Estimating the impact of school closure on influenza transmission from Sentinel data

The threat posed by the highly pathogenic H5N1 influenza virus requires public health authorities to prepare for a human pandemic. Although pre-pandemic vaccines and antiviral drugs might significantly reduce illness rates, their stockpiling is too expensive to be practical for many countries. Consequently, alternative control strategies, based on non-pharmaceutical interventions, are a potentially attractive policy option. School closure is the measure most often considered. The high social and economic costs of closing schools for months make it an expensive and therefore controversial policy, and the current absence of quantitative data on the role of schools during influenza epidemics means there is little consensus on the probable effectiveness of school closure in reducing the impact of a pandemic. Here, from the joint analysis of surveillance data and holiday timing in France, we quantify the role of schools in influenza epidemics and predict the effect of school closure during a pandemic. We show that holidays lead to a 20-29% reduction in the rate at which influenza is transmitted to children, but that they have no detectable effect on the contact patterns of adults. Holidays prevent 16-18% of seasonal influenza cases (18-21% in children). By extrapolation, we find that prolonged school closure during a pandemic might reduce the cumulative number of cases by 13-17% (18-23% in children) and peak attack rates by up to 39-45% (47-52% in children). The impact of school closure would be reduced if it proved difficult to maintain low contact rates among children for a prolonged period.     

Strategies for containing an emerging influenza pandemic in Southeast Asia

Highly pathogenic H5N1 influenza A viruses are now endemic in avian populations in Southeast Asia, and human cases continue to accumulate. Although currently incapable of sustained human-to-human transmission, H5N1 represents a serious pandemic threat owing to the risk of a mutation or reassortment generating a virus with increased transmissibility. Identifying public health interventions that might be able to halt a pandemic in its earliest stages is therefore a priority. Here we use a simulation model of influenza transmission in Southeast Asia to evaluate the potential effectiveness of targeted mass prophylactic use of antiviral drugs as a containment strategy. Other interventions aimed at reducing population contact rates are also examined as reinforcements to an antiviral-based containment policy. We show that elimination of a nascent pandemic may be feasible using a combination of geographically targeted prophylaxis and social distancing measures, if the basic reproduction number of the new virus is below 1.8. We predict that a stockpile of 3 million courses of antiviral drugs should be sufficient for elimination. Policy effectiveness depends critically on how quickly clinical cases are diagnosed and the speed with which antiviral drugs can be distributed.     

最优阻隔控制在一类SIRS多组群传染病中的应用

该文基于一类SIRS多组群传染病模型讨论了传染病控制中的最优阻隔控制.模型中的控制变量表示为达到阻滞和隔离组群之间接触所采取的各种措施的强度.利用Pontryagin 极大值原理求解了最优控制问题并给出了相应的数值迭代算法.仿真结果表明该文提出的最优阻隔控制策略在使传染病代价最小化的同时可以有效地控制传染病的流行,同时也表明现实中采取的"早发现早隔离"策略在传染病控制中的重要性.     

The novel H1N1 Influenza A global airline transmission and early warning without travel containments

A novel influenza A (H1N1) has been spreading worldwide. Early studies implied that international air travels might be key cause of a severe potential pandemic without appropriate containments. In this study, early outbreaks in Mexico and some cities of United States were used to estimate the preliminary epidemic parameters by applying adjusted SEIR epidemiological model, indicating transmissibility infectivity of the virus. According to the findings, a new spatial allocation model totally based on the real-time airline data was established to assess the potential spreading of H1N1 from Mexico to the world. Our estimates find the basic reproductive number R0 of H1N1 is around 3.4, and the effective reproductive number fall sharply by effective containment strategies. The finding also implies Spain, Canada, France, Panama, Peru are the most possible country to be involved in severe endemic H1N1 spreading.     

Transmissibility of 1918 pandemic influenza

The 1918 influenza pandemic killed 20-40 million people worldwide, and is seen as a worst-case scenario for pandemic planning. Like other pandemic influenza strains, the 1918 A/H1N1 strain spread extremely rapidly. A measure of transmissibility and of the stringency of control measures required to stop an epidemic is the reproductive number, which is the number of secondary cases produced by each primary case. Here we obtained an estimate of the reproductive number for 1918 influenza by fitting a deterministic SEIR (susceptible-exposed-infectious-recovered) model to pneumonia and influenza death epidemic curves from 45 US cities: the median value is less than three. The estimated proportion of the population with A/H1N1 immunity before September 1918 implies a median basic reproductive number of less than four. These results strongly suggest that the reproductive number for 1918 pandemic influenza is not large relative to many other infectious diseases. In theory, a similar novel influenza subtype could be controlled. But because influenza is frequently transmitted before a specific diagnosis is possible and there is a dearth of global antiviral and vaccine stores, aggressive transmission reducing measures will probably be required.     

