The AGE reader:a non-invasive method to assess long term tissue damage

AIMS: Advanced glycation endproducts (AGEs) are sugar modified adducts which arise during non-enzymatic glycoxidative stress. These compounds may become systemically elevated in disease states, and accumulate in tissue, especially on long-lived proteins. AGEs have been implicated in various acute, and chronic diseases, stressing the need for reliable and comprehensive measuring techniques. Measurement of AGEs in tissue such as skin requires skin biopsies, which is an invasive procedure. The AGE Reader has been developed to assess skin autofluorescence (SAF) non-invasively by the fluorescent properties of several AGEs. RESULTS/CONCLUSION: Various studies have shown that SAF is a useful marker of disease processes associated with oxidative stress. It is prospectively associated with development of cardiovascular events in patients with diabetes, renal or cardiovascular disease, and it predicts diabetes, cardiovascular disease and mortality in the general population. However, when measuring SAF in individual subjects, several factors may limit the reliability of the measurement, and hamper its use as a systemic biomarker for AGEs. These include endogenous factors present in the skin that absorb emission light such as melanin in dark-skinned subjects, but also factors that lead to temporal changes in SAF such as acute diseases and strenuous physical exercise associated with glycoxidative stress. Also, exogenous factors could potentially influence SAF levels inadvertently such as nutrition, and for example the application of skin care products. This review will give an overview of the AGE Reader functionality and the intrinsic, and exogenous factors which potentially influence the SAF assessment in individual subjects

The TOPSHOCK study: Effectiveness of radial shockwave therapy compared to focused shockwave therapy for treating patellar tendinopath - design of a randomised controlled trial

Background: Patellar tendinopathy is a chronic overuse injury of the patellar tendon that is especially prevalent in people who are involved in jumping activities. Extracorporeal Shockwave Therapy is a relatively new treatment modality for tendinopathies. It seems to be a safe and promising part of the rehabilitation program for patellar tendinopathy. Extracorporeal Shockwave Therapy originally used focused shockwaves. Several years ago a new kind of shockwave therapy was introduced: radial shockwave therapy. Studies that investigate the effectiveness of radial shockwave therapy as treatment for patellar tendinopathy are scarce. Therefore the aim of this study is to compare the effectiveness of focussed shockwave therapy and radial shockwave therapy as treatments for patellar tendinopathy. Methods/design: The TOPSHOCK study (Tendinopathy Of Patella SHOCKwave) is a two-armed randomised controlled trial in which the effectiveness of focussed shockwave therapy and radial shockwave therapy are directly compared. Outcome assessors and patients are blinded as to which treatment is given. Patients undergo three sessions of either focused shockwave therapy or radial shockwave therapy at 1-week intervals, both in combination with eccentric decline squat training. Follow-up measurements are scheduled just before treatments 2 and 3, and 1, 4, 7 and 12 weeks after the final treatment. The main outcome measure is the Dutch VISA-P questionnaire, which asks for pain, function and sports participation in subjects with patellar tendinopathy. Secondary outcome measures are pain determined with a VAS during ADL, sports and decline squats, rating of subjective improvement and overall satisfaction with the treatment. Patients will also record their sports activities, pain during and after these activities, and concurrent medical treatment on a weekly basis in a web-based diary. Results will be analysed according to the intention-to-treat principle. Discussion: The TOPSHOCK study is the first randomised controlled trial that directly compares the effectiveness of focused shockwave therapy and radial shockwave therapy, both in combination with eccentric decline squat training, for treating patellar tendinopathy. Trial registration: Trial registration number NTR2774

Shuttling an electron spin through a silicon quantum dot array

Coherent links between qubits separated by tens of micrometers are expected to facilitate scalable quantum computing architectures for spin qubits in electrically-defined quantum dots. These links create space for classical on-chip control electronics between qubit arrays, which can help to alleviate the so-called wiring bottleneck. A promising method of achieving coherent links between distant spin qubits consists of shuttling the spin through an array of quantum dots. Here, we use a linear array of four tunnel-coupled quantum dots in a 28Si/SiGe heterostructure to create a short quantum link. We move an electron spin through the quantum dot array by adjusting the electrochemical potential for each quantum dot sequentially. By pulsing the gates repeatedly, we shuttle an electron forward and backward through the array up to 250 times, which corresponds to a total distance of approximately 80 {\mu}m. We make an estimate of the spin-flip probability per hop in these experiments and conclude that this is well below 0.01% per hop.Comment: 11 pages, 3 main figures, 6 appendix figure

Reducing charge noise in quantum dots by using thin silicon quantum wells

Charge noise in the host semiconductor degrades the performance of spin-qubits and poses an obstacle to control large quantum processors. However, it is challenging to engineer the heterogeneous material stack of gate-defined quantum dots to improve charge noise systematically. Here, we address the semiconductor-dielectric interface and the buried quantum well of a $^{28}$Si/SiGe heterostructure and show the connection between charge noise, measured locally in quantum dots, and global disorder in the host semiconductor, measured with macroscopic Hall bars. In 5 nm thick $^{28}$Si quantum wells, we find that improvements in the scattering properties and uniformity of the two-dimensional electron gas over a 100 mm wafer correspond to a significant reduction in charge noise, with a minimum value of 0.29$\pm$0.02 $\mu$eV/sqrt(Hz) at 1 Hz averaged over several quantum dots. We extrapolate the measured charge noise to simulated dephasing times to cz-gate fidelities that improve nearly one order of magnitude. These results point to a clean and quiet crystalline environment for integrating long-lived and high-fidelity spin qubits into a larger system

ICON 2019: International Scientific Tendinopathy Symposium Consensus: Clinical Terminology

