor with pressure compensation is proposed to analyze the decomposition component SO2 in high-pressure gas insulation equipment. The multiple influence mechanism of pressure on photoacoustic excitation and cantilever detection has been theoretically analyzed and verified. In the high-pressure environment, the excited photoacoustic signal is enhanced, which compensates for the loss of sensitivity of the cantilever. A fiber-optic F-P cantilever is utilized to simultaneously measure static pressure and dynamic photoacoustic wave, and a spectral demodulation method based on white light interference is applied to calculate the optical path difference of the F-P interferometer (FPI). The real-time pressure is judged through the linear relationship between the average optical path difference of FPI and the pressure, which gives the proposed fiber-optic photoacoustic sensor the inherent advantages of being uncharged and resistant to electromagnetic interference. The average optical path difference of FPI is positively related to pressure, with a responsivity of 0.6 µm/atm, which is based on changes in the refractive index of gas. In the range of 1-4 atm, the SO2 sensor has a higher detection sensitivity at high-pressure, which benefits from the pressure compensation effect. With the pressure environment of gas insulation equipment at 4 atm as the application background, the SO2 gas is tested. The detection limit is 20 ppb with an averaging time of 400 s.

Fiber-Optic Photoacoustic Gas Microsensor Dual Enhanced by Helmholtz Resonator and Interferometric Cantilever.

A high-sensitivity fiber-optic photoacoustic (PA) gas microsensor is demonstrated with dual enhancement based on acoustics and detection. Due to the characteristic of small size, a Helmholtz resonator is integrated into a miniature PA sensor. The acoustically amplified PA signal is detected by a high-sensitivity fiber Fabry-Perot (F-P) interferometric cantilever. The first-order resonant frequencies of the interferometric cantilever and Helmholtz resonator are matched by subtle adjustments. The weak PA signal is significantly enhanced in a volume of only 0.35 mL, which breaks the volume limitation of the resonance modes in traditional PA sensing systems. To improve the resolution of the microsensor, a white light interferometry (WLI)-based spectral demodulation algorithm is utilized. The experimental results indicate that the minimum detection limit of acetylene (C2H2) drops to about 15 ppb with an averaging time of 100 s, corresponding to the normalized noise equivalent absorption (NNEA) coefficient of 2.7 × 10-9 W·cm-1·Hz-1/2. The dual resonance enhanced fiber-optic PA gas microsensor has the merits of high sensitivity, intrinsic safety, and compact structure.

High-Precision Photoacoustic Nitrogen Dioxide Gas Analyzer for Fast Dynamic Measurement.

A high-precision photoacoustic (PA) gas analyzer for fast dynamic measurement of ambient nitrogen dioxide (NO2) was developed. The PA analyzer used a differential PA cell combined with two mufflers to achieve rapid gas flow gas detection. A high-power laser diode (LD) with a center wavelength of 450 nm was used as the PA signal excitation source. To reduce the saturated absorption effect of NO2, ambient air was pumped into the analyzer at a flow rate of 900 sccm. Two mufflers were combined with the differential PA cell to reduce the noise caused by the airflow and pump. The parameters of the mufflers were optimized by using a finite element method. The experimental results showed that the gas flow noise was suppressed by 95%. The response time of the PAS analyzer was 34 s. The detection limits of the analyzer were 0.64 and 0.17 ppb when the integration times were 1 and 15 s, respectively. A 120 h continuous monitoring result was compared with the data from the National Environmental Monitoring Station to demonstrate the high reliability of the analyzer.

Differential Cantilever Enhanced Fiber-Optic Photoacoustic Sensor for Diffusion Gas Detection.

