Clinical Evaluation and Validation of the Dutch Crosslinking for Keratoconus Score

Importance: Defining keratoconus progression is fundamental in clinical decision making because crosslinking treatments are indicated when the disease is considered progressive. Currently, there is no consensus which parameters should be used to define progression. Objective: To assess and validate a novel clinical scoring system as an easy-to-use assessment tool for crosslinking treatment in patients with keratoconus. Design, Setting, and Participants: Prospective cohort study at 2 academic treatment centers. Patients with keratoconus referred between January 1, 2012, and June 30, 2014, with 2-year follow-up were included. Analysis began March 2017. Interventions: The Dutch Crosslinking for Keratoconus (DUCK) score is based on changes in 5 clinical parameters that are routinely assessed: age, visual acuity, refraction error, keratometry, and subjective patient experience. The DUCK score is derived by scoring 0 to 2 points per item, and cutoffs were determined by clinical experience. We compared the DUCK scores to the conventional 1.0-diopter increase in maximum keratometry criterion, within the last 12 months, in a longitudinal discovery and a validation cohort. Sensitivity analyses and intraitem correlations were performed. Main Outcomes and Measures: Overall treatment rate reduction and the duly withheld treatment rate. Results: A total of 504 eyes of 388 patients were available for analysis on disease progression in the course of 12 and 24 months. Baseline patient characteristics of the discovery cohort and the validation cohort were comparable in terms of age (mean [SD], 26.8 [8.3] years vs 26.3 [9.1]), sex (216 of 332 [65%] vs 123 of 172 [72%] men), and maximum keratometry (mean [SD], 53.5 [7.1] vs 52.7 [6.3]). Adhering to the DUCK score, rather than maximum keratometry, was associated with a reduction in overall treatment rate by 23% (95% CI, 18%-30%), without increasing the risk of disease progression (ie, the rate of progression for both groups was equal; ±0%). The DUCK score appears to better identify eyes that were duly withheld treatment by 35% (95% CI, 22%-49%). Conclusions and Relevance: These results provide validation of the DUCK score as a tool to determine whether a crosslinking treatment might be warranted. Compared with the conventional maximum keratometry criterion of more than 1.0 diopter, the DUCK score may better select patients who might benefit from crosslinking treatment. Potentially, it may prevent unnecessary treatments, reduce exposure to treatment risks, and improve the cost effectiveness of crosslinking

Collisionality and safety factor scalings of H-mode energy transport in the MAST spherical tokamak

A factor of 4 dimensionless collisionality scan of H-mode plasmas in MAST shows that the thermal energy confinement time scales as [formula]. Local heat transport is dominated by electrons and is consistent with the global scaling. The neutron rate is in good agreement with the ¿* dependence of tE,th. The gyrokinetic code GYRO indicates that micro-tearing turbulence might explain such a trend. A factor of 1.4 dimensionless safety factor scan shows that the energy confinement time scales as [formula] . These two scalings are consistent with the dependence of energy confinement time on plasma current and magnetic field. Weaker qeng and stronger ¿* dependences compared with the IPB98y2 scaling could be favourable for an ST-CTF device, in that it would allow operation at lower plasma current

Perspective historique de robots humanoïdes en Europe

International audienceFrom the very first humanoid automation designed by Leonardo da Vinci in 1495 to Pyrène – a fully force control humanoid robot – designed for research purpose in 2016, this chapter discusses the contributions of Europe in humanoid robot research and development. It is organized around the presentation of the main influential platforms, followed by thematic contributions covering collaborative robots, control, biomechanics, and neurosciences

Intrinsically Safe Robot Arm: Adjustable Static Balancing and Low Power Actuation

