The effects of scaffold architecture and fibrin gel addition on tendon cell phenotype.

This is the preprint version. The final version is available from Springer via http://dx.doi.org/10.1007/s10856-014-5349-3Development of tissue engineering scaffolds relies on careful selection of pore architecture and chemistry of the cellular environment. Repair of skeletal soft tissue, such as tendon, is particularly challenging, since these tissues have a relatively poor healing response. When removed from their native environment, tendon cells (tenocytes) lose their characteristic morphology and the expression of phenotypic markers. To stimulate tendon cells to recreate a healthy extracellular matrix, both architectural cues and fibrin gels have been used in the past, however, their relative effects have not been studied systematically. Within this study, a combination of collagen scaffold architecture, axial and isotropic, and fibrin gel addition was assessed, using ovine tendon-derived cells to determine the optimal strategy for controlling the proliferation and protein expression. Scaffold architecture and fibrin gel addition influenced tendon cell behavior independently in vitro. Addition of fibrin gel within a scaffold doubled cell number and increased matrix production for all architectures studied. However, scaffold architecture dictated the type of matrix produced by cells, regardless of fibrin addition. Axial scaffolds, mimicking native tendon, promoted a mature matrix, with increased tenomodulin, a marker for mature tendon cells, and decreased scleraxis, an early transcription factor for connective tissue. This study demonstrated that both architectural cues and fibrin gel addition alter cell behavior and that the combination of these signals could improve clinical performance of current tissue engineering constructs

Scaffold architecture and fibrin gels promote meniscal cell proliferation

Stability of the knee relies on the meniscus, a complex connective tissue with poor healing ability. Current meniscal tissue engineering is inadequate, as the signals for increasing meniscal cell proliferation have not been established. In this study, collagen scaffold structure, isotropic or aligned, and fibrin gel addition were tested. Metabolic activity was promoted by fibrin addition. Cellular proliferation, however, was significantly increased by both aligned architectures and fibrin addition. None of the constructs impaired collagen type I production or triggered adverse inflammatory responses. It was demonstrated that both fibrin gel addition and optimized scaffold architecture effectively promote meniscal cell proliferation.The authors gratefully acknowledge the financial support of the Gates Cambridge Trust, the ERC Advanced Grant No. 320598 3D-E, and the Technology Strategy Board UKThis is the final published version which appears at http://dx.doi.org/10.1063/1.490088

Ionic solutes impact collagen scaffold bioactivity.

The structure of ice-templated collagen scaffolds is sensitive to many factors. By adding 0.5 wt% of sodium chloride or sucrose to collagen slurries, scaffold structure could be tuned through changes in ice growth kinetics and interactions of the solute and collagen. With ionic solutes (sodium chloride) the entanglements of the collagen molecule decreased, leading to fibrous scaffolds with increased pore size and decreased attachment of chondrocytes. With non-ionic solutes (sucrose) ice growth was slowed, leading to significantly reduced pore size and up-regulated cell attachment. This highlights the large changes in structure and biological function stimulated by solutes in ice-templating systems.The authors gratefully acknowledge the financial support of the Gates Cambridge Trust, the Newton Trust, NIHR, and ERC Advanced Grant 320598 3D-E. A.H. holds a Daphne Jackson Fellowship funded by the University of Cambridge. Also, the authors thank Dr. S. Butler for help with the rheological measurements.This is the accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s10856-015-5457-8

Characteristics of intracerebral haemorrhage associated with COVID-19: a systematic review and pooled analysis of individual patient and aggregate data