Aiming at the problem of the fiber-optic photoacoustic (PA) sensor being easily disturbed by external vibration and noise, a differential cantilever enhanced fiber-optic PA sensor is proposed for diffusion gas detection. The sensor comprises two PA tubes with the same structure and a pair of differential interferometric cantilevers. The two PA tubes are symmetrically distributed. The laser is incident on the PA tube as the signal channel to excite the PA pressure wave. Another tube without incident laser is used as the reference channel to suppress external disturbance. The external interference signals and PA signals superimposed with disturbance are detected by the differential cantilevers from the two channels. The signals are simultaneously restored by a single white-light interferometry demodulator, which multiplexed the spectral frequency domain of the superimposed interference spectrum. The experimental results show that the suppression effect of the differential cantilever enhanced PA sensor on ambient noise is improved by 80%, compared to the traditional single-cantilever sensor. The external cofrequency disturbance is suppressed by 20.9 dB. The minimum detection limit to acetylene (C2H2) downs to about 60 ppb with an integration time of 100 s. The sensor has excellent antivibration and electromagnetic interference ability.

Rapid Photoacoustic Exhaust Gas Analyzer for Simultaneous Measurement of Nitrogen Dioxide and Sulfur Dioxide.

A rapid photoacoustic (PA) exhaust gas analyzer is presented for simultaneous measurements of nitrogen dioxide (NO2) and sulfur dioxide (SO2). A laser diode (LD) emitting at 450 nm and a light-emitting diode (LED) with a peak wavelength of 275 nm operated simultaneously, producing PA signals of NO2 and SO2, respectively. The LD and LED were modulated at different frequencies of 2568 and 2570 Hz, and their emission light beams were transmitted through two resonant tubes in a differential PA cell (DPAC), respectively. A self-made dual-channel digital lock-in amplifier was used to realize the simultaneous detection of dual-frequency PA signals. Cross interference between the PA signals at the two different frequencies was reduced to 0.02% by using a lock-in amplifier. In order to achieve a rapid dynamic measurement, gas sampling was accelerated by an air pump. The use of mufflers and the differential PA detection technique significantly reduced the gas sampling noise. When the gas flow rate was 1000 sccm, the response time of the PA dual-gas analyzer was 8 and 17 s for NO2 and SO2, respectively. The minimum detection limits of NO2 and SO2 were 1.7 and 26.1 ppb when the averaging time of the system was 10 s, respectively. Due to the wide spectral bandwidth of the LED, NO2 produced an interference to the detection of SO2. The interference was reduced by the precise detection of NO2. Since the radiations of the LD and LED passed through two different PA tubes, the impact of NO2 photochemical dissociation caused by UV LED luminescence on NO2 gas detection was negligible. The sharing of the PA cell, the gas lines, and the signal processing modules significantly reduced the size and cost of the PA dual-gas analyzer.

Fiber-Optic Photoacoustic CO Sensor for Gas Insulation Equipment Monitoring Based on Cantilever Differential Lock-In Amplification and Optical Excitation Enhancement.

A fiber-optic photoacoustic CO sensor for gas insulation equipment is proposed, which relies on F-P interferometric cantilever-based differential lock-in amplification and optical multipass excitation enhancement. The sensor has excellent characteristics of high sensitivity, antielectromagnetic interference, fast response, and long-distance detection. The photoacoustic pressure waves in the two resonators of the differential photoacoustic cell (DPAC) are simultaneously detected by two fiber-optic interferometric cantilevers and processed differentially; thereby, the gas flow noise is effectively suppressed. Based on the comprehensive analysis of the superposition of photoacoustic excitation and multipass absorption, the diameter of the resonator is determined to be 6 mm. The optical power emitted by the 1566.6 nm distributed feedback laser is increased to 500 mW by an erbium-doped fiber amplifier. The near-infrared light is reflected 30 times in the multipass cell, which improves the order of magnitude of optical effective excitation. Due to the low sound velocity of SF6 gas, the resonant frequency of the DPAC with a resonator length of 80 mm is 760 Hz. The response time to CO/SF6 gas is 93 s with a flow rate of 500 sccm. The detection limit of the CO sensor is 53 ppb, which realizes the accurate and timely perception of the SF6 decomposition derivative CO and provides technical support for trouble-free operation of gas insulation equipment.

