The global cardiovascular magnetic resonance registry (GCMR) of the society for cardiovascular magnetic resonance (SCMR): its goals, rationale, data infrastructure, and current developments

GCMR received seed funding from SCMR (SCMR_GRANT_001) for the development and maintenance of GCMR websites and database infrastructure

Dynamics of Co-Transcriptional Pre-mRNA Folding Influences the Induction of Dystrophin Exon Skipping by Antisense Oligonucleotides

Antisense oligonucleotides (AONs) mediated exon skipping offers potential therapy for Duchenne muscular dystrophy. However, the identification of effective AON target sites remains unsatisfactory for lack of a precise method to predict their binding accessibility. This study demonstrates the importance of co-transcriptional pre-mRNA folding in determining the accessibility of AON target sites for AON induction of selective exon skipping in DMD. Because transcription and splicing occur in tandem, AONs must bind to their target sites before splicing factors. Furthermore, co-transcriptional pre-mRNA folding forms transient secondary structures, which redistributes accessible binding sites. In our analysis, to approximate transcription elongation, a “window of analysis” that included the entire targeted exon was shifted one nucleotide at a time along the pre-mRNA. Possible co-transcriptional secondary structures were predicted using the sequence in each step of transcriptional analysis. A nucleotide was considered “engaged” if it formed a complementary base pairing in all predicted secondary structures of a particular step. Correlation of frequency and localisation of engaged nucleotides in AON target sites accounted for the performance (efficacy and efficiency) of 94% of 176 previously reported AONs. Four novel insights are inferred: (1) the lowest frequencies of engaged nucleotides are associated with the most efficient AONs; (2) engaged nucleotides at 3′ or 5′ ends of the target site attenuate AON performance more than at other sites; (3) the performance of longer AONs is less attenuated by engaged nucleotides at 3′ or 5′ ends of the target site compared to shorter AONs; (4) engaged nucleotides at 3′ end of a short target site attenuates AON efficiency more than at 5′ end

Schwarzschild spacetime under generalised Gullstrand-Painlev\'e slicing

We investigate a foliation of Schwarzschild spacetime determined by observers freely falling in the radial direction. This is described using a generalisation of Gullstrand-Painlev\'e coordinates which allows for any possible radial velocity. This foliation provides a contrast with the usual static foliation implied by Schwarzschild coordinates. The $3$-dimensional spaces are distinct for the static and falling observers, so the embedding diagrams, spatial measurement, simultaneity, and time at infinity are also distinct, though the $4$-dimensional spacetime is unchanged. Our motivation is conceptual understanding, to counter Newton-like viewpoints. In future work, this alternate foliation may shed light on open questions regarding quantum fields, analogue gravity, entropy, energy, and other quantities. This article is aimed at experienced relativists, whereas a forthcoming series is intended for a general audience of physicists, mathematicians, and philosophers.Comment: 21 pages, 5 figures, to appear as chapter 9 in Cacciatori, G\"uneysu, and Pigola, eds. (c. 2019), Einstein equations: Physical and mathematical aspects of general relativit

Non-invasive detection of coronary inflammation using computed tomography and prediction of residual cardiovascular risk (the CRISP CT study): a post-hoc analysis of prospective outcome

