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• We analyzed the global reduction of influenza during the COVID-19 pandemic. • With regression trees, we classified trimesters-countries with similar influenza drop. • The decline in influenza was global but heterogeneous across space and time. • Countries with low flu drop had low pandemic preparedness and mild COVID-19 response. • A group of four "zero-COVID" countries experienced the greatest influenza decline. The influenza circulation reportedly declined during the COVID-19 pandemic in many countries. The occurrence of this change has not been studied worldwide nor its potential drivers. The change in the proportion of positive influenza samples reported by country and trimester was computed relative to the 2014-2019 period using the FluNet database. Random forests were used to determine predictors of change from demographical, weather, pandemic preparedness, COVID-19 incidence, and pandemic response characteristics. Regression trees were used to classify observations according to these predictors. During the COVID-19 pandemic, the influenza decline relative to prepandemic levels was global but heterogeneous across space and time. It was more than 50% for 311 of 376 trimesters-countries and even more than 99% for 135. COVID-19 incidence and pandemic preparedness were the two most important predictors of the decline. Europe and North America initially showed limited decline despite high COVID-19 restrictions; however, there was a strong decline afterward in most temperate countries, where pandemic preparedness, COVID-19 incidence, and social restrictions were high; the decline was limited in countries where these factors were low. The "zero-COVID" countries experienced the greatest decline. Our findings set the stage for interpreting the resurgence of influenza worldwide. [ABSTRACT FROM AUTHOR]

Abstract: Cytoplasmic phospholipase A2 (cPLA2) has a key role in prostaglandin production. The role of cPLA2 in intestinal tumorigenesis has been suggested, however, contradictory data are found in the literature. We evaluated cPLA2 and cyclooxygenase-2 (COX-2) protein expression in 65 colon carcinomas by immunohistochemistry, and in eight colorectal cancer cell lines by Western Blot. PGE2 production was evaluated by enzyme-immunoassay in the cell lines. We demonstrate that cPLA2 is overexpressed in approximately 50% of colon cancers and cell lines. cPLA2 expression is correlated with COX-2 expression. Both cPLA2 and COX-2 expressions are important in regard to PGE2 production. Our data suggest that cPLA2 might be involved in colon tumor development. [Copyright &y& Elsevier]

MERS coronavirus cases notified in the Middle East region since the identification of the virus in 2012 have displayed variations in time and across geography. Through a combined modelling approach, we estimate the rates of generation of cases along the zoonotic and human-to-human transmission routes and assess their spatiotemporal heterogeneity. We consider all cases notified to WHO from March 2012 to mid-September 2014. We use a stochastic modelling of the time series of case incidence in the Middle East region to estimate time- and space-dependent zoonotic and human-to-human transmission parameters. The model also accounts for possible lack of identification of secondary transmissions among notified cases. This approach is combined with the analysis of imported cases out of the region to assess the rate of underreporting of cases. Out of a total of 32 possible models, based on different parameterisation and scenario considered, the best-fit model is characterised by a large heterogeneity in time and across space for both zoonotic and human-to-human transmission. The variation in time that occurred during Spring 2014 led to a 17-fold and 3-fold increase in the two transmissions, respectively, bringing the reproductive rate to values above 1 during that period for all regions under study. The model suggests that 75% of MERS-CoV cases are secondary cases (human-to-human transmission), which is substantially higher than the 34% of reported cases with an epidemiological link to another case. Overall, estimated reporting rate is 0.26. Our findings show a higher level of spatial heterogeneity in zoonotic transmission compared to human-to-human, highlighting the strong environmental component of the epidemic. Since sporadic introductions are predicted to be a small proportion of notified cases and are responsible for triggering secondary transmissions, a more comprehensive understanding of zoonotic source and path of transmission could be critical to limit the epidemic spread. [ABSTRACT FROM AUTHOR]

