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This study presents the usability of the high-rate single-frequency Precise Point Positioning (SF-PPP) technique based on 20 Hz Global Positioning Systems (GPS)-only observations in detecting dynamic motions. SF-PPP solutions were obtained from post-mission and real-time GNSS corrections. These include the International GNSS Service (IGS)-Final, IGS real-time (RT), real-time MADOCA (Multi-GNSS Advanced Demonstration tool for Orbit and Clock Analysis), and real-time products from the Australian/New Zealand satellite-based augmentation systems (SBAS, known as SouthPAN). SF-PPP results were compared with LVDT (Linear Variable Differential Transformer) sensor and single-frequency relative positioning (SF-RP) solutions. The findings show that the SF-PPP technique successfully detects the harmonic motions, and the real-time products-based PPP solutions were as accurate as the final post-mission products. In the frequency domain, all GNSS-based methods evaluated in this contribution correctly detect the dominant frequency of short-term harmonic oscillations, while the differences in the amplitude values corresponding to the peak frequency do not exceed 1.1 mm. However, evaluations in the time domain show that SF-PPP needs high-pass filtering to detect accurate displacement since SF-PPP solutions include trends and low-frequency fluctuations, mainly due to atmospheric effects. Findings obtained in the time domain indicate that final, real-time, and MADOCA-based PPP results capture short-term dynamic behaviors with an accuracy ranging from 3.4 mm to 8.5 mm, and SBAS-based PPP solutions have several times higher RMSE values compared to other methods. However, after high-pass filtering, the accuracies obtained from PPP methods decreased to a few mm. The outcomes demonstrate the potential of the high-rate SF-PPP method to reliably monitor structural and earthquake-induced ground motions and vibration frequencies of structures.

The real-time Global Navigation Satellite System (GNSS) precise orbital and clock products are essential prerequisites for the Positioning, Navigation, and Timing (PNT) services and have been assessed in various studies. Compared to the precision of the orbital and clock products, their combined effect expressed in Signal-In-Space Ranging Error (SISRE) is of higher concern for positioning users. As a special user of the GNSS, the Low Earth Orbit (LEO) satellites need high-precision real-time GNSS products for their Precise Orbit Determination (POD) and clock determination in real time, which enables the future LEO-augmented GNSS PNT service. This study performs a comprehensive analysis of the real-time GNSS products from five different analysis centers, including analysis of their continuity, accuracy of their orbits, precision of their clocks, and their SISREs for LEO satellites at different altitudes. Using the tested products, the LEO POD was also performed to verify the correlation between the quality of the GNSS products and the accuracy of the LEO POD. Furthermore, to assess the integrity of real-time GNSS products, the overbounding standard deviations and mean values of the combined clock and orbital errors were computed and compared for different institutions. It was found that the GPS and Galileo SISRE range from a few centimeters to around 8 cm, while the SISRE of the Beidou Satellite Navigation System (BDS) Medium Earth Orbit (MEO) is a bit worse, i.e., around 1-2 dm. It has been demonstrated that there exists a positive correlation between the SISRE and user altitude, which implies a higher bias introduced to LEO satellites than ground users. The overbounding standard deviations and mean values of the GPS and Galileo products are all within 1 dm, whereas for BDS they are about 1-2 dm. Among the tested products, the smallest SISRE and overbounding values were delivered by the National Centre for Space Studies (CNES) in France for GPS and Galileo, while th

Two approaches are discussed for the estimation and prediction of the orbits of low earth orbit (LEO) satellites that can be used for navigation. The first approach relays on using a ground monitoring network of stations. The procedures to generate the LEO orbital products in this approach are proposed at two accuracy levels to facilitate different positioning applications. The first type targets producing orbits at meter-level accuracy, defined here as LEO-specific broadcast ephemeris. The second type of products would produce orbits with an accuracy of cm as polynomial corrections to the first type of orbits. Real and simulated LEO satellite data is used for testing, mimicking LEO satellites that can be used for positioning. For the first type of products, it was found that orbital prediction errors play the dominant role in the total error budget, especially in cases of mid and long-term prediction. For the second type of products, the predicted orbits within a short period of up to 60 s generate errors at a few cm, and fitting the corrections with a quadratic polynomial reduced the fitting range errors to the cm level compared to the case of applying a linear polynomial. This level of accuracy can fulfill the requirement for precise point positioning (PPP). The second approach is computing the orbits in real time applying the kinematic or reduced-dynamic mode, where the orbits are computed in the PPP mode using GNSS observations collected onboard LEO satellites and the GNSS orbits and clock products are received through inter-satellite links such as the free-access SouthPAN service in Australia, Galileo HAS, or Beidou (BDS-3, PPP-B2b service). The limitations of this approach and preliminary results are given. Furthermore, the LEO satellite clocks determined together with the orbits in the reduced-dynamic LEO satellite orbit process in near-real-time are also analysed. Finally, the impact of possible orbital and clock errors in the range of decimetres to several

Precise point positioning (PPP) has been a competitive global navigation satellite system (GNSS) technique for time and frequency transfer. However, the classical PPP is usually based on the ionosphere-free combination of dual-frequency observations, which has limited flexibility in the multi-frequency scenario. More importantly, the unknown integer ambiguities are not restored to the integer nature, making the advantage of high-precision carrier phase observations underutilized. In this contribution, using the undifferenced and uncombined (UDUC) observations, we derive the time and frequency transfer model suitable for multi-constellation and multi-frequency scenarios. Notably, in short- and medium-baseline time and frequency transfer, the ionosphere-fixed and ionosphere-weighted UDUC models are derived, respectively, by making full use of the single-differenced (SD) ionospheric constraints. The proposed model can be applied to short-, medium- and long-baseline time and frequency transfer. The ambiguities are solved in a double-differenced (DD) form and can thus be restored to integers. To verify the feasibility of the model, GPS data from several time laboratories were collected, and the performance of the time and frequency transfer were analyzed with different baseline lengths. The results showed that the ionosphere-fixed and ionosphere-weighted UDUC models with integer ambiguity resolution could improve the frequency stability by 25–60% and 9–30% at an averaging time of several tens of seconds to 1 day for short- and medium-baseline, respectively. Concerning the long-baseline, the UDUC model is 10–25% more stable than PPP for averaging time below a few thousands second and over 1 day.

