关键词： Distribution   Vaccine allocation   Equity   Quarantine   Fractional dosing   COVID-19   LOCATION   MODEL   NETWORK   DESIGN   EQUITY   AGE  

摘要： Once effective vaccines are discovered for a pandemic and initial distribution infrastructure, and mechanisms are implemented, the next concern is an optimal vaccination campaign to stop the disease or minimize the casualties. This paper studies the optimization of a Vaccine Distribution Network (VDN) through a single- objective Mixed-Integer Non-Linear Programming (MINLP) model for minimizing the total cost in terms of governmental aid (to maintain the economy), logistics, vaccination, and hospitalization costs. The proposed model develops the optimal joint vaccination-quarantine strategy under equity considerations to (1) determine the optimal allocation of available vaccine stockpiles to different population classes in different regions and (2) seek to impose quarantine restrictions to different regions optimally. The proposed model was applied to a real case study, the vaccine distribution network in France. Through a comprehensive numerical analysis, the optimal vaccine allocation is calculated, and the impact of equity and quarantine on the performance of the distribution network is investigated. Moreover, fractional dosing on the number of infections is examined. The results show that equity considerations, counter-intuitively, lead to an increased number of infections. Furthermore, it is illustrated that fractional dosing helps policymakers to control the pandemic better under a limited supply of vaccines.

关键词： Colorectal cancer   screening   COVID-19   colonoscopy   COLORECTAL-CANCER   DIAGNOSIS   TIME   UK  

摘要： Background: Colorectal cancer (CRC) screening services in Ireland were cancelled or postponed for periods during the COVID-19 pandemic. The aim of this study was to assess the impact of screening colonoscopy delays after a positive FIT on clinical and histopathological outcomes due to these restrictions. Methods: Participants in the Irish National Bowel Screening Programme with a positive Immunochemical Faecal Test (FIT) during the COVID-19 pandemic (March 2020-December 2021) were included. Patients were categorised into attended for a colonoscopy <3 months and attended for colonoscopy >= 3-17 months post positive FIT. Chi-Square Test of independence was performed using WinPepi. Results: 3227 individuals had a complete index colonoscopy <3 months and 262 attended colonoscopy from >= 3 to 17 months post positive FIT. Of the clients whose colonoscopy was between >= 3-17 months from positive FIT, the median wait time was 3 months. There was no significant difference found between the two groups for CRC (5.8 % vs 5.0%, p=0.544) or for the proportion of cancer stage I, stage II and unknown (33.7 %, 40.6%, 25.7%, p=0.411). There was no difference in the proportions of adenomas (57.8 % vs 58.4 %, p=0.849) and the proportion of advanced adenomas (7.7 % vs 10.7 %, p=0.077) detected between the two groups. A similar proportion of polyps were detected in individuals whose index colonoscopies were postponed <3 months from positive FIT (66.9 % vs 66 %, p=0.786). Conclusion: A median delay of 3 months in screening colonoscopies after a positive FIT does not adversely impact clinical or histopathological outcomes. There was no significant difference in cancer staging, advanced adenomas or polyps detected between those who attended colonoscopies <3 months and >= 3-17 months post positive FIT. COVID-19 related disruptions to the normal functioning of the Irish bowel screening programme did not compromise our key objectives of advanced adenoma and cancer detection.

关键词： Universal vaccine   Influenza   COVID-19   NAIVE T-CELLS   PRIME-BOOST VACCINATION   ORIGINAL ANTIGENIC SIN   MESSENGER-RNA VACCINE   INFLUENZA-A VIRUSES   OF-THE-ART   IMMUNODEFICIENCY-VIRUS   IMMUNE-RESPONSES   REVERSE VACCINOLOGY   NEUTRALIZING ANTIBODIES  

摘要： Even though the use of SARS-CoV-2 vaccines during the COVID-19 pandemic showed unprecedented success in a short time, it also exposed a flaw in the current vaccine design strategy to offer broad protection against emerging variants of concern. However, developing broad-spectrum vaccines is still a challenge for immunologists. The development of universal vaccines against emerging pathogens and their variants appears to be a practical solution to mitigate the economic and physical effects of the pandemic on society. Very few reports are available to explain the basic concept of universal vaccine design and development. This review provides an overview of the innate and adaptive immune responses generated against vaccination and essential insight into immune mechanisms helpful in designing universal vaccines targeting influenza viruses and coronaviruses. In addition, the characteristics, safety, and factors affecting the efficacy of universal vaccines have been discussed. Furthermore, several advancements in methods worthy of designing universal vaccines are described, including chimeric immunogens, heterologous prime-boost vaccines, reverse vaccinology, structure-based antigen design, pan-reactive antibody vaccines, conserved neutralizing epitope-based vaccines, mosaic nanoparticle-based vaccines, etc. In addition to the several advantages, significant potential constraints, such as defocusing the immune response and subdominance, are also discussed.