Avian flu: isolation of drug-resistant H5N1 virus

The persistence of H5N1 avian influenza viruses in many Asian countries and their ability to cause fatal infections in humans have raised serious concerns about a global flu pandemic. Here we report the isolation of an H5N1 virus from a Vietnamese girl that is resistant to the drug oseltamivir, which is an inhibitor of the viral enzyme neuraminidase and is currently used for protection against and treatment of influenza. Further investigation is necessary to determine the prevalence of oseltamivir-resistant H5N1 viruses among patients treated with this drug.     

新冠肺炎疫情下儿童青少年心理健康干预进展

 新型冠状病毒肺炎（新冠肺炎）大流行是全球性事件,严重影响到人们的日常生活。儿童青少年作为此次突发重大公共卫生应激事件的弱势群体,身心受到剧烈冲击。综述了国内外现有研究进展,分别从国家社会、学校社区、家庭及个人层面探讨了新冠肺炎疫情下儿童青少年心理压力的应激源;总结了疫情期间儿童青少年心理问题的类型,包括情绪问题和行为问题;归纳了普通儿童、疫情严重地区儿童和家人患病或抗疫人员子女、隔离儿童、其他患病儿童及感染儿童这5类不同风险的儿童青少年面对疫情的心理特征及干预建议。     

一种高效的蠕虫动态防御抑制策略

通过对目前几种蠕虫抑制策略的分析比较,提出了一种新的高效的动态防御蠕虫抑制策略--DDWC,论证了这种策略对快速和慢速蠕虫抑制的有效性;同时分析了正常网络行为对抑制策略的影响,大大降低了DDWC策略的误报率. 仿真结果证明经过改进的两轮抑制算法策略能够高效地抑制快速和慢速蠕虫,同时具有较好的低误报性.     

Spatial epidemiology of networked metapopulation: an overview

An emerging disease is one infectious epidemic caused by a newly transmissible pathogen, which has either appeared for the first time or already existed in human populations, having the capacity to increase rapidly in incidence as well as geographic range. Adapting to human immune system, emerging diseases may trigger large-scale pandemic spreading, such as the transnational spreading of SARS, the global outbreak of A（H1N1）, and the recent potential invasion of avian influenza A（H7N9）. To study the dynamics mediating the transmission of emerging dis- eases, spatial epidemiology of networked metapopulation provides a valuable modeling framework, which takes spatially distributed factors into consideration. This review elaborates the latest progresses on the spatial metapopula- tion dynamics, discusses empirical and theoretical findings that verify the validity of networked metapopulations, and the sketches application in evaluating the effectiveness of disease intervention strategies as well.     

流感病毒疫苗研究现状、发展趋势和展望

 流感大流行严重威胁人类的生命健康和社会经济的发展。及时提供充足、有效的流感疫苗是目前各国应对流感大流行的首选方法。然而,目前流感疫苗还存在许多问题,如生产周期长、保护范围有限（不具备广谱性）、易产生过敏反应等。为此,各国政府和科研团体都在进行着不懈的努力以应对流感的大流行。本文介绍了目前国内外使用的流感疫苗,比较了流感灭活疫苗和减毒活疫苗的优缺点;针对当前流感病毒疫苗研制中亟待解决的问题,即疫苗的保护时效及合适的培养基问题,探讨了解决的思路以及取得的进展;结合中国在流感方面的主要研究进展,探讨了中国流感病毒疫苗相关基础研究中需要解决的关键科学问题,并对未来流感的防控进行了展望。     

Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors

Investigation of the human antibody response to influenza virus infection has been largely limited to serology, with relatively little analysis at the molecular level. The 1918 H1N1 influenza virus pandemic was the most severe of the modern era. Recent work has recovered the gene sequences of this unusual strain, so that the 1918 pandemic virus could be reconstituted to display its unique virulence phenotypes. However, little is known about adaptive immunity to this virus. We took advantage of the 1918 virus sequencing and the resultant production of recombinant 1918 haemagglutinin (HA) protein antigen to characterize at the clonal level neutralizing antibodies induced by natural exposure of survivors to the 1918 pandemic virus. Here we show that of the 32 individuals tested that were born in or before 1915, each showed seroreactivity with the 1918 virus, nearly 90 years after the pandemic. Seven of the eight donor samples tested had circulating B cells that secreted antibodies that bound the 1918 HA. We isolated B cells from subjects and generated five monoclonal antibodies that showed potent neutralizing activity against 1918 virus from three separate donors. These antibodies also cross-reacted with the genetically similar HA of a 1930 swine H1N1 influenza strain, but did not cross-react with HAs of more contemporary human influenza viruses. The antibody genes had an unusually high degree of somatic mutation. The antibodies bound to the 1918 HA protein with high affinity, had exceptional virus-neutralizing potency and protected mice from lethal infection. Isolation of viruses that escaped inhibition suggested that the antibodies recognize classical antigenic sites on the HA surface. Thus, these studies demonstrate that survivors of the 1918 influenza pandemic possess highly functional, virus-neutralizing antibodies to this uniquely virulent virus, and that humans can sustain circulating B memory cells to viruses for many decades after exposure-well into the tenth decade of life.     