The augmentation of the Global Navigation Satellite System (GNSS) by Low Earth Orbit (LEO) satellites is proposed as an effective method to improve the precision and shorten the convergence time of Precise Point Positioning (PPP). Serving as navigation satellites in the future, LEO satellites need to be provided with their high-accuracy orbits in real-time. This would potentially enable the high-accuracy real-time LEO satellite clock determination, and eventually facilitate the high-accuracy ground-based positioning. Studies have been performed to achieve such real-time orbits using a Kalman filter in both the kinematic and reduced-dynamic modes. Batch Least-Squares (BLS) adjustment delivers more stable orbits in near-real-time, as it performs better phase screening. However, it suffers from longer delays compared to the Kalman filter. With the LEO satellite orbit prediction strategies improved over time, this latency can be bridged by short-term orbit prediction. In this study, using real-time GNSS satellite products, the real-time LEO satellite orbits are obtained based on the batch least-squares adjustment and short-term prediction. LEO ephemeris parameters are generated within specific prediction time windows. Using real data from the 500 km GRACE C satellite and 810 km Sentinel-3B satellite, the near-real-time BLS Precise Orbit Determination (POD) results exhibit good accuracy with an Orbital User Range Error (OURE) of 2–4 cm using different real-time GNSS products. A range of delays of the BLS POD processes are assumed, based on tests performed on different processing machines, leading to various prediction windows, from 3–8 min to 12–17 min that correspond to the real-time usage. The orbital prediction errors are shown to be highly correlated with the orbital height and the prediction time. The computational efficiency thus becomes essential to reduce the prediction errors for a certain LEO satellite. For advanced processing units leading to a prediction wind

Long-baseline time transfer can nowadays reach rather high frequency stability based on post-processed batch least-squares adjustment using the Precise Point Positioning (PPP) or Integer-PPP (IPPP) methods. For real-time PPP users, time transfer results are degraded due to the filter-based processing mode, and the degraded accuracy of the real-time satellite orbits and clocks compared to the final ones. The Real-Time Kinematic (RTK) time transfer can significantly reduce the satellite-related errors, but has limits on the baseline length similar to the RTK positioning. Also, the delivery of raw observations instead of State-Space Representation (SSR) products could result in pressure on data transfer and difficulties related to latency and prediction. In this study, the PPP-RTK technique, which combines the advantages of the PPP and the RTK methods, is tested for real-time long-baseline time transfer. As an alternative approach to the above two methods, it allows for the time transfer of long baselines, while not relying on external high-sampling and high-precision satellite clocks. By delivering the satellite clocks and satellite phase biases produced within the PPP-RTK regional network, time differences can be estimated between users and the reference network station, with which stable time transfer between users separated by long baselines can be realized. Using dual-frequency GPS and Galileo data, the PPP-RTK time transfer is tested using approximately a thousand-kilometer-scale network in Europe. The time transfer results between two hydrogen masers, i.e., those on the 884 km baseline BRUX-ONSA and the 920 km baseline WTZR-ONSA, are computed. At an averaging time of 105 s, Modified Allan Deviation (MDEV) at the level of sub-10-15 to 10-15 can be reached when processing the user coordinates in the station fixed, static, or kinematic modes. The median clock residuals can converge to 1 ns and 0.3 ns within 2 min and 15 min, respectively, in the kinematic mode, whi

Two approaches are discussed for the estimation and prediction of the orbits of low earth orbit (LEO) satellites that can be used for navigation. The first approach relays on using a ground monitoring network of stations. The procedures to generate the LEO orbital products in this approach are proposed at two accuracy levels to facilitate different positioning applications. The first type targets producing orbits at meter-level accuracy, defined here as LEO-specific broadcast ephemeris. The second type of products would produce orbits with an accuracy of cm as polynomial corrections to the first type of orbits. Real and simulated LEO satellite data is used for testing, mimicking LEO satellites that can be used for positioning. For the first type of products, it was found that orbital prediction errors play the dominant role in the total error budget, especially in cases of mid and long-term prediction. For the second type of products, the predicted orbits within a short period of up to 60 s generate errors at a few cm, and fitting the corrections with a quadratic polynomial reduced the fitting range errors to the cm level compared to the case of applying a linear polynomial. This level of accuracy can fulfill the requirement for precise point position ing (PPP). The second approach is computing the orbits in real time applying the kinematic or reduced-dynamic mode, where the orbits are computed in the PPP mode using GNSS observations collected onboard LEO satellites and the GNSS orbits and clock products are received through inter-satellite links such as the free-access SouthPAN service in Australia, Galileo HAS, or Beidou (BDS-3, PPP-B2b service). The limitations of this approach and preliminary results are given. Furthermore, the LEO satellite clocks determined together with the orbits in the reduced-dynamic LEO satellite orbit process in near-real-time are also analysed. Finally, the impact of possible orbital and clock errors in the range of decimetres to severa

Precise Orbit Determination (POD) of Low Earth Orbit (LEO) satellites is essential for future LEO-augmented Positioning, Navigation and Timing (PNT) service based on the use of Global Navigation Satellite Systems (GNSS) measurements. Compared with the ambiguity-float LEO satellite POD, Integer Ambiguity Resolution (IAR) reduces number of parameters, eliminates the high correlations between the ambiguities and other estimable parameters, and strengthens model strength. In this study, using real data from Sentinel-6A tracking dual-frequency GPS and Galileo observations, the wide-lane (WL) and narrow-lane (NL) ambiguity fixing rates and the effects of the IAR on orbital accuracy are assessed in the single- and dual-constellation scenarios. Post-processed high-accuracy GNSS satellite clocks, orbits and Observable-specific Signal Biases (OSBs) from the final products of the Center for Orbit Determination in Europe (CODE) and the rapid products of the GeoForschungsZentrum (GFZ) are used for the analysis. Results showed that both the WL and NL fixing rates in the Galileo-only scenario are higher than those in the GPS-only scenario, reaching more than 98%. This implies a better signal quality of the Galileo observations. Applying IAR has improved the orbital accuracy for all single- and dual-constellation scenarios, and was shown to be especially helpful in reducing the once-per-revolution systematic effects in the along-track orbital errors, with over 50% improvement when using the COM products. With the IAR enabled, when using the COM final products, the 3D RMS of the orbital errors amounts to 1.2, 1.2 and 1.1 cm in the GPS-only, Galileo-only and GPS+Galileo combined scenarios, and the RMS of the Orbital User Range Errors (OUREs) amounts to 0.7, 0.7 and 0.6 cm, respectively. When using the GFZ rapid products, the IAR-enabled 3D RMS were 1.8, 2.1 and 1.4 cm in the GPS-only, Galileo-only and GPS+Galileo combined scenarios, with OURE RMS of about 1 cm.

Bounding satellites’ nominal measurement errors to calculate the protection level (PL) of the position error is a salient step of integrity monitoring of positioning autonomous vehicles (AVs). In this work, the focus is on applying the network RTK approach which is a suitable technique for precise positioning of AVs. A measurement weighting matrix formed from the overbounding standard deviation (STD) and considers the correlation among differenced observations was developed to achieve conservative PLs. Two approaches were designed to estimate the overbounding parameters and compute the correlation coefficients using one full year of different satellites measurements from multiple constellations. The Two-Step Gaussian Bounding method is used to calculate the overbounding parameters. The overbounding mean and STD of both code and phase observation errors for both approaches were in the range of 0.0003–1.369 m and 0.007–2.497 m, respectively. While the first approach provides a tight overbounding results, the second is more conservative.

