Efficacy, safety, and cost-effectiveness of pegylated PEG-rhg-CSF in pediatric patients receiving high-intensity chemotherapy: results from a phase II study.

Background: High-intensity chemotherapy can cause life-threatening complications in pediatric patients. Therefore, this study investigated safety and efficacy of long-acting pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF; Jinyouli®) in children undergoing high-intensity chemotherapy. Methods: Treatment-naive patients received post-chemotherapy PEG-rhG-CSF as primary prophylaxis for two cycles. The primary endpoints were drug-related adverse events (AEs) and bone pain scores. Secondary endpoints included grade 3-4 neutropenia, duration of neutropenia recovery, absolute neutrophil count changes, febrile neutropenia (FN), reduced chemotherapy intensity, antibiotic usage, and AE severity. The cost-effectiveness of PEG-rhG-CSF was compared with that of rhG-CSF (Ruibai®). Results: Here, 307 and 288 patients underwent one and two PEG-rhG-CSF cycles, respectively. Ninety-one patients experienced drug-related AEs, primarily bone pain (12.7%). Moreover, Grade 3-4 neutropenia and FN were observed. Median FN durations were 3.0 days in both cycles. No drug-related delays were observed during chemotherapy. One patient experienced grade 4 neutropenia-induced reduction in chemotherapy intensity during cycle 2. In total, 138 patients received antibiotics. PEG-rhG-CSF exhibited superior cost-effectiveness compared to rhG-CSF. Conclusion: Our findings indicate that PEG-rhG-CSF is safe, efficient, and cost-effective in pediatric patients undergoing high-intensity chemotherapy, providing preliminary evidence warranting further randomized controlled trials.

Dynamic accuracy measurement method for star trackers using a time-synchronized high-accuracy turntable.

Star trackers are typically used in a spacecraft to provide absolute attitude information to the on-board attitude control system so as to promote high accuracy. The performance of the star tracker is rather important. Attitude incorrectness provided by star trackers may lead to bad navigation with big deviations, even failure of satellites. Therefore, how to realize and verify the accuracy is crucial. As a matter of fact, it is difficult to validate accuracy of star trackers on the ground, especially for star trackers under highly dynamic conditions. In this paper, an accuracy measurement method for star trackers under dynamic conditions is proposed, utilizing a high-accuracy swing table to provide reference to compare. To this end, a swing table, star tracker, and the test equipment are synchronized, in order to reduce systematic errors. As the motion trajectory of the swing table can be set beforehand, the initial attitude of the star tracker can be predicted through a set of coordinate transformations. As a result, the star tracker is able to keep tracking, regardless of the angular velocity of the swing table. This makes the statistical sample points more sufficient and the results more reliable. Moreover, it can evaluate the angular velocity of star trackers up to 20°/s. In comparison with the conventional method with simulated stars, this method utilizes real navigation stars as observation targets making the measurement results much closer to the on-orbit performance. Lastly, but much more importantly, it can also verify the performance of a star tracker in one experiment, such as sensitivity, static performance, capture probability, and so on. Experimental results demonstrate that the proposed method is effective, especially for highly dynamic star trackers. Such a measurement environment is close to the in-orbit conditions, and it can satisfy the stringent requirement for star trackers under high dynamics.

Heterogeneous changes in mobility in response to the SARS-CoV-2 Omicron BA.2 outbreak in Shanghai.

The coronavirus disease 2019 (COVID-19) pandemic and the measures taken by authorities to control its spread have altered human behavior and mobility patterns in an unprecedented way. However, it remains unclear whether the population response to a COVID-19 outbreak varies within a city or among demographic groups. Here, we utilized passively recorded cellular signaling data at a spatial resolution of 1 km × 1 km for over 5 million users and epidemiological surveillance data collected during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 outbreak from February to June 2022 in Shanghai, China, to investigate the heterogeneous response of different segments of the population at the within-city level and examine its relationship with the actual risk of infection. Changes in behavior were spatially heterogenous within the city and population groups and associated with both the infection incidence and adopted interventions. We also found that males and individuals aged 30 to 59 y old traveled more frequently, traveled longer distances, and their communities were more connected; the same groups were also associated with the highest SARS-CoV-2 incidence. Our results highlight the heterogeneous behavioral change of the Shanghai population to the SARS-CoV-2 Omicron BA.2 outbreak and the effect of heterogenous behavior on the spread of COVID-19, both spatially and demographically. These findings could be instrumental for the design of targeted interventions for the control and mitigation of future outbreaks of COVID-19, and, more broadly, of respiratory pathogens.