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.Background Persistent tendon pain that impairs function has inconsistent medical terms that can influence choice of treatment.1 When a person is told they have tendinopathy by clinician A or tendinitis by clinician B, they might feel confused or be alarmed at receiving what they might perceive as two different diagnoses. This may lead to loss of confidence in their health professional and likely adds to uncertainty if they were to search for information about their condition. Clear and uniform terminology also assists inter-professional communication. Inconsistency in terminology for painful tendon disorders is a problem at numerous anatomical sites. Historically, the term ‘tendinitis’ was first used to describe tendon pain, thickening and impaired function (online supplementary figure S1). The term ‘tendinosis’ has also been used in a small number of publications, some of which were very influential.2 3 Subsequently, ‘tendinopathy’ emerged as the most common term for persistent tendon pain.4 5 To our knowledge, experts (clinicians and researchers) or patients have never engaged in a formal process to discuss the terminology we use. We believe that health professionals have not yet agreed on the appropriate terminology for painful tendon conditions.Peer reviewedFinal Accepted Versio

ICON 2019—International Scientific Tendinopathy Symposium Consensus: There are nine core health-related domains for tendinopathy (CORE DOMAINS): Delphi study of healthcare professionals and patients

Background: The absence of any agreed-upon tendon health-related domains hampers advances in clinical tendinopathy research. This void means that researchers report a very wide range of outcome measures inconsistently. As a result, substantial synthesis/meta-analysis of tendon research findings is almost futile despite researchers publishing busily. We aimed to determine options for, and then define, core health-related domains for tendinopathy. Methods: We conducted a Delphi study of healthcare professionals (HCP) and patients in a three-stage process. In stage 1, we extracted candidate domains from clinical trial reports and developed an online survey. Survey items took the form: ‘The ‘candidate domain’ is important enough to be included as a core health-related domain of tendinopathy’; response options were: agree, disagree, or unsure. In stage 2, we administered the online survey and reported the findings. Stage 3 consisted of discussions of the findings of the survey at the ICON (International Scientific Tendinopathy Symposium Consensus) meeting. We set 70% participant agreement as the level required for a domain to be considered ‘core’; similarly, 70% agreement was required for a domain to be relegated to ‘not core’ (see Results next). Results: Twenty-eight HCP (92% of whom had >10 years of tendinopathy experience, 71% consulted >10 cases per month) and 32 patients completed the online survey. Fifteen HCP and two patients attended the consensus meeting. Of an original set of 24 candidate domains, the ICON group deemed nine domains to be core. These were: (1) patient rating of condition, (2) participation in life activities (day to day, work, sport), (3) pain on activity/loading, (4) function, (5) psychological factors, (6) physical function capacity, (7) disability, (8) quality of life and (9) pain over a specified time. Two of these (2, 6) were an amalgamation of five candidate domains. We agreed that seven other candidate domains were not core domains: range of motion, pain on clinician applied test, clinical examination, palpation, drop out, sensory modality pain and pain without other specification. We were undecided on the other five candidate domains of physical activity, structure, medication use, adverse effects and economic impact. Conclusion: Nine core domains for tendon research should guide reporting of outcomes in clinical trials. Further research should determine the best outcome measures for each specific tendinopathy (ie, core outcome sets)

Implementing Individually Tailored Prescription of Physical Activity in Routine Clinical Care:Protocol of the Physicians Implement Exercise = Medicine (PIE=M) Development and Implementation Project

BACKGROUND: The prescription of physical activity (PA) in clinical care has been advocated worldwide. This "exercise is medicine" (E=M) concept can be used to prevent, manage, and cure various lifestyle-related chronic diseases. Due to several challenges, E=M is not yet routinely implemented in clinical care. OBJECTIVE: This paper describes the rationale and design of the Physicians Implement Exercise = Medicine (PIE=M) study, which aims to facilitate the implementation of E=M in hospital care. METHODS: PIE=M consists of 3 interrelated work packages. First, levels and determinants of PA in different patient and healthy populations will be investigated using existing cohort data. The current implementation status, facilitators, and barriers of E=M will also be investigated using a mixed-methods approach among clinicians of participating departments from 2 diverse university medical centers (both located in a city, but one serving an urban population and one serving a more rural population). Implementation strategies will be connected to these barriers and facilitators using a systematic implementation mapping approach. Second, a generic E=M tool will be developed that will provide tailored PA prescription and referral. Requirements for this tool will be investigated among clinicians and department managers. The tool will be developed using an iterative design process in which all stakeholders reflect on the design of the E=M tool. Third, we will pilot-implement the set of implementation strategies, including the E=M tool, to test its feasibility in routine care of clinicians in these 2 university medical centers. An extensive learning process evaluation will be performed among clinicians, department managers, lifestyle coaches, and patients using a mixed-methods design based on the RE-AIM framework. RESULTS: This project was approved and funded by the Dutch grant provider ZonMW in April 2018. The project started in September 2018 and continues until December 2020 (depending on the course of the COVID-19 crisis). All data from the first work package have been collected and analyzed and are expected to be published in 2021. Results of the second work package are described. The manuscript is expected to be published in 2021. The third work package is currently being conducted in clinical practice in 4 departments of 2 university medical hospitals among clinicians, lifestyle coaches, hospital managers, and patients. Results are expected to be published in 2021. CONCLUSIONS: The PIE=M project addresses the potential of providing patients with PA advice to prevent and manage chronic disease, improve recovery, and enable healthy ageing by developing E=M implementation strategies, including an E=M tool, in routine clinical care. The PIE=M project will result in a blueprint of implementation strategies, including an E=M screening and referral tool, which aims to improve E=M referral by clinicians to improve patients' health, while minimizing the burden on clinicians