We present a design for a manipulator that is intrinsically mechanically safe, i.e. it can not cause pain (let alone damage) to a human being even if the control system has a failure. Based on the pressure pain thresholds for human skin, we derive a pinching safety constraint that limits the actuator torque, and an impact safety constraint that results in a trade-off between mass and velocity. To fulfill all constraints, the manipulator requires a spring balancing system that counteracts gravity in all configurations of the manipulator. This allows the use of extremely low-power DC motors (only 4.5 W). Thanks to the torque and speed limitations of these motors the manipulator is indeed intrinsically safe, yet still capable of moving a useful payload of 1.2 kg over a distance of 0.8 m in 1.5 s.Biomechanical EngineeringMechanical, Maritime and Materials Engineerin

Lysosomal Storage Diseases. For Better or Worse: Adapting to Defective Lysosomal Glycosphingolipid Breakdown

The cellular recycling of glycosphingolipids (GSLs) is mediated by specific lysosomal glycosidases. Inherited deficiencies in these enzymes cause lysosomal storage disorders. Some of the common disorders are Gaucher disease (GD) and Fabry disease (FD) resulting from the defects in lysosomal glucocerebrosidase (GBA) degrading glucosylceramide and α‐galactosidase A (GLA) degrading globotriaosylceramide. Here, GSL accumulation in tissues slows down with age despite ongoing lysosomal turnover of endogenous and endocytosed GSLs. Biochemical adaptations might explain this phenomenon. One crucial adaptation is the deacylation of accumulating GSLs in lysosomes by acid ceramidase. The soluble bases glucosylsphingosine in GD and globotriaosylsphingosine in FD are capable of leaving lysosomes and cells. In the case of GD, a further adaptation involves the cytosol‐faced enzyme GBA2. This enzyme allows extra‐lysosomal degradation of GlcCer while possibly generating glucosylated cholesterol. The beneficial and harmful effects of these adaptations are discussed.Key concepts: Glycosphingolipids (GSLs) are membrane constituents composed of a ceramide with one or more sugars. The simplest GSL is glucosylceramide (GlcCer). Ongoing recycling of GSLs in cells includes lysosomal degradation by the sequential action of glycosidases and acid ceramidase. Deficiency of lysosomal glycosidase leads to lysosomal storage diseases caused by accumulation of the corresponding substrate in lysosomes. The most common glycosphingolipidoses are Gaucher disease (GD) and Fabry disease (FD). GD is an autosomal recessive disorder caused by deficient activity of the lysosomal enzyme acid β‐glucosidase (glucocerebrosidase; GBA) resulting in lysosomal accumulation of GlcCer. FD is an X‐linked disorder caused by deficient activity of the lysosomal enzyme α‐galactosidase A (GLA) resulting in lysosomal accumulation of globotriaosylceramide (Gb3). Accumulation of storage lipids during GBA and GLA tends to slow down with age, likely partly due to poorly appreciated biochemical adaptations. Active conversion of accumulating GlcCer in lysosomes of GBA‐deficient cells is mediated by acid ceramidase, resulting in the formation of water‐soluble glucosylsphingosine (GlcSph). Likewise, globotriaosylsphingosine (lysoGb3) is formed from accumulating in lysosomes of GLA‐deficient cells. Elevated plasma GlcSph and lysoGb3 levels can be sensitively measured LC–MS and may assist in diagnosing and monitoring of the disease and response to treatment in GD and FD patients, respectively. Increased GlcSph level in GD patients acts as an autoantigen, causing ongoing B‐cell proliferation, leading to multiple myeloma. Increased lysoGb3 level in FD patients is thought to cause damage to nociceptive neurons and podocytes, thus contributing to pain and renal failure. In GD, the cytosol‐faced enzyme β‐glucosidase GBA2 allows degradation of GlcCer outside lysosomes. Through transglycosylation, GBA2 may generate glucosylcholesterol and ceramide from GlcCer and cholesterol. The toxic effects of secondary metabolites such as glycosphingoid bases (GlcSph in GD and lysoGb3 in FD) and glucosylated metabolites (GlcChol in GD) warrant further investigations.info:eu-repo/semantics/publishedVersio