Prevalence and Predictors for Homo- and Heterosubtypic Antibodies Against Influenza A Virus

Heterosubtypic antibodies to influenza A virus will be crucial for the development of a pan-influenza vaccine. Here we show that most individuals already possess heterosubtypic antibodies and that their generation is favored both by vaccination and ag

Prevalence and predictors for homo- and heterosubtypic antibodies against influenza a virus

Background: The effectiveness of trivalent influenza vaccination has been confirmed in several studies. To date, it is not known whether repeated exposure and vaccination to influenza promote production of cross-reactive anti-bodies. Furthermore, how strains encountered earlier in life imprint the immune response is currently poorly understood. Methods: To determine the prevalence for human homo- and heterosubtypic antibody responses, we scruti-nized serum samples from 305 healthy volunteers for hemagglutinin-binding and -neutralizing antibodies against several strains and subtypes of influenza A. Statistical analyses were then performed to establish the association of measured values with potential predictors. Results: It was found that vaccination not only promoted higher binding and neutralizing antibody titers to homosubtypic in fluenza isolates but also increased heterosubtypic human immune responses. Both binding and neutralizing antibody titers in relation with age of the donors mirrored the course of the different influenza strain circulation during the last century. Advanced age appeared to be of advantage for both binding and neutralizing titers to most subtypes. In contrast, the first virus subtype encountered was found to imprint to some degree subsequent antibody responses. Antibodies to recent strains, however, primarily seemed to be promoted by vaccination. Conclusions: We provide evidence that vaccinations stimulate both homo- and heterosubtypic immune responses in young and middle-aged as well as more senior individuals. Our analyses suggest that influenza vaccinations not only prevent infection against currently circulating strains but can also stimulate broader humoral immune responses that potentially attenuate infections with zoonotic or antigenically shifted strains

Criteria for assessing climate change impacts on ecosystems

There is concern about the potential impacts of climate change on species and ecosystems. To address this concern, a large body of literature has developed in which these impacts are assessed. In this study, criteria for conducting reliable and useful assessments of impacts of future climate are suggested. The major decisions involve: clearly defining an emissions scenario; selecting a climate model; evaluating climate model skill and bias; quantifying General Circulation Model (GCM) between-model variability; selecting an ecosystem model and assessing uncertainty; properly considering transient versus equilibrium responses; including effects of CO2 on plant response; evaluating implications of simplifying assumptions; and considering animal linkage with vegetation. A sample of the literature was surveyed in light of these criteria. Many of the studies used climate simulations that were >10 years old and not representative of best current models. Future effects of elevated CO2 on plant drought resistance and productivity were generally included in growth model studies but not in niche (habitat suitability) studies, causing the latter to forecast greater future adverse impacts. Overly simplified spatial representation was frequent and caused the existence of refugia to be underestimated. Few studies compared multiple climate simulations and ecosystem models (including parametric uncertainty), leading to a false impression of precision and potentially arbitrary results due to high between-model variance. No study assessed climate model retrodictive skill or bias. Overall, most current studies fail to meet all of the proposed criteria. Suggestions for improving assessments are provided

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Heterosubtypic antibodies to influenza A virus have limited activity against cell-bound virus but are not impaired by strain-specific serum antibodies

The majority of influenza virus-specific antibodies elicited by vaccination or natural infection are effective only against the eliciting or closely related viruses. Rare stem-specific heterosubtypic monoclonal antibodies (hMAbs) can neutralize multiple strains and subtypes by preventing hemagglutinin (HA)-mediated fusion of the viral membrane with the endosomal membrane. The epitopes recognized by these hMAbs are therefore considered promising targets for the development of pan-influenza virus vaccines. Here, we report the isolation of a novel human HA stem-reactive monoclonal antibody, hMAb 1.12, with exceptionally broad neutralizing activity encompassing viruses from 15 distinct HA subtypes. Using MAb 1.12 and two other monoclonal antibodies, we demonstrate that neutralization by hMAbs is virtually irreversible but becomes severely impaired following virus attachment to cells. In contrast, no interference by human anti-influenza virus serum antibodies was found, indicating that apically binding antibodies do not impair access to the membrane-proximal heterosubtypic epitopes. Our findings therefore encourage development of new vaccine concepts aiming at the induction of stem-specific heterosubtypic antibodies, as we provide support for their effectiveness in individuals previously exposed to influenza virus

Hyperspectral Imaging (HSI) as a new diagnostic tool in free flap monitoring for soft tissue reconstruction: a proof of concept study

Objectives!#!Free flap surgery is an essential procedure in soft tissue reconstruction. Complications due to vascular compromise often require revision surgery or flap removal. We present hyperspectral imaging (HSI) as a new tool in flap monitoring to improve sensitivity compared to established monitoring tools.!##!Methods!#!We performed a prospective observational cohort study including 22 patients. Flap perfusion was assessed by standard clinical parameters, Doppler ultrasound, and HSI on t0 (0 h), t1 (16-28 h postoperatively), and t2 (39-77 h postoperatively). HSI records light spectra from 500 to 1000 nm and provides information on tissue morphology, composition, and physiology. These parameters contain tissue oxygenation (StO2), near-infrared perfusion- (NIR PI), tissue hemoglobin- (THI), and tissue water index (TWI).!##!Results!#!Total flap loss was seen in n = 4 and partial loss in n = 2 cases. Every patient with StO2 or NIR PI below 40 at t1 had to be revised. No single patient with StO2 or NIR PI above 40 at t1 had to be revised. Significant differences between feasable (StO2 = 49; NIR PI = 45; THI = 16; TWI = 56) and flaps with revision surgery [StO2 = 28 (p < 0.001); NIR PI = 26 (p = 0.002); THI = 56 (p = 0.002); TWI = 47 (p = 0.045)] were present in all HSI parameters at t1 and even more significant at t2 (p < 0.0001).!##!Conclusion!#!HSI provides valuable data in free flap monitoring. The technique seems to be superior to the gold standard of flap monitoring. StO2 and NIR PI deliver the most valuable data and 40 could be used as a future threshold in surgical decision making. Clinical Trial Register This study is registered at the German Clinical Trials Register (DRKS) under the registration number DRKS00020926