Assessing changes in incubation period, serial interval, and generation time of SARS-CoV-2 variants of concern: a systematic review and meta-analysis.

BACKGROUND: After the first COVID-19 wave caused by the ancestral lineage, the pandemic has been fueled from the continuous emergence of new SARS-CoV-2 variants. Understanding key time-to-event periods for each emerging variant of concern is critical as it can provide insights into the future trajectory of the virus and help inform outbreak preparedness and response planning. Here, we aim to examine how the incubation period, serial interval, and generation time have changed from the ancestral SARS-CoV-2 lineage to different variants of concern. METHODS: We conducted a systematic review and meta-analysis that synthesized the estimates of incubation period, serial interval, and generation time (both realized and intrinsic) for the ancestral lineage, Alpha, Beta, and Omicron variants of SARS-CoV-2. RESULTS: Our study included 280 records obtained from 147 household studies, contact tracing studies, or studies where epidemiological links were known. With each emerging variant, we found a progressive shortening of each of the analyzed key time-to-event periods, although we did not find statistically significant differences between the Omicron subvariants. We found that Omicron BA.1 had the shortest pooled estimates for the incubation period (3.49 days, 95% CI: 3.13-4.86 days), Omicron BA.5 for the serial interval (2.37 days, 95% CI: 1.71-3.04 days), and Omicron BA.1 for the realized generation time (2.99 days, 95% CI: 2.48-3.49 days). Only one estimate for the intrinsic generation time was available for Omicron subvariants: 6.84 days (95% CrI: 5.72-8.60 days) for Omicron BA.1. The ancestral lineage had the highest pooled estimates for each investigated key time-to-event period. We also observed shorter pooled estimates for the serial interval compared to the incubation period across the virus lineages. When pooling the estimates across different virus lineages, we found considerable heterogeneities (I2 > 80%; I2 refers to the percentage of total variation across studies that is due to heterogeneity rather than chance), possibly resulting from heterogeneities between the different study populations (e.g., deployed interventions, social behavior, demographic characteristics). CONCLUSIONS: Our study supports the importance of conducting contact tracing and epidemiological investigations to monitor changes in SARS-CoV-2 transmission patterns. Our findings highlight a progressive shortening of the incubation period, serial interval, and generation time, which can lead to epidemics that spread faster, with larger peak incidence, and harder to control. We also consistently found a shorter serial interval than incubation period, suggesting that a key feature of SARS-CoV-2 is the potential for pre-symptomatic transmission. These observations are instrumental to plan for future COVID-19 waves.

Efficacy and safety of programmed cell death receptor 1 inhibition-based regimens in patients with pediatric malignancies: the real-world study in China.