Dense Multibutterfly Spots-Enhanced Miniaturized Optical Fiber Photoacoustic Gas Sensor.

A miniaturized optical fiber photoacoustic gas sensor enhanced by dense multibutterfly spots is reported for the first time. The principle of space light transmission of neglecting paraxial approximation is theoretically analyzed for designing a dense multibutterfly spots-based miniature multipass cell. In a multipass photoacoustic tube with a diameter of 16 mm, the light beam is reflected about a hundred times. The light spots on the mirror surfaces at both ends of the photoacoustic tube form a dense multibutterfly distribution. The volume of the micro multipass gas chamber is only 5.3 mL. An optical fiber cantilever based on F-P interference is utilized as a photoacoustic pressure detector. Compared with that of the single-pass structure, the gas detection ability of the photoacoustic system with dense multibutterfly spots is improved by about 50 times. The proposed miniaturized sensor realizes a detection limit of 3.4 ppb for C2H2 gas with an averaging time of 100 s. The recognized coefficients of minimum detectable absorption (αmin) and normalized noise equivalent absorption are 1.9 × 10-8 cm-1 and 8.4 × 10-10 W cm-1 Hz-1/2, respectively.

High-Precision Multipass Fiber-Optic Photoacoustic Gas Analyzer Based on 2f/1f Wavelength Modulation Spectroscopy.

A self-calibration fiber-optic photoacoustic (PA) gas analyzer based on 2f/1f wavelength modulation spectroscopy (WMS) is proposed, which utilizes gas and solid multipass absorption enhancement. The laser light is incident obliquely on the cell wall, and one end of the cell is equipped with a highly reflective mirror. The gas analyzer takes full advantage of the miniature multipass PA cell, which enhances the absorption of gas and solid simultaneously. As a result, the double absorption enhancement of 1f and 2f PA signals are realized. A dual-channel lock-in white-light interferometer based on fiber-optic PA demodulation is designed to simultaneously extract the 1f and 2f PA signals detected by the silicon cantilever. The experimental results of methane gas detection show that the minimum detection limit (MDL) of the PA gas analyzer is 20 ppb when the integration time is 60 s. Moreover, the detection error of gas concentration is within 3% when the laser power is reduced by half. The fiber-optic PA gas analyzer eliminates the influence of changes in the laser power and optical path loss, which can be used for the high-precision detection of trace gases.

Ultrahigh Sensitive Trace Gas Sensing System with Dual Fiber-Optic Cantilever Multiplexing-Based Differential Photoacoustic Detection.

An ultrahigh sensitive trace gas sensing system was presented with dual cantilever-based differential photoacoustic detection. By combining the double enhancement of multipass absorption and optical differential detection, the gas detection sensitivity was significantly improved. The dual-channel synchronous photoacoustic detection was realized by fiber-optic Fabry-Perot interference spectrum multiplexing. The photoacoustic signals detected by two fiber-optic cantilever microphones installed in a differential photoacoustic cell (DPAC) were out of phase, while the detected gas flow noises were in phase. The optical differential detection method achieved both highly sensitive optical interference measurement and differential noise suppression. In the multipass configuration, the interaction path between excitation light and target gas achieved 4.1 m, which improved the photoacoustic signal by an order of magnitude compared with a single reflection. The maximum gas flow allowed by the system based on the DPAC was 250 sccm, which realized the dynamic monitoring of H2S in the SF6 background. The detection limit for H2S in SF6 background was 5.1 ppb, which corresponds to the normalized noise equivalent absorption coefficient of 9 × 10-10 cm-1 W Hz-1/2.

Ultrahigh-speed phase demodulation of a Fabry-Perot sensor based on fiber array parallel spectral detection.

