An ultralight, pulverization-free integrated anode toward lithium-less lithium metal batteries.

The high-capacity advantage of lithium metal anode was compromised by common use of copper as the collector. Furthermore, lithium pulverization associated with "dead" Li accumulation and electrode cracking deteriorates the long-term cyclability of lithium metal batteries, especially under realistic test conditions. Here, we report an ultralight, integrated anode of polyimide-Ag/Li with dual anti-pulverization functionality. The silver layer was initially chemically bonded to the polyimide surface and then spontaneously diffused in Li solid solution and self-evolved into a fully lithiophilic Li-Ag phase, mitigating dendrites growth or dead Li. Further, the strong van der Waals interaction between the bottommost Li-Ag and polyimide affords electrode structural integrity and electrical continuity, thus circumventing electrode pulverization. Compared to the cutting-edge anode-free cells, the batteries pairing LiNi0.8Mn0.1Co0.1O2 with polyimide-Ag/Li afford a nearly 10% increase in specific energy, with safer characteristics and better cycling stability under realistic conditions of 1× excess Li and high areal-loading cathode (4 milliampere hour per square centimeter).

Nanoscale Visualization of Lithium Plating/Stripping Tuned by On-site Formed Solid Electrolyte Interphase in All-Solid-State Lithium-Metal Batteries.

The interfacial processes, mainly the lithium (Li) plating/stripping and the evolution of the solid electrolyte interphase (SEI), are directly related to the performance of all-solid-state Li-metal batteries (ASSLBs). However, the complex processes at solid-solid interfaces are embedded under the solid-state electrolyte, making it challenging to analyze the dynamic processes in real time. Here, using in situ electrochemical atomic force microscopy and optical microscopy, we directly visualized the Li plating/stripping/replating behavior, and measured the morphological and mechanical properties of the on-site formed SEI at nanoscale. Li spheres plating/stripping/replating at the argyrodite solid electrolyte (Li6 PS5 Cl)/Li electrode interface is coupled with the formation/wrinkling/inflating of the SEI on its surface. Combined with in situ X-ray photoelectron spectroscopy, details of the stepwise formation and physicochemical properties of SEI on the Li spheres are obtained. It is shown that higher operation rates can decrease the uniformity of the Li+ -conducting networks in the SEI and worsen Li plating/stripping reversibility. By regulating the applied current rates, uniform nucleation and reversible plating/stripping processes can be achieved, leading to the extension of the cycling life. The in situ analysis of the on-site formed SEI at solid-solid interfaces provides the correlation between the interfacial evolution and the electrochemical performance in ASSLBs.

Transmission dynamics and effect of control measures on the 2022 outbreak of mpox among gay, bisexual, and other men who have sex with men in England: a mathematical modelling study.

BACKGROUND: The 2022 global outbreak of mpox (formerly known as monkeypox) spread primarily among gay, bisexual, and other men who have sex with men (GBMSM), with the initial cluster being identified in England in May, 2022. Understanding its epidemiological characteristics and the reasons for its downturn in July, 2022, will help to control future outbreaks. METHODS: We collated data for all diagnosed mpox cases (3621) from England from May 1, 2022, to Nov 16, 2022. Data from 75 individuals with mpox allowed estimation of the incubation period, while data from 121 case-contact pairs were used to estimate the serial interval. Six methods, including a structured dynamic compartmental transmission model, were used to estimate the basic reproduction number (R0). The structured model assumed all male individuals with mpox were GBMSM, who were then stratified into subgroups for those at low risk and high risk for mpox. This best fitting model was used to estimate the reduction in transmissibility, and the effective infectious period (before isolating), that resulted in the outbreak downturn, and the effect of vaccination initiated from June 27, 2022. Bayesian methods were used for parameter estimation and model calibration. FINDINGS: Most cases occurred in men (3544 of 3621, 97·9%). The median incubation period for mpox was 6·90 days (95% credible interval [CrI] 4·08-20·21), and the serial interval was 8·82 days (5·22-25·81). R0 estimates ranged from 1·41 to 2·17. The structured transmission model estimated that 83·8% of infections (95% CrI 83·5-85·3) resulted from sexual partnerships with GBMSM individuals at high risk of mpox. The outbreak downturn probably resulted from a 44·5% reduction in the sexual partner rate among all GBMSM (24·9-55·8) and 20·0% reduction in the effective infectious period (4·1-33·9), preventing 165 896 infections (115 584-217 730). Vaccination marginally increased the number of infections prevented (166 081, 115 745-217 947), but minimised a resurgence in cases from January, 2023, and could have averted four times more infections if initiated earlier. Our findings were sensitive to assumptions regarding the vaccine's effectiveness and the GBMSM subgroup at high risk of mpox. INTERPRETATION: The mpox outbreak in England probably resulted from high sexual partner rates among some GBMSM, with reductions in partner rates reversing the outbreak, and with vaccination minimising future outbreaks. FUNDING: National Institute for Health Research (UK).