Background: Programmed death receptor 1 (PD-1) inhibition has shown durable response and mild adverse events (AEs) in adult malignancies. However, data on the clinical activity of PD-1 inhibition in pediatric patients are lacking. We comprehensively assessed the efficacy and safety of PD-1 inhibitor-based regimens for pediatric malignancies. Methods: We conducted a real-world, multi-institutional, retrospective analysis of pediatric malignancies treated with PD-1 inhibitor-based regimens. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints included disease control rate (DCR), duration of response (DOR), and AEs. The Kaplan-Meier method was used to calculate PFS and DOR. The National Cancer Institute Common Toxicity Criteria for AEs (version 5.0) were used to grade toxicity. Results: A total of 93 and 109 patients were evaluated for efficacy and safety, respectively. For all efficacy-evaluable patients, PD-1 inhibitor monotherapy, combined chemotherapy, combined histone deacetylase inhibitor, and combined vascular endothelial growth factor receptor tyrosine kinase inhibitor cohorts, the ORR and DCR were 53.76%/81.72%, 56.67%/83.33%, 54.00%/80.00%, 100.00%/100.00%, and 12.50%/75.00%, respectively; the median PFS and DOR were 17.6/31.2 months, not achieved/not achieved, 14.9/31.2 months, 17.6/14.9 months, and 3.7/1.8 months, respectively; the incidence rate of AEs were 83.49%, 55.26%, 100.00%, 80.00%, and 100.00%, respectively. One patient in the PD-1 inhibitor-combined chemotherapy cohort discontinued treatment due to diabetic ketoacidosis. Conclusions: This largest retrospective analysis demonstrate that PD-1 inhibitor-based regimens are potentially effective and tolerable in pediatric malignancies. Our findings provide references for future clinical trials and practice of PD-1 inhibitors in pediatric cancer patients.

A multicenter phase II trial of primary prophylactic PEG-rhG-CSF in pediatric patients with solid tumors and non-Hodgkin lymphoma after chemotherapy: An interim analysis.

BACKGROUND: Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) can be used in pediatric patients. This study assessed the safety and efficacy of PEG-rhG-CSF as a primary prophylactic drug against neutropenia after chemotherapy in pediatric patients with solid tumors or non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: This phase II study (between October 2020 and March 2022) enrolled pediatric patients with solid tumors or NHL treated with high-intensity chemotherapy and with grade ≥3 myelosuppression for at least 14 days during chemotherapy. Prophylactic PEG-rhG-CSF was given at 100 µg/kg body weight (maximum total dosage of 6 mg) once 24-48 h following chemotherapy for two cycles. The primary endpoint was the incidence of PEG-rhG-CSF-related adverse events (AEs). The key secondary endpoints were the rates of grade 3/4 neutropenia and febrile neutropenia (FN). RESULTS: This study included 160 pediatric patients with a median age of 6.22 (0.29, 18.00) years. Fifty-eight patients (36.25%) were diagnosed with sarcoma. AEs potentially related to PEG-rhG-CSF included bone pain (n = 32), fatigue (n = 21), pain at the injection site (n = 21), and myalgia (n = 20). The rates of grade 3/4 neutropenia and FN during treatment were 57.28% and 29.45%, respectively. CONCLUSION: PEG-rhG-CSF is well tolerated and effective in pediatric patients with solid tumors or NHL. These findings should be substantiated with further trials. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04547829.

A Retrospective Modeling Study of the Targeted Non-Pharmaceutical Interventions During the Xinfadi Outbreak in the Early Stage of the COVID-19 Pandemic - Beijing, China, 2020.

What is already known about this topic?: China has repeatedly contained multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks through a comprehensive set of targeted non-pharmaceutical interventions (NPIs). However, the effectiveness of such NPIs has not been systematically assessed. What is added by this report?: A multilayer deployment of case isolation, contact tracing, targeted community lockdowns, and mobility restrictions could potentially contain outbreaks caused by the SARS-CoV-2 ancestral strain, without the requirement of city-wide lockdowns. Mass testing could further aid in the efficacy and speed of containment. What are the implications for public health practice?: Pursuing containment in a timely fashion at the beginning of the pandemic, before the virus had the opportunity to spread and undergo extensive adaptive evolution, could help in averting an overall pandemic disease burden and be socioeconomically cost-effective.

Flame Retardancy and Mechanical Properties of Melt-Spun PA66 Fibers Prepared by End-Group Blocking Technology.