An ultrahigh-speed phase demodulation system was designed for the Fabry-Perot (F-P) interferometric sensor based on fiber array parallel spectral detection. A high-power amplified spontaneous emission (ASE) source served as the broadband detection light. The spectrum generated by the dispersion of the F-P interference light through an arrayed waveguide grating (AWG) was incident into the fiber array and was detected in parallel by 48 photodiodes. The 48-channel signals were acquired synchronously and processed in real time to achieve a phase demodulation for the F-P cavity at 200 kHz. As a result, a low-resolution spectral detection and demodulation system was constructed with high speed. The length demodulation range of the F-P cavity was 60-700 µm, and the demodulation resolution was as high as 0.22 nm. The designed high-sensitivity demodulator is expected to be used for ultrasonic and high-frequency vibration detection.

Multi-pass Differential Photoacoustic Sensor for Real-Time Measurement of SF6 Decomposition Component H2S at the ppb Level.

We designed and implemented a photoacoustic (PA) sensor for H2S detection in SF6 background gas based on a multi-pass differential photoacoustic cell (MDPC) and a near-infrared distributed feedback (DFB) laser. In the MDPC apparatus, two resonators with identical geometric parameters were vertically and symmetrically embedded. The differential processing algorithm of two phase-reversed signals realized the effective enhancement of the PA signal and suppressed the flow noise in the dynamic sampling process. In addition, the λ/4 buffer chamber in the MDPC was utilized as a muffler to further reduce the flow noise and realize the dynamic detection of H2S. The collimated excitation light was reflected 30 times in a multi-pass structure constituted of two gold-plated concave mirrors, and an absorption path length of 4.92 m was achieved. Due to the high gas density of SF6, the relationship between the signal-to-noise ratio (SNR) and the gas flow was different between SF6 and N2 background gases. The maximum flow rate of the characteristic gas components detected in the SF6 background is 150 standard cubic centimeters per minute (SCCM), which is lower than 350 SCCM in N2. The linearity property was analyzed, and the results show that the sensitivity of the sensor to H2S in the SF6 background was 27.3 µV/ppm. With the structure, parameters, temperature, gas flow, and natural frequency of the MDPC been optimized, a minimum detection limit (MDL) of 11 ppb was reached with an averaging time of 1000 s, which furnished an effective preventive implement for the safe operation of gas insulation equipment.

Fiber-Optic Photoacoustic Gas Sensor with Multiplexed Fabry-Pérot Interferometric Cantilevers.

A fiber-optic photoacoustic (PA) gas sensor with multiplexed Fabry-Pérot (F-P) interferometric cantilevers is demonstrated. A compact cylindrical nonresonant PA tube with a volume of only 0.45 mL is designed. The PA signal is measured by two symmetrically installed fiber-optic interferometric cantilever microphones (FOICMs) to improve the signal-to-noise ratio (SNR). For multiplexing the two cantilevers by a single demodulation system, a dual cavity length synchronous measurement method based on total-phase demodulation algorithm with ultrahigh resolution is developed. The PA signal detection is realized by the second-harmonic wavelength modulation spectroscopy (2f-WMS) technique. The sensor performance is verified by conducting the detection of trace acetylene (C2H2). The normalized noise equivalent absorption (NNEA) coefficient is 2.5 × 10-9 cm-1·W·Hz-1/2, and the minimum detection limit (MDL) downs to about 0.2 ppm with an averaging time of 1 s. The fiber-optic PA gas sensor has characteristics of high resolution and immunity to electromagnetic and vibration interference. Furthermore, the technical scheme of the multiplexed cantilever demodulation shows great potential for remote multipoint monitoring of gases in harsh environments.

Serum IFNα2 levels are associated with disease activity and outperform IFN-I gene signature in a longitudinal childhood-onset SLE cohort.