关键词： Network analyses   Persisting COVID   Psychosomatic   Risk factors   Protective factors   COVID-19   Social connectedness   DISEASE  

摘要： Background and objectives: In light of the late stage of COVID-19 pandemic, the occurrence of persistent symptoms after COVID-19 infection has become more frequent. To date, there are no standardized treatments. Underlying mechanisms, risk and protective factors for severe persisting symptoms should be investigated to develop effective interventions. Methods: An online questionnaire was used to assess gender, presence of prior mental disorder, severity of COVID-19 infection, and social connectedness (SCS-R) to determine their influence on symptom severity of persisting symptoms. The sample used to examine risk and protective factors consisted of 693 participants. Results: The analysis revealed no significant gender differences for severity of persisting symptoms. However, prior mental health condition was associated with severity of persisting symptoms. Moreover, there was a positive association between symptom severity during COVID-19 infection and Post COVID 19. Social connectedness was found to be negatively associated with Post COVID 19 symptoms. Social connectedness was shown to be negatively associated with depressive symptoms and disordered self-organization. The symptoms of energy loss and concentration had the highest centrality. Conclusion: The results of the study indicate that severity of post-covid symptoms is associated with higher levels of psychopathological symptoms and a lower level of social connectedness. In conclusion, social connectedness may be an important factor in the development of post-COVID symptoms and should be considered for future interventions. The results from the network analyses provide a first step for a more granular syndrome profile.

关键词： UPLC   Molnupiravir   Human plasma   ICH Q2(R1) guidelines   Greenness assessment   LEVOFLOXACIN   VALIDATION   APIXABAN  

摘要： The global spread of COVID-19 disease has increased the demand for new therapeutic approaches. The clinical studies revealed that remdesivir and molnupiravir have been effective against COVID-19. Remdesivir (REM) is the first FDA-approved antiviral drug for COVID-19, while molnupiravir is the first oral antiviral drug for SARSCoV-2 infections. In addition to antivirals, anticoagulants such as apixaban (APX) and antibiotics such as levofloxacin (LVF) are also included in the treatment protocols. This study suggests and validates a rapid and selective method for the determination of the four drugs involved in the COVID-19 treatment protocol. The simultaneous separation and determination of REM, MLP, LVF, and APX in human plasma were achieved using UPLC with a fluorophenyl column and a mobile phase composed of acetonitrile and water acidified with formic acid (pH = 3) in the ratio of 45: 55, v/v, at a flow rate of 0.1 mL/min. The PDA detector was adjusted at 254 nm. The method could simultaneously determine the four drugs in a single run in less than 6 min. The method exhibited linearity over the concentration ranges of 1.0-15.0 mu g/mL, 0.1-5.0 mu g/mL, 0.1-2.0 mu g /mL, and 0.1-5.0 mu g/mL, for LVF, MLP, APX and REM, respectively. The proposed method was validated following the International Council on Harmonization Q2(R1) guidelines and the findings were compared statistically to previously reported methods. The recovery rates of the drugs from spiked human plasma were satisfactory. The greenness of the suggested method was evaluated using three metrics, namely, Analytical Eco-scale, Green Analytical Procedure Index (GAPI) metric, and the Analytical GREEnness measure approach (AGREE).

关键词： Car-ownership   Carlessness   Economic stimulus payments   Stay-at-home policies   Remote work   Multilevel hurdle model   TRANSPORTATION   SPECIFICATION   OPPORTUNITIES   MOBILITY  

摘要： This research analyzed car-ownership in the US during and after the COVID-19 pandemic, by utilizing a nationally representative household survey spanning from January 2020 to March 2022. Using a multilevel Hurdle model with month and state random effects, vehicle ownership trends are separately modeled for car-owning and carless households within the same modeling framework, while accounting for endogeneity and unobserved heterogeneity. An increase in the total amount of economic stimulus funding received increased the odds of vehicle ownership, while high car prices, high levels of housing expenditures, living in multi-family dwelling, and being from minority and low-skilled worker families negatively affected car-ownership. Greater household labor force participation, increases in household size and young persons in the household, living in states with high COVID caseloads and with moderately stringent Stay-at-Home social distancing mandates affected carownership propensities differently for car-owning and carless households. The significance of the research is that it disentangled pandemic-related and transportation policy variables from changes in household structure, living arrangements and employment-related characteristics. The analysis jointly considered how short-term pandemic-related influences as well as long-term demographic and occupational factors differently affect carownership for car-owning households and those without cars. Policy implications are drawn for consumer protection in the car ownership process, auto loan forbearance in future economic disruptions, strategies for public transportation which has continued to suffer from lower levels of use, and sustainability programs due to higher volumes of older used cars.