Preparing flame-retardant polyamide 66 (PA66) fibers through melt spinning remains one of the biggest challenges nowadays. In this work, dipentaerythritol (Di-PE), an eco-friendly flame retardant, was blended into PA66 to prepare PA66/Di-PE composites and fibers. It was confirmed that Di-PE could significantly improve the flame-retardant properties of PA66 by blocking the terminal carboxyl groups, which was conducive to the formation of a continuous and compact char layer and the reduced production of combustible gas. The combustion results of the composites showed that the limiting oxygen index (LOI) increased from 23.5% to 29.4%, and underwriter laboratories 94 (UL-94) passed the V-0 grade. The peak of heat release rate (PHRR), total heat release (THR), and total smoke production (TSP) decreased by 47.3%, 47.8%, and 44.8%, respectively, for the PA66/6 wt% Di-PE composite compared to those recorded for pure PA66. More importantly, the PA66/Di-PE composites possessed excellent spinnability. The prepared fibers still had good mechanical properties (tensile strength: 5.7 ± 0.2 cN/dtex), while maintaining good flame-retardant properties (LOI: 28.6%). This study provides an outstanding industrial production strategy for fabricating flame-retardant PA66 plastics and fibers.

Transmission Dynamics and Epidemiological Characteristics of the SARS-CoV-2 Delta Variant - Hunan Province, China, 2021.

What is already known about this topic?: Little is known about the epidemiology, natural history, and transmission patterns of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant. Monitoring the evolution of viral fitness of SARS-CoV-2 in the host population is key for preparedness and response planning. What is added by this report?: We analyzed a successfully contained local outbreak of Delta that took place in Hunan, China, and provided estimates of time-to-key event periods, infectiousness over time, and risk factors for SARS-CoV-2 infection and transmission for a still poorly understood variant. What are the implications for public health practice?: Our findings simultaneously shed light on both the characteristics of the Delta variant, by identifying key age groups, risk factors, and transmission pathways, and planning a future response effort against SARS-CoV-2.

Vaccination effects on post-infection outcomes in the Omicron BA.2 outbreak in Shanghai.

Omicron and its sublineages are currently predominant and have triggered epidemiological waves of SARS-CoV-2 around the world due to their high transmissibility and strong immune escape ability. Vaccines are key measures to control the COVID-19 burden. Omicron BA.2 caused a large-scale outbreak in Shanghai since March 2022 and resulted in over 0.6 million laboratory-confirmed infections. The vaccine coverage of primary immunization among residents aged 3 years and older in Shanghai exceeded 90%, and inactivated COVID-19 vaccines were mainly delivered. In the context of high vaccine coverage, we conducted a cohort study to assess vaccine effects on reducing the probability of developing symptoms or severity of disease in infections or nonsevere cases. A total of 48,243 eligible participants were included in this study, the majority of whom had asymptomatic infections (31.0%) and mild-to-moderate illness (67.9%). Domestically developed COVID-19 vaccines provide limited protection to prevent asymptomatic infection from developing into mild-to-moderate illness and durable protection to prevent nonsevere illness from progressing to severe illness caused by Omicron BA.2. Partial vaccination fails to provide effective protection in any situation. The level of vaccine effects on disease progression in the elderly over 80 years old was relatively lower compared with other age groups. Our study results added robust evidence for the vaccine performance against Omicron infection and could improve vaccine confidence.

Midwife empathy and its association with the childbirth experience: a cross-sectional study.

BACKGROUND: Although pregnancy and childbirth comprise a life-course that most midwives experience, whether their own experiences of childbirth resonate with other women during childbirth remains to be determined. In this study, we therefore characterized midwives' empathic capabilities and defined their underlying factors. METHOD: We conducted a cross-sectional study with data from 464 midwives in Guangdong, China, that were collected through the "Chinese version of the Jefferson Scale of Empathy for Health Professionals (JSE-HP)." This questionnaire contains sections related to midwife demographics and delivery characteristics. We then implemented multivariate logistic regression analysis to identify empathy-related factors. RESULTS: Our analysis revealed 303 (65.3%) participants in the high-empathy group while 161 (34.7%) were in the middle-empathy group. Compared with the reference groups, these results indicated that higher empathy was associated with an elevated educational level (OR, 1.83; 95% CI, 1.04-3.25), high monthly salary (OR, 2.30; 95% CI, 1.11-4.80), and no shift work (OR, 2.89; 95% CI, 1.09-7.63). The odds of a high empathy score were higher for midwives who experienced two childbirths (2.27, 1.11-4.66) and for those who had children under the age of 3 years (2.81, 1.34-5.92). CONCLUSION: Midwives possess a moderate-to-high level of empathy, and the greater the number of childbirths they experienced and the younger their children, the higher their reported empathy score. This study contributes novel information regarding the empathic behavior of midwives toward women who give birth in China.

