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ABSTRACT: Mastitis is one of the most common diseases of dairy cattle. It has a high impact on-farm economy, farmers' working time, and antimicrobial usage (AMU). Selective dry cow therapy (SDCT) is an effective means of reducing AMU without negatively affecting udder health. The objective of our study was to evaluate the impact of SDCT implementation on farmer income, working time, and AMU, using a bioeconomic model. A stochastic dairy simulation model (DairyHealthSim) based on a weekly model was used to simulate herd dynamics, reproduction, milk production, culling decisions, health outcomes, and the management of health events. A specific module was developed for the simulation of quarter-level IMI acquisition and elimination during the lactation and dry-off periods, and 25 different farm settings were defined to represent herds with various udder health situations. We then defined 20 scenarios of SDCT by combining both the use of different thresholds of SCC and milk bacteriology for treatment allocation and the use of internal teat sealant (ITS). All SDCT protocols had little effect on farmer income, and we identified some protocols with a positive farm gross margin (up to Can$15.83/dried cow; at time of writing, Can$1 = US$0.72). We also found that adding an ITS to all cows led to greater economic gain. The application of SDCT had little effect on farmers' working time, except when milk bacteriology was used for decision making. Antimicrobial treatment to all cows above 200,000 cells/mL at last control, with the use of ITS on all cows, seems a good choice in most dairy farms. These findings could be used to convince farmers to adopt this strategy at dry-off.

Abstract Establishing long-term microbiome-based monitoring programs is critical for managing and conserving wild fish populations in response to climate change. In most cases, these studies have been conducted on gut and, to a lesser extent, skin (mucus) microbiomes. Here, we exploited the concept of liquid biopsy to study the circulating bacterial microbiome of two Northern halibut species of economic and ecological importance. Amplification and sequencing of the 16S rRNA gene were achieved using a single drop of blood fixed on FTA cards to identify the core blood microbiome of Atlantic and Greenland halibut populations inhabiting the Gulf of St. Lawrence, Canada. We provide evidence that the circulating microbiome DNA (cmDNA) is driven by genetic and environmental factors. More specifically, we found that the circulating microbiome signatures are species-specific and vary according to sex, size, temperature, condition factor, and geographical localization. Overall, our study provides a novel approach for detecting dysbiosis signatures and the risk of disease in wild fish populations for fisheries management, most notably in the context of climate change.

ABSTRACT: Foot disorders are costly health disorders in dairy farms, and their prevalence is related to several factors such as breed, nutrition, and farmer's management strategy. Very few modeling approaches have considered the dynamics of foot disorders and their interaction with farm management strategies within a holistic farm simulation model. The aim of this study was to estimate the cost of foot disorders in dairy herds by simulating strategies for managing lameness. A dynamic and stochastic simulation model (DairyHealthSim) was used to simulate the herd dynamics, reproduction management, and health events. A specific module was built for lameness and related herd-level management strategies. Foot disorder occurrences were simulated with a base risk for each etiology [digital dermatitis (DD), interdigital dermatitis, interdigital phlegmon, sole ulcer (SU), white line disease (WLD)]. Two state machines were implemented in the model: the first was related to the disease-induced lameness score (from 1 to 5), and the second concerned DD-state transitions. A total of 880 simulations were run to represent the combination of the following 5 scenarios: (1) housing (concrete vs. textured), (2) hygiene (2 different scraping frequencies), (3) the existence of preventive trimming, (4) different thresholds of DD prevalence detected and from which a collective footbath is applied to treat DD, and (5) farmer's ability to detect lameness (detection rate). Housing, hygiene, and trimming scenarios were associated with risk factors applied for each foot disorder etiologies. The footbath and lameness detection scenarios both determined the treatment setup and the policy of herd observance. The economic evaluation outcome was the gross margin per year. A linear regression model was run to estimate the cost per lame cow (lameness score ≥3), per case of DD and per week of a cow's medium lameness duration. The bioeconomic model reproduced a lameness prevalence varying from 26 to 98% depending on the management scenario, demonstrating a high capacity of the model to represent the diversity of the field situations. Digital dermatitis represented half of the total lameness cases, followed by interdigital dermatitis (28%), SU (19%), WLD (13%), and interdigital phlegmon (4%). The housing scenarios dramatically influenced the prevalence of SU and WLD, whereas scraping frequency and threshold for footbath application mainly determined the presence of DD. Interestingly, the results showed that preventive trimming allowed a better reduction in lameness prevalence than spending time on early detection. Scraping frequency was highly associated with DD occurrence, especially with a textured floor. The regression showed that costs were homogeneous (i.e., did not change with lameness prevalence; marginal cost equals average cost). A lame cow and a DD-affected cow cost €307.50 ± 8.40 (SD) and €391.80 ± 10.0 per year on average, respectively. The results also showed a cost of €12.10 ± 0.36 per week-cow lameness. The present estimation is the first to account for interactions between etiologies and for the complex DD dynamics with all the M-stage transitions, bringing a high level of accuracy to the results.

