What is the best treatment for Osgood-Schlatter disease?

Osgood-Schlatter disease is a common cause of pain and tenderness at the tibial tuberosity in active adolescents. It is typically a self-limited condition that waxes and wanes, but which often takes months to years to resolve entirely. It is best managed with conservative measures (activity modification, ice, anti- inflammatory agents) and time (strength of recommendation [SOR]: B, several case series and retrospective studies). In chronic cases that are refractory to conservative treatment, surgical intervention yields good results, particularly for patients with bony or cartilaginous ossicles. Excision of these ossicles produces resolution of symptoms and return to activity in several weeks (SOR: C, several case series). Corticosteroid injections are not recommended (SOR: C, case reports and expert opinion)

Do antioxidants (vitamins C, E) improve outcomes in patients with coronary artery disease?

Antioxidant supplements of vitamins E and C do not reduce cardiovascular death in people with coronary artery disease. Vitamin E supplementation, in a variety of doses, does not decrease the incidence of cardiovascular or all-cause mortality (grade of recommendation: A, 4 high quality randomized controlled trials [RCTs]). There is no evidence that vitamin C decreases mortality in patients at risk for coronary disease (grade of recommendation: A, meta-analysis of 3 small RCTs). Combination antioxidant regimens (Vitamins E, C, and betacarotene) seem safe, but do not decrease mortality or incidence of major coronary and vascular events (grade recommendation: A, 1 high-quality RCT)

The diffusion of disruptive technologies

We identify novel technologies using textual analysis of patents, job postings, and earnings calls. Our approach enables us to identify and document the diffusion of 29 disruptive technologies across firms and labor markets in the U.S. Five stylized facts emerge from our data. First, the locations where technologies are developed that later disrupt businesses are geographically highly concentrated, even more so than overall patenting. Second, as the technologies mature and the number of new jobs related to them grows, they gradually spread across space. While initial hiring is concentrated in high-skilled jobs, over time the mean skill level in new positions associated with the technologies declines, broadening the types of jobs that adopt a given technology. At the same time, the geographic diffusion of low-skilled positions is significantly faster than higher-skilled ones, so that the locations where initial discoveries were made retain their leading positions among high-paying positions for decades. Finally, these technology hubs are more likely to arise in areas with universities and high skilled labor pools

Determining absolute protein numbers by quantitative fluorescence microscopy

Biological questions are increasingly being addressed using a wide range of quantitative analytical tools to examine protein complex composition. Knowledge of the absolute number of proteins present provides insights into organization, function, and maintenance and is used in mathematical modeling of complex cellular dynamics. In this chapter, we outline and describe three microscopy-based methods for determining absolute protein numbers—fluorescence correlation spectroscopy, stepwise photobleaching, and ratiometric comparison of fluorescence intensity to known standards. In addition, we discuss the various fluorescently labeled proteins that have been used as standards for both stepwise photobleaching and ratiometric comparison analysis. A detailed procedure for determining absolute protein number by ratiometric comparison is outlined in the second half of this chapter. Counting proteins by quantitative microscopy is a relatively simple yet very powerful analytical tool that will increase our understanding of protein complex composition

Entropy gives rise to topologically associating domains

We investigate chromosome organization within the nucleus using polymer models whose formulation is closely guided by experiments in live yeast cells. We employ bead-spring chromosome models together with loop formation within the chains and the presence of nuclear bodies to quantify the extent to which these mechanisms shape the topological landscape in the interphase nucleus. By investigating the genome as a dynamical system, we show that domains of high chromosomal interactions can arise solely from the polymeric nature of the chromosome arms due to entropic interactions and nuclear confinement. In this view, the role of bio-chemical related processes is to modulate and extend the duration of the interacting domains