新时期农村居民出游限制因素研究——以河南省为例

以农村居民出游限制因素研究为基点,采用社会心理学的面对面访谈调查法,选取河南省7个行政村,18个自然村78户农村居民作为访谈对象,以农村居民出游限制因素为访谈核心内容,结合历年中国旅游统计年鉴及相关统计信息,系统分析了农村居民出游限制因素.结果显示,现阶段我国农村居民出游主要受以下几种因素限制:农村居民的收入水平仍相对较低;受传统思想影响较深;出游意识较差;旅游营销活动接触较少.最后提出了3点建议,即培养农村居民出游意识,争取国家与企业的扶持以及学界予以重视.     

On the Security of Information Dissemination in the Internet-of-Vehicles

Internet of Vehicles(IoV) is regarded as an emerging paradigm for connected vehicles to exchange their information with other vehicles using vehicle-to-vehicle(V2V) communications by forming a vehicular ad hoc networks(VANETs), with roadside units using vehicle-to-roadside(V2R) communications. IoV offers several benefits such as road safety, traffic efficiency, and infotainment by forwarding up-to-date traffic information about upcoming traffic. For instance, IoV is regarded as a technology that could help reduce the number of deaths caused by road accidents, and reduce fuel costs and travel time on the road. Vehicles could rapidly learn about the road condition and promptly respond and notify drivers for making informed decisions. However, malicious users in IoV may mislead the whole communications and create chaos on the road. Data falsification attack is one of the main security issues in IoV where vehicles rely on information received from other peers/vehicles. In this paper,we present data falsification attack detection using hashes for enhancing network security and performance by adapting contention window size to forward accurate information to the neighboring vehicles in a timely manner(to improve throughput while reducing end-to-end delay). We also present clustering approach to reduce travel time in case of traffic congestion. Performance of the proposed approach is evaluated using numerical results obtained from simulations. We found that the proposed adaptive approach prevents IoV from data falsification attacks and provides higher throughput with lower delay.     

Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus

The 'Spanish' influenza pandemic of 1918-19 was the most devastating outbreak of infectious disease in recorded history. At least 20 million people died from their illness, which was characterized by an unusually severe and rapid clinical course. The complete sequencing of several genes of the 1918 influenza virus has made it possible to study the functions of the proteins encoded by these genes in viruses generated by reverse genetics, a technique that permits the generation of infectious viruses entirely from cloned complementary DNA. Thus, to identify properties of the 1918 pandemic influenza A strain that might be related to its extraordinary virulence, viruses were produced containing the viral haemagglutinin (HA) and neuraminidase (NA) genes of the 1918 strain. The HA of this strain supports the pathogenicity of a mouse-adapted virus in this animal. Here we demonstrate that the HA of the 1918 virus confers enhanced pathogenicity in mice to recent human viruses that are otherwise non-pathogenic in this host. Moreover, these highly virulent recombinant viruses expressing the 1918 viral HA could infect the entire lung and induce high levels of macrophage-derived chemokines and cytokines, which resulted in infiltration of inflammatory cells and severe haemorrhage, hallmarks of the illness produced during the original pandemic.     

新型冠状病毒在家庭环境中的主要传播途径

 通过构建数学模型,定量研究了1个3人家庭环境中飞沫传播、接触传播和气溶胶传播在COVID-19传播中的作用。研究表明,飞沫传播和接触传播在COVID-19传播中起着最重要的作用。和患者交流时保持1.5~2 m的空间距离对控制飞沫传播至关重要,洗手和保护环境表面清洁是控制接触传播的最有效手段。虽然通过气溶胶途径传播风险相对较小,但当患者呼出飞沫中病原体浓度较高时（患者可能为超级感染者）,在家庭环境中24 h暴露下,气溶胶传播风险依然可以高达26%。     

Public health vaccination policies for containing an anthrax outbreak

Concern about biological weapons has raised questions about the most effective public health policies to contain an anthrax outbreak. We developed a probability model to predict the impact of different anthrax antibiotic and vaccination policies. An anthrax outbreak can be significantly contained by minimizing the delay until initiation of antibiotic prophylaxis. However, even if mass distribution of antibiotics is completed within six days of the initial exposure, then at most about 70% of cases can be prevented. Post-exposure vaccination will not significantly increase that prevention rate if adherence to antibiotic regimens is similar or higher than that attained in the 2001 US outbreak. However, post-exposure vaccination can be useful either in shortening the duration of a prolonged antibiotic regimen, in the event of an antibiotic-resistant strain, or if antibiotic adherence rates are very low. Here we show that a mass pre-exposure vaccination programme for the general population would require very high population coverage rates to significantly increase prevention rates from that achieved with targeted and rapid post-exposure prophylaxis programmes.     

Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virus

The influenza pandemic of 1918-19 was responsible for about 50 million deaths worldwide. Modern histopathological analysis of autopsy samples from human influenza cases from 1918 revealed significant damage to the lungs with acute, focal bronchitis and alveolitis associated with massive pulmonary oedema, haemorrhage and rapid destruction of the respiratory epithelium. The contribution of the host immune response leading to this severe pathology remains largely unknown. Here we show, in a comprehensive analysis of the global host response induced by the 1918 influenza virus, that mice infected with the reconstructed 1918 influenza virus displayed an increased and accelerated activation of host immune response genes associated with severe pulmonary pathology. We found that mice infected with a virus containing all eight genes from the pandemic virus showed marked activation of pro-inflammatory and cell-death pathways by 24 h after infection that remained unabated until death on day 5. This was in contrast with smaller host immune responses as measured at the genomic level, accompanied by less severe disease pathology and delays in death in mice infected with influenza viruses containing only subsets of 1918 genes. The results indicate a cooperative interaction between the 1918 influenza genes and show that study of the virulence of the 1918 influenza virus requires the use of the fully reconstructed virus. With recent concerns about the introduction of highly pathogenic avian influenza viruses into humans and their potential to cause a worldwide pandemic with disastrous health and economic consequences, a comprehensive understanding of the global host response to the 1918 virus is crucial. Moreover, understanding the contribution of host immune responses to virulent influenza virus infections is an important starting point for the identification of prognostic indicators and the development of novel antiviral therapies.     

Drosophila RNAi screen identifies host genes important for influenza virus replication

All viruses rely on host cell proteins and their associated mechanisms to complete the viral life cycle. Identifying the host molecules that participate in each step of virus replication could provide valuable new targets for antiviral therapy, but this goal may take several decades to achieve with conventional forward genetic screening methods and mammalian cell cultures. Here we describe a novel genome-wide RNA interference (RNAi) screen in Drosophila that can be used to identify host genes important for influenza virus replication. After modifying influenza virus to allow infection of Drosophila cells and detection of influenza virus gene expression, we tested an RNAi library against 13,071 genes (90% of the Drosophila genome), identifying over 100 for which suppression in Drosophila cells significantly inhibited or stimulated reporter gene (Renilla luciferase) expression from an influenza-virus-derived vector. The relevance of these findings to influenza virus infection of mammalian cells is illustrated for a subset of the Drosophila genes identified; that is, for three implicated Drosophila genes, the corresponding human homologues ATP6V0D1, COX6A1 and NXF1 are shown to have key functions in the replication of H5N1 and H1N1 influenza A viruses, but not vesicular stomatitis virus or vaccinia virus, in human HEK 293 cells. Thus, we have demonstrated the feasibility of using genome-wide RNAi screens in Drosophila to identify previously unrecognized host proteins that are required for influenza virus replication. This could accelerate the development of new classes of antiviral drugs for chemoprophylaxis and treatment, which are urgently needed given the obstacles to rapid development of an effective vaccine against pandemic influenza and the probable emergence of strains resistant to available drugs.     

基于滚动时域控制的轨道交通车站单站限流策略研究

针对部分高负载节点车站存在站台拥挤的问题,建立数学模型优化乘客的平均等待时间,制定相应限流策略。以乘客在车站各处的等待时间最小为优化目标,进站口单位时间的限流人数作为决策变量,通过乘客在车站中不同位置的行为特征,制定站台容量、列车容量、限流区域3个约束条件,同时设计了基于滚动时域控制的算法进行模拟计算。结果表明,该算法较于一般的限流策略,在超限次数和超限人数上都有较大优势,能够在保证站台安全性的前提下,在繁忙时期有效减少超限次数,站台超限人数降低9%,并将乘客出行的总延误时间降低11%。该研究可为城市轨道交通限流提供有效参考。     

论杂交水稻的国际发展

杂交水稻是我国自主创新、国际领先的重大技术,对保障世界粮食安全具有重要意义。我国的杂交水稻技术输出与国际发展,形势较好、来势很旺,发展的市场潜力大、技术与人才优势强、基础条件好;但目前尚处于初级阶段,遇到了种子检疫限制、前期投入不足、技术本身缺陷、出口经营无序、出口限制过多等问题及制约因素。应采取优化策略、规范输出、破解壁垒、提高质量、政策扶持等推进发展的对策。