Apramycin treatment affects selection and spread of a multidrug-resistant Escherichia coli strain able to colonize the human gut in the intestinal microbiota of pigs

International audienceAbstractThe effect of apramycin treatment on transfer and selection of an Escherichia coli strain (E. coli 912) in the intestine of pigs was analyzed through an in vivo experiment. The strain was sequenced and assigned to the sequence type ST101 and serotype O11. It carried resistance genes to apramycin/gentamicin, sulphonamide, tetracycline, hygromycin B, β-lactams and streptomycin [aac(3)-IV, sul2, tet(X), aph(4), blaTEM-1 and strA/B], with all but tet(X) located on the same conjugative plasmid. Nineteen pigs were randomly allocated into two inoculation groups, one treated with apramycin (pen 2) and one non-treated (pen 3), along with a non-inoculated control group (pen 1). Two pigs of pen 2 and 3 were inoculated intragastrically with a rifampicin resistant variant of the strain. Apramycin treatment in pen 2 was initiated immediately after inoculation. Strain colonization was assessed in the feces from all pigs. E. coli 912 was shown to spread to non-inoculated pigs in both groups. The selective effect did not persist beyond 3 days post-treatment, and the strain was not detected from this time point in pen 2. We demonstrated that E. coli 912 was able to spread between pigs in the same pen irrespective of treatment, and apramycin treatment resulted in significantly higher counts compared to the non-treated group. This represents the first demonstration of how antimicrobial treatment affects spread of resistant bacteria in pig production. The use of apramycin may lead to enhanced spread of gentamicin-resistant E. coli. Since gentamicin is a first-choice drug for human bacteremia, this is of concern

Supercurrent 0-π oscillations induced by spin-orbit coupling

Denne masteroppgaven presenterer det teoretiske rammeverket innen superledning og spinn-bane kobling. Dette rammeverket brukes for å undersøke visse kvanteeffekter i Josephson-overganger (S-X-S). Josephson-overganger består av et ikke-superledende materiale (X) klemt inn mellom to superledere (S). Order-parameteren til de to superlederne vil generelt ha forskjellige faser som påvirker eller blir påvirket av strømmen over overgangen. I en S-N-S overgang (N-normalt metall) viser det seg at faseforskjellen i grunntilstanden blir null. Dette betyr at den kritiske superstrømmen over overgangen har samme fortegn som den påtrykte strømmen. En S-F-S overgang (F-ferromagnet) er mer interessant fordi faseforskjellen i grunntilstanden er avhengig av visse parametere. En av disse parameterne er bredden på materialet som går imellom superlederne. Ved å endre denne bredden kan vi enten få en faseforskjell lik 0 eller π, derav 0-π oscillasjoner i tittelen. I en π-overgang vil fortegnet til den kritiske superstrømmen over overgangen være motsatt relativ til den ytre påtrykte strømmen. For mange av bruksområdene til Josephson-overganger, som f.eks. kretskomponenter, er dette en ønsket egenskap. Men ferromagneter produserer strøfelt som kan påvirke og skape uønskede effekter i andre kretskomponenter. Det er dette problemet vi ønsker å løse i denne masteroppgaven: Kan vi oppnå 0-π oscillasjoner uten ferromagneter? Svaret er spinn-bane-kobling (SOC). SOC er en relativistisk effekt som kobler spinnet til partikler i bevegelse til elektriske felt. Partikkelen føler et effektivt magnetisk felt, og det er derfor vi har valgt å bytte ut ferromagneten med et spinn-bane-koblet materiale. I denne oppgaven bruker vi BTK-formalismen og en numerisk 2D gittermodell for å vise at det er mulig å oppnå 0-π oscillasjoner ved å bruke spinn-bane-kobling og ukonvensjonelle p-bølge superledere.This master's thesis presents the theoretical background within superconductivity and spin-orbit coupling (SOC) needed to investigate certain quantum effects in Josephson junctions (S-X-S), which consists of sandwiching a non-superconducting material (X) between two superconductors (S). The order parameter of the two superconductors will in general have different phases, influencing or influenced by the current across the junction. In an S-N-S junction (N-normal state metal), the ground state phase difference turns out to be zero. This means that the critical supercurrent across the junction will have the same sign as the applied current. In the more interesting case of an S-F-S junction (F-Ferromagnet), the ground state phase difference depends on certain parameters. One of these parameters is the width of the junction. By changing it, the ground state phase difference can go from 0 to π, hence 0-π oscillations. In a π-junction, the sign of the critical supercurrent will be opposite to the external current, which is a desirable feature in many uses of the Josephson junction, e.g. as a circuit component. However, the ferromagnet produces stray fields which could interfere with other components and cause unwanted effects. This is the problem we want to solve in this thesis. Can we achieve 0-π oscillations without using ferromagnets? The answer is spin-orbit coupling (SOC). SOC is a relativistic effect, causing the spin of moving particles to couple to electric fields. The particle experiences an effective magnetic field, which is why we have chosen to exchange the ferromagnet with a SOC material. In this thesis, we use the BTK-formalism as well as a numerical 2D lattice approach, to show that it is possible to achieve 0-π oscillations using spin-orbit coupling and unconventional p-wave superconductors