Assessing the feasibility of sustaining SARS-CoV-2 local containment in China in the era of highly transmissible variants.

BACKGROUND: The SARS-CoV-2 containment strategy has been successful in mainland China prior to the emergence of Omicron. However, in the era of highly transmissible variants, whether it is possible for China to sustain a local containment policy and under what conditions China could transition away from it are of paramount importance at the current stage of the pandemic. METHODS: We developed a spatially structured, fully stochastic, individual-based SARS-CoV-2 transmission model to evaluate the feasibility of sustaining SARS-CoV-2 local containment in mainland China considering the Omicron variants, China's current immunization level, and nonpharmaceutical interventions (NPIs). We also built a statistical model to estimate the overall disease burden under various hypothetical mitigation scenarios. RESULTS: We found that due to high transmissibility, neither Omicron BA.1 nor BA.2 could be contained by China's pre-Omicron NPI strategies which were successful prior to the emergence of the Omicron variants. However, increased intervention intensity, such as enhanced population mobility restrictions and multi-round mass testing, could lead to containment success. We estimated that an acute Omicron epidemic wave in mainland China would result in significant number of deaths if China were to reopen under current vaccine coverage with no antiviral uptake, while increasing vaccination coverage and antiviral uptake could substantially reduce the disease burden. CONCLUSIONS: As China's current vaccination has yet to reach high coverage in older populations, NPIs remain essential tools to maintain low levels of infection while building up protective population immunity, ensuring a smooth transition out of the pandemic phase while minimizing the overall disease burden.

SARS-CoV-2 containment was achievable during the early stage of the pandemic: a retrospective modelling study of the Xinfadi outbreak in Beijing.

Prior to the emergence of the Omicron variant, many cities in China had been able to maintain a "Zero-COVID" policy. They were able to achieve this without blanket city-wide lockdown and through widespread testing and an extensive set of nonpharmaceutical interventions (NPIs), such as mask wearing, contact tracing, and social distancing. We wanted to examine the effectiveness of such a policy in containing SARS-CoV-2 in the early stage of the pandemic. Therefore, we developed a fully stochastic, spatially structured, agent-based model of SARS-CoV-2 ancestral strain and reconstructed the Beijing Xinfadi outbreak through computational simulations. We found that screening for symptoms and among high-risk populations served as methods to discover cryptic community transmission in the early stage of the outbreak. Effective contact tracing could greatly reduce transmission. Targeted community lockdown and temporal mobility restriction could slow down the spatial spread of the virus, with much less of the population being affected. Population-wide mass testing could further improve the speed at which the outbreak is contained. Our analysis suggests that the containment of SARS-CoV-2 ancestral strains was certainly possible. Outbreak suppression and containment at the beginning of the pandemic, before the virus had the opportunity to undergo extensive adaptive evolution with increasing fitness in the human population, could be much more cost-effective in averting the overall pandemic disease burden and socioeconomic cost.

Epidemiological characteristics and transmission dynamics of the outbreak caused by the SARS-CoV-2 Omicron variant in Shanghai, China: A descriptive study.

