Eligibility of patients with Staphylococcus aureus bacteraemia for early oral switch

To identify people with low-risk Staphylococcus aureus bacteraemia (SAB), the SABATO investigators screened 5063 people, finding 213 (4·2%) meeting their eligibility criteria1. This low proportion of eligible patients led the authors to question if low-risk SAB is clinically relevant. We aimed to determine the clinical relevance of the SABATO definition of low-risk SAB, and if the trial population was representative of potentially eligible real-world patients. Data was collected retrospectively for 464 consecutive adults with SAB at our institution (Supplementary Figure), approved by the South East Scotland Research Ethics Committee (23/SS/0025). We then applied the SABATO inclusion and exclusion criteria to identify potentially eligible real-world patients.Of the 464 patients in our cohort, 71 (15·3%) would have been potentially eligible for inclusion in the trial. Acquisition of SAB in these patients was mainly nosocomial (35/71, 49·3%). Key cohort characteristics reported by the trial were very similar when comparing trial participants with potentially eligible real-world patients, although the median Charlson Comorbidity Index was lower in the trial cohort (Table). An intravenous catheter was the most common source of SAB in both cohorts, but there was a higher proportion of SAB from an unknown source in the real-world group (p=0·0015). An unknown source is a risk factor for complications2,3 and further evaluation combined with intensive follow-up of early oral switch should be considered in this group.Implanted prosthetic material is a component of the IDSA definition of complicated SAB4 but with certain caveats was not an absolute exclusion criterion in the SABATO trial. Nine potentially eligible real-world patients had prosthetic material in situ (n=4 cardiac devices and n=5 orthopaedic implants). This data was not reported for trial participants but could further increase confidence in applicability of the findings. No laboratory or physiology data from the time of the index blood culture was reported but might have been helpful to quantify disease severity and guide patient selection (Supplementary Table). We suggest this supports standardised collection and reporting of cohort characteristics in SAB trials to improve comparability between studies, which is often complicated by variability in the cohort characteristics reported5.We conclude that the sub-group of low-risk SAB studied in the SABATO trial is clinically relevant and find the similarities between randomised and real-world eligible patients re-assuring. Implementation of SABATO findings should be done cautiously and studied prospectively, especially when applied to patients with SAB of unknown source who were infrequently included in the trial.<br/

Looking for Landmarks: The Role of Expert Review and Bibliometric Analysis in Evaluating Scientific Publication Outputs

To compare expert assessment with bibliometric indicators as tools to assess the quality and importance of scientific research papers.Shortly after their publication in 2005, the quality and importance of a cohort of nearly 700 Wellcome Trust (WT) associated research papers were assessed by expert reviewers; each paper was reviewed by two WT expert reviewers. After 3 years, we compared this initial assessment with other measures of paper impact.Shortly after publication, 62 (9%) of the 687 research papers were determined to describe at least a ‘major addition to knowledge’ –6 were thought to be ‘landmark’ papers. At an aggregate level, after 3 years, there was a strong positive association between expert assessment and impact as measured by number of citations and F1000 rating. However, there were some important exceptions indicating that bibliometric measures may not be sufficient in isolation as measures of research quality and importance, and especially not for assessing single papers or small groups of research publications. expert peer reviews of research paper quality and importance to more quantitative indicators, such as citation analysis would be valuable additions to the field of research assessment and evaluation

Sex and the Cinema: What American Pie Teaches the Young

This paper focuses upon the wildly successful blockbuster American Pie teenpics, especially American Pie 3 – the Wedding. I argue that these films, which are sited so securely within the visual and pedagogical machinery of Hollywood culture, are specifically designed to appeal to teenage male audiences, and to provide lessons in sex and romance. Movies like this are especially important as they are experienced by far more teenagers than, for example, instructional films or other classroom materials; indeed, as Henry Giroux has observed, "teens and youth learn how to define themselves outside of the traditional sites of instruction, such as the home and the school… Learning in the postmodern age is located elsewhere – in popular spheres that shape their identities, through forms of knowledge and desires that appear absent from what is taught in schools" (Giroux, 1997, p.49). In this paper I discuss whether the American Pie series is actually a "new age" effort which, via insubordinate performances of gender, contests the hegemonic field of signification which regulates the production of sex, gender and desire, or whether it is more accurately described as a retrogressive hetero-conservative opus with a veneer of sexual radicalism. In short, I intend to probe whether this filmic vector for sex education is all about the shaping of responsible, caring, vulnerable men, or is it guiding them to become just like their heterosexual, middle-class fathers? And whether, despite its riotous and raunchy advertising, American Pie really dishes up something spicy or something terribly wholesome instead

Effectiveness and Safety of Adalimumab Biosimilar SB5 in IBD:Outcomes in Originator to SB5 Switch, Double Biosimilar Switch and Bio-Naieve SB5 Observational Cohorts