Moral experts as members of ethics commissions as seen through the prism of comprehensive doctrines

Ethics commissions provide expert advice to governments on what policies to implement regarding pressing ethical issues, most often in bioethics. These commissions distinguish themselves by having members from the professions we are most likely to think of as moral experts, if we believe that these exist. The relationship between moral experts and the composition of ethics commissions is worthy of further exploration, especially because of the highly controversial nature of whether moral expertise exists and, if so, how, and whether, we can identify moral experts. Moreover, it has been argued that the emergence of ethics commissions and how they have been composed have led to a “thinner” debate. In the first part of the article, the problem regarding checks for identifying moral experts is discussed. I argue that one way to handle this difficulty is through the application of Rawls’ concept of comprehensive doctrines. These doctrines have inherent standards that function similarly to independent checks, making it possible to identify moral experts from within such different doctrines. Using this approach makes it manageable to appoint moral experts to ethics commissions. In the second part, I consider the implications of seeing moral expertise through the prism of comprehensive doctrines for the composition of ethics commissions. One natural conclusion is that we should select moral experts representing different reasonable comprehensive doctrines to serve as members of ethics commissions. I consider six challenges to my proposal and demonstrate why these lack merit, and I point out some practical concerns that need further inquiry.publishedVersio

The development of a Messianic Jewish theology : affirmations and questions

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The proper role of ethics commissions - (Bio)ethics, moral expertise and democracy

Experts play an important role in modern governing, including participating on government advisory commissions which give policymakers advice on what policies they should implement. Ethics commissions, which are a type of government advisory commission, are asked to advise on ethical issues, most often in the area of bioethics. Professional ethicists, such as bioethicists, philosophers and theologians are prominent members of these commissions. Ethics commissions raise questions about the nature of their expertise, and what authority, if any, the advice from these commissions should be given. The aim of this thesis has therefore been to investigate the research question: What is the proper role of ethics commissions in democracies? The research question has been explored by combining both empirical and normative work. To answer the question of what the proper role of ethics commissions is it was necessary to gain understanding of how ethics commissions work and the salient normative issues concerning them. For this purpose, two main sources were used. Firstly, the thesis engaged the relevant scholarly literature on ethics commissions and the status of moral expertise. Secondly, members of the Norwegian Biotechnology Advisory Board (NBAB) were interviewed. The research question was investigated through four articles. Article 1 locates the main disagreement in the literature along two dimensions: the expertise and public/political dimensions. The expertise dimension concerns whether there is moral expertise or not, while the public/political dimension is about whether the public or policymakers should be the main audience of ethics commissions. These two dimensions are used to construct four normative models. Article 2 analyses the interviews with members of NBAB seen through the lens of the epistemic-democratic tension, focusing on members’ views on expertise, consensus and the main audience of the board. The article contributes to our understanding of the epistemic-democratic tension, and how this can be handled in the case of ethics commissions. In addition, the question of whether NBAB is a best case of handling this tension is considered. One of the key normative questions related to ethics commissions are their composition. Article 3 focuses on the issue of moral expertise, particularly the difficulty of identifying these experts. In the article, I propose that viewing moral experts through the prism of what John Rawls calls ‘comprehensive doctrines’ makes it manageable to appoint moral experts, along with other experts that are necessary for ethics commissions to perform well. In article 4, a political standard for evaluating ethics commissions is developed. I argue that in order to make an overall judgment of how they perform we need to understand what the political context means for the work of ethics commissions. More concretely, this involves contributing to the epistemic, democratic and ethical functions of public deliberation. The implications for the work of ethics commissions are discussed, and it is argued that ethics commissions should focus on seriously considering a range of views including those based on comprehensive doctrines, but that commissions should be mindful that the recommendations they make are justifiable to a public characterized by pluralism. Overall, most importantly, the thesis contributes to the literature by setting out a way to think about the proper role of an expert institution: namely ethics commissions. Furthermore, the analysis of the main points of disagreement about ethics commissions can be a fruitful starting point for future discussions, as well as a tool for analyzing real-world ethics commissions. The interview study with NBAB members is also an important addition to the literature as there are relatively few case studies of ethics commissions. Eksperter spiller en sentral rolle i politikkutforming, blant annet gjennom deltagelse i offentlige komiteer, som rådgir myndighetene om politikken de bør føre. Etikkomiteer er et eksempel på slike komiteer som gir råd om etiske spørsmål, særlig på bioteknologifeltet. Profesjonelle etikere, slik som bioetikere, filosofer og teologer er som oftest medlemmer av disse komiteene. Etikkomiteene reiser spørsmål om basisen for deres ekspertise og i hvilken grad deres anbefalinger bør gis noen form for autoritet. Denne avhandlingen stiller derfor spørsmålet: Hvilken rolle bør etikkomiteer spille i demokratier? Forskningsspørsmålet undersøkes ved å kombinere empiriske og normative tilnærminger. For å kunne besvare spørsmålet om hvilken rolle etikkomiteer bør spille er det nødvendig å forstå hvordan disse komiteene fungerer, noe som er en forutsetning for å identifisere de sentrale normative spørsmålene når det gjelder etikkomiteene. To hovedkilder ble brukt i dette arbeidet. For det første, ble den relevante akademiske litteraturen om etikkomiteer og moralske eksperter studert. For det andre, ble det gjennomført intervjuer med medlemmer av Bioteknologirådet. Forskningsspørsmålet er undersøkt gjennom fire artikler i denne avhandlingen. Den første artikkelen analyserer litteraturen om etikkomiteer langs to hoveddimensjoner: ekspertise og offentlighet/politikkdimensjonen. Ekspertisedimensjonen handler om hvorvidt det finnes moralsk ekspertise. Offentlighet/politikkdimensjonen handler om det er den brede offentlighet eller politiske beslutningstakere som er komiteens hovedadressat. Disse to dimensjonene danner grunnlaget for utformingen av fire normative modeller som besvarer spørsmålet om hvilken rolle etikkomiteer bør spille. Den andre artikkelen analyserer intervjuer med medlemmer av Bioteknologirådet, sett i lys av spenningen mellom epistemiske og demokratiske hensyn. Analysen fokuserer på medlemmenes syn på ekspertise, konsensus og hovedpublikummet til rådet. Artikkelen bidrar vi til en bedre forståelse av spenningen mellom epistemiske og demokratiske hensyn og hvordan denne kan håndteres av etikkomiteer. I tillegg diskuteres det om Bioteknologirådet kan sies å være et eksempel til etterfølgelse i måten de håndterer denne spenningen. Et sentralt normativt spørsmål er etikkomiteers sammensetning. Den tredje artikkelen tar for seg problemet med moralsk ekspertise med fokus på identifiseringen av moralske eksperter. I artikkelen argumenterer jeg for moralske eksperter kan identifiseres som eksperter innenfor ulike etiske doktriner og at dette gjør det mulig å oppnevne slike eksperter til etikkomiteer, sammen med eksperter på andre områder. Den fjerde artikkelen spør hva den politiske konteksten betyr for etikkomiteers arbeid. Den politiske standarden, som utarbeides i artikkelen, tar utgangpunkt i at vi må forstå hva den politiske konteksten etikkomiteer arbeider innenfor betyr for deres arbeid for å gjøre en helhetlig evaluering. Dette involverer å bidra til den epistemiske, demokratiske og etiske funksjonen til offentlig diskurs. Hva dette impliserer for etikkomiteers arbeid blir så diskutert. Det argumenteres for at det innebærer å seriøst vurdere et mangfold av standpunkter inkludert de som har en klar forankring i et bestemt livssyn. Anbefalinger som komiteen gir bør være begrunnet med tanke på at de skal rettferdiggjøres ovenfor borgere med ulike oppfatninger. Avhandlingen bidrar til å klargjøre hvilken rolle etikkomiteer bør spille i demokratier. Analysen av uenigheten når det gjelder etikkomiteers rolle kan være et fruktbart utgangspunkt for videre diskusjon om etikkomiteer, i tillegg til å kunne være et rammeverk for analyse av slike komiteer. Intervjustudien, med medlemmer av Bioteknologirådet, er også et viktig bidrag til litteraturen i og med at det finnes relativt få case-studier av etikkomiteer.publishedVersio