The spectrum of information related to precision medicine in diabetes generally includes clinical data, genetics, and omics-based biomarkers that can guide personalized decisions on diabetes care. Given the remarkable progress in patient risk characterization, there is particular interest in using molecular biomarkers to guide diabetes management. Metabolomics is an emerging molecular approach that helps better understand the etiology and promises the identification of novel biomarkers for complex diseases. Both targeted or untargeted metabolites extracted from cells, biofluids, or tissues can be investigated by established high-throughput platforms, like nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques. Metabolomics is proposed as a valuable tool in precision diabetes medicine to discover biomarkers for diagnosis, prognosis, and management of the progress of diabetes through personalized phenotyping and individualized drug-response monitoring. This review offers an overview of metabolomics knowledge as potential biomarkers in type 2 diabetes mellitus (T2D) diagnosis and the response to glucose-lowering medications.

Absolute or relative precise orbit determination (POD) is an essential prerequisite for many low earth orbit (LEO) missions. The POD of LEO satellites typically relays on processing the onboard global navigation satellite system (GNSS) measurements. The absolute POD is usually based on an ionosphere-free (IF) combination, and currently, integer ambiguity resolution (IAR) can be achieved only when external GNSS satellite phase bias (SPB) products are used. The use of these products is not flexible in multi-frequency/multi-constellation scenarios and is difficult to achieve in real-time missions. For relative POD, the double-differenced (DD) with IAR is the most general method. However, the differencing process amplifies observation noise and loses the opportunity to impose dynamic constraints on some eliminated parameters. In this contribution, based on the use of undifferenced and uncombined (UDUC) observations, a new model for both absolute and relative POD is proposed. In this model, the ambiguities of common-view satellites are constructed into DD form, thus IAR can be achieved without any external SPB products. Working with the UDUC observations, multi-frequency scenarios can be easily applied, and residuals can be separated for each frequency. In addition, with precise GNSS satellite clock/orbit products, both the absolute and relative orbits can be derived, which supports absolute and relative LEO POD. Based on onboard GPS observations of T-A and T-B satellites in formation flying, the performance of the UDUC POD model with DD ambiguity was evaluated. With the UDUC algorithm and IAR, the proposed model presented a consistency of 2.8–3.8 cm in 3D with the reference orbits, and the orbit difference was reduced by 16.3% and 10.6% for T-A and T-B compared with the IF-based POD, respectively. In addition, the relative orbit of the two satellites derived from the proposed model showed a consistency of 1.1–1.5 mm, which proved the feasibility of the UDUC POD model wi

The aims of this thesis were to investigate the role of cardiometabolic health in type 2 diabetes development, and to examine the burden of complications, including cardiovascular diseases, cognitive decline, physical disability, and multimorbidity of non-communicable diseases, across the glycemic spectrum.

Objective: Evidence about the decline of cognition and physical function across glycemic status (normoglycemia, prediabetes, and diabetes) is inconsistent. We evaluated longitudinal changes in cognition and physical function according to glycemic status and also different glycemic transitions. Study design: Population-based cohort study. Methods: 9307 participants (mean age 59.7 years, 53.7 % women) were included from the China Health and Retirement Longitudinal Study (2011–2018). Global cognition (assessed by orientation, memory, and executive function) and physical function (calculated as the sum of impaired basic and instrumental activities of daily living) were assessed in each wave. The glycemic status was assessed in waves 2011 and 2015. Diabetes was defined as fasting blood glucose ≥7.0 mmol/L, HbA1c ≥6.5 %, self-reported diabetes, or glucose-lowering medication use. Prediabetes was defined as fasting blood glucose 5.6–6.9 mmol/L or an HbA1c of 5.7–6.4 %. Results: Compared with normoglycemia, baseline diabetes was associated with a faster decline in orientation (−0.018 SD/year, 95%CI -0.032, −0.004) and a faster increase in physical function score (0.082 /year, 95%CI 0.038, 0.126). We did not observe any effect of prediabetes on the changing rate of cognition and physical function. Progression from normoglycemia to diabetes between waves 2011 and 2015 was associated with a significantly faster decline in global cognition, memory, executive function, and physical function compared with stable normoglycemia. Conclusions: Baseline diabetes was associated with accelerated decline of cognition and physical function. Associations with prediabetes were not observed, suggesting an important short diagnostic window when diabetes presents de novo.

Objective: We studied if large artery stiffness is involved in type 2 diabetes pathogenesis. We also investigated the effect of genetic risk for type 2 diabetes in these associations and the causality. Research design and Methods: In the prospective population-based Rotterdam Study (n = 3,055; mean age, 67.2 years), markers of aortic and carotid stiffnesses and measures of arterial remodeling were assessed. Cox proportional hazard regression analysis estimated the associations between arterial stiffness measures with incident type 2 diabetes. We used 403 single nucleotide polymorphisms to calculate the genetic risk score (GRS) for type 2 diabetes. We adopted Mendelian randomization (MR) analysis to evaluate the causal associations. Results: Over a median follow-up of 14.0 years, higher carotid-femoral pulse wave velocity (hazard ratio,1.18; 95 %CI: 1.04–1.35), carotid distensibility coefficient (1.17; 1.04–1.32), and carotid intima-media thickness (1.15; 1.01–1.32) were independently associated with incident diabetes. The associations were stronger among individuals with a higher GRS for type 2 diabetes. MR analysis did not support the causality of the observed associations. Conclusions: Elevated arterial stiffness is independently associated with incident type 2 diabetes. For most arterial stiffness markers, the associations with incident type 2 diabetes were more robust in individuals with a higher GRS for diabetes.

Background: Relative fat mass (RFM) is a novel sex-specific anthropometric equation (based on height and waist measurements) to estimate whole-body fat percentage. Objective: To examine associations of RFM with incident type-2 diabetes (T2D), and to benchmark its performance against body-mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR). Methods: This prospective longitudinal study included data from three Dutch community-based cohorts free of baseline diabetes. First, we examined data from the PREVEND cohort (median age and follow-up duration: 48.0 and 12.5 years, respectively) using Cox regression models. Validation was performed in the Lifelines (median age and follow-up duration: 45.5 and 3.8 years, respectively) and Rotterdam (median age and follow-up duration: 68.0 and 13.9 years, respectively) cohorts. Results: Among 7961 PREVEND participants, 522 (6.6%) developed T2D. In a multivariable model, all adiposity indices were significantly associated with incident T2D (P all<0.001). While 1 SD increase in BMI, WC and WHR were associated with 68%, 77% and 61% increased risk of developing T2D [Hazard ratio (HR) BMI: 1.68 (95%CI: 1.57-1.80), HR WC: 1.77 (95% CI: 1.63-1.92) and HR WHR: 1.61 (95%CI: 1.48-1.75)], an equivalent increase in RFM was associated with 119% increased risk [HR: 2.19 (95%CI: 1.96-2.44)]. RFM was associated with incident T2D across all age groups, with the largest effect size in the youngest (<40 years) age category [HR: 2.90 (95%CI: 2.15-3.92)]. Results were broadly similar in Lifelines (n = 93,870) and Rotterdam (n = 5279) cohorts. Conclusions: RFM is strongly associated with new-onset T2D and displays the potential to be used in the general practice setting to estimate the risk of future diabetes.