Background: In early March 2022, a major outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant spread rapidly throughout Shanghai, China. Here we aimed to provide a description of the epidemiological characteristics and spatiotemporal transmission dynamics of the Omicron outbreak under the population-based screening and lockdown policies implemented in Shanghai. Methods: We extracted individual information on SARS-CoV-2 infections reported between January 1 and May 31, 2022, and on the timeline of the adopted non-pharmaceutical interventions. The epidemic was divided into three phases: i) sporadic infections (January 1-February 28), ii) local transmission (March 1-March 31), and iii) city-wide lockdown (April 1 to May 31). We described the epidemic spread during these three phases and the subdistrict-level spatiotemporal distribution of the infections. To evaluate the impact on the transmission of SARS-CoV-2 of the adopted targeted interventions in Phase 2 and city-wide lockdown in Phase 3, we estimated the dynamics of the net reproduction number (Rt ). Findings: A surge in imported infections in Phase 1 triggered cryptic local transmission of the Omicron variant in early March, resulting in the largest outbreak in mainland China since the original wave. A total of 626,000 SARS-CoV-2 infections were reported in 99.5% (215/216) of the subdistricts of Shanghai until the end of May. The spatial distribution of the infections was highly heterogeneous, with 37% of the subdistricts accounting for 80% of all infections. A clear trend from the city center towards adjacent suburban and rural areas was observed, with a progressive slowdown of the epidemic spread (from 463 to 244 meters/day) prior to the citywide lockdown. During Phase 2, Rt remained well above 1 despite the implementation of multiple targeted interventions. The citywide lockdown imposed on April 1 led to a marked decrease in transmission, bringing Rt below the epidemic threshold in the entire city on April 14 and ultimately leading to containment of the outbreak. Interpretation: Our results highlight the risk of widespread outbreaks in mainland China, particularly under the heightened pressure of imported infections. The targeted interventions adopted in March 2022 were not capable of halting transmission, and the implementation of a strict, prolonged city-wide lockdown was needed to successfully contain the outbreak, highlighting the challenges for containing Omicron outbreaks. Funding: Key Program of the National Natural Science Foundation of China (82130093); Shanghai Rising-Star Program (22QA1402300).

Ultrasonic-assisted preparation of ultrafine Pd nanocatalysts loaded on Cl--intercalated MgAl layered double hydroxides for the catalytic dehydrogenation of dodecahydro-N-ethylcarbazole.

N-ethylcarbazole/dodecahydro-N-ethylcarbazole (NEC/H12-NEC) is a promising LOHC, and the development of a catalyst with high activity and stability is the key to realizing its reversible hydrogen storage process. In this paper, ultrafine Pd nanocrystalline catalysts (Pd/LDHs-us) supported on Cl--intercalated MgAl LDHs were prepared by a simple ultrasonic-assisted reduction method and applied in the dehydrogenation of 12H-NEC. In the process of ultrasonic-assisted reduction, the instantaneous high temperature generated by cavitation decomposed part of the CO32- in LDHs interlayer, and promoted PdCl42- to enter the interlayer and become new intercalated ions. At the same time, hydroxyl groups on the surface of LDHs were excited to generate hydrogen radicals (•H) with strong reducibility, which reduced PdCl42- to Pd nanoparticles (PdNPs) in situ. The remaining Cl- ions continued to exist in the interlayer as intercalated ions. The agglomeration of PdNPs was effectively inhibited, and the average particle size was 1.8 nm, which was uniformly dispersed on LDHs, which improved the catalytic activity of Pd/LDHs-us. The coordination between PdNPs and oxygen in the hydroxyl groups on the surface of LDHs improved its catalytic stability. Using Pd/LDHs-us catalyst, the conversion rate of H12-NEC was 100.0 %, and the dehydrogenation efficiency was 99.3 % at 180℃. When the reaction temperature drops to 170℃, the dehydrogenation efficiency can still reach 94.6 %, showing excellent catalytic performance. The study of dehydrogenation kinetics shows that the apparent activation energy of Pd/LDHs-us catalyst is only 90.97 kJ/mol. This provides a new method and idea for the preparation of efficient dehydrogenation catalysts in the future.

Epidemiological characteristics and transmission dynamics of the outbreak caused by the SARS-CoV-2 Omicron variant in Shanghai, China: a descriptive study.