Abstract The causal protein of amyloid light‐chain (AL) amyloidosis is a monoclonal immunoglobulin free light chain (mFLC), which must be quantified in the serum for patient diagnosis and monitoring. Several manufacturers commercialize immunoassays that quantify total kappa (κ) and lambda (λ) FLC, but results can differ greatly between these tests. Here, we compared a recently developed enzyme‐linked immunosorbent assay (ELISA) (Sebia) with N‐Latex immunonephelometry (Siemens) in 96 patients diagnosed with AL amyloidosis (histologically confirmed) and 48 non‐AL patients sent to our referral center for suspicion of cardiac amyloidosis. ELISA free‐light chain difference (dFLC) were lower than N‐Latex values, and agreement between methods was reduced in the case of involved λ FLC. Diagnosis sensitivity and specificity were >85% with both assays. A receiver operating characteristic analysis indicated that ELISA performances could be improved by using a higher value for the lower limit of the κ/λ ratio. We also assessed Freelite (The Binding Site) in a subgroup of these same AL patients, including 18 cases with normal κ/λ ratio by at least one assay. Only two patients had normal κ/λ ratio with all three assays. Overall, ELISA demonstrated slightly lower sensitivity than N‐Latex but may be an alternative to nephelometry/turbidimetry in certain difficult cases.

Abstract Liquid biopsy (LB) is a concept that is rapidly gaining ground in the biomedical field. Its concept is largely based on the detection of circulating cell-free DNA (ccfDNA) fragments that are mostly released as small fragments following cell death in various tissues. A small percentage of these fragments are from foreign (nonself) tissues or organisms. In the present work, we applied this concept to mussels, a sentinel species known for its high filtration capacity of seawater. We exploited the capacity of mussels to be used as natural filters to capture environmental DNA fragments of different origins to provide information on the biodiversity of marine coastal ecosystems. Our results showed that hemolymph of mussels contains DNA fragments that varied considerably in size, ranging from 1 to 5 kb. Shotgun sequencing revealed that a significant amount of DNA fragments had a nonself microbial origin. Among these, we found DNA fragments derived from bacteria, archaea, and viruses, including viruses known to infect a variety of hosts that commonly populate coastal marine ecosystems. Taken together, our study shows that the concept of LB applied to mussels provides a rich and yet unexplored source of knowledge regarding the microbial biodiversity of a marine coastal ecosystem.

Abstract Impacts of climate changes are particularly severe in polar regions where warmer temperatures and reductions in sea-ice covers threaten the ecological integrity of marine coastal ecosystems. Because of their wide distribution and their ecological importance, mussels are currently used as sentinel organisms in monitoring programs of coastal ecosystems around the world. In the present study, we exploited the concept of liquid biopsy combined to a logistically friendly sampling method to study the hemolymphatic bacterial microbiome in two mussel species (Aulacomya atra and Mytilus platensis) in Kerguelen Islands, a remote Subantarctic volcanic archipelago. We found that the circulating microbiome signatures of both species differ significantly even though their share the same mussel beds. We also found that the microbiome differs significantly between sampling sites, often correlating with the particularity of the ecosystem. Predictive models also revealed that both species have distinct functional microbiota, and that the circulating microbiome of Aulacomya atra was more sensitive to changes induced by acute thermal stress when compared to Mytilus platensis. Taken together, our study suggests that defining circulating microbiome is a useful tool to assess the health status of marine ecosystems and to better understand the interactions between the sentinel species and their habitat.