The use of global navigation satellite systems (GNSS) has been a competitive way to provide high-precision and low-cost time and frequency transfer results. However, the traditional GNSS method, the precise point positioning (PPP), is usually based on the ionosphere-free (IF) combination, which is not flexible when applying multi-frequency scenarios. In addition, PPP relies on precise satellite clock products with an accuracy of tens of picoseconds, limiting the time and frequency transfer performance. More importantly, achieving integer ambiguity resolution (IAR) is challenging, which makes high-precision phase observations underutilized. To achieve a better time transfer performance, we must consider all those factors from the GNSS end. In this contribution, a new GNSS time and frequency model at the undifferenced and uncombined (UDUC) level is first derived. In the UDUC model, the satellite clocks are estimated together with other parameters, and the integer ambiguities are resolved in the double-differenced (DD) form for their reliable estimation. Our numerical tests suggest three major findings. First, with integer ambiguities resolved, the UDUC model with satellite clocks fixed showed a 20% to 50% improvement compared with the UDUC PPP model. Second, with IAR and satellite clocks estimated, the proposed UDUC model shows a 10%–40% improvement over the model with satellite clocks fixed. Third, with integer ambiguities resolved and satellite clocks estimated, GPS, Galileo, and BDS-3 all have the potential to achieve frequency transfer in the low-mid 10 - 17 range for averaging times within one day.

Context Hyperglycemia and autonomic dysfunction are bidirectionally related. Objective We investigated the association of longitudinal evolution of heart rate variability (HRV) with incident type 2 diabetes (T2D) among the general population. Methods We included 7630 participants (mean age 63.7 years, 58% women) from the population-based Rotterdam Study who had no history of T2D and atrial fibrillation at baseline and had repeated HRV assessments at baseline and during follow-up. We used joint models to assess the association between longitudinal evolution of heart rate and different HRV metrics (including the heart rate-corrected SD of the normal-to-normal RR intervals [SDNNc], and root mean square of successive RR-interval differences [RMSSDc]) with incident T2D. Models were adjusted for cardiovascular risk factors. Bidirectional Mendelian randomization (MR) using summary-level data was also performed. Results During a median follow-up of 8.6 years, 871 individuals developed incident T2D. One SD increase in heart rate (hazard ratio [HR] 1.20; 95% CI, 1.09-1.33), and log(RMSSDc) (HR 1.16; 95% CI, 1.01-1.33) were independently associated with incident T2D. The HRs were 1.54 (95% CI, 1.08-2.06) for participants younger than 62 years and 1.15 (95% CI, 1.01-1.31) for those older than 62 years for heart rate (P for interaction <.001). Results from bidirectional MR analyses suggested that HRV and T2D were not significantly related to each other. Conclusion Autonomic dysfunction precedes development of T2D, especially among younger individuals, while MR analysis suggests no causal relationship. More studies are needed to further validate our findings.

Deterministic routing has emerged as a promising technology for future non-terrestrial networks (NTNs), offering the potential to enhance service performance and optimize resource utilization. However, the dynamic nature of network topology and resources poses challenges in establishing deterministic routing. These challenges encompass the intricacy of jointly scheduling transmission links and cycles, as well as the difficulty of maintaining stable end-to-end (E2E) routing paths. To tackle these challenges, our work introduces an efficient temporal graph-based deterministic routing strategy. Initially, we utilize a time-expanded graph (TEG) to represent the heterogeneous resources of an NTN in a time-slotted manner. With TEG, we meticulously define each necessary constraint and formulate the deterministic routing problem. Subsequently, we transform this nonlinear problem equivalently into solvable integer linear programming (ILP), providing a robust yet time-consuming performance upper bound. To address the considered problem with reduced complexity, we extend TEG by introducing virtual nodes and edges. This extension facilitates a uniform representation of heterogeneous network resources and traffic transmission requirements. Consequently, we propose a polynomial-time complexity algorithm, enabling the dynamic selection of optimal transmission links and cycles on a hop-by-hop basis. Simulation results validate that the proposed algorithm yields significant performance gains in traffic acceptance, justifying its additional complexity compared to existing routing strategies.

Video-based person re-identification (ReID) is challenging due to the presence of various interferences in video frames. Recent approaches handle this problem using temporal aggregation strategies. In this work, we propose a novel Context Sensing Attention Network (CSA-Net), which improves both the frame feature extraction and temporal aggregation steps. First, we introduce the Context Sensing Channel Attention (CSCA) module, which emphasizes responses from informative channels for each frame. These informative channels are identified with reference not only to each individual frame, but also to the content of the entire sequence. Therefore, CSCA explores both the individuality of each frame and the global context of the sequence. Second, we propose the Contrastive Feature Aggregation (CFA) module, which predicts frame weights for temporal aggregation. Here, the weight for each frame is determined in a contrastive manner: i.e., not only by the quality of each individual frame, but also by the average quality of the other frames in a sequence. Therefore, it effectively promotes the contribution of relatively good frames. Extensive experimental results on four datasets show that CSA-Net consistently achieves state-of-the-art performance.

Wheat is one of the major staple crops around the world. A transient expression system is crucial for gene functional studies in wheat as stable transfection is still difficult in most cultivars. Protoplasts could serve as a versatile transient expression tool in wheat research. Here, we describe protocols for wheat protoplast isolation and transfection that are enabled by cellulase R-10 and macerozyme R-10 containing enzymatic solution and polyethylene glycol-mediated method, respectively. In addition, we show an example of efficiency evaluation of the emerging base editors in wheat protoplasts. These protocols are of wide use in both conventional gene functional analysis and reagent functionality evaluation of genome editing in wheat.

ZBP1 is an interferon-induced cytosolic nucleic acid sensor that facilitates antiviral responses via RIPK3. Although ZBP1-mediated programmed cell death is widely described, whether and how it promotes inflammatory signaling is unclear. Here, we report a ZBP1-induced inflammatory signaling pathway mediated by K63- and M1-linked ubiquitin chains, which depends on RIPK1 and RIPK3 as scaffolds independently of cell death. In human HT29 cells, ZBP1 associated with RIPK1 and RIPK3 as well as ubiquitin ligases cIAP1 and LUBAC. ZBP1-induced K63- and M1-linked ubiquitination of RIPK1 and ZBP1 to promote TAK1- and IKK-mediated inflammatory signaling and cytokine production. Inhibition of caspase activity suppressed ZBP1-induced cell death but enhanced cytokine production in a RIPK1- and RIPK3 kinase activity-dependent manner. Lastly, we provide evidence that ZBP1 signaling contributes to SARS-CoV-2-induced cytokine production. Taken together, we describe a ZBP1-RIPK3-RIPK1-mediated inflammatory signaling pathway relayed by the scaffolding role of RIPKs and regulated by caspases, which may induce inflammation when ZBP1 is activated below the threshold needed to trigger a cell death response.

