ABSTRACT
In the classical infectious disease compartment model, the parameters are fixed. In reality, the probability of virus transmission in the process of disease transmission depends on the concentration of virus in the environment, and the concentration depends on the proportion of patients in the environment. Therefore, the probability of virus transmission changes with time. Then how to fit the parameters and get the trend of the parameters changing with time is the key to predict the disease course with the model. In this paper, based on the US COVID-19 epidemic statistics during calibration period, the parameters such as infection rate and recovery rate are fitted by using the linear regression algorithm of machine science, and the laws of these parameters changing with time are obtained. Then a SIR model with time delay and vaccination is proposed, and the optimal control strategy of epidemic situation is analyzed by using the optimal control theory and Pontryagin maximum principle, which proves the effectiveness of the control strategy in restraining the transmission of COVID-19. The numerical simulation results show that the time-varying law of the number of active cases obtained by our model basically conforms to the real changing law of the US COVID-19 epidemic statistics during calibration period. In addition, we have predicted the changes in the number of active cases in the COVID-19 epidemic in the USA over time in the future beyond the calibration cycle, and the predicted results are more in line with the actual epidemic data.
ABSTRACT
In the classical infectious disease compartment model, the parameters are fixed. In reality, the probability of virus transmission in the process of disease transmission depends on the concentration of virus in the environment, and the concentration depends on the proportion of patients in the environment. Therefore, the probability of virus transmission changes with time. Then how to fit the parameters and get the trend of the parameters changing with time is the key to predict the disease course with the model. In this paper, based on the US COVID-19 epidemic statistics during calibration period, the parameters such as infection rate and recovery rate are fitted by using the linear regression algorithm of machine science, and the laws of these parameters changing with time are obtained. Then a SIR model with time delay and vaccination is proposed, and the optimal control strategy of epidemic situation is analyzed by using the optimal control theory and Pontryagin maximum principle, which proves the effectiveness of the control strategy in restraining the transmission of COVID-19. The numerical simulation results show that the time-varying law of the number of active cases obtained by our model basically conforms to the real changing law of the US COVID-19 epidemic statistics during calibration period. In addition, we have predicted the changes in the number of active cases in the COVID-19 epidemic in the USA over time in the future beyond the calibration cycle, and the predicted results are more in line with the actual epidemic data.
ABSTRACT
BACKGROUND: We hypothesised that zanubrutinib, a highly selective next-generation Bruton tyrosine kinase (BTK) inhibitor, would be a safe and active treatment for patients intolerant of ibrutinib, acalabrutinib, or both. We aimed to assess whether zanubrutinib would prolong treatment duration by minimising treatment-related toxicities and discontinuations in patients with previously treated B-cell malignancies. METHODS: This ongoing, phase 2, multicentre, open-label, single-arm study was done in 20 centres in the USA. Patients aged 18 or older with previously treated B-cell malignancies (chronic lymphocytic leukaemia, small lymphocytic lymphoma, mantle cell lymphoma, Waldenström macroglobulinaemia, or marginal zone lymphoma) who became intolerant of ibrutinib, acalabrutinib, or both, were orally administered zanubrutinib 160 mg twice daily or 320 mg once daily per investigator. The primary endpoint was recurrence and change in severity of ibrutinib or acalabrutinib intolerance events based on investigator-assessed adverse events. Secondary endpoints were investigator-assessed overall response rate; duration of response; disease control rate; and progression-free survival. Analyses included all patients who received any dose of the study drug. This study is registered with ClinicalTrials.gov, NCT04116437. FINDINGS: Between Oct 14, 2019, and Sept 8, 2021, 67 patients (36 [54%] men and 31 [46%] women) who were intolerant of ibrutinib (n=57; cohort 1) or of acalabrutinib or acalabrutinib and ibrutinib (n=10; cohort 2) were enrolled. 63 (94%) patients were White, one (2%) had multiple ethnicities, and three (5%) had unreported or unknown ethnicity. Most intolerance events (81 [70%] of 115 for ibrutinib; 15 [83%] of 18 for acalabrutinib) did not recur with zanubrutinib. Of the recurring events, seven (21%) of 34 ibrutinib intolerance events and two (67%) of three acalabrutinib intolerance events recurred at the same severity with zanubrutinib; 27 (79%) ibrutinib intolerance events and one (33%) acalabrutinib intolerance event recurred at a lower severity with zanubrutinib. No events recurred at higher severity. No grade 4 intolerance events recurred. 