BACKGROUND: Coronary artery inflammation inhibits adipogenesis in adjacent perivascular fat. A novel imaging biomarker—the perivascular fat attenuation index (FAI)—captures coronary inflammation by mapping spatial changes of perivascular fat attenuation on coronary computed tomography angiography (CTA). However, the ability of the perivascular FAI to predict clinical outcomes is unknown. METHODS: In the Cardiovascular RISk Prediction using Computed Tomography (CRISP-CT) study, we did a post-hoc analysis of outcome data gathered prospectively from two independent cohorts of consecutive patients undergoing coronary CTA in Erlangen, Germany (derivation cohort) and Cleveland, OH, USA (validation cohort). Perivascular fat attenuation mapping was done around the three major coronary arteries—the proximal right coronary artery, the left anterior descending artery, and the left circumflex artery. We assessed the prognostic value of perivascular fat attenuation mapping for all-cause and cardiac mortality in Cox regression models, adjusted for age, sex, cardiovascular risk factors, tube voltage, modified Duke coronary artery disease index, and number of coronary CTA-derived high-risk plaque features. FINDINGS: Between 2005 and 2009, 1872 participants in the derivation cohort underwent coronary CTA (median age 62 years [range 17–89]). Between 2008 and 2016, 2040 patients in the validation cohort had coronary CTA (median age 53 years [range 19–87]). Median follow-up was 72 months (range 51–109) in the derivation cohort and 54 months (range 4–105) in the validation cohort. In both cohorts, high perivascular FAI values around the proximal right coronary artery and left anterior descending artery (but not around the left circumflex artery) were predictive of all-cause and cardiac mortality and correlated strongly with each other. Therefore, the perivascular FAI measured around the right coronary artery was used as a representative biomarker of global coronary inflammation (for prediction of cardiac mortality, hazard ratio [HR] 2·15, 95% CI 1·33–3·48; p=0·0017 in the derivation cohort, and 2·06, 1·50–2·83; p<0·0001 in the validation cohort). The optimum cutoff for the perivascular FAI, above which there is a steep increase in cardiac mortality, was ascertained as −70·1 Hounsfield units (HU) or higher in the derivation cohort (HR 9·04, 95% CI 3·35–24·40; p<0·0001 for cardiac mortality; 2·55, 1·65–3·92; p<0·0001 for all-cause mortality). This cutoff was confirmed in the validation cohort (HR 5·62, 95% CI 2·90–10·88; p<0·0001 for cardiac mortality; 3·69, 2·26–6·02; p<0·0001 for all-cause mortality). Perivascular FAI improved risk discrimination in both cohorts, leading to significant reclassification for all-cause and cardiac mortality. Interpretation The perivascular FAI enhances cardiac risk prediction and restratification over and above current state-of-the-art assessment in coronary CTA by providing a quantitative measure of coronary inflammation. High perivascular FAI values (cutoff ≥–70·1 HU) are an indicator of increased cardiac mortality and, therefore, could guide early targeted primary prevention and intensive secondary prevention in patients. FUNDING: British Heart Foundation, and the National Institute of Health Research Oxford Biomedical Research Centre

