Bandlimited approximations to the truncated Gaussian and applications

In this paper we extend the theory of optimal approximations of functions $f: \R \to \R$ in the $L^1(\R)$-metric by entire functions of prescribed exponential type (bandlimited functions). We solve this problem for the truncated and the odd Gaussians using explicit integral representations and fine properties of truncated theta functions obtained via the maximum principle for the heat operator. As applications, we recover most of the previously known examples in the literature and further extend the class of truncated and odd functions for which this extremal problem can be solved, by integration on the free parameter and the use of tempered distribution arguments. This is the counterpart of the work \cite{CLV}, where the case of even functions is treated.Comment: to appear in Const. Appro

Highly porous scaffolds of PEDOT:PSS for bone tissue engineering.

UNLABELLED: Conjugated polymers have been increasingly considered for the design of conductive materials in the field of regenerative medicine. However, optimal scaffold properties addressing the complexity of the desired tissue still need to be developed. The focus of this study lies in the development and evaluation of a conductive scaffold for bone tissue engineering. In this study PEDOT:PSS scaffolds were designed and evaluated in vitro using MC3T3-E1 osteogenic precursor cells, and the cells were assessed for distinct differentiation stages and the expression of an osteogenic phenotype. Ice-templated PEDOT:PSS scaffolds presented high pore interconnectivity with a median pore diameter of 53.6±5.9µm and a total pore surface area of 7.72±1.7m2·g-1. The electrical conductivity, based on I-V curves, was measured to be 140µS·cm-1 with a reduced, but stable conductivity of 6.1µS·cm-1 after 28days in cell culture media. MC3T3-E1 gene expression levels of ALPL, COL1A1 and RUNX2 were significantly enhanced after 4weeks, in line with increased extracellular matrix mineralisation, and osteocalcin deposition. These results demonstrate that a porous material, based purely on PEDOT:PSS, is suitable as a scaffold for bone tissue engineering and thus represents a promising candidate for regenerative medicine. STATEMENT OF SIGNIFICANCE: Tissue engineering approaches have been increasingly considered for the repair of non-union fractions, craniofacial reconstruction or large bone defect replacements. The design of complex biomaterials and successful engineering of 3-dimensional tissue constructs is of paramount importance to meet this clinical need. Conductive scaffolds, based on conjugated polymers, present interesting candidates to address the piezoelectric properties of bone tissue and to induce enhanced osteogenesis upon implantation. However, conductive scaffolds have not been investigated in vitro in great measure. To this end, we have developed a highly porous, electrically conductive scaffold based on PEDOT:PSS, and provide evidence that this purely synthetic material is a promising candidate for bone tissue engineering

The NY-Ålesund TurbulencE Fiber Optic eXperiment (NYTEFOX): investigating the Arctic boundary layer, Svalbard

The NY-Ålesund TurbulencE Fiber Optic eXperiment (NYTEFOX) was a field experiment at the Ny-Ålesund Arctic site (78.9◦ N, 11.9◦ E) and yielded a unique meteorological data set. These data describe the distribution of heat, airflows, and exchange in the Arctic boundary layer for a period of 14 d from 26 February to 10 March 2020. NYTEFOX is the first field experiment to investigate the heterogeneity of airflow and its transport of temperature, wind, and kinetic energy in the Arctic environment using the fiber-optic distributed sensing (FODS) technique for horizontal and vertical observations. FODS air temperature and wind speed were observed at a spatial resolution of 0.127 m and a temporal resolution of 9 s along a 700 m horizontal array at 1 m above ground level (a.g.l.) and along three 7 m vertical profiles. Ancillary data were collected from three sonic anemometers and an acoustic profiler (minisodar; sodar is an acronym for “sound detection and ranging”) yielding turbulent flow statistics and vertical profiles in the lowest 300 m a.g.l., respectively. The observations from this field campaign are publicly available on Zenodo (https://doi.org/10.5281/zenodo.4756836, Huss et al., 2021) and supplement the meteorological data set operationally collected by the Baseline Surface Radiation Network (BSRN) at Ny-Ålesund, Svalbard

Cobalt containing glass fibres and their synergistic effect on the HIF-1 pathway for wound healing applications

