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The production and removal of ammonium (NH4+) are essential upper-ocean nitrogen cycle pathways, yet in the Southern Ocean where NH4+ has been observed to accumulate in surface waters, its mixed-layer cycling remains poorly understood. For surface seawater samples collected between Cape Town and the Marginal Ice Zone in winter 2017, we found that NH4+ concentrations were 5-fold higher than is typical for summer and lower north than south of the Subantarctic Front (0.01–0.26 µM versus 0.19–0.70 µM). Our observations confirm that NH4+ accumulates in the Southern Ocean's winter mixed layer, particularly in polar waters. NH4+ assimilation rates were highest near the Polar Front (12.9 ± 0.4 nM d−1) and in the Subantarctic Zone (10.0 ± 1.5 nM d−1), decreasing towards the Marginal Ice Zone (3.0 ± 0.8 nM d−1) despite the high ambient NH4+ concentrations in these southernmost waters, likely due to the low temperatures and limited light availability. By contrast, rates of NH4+ oxidation were higher south than north of the Polar Front (16.0 ± 0.8 versus 11.1 ± 0.5 nM d−1), perhaps due to the lower-light and higher-iron conditions characteristic of polar waters. NH4+ concentrations were also measured along five transects of the Southern Ocean (Subtropical Zone to Marginal Ice Zone) spanning the 2018/19 annual cycle. These measurements reveal that mixed-layer NH4+ accumulation south of the Subantarctic Front derives from sustained heterotrophic NH4+ production in late summer through winter that, in net, outpaces NH4+ removal by temperature-, light-, and iron-limited microorganisms. Our observations thus imply that the Southern Ocean becomes a biological source of CO2 to the atmosphere in autumn and winter not only because nitrate drawdown is weak but also because the ambient conditions favour net heterotrophy and NH4+ accumulation.

Abstract Exacerbation triggered by respiratory infection is an important cause of morbidity and mortality in chronic obstructive pulmonary disease (COPD) patients. Strategies aiming to preventing infection may have significant public health impact. Our previous study demonstrated decreased immunological response to seasonal flu vaccination in COPD patients, questioning the efficiency of other vaccines in this group of patients. We performed a prospective, monocenter, longitudinal study that evaluated the humoral and cellular responses upon pertussis vaccination. We included 13 patients with stable COPD and 8 healthy volunteers. No difference in circulating B and T cell subsets at baseline was noted. Both groups presented similar levels of TFH, plasmablasts and pertussis specific antibodies induction after vaccination. Moreover, monitoring T cell immunity after ex-vivo peptide stimulation revealed equivalent induction of functional and specific CD4+ T cells (IFNγ, TNFα and IL-2-expressing T cells) in both groups. Our results highlight the immunological efficiency of pertussis vaccination in this particularly vulnerable population and challenge the concept that COPD patients are less responsive to all immunization strategies. Healthcare providers should stress the necessity of decennial Tdap booster vaccination in COPD patients.

Late opportunistic infections (OI) occurring beyond the first year after kidney transplantation (KT) are poorly described and not targeted by prophylactic strategies. We performed a ten-year retrospective monocentric cohort study describing epidemiology, risk factors and impact of late OI occurring 1 year after KT. We included clinically symptomatic OI requiring treatment besides BK virus nephropathy. Control groups included early OI occurring in the first year after KT, and KT recipients without OI since KT and alive with a functional allograft at 1 year. Among 1066 KT recipients, 185 (19.4%) presented a first episode of OI 21.0 (8.0–45.0) months after KT: 120 late OI (64.9%) and 65 early OI (35.1%). Late OI were mainly viral (N = 83, 69.2%), mostly herpes zoster (HZ) (N = 36, 43.4%). Pneumocystis represented most late fungal infections (N = 12/25, 48%). Compared to early OI, we reported more pneumocystis (p = 0.002) and less invasive aspergillosis (p = 0.01) among late OI. Patients with late OI were significatively younger at KT (54.0 ± 13.3 vs. 60.2 ± 14.3 years, p = 0.05). Patient and allograft survival rates between late OI and control groups were similar. Only age was independently associated with mortality. While late OI were not associated with higher mortality or graft loss, implementing prophylactic strategies might prevent such infections.

Abstract Background Venous thromboembolism (VTE) causes significant mortality and morbidity in hospitalised patients. Risk factors for VTE are well known and there are validated risk assessment tools to support the use of prophylactic therapies. In England, reporting the percentage of patients with a completed VTE risk assessment is mandated, but this does not include whether that risk assessment resulted in appropriate prescribing. Full guideline compliance, defined as an assessment which led to an appropriate action—here prescribing prophylactic low molecular weight heparin where indicated, is rarely reported. Education, audit and feedback enhance guideline compliance but electronic prescribing systems (EPS) can mandate guideline-compliant actions. We hypothesised that a systems-based EPS intervention (prescribing rules which mandate approval or rejection of a proposed prescription of prophylactic low molecular weight heparin based on the mandated VTE assessment) would increase full VTE guideline compliance more than interventions which focused on targeting individual prescribers. Methods All admitted patients within University Hospitals Birmingham NHS Foundation Trust were included for analysis between 2011 and 2020. The proportion of patients who received a fully compliant risk assessment and action was assessed over time. Interventions included teaching sessions and face-to-face feedback based on measured performance (an approach targeting individual prescribers) and mandatory risk assessment and prescribing rules into an EPS (a systems approach). Results Data from all 235,005 admissions and all 5503 prescribers were included in the analysis. Risk assessments were completed in > 90–95% of all patients at all times, but full guideline compliance was lower (70% at the start of this study). Face-to-face feedback improved full VTE guideline compliance from 70 to 77% (p ≤ 0.001). Changes to the EPS to mandate assessment with prescribing rules increased full VTE compliance to 95% (p ≤ 0.001). Further amendments to the EPS system to reduce erroneous VTE assessments slightly reduced full compliance to 92% (p