OBJECTIVE: To study the association of serum IFNα2 levels measured by ultrasensitive single-molecule array (Simoa) and the IFN-I gene signature (IGS) with disease activity and determine whether these assays can mark disease activity states in a longitudinal cohort of childhood-onset SLE (cSLE) patients. METHODS: Serum IFNα2 levels were measured in 338 samples from 48 cSLE patients and 67 healthy controls using an IFNα Simoa assay. Five-gene IGS was measured by RT-PCR in paired whole blood samples. Disease activity was measured by clinical SELENA-SLEDAI and BILAG-2004. Low disease activity was defined by Low Lupus Disease Activity State (LLDAS) and flares were characterized by SELENA-SLEDAI flare index. Analysis was performed using linear mixed models. RESULTS: A clear positive correlation was present between serum IFNα2 levels and the IGS (r = 0.78, P < 0.0001). Serum IFNα2 levels and IGS showed the same significant negative trend in the first 3 years after diagnosis. In this timeframe, mean baseline serum IFNα2 levels decreased by 55.1% (Δ 201 fg/ml, P < 0.001) to a mean value of 164 fg/ml, which was below the calculated threshold of 219.4 fg/ml that discriminated between patients and healthy controls. In the linear mixed model, serum IFNα2 levels were significantly associated with both cSELENA-SLEDAI and BILAG-2004, while the IGS did not show this association. Both IFN-I assays were able to characterize LLDAS and disease flare in receiver operating characteristic analysis. CONCLUSIONS: Serum IFNα2 levels measured by Simoa technology are associated with disease activity scores and characterize disease activity states in cSLE.

Dynamic detection of ppb-level SO2 based on a differential photoacoustic cell coupled with UV-LED.

We design a photoacoustic (PA) SO2 sensor based on the coupling of a differential photoacoustic cell (DPAC) and cost-effective UV-LED, which realized the dynamic monitoring of SO2 gas at the ppb level. Aiming at the limitation of UV-LED divergence, a light source combination module with high condensing efficiency was devised based on a lens through theoretical derivation and experimental analysis. The PA signal with the optimum matching of the lens was 20-times larger than the direct coupling of the UV-LED. Due to the excellent beam collimation effect of the lens assembly, the background interference was only 1 ppm. In addition, the DPAC gathered the merits of doubling the PA signal and reducing the flow noise interference. The analysis of Allan-Werle deviation showed that the detection limit of SO2 was 1.3 ppb with the averaging time of 100 s.

Objective light exposure measurements and circadian rhythm in patients with erythropoietic protoporphyria: A case-control study.

BACKGROUND: Erythropoietic protoporphyria (EPP) patients suffer from painful phototoxicity. Sunlight-avoiding behaviour has not yet been quantified objectively in EPP patients. OBJECTIVE: To study total white light exposure obtained with an actigraph device, before and during afamelanotide treatment, in EPP patients compared to healthy controls. Effects on circadian rhythm, pain and sleep were also investigated. METHODS: Adult EPP patients visiting the Porphyria Center Rotterdam of the Erasmus MC were included in this single-center longitudinal case-control open-label intervention study. Controls were age and place of residence matched. Participants wore an actigraph (Actiwatch Pro) during two weeks for multiple periods. Afamelanotide was given to EPP patients as part of standard care. RESULTS: Twenty-six EPP patients and 23 matched controls participated. Controls were statistically significantly more exposed to white light than EPP patients off treatment during autumn (95.4%), spring (69.9%), and summer (105.4%; p = 0.01). EPP patients on afamelanotide treatment had 71.6% more light exposure during spring compared to EPP patients off treatment (p < 0.01). Afamelanotide treatment resulted in a reduction of painful moments in the morning (6.5% decrease) and the evening (8.1% decrease; p < 0.05). Bedtime differed between EPP patients off treatment, controls and EPP patients on treatment (23:45 h ± 1:51 versus 23:02 ± 1:41 and 23:14 ± 1:29, respectively; p < 0.0001). CONCLUSION: Actigraphy is a useful method to objectively measure white light exposure and treatment effects in EPP. In EPP patients afamelanotide treatment is associated with increased white light exposure during spring, and overall less pain. Treatment with afamelanotide is also associated with normalization of circadian rhythm.

