The NorthStar Ambulatory Assessment in Duchenne muscular dystrophy: considerations for the design of clinical trials.

With the emergence of experimental therapies for Duchenne muscular dystrophy (DMD), it is fundamental to understand the natural history of this disorder to properly design clinical trials. The aims of this study were to assess the effects produced on motor function by different DMD genotypes and early initiation of glucocorticoids

An On-Farm experimental philosophy for farmer-centric digital innovation

In this paper, we review learnings gained from early On-Farm Experiments (OFE) conducted in the broad acre Australian grain industry from the 1990s to the present day. Although the initiative was originally centered around the possibilities of new data and analytics in precision agriculture, we discovered that OFEs could represent a platform for engaging farmers around digital technologies and innovation. Insight from interacting closely with farmers and advisors leads us to argue for a change in the ways we approach OFE research. Acknowledging that conditions have changed and drawing from business and social sciences, we suggest that OFE approaches today should develop aspects related to skill development, value generation and value sharing, the social dimension of change, and a renewed focus on farmer-centric research to better bridge industry requirements and scientist inputs

The Art of Adapting Open Educational Resources for Street Law: Copyright the Card Game a Case Study

The Street Law community is well practiced in designing bespoke activities for particular community groups. Starting with a blank canvas can often be the easier forma. How often do we consider inviting our Street Law students to adapt works, games, and materials designed for one purpose or audience (i.e. not Street Law) and transform them into a different format? This paper highlights a case study involving undergraduate law students adapting an openly licensed card game originally designed for use with academic librarians, and using it as a tool to raise awareness with sixth form students about the laws and issues of copyright

Arctic sea surface height variability and change from satellite radar altimetry and GRACE, 2003-2014

Arctic sea surface height (SSH) is poorly observed by radar altimeters due to the poor coverage of the polar oceans provided by conventional altimeter missions and because large areas are perpetually covered by sea ice, requiring specialized data processing. We utilize SSH estimates from both the ice-covered and ice-free ocean to present monthly estimates of Arctic Dynamic Ocean Topography (DOT) from radar altimetry south of 81.5°N and combine this with GRACE ocean mass to estimate steric height. Our SSH and steric height estimates show good agreement with tide gauge records and geopotential height derived from Ice-Tethered Profilers. The large seasonal cycle of Arctic SSH (amplitude ∼5 cm) is dominated by seasonal steric height variation associated with seasonal freshwater fluxes, and peaks in October–November. Overall, the annual mean steric height increased by 2.2 ± 1.4 cm between 2003 and 2012 before falling to circa 2003 levels between 2012 and 2014 due to large reductions on the Siberian shelf seas. The total secular change in SSH between 2003 and 2014 is then dominated by a 2.1 ± 0.7 cm increase in ocean mass. We estimate that by 2010, the Beaufort Gyre had accumulated 4600 km3 of freshwater relative to the 2003–2006 mean. Doming of Arctic DOT in the Beaufort Sea is revealed by Empirical Orthogonal Function analysis to be concurrent with regional reductions in the Siberian Arctic. We estimate that the Siberian shelf seas lost ∼180 km3 of freshwater between 2003 and 2014, associated with an increase in annual mean salinity of 0.15 psu yr−1. Finally, ocean storage flux estimates from altimetry agree well with high-resolution model results, demonstrating the potential for altimetry to elucidate the Arctic hydrological cycle

A Note on the Equality of Algebraic and Geometric D-Brane Charges in WZW Models

The algebraic definition of charges for symmetry-preserving D-branes in Wess-Zumino-Witten models is shown to coincide with the geometric definition, for all simple Lie groups. The charge group for such branes is computed from the ambiguities inherent in the geometric definition.Comment: 12 pages, fixed typos, added references and a couple of remark

Cohort study of intervened functionally univentricular heart in England and Wales (2000-2018)

Objective: Given the paucity of long-term outcome data for complex congenital heart disease (CHD), we aimed to describe the treatment pathways and survival for patients who started interventions for functionally univentricular heart (FUH) conditions, excluding hypoplastic left heart syndrome. // Methods: We performed a retrospective cohort study using all procedure records from the National Congenital Heart Diseases Audit for children born in 2000–2018. The primary outcome was mortality, ascertained from the Office for National Statistics in 2020. // Results: Of 53 615 patients, 1557 had FUH: 55.9% were boys and 67.4% were of White ethnic groups. The largest diagnostic categories were tricuspid atresia (28.9%), double inlet left ventricle (21.0%) and unbalanced atrioventricular septal defect (AVSD) (15.2%). The ages at staged surgery were: initial palliation 11.5 (IQR 5.5–43.5) days, cavopulmonary shunt 9.2 (IQR 6.0–17.1) months and Fontan 56.2 (IQR 45.5–70.3) months. The median follow-up time was 10.8 (IQR 7.0–14.9) years and the 1, 5 and 10-year survival rates after initial palliation were 83.6% (95% CI 81.7% to 85.4%), 79.4% (95% CI 77.3% to 81.4%) and 77.2% (95% CI 75.0% to 79.2%), respectively. Higher hazards were present for unbalanced AVSD HR 2.75 (95% CI 1.82 to 4.17), atrial isomerism HR 1.75 (95% CI 1.14 to 2.70) and low weight HR 1.65 (95% CI 1.13 to 2.41), critical illness HR 2.30 (95% CI 1.67 to 3.18) or acquired comorbidities HR 2.71 (95% CI 1.82 to 4.04) at initial palliation. // Conclusion: Although treatment pathways for FUH are complex and variable, nearly 8 out of 10 children survived to 10 years. Longer-term analyses of outcome based on diagnosis (rather than procedure) can inform parents, patients and clinicians, driving practice improvements for complex CHD