Introduction and Methods: Chronic wounds are a major healthcare problem, but their healing may be improved by developing biomaterials which can stimulate angiogenesis, e.g. by activating the Hypoxia Inducible Factor (HIF) pathway. Here, novel glass fibres were produced by laser spinning. The hypothesis was that silicate glass fibres that deliver cobalt ions will activate the HIF pathway and promote the expression of angiogenic genes. The glass composition was designed to biodegrade and release ions, but not form a hydroxyapatite layer in body fluid. Results and Discussion: Dissolution studies demonstrated that hydroxyapatite did not form. When keratinocyte cells were exposed to conditioned media from the cobalt-containing glass fibres, significantly higher amounts of HIF-1α and Vascular Endothelial Growth Factor (VEGF) were measured compared to when the cells were exposed to media with equivalent amounts of cobalt chloride. This was attributed to a synergistic effect of the combination of cobalt and other therapeutic ions released from the glass. The effect was also much greater than the sum of HIF-1α and VEGF expression when the cells were cultured with cobalt ions and with dissolution products from the Co-free glass, and was proven to not be due to a rise in pH. The ability of the glass fibres to activate the HIF-1 pathway and promote VEGF expression shows the potential for their use in chronic wound dressings

Antimicrobial Footprints, Fairness, and Collective Harm

This chapter explores the question of whether or not individual agents are under a moral obligation to reduce their ‘antimicrobial footprint’. An agent’s antimicrobial footprint measures the extent to which her actions are causally linked to the use of antibiotics. As such, it is not necessarily a measure of her contribution to antimicrobial resistance. Talking about people’s antimicrobial footprint in a way we talk about our carbon footprint may be helpful for drawing attention to the global effects of individual behaviour and for highlighting that our choices can collectively make a real difference. But can we be morally obligated to make a contribution to resolving a collective action problem when our individual contributions by themselves make no discernible difference? I will focus on two lines of argument in favour of such obligations: whether a failure to reduce one’s antimicrobial footprint is unfair and whether it constitutes wrongdoing because it is harmful. I conclude by suggesting that the argument from collective harm is ultimately more successful

Chapter 9 Moral Responsibility and the Justification of Policies to Preserve Antimicrobial Effectiveness

Restrictive policies that limit antimicrobial consumption, including therapeutically justified use, might be necessary to tackle the problem of antimicrobial resistance. We argue that such policies would be ethically justified when forgoing antimicrobials constitutes a form of easy rescue for an individual. These are cases of mild and self-limiting infections in otherwise healthy patients whose overall health is not significantly compromised by the infection. In such cases, restrictive policies would be ethically justified because they would coerce individuals into fulfilling a moral obligation they independently have. However, to ensure that such justification is the strongest possible, states also have the responsibility to ensure that forgoing antimicrobials is as easy as possible for patients by implementing adequate compensation measures

Crystalline iron oxides stimulate methanogenic benzoate degradation in marine sediment- derived enrichment cultures

Elevated dissolved iron concentrations in the methanic zone are typical geochemical signatures of rapidly accumulating marine sediments. These sediments are often characterized by co-burial of iron oxides with recalcitrant aromatic organic matter of terrigenous origin. Thus far, iron oxides are predicted to either impede organic matter degradation, aiding its preservation, or identified to enhance organic carbon oxidation via direct electron transfer. Here, we investigated the effect of various iron oxide phases with differing crystallinity (magnetite, hematite, and lepidocrocite) during microbial degradation of the aromatic model compound benzoate in methanic sediments. In slurry incubations with magnetite or hematite, concurrent iron reduction, and methanogenesis were stimulated during accelerated benzoate degradation with methanogenesis as the dominant electron sink. In contrast, with lepidocrocite, benzoate degradation, and methanogenesis were inhibited. These observations were reproducible in sediment-free enrichments, even after five successive transfers. Genes involved in the complete degradation of benzoate were identified in multiple metagenome assembled genomes. Four previously unknown benzoate degraders of the genera Thermincola (Peptococcaceae, Firmicutes), Dethiobacter (Syntrophomonadaceae, Firmicutes), Deltaproteobacteria bacteria SG8_13 (Desulfosarcinaceae, Deltaproteobacteria), and Melioribacter (Melioribacteraceae, Chlorobi) were identified from the marine sediment-derived enrichments. Scanning electron microscopy (SEM) and catalyzed reporter deposition fluorescence in situ hybridization (CARD-FISH) images showed the ability of microorganisms to colonize and concurrently reduce magnetite likely stimulated by the observed methanogenic benzoate degradation. These findings explain the possible contribution of organoclastic reduction of iron oxides to the elevated dissolved Fe2+ pool typically observed in methanic zones of rapidly accumulating coastal and continental margin sediments

Extent of non-publication in cohorts of studies approved by research ethics committees or included in trial registries

