Neurophysiological investigations of drug resistant epilepsy patients treated with vagus nerve stimulation to differentiate responders from non-responders

Background and purpose In patients treated with vagus nerve stimulation (VNS) for drug resistant epilepsy (DRE), up to a third of patients will eventually not respond to the therapy. As VNS therapy requires surgery for device implantation, prediction of response prior to surgery is desirable. It is hypothesized that neurophysiological investigations related to the mechanisms of action of VNS may help to differentiate VNS responders from non-responders prior to the initiation of therapy. Methods In a prospective series of DRE patients, polysomnography, heart rate variability (HRV) and cognitive event related potentials were recorded. Polysomnography and HRV were repeated after 1 year of treatment with VNS. Polysomnography, HRV and cognitive event related potentials were compared between VNS responders (>= 50% reduction in seizure frequency) and non-responders. Results Fifteen out of 30 patients became VNS responders after 1 year of VNS treatment. Prior to treatment with VNS, the amount of deep sleep (NREM 3), the HRV high frequency (HF) power and the P3b amplitude were significantly different in responders compared to non-responders (P = 0.007; P = 0.001; P = 0.03). Conclusion Three neurophysiological parameters, NREM 3, HRV HF and P3b amplitude, were found to be significantly different in DRE patients who became responders to VNS treatment prior to initiation of their treatment with VNS. These non-invasive recordings may be used as characteristics for response in future studies and help avoid unsuccessful implantations. Mechanistically these findings may be related to changes in brain regions involved in the so-called vagal afferent network

Understanding for whom, under which circumstances and how sedentary behavior interventions for older adults work: a realist review

This realist review aims to identify the working mechanisms and contextual preconditions for sedentary behavior (SB) change in older adults to guide the development of future interventions. The review followed the iterative process of Pawson et al. (1997). First, research questions were defined and an initial program theory (IPT) was established. Second, evidence was searched in four scientific databases and the grey literature. Third, data from 58 studies (explained in 61 papers) that contained relevant information to refine, refute or confirm the IPT were coded. And based on these codes, context-mechanism-outcome configurations were made and a final program theory was developed. As a result, three contexts for SB change became clear: (1) motivation, (2) opportunities, and (3) capabilities of older adults. Depending on the context, other behavior change techniques should be used to trigger specific mechanisms and reduce SB. Especially, the impact of automatic processes of SB on the effectiveness of SB interventions became clear. Currently, the focus is primarily on the reflective processes guiding SB, without taking into account that SB is often an automatic response which makes SB an ingrained habit. It can be concluded that the effectiveness of SB interventions in older adults highly depends on the intervention context

Built environmental correlates of cycling for transport across Europe.

This cross-sectional study aimed to determine which objective built environmental factors, identified using a virtual neighbourhood audit, were associated with cycling for transport in adults living in five urban regions across Europe. The moderating role of age, gender, socio-economic status and country on these associations was also investigated. Overall, results showed that people living in neighbourhoods with a preponderance of speed limits below 30km/h, many bicycle lanes, with less traffic calming devices, more trees, more litter and many parked cars forming an obstacle on the road were more likely to cycle for transport than people living in areas with lower prevalence of these factors. Evidence was only found for seven out of 56 possible moderators of these associations. These results suggest that reducing speed limits for motorized vehicles and the provision of more bicycle lanes may be effective interventions to promote cycling in Europe

Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis

Background: Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of cases, attributable deaths, and disability-adjusted life-years (DALYs). Methods: We estimated the incidence of infections with 16 antibiotic resistance–bacterium combinations from European Antimicrobial Resistance Surveillance Network (EARS-Net) 2015 data that was country-corrected for population coverage. We multiplied the number of bloodstream infections (BSIs) by a conversion factor derived from the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections in European acute care hospitals in 2011–12 to estimate the number of non-BSIs. We developed disease outcome models for five types of infection on the basis of systematic reviews of the literature. Findings: From EARS-Net data collected between Jan 1, 2015, and Dec 31, 2015, we estimated 671 689 (95% uncertainty interval [UI] 583 148–763 966) infections with antibiotic-resistant bacteria, of which 63·5% (426 277 of 671 689) were associated with health care. These infections accounted for an estimated 33 110 (28 480–38 430) attributable deaths and 874 541 (768 837–989 068) DALYs. The burden for the EU and EEA was highest in infants (aged <1 year) and people aged 65 years or older, had increased since 2007, and was highest in Italy and Greece. Interpretation: Our results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases

Serum microRNA screening and functional studies reveal miR-483-5p as a potential driver of fibrosis in systemic sclerosis

Abstract Objective MicroRNAs (miRNAs) are regulatory molecules, which have been addressed as potential biomarkers and therapeutic targets in rheumatic diseases. Here, we investigated the miRNA signature in the serum of systemic sclerosis (SSc) patients and we further assessed their expression in early stages of the disease. Methods The levels of 758 miRNAs were evaluated in the serum of 26 SSc patients as compared to 9 healthy controls by using an Openarray platform. Three miRNAs were examined in an additional cohort of 107 SSc patients and 24 healthy donors by single qPCR. MiR-483-5p expression was further analysed in the serum of patients with localized scleroderma (LoS) (n = 22), systemic lupus erythematosus (SLE) (n = 33) and primary Sjogren's syndrome (pSS) (n = 23). The function of miR-483-5p was examined by transfecting miR-483-5p into primary human dermal fibroblasts and pulmonary endothelial cells. Results 30 miRNAs were significantly increased in patients with SSc. Of these, miR-483-5p showed reproducibly higher levels in an independent SSc cohort and was also elevated in patients with preclinical-SSc symptoms (early SSc). Notably, miR-483-5p was not differentially expressed in patients with SLE or pSS, whereas it was up-regulated in LoS, indicating that this miRNA could be involved in the development of skin fibrosis. Consistently, miR-483-5p overexpression in fibroblasts and endothelial cells modulated the expression of fibrosis-related genes. Conclusions Our findings showed that miR-483-5p is up-regulated in the serum of SSc patients, from the early stages of the disease onwards, and indicated its potential function as a fine regulator of fibrosis in SSc

Challenges in scaling of CMOS devices towards 65 nm node, Journal of Telecommunications and Information Technology, 2005, nr 1

The current trend in scaling transistor gate length below 60 nm is posing great challenges both related to process technology and circuit/system design. From the process technology point of view it is becoming increasingly difficult to continue scaling in traditional way due to fundamental limitations like resolution, quantum effects or random fluctuations. In turn, this has an important impact on electricaldevice specifications especially leakage current and the circuit power dissipation