关键词： public health   Machine learning   Transfer learning   COVID-19   Vaccine   TIME  

摘要： Timely vaccination for new respiratory infectious diseases like COVID-19 is crucial for controlling pandemics. Accurate vaccination rate prediction is essential for aiding decision-makers and vaccine manufacturers in vaccine production and distribution planning, particularly in developing countries with limited resources. However, insufficient historical vaccination records in these countries challenge traditional machine learning models. This study proposes a multi-source window-dependent transfer learning (WDTL) approach integrated with a Convolutional Neural Networks with Long Short-Term Memory (CNN-LSTM) model, enabling target countries with limited vaccination record to learn from multiple source countries with similar COVID-19, policy, and economic factors within a temporal window. A case study is conducted on three developing countries from different continents, each with limited resources and significant challenges regarding vaccine supply and hesitancy during the early stages of the pandemic. The model's effectiveness was tested against a CNN-LSTM model and a multi-source TL model without window-dependent similarity evaluation, showing significant improvements with average Mean Absolute Percentage Error (MAPE) reductions of 45% and 19%, respectively. These results underscore the importance of selecting appropriate source countries across temporal windows, considering the evolving COVID-19 situation over time.

关键词： JMDC claims database   DeSC healthcare database   Coronavirus disease 2019   Health resource use   Surge capacity  

摘要： Background: The COVID-19 pandemic posed substantial challenges to healthcare systems. Understanding the responses of pediatric health services is crucial for future pandemic planning and preparedness, yet such data remains limited. Methods: In this retrospective cohort study, we analyzed data from administrative databases developed by Japan Medical Data Center and DeSC Healthcare Inc. The dataset comprised records of 2,612,511 children, totaling 60,224,888 person-months, from January 2020 to May 2022. Multivariate generalized estimation equations were used to examine the incidence rates of COVID-19 and associated health resource use. Results: Our analysis revealed that the incidence rates of COVID-19 gradually increased from Wave I (2.2 cases per 100,000 person-months) to Wave V (177.8cases per 100,000 person-months), with a notable elevation during Wave VI (2367.7 cases per 100,000 person-months). While nucleic acid amplification tests were primarily used during Waves I-V, the use of rapid antigen tests markedly increased in Wave VI. The hospitalization rates increased gradually from 0.2 in Wave I to 10.2 events per 100,000 person-months in Wave VI, and the casehospitalization risk decreased from 14.9% in Wave II to 0.7% in Wave VI. Additionally, we observed decreasing trends in the use of antibiotics (Wave I, 31.8%; Wave VI, 9.0%), whereas antipyretic use rose from Wave I (56.1%) to Wave VI (86.6%). Conclusions: Our study highlighted essential changes in the nationwide pediatric healthcare system's response to the COVID-19 pandemic. These findings provide valuable insights into the future pandemic planning and preparedness.

关键词： COVID-19   Machine learning   Medical image analysis challenge   SEGMENTATION   CT   ALGORITHMS   PREDICTION   VALIDATION   DIAGNOSIS   IMAGES   AREAS  

摘要： Challenges drive the state-of-the-art of automated medical image analysis. The quantity of public training data that they provide can limit the performance of their solutions. Public access to the training methodology for these solutions remains absent. This study implements the Type Three (T3) challenge format, which allows for training solutions on private data and guarantees reusable training methodologies. With T3, challenge organizers train a codebase provided by the participants on sequestered training data. T3 was implemented in

关键词： COVID-19   coworker conflict   stress   workforce safety   BURNOUT   VACCINATION   ASSOCIATION   DEPRESSION   ANXIETY   STRESS   HEALTH  

摘要： ObjectivesSafety policies enacted in response to the emergence of coronavirus disease 2019 (COVID-19) have greatly affected the working environments of emergency medical service (EMS) clinicians. Our objective was to evaluate whether changes in the EMS environment during the COVID-19 pandemic were associated with increased workplace *** evaluation was a cross-sectional analysis of a random sample of 19,497 national certified EMS clinicians who were selected to receive an electronic survey in April 2022. The survey included an assessment of their level of stress using the Perceived Stress Scale instrument and examined changes in their working environment they perceived had occurred due to the emergence of COVID-19. Logistic regression modeling was used to evaluate the associations between workforce demographics, infrastructure, scheduling, and policies to and COVID-19-induced coworker *** total of 1686 responses were evaluated (response rate 10%). We found that COVID-19 was reported to have exacerbated conflict between coworkers in 51% of responses. Respondents who perceived an increase in coworker conflict due to COVID-19 self-reported higher levels of stress than the rest of the respondents. Perceptions of the impact of COVID-19 on conflict had also an association with the level of certification, indicating that national registered paramedics were more likely than emergency medical technicians to report coworker conflict due to COVID-19 (adjusted odds ratio [AOR] 1.30, 95% confidence interval [CI] 1.05-1.61). Multivariable analysis highlighted the impact of mandatory overtime policies, reported by 27% of the respondents and associated with higher odds of exacerbated coworker conflict in our model (AOR 2.05, 95% CI 1.62-2.60).ConclusionsThese findings indicate that conflict can be considered a potential indicator of high levels of stress in the EMS workforce and may be a reliable signal to monitor when implementing mandates that affect