Nursing homes and mortality in Europe: Uncertain causality.

The current health crisis has particularly affected the elderly population. Nursing homes have unfortunately experienced a relatively large number of deaths. On the basis of this observation and working with European data (from SHARE), we want to check whether nursing homes were lending themselves to excess mortality even before the pandemic. Controlling for a number of important characteristics of the elderly population in and outside nursing homes, we conjecture that the difference in mortality between those two samples is to be attributed to the way nursing homes are designed and organized. Using matching methods, we observe excess mortality in Sweden, Belgium, Germany, Switzerland, Czech Republic and Estonia but not in the Netherlands, Denmark, Austria, France, Luxembourg, Italy and Spain. This raises the question of the organization and management of these nursing homes, but also of their design and financing.

Long-lasting effects of incentives and social preference: A public goods experiment.

This paper addresses the question of the effectiveness and permanence of temporary incentives to contribute to a public good. Using a common experimental framework, we investigate the effects of a recommendation that takes the form of an exhortative message to contribute, a monetary punishment and a non-monetary reward to sustain high levels of contributions. In particular, we shed light on the differential impact these mechanisms have on heterogeneous types of agents. The results show that all three incentives increase contributions compared to a pre-phase where there is no incentive. Monetary sanctions lead to the highest contributions, but a sudden drop in contributions is observed once the incentive to punish is removed. On the contrary, Recommendation leads to the lowest contributions but maintains a long-lasting impact in the Post-policy phase. In particular, it makes free-riders increase their contribution over time in the post-incentive phase. Finally, non-monetary reward backfires against those who are weakly conditional cooperators. Our findings emphasize the importance of designing and maintaining incentives not only for free-riders, but for strong and weak conditional cooperators as well, depending on characteristics of the incentives.

Lockdown impact on age-specific contact patterns and behaviours, France, April 2020.

BackgroundMany countries implemented national lockdowns to contain the rapid spread of SARS-CoV-2 and avoid overburdening healthcare capacity.AimWe aimed to quantify how the French lockdown impacted population mixing, contact patterns and behaviours.MethodsWe conducted an online survey using convenience sampling and collected information from participants aged 18 years and older between 10 April and 28 April 2020.ResultAmong the 42,036 survey participants, 72% normally worked outside their home, and of these, 68% changed to telework during lockdown and 17% reported being unemployed during lockdown. A decrease in public transport use was reported from 37% to 2%. Participants reported increased frequency of hand washing and changes in greeting behaviour. Wearing masks in public was generally limited. A total of 138,934 contacts were reported, with an average of 3.3 contacts per individual per day; 1.7 in the participants aged 65 years and older compared with 3.6 for younger age groups. This represented a 70% reduction compared with previous surveys, consistent with SARS-CoV2 transmission reduction measured during the lockdown. For those who maintained a professional activity outside home, the frequency of contacts at work dropped by 79%.ConclusionThe lockdown affected the population's behaviour, work, risk perception and contact patterns. The frequency and heterogeneity of contacts, both of which are critical factors in determining how viruses spread, were affected. Such surveys are essential to evaluate the impact of lockdowns more accurately and anticipate epidemic dynamics in these conditions.

Short- & long-term effects of monetary and non-monetary incentives to cooperate in public good games: An experiment.

Using a common experimental framework, this paper addresses both the question of the short-term and the long-lasting effects of temporary monetary and non-monetary incentive mechanisms on increasing individual contributions to the public good. The results show that both punishments and rewards significantly increase contributions compared to the baseline, but that monetary sanctions lead to the highest contributions, whereas non-monetary sanctions lead to the lowest contributions. The four types of incentives display long-lasting effects, i.e., contributions do not go back to baseline levels directly after the withdrawal of the incentives. However, rewards appear to have much stronger persistent effects than sanctions, revealing some sort of delayed reciprocity.

Market analyses of livestock trade networks to inform the prevention of joint economic and epidemiological risks.

Conventional epidemiological studies of infections spreading through trade networks, e.g., via livestock movements, generally show that central large-size holdings (hubs) should be preferentially surveyed and controlled in order to reduce epidemic spread. However, epidemiological strategies alone may not be economically optimal when costs of control are factored in together with risks of market disruption from targeting core holdings in a supply chain. Using extensive data on animal movements in supply chains for cattle and swine in France, we introduce a method to identify effective strategies for preventing outbreaks with limited budgets while minimizing the risk of market disruptions. Our method involves the categorization of holdings based on position along the supply chain and degree of market share. Our analyses suggest that trade has a higher risk of propagating epidemics through cattle networks, which are dominated by exchanges involving wholesalers, than for swine. We assess the effectiveness of contrasting interventions from the perspectives of regulators and the market, using percolation analysis. We show that preferentially targeting minor, non-central agents can outperform targeting of hubs when the costs to stakeholders and the risks of market disturbance are considered. Our study highlights the importance of assessing joint economic-epidemiological risks in networks underlying pathogen propagation and trade.