64 (96%) of 67 patients had one or more adverse events with zanubrutinib; the most common adverse events were contusion (in 15 [22%] of 67 patients), fatigue (14 [21%]), myalgia (ten [15%]), arthralgia (nine [13%]), and diarrhoea (nine [13%]). Atrial fibrillation occurred in three (4%) patients (all grade 2). Eight (12%) of 67 patients had serious adverse events (anaemia, atrial fibrillation, bronchitis, COVID-19, COVID-19 pneumonia, febrile neutropenia, salmonella gastroenteritis, transfusion reaction, trigeminal nerve disorder, and urinary tract infection). No treatment-related deaths occurred. The median follow-up time was 12·0 months (IQR 8·2-15·6). Among the 64 efficacy-evaluable patients, disease control rate was 93·8% (60; 95% CI 84·8-98·3) and overall response rate was 64·1% (41; 95% CI 51·1-75·7). The median duration of response was not reached; the 12-month event-free duration of response rate was 95·0% (95% CI 69·5-99·3). Similarly, median progression-free survival was not reached; 18-month progression-free survival was 83·8% (95% CI 62·6-93·6). INTERPRETATION: Patients intolerant of previous BTK inhibitors have limited treatment options. These results suggest that zanubrutinib, a safe and viable treatment for patients with B-cell malignancies, might fill that unmet need for those who exhibit intolerance to ibrutinib or acalabrutinib. FUNDING: BeiGene.
ABSTRACT
The COVID-19 pandemic has dealt a serious blow to the global tourism industry, causing a fracturing of and decline in tourism development efficiency and even a stagnation of tourism development in some regions. To solve the contradiction between efficiency and quality, it is necessary to ensure the endogenous power of tourism resilience while pursuing the efficiency of tourism development. This study assumes that Hainan Province follows a tourism development path led by resilience. The improved weighting method, EBM model and Haken model are used to evaluate the level of resilience, the level of efficiency and their co-evolution. The findings indicate that the core tourism cities represented by Sanya and Haikou have a high level in the individual fields of tourism development efficiency and tourism economic resilience but have limited performance in the synergistic relationship between tourism development efficiency and tourism economic resilience. In contrast, the marginal tourism cities represented by Tunchang County and Ledong County have low tourism development efficiency and resilience, but their synergistic development level is high. This result proves that co-evolution plays a dual forward and reverse driving role. Based on the identification of the order parameters, it is concluded that Hainan Province is characterized by a synergistic evolutionary synergy dominated by resilience, which is in line with the trend of social development and the sustainable development of tourism. While reasonably pursuing the tourism economy and development efficiency, we should pay attention to strengthening resilience construction based on multiple aspects, such as tourists, enterprises, organizations, governments and destinations.
ABSTRACT
ABSTRACTA wave of Omicron infections rapidly emerged in China in 2022, but large-scale data concerning the safety profile of vaccines and Coronavirus disease 2019 (COVID-19) infection features in liver transplant (LT) recipients have not been collected. Therefore, the aim of this study was to assess the protectiveness and safety profile of the inactivated vaccines in LT patients against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infections. A multi-centre retrospective study was conducted in a cohort with a history of liver transplantation. A total of 1881 participants (487 vaccinated and 1394 unvaccinated patients) were enrolled from seven centres in China. Fourteen of the participants were infected by Omicron, and 50% patients had over 14 days of viral shedding duration. The protection rate of COVID-19 vaccinations to Omicron was 2.59%. The three breakthrough infections occurred more than 6 months after fully vaccinated. A total of 96 (19.7%) vaccinated patients had adverse events, including fatigue, myalgia, liver dysfunction, swelling, and scleroma. There were more Grade 3 adverse events in the preoperative vaccination group than those in the postoperative vaccination group. Inactivated whole-virion SARS-CoV-2 vaccines are safe in patients with post-liver transplantation. The efficacy of inactivated vaccines decreases after 6 months of vaccination, it is recommended that liver transplant patients get boosted vaccinations as early as possible even when they are fully vaccinated. Although clinical manifestations of Omicron infections were mild in LT patients, unvaccinated patients might have a higher risk of liver dysfunction during infections.