Absolute or relative precise orbit determination (POD) is an essential prerequisite for different low earth orbit (LEO) missions. For the POD of LEO satellites, the onboard global navigation satellite system (GNSS) is an important reliance. Classical absolute POD is usually based on an ionosphere-free (IF) combination, which causes a waste of observation information and is not flexible in multi-frequency scenarios. Integer ambiguity resolution (IAR) can only be achieved with external GNSS satellite phase bias (SPB) products, which is difficult to achieve for real-time missions. Concerning relative POD, the double-differenced (DD) with IAR is the most classical method. However, the differencing process amplifies observation noise and loses the opportunity to impose dynamic constraints on some eliminated parameters. In this contribution, based on the undifferenced and uncombined (UDUC) observations, a new model that can be used for both absolute and relative POD is proposed. In this model, the ambiguities of common-view satellites are constructed into DD form, thus IAR can be achieved without any external SPB products. Working with the UDUC observations, multi-frequency scenarios can be easily extended, and residuals can be separated for each frequency. In addition, with precise products, both the absolute and relative orbits can be derived, thus can be beneficial for absolute and relative LEO POD. Based on onboard GPS observations of TH02-2A and TH02-2B missions, the performance of the UDUC POD model with DD ambiguity was evaluated. With the UDUC algorithm and IAR, the proposed model presented a consistency of 3-4 cm in 3D with the reference orbits, and the orbit difference was reduced by 32.7% and 20.1% for TH02-2A and TH02-2B compared with the classical IF POD, respectively. In addition, the relative orbit of the two satellites derived from the proposed model showed a consistency of 1.1-1.3 mm, which proved the feasibility of the UDUC POD model with DD ambiguity fo

ZBP1 is an interferon-induced cytosolic nucleic acid sensor that facilitates antiviral responses via RIPK3. Although ZBP1-mediated programmed cell death is widely described, whether and how it promotes inflammatory signaling is unclear. Here, we report a ZBP1-induced inflammatory signaling pathway mediated by K63- and M1-linked ubiquitin chains, which depends on RIPK1 and RIPK3 as scaffolds independently of cell death. In human HT29 cells, ZBP1 associated with RIPK1 and RIPK3 as well as ubiquitin ligases cIAP1 and LUBAC. ZBP1-induced K63- and M1-linked ubiquitination of RIPK1 and ZBP1 to promote TAK1- and IKK-mediated inflammatory signaling and cytokine production. Inhibition of caspase activity suppressed ZBP1-induced cell death but enhanced cytokine production in a RIPK1- and RIPK3 kinase activity-dependent manner. Lastly, we provide evidence that ZBP1 signaling contributes to SARS-CoV-2-induced cytokine production. Taken together, we describe a ZBP1-RIPK3-RIPK1-mediated inflammatory signaling pathway relayed by the scaffolding role of RIPKs and regulated by caspases, which may induce inflammation when ZBP1 is activated below the threshold needed to trigger a cell death response.

Background and aimPrevious studies on cardiovascular risk burden assessed by the Framingham General Cardiovascular Risk Score (FGCRS) and cognitive trajectories mainly focus on Western populations and most of them have used a single measure of cardiovascular risk. In this study, among middle-aged and older Chinese, we investigated (i) the association of baseline FGCRS with subsequent cognitive decline and (ii) the association of FGCRS change with concomitant cognitive decline. Materials and methodsIn wave 1 to wave 4 (2011-2018) of the China Health and Retirement Longitudinal Study, global cognition was assessed by orientation, memory, and executive function. FGCRS was assessed and categorized into tertiles (low, intermediate, and high) at baseline (2011) and 4 years after (2015). Furthermore, external validation was performed to check its generalizability using the English Longitudinal Study of Ageing (ELSA) 2008-2018. ResultsIn total, 6,402 participants with a mean [standard deviation (SD) age of 57.8 (8.4) years, 49.0% women] with complete baseline data and at least one reassessment of cognitive function were included. A 10% increment in baseline FGCRS was associated with a faster decline in global cognition (-0.010 SD/year, 95% CI -0.013, -0.008). Among 4,336 participants [mean (SD) age of 57.8 (8.2) years, 50.0% women] with data on FGCRS changes, compared to individuals with the consistently low FGCRS (reference group), a faster global cognition decline rate was observed in the low to intermediate group (-0.026 SD/year, 95% CI -0.045, -0.007), the low to high group (-0.052 SD/year, 95% CI -0.102, -0.001), the consistently intermediate group (-0.019 SD/year, 95% CI -0.033, -0.005), the intermediate to high group (-0.040 SD/year, 95% CI -0.058, -0.022), the high to intermediate group (-0.024 SD/year, 95% CI -0.047, -0.002), and the consistently high group (-0.047 SD/year, 95% CI -0.060, -0.034). Similar trends were observed for individual cognitive domains. Re

CubeSats can be used for many space missions and Earth science applications if their orbits can be determined precisely. The Precise Orbit Determination (POD) methods are well developed for large LEO satellites during the last two decades. However, CubeSats are built from Commercial Off-The-Shelf (COTS) components and have their own characteristics, which need more investigations. In this paper, precise orbits of 17 3U-CubeSats in the Spire Global constellation are determined using both the reduced-dynamic and the kinematic POD methods. The limitations in using elevation-dependent weighting models for CubeSats POD are also discussed and, as an alternative approach, a weighting model based on the Signal-to-Noise Ratio (SNR) has been proposed. One-month processing of these CubeSats revealed that around 40% of orbits can be determined at the decimeter accuracy, while 50% have accuracy at centimeters. Such precise orbits fulfil most mission requirements that require such POD accuracy. Internal validation methods confirmed the POD procedure and approved the distinction of weighting based on SNR values over the elevation angles.

Signals from the emerging Low Earth Orbit (LEO) satellites from mega-constellations that broadcast internet, such as Starlink (Space X), OneWeb, Iridium etc., also known as “signals of opportunity” (SOP), can potentially aid positioning. These LEO satellites are approximately 20 times closer to Earth compared to the GNSS medium-earth orbit (MEO) satellites – with 300-1500km altitudes, and 90-120 minutes orbital periods. Hence, LEO satellites provide a new navigation space infrastructure with much stronger signal power than GNSS signals. This makes these LEO signals more resilient to interference and available in deep attenuation settings. In challenging environments, with limited GNSS observations that may not allow positioning, such as in urban canyons, bushland, or bottom of mining pits, integrating LEO signals with the available GNSS observations can enable positioning. Moreover, the corresponding high speed of LEO satellites enables faster satellite geometry change, and hereby significantly shortens the convergence time for precise point positioning (PPP). In this contribution, the positioning from LEO Doppler shift time variation integrated with GNSS and two challenges in positioning using LEO will be briefly discussed. For positioning, the orbits of LEO satellites and their clock behaviour must be known. In addition, unlike GNSS satellites, LEO satellites are not equipped with atomic clocks, and typically use ultra-stable oscillators (USOs) or oven-controlled crystal oscillators (OCXOs), nor are they tightly time-synchronised with each other. The estimation and prediction of these orbits and clock errors and drift are discussed.