Tailoring chemical composition of solid electrolyte interphase by selective dissolution for long-life micron-sized silicon anode.

Micron-sized Si anode promises a much higher theoretical capacity than the traditional graphite anode and more attractive application prospect compared to its nanoscale counterpart. However, its severe volume expansion during lithiation requires solid electrolyte interphase (SEI) with reinforced mechanical stability. Here, we propose a solvent-induced selective dissolution strategy to in situ regulate the mechanical properties of SEI. By introducing a high-donor-number solvent, gamma-butyrolactone, into conventional electrolytes, low-modulus components of the SEI, such as Li alkyl carbonates, can be selectively dissolved upon cycling, leaving a robust SEI mainly consisting of lithium fluoride and polycarbonates. With this strategy, raw micron-sized Si anode retains 87.5% capacity after 100 cycles at 0.5 C (1500 mA g-1, 25°C), which can be improved to >300 cycles with carbon-coated micron-sized Si anode. Furthermore, the Si||LiNi0.8Co0.1Mn0.1O2 battery using the raw micron-sized Si anode with the selectively dissolved SEI retains 83.7% capacity after 150 cycles at 0.5 C (90 mA g-1). The selective dissolution effect for tailoring the SEI, as well as the corresponding cycling life of the Si anodes, is positively related to the donor number of the solvents, which highlights designing high-donor-number electrolytes as a guideline to tailor the SEI for stabilizing volume-changing alloying-type anodes in high-energy rechargeable batteries.

[Cost-effectiveness analysis of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in treatment of chronic rhinosinusitis].

This study aims to evaluate the effectiveness and economic efficiency of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in the treatment of chronic rhinosinusitis(CRS). The randomized controlled trial(RCT) of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in the treatment of CRS was searched against EMbase, PubMed, Cochrane Library, CNKI, VIP, SinoMed, and Wanfang. The efficacy, nasal mucociliary transport time, and safety of the therapy above in the treatment of CRS were analyzed with single-group rate and Meta-analysis, and the economy and sensitivity were evaluated from the perspective of payer. A total of 9 RCTs were included, including 1 145 patients. Meta-analysis showed that compared with Triamcinolone Acetonide Nasal Spray alone, Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in the treatment of CRS patients increased the effective rate(RR=1.17, 95%CI[1.11, 1.24], P<0.000 01) and shortened the nasal mucociliary transport time(MD=-3.32, 95%CI[-5.86,-0.78], P=0.01), there was no significant difference in the incidence of adverse reactions between the two groups. The incremental cost-effectiveness analysis showed that the treatment costs of the control group and the observation group were 44.15 yuan and 1 044.96 yuan, respectively. In the Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray treatment group, 75.48 yuan was spent to improve the effective rate of CRS by 1%. The one-way sensitivity analysis indicated the days of treatment, the RR of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray, the price of unit preparation of Biyuan Tongqiao Granules, and the effective rate of Triamcinolone Acetonide Nasal Spray alone had great influence on the incremental cost-effectiveness ratio. In conclusion, Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray improves the therapeutic effect on CRS. The probabilistic sensitivity analysis showed that when the willingness to pay was greater than 7 920 yuan(less than 0.1 of GDP per capita 8 098 yuan), the combined therapy was economically superior to the control. Due to the limited number of articles published, it is necessary to carry out a real-world clinical trial of Biyuan Tongqiao Gra-nules and Triamcinolone Acetonide Nasal Spray in the treatment of CRS, so as to compare the cost-effectiveness of Biyuan Tongqiao Granules and Triamcinolone Acetonide Nasal Spray.