La contribution relative de l’usage des antibiotiques en production animale sur la baisse de l’efficacité des antibiotiques utilisés en médecine humaine reste mal documentée, mais l’importance de ce problème de santé publique requiert de réduire leur usage. Le plan Ecoantibio 1, mis en œuvre entre 2012 et 2016, consiste en une approche volontaire coordonnée par le Ministère de l’Agriculture afin de limiter l’usage des antibiotiques dans les filières d’élevage. Ce plan, ainsi que l’ensemble des initiatives privées et publiques mises en place sur cette période ont permis une réduction massive de l’usage des antibiotiques. L’évaluation rétrospective présentée ici identifie les effets socio-économiques, aux niveaux individuels et structurels, de ce plan sur la filière porcine française, perçue comme forte utilisatrice d’antibiotiques. Pour ce faire, une enquête a été conduite auprès des parties prenantes. Les impacts socio-économiques du plan Ecoantibio 1 apparaissent modérés, au niveau des changements de pratiques, des transformations structurelles, et des effets économiques. Ce plan s’est inséré dans une dynamique professionnelle, amorcée par d’autres politiques publiques et des initiatives privées. D’un point de vue technique, la plupart des alternatives aux antibiotiques existaient avant la mise en œuvre du plan, comme la vaccination ou la biosécurité. Les relations entre parties prenantes de la filière porcine ont été soit peu impactées, soit renforcées. Enfin, ce plan n’a pas eu d’impact significatif sur la croissance des porcs ni sur les revenus des différents acteurs. In fine, le plan Ecoantibio 1 est venu confirmer la dynamique déjà à l’œuvre, tout en donnant une assise règlementaire à des pratiques déjà en place.

The objective of this study is to determine the most effective time allocation for digital dermatitis management and to quantify the marginal economic gain from extra time devoted to digital dermatitis management. The model simulating foot disease occurrence and the associated management was Dairy Health Simulator©. Then, an econometric model was applied to identify the relationship between the dairy workshop’s gross margin and time for lameness management as well as the hourly marginal gain curve associated with lameness management. The gross margin was optimized under two constraints, i.e., the overall time spent for lameness management and the mean lameness duration (mimicking cow welfare). The results show that allocating less time to lameness detection and more to footbath application can contribute as follows: (i) reduces time spent for lameness management, (ii) maintains the best welfare level, and (iii) obtains the highest gross margin. The optimal time to devote to footbath application ranged from 17.8 to 22.3 h/month. A hiring strategy was investigated, and the break-even point ranged from 16.1 to 19.8 h/month. The recommended time to spend on footbath application is relatively important; therefore, stakeholders should consider the importance of lameness to the dairy industry and should devote enough time for footbath applications.

Our understanding of how microbiome signatures are modulated in wild fish populations remains poorly developed and has, until now, mostly been inferred from studies in commercial and farmed fish populations. Here, for the first time, we have studied changes in the skin and blood microbiomes of the Salmo trutta population of the volcanic Kerguelen archipelago located at the northern limit of the Antarctic Ocean. The Kerguelen Islands present a natural framework of population expansion and reveal a likely situation representing further climate change in distribution areas. Our results showed that S. trutta of the Kerguelen Islands has a microbiome signature distinct from those of salmonids of the Northern Hemisphere. Our study also revealed that the skin and blood microbiomes differ between sedentary and migratory S. trutta. While 18 phyla were shared between both groups of trout, independent of the compartment, 6 phyla were unique to migratory trout. Further analyses showed that microbiome signatures undergo significant site-specific variations that correlate, in some cases, with the peculiarity of specific ecosystems. Our study also revealed the presence of potential pathogens at particular sites and the impact of abiotic factors on the microbiome, most notably due to the volcanic nature of the environment. This study contributes to a better understanding of the factors that modulate the microbiome signatures of migratory and sedentary fish populations. It will also help to better monitor the impacts of climate change on the colonization process in the sub-Antarctic region.

