Antimicrobial resistance to 14 antimicrobials in marine coastal waters around Northern Ireland: Use of the novel Relative Resistance Index as a marker of ecological status

Relatively little work has been published on the incidence of antibiotic resistance (ABR) in the marine microbiological environment, which is of importance to animal (fish, mammals, birds) health, zoonotic transmission, distribution of ABR bacteria with oceanic drift, and ultimately human health. A study was performed to determine the diversity of total ABR (intrinsic and acquired resistance) in marine bacteria in shallow coastal waters surrounding Northern Ireland through the use of a novel Relative Resistance Index (RRI) as a surrogate marker for ecological change, particularly in comparing marine water in commercial versus non-commercial sites. Total antibiotic resistance was observed to varying degrees in all marine water specimens and specific resistance levels were as follows, in order of diminishing antibacterial effectiveness: fluoroquinolones \u3e rifampicin \u3e polymyxin \u3e tetracycline \u3e sulphamethoxazole/trimethoprim \u3e third generation cephalosporin and streptomycin \u3e carbapenem \u3e macrolide \u3e clindamycin \u3e vancomycin \u3e fucidic acid \u3e penicillin. None of the sampling sites contained endogenous bacteria that were resistant to ciprofloxacin, while nearly all (19 of 20 sites; 95%) contained bacteria that were resistant to penicillin. Commercial sites had a higher mean RRI score of 6.57±3.58 than non-commercial sites (RRI = 4.08 ± 2.02), which was statistically significant (p = 0.037), indicating that bacteria isolated from seawater in commercial coastal harbors had a higher frequency of antibiotic resistance than non-commercial sources. This novel RRI marker may be useful in assessing ecological change in marine water environments. In conclusion, this study demonstrated that there can be a high level of total ABR (intrinsic and acquired) in bacterial populations in marine water environments, which are multi- and pan-resistant to up to 11 major classes of antibiotics simultaneously. Ecological studies are urgently needed to help define the fate of ABR marine bacteria in their natural environment and their ability to act as reservoirs and donors of ABR to pathogenic bacteria, many of which transiently inhabit the natural environment

Epidemiological study of E. coli O157:H7 isolated in Northern Ireland using pulsed-field gel electrophoresis (PFGE)

In Northern Ireland over the last 7 years, there is a mean of 41.9 laboratory reports per annum of human gastrointestinal infection (range 19-54) caused by Escherichia coli O157:H7. In the preceding years 1992-1996, reports were 5.4 per annum, whereas in 1997-2000, reports increased from 30 to 54 per annum. This high level has continued on an annual basis to date. The aim of this study was therefore to retrospectively examine this period of exponential increase in reports to help ascertain the genetic relatedness of strains employing pulsed-field gel electrophoresis (PFGE), as no data on the molecular epidemiology of E. coli O157:H7 in Northern Ireland has yet been published. Clinical isolates (n=84) were PFGE typed employing Xba I digestion and resulting band profiles demonstrated the presence of 13, 9 and 16 clonal types, for 1997, 1998 and 1999, respectively. In 1998, five clonal types remained from 1997 with the introduction of 4 new clonal types, whereas in 1999, 10 new clonal types were observed, accounting for over half (58%) of the E. coli O157 isolates for that year. These data suggest that, unlike gastrointestinal infections due to thermophilic campylobacters, there was considerable genetic evolution of PFGE clonal types of E. coli O157, through the displacement and emergence of genotypes. Further studies are now required to find the environmental reservoirs of these common clonal types of clinical E. coli O157:H7 in Northern Ireland to help define sources and routes of transmission of this infection locally

Country Concepts and the Rational Actor Trap: Limitations to Strategic Management of International NGOs

