Silicon central pattern generators for cardiac diseases

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Silicon central pattern generators for cardiac diseases

Cardiac rhythm management devices provide therapies for both arrhythmias and resynchronisation but not heart failure, which affects millions of patients worldwide. This paper reviews recent advances in biophysics and mathematical engineering that provide a novel technological platform for addressing heart disease and enabling beat-to-beat adaptation of cardiac pacing in response to physiological feedback. The technology consists of silicon hardware central pattern generators (hCPGs) that may be trained to emulate accurately the dynamical response of biological central pattern generators (bCPGs). We discuss the limitations of present CPGs and appraise the advantages of analog over digital circuits for application in bioelectronic medicine. To test the system, we have focused on the cardio-respiratory oscillators in the medulla oblongata that modulate heart rate in phase with respiration to induce respiratory sinus arrhythmia (RSA). We describe here a novel, scalable hCPG comprising physiologically realistic (Hodgkin–Huxley type) neurones and synapses. Our hCPG comprises two neurones that antagonise each other to provide rhythmic motor drive to the vagus nerve to slow the heart. We show how recent advances in modelling allow the motor output to adapt to physiological feedback such as respiration. In rats, we report on the restoration of RSA using an hCPG that receives diaphragmatic electromyography input and use it to stimulate the vagus nerve at specific time points of the respiratory cycle to slow the heart rate. We have validated the adaptation of stimulation to alterations in respiratory rate. We demonstrate that the hCPG is tuneable in terms of the depth and timing of the RSA relative to respiratory phase. These pioneering studies will now permit an analysis of the physiological role of RSA as well as its any potential therapeutic use in cardiac disease

Population Impact of Girls-Only Human Papillomavirus 16/18 Vaccination in the Netherlands: Cross-Protective and Second-Order Herd Effects

Background: Human papillomavirus (HPV) vaccination programs achieve substantial population-level impact, with effects extending beyond protection of vaccinated individuals. We assessed trends in HPV prevalence up to 8 years postvaccination among men and women in the Netherlands, where bivalent HPV vaccination, targeting HPV types 16/18, has been offered to (pre)adolescent girls since 2009 with moderate vaccination coverage. Methods: We used data from the PASSYON study, a survey initiated in 2009 (prevaccination) and repeated biennially among 16-to 24-year-old visitors of sexual health centers. We studied genital HPV positivity from 2009 to 2017 among women, heterosexual men, and unvaccinated women using Poisson generalized estimating equation models, adjusted for individual-and population-level confounders. Trends were studied for 25 HPV types detected by the SPF10-LiPA25 platform. Results: A total of 6354 women (64.7% self-reported unvaccinated) and 2414 heterosexual men were included. Percentual declines in vaccine types HPV-16/18 were observed for all women (12.6% per year [95% confidence interval {CI}, 10.6-14.5]), heterosexual men (13.0% per year [95% CI, 8.3-17.5]), and unvaccinated women (5.4% per year [95% CI, 2.9-7.8]). We observed significant declines in HPV-31 (all women and heterosexual men), HPV-45 (all women), and in all high-risk HPV types pooled (all women and heterosexual men). Significant increases were observed for HPV-56 (all women) and HPV-52 (unvaccinated women). Conclusions: Our results provide evidence for first-order herd effects among heterosexual men against HPV-16/18 and cross-protective types. Additionally, we show second-order herd effects against vaccine types among unvaccinated women. These results are promising regarding population-level and clinical impact of girls-only bivalent HPV vaccination in a country with moderate vaccine uptake

The downward spiral of mental disorders and educational attainment: a systematic review on early school leaving.

BACKGROUND: Most psychiatric disorders present symptom patterns that cause severe impairment on the emotional, cognitive and social level. Thus, adolescents who suffer from a mental disorder risk finding themselves in a downward spiral caused by the reciprocal association of psychological symptoms and negative school experiences that may culminate in early school leaving. In addition to previous collective work that mainly focused on school refusing behaviour among children and was presented as an expert's opinion, the following systematic review fills the knowledge gap by providing a structured overview of the bidirectional association between mental health and secondary school dropout based on a sound methodology and with a particular focus on mediating factors. METHODS: Four electronic databases were searched from January 1990 until June 2014. Selected references were assessed for study details, main results, mediating factors and methodological limitations. Standardized risk of bias assessment was conducted. RESULTS: Mood and anxiety disorders seemed to have a less consequential direct effect on early school leaving than substance use and disruptive behaviour disorders. The association between externalizing disorders and educational attainment was even stronger when the disorder occurred early in life. On the other hand, internalizing disorders were reported to develop as a consequence of school dropout. Only few studies had addressed gender differences, with discrepant results. Socio-economic background, academic achievement and family support were identified as significant mediating factors of the association between mental disorders and subsequent educational attainment. CONCLUSIONS: Findings suggested a strong association between mental health and education, in both directions. However, most studies focused on mediating factors that could not be targeted by intervention programs

Passend onderwijs voor kinderen met een licht verstandelijke beperking: terugblikken en vooruitzien.

Pathways through Adolescenc