Insights into Anion-Solvent Interactions to Boost Stable Operation of Ether-Based Electrolytes in Pure-SiOx ||LiNi0.8 Mn0.1 Co0.1 O2 Full Cells.

Ether solvents with superior reductive stability promise excellent interphasial stability with high-capacity anodes while the limited oxidative resistance hinders their high-voltage operation. Extending the intrinsic electrochemical stability of ether-based electrolytes to construct stable-cycling high-energy-density lithium-ion batteries is challenging but rewarding. Herein, the anion-solvent interactions were concerned as the key point to optimize the anodic stability of the ether-based electrolytes and an optimized interphase was realized on both pure-SiOx anodes and LiNi0.8 Mn0.1 Co0.1 O2 cathodes. Specifically, the small-anion-size LiNO3 and tetrahydrofuran with high dipole moment to dielectric constant ratio realized strengthened anion-solvent interactions, which enhance the oxidative stability of the electrolyte. The designed ether-based electrolyte enabled a stable cycling performance over 500 cycles in pure-SiOx ||LiNi0.8 Mn0.1 Co0.1 O2 full cell, demonstrating its superior practical prospects. This work provides new insight into the design of new electrolytes for emerging high-energy density lithium-ion batteries through the regulation of interactions between species in electrolytes.

A Self-Reconfigured, Dual-Layered Artificial Interphase Toward High-Current-Density Quasi-Solid-State Lithium Metal Batteries.

The uncontrollable dendrite growth and unstable solid electrolyte interphase have long plagued the practical application of Li metal batteries. Herein, a dual-layered artificial interphase LiF/LiBO-Ag is demonstrated that is simultaneously reconfigured via an electrochemical process to stabilize the lithium anode. This dual-layered interphase consists of a heterogeneous LiF/LiBO glassy top layer with ultrafast Li-ion conductivity and lithiophilic Li-Ag alloy bottom layer, which synergistically regulates the dendrite-free Li deposition, even at high current densities. As a result, Li||Li symmetric cells with LiF/LiBO-Ag interphase achieve an ultralong lifespan (4500 h) at an ultrahigh current density and area capacity (20 mA cm-2 , 20 mAh cm-2 ). LiF/LiBO-Ag@Li anodes are successfully applied in quasi-solid-state batteries, showing excellent cycling performances in symmetric cells (8 mA cm-2 , 8 mAh cm-2 , 5000 h) and full cells. Furthermore, a practical quasi-solid-state pouch cell coupling with a high-nickel cathode exhibits stable cycling with a capacity retention of over 91% after 60 cycles at 0.5 C, which is comparable or even better than that in liquid-state pouch cells. Additionally, a high-energy-density quasi-solid-state pouch cell (10.75 Ah, 448.7 Wh kg-1 ) is successfully accomplished. This well-orchestrated interphase design provides new guidance in engineering highly stable interphase toward practical high-energy-density lithium metal batteries.

Estimating Dengue Transmission Intensity in China Using Catalytic Models Based on Serological Data.

In recent decades, the global incidence of dengue has risen sharply, with more than 75% of infected people showing mild or no symptoms. Since the year 2000, dengue in China has spread quickly. At this stage, there is an urgent need to fully understand its transmission intensity and spread in China. Serological data provide reliable evidence for symptomatic and recessive infections. Through a literature search, we included 23 studies that collected age-specific serological dengue data released from 1980 to 2021 in China. Fitting four catalytic models to these data, we distinguished the transmission mechanisms by deviation information criterion and estimated force of infection and basic reproduction number (R0), important parameters for quantifying transmission intensity. We found that transmission intensity varies over age in most of the study populations, and attenuation of antibody protection is identified in some study populations; the R0 of dengue in China is between 1.04-2.33. Due to the scarceness of the data, the temporal trend cannot be identified, but data shows that transmission intensity weakened from coastal to inland areas and from southern to northern areas in China if assuming it remained temporally steady during the study period. The results should be useful for the effective control of dengue in China.

Combined TIM-3 and PD-1 blockade restrains hepatocellular carcinoma development by facilitating CD4+ and CD8+ T cell-mediated antitumor immune responses.