Epidemics in markets with trade friction and imperfect transactions.

Market trade-routes can support infectious-disease transmission, impacting biological populations and even disrupting trade that conduces the disease. Epidemiological models increasingly account for reductions in infectious contact, such as risk-aversion behaviour in response to pathogen outbreaks. However, responses in market dynamics clearly differ from simple risk aversion, as are driven by other motivation and conditioned by "friction" constraints (a term we borrow from labour economics). Consequently, the propagation of epidemics in markets of, for example livestock, is frictional due to time and cost limitations in the production and exchange of potentially infectious goods. Here we develop a coupled economic-epidemiological model where transient and long-term market dynamics are determined by trade friction and agent adaptation, and can influence disease transmission. The market model is parameterised from datasets on French cattle and pig exchange networks. We show that, when trade is the dominant route of transmission, market friction can be a significantly stronger determinant of epidemics than risk-aversion behaviour. In particular, there is a critical level of friction above which epidemics do not occur, which suggests some epidemics may not be sustained in highly frictional markets. In addition, friction may allow for greater delay in removal of infected agents that still mitigates the epidemic and its impacts. We suggest that policy for minimising contagion in markets could be adjusted to the level of market friction, by adjusting the urgency of intervention or by increasing friction through incentivisation of larger-volume less-frequent transactions that would have limited effect on overall trade flow. Our results are robust to model specificities and can hold in the presence of non-trade disease-transmission routes.

Epidemic spread on weighted networks.

The contact structure between hosts shapes disease spread. Most network-based models used in epidemiology tend to ignore heterogeneity in the weighting of contacts between two individuals. However, this assumption is known to be at odds with the data for many networks (e.g. sexual contact networks) and to have a critical influence on epidemics' behavior. One of the reasons why models usually ignore heterogeneity in transmission is that we currently lack tools to analyze weighted networks, such that most studies rely on numerical simulations. Here, we present a novel framework to estimate key epidemiological variables, such as the rate of early epidemic expansion (r0) and the basic reproductive ratio (R0), from joint probability distributions of number of partners (contacts) and number of interaction events through which contacts are weighted. These distributions are much easier to infer than the exact shape of the network, which makes the approach widely applicable. The framework also allows for a derivation of the full time course of epidemic prevalence and contact behaviour, which we validate with numerical simulations on networks. Overall, incorporating more realistic contact networks into epidemiological models can improve our understanding of the emergence and spread of infectious diseases.

Weighting for sex acts to understand the spread of STI on networks.

Human sexual networks exhibit a heterogeneous structure where few individuals have many partners and many individuals have few partners. Network theory predicts that the spread of sexually transmitted infections (STI) on such networks should exhibit striking properties (e.g. rapid spread). However, these properties cannot be found in epidemiological data. Current network models typically assume a constant STI transmission risk per partnership, which is unrealistic because it implies that sexual activity is proportional to the number of partners and that individuals have the same activity with each partner. We develop a framework that allows us to weight any sexual network based on biological assumptions. Our results indicate that STI spreading on the resulting weighted networks do not have heterogeneous-related properties, which is consistent with data and earlier studies.

SIS along a continuum (SIS(c)) epidemiological modelling and control of diseases on directed trade networks.

Network theory has been applied to many aspects of biosciences, including epidemiology. Most epidemiological models in networks, however, have used the standard assumption of either susceptible or infected individuals. In some cases (e.g. the spread of Phytophthora ramorum in plant trade networks), a continuum in the infection status of nodes can better capture the reality of epidemics in networks. In this paper, a Susceptible-Infected-Susceptible model along a continuum in the infection status (SIS(c)) is presented, using as a case study directed networks and two parameters governing the epidemic process (probability of infection persistence (p(p)) and of infection transmission (p(t)). The previously empirically reported linear epidemic threshold in a plot of p(p) as a function of p(t) (Pautasso and Jeger, 2008) is derived analytically. Also the previously observed negative correlation between the epidemic threshold and the correlation between links in and out of nodes (Moslonka-Lefebvre et al., 2009) is justified analytically. A simple algorithm to calculate the threshold conditions is introduced. Additionally, a control strategy based on targeting market hierarchical categories such as producers, wholesalers and retailers is presented and applied to a realistic reconstruction of the UK horticultural trade network. Finally, various applications (e.g., seed exchange networks, food trade, spread of ideas) and potential refinements of the SIS(c) model are discussed.

Networks in plant epidemiology: from genes to landscapes, countries, and continents.

There is increasing use of networks in ecology and epidemiology, but still relatively little application in phytopathology. Networks are sets of elements (nodes) connected in various ways by links (edges). Network analysis aims to understand system dynamics and outcomes in relation to network characteristics. Many existing natural, social, and technological networks have been shown to have small-world (local connectivity with short-cuts) and scale-free (presence of super-connected nodes) properties. In this review, we discuss how network concepts can be applied in plant pathology from the molecular to the landscape and global level. Wherever disease spread occurs not just because of passive/natural dispersion but also due to artificial movements, it makes sense to superimpose realistic models of the trade in plants on spatially explicit models of epidemic development. We provide an example of an emerging pathosystem (Phytophthora ramorum) where a theoretical network approach has proven particularly fruitful in analyzing the spread of disease in the UK plant trade. These studies can help in assessing the future threat posed by similar emerging pathogens. Networks have much potential in plant epidemiology and should become part of the standard curriculum.