Summary Background An epidemic of Ebola virus disease of unprecedented size continues in parts of west Africa. For the first time, large urban centres such as Conakry, the capital of Guinea, are affected. We did an observational study of patients with Ebola virus disease in three regions of Guinea, including Conakry, aiming to map the routes of transmission and assess the effect of interventions. Methods Between Feb 10, 2014, and Aug 25, 2014, we obtained data from the linelist of all confirmed and probable cases in Guinea (as of Sept 16, 2014), a laboratory database of information about patients, and interviews with patients and their families and neighbours. With this information, we mapped chains of transmission, identified which setting infections most probably originated from (community, hospitals, or funerals), and computed the context-specific and overall reproduction numbers. Findings Of 193 confirmed and probable cases of Ebola virus disease reported in Conakry, Boffa, and Télimélé, 152 (79%) were positioned in chains of transmission. Health-care workers contributed little to transmission. In March, 2014, individuals with Ebola virus disease who were not health-care workers infected a mean of 2·3 people (95% CI 1·6–3·2): 1·4 (0·9–2·2) in the community, 0·4 (0·1–0·9) in hospitals, and 0·5 (0·2–1·0) at funerals. After the implementation of infection control in April, the reproduction number in hospitals and at funerals reduced to lower than 0·1. In the community, the reproduction number dropped by 50% for patients that were admitted to hospital, but remained unchanged for those that were not. In March, hospital transmissions constituted 35% (seven of 20) of all transmissions and funeral transmissions constituted 15% (three); but from April to the end of the study period, they constituted only 9% (11 of 128) and 4% (five), respectively. 82% (119 of 145) of transmission occurred in the community and 72% (105) between family members. Our simulations show that a 10% increase in hospital admissions could have reduced the length of chains by 26% (95% CI 4–45). Interpretation In Conakry, interventions had the potential to stop the epidemic, but reintroductions of the disease and poor cooperation of a few families led to prolonged low-level spread, showing the challenges of Ebola virus disease control in large urban centres. Monitoring of chains of transmission is crucial to assess and optimise local control strategies for Ebola virus disease. Funding Labex IBEID, Reacting, PREDEMICS, NIGMS MIDAS initiative, Institut Pasteur de Dakar. [ABSTRACT FROM AUTHOR]

Background Hepatocellular carcinoma (HCC) often recurs after curative resection, and thus the optimal treatment strategy to treat recurrences remains uncertain. We analyzed the results of different options to treat recurrent HCC and emphasized the impact of pathologic patterns of the tumor at initial resection. Methods Between 2000 and 2014, 293 patients underwent potentially curative hepatic resection for HCC. Among them, 150 experienced a recurrence and have been treated by repeat resection (RR), radiofrequency ablation (RFA), salvage liver transplantation (SLT), transarterial chemoembolization (TACE), or conservative treatment, including systemic or targeted chemotherapy. Clinical outcomes were analyzed and compared between the treatment groups, focusing on clinical and pathologic characteristics of the tumor at initial resection. Results After a median follow-up of 26 months, the overall survival (OS) at 1, 3, and 5 years after recurrence was 62%, 48%, and 40%, respectively. Survival rates were greater in patients treated by a curative approach (RR, RFA, SLT) than those treated by TACE, with 5-year OS of >70% and 37%, respectively. Univariate analysis showed satellitosis and microvascular invasion (MVI) at initial resection as negative prognostic factors of survival after recurrence ( P < .05). On multivariate analysis, type of treatment was the only independent factor associated with survival. A subgroup analysis showed that RR/RFA led to better survival outcomes than TACE for early stage intrahepatic recurrences in the absence of satellitosis or MVI on the primary resected tumor. Conclusion Curative treatments of recurrent HCC improve patient survival. Satellitosis and MVI on the primary resected specimen may be used as selection criteria for the best treatment strategy for intrahepatic recurrences. [ABSTRACT FROM AUTHOR]

Highlights: [•] Many of initiatives exist in scientific domains to publish data using standard way. [•] Exposing PHS data and metadata is feasible using SDMX/SDMX-HD or OData. [•] Standards and harmonization of metadata are a first step to PHS interoperability. [ABSTRACT FROM AUTHOR]

Abstract: Following the emergence of a novel strain of influenza A(H1N1) in Mexico and the United States in April 2009, its epidemiology in Europe during the summer was limited to sporadic and localised outbreaks. Only the United Kingdom experienced widespread transmission declining with school holidays in late July. Using statistical modelling where applicable we explored the following causes that could explain this surprising difference in transmission dynamics: extinction by chance, differences in the susceptibility profile, age distribution of the imported cases, differences in contact patterns, mitigation strategies, school holidays and weather patterns. No single factor was able to explain the differences sufficiently. Hence an additive mixed model was used to model the country-specific weekly estimates of the effective reproductive number using the extinction probability, school holidays and weather patterns as explanatory variables. The average extinction probability, its trend and the trend in absolute humidity were found to be significantly negatively correlated with the effective reproduction number — although they could only explain about 3% of the variability in the model. By comparing the initial epidemiology of influenza A (H1N1) across different European countries, our analysis was able to uncover a possible role for the timing of importations (extinction probability), mixing patterns and the absolute humidity as underlying factors. However, much uncertainty remains. With better information on the role of these epidemiological factors, the control of influenza could be improved. [Copyright &y& Elsevier]