Background and purpose: There are very few studies of the characteristics and causes of ICH in COVID-19, yet such data are essential to guide clinicians in clinical management, including challenging anticoagulation decisions. We aimed to describe the characteristics of spontaneous symptomatic intracerebral haemorrhage (ICH) associated with COVID-19. Methods: We systematically searched PubMed, Embase and the Cochrane Central Database for data from patients with SARS-CoV-2 detected prior to or within 7 days after symptomatic ICH. We did a pooled analysis of individual patient data, then combined data from this pooled analysis with aggregate-level data. Results: We included data from 139 patients (98 with individual data and 41 with aggregate-level data). In our pooled individual data analysis, the median age (IQR) was 60 (53–67) years and 64% (95% CI 54–73.7%) were male; 79% (95% CI 70.0–86.9%) had critically severe COVID-19. The pooled prevalence of lobar ICH was 67% (95% CI 56.3–76.0%), and of multifocal ICH was 36% (95% CI 26.4–47.0%). 71% (95% CI 61.0–80.4%) of patients were treated with anticoagulation (58% (95% CI 48–67.8%) therapeutic). The median NIHSS was 28 (IQR 15–28); mortality was 54% (95% CI 43.7–64.2%). Our combined analysis of individual and aggregate data showed similar findings. The pooled incidence of ICH across 12 cohort studies of inpatients with COVID-19 (n = 63,390) was 0.38% (95% CI 0.22–0.58%). Conclusions: Our data suggest that ICH associated with COVID-19 has different characteristics compared to ICH not associated with COVID-19, including frequent lobar location and multifocality, a high rate of anticoagulation, and high mortality. These observations suggest different underlying mechanisms of ICH in COVID-19 with potential implications for clinical treatment and trials

Interpreting radiative efficiency in radio-loud AGNs

Author submitted version of unrefereed Nature Astronomy comment. Version in journal format available at https://rdcu.be/KH6WRadiative efficiency in radio-loud active galactic nuclei is governed by the accretion rate onto the central black hole rather than directly by the type of accreted matter; while it correlates with real differences in host galaxies and environments, it does not provide unambiguous information about particular objects.Non peer reviewedFinal Accepted Versio

Measuring capital in active addiction and recovery: the development of the strengths and barriers recovery scale (SABRS).

BACKGROUND: The international Life In Recovery (LiR) surveys have provided an important message to the public and policy makers about the reality of change from addiction to recovery, consistently demonstrating both that there are marked gains across a range of life domains and that the longer the person is in recovery the better their recovery strengths and achievements. However, to date, no attempt has been made to quantify the Life In Recovery scales and to assess what levels of change in removing barriers and building strengths is achieved at which point in the recovery journey. METHODS: The current study undertakes a preliminary analysis of strengths and barriers from the Life in Recovery measure, using data from a European survey on drug users in recovery (n = 480), and suggests that the instrument can be edited into a Strengths And Barriers Recovery Scale (SABRS). The new scale provides a single score for both current recovery strengths and barriers to recovery. RESULTS: The resulting data analysis shows that there are stepwise incremental changes in recovery strengths at different recovery stages, but these occur with only very limited reductions in barriers to recovery, with even those in stable recovery typically having at least two barriers to their quality of life and wellbeing. Greater strengths in active addiction are associated with greater strengths and resources in recovery. CONCLUSION: As well as demonstrating population changes in each of the domains assessed, the current study has shown the potential of the Life In Recovery Scale as a measure of recovery capital that can be used to support recovery interventions and pathways

Rapid Divergence of Predator Functional Traits Affects Prey Composition in Aquatic Communities

AbstractIdentifying traits that underlie variation in individual performance of consumers (i.e., trait utility) can help reveal the ecological causes of population divergence and the subsequent consequences for species interactions and community structure. Here, we document a case of rapid divergence (over the past 100 generations, or ?150 years) in foraging traits and feeding efficiency between a lake and stream population pair of threespine stickleback. Building on predictions from functional trait models of fish feeding, we analyzed foraging experiments with a Bayesian path analysis and elucidated the traits explaining variation in foraging performance and the species composition of ingested prey. Despite extensive previous research on the divergence of foraging traits among populations and ecotypes of stickleback, our results provide novel experimental evidence of trait utility for jaw protrusion, gill raker length, and gill raker spacing when foraging on a natural zooplankton assemblage. Furthermore, we discuss how these traits might contribute to the differential effects of lake and stream stickleback on their prey communities, observed in both laboratory and mesocosm conditions. More generally, our results illustrate how the rapid divergence of functional foraging traits of consumers can impact the biomass, species composition, and trophic structure of prey communities