Regulation by glutathionylation of isocitrate lyase from Chlamydomonas reinhardtii.

Post-translational modification of protein cysteine residues is emerging as an important regulatory and signaling mechanism. We have identified numerous putative targets of redox regulation in the unicellular green alga Chlamydomonas reinhardtii. One enzyme, isocitrate lyase (ICL), was identified both as a putative thioredoxin target and as an S-thiolated protein in vivo. ICL is a key enzyme of the glyoxylate cycle that allows growth on acetate as a sole source of carbon. The aim of the present study was to clarify the molecular mechanism of the redox regulation of Chlamydomonas ICL using a combination of biochemical and biophysical methods. The results clearly show that purified C. reinhardtii ICL can be inactivated by glutathionylation and reactivated by glutaredoxin, whereas thioredoxin does not appear to regulate ICL activity, and no inter- or intramolecular disulfide bond could be formed under any of the conditions tested. Glutathionylation of the protein was investigated by mass spectrometry analysis, Western blotting, and site-directed mutagenesis. The enzyme was found to be protected from irreversible oxidative inactivation by glutathionylation of its catalytic Cys(178), whereas a second residue, Cys(247), becomes artifactually glutathionylated after prolonged incubation with GSSG. The possible functional significance of this post-translational modification of ICL in Chlamydomonas and other organisms is discussed.

Disease spread in small-size directed networks: epidemic threshold, correlation between links to and from nodes, and clustering.

Network epidemiology has mainly focused on large-scale complex networks. It is unclear whether findings of these investigations also apply to networks of small size. This knowledge gap is of relevance for many biological applications, including meta-communities, plant-pollinator interactions and the spread of the oomycete pathogen Phytophthora ramorum in networks of plant nurseries. Moreover, many small-size biological networks are inherently asymmetrical and thus cannot be realistically modelled with undirected networks. We modelled disease spread and establishment in directed networks of 100 and 500 nodes at four levels of connectance in six network structures (local, small-world, random, one-way, uncorrelated, and two-way scale-free networks). The model was based on the probability of infection persistence in a node and of infection transmission between connected nodes. Regardless of the size of the network, the epidemic threshold did not depend on the starting node of infection but was negatively related to the correlation coefficient between in- and out-degree for all structures, unless networks were sparsely connected. In this case clustering played a significant role. For small-size scale-free directed networks to have a lower epidemic threshold than other network structures, there needs to be a positive correlation between number of links to and from nodes. When this correlation is negative (one-way scale-free networks), the epidemic threshold for small-size networks can be higher than in non-scale-free networks. Clustering does not necessarily have an influence on the epidemic threshold if connectance is kept constant. Analyses of the influence of the clustering on the epidemic threshold in directed networks can also be spurious if they do not consider simultaneously the effect of the correlation coefficient between in- and out-degree.

[Epigenetic changes and liver carcinogenesis]. / Anomalies épigénétiques et carcinogenèse hépatique.

The molecular mechanisms involved in liver carcinogenesis are poorly understood. Over the past decade, epigenetic changes (DNA methylation) have received increasing attention for their potential involvement in the development of hepatocarcinoma. The DNA methylation level is influenced by environmental factors (folate and methionine diet), as well as by genetic factors (methylenetetrahydrofolate reductase/MTHFR polymorphisms). These findings provide new insight into the understanding of liver carcinogenesis. Interventional studies are now required to determine the role of folate supplementation in the development of liver tumors in targeted patients.

[Pancreatic pseudocysts of the right hepatic lobe during acute biliary pancreatitis]. / Pseudokystes hépatiques du foie droit au décours d'une pancréatite aiguë biliaire.

The occurrence of pancreatic pseudocysts of the right hepatic lobe during acute biliary pancreatitis is a rare event. We report the unusual case of a 69-year-old woman who was hospitalised for biliary pancreatitis. The patient suffered from right hypochondrial pain. A CT-scan performed at day 12 showed pancreatic pseudocysts in the right hepatic lobe. A favorable outcome was obtained after percutaneous drainage. Most hepatic pseudocysts are described in the left hepatic lobe after alcoholic pancreatitis. Different hypotheses have been suggested to explain the extension of pancreatic pseudocysts in the liver, due to proteolytic effect of pancreatic enzymes that reach the lesser sac and then the liver either directly through the liver capsule, or indirectly through the hepatic hilum vessels, or the hepatic ligament. We suggest another reason for hepatic invasion: pancreatic enzymes could also cause liver damage, through the para - renal anterior space, often infiltrated during acute pancreatitis, reaching right hepatic lobe through area nuda.