Growing criticism of inefficient development aid demanded new planning instruments of donors, including international NGOs (INGOs). A reorientation from isolated project-planning towards holistic country concepts and the increasing rationality of a result-orientated planning process were seen as answer. However, whether these country concepts - newly introduced by major INGOs too - have increased the efficiency of development cooperation is open to question. Firstly, there have been counteracting external factors, like the globalization of the aid business, that demanded structural changes in the composition of INGO portfolios towards growing short-term humanitarian aid; this was hardly compatible with the requirements of medium-term country planning. Secondly, the underlying vision of rationality as a remedy for the major ills of development aid was in itself a fallacy. A major change in the methodology of planning, closely connected with a shift of emphasis in the approach to development cooperation, away from project planning and service delivery, towards supporting the socio-cultural and political environment of the recipient communities, demands a reorientation of aid management: The most urgent change needed is by donors, away from the blinkers of result-orientated planning towards participative organizational cultures of learning.Des critiques croissantes de l'aide au développement inefficace exigent de nouveaux instruments de planification des bailleurs de fonds, y compris les ONG internationales (ONGI). Une réorientation de la planification des projets isolés vers des concepts holistiques de la planification de l’aide par pays ainsi que la rationalité croissante d'un processus de planification orientée vers les résultats ont été considérés comme réponse. Toutefois, si ces concepts de pays - nouvellement introduites par les grandes OING eux aussi - ont augmenté l'efficacité de la coopération au développement est ouvert à la question. Tout d'abord, il y a eu l’impact des facteurs externes, comme la mondialisation de l'entreprise de l'aide, qui a exigé des changements structurels dans la composition des portefeuilles des OING vers la croissance de l'aide humanitaire à court terme. Cela était difficilement compatible avec les exigences de l'aménagement du territoire à moyen terme. Deuxièmement, la vision sous-jacente de la rationalité accrue de la planification, concentré sur les resultats, comme un remède pour les grands maux de l'aide au développement était en soi une erreur. Un changement majeur dans la méthodologie de la planification, étroitement liée à un changement d'orientation dans l'approche de la coopération au développement, qui n’est pas concentrer sur planification du projet et la prestation de services, mais qui soutienne l'environnement socio-culturel et politique des communautés bénéficiaires, exige une réorientation de la gestion de l’aide: Le changement le plus urgent est un changement par les donateurs eux-mêmes, qui devrait implanter des cultures de collaboration étroit avec les partenaires et la population locale

On the origin and evolution of the material in 67P/Churyumov-Gerasimenko

International audiencePrimitive objects like comets hold important information on the material that formed our solar system. Several comets have been visited by spacecraft and many more have been observed through Earth- and space-based telescopes. Still our understanding remains limited. Molecular abundances in comets have been shown to be similar to interstellar ices and thus indicate that common processes and conditions were involved in their formation. The samples returned by the Stardust mission to comet Wild 2 showed that the bulk refractory material was processed by high temperatures in the vicinity of the early sun. The recent Rosetta mission acquired a wealth of new data on the composition of comet 67P/Churyumov-Gerasimenko (hereafter 67P/C-G) and complemented earlier observations of other comets. The isotopic, elemental, and molecular abundances of the volatile, semi-volatile, and refractory phases brought many new insights into the origin and processing of the incorporated material. The emerging picture after Rosetta is that at least part of the volatile material was formed before the solar system and that cometary nuclei agglomerated over a wide range of heliocentric distances, different from where they are found today. Deviations from bulk solar system abundances indicate that the material was not fully homogenized at the location of comet formation, despite the radial mixing implied by the Stardust results. Post-formation evolution of the material might play an important role, which further complicates the picture. This paper discusses these major findings of the Rosetta mission with respect to the origin of the material and puts them in the context of what we know from other comets and solar system objects

Implementation of corticosteroids in treating COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK:prospective observational cohort study

BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. FINDINGS: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. FUNDING: UK National Institute for Health Research and UK Medical Research Council

Nephrocalcinosis (enamel renal syndrome) caused by autosomal recessive FAM20A mutations

Calcium homeostasis requires regulated cellular and interstitial systems interacting to modulate the activity and movement of this ion. Disruption of these systems in the kidney results in nephrocalcinosis and nephrolithiasis, important medical problems whose pathogenesis is incompletely understood

Viral coinfections in hospitalized coronavirus disease 2019 patients recruited to the international severe acute respiratory and emerging infections consortium WHO clinical characterisation protocol UK study

Background We conducted this study to assess the prevalence of viral coinfection in a well characterized cohort of hospitalized coronavirus disease 2019 (COVID-19) patients and to investigate the impact of coinfection on disease severity. Methods Multiplex real-time polymerase chain reaction testing for endemic respiratory viruses was performed on upper respiratory tract samples from 1002 patients with COVID-19, aged <1 year to 102 years old, recruited to the International Severe Acute Respiratory and Emerging Infections Consortium WHO Clinical Characterisation Protocol UK study. Comprehensive demographic, clinical, and outcome data were collected prospectively up to 28 days post discharge. Results A coinfecting virus was detected in 20 (2.0%) participants. Multivariable analysis revealed no significant risk factors for coinfection, although this may be due to rarity of coinfection. Likewise, ordinal logistic regression analysis did not demonstrate a significant association between coinfection and increased disease severity. Conclusions Viral coinfection was rare among hospitalized COVID-19 patients in the United Kingdom during the first 18 months of the pandemic. With unbiased prospective sampling, we found no evidence of an association between viral coinfection and disease severity. Public health interventions disrupted normal seasonal transmission of respiratory viruses; relaxation of these measures mean it will be important to monitor the prevalence and impact of respiratory viral coinfections going forward

A prenylated dsRNA sensor protects against severe COVID-19

Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that OAS1, through RNase L, potently inhibits SARS-CoV-2. We show that a common splice-acceptor SNP (Rs10774671) governs whether people express prenylated OAS1 isoforms that are membrane-associated and sense specific regions of SARS-CoV-2 RNAs, or only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. Importantly, in hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting this antiviral defense is a major component of a protective antiviral response