BACKGROUND: Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) and T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) are beneficial to the resumption of anti-tumor immunity response and hold extreme potential as efficient therapies for certain malignancies. However, ICIs with a single target exhibit poor overall response rate in hepatocellular carcinoma (HCC) patients due to the complex pathological mechanisms of HCC. AIM: To investigate the effects of combined TIM-3 and PD-1 blockade on tumor development in an HCC mouse model, aiming to identify more effective immunotherapies and provide more treatment options for HCC patients. METHODS: The levels of PD-1 and TIM-3 on CD4+ and CD8+ T cells from tumor tissues, ascites, and matched adjacent tissues from HCC patients were determined with flow cytometry. An HCC xenograft mouse model was established and treated with anti-TIM-3 monoclonal antibody (mAb) and/or anti-PD-1 mAb. Tumor growth in each group was measured. Hematoxylin and eosin staining and immunohistochemical staining were used to evaluate T cell infiltration in tumors. The percentage of CD4+ and CD8+ T cells in tissue samples from mice was tested with flow cytometry. The percentages of PD-1+CD8+, TIM-3+CD8+, and PD-1+TIM-3+ CD8+ T cells was accessed by flow cytometry. The levels of the cytokines including tumor necrosis factor alpha (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-6, and IL-10 in tumor tissues were gauged with enzyme-linked immunosorbent assay kits. RESULTS: We confirmed that PD-1 and TIM-3 expression was substantially upregulated in CD4+ and CD8+ T cells isolated from tumor tissues and ascites of HCC patients. TIM-3 mAb and PD-1 mAb treatment both reduced tumor volume and weight, while combined blockade had more substantial anti-tumor effects than individual treatment. Then we showed that combined therapy increased T cell infiltration into tumor tissues, and downregulated PD-1 and TIM-3 expression on CD8+ T cells in tumor tissues. Moreover, combined treatment facilitated the production of T cell effector cytokines TNF-α and IFN-γ, and reduced the production of immunosuppressive cytokines IL-10 and IL-6 in tumor tissues. Thus, we implicated that combined blockade could ameliorate T cell exhaustion in HCC mouse model. CONCLUSION: Combined TIM-3 and PD-1 blockade restrains HCC development by facilitating CD4+ and CD8+ T cell-mediated antitumor immune responses.

Importation, Local Transmission, and Model Selection in Estimating the Transmissibility of COVID-19: The Outbreak in Shaanxi Province of China as a Case Study.

Background: Since the emergence of the COVID-19 pandemic, many models have been applied to understand its epidemiological characteristics. However, the ways in which outbreak data were used in some models are problematic, for example, importation was mixed up with local transmission. Methods: In this study, five models were proposed for the early Shaanxi outbreak in China. We demonstrated how to select a reasonable model and correctly use the outbreak data. Bayesian inference was used to obtain parameter estimates. Results: Model comparison showed that the renewal equation model generates the best model fitting and the Susceptible-Exposed-Diseased-Asymptomatic-Recovered (SEDAR) model is the worst; the performance of the SEEDAR model, which divides the exposure into two stages and includes the pre-symptomatic transmission, and SEEDDAAR model, which further divides infectious classes into two equally, lies in between. The Richards growth model is invalidated by its continuously increasing prediction. By separating continuous importation from local transmission, the basic reproduction number of COVID-19 in Shaanxi province ranges from 0.45 to 0.61, well below the unit, implying that timely interventions greatly limited contact between people and effectively contained the spread of COVID-19 in Shaanxi. Conclusions: The renewal equation model provides the best modelling; mixing continuous importation with local transmission significantly increases the estimate of transmissibility.

Transmission dynamics of the 2016-18 outbreak of hepatitis A among men who have sex with men in England and cost-effectiveness analysis of vaccination strategies to prevent future outbreaks.