BACKGROUND AND AIMS: Multiple adalimumab [ADA] biosimilars are now approved for use in inflammatory bowel disease [IBD]; however, effectiveness and safety data remain scarce. We aimed to investigate long-term outcomes of the ADA biosimilar SB5 in IBD patients following a switch from the ADA originator [SB5-switch cohort] or after start of SB5 [SB5-start cohort]. METHODS: We performed an observational cohort study in a tertiary IBD referral centre. All IBD patients treated with Humira underwent an elective switch to SB5. We identified all these patients in a biological prescription database that prospectively registered all ADA start and stop dates including brand names. Data on IBD phenotype, C-reactive protein [CRP], drug persistence, ADA drug and antibody levels, and faecal calprotectin were collected. RESULTS: In total, 481 patients were treated with SB5, 256 in the SB5-switch cohort (median follow-up: 13.7 months [IQR 8.6–15.2]) and 225 in the SB5-start cohort [median follow-up: 8.3 months [4.2–12.8]). Of the SB5-switch cohort, 70.8% remained on SB5 beyond 1 year; 90/256 discontinued SB5, mainly due to adverse events [46/90] or secondary loss of response [37/90]. In the SB5-start cohort, 81/225 discontinued SB5, resulting in SB5-drug persistence of 60.3% beyond 1 year. No differences in clinical remission [p = 0.53], CRP [p = 0.80], faecal calprotectin [p = 0.40] and ADA trough levels [p = 0.55] were found between baseline, week 26 and week 52 following switch. Injection site pain was the most frequently reported adverse event. CONCLUSION: Switching from ADA originator to SB5 appeared effective and safe in this study with over 12 months of follow-up

Microscopic self-consistent theory of Josephson junctions including dynamical electron correlations

We formulate a fully self-consistent, microscopic model to study the retardation and correlation effects of the barrier within a Josephson junction. The junction is described by a series of planes, with electronic correlation included through a local self energy for each plane. We calculate current-phase relationships for various junctions, which include non-magnetic impurities in the barrier region, or an interfacial scattering potential. Our results indicate that the linear response of the supercurrent to phase across the barrier region is a good, but not exact indicator of the critical current. Our calculations of the local density of states show the current-carrying Andreev bound states and their energy evolution with the phase difference across the junction. We calculate the figure of merit for a Josephson junction, which is the product of the critical current, Ic, and the normal state resistance, R(N), for junctions with different barrier materials. The normal state resistance is calculated using the Kubo formula, for a system with zero current flow and no superconducting order. Semiclassical calculations would predict that these two quantities are determined by the transmission probabilities of electrons in such a way that the product is constant for a given superconductor at fixed temperature. Our self-consistent solutions for different types of barrier indicate that this is not the case. We suggest some forms of barrier which could increase the Ic.R(N) product, and hence improve the frequency response of a Josephson device.Comment: 46 pages, 21 figure

An Analysis of How Interactive Technology Supports the Appreciation of Traditional Chinese Puppetry: A Review of Case Studies

From the perspective of safeguarding Chinese Cultural Heritage, this paper discusses how to enhance the appreciation of traditional Chinese puppetry through the support of interactive technology. The author analyses extensive, yet current case studies, based on the findings described in the interactive systems for puppetry performances and interactive technology for puppetry appreciation. The author summarises four aspects of how to enhance the appreciation of, and engagement with, traditional Chinese puppetry: (1) maintaining originality is necessary for the design phase; (2) it is crucial to explore how to use interactive technology in order to design a way for adults to appreciate this form of art; (3) it is also necessary to determine ways to support adult audiences in grasping the cultural significance and folk customs of traditional Chinese puppetry; and (4) the study’s further main research goals are to investigate ways to use emotional expressions, digital storytelling and other methods in conjunction with interactive technology to help multi-cultural users comprehend traditional Chinese puppetry

Modeling Statistical Properties of Written Text

Written text is one of the fundamental manifestations of human language, and the study of its universal regularities can give clues about how our brains process information and how we, as a society, organize and share it. Among these regularities, only Zipf's law has been explored in depth. Other basic properties, such as the existence of bursts of rare words in specific documents, have only been studied independently of each other and mainly by descriptive models. As a consequence, there is a lack of understanding of linguistic processes as complex emergent phenomena. Beyond Zipf's law for word frequencies, here we focus on burstiness, Heaps' law describing the sublinear growth of vocabulary size with the length of a document, and the topicality of document collections, which encode correlations within and across documents absent in random null models. We introduce and validate a generative model that explains the simultaneous emergence of all these patterns from simple rules. As a result, we find a connection between the bursty nature of rare words and the topical organization of texts and identify dynamic word ranking and memory across documents as key mechanisms explaining the non trivial organization of written text. Our research can have broad implications and practical applications in computer science, cognitive science and linguistics

Improving the outcome of infants born at <30 weeks' gestation - a randomized controlled trial of preventative care at home

Background: Early developmental interventions to prevent the high rate of neurodevelopmental problems in very preterm children, including cognitive, motor and behavioral impairments, are urgently needed. These interventions should be multi-faceted and include modules for caregivers given their high rates of mental health problems