Testosterone replacement in young male cancer survivors: A 6-month double-blind randomised placebo-controlled trial

Background Young male cancer survivors have lower testosterone levels, higher fat mass, and worse quality of life (QoL) than age-matched healthy controls. Low testosterone in cancer survivors can be due to orchidectomy or effects of chemotherapy and radiotherapy. We have undertaken a double-blind, placebo-controlled, 6-month trial of testosterone replacement in young male cancer survivors with borderline low testosterone (7–12 nmol/l). Methods and findings This was a multicentre United Kingdom study conducted in secondary care hospital outpatients. Male survivors of testicular cancer, lymphoma, and leukaemia aged 25–50 years with morning total serum testosterone 7–12 nmol/l were recruited. A total of 136 men were randomised between July 2012 and February 2015 (42.6% aged 25–37 years, 57.4% 38–50 years, 88% testicular cancer, 10% lymphoma, matched for body mass index [BMI]). Participants were randomised 1:1 to receive testosterone (Tostran 2% gel) or placebo for 26 weeks. A dose titration was performed after 2 weeks. The coprimary end points were trunk fat mass and SF36 Physical Functioning score (SF36-PF) at 26 weeks by intention to treat. At 26 weeks, testosterone treatment compared with placebo was associated with decreased trunk fat mass (−0.9 kg, 95% CI −1.6 to −0.3, p = 0.0073), decreased whole-body fat mass (−1.8 kg, 95% CI −2.9 to −0.7, p = 0.0016), and increased lean body mass (1.5 kg, 95% CI 0.9–2.1, p < 0.001). Decrease in fat mass was greatest in those with a high truncal fat mass at baseline. There was no treatment effect on SF36-PF or any other QoL scores. Testosterone treatment was well tolerated. The limitations of our study were as follows: a relatively short duration of treatment, only three cancer groups included, and no hard end point data such as cardiovascular events. Conclusions In young male cancer survivors with low-normal morning total serum testosterone, replacement with testosterone is associated with an improvement in body composition. Trial registration ISRCTN: 70274195, EudraCT: 2011-000677-31

Necessary and sufficient conditions of solution uniqueness in ℓ1\ell_1 minimization

This paper shows that the solutions to various convex $\ell_1$ minimization problems are \emph{unique} if and only if a common set of conditions are satisfied. This result applies broadly to the basis pursuit model, basis pursuit denoising model, Lasso model, as well as other $\ell_1$ models that either minimize $f(Ax-b)$ or impose the constraint $f(Ax-b)\leq\sigma$, where $f$ is a strictly convex function. For these models, this paper proves that, given a solution $x^*$ and defining I=\supp(x^*) and s=\sign(x^*_I), $x^*$ is the unique solution if and only if $A_I$ has full column rank and there exists $y$ such that $A_I^Ty=s$ and $|a_i^Ty|_\infty<1$ for $i\not\in I$. This condition is previously known to be sufficient for the basis pursuit model to have a unique solution supported on $I$. Indeed, it is also necessary, and applies to a variety of other $\ell_1$ models. The paper also discusses ways to recognize unique solutions and verify the uniqueness conditions numerically.Comment: 6 pages; revised version; submitte

High-speed camera characterization of voluntary eye blinking kinematics.

Blinking is vital to maintain the integrity of the ocular surface and its characteristics such as blink duration and speed can vary significantly, depending on the health of the eyes. The blink is so rapid that special techniques are required to characterize it. In this study, a high-speed camera was used to record and characterize voluntary blinking. The blinking motion of 25 healthy volunteers was recorded at 600 frames per second. Master curves for the palpebral aperture and blinking speed were constructed using palpebral aperture versus time data taken from the high-speed camera recordings, which show that one blink can be divided into four phases; closing, closed, early opening and late opening. Analysis of data from the high-speed camera images was used to calculate the palpebral aperture, peak blinking speed, average blinking speed and duration of voluntary blinking and compare it with data generated by other methods previously used to evaluate voluntary blinking. The advantages of the high-speed camera method over the others are discussed, thereby supporting the high potential usefulness of the method in clinical research