Abstract Background Biomarkers of disease severity might help individualizing the management of patients with the acute respiratory distress syndrome (ARDS). Whether the alveolar compartmentalization of biomarkers has a clinical significance in patients with pneumonia-related ARDS is unknown. This study aimed at assessing the interrelation of ARDS/sepsis biomarkers in the alveolar and blood compartments and explored their association with clinical outcomes. Methods Immunocompetent patients with pneumonia-related ARDS admitted between 2014 and 2018 were included in a prospective monocentric study. Bronchoalveolar lavage (BAL) fluid and blood samples were obtained within 48 h of admission. Twenty-two biomarkers were quantified in BAL fluid and serum. HLA-DR+ monocytes and CD8+ PD-1+ lymphocytes were quantified using flow cytometry. The primary clinical endpoint of the study was hospital mortality. Patients undergoing a bronchoscopy as part of routine care were included as controls. Results Seventy ARDS patients were included. Hospital mortality was 21.4%. The BAL fluid-to-serum ratio of IL-8 was 20 times higher in ARDS patients than in controls (p

Abstract Conservation of whales, considered as umbrella species in marine environments, requires to be able to understand their relationships with ecosystem components such as prey species, including pelagic fish. However, studying such relationships in nature is a technical challenge. In this study, we used two noninvasive methods in combination, namely hydroacoustics and environmental DNA (eDNA), to detect five pelagic or semipelagic fish species in the Saguenay–St. Lawrence Marine Park (Québec, Canada): the sandlance Ammodytes sp., the Atlantic herring Clupea harengus, the capelin Mallotus villosus, the rainbow smelt Osmerus mordax, and the redfish Sebastes sp. The Marine Park is a major summer feeding ground for a wide diversity of marine wildlife species, including the endangered St. Lawrence beluga whale population. Up to now, scarce research efforts have been dedicated to the estimation of pelagic fish abundance and diversity in this area. Hydroacoustics allowed to easily discriminate the classification of echoes from fish, and with certain limitations to distinguish swim bladder fish from fish without swim bladder. We used eDNA to groundtruth acoustics data and to improve species identification. eDNA analyses especially demonstrated that the capelin was the most predominant species, while the abundance of the redfish and the sandlance was strongly variable over the 2 years of the study. Our results also suggest that there are annual fluctuations in prey availability that marine mammals encounter in this area. Although the approach we used is not without constraints that should be addressed in future studies, we hope that this study will contribute to science‐based conservation and fisheries management policies.

Maintaining udder health is the primary indication for antimicrobial use (AMU) in dairy production, and modulating this application is a key factor in decreasing AMU. Defining the optimal AMU and the associated practical rules is challenging since AMU interacts with many parameters. To define the trade-offs between decreased AMU, labor and economic performance, the bioeconomic stochastic simulation model DairyHealthSim (DHS)© was applied to dairy cow mastitis management and coupled to a mean variance optimization model and marginal abatement cost curve (MACC) analysis. The scenarios included three antimicrobial (AM) treatment strategies at dry-off, five types of general barn hygiene practices, five milking practices focused on parlor hygiene levels and three milk withdrawal strategies. The first part of economic results showed similar economic performances for the blanked dry-off strategy and selective strategy but demonstrated the trade-off between AMU reduction and farmers’ workload. The second part of the results demonstrated the optimal value of the animal level of exposure to AM (ALEA). The MACC analysis showed that reducing ALEA below 1.5 was associated with a EUR 10,000 loss per unit of ALEA on average for the farmer. The results call for more integrative farm decision processes and bioeconomic reasoning to prompt efficient public interventions.

To respond to the antimicrobial resistance (AMR) threat, public health entities implement policies aiming to reduce antimicrobial use (AMU) in livestock systems, in which policy success and sustainability might be subject to the social acceptability of the novel regulatory environment. Therefore, consistent methods that gather and synthesize preferences of stakeholder groups are needed during the policy design. The objective of this study was to present a methodology for evaluating the acceptability of potential strategies to reduce AMU using multi-criteria decision analysis (MCDA) using French dairy industry as a model. Preference-ranking organization methods for enrichment evaluations were applied to rank stakeholders’ acceptance of four different potential AMU reduction strategies: 1. Baseline AMU regulations in France; 2. Total interdiction of AMU; 3. Interdiction of prophylaxis and metaphylaxis AMU; and 4. Subsidies to reduce AMU by 25%. A total of 15 stakeholders (consumers, n = 10; farmers, n = 2; public health representatives, n = 3) representing the French dairy sector and public health administration participated in the acceptance weighting of the strategies in relation with their impact on environmental, economic, social, and political criteria. We established a MCDA methodology and result-interpretation approach that can assist in prioritizing alternatives to cope with AMR in the French dairy industry or in other livestock systems. Our MCDA framework showed that consumers and public health representatives preferred alternatives that consider the restriction of AMU, whereas farmers preferred to maintain baseline policy.