Objective: To analyze graft survival and the outcome of the corneal endothelium after corneal transplantation in a single model to predict the long-term prognosis of these grafts. Design: Cohort study. Data were recorded prospectively and then analyzed retrospectively. Participants: One thousand one hundred forty-four consecutive eyes of 1144 patients who underwent corneal transplantation between 1992 and 2006. Interventions: Penetrating keratoplasty and deep anterior lamellar keratoplasty. Main Outcome Measures: Slit-lamp examination and wide-field specular microscopy results. A joint analysis of endothelial cell loss and time to graft failure was undertaken. From midterm simultaneous analysis of graft survival and endothelial cell loss, long-term graft survival was predicted. Results: The observed 5- and 10-year graft survival estimates were, respectively, 74% and 64%. The average endothelial cell density (cell loss) was 2270 cells/mm2 before surgery, 1058 cells/mm2 (–53%) during the sixth postoperative year, and 865 cells/mm2 (–61%) during the 10th postoperative year. Overall, the predicted graft survival estimate was 27% at 20 years and 2% at 30 years. Both observed and predicted graft survival were higher in patients who had undergone lamellar keratoplasty than in patients who had undergone penetrating keratoplasty and had normal recipient endothelium and higher in patients who had undergone penetrating keratoplasty and had normal recipient endothelium than in patients who had undergone penetrating keratoplasty and had impaired recipient endothelium. Conclusions: For corneal diseases involving the endothelium, penetrating keratoplasty seems to be a good therapeutic approach in elderly patients because the graft life-span may be similar to the patient life expectancy. Conversely, for younger patients, penetrating keratoplasty is only a midterm therapeutic approach. For corneal diseases not involving the endothelium, deep anterior lamellar keratoplasty seems to be a promising therapeutic approach with higher long-term expected survival. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. [Copyright &y& Elsevier]

We quantify here the risk factors of influenza transmission in households from a prospective study conducted in the 1999–2000 winter season in France. Two hundred seventy-nine households were enrolled in the study, where a member—the index case—visited his/her general practitioner for influenza-like illness and tested positive for influenza A/H3N2. A standardized daily questionnaire allowed for identification of secondary cases of clinical influenza among the 543 contacts followed up for 15 days.Overall, 131 secondary cases occurred among the 543 household contacts (24.1%). There was an increased risk of clinical influenza in preschool contacts as compared with older contacts. There was also an increased risk in contacts exposed to preschool index cases and school-age index cases as compared with those exposed to adult index cases. No other factor was associated with transmission of the disease. [Copyright &y& Elsevier]

Age-specific force of varicella infection, hospitalisation and death rates in non-immune persons were calculated using an age-based mathematical model and national data for France. A cost-effectiveness model was then applied to hypothetical cohorts of persons aged 15–45 years with a negative or uncertain history of varicella. Vaccination strategies with and without prior serotesting, and healthcare payer perspective and societal perspective were considered. A sensitivity analysis was performed. Vaccination prevented more than one third of all varicella-related deaths. With serotesting, compared with no intervention, the cost per case avoided and per year of life saved for subjects aged 15 years were €335 and 55,100, respectively. When work-loss costs were also included, savings were associated with screening and vaccination of subjects less than 30 years old. Without serotesting, the costs raised markedly, with an almost identical effectiveness, resulting in an unfavourable incremental cost-effectiveness. Based on medical costs, routine serotesting and varicella vaccination for French adolescents and young adults with a negative or uncertain history of varicella affords health benefits at a cost comparable to those of other very expensive therapies considered worthwhile. From the societal perspective, such screening and vaccination might save costs. [Copyright &y& Elsevier]