Positioning integrity monitoring (IM) is essential for liability- and safety-critical land applications such as road transport. IM methods such as solution separation apply multiple filters, which necessitates the use of computationally efficient algorithms in real-time applications. In this contribution, a new approach that significantly improves the computation time of the measurement update of the Kalman filter is presented, where only one matrix inversion is applied for all filters with measurement subsets. The fault detection and identification method and computation of the protection levels (PLs) are discussed. The computational improvement comes at the expense of a small increase in the PL. Test results for precise point positioning (PPP) with float ambiguities in an open-sky and suburban environment demonstrate the reduced computation time using the proposed approach compared to the traditional method, with 23%-42% improvement. The availability of IM for PPP, i.e. when the PL is less than a selected alert limit of 1.625 m, ranged between 92% and 99%, depending on the allowable integrity risk, tested at 10-5 and 10-6, and the observation environment.

In recent years, low Earth orbit (LEO) satellites have been frequently discussed for their benefits in positioning and navigation services as an augmentation to the global navigation satellite systems (GNSSs). Similar to the positioning concept based on ranging to GNSS satellites, precise positioning of single-receiver users needs high-accuracy orbits and clocks of LEO satellites as a pre-condition. For real-time users, high prediction accuracies of these orbits at different latencies are needed. Unlike the satellite clocks, the GNSS orbits can be typically predicted for hours with high accuracy. LEO satellites, however, face more complicated perturbing dynamic terms due to their low altitudes. Therefore, the prediction accuracy and integrity of their orbits need to be addressed. In this study, using real data of three test LEO satellites GRACE C, Sentinel-1A and Sentinel-3B of different altitudes, various reduced-dynamic prediction strategies are assessed, with the appropriate methods selected for different prediction times up to 6 h. The global-averaged orbital user range errors (OUREs) are shown to be altitude-related. For the 700–800 km Sentinel satellites and 500 km GRACE satellite, the RMS of the OUREs is at sub-dm and dm-level for the prediction time of 1 h, respectively, and around 0.2 m and 0.6 m at the prediction time of 6 h, respectively. For integrity purposes, the worst-location OURE are calculated for the predicted orbits using a proposed algorithm considering the Earth as an Ellipsoid, not a sphere as usually done for the GNSS satellites. The orbital user range accuracy (OURA) is then evaluated for different prediction periods, having a time-dependent model proposed to compute the overbounding OURA at any prediction time within 6 h. With an integrity risk of 10 5, using hourly quadratic polynomials as the time-dependent model, the overbounding OURA is around 0.1 m at the prediction of 1 h, and at the sub-meter level for the prediction of 6 h for the S

The Low Earth Orbit (LEO) satellites have shown various benefits in augmenting the Positioning, Navigation and Timing (PNT) service based on Global Navigation Satellite Systems (GNSSs). The higher number of LEO satellites and their much smaller footprints than those of the GNSS satellites motivate studies of the ground tracking network design to pursue higher visibilities to LEO satellites. This contribution proposes an algorithm, called here ‘MaxVis’ to select network stations for LEO satellites of different inclinations and altitudes. The goal is to increase the general visibility and shorten the visibility gaps of LEO satellite that can be observed from the entire ground network, i.e., when at least one of the network stations are visible to the satellite. A parameter can be set to balance the priority of the two objectives. It was found that LEO satellites with high altitudes and low inclinations tend to deliver high visibility. With only the polar regions excluded from the design area for demonstration purposes, the general visibility could reach above 98% with less than 30 stations when the LEO satellite has an altitude of 1200 km and an inclination of 50 degrees. The visibility could be significantly reduced when island areas are excluded from the design area.

Low Earth orbit (LEO) satellites benefit future ground-based positioning with their high number, strong signal strength and high speed. The rapid geometry change with the LEO augmentation offers acceleration of the convergence of the precision point positioning (PPP) solution. This contribution discusses the influences of the LEO augmentation on the precise point positioning—real-time kinematic (PPP-RTK) positioning and its integrity monitoring. Using 1 Hz simulated data around Beijing for global positioning system (GPS)/Galileo/Beidou navigation satellite system (BDS)-3 and the tested LEO constellation with 150 satellites on L1/L5, it was found that the convergence of the formal horizontal precision can be significantly shortened in the ambiguity-float case, especially for the single-constellation scenarios with low precision of the interpolated ionospheric delays. The LEO augmentation also improves the efficiency of the user ambiguity resolution and the formal horizontal precision with the ambiguities fixed. Using the integrity monitoring (IM) procedure introduced in the first part of this series of papers, the ambiguity-float horizontal protection levels (HPLs) are sharply reduced in various tested scenarios, with an improvement of more than 60% from 5 to 30 min after the processing start. The ambiguity-fixed HPLs can generally be improved by 10% to 60% with the LEO augmentation, depending on the global navigation satellite system (GNSS) constellations used and the precision of the ionospheric interpolation.

In recent years, mega-constellation Low Earth Orbit (LEO) satellites have been proposed as an augmentation to the Global Navigation Satellite System (GNSS) for positioning on the ground, especially for those in measurement environments with limited satellite visibility. The fast geometry change of these LEO satellites also reduces the convergence time of Precise Point Positioning (PPP) techniques. To realize the benefits brought by these LEO satellites, their precise orbits and clocks need to be delivered to users, which would typically be based on processing the GNSS signals collected onboard LEO satellites. Assuming that this will be possible in the future, during data reception, storage and transmission, however, data gaps could exist in the collected GNSS measurements, which would result in gaps in the LEO clock estimates. The transmission of the LEO satellite clock corrections to users could also experience outages. In this study, taking the Ultra-Stable Oscillator (USO) onboard GRACE FO-1 as an example of LEO satellites that has similar operational conditions to the expected LEO mega-constellations, three different models are proposed for bridging clock gaps varying from 1 to 60 minutes. Model A considers its mid- to long-term systematic effects, Model B bridges the gaps using low-order polynomials employing the data near the gap, and Model C exploits the benefits of both Models A and B. Results show that Model A results in larger errors than the other two models for short clock gaps, while Model B could lead to a dramatic increase in the bridging errors for long gaps, e.g., 1h. Applying Model C for the USO on GRACE FO-1, the mean absolute bridging errors (in range) are within 1cm for gaps shorter than 10min, and within 0.2m for gaps not exceeding 1h. Increasing the polynomial degree of Model C from quadratic to cubic can lead to a reduction in the mean absolute bridging errors to mm- to cm-level.