The provision of healthcare by veterinarians consists of a blend of activities ensuring welfare for animals. It also contributes in the control of infectious diseases and food safety. In general practices, most of the activities generate incomes for veterinarians, notably acts (consultations, surgery, etc.) and sales (drugs, pet food, etc.). Increased size of veterinary practices and the arrival of corporate companies modify the veterinary landscape in many countries. In a context of rapid growth of the companion animal health market, the question of the profitability of veterinary activities is relevant. Indeed, beyond a certain threshold, veterinarians may be tempted to leave behind food-producing animals' acts and focus on companion animals' acts, which are generally recognized to be more profitable and more attractive for new generations of veterinarians. A survey was conducted in French veterinary mixed practices, and a regression analysis was used to quantify the relationships between the turnover and the characteristics of veterinary practices, the time to perform veterinary acts, and the characteristics of veterinarians. We found that the characteristics of veterinary practices are positively associated with the turnover and the price of acts, and that there was an association between the status of veterinarians (associate, collaborator, or employee) and the time required to perform companion animals' and food-producing animals' acts. The present study is the first study showing the association between the characteristics of veterinary practices and the turnover, by investigating the price of veterinary acts and the time required.

Abstract Objective To explore the sociodemographic characteristics that might explain the increased incidence of psychosis among immigrants and their descendants in France. Methods Data were collected for all subjects with first contact for psychosis aged between 18 and 64 years, in two catchment areas in the Paris region. Incidence rates (IR) and incidence rate ratios (IRR) were adjusted for gender and age. Results During 805,396 persons‐year at risk, we identified 321 cases of first‐episode psychosis, of which 129 were immigrants and 78 descendants of immigrants. We found that the geographic origin was associated with the risk of psychosis although generation has little impact. Sub‐Saharan African immigrants and their descendants showed the highest risk (IRR = 3.1 and IRR = 2.9, respectively). We observed that living in deprived areas increased the incidence of psychosis (IRR = 1.3, 95CI%: 1.0–1.6), particularly among immigrants (IRR = 1.6; 95% CI: 1.1–2.5). Finally, our study showed that subjects having unstable housing (a proxy for “hard to count population”) could inflate the incidence rates among immigrants. Conclusion The current study shows that the increased risk of psychosis in groups with an immigration background in France is associated with their origin and highlights the importance of socioeconomic factors in modulating this risk.

Antimicrobial resistance (AMR) is a global public health threat driven by a combination of factors, including antimicrobial use (AMU) and interactions among microorganisms, people, animals and the environment. The emergence and spread of AMR in veterinary medicine (AMR-V) arising from AMU in veterinary medicine (AMU-V) can be linked to individuals' economic behaviour and institutional context. We highlight the limitations of current microeconomic approaches and propose a mesoeconomic conceptual model of AMR-V that integrates actors' strategic and routine behaviours in their context from a dynamic perspective using the concepts of externality, globality and futurity. The global solution to AMR-V management relies on a trade-off between i) the global externality assessment of AMU-V with respect to AMR-V (public perspective) and ii) farm- or value chain-level marginal abatement cost evaluation (private perspective). The improvements realized by the proposed mesoeconomic conceptual model include i) the simultaneous fight against the emergence and spread of AMR-V and ii) a local decrease in AMU-V without any loss of competitiveness for private actors due to the development of adequate production standards. A set of generic equations describing the stepwise change in the scale of analysis is finally proposed. This original contribution to the global challenge of AMR through a mesoeconomic approach bring substantial improvement for better AMU. This model can be considered a way to smoothly promote institutional change and a call for public policies that support public private partnership in the development of adequate incentives. The model requires further development prior to its application in a given value-chain or territory.