ART DEMONSTRATES THAT FOOTBALL IS METASTASIZED, AND GIVES IT REFUGE

U ovom se radu problemski analiziraju obilježja nogometa u hit-romanu Alena Bovića Metastaze (2006) te u dvjema kasnijim obradama tog književnog djela – u kazališnoj predstavi Metastaze i istoimenom igranom filmu. Otuda ideja da se ondje zatečen, devijantnim pojavama obilježen nogomet, koji više baš i nema puno dodirnih točaka s igrom koja mu leži u korijenima, nazove metastaziralim. Umjetnička se stvarnost pritom promatra kao korespondentna društvenoj stvarnosti pa se za takvo etiketiranje nogometa prepoznaju razlozi na objema razinama. Na temelju takvog pristupa Metastazama, ali i na osnovi prethodno ponuđenog komparativnog uvida u nogometnu tematiku u nekim drugim književnim, kazališnim i filmskim ostvarenjima u Hrvatskoj i izvan nje, postavlja se teza o umjetnosti kao dokazu metastaziralog nogometa. No, još je izazovnije utvrditi može li umjetnost istodobno poslužiti i kao utočište metastaziralom nogometu tako da se njome revitalizira ponajprije estetska, ali istodobno i etička dimenzija tog sporta. Iz tih pobuda argumentacija u ovome radu uključuje tekstove i autore u širokom rasponu od književne kritike, antropologije igara i sociologije sporta do semiotike, kulturalnih studija i estetike. U ovom se radu problemski analiziraju obilježja nogometa u hit-romanu Alena Bovića Metastaze (2006) te u dvjema kasnijim obradama tog književnog djela – u kazališnoj predstavi Metastaze i istoimenom igranom filmu. Otuda ideja da se ondje zatečen, devijantnim pojavama obilježen nogomet, koji više baš i nema puno dodirnih točaka s igrom koja mu leži u korijenima, nazove metastaziralim. Umjetnička se stvarnost pritom promatra kao korespondentna društvenoj stvarnosti pa se za takvo etiketiranje nogometa prepoznaju razlozi na objema razinama. Na temelju takvog pristupa Metastazama, ali i na osnovi prethodno ponuđenog komparativnog uvida u nogometnu tematiku u nekim drugim književnim, kazališnim i filmskim ostvarenjima u Hrvatskoj i izvan nje, postavlja se teza o umjetnosti kao dokazu metastaziralog nogometa. No, još je izazovnije utvrditi može li umjetnost istodobno poslužiti i kao utočište metastaziralom nogometu tako da se njome revitalizira ponajprije estetska, ali istodobno i etička dimenzija tog sporta. Iz tih pobuda argumentacija u ovome radu uključuje tekstove i autore u širokom rasponu od književne kritike, antropologije igara i sociologije sporta do semiotike, kulturalnih studija i estetike.This article presents an analysis of the characteristics of football as depicted in the bestselling novel Metastaze (Metastases) (2006) by Alen Bović and in its two subsequent adaptations – the play Metastaze (Metastases) directed by Boris Svrtan and the film Metastaze (Metastases) directed by Branko Schmidt. Football as it appears in these three pieces is metastasized: it is deviant and in fact undergoes so many significant changes that it no longer has much in common with the original game. Artistic reality is seen as corresponding to social reality, and reasons for the metastasized nature of football are found on both levels. Based on the proposed analysis of Metastaze and a comparative analysis of descriptions of football in other books, plays and films in Croatia and abroad a hypothesis is put forward whereby art offers evidence as to the metastasized nature of football. A greater challenge still is to establish whether art might, at the same time, provide refuge to the metastasized football, revitalizing its aesthetic and ethical dimension. Given the scope of these claims, the arguments in the article are based on a wide array of texts and authors ranging from literary criticism, anthropology of games and sociology of sport to semiotics, cultural studies and aesthetics

Real-Life Evidence for Tedizolid Phosphate in the Treatment of Cellulitis and Wound Infections: A Case Series

Introduction Tedizolid phosphate 200 mg, once daily for 6 days, has recently been approved for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSIs) in several countries; however, clinical experience in real-life settings is currently limited. Here, we report on the use of tedizolid with an extended treatment duration for complex and severe ABSSSIs in real-world clinical settings. Methods Two patients with cellulitis and two patients with surgical site infection (SSI), aged 26–60 years, were treated with tedizolid phosphate 200 mg, intravenous/oral (IV/PO) or IV only, once daily at four different institutions. Results Two morbidly obese patients had non-necrotizing, non-purulent severe cellulitis, which were complicated by sepsis or systemic inflammatory response syndrome plus myositis. One female patient failed on first-line empiric therapy with IV cefalotin, clindamycin and imipenem (3–4 days), and was switched to IV/PO tedizolid (7 + 5 days). One male patient received IV clindamycin plus IV/PO tedizolid (5 + 5 days), but clindamycin was discontinued on Day 3 due to an adverse event. For both patients, clinical signs and symptoms improved within 72 h, and laboratory results were normalized by Days 7 and 8, respectively. Two other patients (one obese, diabetic female with chronic hepatitis and chronic obstructive pulmonary disease) had complicated SSIs occurring 10 days after hernia repair with mesh or 3 months after spinal fusion surgery with metal implant. First patient with previous methicillin-resistant Staphylococcus aureus (MRSA) bacteremia received a 7-day tedizolid IV course empirically. The second patient with culture-confirmed MRSA infection received a 14-day IV course. Both patients responded within 72 h, and local and systemic signs normalized by end of treatment. There were no reports of thrombocytopenia. Conclusion Tedizolid phosphate 200 mg for 7–14 days was a favored treatment option for patients with severe/complex ABSSSIs, and was effective following previous treatment failure or in late-onset infections