Background: Schools were closed extensively in 2020-21 to counter SARS-CoV-2 spread, impacting students' education and wellbeing. With highly contagious variants expanding in Europe, safe options to maintain schools open are urgently needed. By estimating school-specific transmissibility, our study evaluates costs and benefits of different protocols for SARS-CoV-2 control at school.Methods: We developed an agent-based model of SARS-CoV-2 transmission in schools. We used empirical contact data in a primary and a secondary school and data from pilot screenings in 683 schools during the alpha variant (B.1.1.7) wave in March-June, 2021, in France. We fitted the model to observed school prevalence to estimate the school-specific effective reproductive number for the alpha (Ralpha) and delta (B.1.617.2; Rdelta) variants and performed a cost-benefit analysis examining different intervention protocols.Findings: We estimated Ralpha to be 1·40 (95% CI 1·35-1·45) in the primary school and 1·46 (1·41-1·51) in the secondary school during the spring wave, higher than the time-varying reproductive number estimated from community surveillance. Considering the delta variant and vaccination coverage in Europe as of mid-September, 2021, we estimated Rdelta to be 1·66 (1·60-1·71) in primary schools and 1·10 (1·06-1·14) in secondary schools. Under these conditions, weekly testing of 75% of unvaccinated students (PCR tests on saliva samples in primary schools and lateral flow tests in secondary schools), in addition to symptom-based testing, would reduce cases by 34% (95% CI 32-36) in primary schools and 36% (35-39) in secondary schools compared with symptom-based testing alone. Insufficient adherence was recorded in pilot screening (median ≤53%). Regular testing would also reduce student-days lost up to 80% compared with reactive class closures. Moderate vaccination coverage in students would still benefit from regular testing for additional control-ie, weekly testing 75% of unvaccinated students would reduce cases compared with symptom-based testing only, by 23% in primary schools when 50% of children are vaccinated.Interpretation: The COVID-19 pandemic will probably continue to pose a risk to the safe and normal functioning of schools. Extending vaccination coverage in students, complemented by regular testing with good adherence, are essential steps to keep schools open when highly transmissible variants are circulating.Funding: EU Framework Programme for Research and Innovation Horizon 2020, Horizon Europe Framework Programme, Agence Nationale de la Recherche, ANRS-Maladies Infectieuses Émergentes. [ABSTRACT FROM AUTHOR]

Airway epithelial cells form a physical barrier against inhaled pathogens and coordinate innate immune responses in the lungs. Bronchial cells in people with cystic fibrosis (pwCF) are colonized by Pseudomonas aeruginosa because of the accumulation of mucus in the lower airways and an altered immune response. This leads to chronic inflammation, lung tissue damage, and accelerated decline in lung function. Thus, identifying the molecular factors involved in the host response in the airways is crucial for developing new therapeutic strategies. The septin (SEPT) cytoskeleton is involved in tissue barrier integrity and anti-infective responses. SEPT7 is critical for maintaining SEPT complexes and for sensing pathogenic microbes. In the lungs, SEPT7 may be involved in the epithelial barrier resistance to infection; however, its role in cystic fibrosis (CF) P. aeruginosa infection is unknown. This study aimed to investigate the role of SEPT7 in controlling P. aeruginosa infection in bronchial epithelial cells, particularly in CF. The study findings showed that SEPT7 encages P. aeruginosa in bronchial epithelial cells and its inhibition downregulates the expression of other SEPTs. In addition, P. aeruginosa does not regulate SEPT7 expression. Finally, we found that inhibiting SEPT7 expression in bronchial epithelial cells (BEAS-2B 16HBE14o- and primary cells) resulted in higher levels of internalized P. aeruginosa and decreased IL-6 production during infection, suggesting a crucial role of SEPT7 in the host response against this bacterium. However, these effects were not observed in the CF cells (16HBE14o-/F508del and primary cells) which may explain the persistence of infection in pwCF. The study findings suggest the modification of SEPT7 expression as a potential approach for the anti-infective control of P. aeruginosa , particularly in CF. • SEPT7 inhibition reduced the expression of SEPT2, 6, 9, and 11 • SEPT7 encages intracellular P. aeruginosa in bronchial epithelial cells (BEC) • SEPT7 inhibition alters IL-6 levels in P. aeruginosa -infected BEC • SEPT7 inhibition further populates intracellular P. aeruginosa in CFTR sufficient BEC [ABSTRACT FROM AUTHOR]

