A circular RNA generated from an intron of the insulin gene controls insulin secretion.

Fine-tuning of insulin release from pancreatic β-cells is essential to maintain blood glucose homeostasis. Here, we report that insulin secretion is regulated by a circular RNA containing the lariat sequence of the second intron of the insulin gene. Silencing of this intronic circular RNA in pancreatic islets leads to a decrease in the expression of key components of the secretory machinery of β-cells, resulting in impaired glucose- or KCl-induced insulin release and calcium signaling. The effect of the circular RNA is exerted at the transcriptional level and involves an interaction with the RNA-binding protein TAR DNA-binding protein 43 kDa (TDP-43). The level of this circularized intron is reduced in the islets of rodent diabetes models and of type 2 diabetic patients, possibly explaining their impaired secretory capacity. The study of this and other circular RNAs helps understanding β-cell dysfunction under diabetes conditions, and the etiology of this common metabolic disorder

New values of time and reliability in passenger transport in The Netherlands

We have established new values of time (VOTs) and values of travel time reliability (VORs) for use in cost-benefit analysis (CBA) of transport projects in The Netherlands. This was the first national study in The Netherlands (and one of the first world-wide) to investigate these topics empirically in a joint framework. Stated preference (SP) questionnaires were designed for interviewing travellers, where the hypothetical alternatives were described in terms of travel time, travel costs and travel time reliability, the latter being presented to the respondents in the form of five possible travel times having equal probability. For passenger transport, we first collected interviews using an existing internet panel. Additional data collection recruitment was done by asking travellers at petrol stations/service areas, parking garages, stations, bus stops, airports and ports to participate in the survey. One important conclusion is that the SP survey using members of this internet panel leads to substantially lower VOTs than the SP survey with en-route recruitment, probably because of self-selection bias in the internet panel. We estimated discrete choice models in which the values of time differ between trips with different time and costs levels, different time and costs changes offered in the SP, and different observed characteristics of the respondents (e.g. education, income, age, household composition). By using a panel latent class model, we also account for unobserved differences between respondents in the value of time and for repeated measurements/panel effects. The reference values of time and the reference reliability ratios were estimated on the 2011 sample only, but the effect of time and cost level, time and cost changes offered and socio-economic attributes was estimated on both the 2009 and 2011 samples

The Physiology of Vasodilatation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68237/2/10.1177_000331976101200602.pd

Bimanual coordination in children with hemiplegic cerebral palsy

ndividuals with hemiplegic cerebral palsy (CP) have largely unilateral impairments in upper extremity movement. They often avoid engaging in certain bimanual activities, and despite the fact that compensatory strategies may be functional, they often lack efficiency. This chapter starts with a description of the development of bimanual coordination and the motor-related constraints (temporal and spatial) under which such actions are performed. Subsequently, an overview of experimental studies on bimanual movement performance in children with hemiplegic CP is provided. Finally, recent advances in rehabilitation that aim to improve bimanual coordination and thereby the performance activities of daily living are discussed. This is illustrated by preliminary findings of a new intervention for children that focuses on coordination of both hands together, the Hand-Arm Bimanual Intensive Training (HABIT

Predictive validity of the Hand Assessment for Infants in infants at risk of unilateral cerebral palsy

Aim To evaluate the sensitivity, specificity, and predictive value of the Hand Assessment for Infants (HAI) in identifying infants at risk of being diagnosed with unilateral cerebral palsy (CP), and to determine cut-off values for this purpose.Method A convenience sample of 203 infants (106 females, 97 males) was assessed by the HAI at 3, 6, 9, and 12 months. Sensitivity, specificity, predictive values, and likelihood ratios were calculated using receiver operating characteristic curve analysis. Cut-off values were derived for different ages. The clinical outcome (unilateral CP yes/no) at 24 months or more served as an external criterion to investigate the predictive validity of HAI.Results Half of the infants developed unilateral CP. The area under the curve ranged from 0.77 (95% CI [confidence interval] 0.63-0.91) to 0.95 (95% CI 0.90-1.00) across HAI scales and age intervals. Likewise, sensitivity ranged from 63% to 93%, specificity from 62% to 91%, and accuracy from 73% to 94%.Interpretation HAI scores demonstrated overall accuracy that ranged from very good to excellent in predicting unilateral CP in infants at risk aged between 3.5 and 12 months. This accuracy increased with age at assessment and the earliest possible prediction was at 3.5 months of age, when appropriate HAI cut-off values for different ages were applied