Background: Despite being vaccine-preventable, hepatitis A virus (HAV) outbreaks occur among men who have sex with men (MSM). We modelled the cost-effectiveness of vaccination strategies to prevent future outbreaks. Methods: A HAV transmission model was calibrated to HAV outbreak data for MSM in England over 2016-2018, producing estimates for the basic reproduction number (R0) and immunity levels (seroprevalence) post-outbreak. For a hypothetical outbreak in 2023 (same R0 and evolving immunity), the cost-effectiveness of pre-emptive (vaccination between outbreaks among MSM attending sexual health services (SHS)) and reactive (vaccination during outbreak among MSM attending SHS and primary care) vaccination strategies were modelled. Effectiveness in quality-adjusted life-years (QALYs) and costs were estimated (2017 UK pounds) from a societal perspective (10-year time horizon; 3% discount rate). The incremental cost-effectiveness ratio (ICER) was estimated. Findings: R0 for the 2016-2018 outbreak was 3·19 (95% credibility interval (95%CrI) 2·87-3·46); seroprevalence among MSM increased to 70·4% (95%CrI 67·3-72·8%) post-outbreak. For our hypothetical HAV outbreak in 2023, pre-emptively vaccinating MSM over the preceding five-years was cost-saving (compared to no vaccination) if the yearly vaccine coverage rate among MSM attending SHS was <9·1%. Reactive vaccination was also cost-saving compared to no vaccination, but was dominated by pre-emptive vaccination if the yearly vaccination rate was >8%. If the pre-emptive yearly vaccination rate fell below this threshold, it became cost-saving to add reactive vaccination to pre-emptive vaccination. Interpretation: Although highly transmissible, existing immunity limited the recent HAV outbreak among MSM in England. Pre-emptive vaccination between outbreaks, with reactive vaccination if indicated, is the best strategy for limiting future HAV outbreaks. Funding: NIHR.

Shigellosis seasonality and transmission characteristics in different areas of China: A modelling study.

Objective: In China, the burden of shigellosis is unevenly distributed, notably across various ages and geographical areas. Shigellosis temporal trends appear to be seasonal. We should clarify seasonal warnings and regional transmission patterns. Method: This study adopted a Logistic model to assess the seasonality and a dynamics model to compare the transmission in different areas. The next-generation matrix was used to calculate the effective reproduction number (R eff) to quantify the transmissibility. Results: In China, the rate of shigellosis fell from 35.12 cases per 100,000 people in 2005 to 7.85 cases per 100,000 people in 2017, peaking in June and August. After simulation by the Logistic model, the 'peak time' is mainly concentrated from mid-June to mid-July. China's 'early warning time' is primarily focused on from April to May. We predict the 'peak time' of shigellosis is the 6.30th month and the 'early warning time' is 3.87th month in 2021. According to the dynamics model results, the water/food transfer pathway has been mostly blocked off. The transmissibility of different regions varies greatly, such as the mean R eff of Longde County (3.76) is higher than Xiamen City (3.15), higher than Chuxiong City (2.52), and higher than Yichang City (1.70). Conclusion: The 'early warning time' for shigellosis in China is from April to May every year, and it may continue to advance in the future, such as the early warning time in 2021 is in mid-March. Furthermore, we should focus on preventing and controlling the person-to-person route of shigellosis and stratified deploy prevention and control measures according to the regional transmission.

Lithium/Boron Co-doped Micrometer SiOx as Promising Anode Materials for High-Energy-Density Li-Ion Batteries.

The carbon-coated silicon monoxide (SiOx@C) has been considered as one of the most promising high-capacity anodes for the next-generation high-energy-density lithium-ion batteries (LIBs). However, the relatively low initial Coulombic efficiency (ICE) and the still existing huge volume expansion during repeated lithiation/delithiation cycling remain the greatest challenges to its practical application. Here, we developed a lithium and boron (Li/B) co-doping strategy to efficiently enhance the ICE and alleviate the volume expansion or pulverization of SiOx@C anodes. The in situ generated Li silicates (LixSiOy) by Li doping will reduce the active Li loss during the initial cycling and enhance the ICE of SiOx@C anodes. Meanwhile, B doping works to promote the Li+ diffusion and strengthen the internal bonding networks within SiOx@C, enhancing its resistance to cracking and pulverization during cycling. As a result, the enhanced ICE (83.28%), suppressed volume expansion, and greatly improved cycling (85.4% capacity retention after 200 cycles) and rate performance could be achieved for the Li/B co-doped SiOx@C (Li/B-SiOx@C) anodes. Especially, the Li/B-SiOx@C and graphite composite anodes with a capacity of 531.5 mA h g-1 were demonstrated to show an ICE of 90.1% and superior cycling stability (90.1% capacity retention after 250 cycles), which is significant for the practical application of high-energy-density LIBs.