Plain English summary Health data from routine care can be pseudonymised (with a link remaining to the patient but identifying features removed) or anonymised (with identifying features removed and the link to the patient severed) and used for research and health planning; termed “secondary use”. The National Health Service (NHS) is a single publicly-funded health service for the United Kingdom (UK). The NHS supports secondary data use with a National Data opt-out system. The potential benefits of data secondary use are clear but concerns have been raised. Although the Data Opt-Out is publicised, it is unclear how much public awareness there is of this scheme. We report a patient and publicly created and delivered series of activities including > 350 people; with young adults, patients, NHS staff and the public; to assess concerns, knowledge and acceptance of data sharing. Perceptions of and support for secondary health data use varied depending on who was asked (by age, gender) and their experience of health services (Staff member, patient, member of the public). Knowledge of schemes to limit secondary data use (such as the UK National Data Op-Out) was low, even among NHS staff. The main concerns of sharing health data included onward data use, the potential for discrimination and exploitation and commercial gain from data use with no benefit to patients. Despite this, most participants agreed with health data sharing with NHS, academic and commercial health-based entities. Agreed, co-created themes to increase the acceptability of health data secondary use included education about ‘Opt-out’ schemes, health service oversight of data use (as the most trusted partner), public and patient involvement in data sharing decisions and public transparency.

Objectives: Isoniazid-monoresistant tuberculosis (HR-TB) is the most prevalent form of drug-resistant TB worldwide and in France and is associated with poorer treatment outcomes compared with drug-susceptible TB (DS-TB). The objective of this study was to determine the characteristics of HR-TB patients in France and to compare outcomes and safety of treatment for HR-TB and DS-TB. Methods: We performed a case-control multicenter study to identify risk factors associated with HR-TB and compare treatment outcomes and safety between HR-TB patients and DS-TB patients. Results: Characteristics of 99 HR-TB patients diagnosed and treated in the university hospitals of Paris, Lille, Caen and Strasbourg were compared with 99 DS-TB patients. Female sex (OR = 2.2; 1.0–4.7), birth in the West-Pacific World Health Organization region (OR = 4.6; 1.1–18.7) and resistance to streptomycin (OR = 77.5; 10.1–594.4) were found to be independently associated with HR-TB. Rates of treatment success did not differ significantly between HR-TB and DS-TB. Conclusions: Factors associated with HR-TB are not significant enough to efficiently screen TB patients at risk of HR-TB. The systematic implementation of rapid molecular testing on clinical samples remains the only effective way to make the early diagnosis of HR-TB and adapt treatment.

Abstract Pigs infected by porcine epidemic diarrhea virus (PEDV) are affected by severe diarrhea, vomiting and dehydration. The severity of clinical signs depends on the virus strain. Two genetically different PEDV strains are known to infect pigs, the PEDV S-InDel strains which circulate on all continents and the highly virulent PEDV S-non-InDel strains found in Asia and in America. We have previously demonstrated the presence of PEDV RNA in semen from boars experimentally infected with an S-non-InDel PEDV strain. If naturally infected boars may shed PEDV in semen, this would have important consequences for the breeding sector. Thus we sought to determine whether PEDV has been circulating in populations of breeding boars from French artificial insemination (AI) centers. The current study reports on a serological survey conducted on one hundred and twenty boars from six AI centers, representing 18.6% of the total population of breeding boars in French AI centers in 2015. All of them were found negative for PEDV antibodies, showing no evidence of PEDV circulation in French AI centers at that time.

Staphylococcus aureus induces severe infective endocarditis (IE) where embolic complications are a major cause of death. Risk factors for embolism have been reported such as a younger age or larger IE vegetations, while methicillin resistance conferred by the mecA gene appeared as a protective factor. It is unclear, however, whether embolism is influenced by other S. aureus characteristics such as clonal complex (CC) or virulence pattern. We examined clinical and microbiological predictors of embolism in a prospective multicentric cohort of 98 French patients with monomicrobial S. aureus IE. The genomic contents of causative isolates were characterized using DNA array. To preserve statistical power, genotypic predictors were restricted to CC, secreted virulence factors and virulence regulators. Multivariate regularized logistic regression identified three independent predictors of embolism. Patients at higher risk were younger than the cohort median age of 62.5 y (adjusted odds ratio [OR] 0.14; 95% confidence interval [CI] 0.05–0.36). S. aureus characteristics predicting embolism were a CC30 genetic background (adjusted OR 9.734; 95% CI 1.53–192.8) and the absence of pIB485-like plasmid-borne enterotoxin-encoding genes sed, sej, and ser (sedjr; adjusted OR 0.07; 95% CI 0.004–0.457). CC30 S. aureus has been repeatedly reported to exhibit enhanced fitness in bloodstream infections, which might impact its ability to cause embolism. sedjr-encoded enterotoxins, whose superantigenic activity is unlikely to protect against embolism, possibly acted as a proxy to others genes of the pIB485-like plasmid found in genetically unrelated isolates from mostly embolism-free patients. mecA did not independently predict embolism but was strongly associated with sedjr. This mecA-sedjr association might have driven previous reports of a negative association of mecA and embolism. Collectively, our results suggest that the influence of S. aureus genotypic features on the risk of embolism may be stronger than previously suspected and independent of clinical risk factors.