Risk factors for metastatic cutaneous squamous cell carcinoma: Refinement and replication based on 2 nationwide nested case-control studies.

BACKGROUND: Risk factors for cutaneous squamous cell carcinoma (cSCC) metastasis have been investigated only in relatively small data sets. OBJECTIVE: To analyze and replicate risk factors for metastatic cSCC. METHODS: From English and Dutch nationwide cancer registry cohorts, metastatic cases were selected and 1:1 matched to controls. The variables were extracted from pathology reports from the National Disease Registration Service in England. In the Netherlands, histopathologic slides from the Dutch Pathology Registry were revised by a dermatopathologist. Model building was performed in the English data set using backward conditional logistic regression, whereas replication was performed using the Dutch data set. RESULTS: In addition to diameter and thickness, the following variables were significant risk factors for metastatic cSCC in the English data set (n = 1774): poor differentiation (odds ratio [OR], 4.56; 95% CI, 2.99-6.94), invasion in (OR, 1.69; 95% CI, 1.05-2.71)/beyond (OR, 4.43; 95% CI, 1.98-9.90) subcutaneous fat, male sex (OR, 2.59; 95% CI, 1.70-3.96), perineural/lymphovascular invasion (OR, 2.12; 95% CI, 1.21-3.71), and facial localization (OR, 1.57; 95% CI, 1.02-2.41). Diameter and thickness showed significant nonlinear relationships with metastasis. Similar ORs were observed in the Dutch data set (n = 434 cSCCs). LIMITATIONS: Retrospective use of pathology reports in the English data set. CONCLUSION: cSCC staging systems can be improved by including differentiation, clinical characteristics such as sex and tumor location, and nonlinear relationships for diameter and thickness.

Incorporating historical controls in clinical trials with longitudinal outcomes using the modified power prior.

Several dynamic borrowing methods, such as the modified power prior (MPP), the commensurate prior, have been proposed to increase statistical power and reduce the required sample size in clinical trials where comparable historical controls are available. Most methods have focused on cross-sectional endpoints, and appropriate methodology for longitudinal outcomes is lacking. In this study, we extend the MPP to the linear mixed model (LMM). An important question is whether the MPP should use the conditional version of the LMM (given the random effects) or the marginal version (averaged over the distribution of the random effects), which we refer to as the conditional MPP and the marginal MPP, respectively. We evaluated the MPP for one historical control arm via a simulation study and an analysis of the data of Alzheimer's Disease Cooperative Study (ADCS) with the commensurate prior as the comparator. The conditional MPP led to inflated type I error rate when there existed moderate or high between-study heterogeneity. The marginal MPP and the commensurate prior yielded a power gain (3.6%-10.4% vs. 0.6%-4.6%) with the type I error rates close to 5% (5.2%-6.2% vs. 3.8%-6.2%) when the between-study heterogeneity is not excessively high. For the ADCS data, all the borrowing methods improved the precision of estimates and provided the same clinical conclusions. The marginal MPP and the commensurate prior are useful for borrowing historical controls in longitudinal data analysis, while the conditional MPP is not recommended due to inflated type I error rates.