A highly stable pre-lithiated SiOx anode coated with a "salt-in-polymer" layer.

An artificial "salt-in-polymer" SEI, composed of poly-(1,3-dioxolane) and high-modulus fluorinated products generated from the in situ decomposition of Li salts, was constructed on the surface of Li-MSiOx particles. This LiF-rich SEI helps to maintain the structural integrity of Li-MSiOx particles and improves the Li storage reversibility of the Li-MSiOx anode.

Transmission dynamics of COVID-19 in household and community settings in the United Kingdom, January to March 2020.

BackgroundHouseholds appear to be the highest risk setting for COVID-19 transmission. Large household transmission studies in the early stages of the pandemic in Asia reported secondary attack rates ranging from 5 to 30%.AimWe aimed to investigate the transmission dynamics of COVID-19 in household and community settings in the UK.MethodsA prospective case-ascertained study design based on the World Health Organization FFX protocol was undertaken in the UK following the detection of the first case in late January 2020. Household contacts of cases were followed using enhanced surveillance forms to establish whether they developed symptoms of COVID-19, became confirmed cases and their outcomes. We estimated household secondary attack rates (SAR), serial intervals and individual and household basic reproduction numbers. The incubation period was estimated using known point source exposures that resulted in secondary cases.ResultsWe included 233 households with two or more people with 472 contacts. The overall household SAR was 37% (95% CI: 31-43%) with a mean serial interval of 4.67 days, an R0 of 1.85 and a household reproduction number of 2.33. SAR were lower in larger households and highest when the primary case was younger than 18 years. We estimated a mean incubation period of around 4.5 days.ConclusionsRates of COVID-19 household transmission were high in the UK for ages above and under 18 years, emphasising the need for preventative measures in this setting. This study highlights the importance of the FFX protocol in providing early insights on transmission dynamics.

Early warning of hand, foot, and mouth disease transmission: A modeling study in mainland, China.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a global infectious disease; particularly, it has a high disease burden in China. This study was aimed to explore the temporal and spatial distribution of the disease by analyzing its epidemiological characteristics, and to calculate the early warning signals of HFMD by using a logistic differential equation (LDE) model. METHODS: This study included datasets of HFMD cases reported in seven regions in Mainland China. The early warning time (week) was calculated using the LDE model with the key parameters estimated by fitting with the data. Two key time points, "epidemic acceleration week (EAW)" and "recommended warning week (RWW)", were calculated to show the early warning time. RESULTS: The mean annual incidence of HFMD cases per 100,000 per year was 218, 360, 223, 124, and 359 in Hunan Province, Shenzhen City, Xiamen City, Chuxiong Prefecture, Yunxiao County across the southern regions, respectively and 60 and 34 in Jilin Province and Longde County across the northern regions, respectively. The LDE model fitted well with the reported data (R2 > 0.65, P < 0.001). Distinct temporal patterns were found across geographical regions: two early warning signals emerged in spring and autumn every year across southern regions while one early warning signals in summer every year across northern regions. CONCLUSIONS: The disease burden of HFMD in China is still high, with more cases occurring in the southern regions. The early warning of HFMD across the seven regions is heterogeneous. In the northern regions, it has a high incidence during summer and peaks in June every year; in the southern regions, it has two waves every year with the first wave during spring spreading faster than the second wave during autumn. Our findings can help predict and prepare for active periods of HFMD.

Transmission dynamics and control measures of COVID-19 outbreak in China: a modelling study.