As of mid-2020, eradicating COVID-19 seems not to be an option, at least in the short term. The challenge for policy makers consists of implementing a suitable approach to contain the outbreak and limit extra deaths without exhausting healthcare forces while mitigating the impact on the country's economy and on individuals' well-being. To better describe the trade-off between the economic, societal and public health dimensions, we developed an integrated bioeconomic optimization approach. We built a discrete age-structured model considering three main populations (youth, adults and seniors) and 8 socio-professional characteristics for the adults. Fifteen lockdown exit strategies were simulated for several options: abrupt or progressive (4 or 8 weeks) lockdown lift followed by total definitive transitory final unlocking. Three values of transmission rate (Tr) were considered to represent individuals' barrier gesture compliance. Optimization under constraint to find the best combination of scenarios and options was performed on the minimal total cost for production losses due to contracted activities and hospitalization in the short and mid-term, with 3 criteria: mortality, person-days locked and hospital saturation. The results clearly show little difference between the scenarios based on the economic impact or the 3 criteria. This means that policy makers should focus on individuals' behaviors (represented by the Tr value) more than on trying to optimize the lockdown strategy (defining who is unlocked and who is locked). For a given Tr, the choices of scenarios permit the management of the hospital saturation level with regard to both its intensity and its duration, which remains a key point for public health. The results highlight the need for behavioral or experimental economics to address COVID-19 issues through a better understanding of individual behavior motivations and the identification of ways to improve biosecurity compliance.

The literature contains an extensive panel of studies focusing on the costs of animal diseases. The losses of an agriculture holding can be influenced by many factors since farming is a complex system and diseases are closely interrelated. Meta-analysis can be used to detect effects (i.e., change in clinical mastitis losses here) across studies and to identify factors that may influence those effects. This includes the external validity of the published study results with regard to the input parameters and the internal validity of the study, particularly how other diseases related to the target disease were accounted for. Mixed-effect meta-regressions were performed to estimate the mean clinical mastitis losses per case across the literature and to elucidate to what extent clinical mastitis losses are influenced by (i) general factors, such as etiology; (ii) the types of losses that contribute to the total mastitis losses; and (iii) prices. In total, 82 observations from nine studies were included in the meta-analysis to assess mean clinical mastitis losses per case. The multivariate meta-regression showed that etiology significantly influenced the clinical mastitis loss per case. The mean loss was determined to be €224 per case for all published etiologies. In detail, mean losses equalled €457 and €101 per case of clinical mastitis due to gram-negative and gram-positive bacteria, respectively, and €428 and €74 per case of clinical mastitis due to Escherichia coli and Staphylococcus aureus, respectively. Additionally, the mean loss obtained depended on whether diagnostic costs and reduced feed intake in cases of mastitis were included in the clinical mastitis loss calculation. The monetary values of labor cost, drug cost and culling cost, as well as treatment price (all included), significantly influenced the clinical mastitis losses per case. All other tested moderators were not associated with mastitis losses, highlighting the need for more standardized economic studies, for both methods and ways results are presented, and suggesting that the mastitis losses assessed in the literature cannot be extrapolated (limited external validity). Although meta-analyses are useful to overview the burden of diseases across studies, their ability to summarize extensive literature with various economic assessments is limited. These limitations in loss assessments also suggest the need to focus on management strategies rather than on pure monetary estimations of disease costs, at least for production diseases at the farm level.

The rising public health threat of antimicrobial resistance, the influence of food service companies, as well as the overall lack of positive image of using medical products in intensive farming are major drivers curbing antimicrobial use. In the future, government policies may affect practices of antimicrobial use in beef production in feedlots, a prominent current user of antimicrobials in animal agriculture, but also the agricultural industry generating the highest cash receipt in the U.S. Our objective was to estimate the cost effect from the following policies in feedlots: 1) using antimicrobials for disease prevention, control, and treatment; 2) using antimicrobials only for treatment of disease; and 3) not using antimicrobials for any reason. We modelled a typical U.S. feedlot, where high risk cattle may be afflicted by diseases requiring antimicrobial therapy, namely respiratory diseases, liver abscesses and lameness. We calculated the net revenue loss under each policy of antimicrobial use restriction. With moderate disease incidence, the median net revenue loss was $66 and $96 per animal entering the feedlot, for not using antimicrobials for disease prevention and control, or not using any antimicrobials, respectively, compared to using antimicrobials for disease prevention, control, and treatment. Losses arose mainly from an increase of fatality and morbidity rates, almost doubling for respiratory diseases in the case of antimicrobial use restrictions. In the case of antimicrobial use prohibition, decreasing the feeder cattle price by 9%, or alternatively, increasing the slaughter cattle price by 6.3%, would offset the net revenue losses for the feedlot operator. If no alternatives to antimicrobial therapy for prevention, control and treatment of current infectious diseases are implemented, policies that economically incentivize adoption of non-antimicrobial prevention and control strategies for infectious diseases would be necessary to maintain animal welfare and the profitability of beef production while simultaneously curbing antimicrobial use.