Transient crosslinking kinetics optimize gene cluster interactions

Our understanding of how chromosomes structurally organize and dynamically interact has been revolutionized through the lens of long-chain polymer physics. Major protein contributors to chromosome structure and dynamics are condensin and cohesin that stochastically generate loops within and between chains, and entrap proximal strands of sister chromatids. In this paper, we explore the ability of transient, protein-mediated, gene-gene crosslinks to induce clusters of genes, thereby dynamic architecture, within the highly repeated ribosomal DNA that comprises the nucleolus of budding yeast. We implement three approaches: live cell microscopy; computational modeling of the full genome during G1 in budding yeast, exploring four decades of timescales for transient crosslinks between 5k bp domains in the nucleolus on Chromosome XII; and, temporal network models with automated community detection algorithms applied to the full range of 4D modeling datasets. The data analysis tools detect and track gene clusters, their size, number, persistence time, and their plasticity. Of biological significance, our analysis reveals an optimal mean crosslink lifetime that promotes pairwise and cluster gene interactions through "flexible" clustering. In this state, large gene clusters self-assemble yet frequently interact, marked by gene exchanges between clusters, which in turn maximizes global gene interactions in the nucleolus. This regime stands between two limiting cases each with far less global gene interactions: with shorter crosslink lifetimes, "rigid" clustering emerges with clusters that interact infrequently; with longer crosslink lifetimes, there is a dissolution of clusters. These observations are compared with imaging experiments on a normal yeast strain and two condensin-modified mutant cell strains, applying the same image analysis pipeline to the experimental and simulated datasets

ChromoShake: a chromosome dynamics simulator reveals that chromatin loops stiffen centromeric chromatin

A novel chromosome simulator recapitulates the position and dynamics of centromeric chromatin in a model composed of cross-linked intramolecular loops. Simulations reveal that chromatin loops stiffen the centromere and dictate the distribution of pericentric cohesin.ChromoShake is a three-dimensional simulator designed to find the thermodynamically favored states for given chromosome geometries. The simulator has been applied to a geometric model based on experimentally determined positions and fluctuations of DNA and the distribution of cohesin and condensin in the budding yeast centromere. Simulations of chromatin in differing initial configurations reveal novel principles for understanding the structure and function of a eukaryotic centromere. The entropic position of DNA loops mirrors their experimental position, consistent with their radial displacement from the spindle axis. The barrel-like distribution of cohesin complexes surrounding the central spindle in metaphase is a consequence of the size of the DNA loops within the pericentromere to which cohesin is bound. Linkage between DNA loops of different centromeres is requisite to recapitulate experimentally determined correlations in DNA motion. The consequences of radial loops and cohesin and condensin binding are to stiffen the DNA along the spindle axis, imparting an active function to the centromere in mitosis

Creative Radar 2021: the impact of COVID-19 on the UK's creative industries

This report provides new evidence on the impact of the COVID-19 pandemic on businesses in the creative industries. Following on from the Creative Radar survey data, which collected responses from 976 firms in January-March 2020 just before the first lockdown, we interviewed 417 companies that consented to be re-contacted to understand how they had been impacted by the pandemic in April and May 2021. Our key findings are: • Only 4 per cent of the 675 companies we were able to contact had definitely closed or appeared to be no longer trading. The companies in our sample appear to have survived the crisis by furloughing employees and reducing the number of freelancers they worked with. •The impact of the pandemic was very uneven. The Music & performing arts, Film & TV and Publishing businesses in our sample were particularly affected, in line with recent DCMS estimates. But some businesses thrived, with 18 per cent of businesses hiring more employees during the pandemic. These thriving companies were found across all creative sub-sectors. •At the firm level we see that far from becoming redundant, freelancers have become even more vital to businesses that had been making greater use of them prior to the pandemic. Freelancers were important for those businesses that introduced new products as a result of the pandemic. •At the firm level we did not see substantial regional and national differences in the impact of pandemic. The impacts of the pandemic appeared to be relatively evenly spread across the UK. •Businesses in the UK’s creative clusters saw reduced turnover outside their immediate regions (from the rest of the UK and from overseas) but local and regional business appeared to keep them operating. •The creative microclusters that are located outside of the major creative clusters, were more likely to have added new employees. In the past year they increased their sales to the rest of UK, rather than focusing only on local markets. •Companies across the UK kept investing in their businesses through the pandemic, with 66 per cent of businesses increasing investments in R&D, design, marketing, training or IT. Companies in microclusters were more likely to have increased investment in R&D. •More than 25 per cent of the companies in our sample changed or downsized office space during the pandemic. Companies in London were particularly likely to have downsized. •The companies in our sample have substantial investment needs, with 78 per cent requiring further investment but 45 per cent of those not having the resources for those to invest. In particular, companies wanting to invest in R&D and design are more likely to export but also more likely to view access to finance as a barrier to growth