Background: In early March 2022, a major outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant spread rapidly throughout Shanghai, China. Here we aimed to provide a description of the epidemiological characteristics and spatiotemporal transmission dynamics of the Omicron outbreak under the population-based screening and lockdown policies implemented in Shanghai. Methods: We extracted individual information on SARS-CoV-2 infections reported between January 1 and May 31, 2022, and on the timeline of the adopted non-pharmacological interventions. The epidemic was divided into three phases: i) sporadic infections (January 1-February 28), ii) local transmission (March 1-March 31), and iii) city-wide lockdown (April 1 to May 31). We described the epidemic spread during these three phases and the subdistrict-level spatiotemporal distribution of the infections. To evaluate the impact on the transmission of SARS-CoV-2 of the adopted targeted interventions in Phase 2 and city-wide lockdown in Phase 3, we estimated the dynamics of the net reproduction number ( R t ). Findings: A surge in imported infections in Phase 1 triggered cryptic local transmission of the Omicron variant in early March, resulting in the largest coronavirus disease 2019 (COVID-19) outbreak in mainland China since the original wave. A total of 626,000 SARS-CoV-2 infections were reported in 99.5% (215/216) of the subdistricts of Shanghai. The spatial distribution of the infections was highly heterogeneous, with 40% of the subdistricts accounting for 80% of all infections. A clear trend from the city center towards adjacent suburban and rural areas was observed, with a progressive slowdown of the epidemic spread (from 544 to 325 meters/day) prior to the citywide lockdown. During Phase 2, R t remained well above 1 despite the implementation of multiple targeted interventions. The citywide lockdown imposed on April 1 led to a marked decrease in transmission, bringing R t below the epidemic threshold in the entire city on April 14 and ultimately leading to containment of the outbreak. Interpretation: Our results highlight the risk of widespread outbreaks in mainland China, particularly under the heightened pressure of imported infections. The targeted interventions adopted in March 2022 were not capable of halting transmission, and the implementation of a strict, prolonged city-wide lockdown was needed to successfully contain the outbreak, highlighting the challenges for successfully containing Omicron outbreaks. Funding: Key Program of the National Natural Science Foundation of China (82130093). Research in context: Evidence before this study: On May 24, 2022, we searched PubMed and Europe PMC for papers published or posted on preprint servers after January 1, 2022, using the following query: ("SARS-CoV-2" OR "Omicron" OR "BA.2") AND ("epidemiology" OR "epidemiological" OR "transmission dynamics") AND ("Shanghai"). A total of 26 studies were identified; among them, two aimed to describe or project the spread of the 2022 Omicron outbreak in Shanghai. One preprint described the epidemiological and clinical characteristics of 376 pediatric SARS-CoV-2 infections in March 2022, and the other preprint projected the epidemic progress in Shanghai, without providing an analysis of field data. In sum, none of these studies provided a comprehensive description of the epidemiological characteristics and spatiotemporal transmission dynamics of the outbreak.Added value of this study: We collected individual information on SARS-CoV-2 infection and the timeline of the public health response. Population-based screenings were repeatedly implemented during the outbreak, which allowed us to investigate the spatiotemporal spread of the Omicron BA.2 variant as well as the impact of the implemented interventions, all without enduring significant amounts of underreporting from surveillance systems, as experienced in other areas. This study provides the first comprehensive assessment of the Omicron outbreak in Shanghai, China.Implications of all the available evidence: This descriptive study provides a comprehensive understanding of the epidemiological features and transmission dynamics of the Omicron outbreak in Shanghai, China. The empirical evidence from Shanghai, which was ultimately able to curtail the outbreak, provides invaluable information to policymakers on the impact of the containment strategies adopted by the Shanghai public health officials to prepare for potential outbreaks caused by Omicron or novel variants.

Assessing the feasibility of sustaining SARS-CoV-2 local containment in China in the era of highly transmissible variants.