Integrity monitoring (IM) is a vital task for precise real-time positioning in road transportation, autonomous driving, and drones, where safety is essential. IM has the main tasks of detection and exclusion of faulty observations and ensuring that the continuity and integrity requirements of the positioning system are met, otherwise alert the user to switch to another system. The traditional receiver-autonomous-integrity-monitoring (RAIM) methods have evolved into the new advanced RAIM (ARAIM) methodology that takes into consideration the use of multi-constellation multi-frequency data with the capability of monitoring simultaneous multiple faults. The ARAIM method has been originally developed primarily for aviation based on the use of the single-point positioning method, which can achieve accuracy typically less than 10 m, or with augmentation at a few m. However, applications such as navigation of drones, or autonomous driving require better accuracy at the dm-level or better, such as for the in-lane accuracy. Such a level of accuracy requires the use of more precise methods such as precise point positioning (PPP), real-time kinematic (RTK), or Network RTK. However, PPP has a serious limitation related to the need for approximately 30 minutes of initialization time for the solution to converge. Therefore, the use of Network RTK (NRTK), with its widespread coverage over most populated areas in developed countries and many others, would be attractive. In our previous work, we discussed integrity monitoring for PPP-RTK and RTK. We also discussed the vulnerabilities from different sources and those at the network stations and at the user, in addition to discussing the observation and stochastic models, and the formulation of the integrity monitoring algorithm. In this contribution, we shift the focus to the user side of Network RTK, assuming the use of the Virtual Reference Station (VRS) methodology. In our algorithm, on one hand, although fixed ambiguity resolution

Global Navigation Satellite Systems’ radio occultation (GNSS-RO) provides the upper troposphere-lower stratosphere (UTLS) vertical atmospheric profiles that are complementing radiosonde and reanalysis data. Such data are employed in the numerical weather prediction (NWP) models used to forecast global weather as well as in climate change studies. Typically, GNSS-RO operates by remotely sensing the bending angles of an occulting GNSS signal measured by larger low Earth orbit (LEO) satellites. However, these satellites are faced with complexities in their design and costs. CubeSats, on the other hand, are emerging small and cheap satellites; the low prices of building them and the advancements in their components make them favorable for the GNSS-RO. In order to be compatible with GNSS-RO requirements, the clocks of the onboard receivers that are estimated through the precise orbit determination (POD) should have short-term stabilities. This is essential to correctly time tag the excess phase observations used in the derivation of the GNSS-RO UTLS atmospheric profiles. In this study, the stabilities of estimated clocks of a set of CubeSats launched for GNSS-RO in the Spire Global constellation are rigorously analysed and evaluated in comparison to the ultra-stable oscillators (USOs) onboard the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC-2) satellites. Methods for improving their clock stabilities are proposed and tested. The results (i) show improvement of the estimated clocks at the level of several microseconds, which increases their short-term stabilities, (ii) indicate that the quality of the frequency oscillator plays a dominant role in CubeSats’ clock instabilities, and (iii) show that CubeSats’ derived UTLS (i.e., tropopause) atmospheric profiles are comparable to those of COSMIC-2 products and in situ radiosonde observations, which provided external validation products. Different comparisons confirm that CubeSats, even those

Due to an increasing requirement for high accuracy orbital information for low Earth orbit (LEO) satellites, precise orbit determination (POD) of LEO satellites is a topic of growing interest. To assure the safety and reliability of the applications requiring high accuracy LEO orbits in near-real-time, integrity monitoring (IM) is an essential operation of the POD process. In this contribution, the IM strategy for LEO POD in both the kinematic and reduced-dynamic modes is investigated. The overbounding parameters of the signal-in-space range error are investigated for the GPS products provided by the International GNSS Service’s Real-Time Service and the Multi-GNSS Advanced Demonstration of Orbit and Clock Analysis service. Benefting from the dynamic models used and the improved model strength, the test results based on the data of the LEO satellite GRACE FO-1 show that the average-case mean protection levels (PLs) can be reduced from about 3–4 m in the kinematic mode to about 1 m in the reduced-dynamic mode in the radial, along-track and cross-track directions. The overbounding mean values of the SISRE play the dominant role in the fnal PLs. In the reduced-dynamic mode and averagecase projection, the IM availabilities reach above 99% in the radial, along-track and cross-track directions with the alert limit (AL) set to 2 m. The values are still above 98% with the AL set to 4 m, when the duty cycle of tracking is reduced to 40%, e.g., in the case of power limits for miniature satellites such as CubeSats.

Nowadays, integrity monitoring (IM) is required for diverse safety-related applications using intelligent transport systems (ITS). To ensure high availability for road transport users for in-lane positioning, a sub-meter horizontal protection level (HPL) is expected, which normally requires a much higher horizontal positioning precision of, e.g., a few centimeters. Precise point positioning-real-time kinematic (PPP-RTK) is a positioning method that could achieve high accuracy without long convergence time and strong dependency on nearby infrastructure. As the first part of a series of papers, this contribution proposes an IM strategy for multi-constellation PPP-RTK positioning based on global navigation satellite system (GNSS) signals. It analytically studies the form of the variance-covariance (V-C) matrix of ionosphere interpolation errors for both accuracy and integrity purposes, which considers the processing noise, the ionosphere activities and the network scale. In addition, this contribution analyzes the impacts of diverse factors on the size and convergence of the HPLs, including the user multipath environment, the ionosphere activity, the network scale and the horizontal probability of misleading information (PMI). It is found that the user multipath environment generally has the largest influence on the size of the converged HPLs, while the ionosphere interpolation and the multipath environments have joint impacts on the convergence of the HPL. Making use of 1 Hz data of Global Positioning System (GPS)/Galileo/Beidou Navigation Satellite System (BDS) signals on L1 and L5 frequencies, for small-to mid-scaled networks, under nominal multipath environments and for a horizontal PMI down to 2 × 10−6, the ambiguity-float HPLs can converge to 1.5 m within or around 50 epochs under quiet to medium ionosphere activities. Under nominal multipath conditions for small-to mid-scaled networks, with the partial ambiguity resolution enabled, the HPLs can converge to 0.3 m

The positioning service aided by low Earth orbit (LEO) mega-constellations has become a hot topic in recent years. To achieve precise positioning, accuracy of the LEO clocks is important for single-receiver users. To bridge the gap between the applicable time of the clock products and the time of positioning, the precise LEO clocks need to be predicted over a certain period depending on the sampling interval of the clock products. This study discusses the prediction errors for periods from 10 s to 1 h for two typical LEO clock types, i.e. the ultra-stable oscillator (USO) and the oven-controlled crystal oscillator (OCXO). The prediction is based on GNSSdetermined precise clock estimates, where the clock stability is related to the GNSS estimation errors, the behaviors of the oscillators themselves, the systematic effects related to the environment and the relativistic effects, and the stability of the time reference. Based on real data analysis, LEO clocks of the two different types are simulated under different conditions, and a prediction model considering the systematic effects is proposed. Compared to a simple polynomial fitting model usually applied, the proposed model can significantly reduce the prediction errors, i.e. by about 40%-70% in simulations and about 5%-30% for real data containing different miss-modeled effects. For both clock types, short-term prediction of 1 min would result in a root mean square error (RMSE) of a few centimeters when using a very stable time reference. The RMSE amounts to about 0.1 m, when a typical real-time time reference of the national center for space studies (CNES) real-time clocks was used. For longterm prediction of 1 h, the RMSE could range from below 1 m to a few meters for the USOs, depending on the complexity of the miss-modeled effects. For OCXOs, the 1 h prediction could lead to larger errors with an RMSE of about 10 m.