Added Value of Radiotherapy Following Neoadjuvant FOLFIRINOX for Resectable and Borderline Resectable Pancreatic Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: The added value of radiotherapy following neoadjuvant FOLFIRINOX chemotherapy in patients with resectable or borderline resectable pancreatic cancer ((B)RPC) is unclear. The objective of this meta-analysis was to compare outcomes of patients who received neoadjuvant FOLFIRINOX alone or combined with radiotherapy. METHODS: A systematic literature search was performed in Embase, Medline (ovidSP), Web of Science, Scopus, Cochrane, and Google Scholar. The primary endpoint was pooled median overall survival (OS). Secondary endpoints included resection rate, R0 resection rate, and other pathologic outcomes. RESULTS: We included 512 patients with (B)RPC from 15 studies, of which 7 were prospective nonrandomized studies. In total, 351 patients (68.6%) were treated with FOLFIRINOX alone (8 studies) and 161 patients (31.4%) were treated with FOLFIRINOX and radiotherapy (7 studies). The pooled estimated median OS was 21.6 months (range 18.4-34.0 months) for FOLFIRINOX alone and 22.4 months (range 11.0-37.7 months) for FOLFIRINOX with radiotherapy. The pooled resection rate was similar (71.9% vs. 63.1%, p = 0.43) and the pooled R0 resection rate was higher for FOLFIRINOX with radiotherapy (88.0% vs. 97.6%, p = 0.045). Other pathological outcomes (ypN0, pathologic complete response, perineural invasion) were comparable. CONCLUSIONS: In this meta-analysis, radiotherapy following neoadjuvant FOLFIRINOX was associated with an improved R0 resection rate as compared with neoadjuvant FOLFIRINOX alone, but a difference in survival could not be demonstrated. Randomized trials are needed to determine the added value of radiotherapy following neoadjuvant FOLFIRINOX in patients with (B)PRC.

To screen or not to screen? The development of a prediction model for aorto-iliac stenosis in kidney transplant candidates.

Screening for aorto-iliac stenosis is important in kidney transplant candidates as its presence affects pre-transplantation decisions regarding side of implantation and the need for an additional vascular procedure. Reliable imaging techniques to identify this condition require contrast fluid, which can be harmful in these patients. To guide patient selection for these imaging techniques, we aimed to develop a prediction model for the presence of aorto-iliac stenosis. Patients with contrast-enhanced imaging available in the pre-transplant screening between January 1st, 2000 and December 31st, 2018 were included. A prediction model was developed using multivariable logistic regression analysis and internally validated using bootstrap resampling. Model performance was assessed with the concordance index and calibration slope. Three hundred and seventy-three patients were included, 90 patients (24.1%) had imaging-proven aorto-iliac stenosis. Our final model included age, smoking, peripheral arterial disease, coronary artery disease, a previous transplant, intermittent claudication and the presence of a femoral artery murmur. The model yielded excellent discrimination (optimism-corrected concordance index: 0.83) and calibration (optimism-corrected calibration slope: 0.91). In conclusion, this prediction model can guide the development of standardized protocols to decide which patients should receive vascular screening to identify aorto-iliac stenosis. External validation is needed before this model can be implemented in patient care.

Meteorological conditions are heterogeneous factors for COVID-19 risk in China.

Whether meteorological factors influence COVID-19 transmission is an issue of major public health concern, but available evidence remains unclear and limited for several reasons, including the use of report date which can lag date of symptom onset by a considerable period. We aimed to generate reliable and robust evidence of this relationship based on date of onset of symptoms. We evaluated important meteorological factors associated with daily COVID-19 counts and effective reproduction number (Rt) in China using a two-stage approach with overdispersed generalized additive models and random-effects meta-analysis. Spatial heterogeneity and stratified analyses by sex and age groups were quantified and potential effect modification was analyzed. Nationwide, there was no evidence that temperature and relative humidity affected COVID-19 incidence and Rt. However, there were heterogeneous impacts on COVID-19 risk across different regions. Importantly, there was a negative association between relative humidity and COVID-19 incidence in Central China: a 1% increase in relative humidity was associated with a 3.92% (95% CI, 1.98%-5.82%) decrease in daily counts. Older population appeared to be more sensitive to meteorological conditions, but there was no obvious difference between sexes. Linear relationships were found between meteorological variables and COVID-19 incidence. Sensitivity analysis confirmed the robustness of the association and the results based on report date were biased. Meteorological factors play heterogenous roles on COVID-19 transmission, increasing the possibility of seasonality and suggesting the epidemic is far from over. Considering potential climatic associations, we should maintain, not ease, current control measures and surveillance.