Invisible Church? : an ecclesiological idea reconsidered

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Critics Float Legal Theories To Challenge Pruitt\u27s Science Advisor Policy

House Democrats and a Columbia University law professor are detailing possible legal arguments that could be used to challenge Administrator Scott Pruitt’s controversial new directive barring scientists who are receiving an EPA research grant from serving on one of its scientific advisory committees

A multi-resolution, non-parametric, Bayesian framework for identification of spatially-varying model parameters

This paper proposes a hierarchical, multi-resolution framework for the identification of model parameters and their spatially variability from noisy measurements of the response or output. Such parameters are frequently encountered in PDE-based models and correspond to quantities such as density or pressure fields, elasto-plastic moduli and internal variables in solid mechanics, conductivity fields in heat diffusion problems, permeability fields in fluid flow through porous media etc. The proposed model has all the advantages of traditional Bayesian formulations such as the ability to produce measures of confidence for the inferences made and providing not only predictive estimates but also quantitative measures of the predictive uncertainty. In contrast to existing approaches it utilizes a parsimonious, non-parametric formulation that favors sparse representations and whose complexity can be determined from the data. The proposed framework in non-intrusive and makes use of a sequence of forward solvers operating at various resolutions. As a result, inexpensive, coarse solvers are used to identify the most salient features of the unknown field(s) which are subsequently enriched by invoking solvers operating at finer resolutions. This leads to significant computational savings particularly in problems involving computationally demanding forward models but also improvements in accuracy. It is based on a novel, adaptive scheme based on Sequential Monte Carlo sampling which is embarrassingly parallelizable and circumvents issues with slow mixing encountered in Markov Chain Monte Carlo schemes