Aims: Data on the lifetime risk of type 2 diabetes (T2D) incidence across different cardiovascular health (CVH) categories are scarce. Moreover, it remains unclear whether a genetic predisposition modifies this association. Methods and results: Using data from the prospective population-based Rotterdam Study, a CVH score (body mass index, blood pressure, total cholesterol, smoking status, diet, and physical activity) was calculated and further categorized at baseline. Genetic predisposition to T2D was assessed and divided into tertiles by creating a genetic risk score (GRS). We estimated the lifetime risk for T2D within different CVH and GRS categories. Among 5993 individuals free of T2D at baseline [mean (standard deviation) age, 69.1 (8.5) years; 58% female], 869 individuals developed T2D during follow-up. At age 55 years, the remaining lifetime risk of T2D was 22.6% (95% CI: 19.4-25.8) for ideal, 28.3% (25.8-30.8) for intermediate, and 32.6% (29.0-36.2) for poor CVH. After further stratification by GRS tertiles, the lifetime risk for T2D was still the lowest for ideal CVH in the lowest GRS tertiles [21.5% (13.7-29.3)], in the second GRS tertile [20.8% (15.9-25.8)], and in the highest tertile [23.5% (18.5-28.6)] when compared with poor and intermediate CVH. Conclusion: Our results highlight the importance of favourable CVH in preventing T2D among middle-aged individuals regardless of their genetic predisposition.

Background: The cognitive impact of changes in late-life blood pressure is less clear. We aimed to investigate the association between late-life blood pressure changing pattern and risk of cognitive impairment. Methods: Using data from the community-based Chinese Longitudinal Healthy Longevity Survey, change in systolic (SBP) or diastolic (DBP) blood pressure was calculated as the difference between follow-up and baseline, cognitive impairment was defined based on both the Mini-Mental State Examination and education level. The generalized additive model with penalized spline and multivariate logistic regression model were used, respectively, to examine the associations between continuous and categorized blood pressure changes with cognitive impairment at the follow-up wave. Results: A total of 8493 Chinese elderly without cognitive impairment were included, with mean (standard deviation) age 80.6 (10.7) years. U-shaped associations between late-life blood pressure changes and risk of cognitive impairment were found, with only stable optimal blood pressure related to the lowest risk. For participants with baseline SBP around 130–150 mmHg, the adjusted odds ratio was 1.48 (1.13–1.93) for increasing follow-up SBP (> 150 mmHg), 1.28 (1.02–1.61) for decreasing follow-up SBP (< 130 mmHg), compared to stable follow-up SBP (130–150 mmHg). For participants with relative lower baseline DBP (< 80 mmHg), increasing their DBP to 80–90 mmHg during follow-up was associated with lower cognitive impairment risk (0.73 (0.58–0.93)), compared to steady low follow-up DBP (< 80 mmHg). Sex-specific analysis suggested that men were more vulnerable in term of SBP change. Conclusions: Adhering to a stable optimal level of blood pressure in late-life is related to lower risk of cognitive impairment in Chinese elderly.

Background: Blood pressure targets for oldest-old people have been long debated due to the concern that more stringent targets are associated with increased mortality. We aimed to investigate the association between changes of late-life systolic blood pressure (SBP), mean SBP and SBP variability (SBPV), and all-cause mortality in oldest-old. Methods: Based on the community-based Chinese Longitudinal Healthy Longevity Survey with follow-up conducted in the 3-year interval, we assembled a retrospective cohort of 6639 participants ≥ 80 years with available blood pressure measurements at baseline and second wave. The primary exposures were mean SBP and SBPV (defined as the annual difference in SBP divided by mean SBP) measured between baseline and second wave. The primary outcome was all-cause mortality assessed from the second wave. Results: During 21443.1 person-years of follow-up, 4622 death was recorded. U-shaped associations of mortality with mean SBP and SBPV were identified; the value of 137 mmHg and 4.0 %/year conferred the minimum mortality risk, respectively. The associations of a larger SBPV with an increased mortality risk were observed for both rises and large falls in SBP. The hazard ratio was 1.11 (comparing lowest versus middle quintile; 95 % CI: 1.01, 1.22) with large falls in SBPV and 1.08 (comparing highest versus middle quintile; 95 % CI: 0.98, 1.18) with large rises in SBPV. Conclusions: U-shaped associations between late-life SBP and SBPV and all-cause mortality were found. Our study suggests that a stable SBP level in the middle range is related to lower mortality risk in the oldest-old.

Introduction Data on sex-specific lifetime risk of cardiovascular disease (CVD) across the glycemic spectrum, in particular in impaired fasting glucose (IFG) state, are scarce. Whether overweight/obesity modifies the CVD burden also remains unclear. Research design and methods Using a prospective population-based Rotterdam Study, normoglycemia, IFG, and type 2 diabetes mellitus (T2D) were defined. First incident cases of coronary heart disease, heart failure, and stroke during a follow-up time until January 1, 2015 were identified and formed the composite CVD end point. The remaining lifetime risks of CVD were estimated in each glucose category at 55, 65, 75, and 85 years of age, using a modified version of survival analysis adjusted for the competing risk of death. Results Among 5698 women and 3803 men free of CVD at baseline, the mean age was 64.5 years (SD 9.6) and 60.0% of participants were women. At age 55 years, the remaining lifetime risk of any CVD event among women was 55.1% (95% CI 48.3 to 61.9) for IFG, compared with 52.7% (95% CI 49.5 to 55.9) for normoglycemia and 61.5% (95% CI 54.7 to 68.3) for T2D. For men, the remaining lifetime risk of any CVD event was 62.1% (95% CI 55.2 to 69.1) for IFG, compared with 59.1% (95% CI 55.5 to 62.7) for normoglycemia and 60.3% (95% CI 53.1 to 67.5) for T2D. At age 55 years, the lifetime risk for incident CVD was higher, although not statistically significant, among women and men with IFG who were overweight or had obesity compared with normal-weight women and men. Conclusion IFG carried a large lifetime risk for incident CVD among both women and men compared with normoglycemia. In particular among men, the risk was comparable to that of T2D. Overweight/Obesity modifies the risk and conferred a larger burden of lifetime CVD risk among women and men with IFG.

For real-time precise orbit determination (POD) of low earth orbit (LEO) satellites, high-accuracy global navigation satellite system (GNSS) orbit and clock products are necessary in real time. Recently, the Japanese multi-GNSS advanced demonstration of orbit and clock analysis precise point positioning (PPP) service and the new generation of the Australian/New Zealand satellite-based augmentation system (SBAS)-aided PPP service provide free and precise GNSS products that are directly broadcast through the navigation and geostationary earth orbit satellites, respectively. With the high quality of both products shown in this study, a 3D accuracy of centimeters can be achieved in the post-processing mode for the reduced-dynamic orbits of small LEO satellites having a duty cycle down to 40% and at sub-dm to dm level for the kinematic orbits. The results show a promising future for high-accuracy real-time POD onboard LEO satellites benefiting from the precise free-of-charge PPP corrections broadcast by navigation systems or SBAS.