Purpose: Varicella has a high incidence affecting the vast majority of the population in France and can lead to severe complications. Almost every individual infected by varicella becomes susceptible to herpes zoster later in life due to reactivation of the latent virus. Zoster is characterized by pain that can be long-lasting in some cases and has no satisfactory treatment. Routine varicella vaccination can prevent varicella. The vaccination strategy of replacing both doses of measles, mumps, and rubella (MMR) with a combined MMR and varicella (MMRV) vaccine is a means of reaching high vaccination coverage for varicella immunization. The objective of this analysis was to assess the impact of routine varicella vaccination, with MMRV in place of MMR, on the incidence of varicella and zoster diseases in France and to assess the impact of exogenous boosting of zoster incidence, age shift in varicella cases, and other possible indirect effects. Methods: A dynamic transmission population-based model was developed using epidemiological data for France to determine the force of infection, as well as an empirically derived contact matrix to reduce assumptions underlying these key drivers of dynamic models. Scenario analyses tested assumptions regarding exogenous boosting, vaccine waning, vaccination coverage, risk of complications, and contact matrices. Findings: The model provides a good estimate of the incidence before varicella vaccination implementation in France. When routine varicella vaccination is introduced with French current coverage levels, varicella incidence is predicted to decrease by 57%, and related complications are expected to decrease by 76% over time. After vaccination, it is observed that exogenous boosting is the main driver of change in zoster incidence. When exogenous boosting is assumed, there is a temporary increase in zoster incidence before it gradually decreases, whereas without exogenous boosting, varicella vaccination leads to a gradual decrease in zoster incidence. Changing vaccine efficacy waning levels and coverage assumptions are still predicted to result in overall benefits with varicella vaccination. Implications: In conclusion, the model predicted that MMRV vaccination can significantly reduce varicella incidence. With suboptimal coverage, a limited age shift of varicella cases is predicted to occur post-vaccination with MMRV. However, it does not result in an increase in the number of complications. GSK study identifier: HO-12-6924. [ABSTRACT FROM AUTHOR]

Background Varicella can be severe in adults. When universal vaccination is not adopted, post-exposure prophylaxis has been recommended in adults with uncertain history of varicella to reduce the burden of the disease in adults, however its impact is not quantified. Methods We developed a Bayesian probabilistic framework to estimate the impact of post-exposure prophylaxis in adults. We hypothesized that post-exposure vaccination would be proposed only after varicella exposure in close relatives. Information regarding the nature of the culprit exposure was obtained from a sample of 221 adult varicella cases. The lifelong probability that adults aged 18 would be infected with varicella was determined using data from the French Sentinelles surveillance network. Estimates of post-exposure vaccination efficacy were then used to compute the number of cases and hospitalizations prevented in adults. Results Familial exposure to varicella was reported by 81 adult cases out of 221. The probability of infection after exposure was 32%, so that six exposures on average were necessary to explain the observed cumulated lifetime incidence of varicella in non-immune 18 years old and over adults. Among the 35% of the 18 years old population with uncertain history of varicella, 11% would truly be non-immune. Post-exposure vaccination would prevent 26% of the cases (13 cases prevented per 100,000 adults per year) and 31% of the hospitalizations (0.2 hospitalizations prevented per 100,000 adults per year) if vaccination acceptance was 70%. An average of 16 adults would be vaccinated to avert one varicella case. Conclusions Post-exposure vaccination is associated with a substantial decrease in the burden of the disease in adults in a country where universal vaccination is not recommended. This quantitative information may help inform professionals to uphold the recommendation. [ABSTRACT FROM AUTHOR]

Background: The reasons for the seasonality and annual changes in the impact of influenza epidemics remain poorly understood. A strong coherence of influenza epidemics at a hemispheric level may suggest the role of global factors, such as climate, as a driving force of seasonality. The El Nin˜o Southern Oscillation (ENSO) represents the largest signal in inter-annual climate variation, affecting global atmospheric and oceanic circulation patterns. The phenomenon undergoes cycles between warm ENSO conditions (which are extreme during El Nin˜o episodes) and cold ENSO conditions (extreme during La Nina episodes). Materials and methods: We investigated the covariations between ENSO and the impact of influenza as measured by the number of pneumonia and influenza (P&I) excess deaths in France and the USA during the winter epidemics of 1971–1997. Results: On average in France (60.2 (M) million inhabitants in 2003), 2500 P&I excess deaths occurred per season (range 0–9500) during the 1971–1997 period. An average of 6215 excess deaths (range 0–13,600) occurred in the USA (290.3 M inhabitants in 2003). In both countries, the number of P&I excess deaths was significantly higher during the 10 seasons with cold ENSO conditions (mean±S.E.; 3530±654 excess deaths in France; 8290±900 in the USA) than during the 16 seasons with warm ENSO conditions (1856±574; 4919±977) (Wilcoxon rank test for France P=0.05 and for the USA P=0.03). Conclusion: These findings suggest that the impact of influenza epidemics, in terms of excess mortality, is associated with the ENSO conditions. An understanding of the mechanisms responsible for this association could lead to improved early warning and better control of influenza. [Copyright &y& Elsevier]