The induction of specific and sustainable tolerance is a challenging issue in organ transplantation. The discovery of the immunosuppressive properties of apoptotic cells in animal models has paved the way for their use in human transplantation. In this work, we aimed to define a stable, reproducible, and clinically compatible production procedure of human apoptotic cells (Apo-cells). Using a clinically approved extracorporeal photopheresis technique, we have produced and characterized phenotypically and functionally human apoptotic cells. These Apo-cells have immunosuppressive properties proved in vitro and in vivo in NOD/SCID/γC mice by their capacity to modulate an allogeneic response following both a direct and an indirect antigen presentation. These results brought the rationale for the use of Apo-cells in tolerance induction protocol for organ transplantation.

Abstract: Outcomes for follicular lymphoma (FL) have greatly improved, but most patients will ultimately relapse. High total metabolic tumor volume (TMTV), computed from baseline 18F-fluorodeoxyglucose–positron emission tomography (PET), is associated with shorter progression-free survival (PFS), but circulating tumor cells (CTCs) and cell-free DNA (cfDNA) may also reflect tumor burden and be of prognostic value. The aim of our study was to correlate CTCs and cfDNA with TMTV in FL at diagnosis and to determine their prognostic values. We retrospectively analyzed 133 patients (with previously untreated FL and a baseline PET) from 2 cohorts with either a baseline plasma sample (n = 61) or a bcl2-JH-informative peripheral blood (PB) sample (n = 68). Quantification of circulating bcl2-JH+ cells and cfDNA was performed by droplet digital polymerase chain reaction. A significant correlation was found between TMTV and both CTCs (P < .0001) and cfDNA (P < .0001). With a median 48-month follow-up, 4-year PFS was lower in patients with TMTV > 510 cm3 (P = .0004), CTCs >0.0018 PB cells (P = .03), or cfDNA >2550 equivalent-genome/mL (P = .04). In comparison with TMTV alone, no additional prognostic information was obtained by measuring CTCs. In contrast, Cox multivariate analysis, including cfDNA and TMTV, showed that both cfDNA and TMTV remained predictive of outcome. In conclusion, CTCs and cfDNA correlate with TMTV in FL, and all 3 influence patient outcome. PFS was shorter for patients with high cfDNA and TMTV, suggesting that these parameters provide relevant information for tumor-tailored therapy.

Biomarkers of disease severity might help with individualizing the management of patients with acute respiratory distress syndrome (ARDS). During sepsis, a sustained decreased expression of the antigen-presenting molecule human leucocyte antigen-DR (HLA-DR) on circulating monocytes is used as a surrogate marker of immune failure. This study aimed at assessing whether HLA-DR expression on alveolar monocytes in the setting of a severe lung infection is associated with their functional alterations. BAL fluid and blood from immunocompetent patients with pneumonia-related ARDS admitted between 2016 and 2018 were isolated in a prospective monocentric study. Alveolar and blood monocytes were immunophenotyped using flow cytometry. Functional tests were performed on alveolar and blood monocytes after in vitro lipopolysaccharide (LPS) stimulation. Phagocytosis activity and intracellular tumor necrosis factor (TNF) production were quantified using fluorochrome-conjugated-specific antibodies. Ten ARDS and seven non-ARDS control patients were included. Patients with pneumonia-related ARDS exhibited significantly lower HLA-DR expression both on circulating (p < 0.0001) and alveolar (p = 0.0002) monocytes. There was no statistically significant difference observed between patient groups (ARDS vs. non-ARDS) regarding both alveolar and blood monocytes phagocytosis activity. After LPS stimulation, alveolar (p = 0.027) and blood (p = 0.005) monocytes from pneumonia-related ARDS patients had a significantly lower intracellular TNF expression than non-ARDS patients. Monocytes from pneumonia-related ARDS patients have a deactivated status and an impaired TNF production capacity but display potent phagocytic activity. HLA-DR level expression should not be used as a surrogate marker of the phagocytic activity or the TNF production capacity of alveolar monocytes.