We developed a spatially structured, fully stochastic, individual-based SARS-CoV-2 transmission model to evaluate the feasibility of sustaining SARS-CoV-2 local containment in mainland China considering currently dominant Omicron variants, China's current immunization level, and non-pharmaceutical interventions (NPIs). We also built a statistical model to estimate the overall disease burden under various hypothetical mitigation scenarios. We found that due to high transmissibility, neither Omicron BA.1 or BA.2 could be contained by China's pre-Omicron NPI strategies which were successful prior to the emergence of the Omicron variants. However, increased intervention intensity, such as enhanced population mobility restrictions and multi-round mass testing, could lead to containment success. We estimated that an acute Omicron epidemic wave in mainland China would result in significant number of deaths if China were to reopen under current vaccine coverage with no antiviral uptake, while increasing vaccination coverage and antiviral uptake could substantially reduce the disease burden. As China's current vaccination has yet to reach high coverage in older populations, NPIs remain essential tools to maintain low levels of infection while building up protective population immunity, ensuring a smooth transition out of the pandemic phase while minimizing the overall disease burden.

The Nadir Oxygen-Specific Heart Rate Response in Sleep Apnea Links With the Occurrence of Acute Myocardial Infarction.

Background: Little is known regarding the quantification of sleep apnea- and hypoxemia-elicited heart rate (HR) response and its prognostic significance of the cardiovascular risk. We sought to explore the impact of HR response and variability specific to obstructive sleep apnea (OSA) on the occurrence of a common cardiovascular event - acute myocardial infarction (AMI). Methods: Consecutive patients with suspected OSA were enrolled and underwent nocturnal respiratory study and electrocardiography monitoring. The minimal oxygen saturation (minSpO2) was determined from the oxygen saturation curve under a subject-specific search window. Primary HR metrics such as maximal HR in response to minSpO2 and respiratory event-specific HR variability were computed from the synchronized recordings. Multivariate regression analyses were conducted to analyze the associations between individualized HR metrics and the occurrence of AMI. Results: Of 2,748 patients recruited, 39% (n = 1,071) had moderate-to-severe OSA (respiratory event index, REI ≥ 15), and 11.4% (n = 313) patients had AMI. Patients with AMI experienced severe OSA, severe minSpO2, and greater HR reactions. Patients with minSpO2 <90% had an adjusted odds ratio (OR) of 1.48 [95% confidence interval (CI): 1.09-2.00, p = 0.012) for AMI. Notably, minSpO2-induced elevated mean HR response (HRmean > 73 bpm) was significantly associated with AMI (OR 1.72, 95% CI: 1.32-2.23, p < 0.001). Patients with both severe minSpO2 (<90%) and elevated HRmean carried an additive OR of 2.65 (95% CI: 1.74-4.05, p < 0.001) for the risk of AMI after adjustment for potential confounders. A large total power spectrum specific to respiratory events was correlated with an adjusted OR of 0.61 for AMI risk. Conclusion: Patients with substantial HR reactions to OSA-induced oxygen nadir and restricted cardiac cycle shifting to respiratory events were likely at increased risk of developing AMI. Detection of nocturnal HR response to hypoxemia may help improve cardiovascular risk stratification.

Bayesian two-stage design for phase II oncology trials with binary endpoint.

In phase II oncology trials, two-stage design allowing early stopping for futility and/or efficacy is frequently used. However, this design based on frequentist statistical approaches could not guarantee a high posterior probability of attending the pre-specified clinically interesting rate from a Bayesian perspective. Here, we proposed a new Bayesian design enabling early terminating for efficacy as well as futility. In addition to the clinically uninteresting and interesting response rate, a prior distribution of response rate, the minimum posterior threshold probabilities and the lengths of the highest posterior density intervals were specified in the design. Finally, we defined the feasible design with the highest total effective predictive probability. We studied the properties of the proposed design and applied it to an oncology trial as an example. The proposed design ensured that the observed response rate fell within prespecified levels of posterior probability. The proposed design provides an alternative design to single-arm two-stage trials.