Cardiorespiratory Progression Over 5 Years and Role of Corticosteroids in Duchenne Muscular Dystrophy: A Single-Site Retrospective Longitudinal Study

Background: Duchenne muscular dystrophy (DMD) boys treated with corticosteroids (CS) have prolonged survival and respiratory function when compared to CS-naïve. /\ud Research question: The differential impact of frequently used corticosteroids and their regimens on long-term (>5 years) cardiorespiratory progression in DMD children is unknown. / Study Design and Methods: Retrospective longitudinal study including DMD children followed at Dubowitz Neuromuscular Centre (Great Ormond Street Hospital London), May 2000-June 2017. Patients enrolled in any interventional clinical trials were excluded. We collected patients’ anthropometrics, respiratory (forced vital capacity, FVC% predicted and absolute FVC, non-invasive ventilation requirement, NIV) and cardiac (left ventricular shortening function, LVFS%) function. CS-naïve patients had never received CS. CS-treated took either deflazacort or prednisolone, daily or intermittently (10 days on/10 days off) for >1 month. Average longitudinal models were fitted for yearly respiratory (FVC%P) and cardiac (LVFS%) progression. A time-to-event analysis to FVC%P<50%, NIV start and cardiomyopathy (LVFS<28%) was performed in CS-treated (daily and intermittent) vs CS-naïve patients. / Results: There were 270 patients, mean age at baseline 6.2 (±2.3) years. Median follow-up 5.6 (± 3.5) years. At baseline, 263 were ambulant. Sixty-six were CS-daily, 182 CS-intermittent >60% treatment, 22 CS-naïve. Yearly FVC%P declined similarly from 9 years (5.9% and 6.9%/year, p=0.27) in CS-daily and CS-intermittent. CS-daily declined from a higher FVC%P than CS-intermittent (p2 years later than CS-treated. LVFS% declined by 0.53%/year in CS-treated irrespective of CS regimen, significantly slower (p<0.01) than CS-naïve progressing by 1.17%/year. Age at cardiomyopathy was 16.6 in CS-treated (p<0.05) irrespective of regimen and 13.9 years in CS-naïve. / Interpretation: CS irrespective of their regimen significantly improved respiratory function and delayed NIV requirement and cardiomyopathy

Cross-sectional study of a UK cohort of neonatal vein of Galen malformation

Objective: Describe the course and outcomes in a UK national cohort of neonates with vein of Galen malformation (VGM) identified before 28 days of life. // Methods: Neonates with angiographically confirmed vein of Galen malformation presenting to one of the two UK treatment centres (2006‐2016) were included; those surviving were invited to participate in neurocognitive assessment. Results in each domain were dichotomised into “good” and “poor” categories. Cross‐sectional and angiographic brain imaging studies were systematically interrogated. Logistic regression was used to explore potential outcome predictors. // Results: Of 85 children with neonatal vein of Galen malformation, 51 had survived. Thirty‐four participated in neurocognitive assessment. Outcomes were approximately evenly split between “good” and “poor” categories across all domains, namely neurological status, general cognition, neuromotor skills, adaptive behaviour, and emotional and behavioural development. Important predictors of poor cognitive outcome were initial Bicetre score </=12 and presence of brain injury, specifically white matter injury, on initial imaging; in multivariable analysis only Bicetre score </=12 remained significant. // Interpretation: Despite modern supportive and endovascular treatment, over a third of unselected newborns with vein of Galen malformation did not survive. Outcome was good in around half of survivors. The importance of white matter injury suggests that abnormalities of venous, as well as arterial, circulation are important in pathophysiology of brain injury

Geometric Exponents, SLE and Logarithmic Minimal Models

In statistical mechanics, observables are usually related to local degrees of freedom such as the Q < 4 distinct states of the Q-state Potts models or the heights of the restricted solid-on-solid models. In the continuum scaling limit, these models are described by rational conformal field theories, namely the minimal models M(p,p') for suitable p, p'. More generally, as in stochastic Loewner evolution (SLE_kappa), one can consider observables related to nonlocal degrees of freedom such as paths or boundaries of clusters. This leads to fractal dimensions or geometric exponents related to values of conformal dimensions not found among the finite sets of values allowed by the rational minimal models. Working in the context of a loop gas with loop fugacity beta = -2 cos(4 pi/kappa), we use Monte Carlo simulations to measure the fractal dimensions of various geometric objects such as paths and the generalizations of cluster mass, cluster hull, external perimeter and red bonds. Specializing to the case where the SLE parameter kappa = 4p'/p is rational with p < p', we argue that the geometric exponents are related to conformal dimensions found in the infinitely extended Kac tables of the logarithmic minimal models LM(p,p'). These theories describe lattice systems with nonlocal degrees of freedom. We present results for critical dense polymers LM(1,2), critical percolation LM(2,3), the logarithmic Ising model LM(3,4), the logarithmic tricritical Ising model LM(4,5) as well as LM(3,5). Our results are compared with rigourous results from SLE_kappa, with predictions from theoretical physics and with other numerical experiments. Throughout, we emphasize the relationships between SLE_kappa, geometric exponents and the conformal dimensions of the underlying CFTs.Comment: Added reference