Twenty weeks of home-based interactive training of children with cerebral palsy improves functional abilities

BACKGROUND: Home-based training is becoming ever more important with increasing demands on the public health systems. We investigated whether individualized and supervised interactive home-based training delivered through the internet improves functional abilities in children with cerebral palsy (CP). METHODS: Thirty four children with CP (aged 9–16; mean age 10.9 ± 2.4 years) (GMFCS I-II; MACS I-II) were included in this non-randomized controlled clinical training study. 12 children (aged 7–16; mean age: 11.3+/−0.9 years) were allocated to a control group in which measurements were performed with 20 weeks interval without any intervening training. Daily activities, functional abilities of upper- and lower limbs, and balance were evaluated before, immediately after training and 12 weeks after training. The training consisted of 30 min daily home-based training for 20 weeks delivered through the internet. RESULTS: The training group on average completed 17 min daily training for the 20 week period (total of 40 h of training). The training group showed significant improvements of daily activities (AMPS), upper limb function (AHA) and functional tests of lower limbs (sit to stand, lateral step up, half knee to standing) after 20 weeks of training. No difference was found between the test after 20 weeks of training and the test 12 weeks after training. No significance was reached for balance after training. No difference was found for any parameter for the control group. CONCLUSIONS: Interactive home training of children with CP is an efficient way to deliver training, which can enable functional motor improvements and increased activity to perform daily activities. TRIAL REGISTRATION: ISRCTN13188513. Date of registration: 04/12/201

Circulating Glucagon 1-61 Regulates Blood Glucose by Increasing Insulin Secretion and Hepatic Glucose Production

Glucagon is secreted from pancreatic a cells, and hypersecretion (hyperglucagonemia) contributes to diabetic hyperglycemia. Molecular heterogeneity in hyperglucagonemia is poorly investigated. By screening human plasma using high-resolution-proteomics, we identified several glucagon variants, among which proglucagon 1-61 (PG 1-61) appears to be the most abundant form. PG 1-61 is secreted in subjects with obesity, both before and after gastric bypass surgery, with protein and fat as the main drivers for secretion before surgery, but glucose after. Studies in hepatocytes and in b cells demonstrated that PG 1-61 dose-dependently increases levels of cAMP, through the glucagon receptor, and increases insulin secretion and protein levels of enzymes regulating glycogenolysis and gluconeogenesis. In rats, PG 1-61 increases blood glucose and plasma insulin and decreases plasma levels of amino acids in vivo. We conclude that glucagon variants, such as PG 1-61, may contribute to glucose regulation by stimulating hepatic glucose production and insulin secretion

Altered sense of Agency in children with spastic cerebral palsy

<p>Abstract</p> <p>Background</p> <p>Children diagnosed with spastic Cerebral Palsy (CP) often show perceptual and cognitive problems, which may contribute to their functional deficit. Here we investigated if altered ability to determine whether an observed movement is performed by themselves (sense of agency) contributes to the motor deficit in children with CP.</p> <p>Methods</p> <p>Three groups; ₁₎CP children, ₂₎healthy peers, and ₃₎healthy adults produced straight drawing movements on a pen-tablet which was not visible for the subjects. The produced movement was presented as a virtual moving object on a computer screen. Subjects had to evaluate after each trial whether the movement of the object on the computer screen was generated by themselves or by a computer program which randomly manipulated the visual feedback by angling the trajectories 0, 5, 10, 15, 20 degrees away from target.</p> <p>Results</p> <p>Healthy adults executed the movements in 310 seconds, whereas healthy children and especially CP children were significantly slower (p < 0.002) (on average 456 seconds and 543 seconds respectively). There was also a statistical difference between the healthy and age matched CP children (p = 0.037). When the trajectory of the object generated by the computer corresponded to the subject's own movements all three groups reported that they were responsible for the movement of the object. When the trajectory of the object deviated by more than 10 degrees from target, healthy adults and children more frequently than CP children reported that the computer was responsible for the movement of the object. CP children consequently also attempted to compensate more frequently from the perturbation generated by the computer.</p> <p>Conclusions</p> <p>We conclude that CP children have a reduced ability to determine whether movement of a virtual moving object is caused by themselves or an external source. We suggest that this may be related to a poor integration of their intention of movement with visual and proprioceptive information about the performed movement and that altered sense of agency may be an important functional problem in children with CP.</p

Relationship Between Maximal Left Ventricular Wall Thickness and Sudden Cardiac Death in Childhood Onset Hypertrophic Cardiomyopathy

Background: Maximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular hypertrophy has a nonlinear relationship with SCD, but it is not known whether the same complex relationship is seen in childhood. The aim of this study was to describe the relationship between left ventricular hypertrophy and SCD risk in a large international pediatric HCM cohort. Methods: The study cohort comprised 1075 children (mean age, 10.2 years [+/- 4.4]) diagnosed with HCM (1-16 years) from the International Paediatric Hypertrophic Cardiomyopathy Consortium. Anonymized, noninvasive clinical data were collected from baseline evaluation and follow-up, and 5-year estimated SCD risk was calculated (HCM Risk-Kids). Results: MLVWT Z score was = 10 to = 20 in 143 (13.3%). Higher MLVWT Z scores were associated with heart failure symptoms, unexplained syncope, left ventricular outflow tract obstruction, left atrial dilatation, and nonsustained ventricular tachycardia. One hundred twenty-two patients (71.3%) with MLVWT Z score >= 20 had coexisting risk factors for SCD. Over a median follow-up of 4.9 years (interquartile range, 2.3-9.3), 115 (10.7%) had an SCD event. Freedom from SCD event at 5 years for those with MLVWT Z scores = 10 to = 20 was 95.6%, 87.4%, and 86.0, respectively. The estimated SCD risk at 5 years had a nonlinear, inverted U-shaped relationship with MLVWT Z score, peaking at Z score +23. The presence of coexisting risk factors had a summative effect on risk. Conclusions: In children with HCM, an inverted U-shaped relationship exists between left ventricular hypertrophy and estimated SCD risk. The presence of additional risk factors has a summative effect on risk. While MLVWT is important for risk stratification, it should not be used either as a binary variable or in isolation to guide implantable cardioverter defibrillator implantation decisions in children with HCM.Peer reviewe

Overview of the TCV tokamak experimental programme

The tokamak a configuration variable (TCV) continues to leverage its unique shaping capabilities, flexible heating systems and modern control system to address critical issues in preparation for ITER and a fusion power plant. For the 2019-20 campaign its configurational flexibility has been enhanced with the installation of removable divertor gas baffles, its diagnostic capabilities with an extensive set of upgrades and its heating systems with new dual frequency gyrotrons. The gas baffles reduce coupling between the divertor and the main chamber and allow for detailed investigations on the role of fuelling in general and, together with upgraded boundary diagnostics, test divertor and edge models in particular. The increased heating capabilities broaden the operational regime to include T (e)/T (i) similar to 1 and have stimulated refocussing studies from L-mode to H-mode across a range of research topics. ITER baseline parameters were reached in type-I ELMy H-modes and alternative regimes with \u27small\u27 (or no) ELMs explored. Most prominently, negative triangularity was investigated in detail and confirmed as an attractive scenario with H-mode level core confinement but an L-mode edge. Emphasis was also placed on control, where an increased number of observers, actuators and control solutions became available and are now integrated into a generic control framework as will be needed in future devices. The quantity and quality of results of the 2019-20 TCV campaign are a testament to its successful integration within the European research effort alongside a vibrant domestic programme and international collaborations

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The ALICE experiment at the CERN LHC

ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries. Its overall dimensions are 161626 m3 with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008