Background: The synthesis of published research in systematic reviews is essential when providing evidence to inform clinical and health policy decisionmaking. However, the validity of systematic reviews is threatened if journal publications represent a biased selection of all studies that have been conducted (dissemination bias). To investigate the extent of dissemination bias we conducted a systematic review that determined the proportion of studies published as peerreviewed journal articles and investigated factors associated with full publication in cohorts of studies (i) approved by research ethics committees (RECs) or (ii) included in trial registries. Copyright:Methods and Findings: Four bibliographic databases were searched for methodological research projects (MRPs) without limitations for publication year, language or study location. The searches were supplemented by handsearching the references of included MRPs. We estimated the proportion of studies published using prediction intervals (PI) and a random effects meta-analysis. Pooled odds ratios (OR) were used to express associations between study characteristics and journal publication. Seventeen MRPs (23 publications) evaluated cohorts of studies approved by RECs; the proportion of published studies had a PI between 22% and 72% and the weighted pooled proportion when combining estimates would be 46.2% (95% CI 40.2%-52.4%, I2594.4%). Twenty-two MRPs (22 publications) evaluated cohorts of studies included in trial registries; the PI of the proportion published ranged from 13% to 90% and the weighted pooled proportion would be 54.2% (95% CI 42.0%-65.9%, I2598.9%). REC-approved studies with statistically significant results (compared with those without statistically significant results) were more likely to be published (pooled OR 2.8; 95% CI 2.2-3.5). Phase-III trials were also more likely to be published than phase II trials (pooled OR 2.0; 95% CI 1.6- 2.5). The probability of publication within two years after study completion ranged from 7% to 30%.Conclusions: A substantial part of the studies approved by RECs or included in trial registries remains unpublished. Due to the large heterogeneity a prediction of the publication probability for a future study is very uncertain. Non-publication of research is not a random process, e.g., it is associated with the direction of study findings. Our findings suggest that the dissemination of research findings is biased

Mapping the decision pathways of acute infection management in secondary care among UK medical physicians: a qualitative study.

BACKGROUND: The inappropriate use of antimicrobials drives antimicrobial resistance. We conducted a study to map physician decision-making processes for acute infection management in secondary care to identify potential targets for quality improvement interventions. METHODS: Physicians newly qualified to consultant level participated in semi-structured interviews. Interviews were audio recorded and transcribed verbatim for analysis using NVIVO11.0 software. Grounded theory methodology was applied. Analytical categories were created using constant comparison approach to the data and participants were recruited to the study until thematic saturation was reached. RESULTS: Twenty physicians were interviewed. The decision pathway for the management of acute infections follows a Bayesian-like step-wise approach, with information processed and systematically added to prior assumptions to guide management. The main emerging themes identified as determinants of the decision-making of individual physicians were (1) perceptions of providing 'optimal' care for the patient with infection by providing rapid and often intravenous therapy; (2) perceptions that stopping/de-escalating therapy was a senior doctor decision with junior trainees not expected to contribute; and (3) expectation of interactions with local guidelines and microbiology service advice. Feedback on review of junior doctor prescribing decisions was often lacking, causing frustration and confusion on appropriate practice within this cohort. CONCLUSION: Interventions to improve infection management must incorporate mechanisms to promote distribution of responsibility for decisions made. The disparity between expectations of prescribers to start but not review/stop therapy must be urgently addressed with mechanisms to improve communication and feedback to junior prescribers to facilitate their continued development as prudent antimicrobial prescribers

Optimizing design of research to evaluate antibiotic stewardship interventions: consensus recommendations of a multinational working group.

BACKGROUND: Antimicrobial stewardship interventions and programmes aim to ensure effective treatment while minimizing antimicrobial-associated harms including resistance. Practice in this vital area is undermined by the poor quality of research addressing both what specific antimicrobial use interventions are effective and how antimicrobial use improvement strategies can be implemented into practice. In 2016 we established a working party to identify the key design features that limit translation of existing research into practice and then to make recommendations for how future studies in this field should be optimally designed. The first part of this work has been published as a systematic review. Here we present the working group's final recommendations. METHODS: An international working group for design of antimicrobial stewardship intervention evaluations was convened in response to the fourth call for leading expert network proposals by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR). The group comprised clinical and academic specialists in antimicrobial stewardship and clinical trial design from six European countries. Group members completed a structured questionnaire to establish the scope of work and key issues to develop ahead of a first face-to-face meeting that (a) identified the need for a comprehensive systematic review of study designs in the literature and (b) prioritized key areas where research design considerations restrict translation of findings into practice. The working group's initial outputs were reviewed by independent advisors and additional expertise was sought in specific clinical areas. At a second face-to-face meeting the working group developed a theoretical framework and specific recommendations to support optimal study design. These were finalized by the working group co-ordinators and agreed by all working group members. RESULTS: We propose a theoretical framework in which consideration of the intervention rationale the intervention setting, intervention features and the intervention aims inform selection and prioritization of outcome measures, whether the research sets out to determine superiority or non-inferiority of the intervention measured by its primary outcome(s), the most appropriate study design (e.g. experimental or quasi- experimental) and the detailed design features. We make 18 specific recommendation in three domains: outcomes, objectives and study design. CONCLUSIONS: Researchers, funders and practitioners will be able to draw on our recommendations to most efficiently evaluate antimicrobial stewardship interventions