COVID-19 is reported to have been brought under control in China. To understand the COVID-19 outbreak in China and provide potential lessons for other parts of the world, in this study we apply a mathematical model with multiple datasets to estimate the transmissibility of the SARS-CoV-2 virus and the severity of the illness associated with the infection, and how both were affected by unprecedented control measures. Our analyses show that before 19th January 2020, 3.5% (95% CI 1.7-8.3%) of  infected people were detected; this percentage increased to 36.6% (95% CI 26.1-55.4%) thereafter. The basic reproduction number (R0) was 2.33 (95% CI 1.96-3.69) before 8th February 2020; then the effective reproduction number dropped to 0.04(95% CI 0.01-0.10). This estimation also indicates that control measures taken since 23rd January 2020 affected the transmissibility about 2 weeks after they were introduced. The confirmed case fatality rate is estimated at 9.6% (95% CI 8.1-11.4%) before 15 February 2020, and then it reduced to 0.7% (95% CI 0.4-1.0%). This shows that SARS-CoV-2 virus is highly transmissible but may be less severe than SARS-CoV-1 and MERS-CoV. We found that at the early stage, the majority of R0 comes from undetected infectious people. This implies that successful control in China was achieved through reducing the contact rates among people in the general population and increasing the rate of detection and quarantine of the infectious cases.

Forecasting the 2017/2018 seasonal influenza epidemic in England using multiple dynamic transmission models: a case study.

BACKGROUND: Since the 2009 A/H1N1 pandemic, Public Health England have developed a suite of real-time statistical models utilising enhanced pandemic surveillance data to nowcast and forecast a future pandemic. Their ability to track seasonal influenza and predict heightened winter healthcare burden in the light of high activity in Australia in 2017 was untested. METHODS: Four transmission models were used in forecasting the 2017/2018 seasonal influenza epidemic in England: a stratified primary care model using daily, region-specific, counts and virological swab positivity of influenza-like illness consultations in general practice (GP); a strain-specific (SS) model using weekly, national GP ILI and virological data; an intensive care model (ICU) using reports of ICU influenza admissions; and a synthesis model that included all data sources. For the first 12 weeks of 2018, each model was applied to the latest data to provide estimates of epidemic parameters and short-term influenza forecasts. The added value of pre-season population susceptibility data was explored. RESULTS: The combined results provided valuable nowcasts of the state of the epidemic. Short-term predictions of burden on primary and secondary health services were initially highly variable before reaching consensus beyond the observed peaks in activity between weeks 3-4 of 2018. Estimates for R0 were consistent over time for three of the four models until week 12 of 2018, and there was consistency in the estimation of R0 across the SPC and SS models, and in the ICU attack rates estimated by the ICU and the synthesis model. Estimation and predictions varied according to the assumed levels of pre-season immunity. CONCLUSIONS: This exercise successfully applied a range of pandemic models to seasonal influenza. Forecasting early in the season remains challenging but represents a crucially important activity to inform planning. Improved knowledge of pre-existing levels of immunity would be valuable.

New approaches to controlling an outbreak of chickenpox in a large immigration detention setting in England: the role of serological testing and mathematical modelling.

Chickenpox is caused by varicella-zoster-virus (VZV) and is highly contagious. Immigration detention settings are a high-risk environment for primary VZV transmission, with large, rapidly-changing populations in close quarters, and higher susceptibility among non-UK-born individuals. During outbreaks, operational challenges occur in detention settings because of high-turnover and the potential need to implement population movement restriction for prolonged periods. Between December 2017 and February 2018, four cases of chickenpox were notified amongst 799 detainees in an immigration removal centre (IRC). Microbiological investigations included case confirmation by vesicular fluid polymerase chain reaction, and VZV serology for susceptibility testing. Control measures involved movement restrictions, isolation of cases, quarantining and cohorting of non-immune contacts and extending VZV immunity testing to the wider detainee population to support outbreak management. Immunity was tested for 301/532 (57%) detainees, of whom 24 (8%) were non-immune. The level of non-immunity was lower than expected based on the existing literature on VZV seroprevalence in detained populations in England. Serology results identified non-immune contacts who could be cohorted and, due to the lack of isolation capacity, allowed the placement of cases with immune detainees. The widespread immunity testing of all detainees was proving challenging to sustain because it required significant resources and was having a severe impact on operational capacity and the ability to maintain core business activities at the IRC. Therefore, mathematical modelling was used to assess the impact of scaling back mass immunity testing. Modelling demonstrated that interrupting testing posed a risk of one additional case compared to continuing with testing. As such, the decision was made to stop testing, and the outbreak was successfully controlled without excessive strain on resources. Operational challenges generated learning for future outbreaks, with implications for a local and national policy on IRC staff occupational health requirements, and proposed reception screening of detainees for VZV immunity.