The congenital myasthenic syndromes: expanding genetic and phenotypic spectrums and refining treatment strategies.

PURPOSE OF REVIEW: Congenital myasthenic syndromes (CMS) are a group of heterogeneous inherited disorders caused by mutations in genes encoding proteins whose function is essential for the integrity of neuromuscular transmission. This review updates the reader on the expanding phenotypic spectrum and suggested improved treatment strategies. RECENT FINDINGS: As next-generation sequencing is taken into the clinic, its use is both continuing to unearth new causative genes in which mutations underlie CMS and also broadening the phenotypic spectrum for known CMS genes. The number of genes in which mutations may cause neuromuscular transmission defects has now passed 30. The defective transmission may be part of an overall more complex phenotype in which there may be muscle, central nervous system or other involvement. Notably, mutations in series of genes encoding proteins located in the presynatic motor bouton have been identified. Rare cases of mutations in basal laminar proteins of the synaptic cleft are coming to light and additional mutations/phenotypic features have been located in some of the larger neuromuscular junction proteins such as AGRN and MUSK, where previously mutation screening by sanger sequencing was time consuming and costly. Finally, there are more reports of the beneficial effects of treatment with β2-adrenergic receptor agonists in patients, and the study of their action in disease models. SUMMARY: Recent studies of the CMS illustrate the increasing complexity of the genetics and pathophysiological mechanisms involved. With therapy tailored for the underlying disease mechanism treatment, although incomplete, is usually life-transforming. However, treatment for newly identified conditions in which myasthenia is only one component within complex multisystem disorder will prove challenging.Welllcome trus

Extremely preterm born children at very high risk for developing autism spectrum disorder

This study aimed to provide a more comprehensive picture of the prevalence of autism spectrum disorder (ASD) in a geographic cohort of extremely preterm born adolescents by using established diagnostic instruments in addition to screening instruments. 53 participants passed a screening procedure with two screening instruments and a diagnostic evaluation with a semi-structured assessment and a parent interview. 28 % of the adolescents had a community based clinical diagnosis of ASD. When research diagnoses were also taken into account, this rate increased to 40 %. Intellectual disability, language impairment and behavioural difficulties are characteristic for these children with ASD. This study is to our knowledge the first to use ASD-specific diagnostic instruments to confirm ASD diagnoses in extremely preterm born children in early adolescence. The study expands findings of previous research and raises the need for follow-up into late childhood and early adolescence

Predictability of cerebral palsy and its characteristics through neonatal cranial ultrasound in a high-risk neonatal intensive care unit population

The aim of the study is to evaluate the predictive value of various types of brain injury detected by ultrasound in the neonatal period for the occurrence of cerebral palsy and its characteristics in a large cohort of high-risk infants. Thousand twenty-one consecutively NICU-admitted high-risk infants were assessed up to the corrected age of at least 2 years. Cerebral palsy (CP) was categorised into spastic or non-spastic, bilateral or unilateral and mild, moderate or severe CP. Different types of brain injury were identified by serial cranial ultrasound (US) during the NICU stay: white matter disease (WMD), haemorrhage, cerebral infarction, deep grey matter and parasagittal cerebral injury. There is a significant overall association between different types of brain injury and gestational age. Only 4% of the children with normal US develop CP. In the presence of any abnormal US image, the likeliness to develop CP is at least seven times higher. Within the group of infants with WMD and haemorrhage, the degree of brain involvement has a clear impact on the occurrence of CP. Concerning the characteristics of CP, deep grey matter lesion predict non-spastic CP versus spastic CP (OR = 31, P < 0.001). Cerebral infarction and haemorrhage grade IV are strong predictors of unilateral spastic CP versus bilateral spastic CP (OR = 49 and 24, respectively, P < 0.001). Deep grey matter lesion is a significant predictor for severe versus mild and moderate CP (OR = 6). In conclusion, neonatal cranial US is a useful tool in predicting CP and its characteristics

Decentralized Collaborative Learning of Personalized Models over Networks

We consider a set of learning agents in a col-laborative peer-to-peer network, where each agent learns a personalized model according to its own learning objective. The question addressed in this paper is: how can agents improve upon their locally trained model by communicating with other agents that have similar objectives? We introduce and analyze two asynchronous gossip algorithms running in a fully decentralized manner. Our first approach , inspired from label propagation, aims to smooth pre-trained local models over the network while accounting for the confidence that each agent has in its initial model. In our second approach, agents jointly learn and propagate their model by making iterative updates based on both their local dataset and the behavior of their neighbors. Our algorithm to optimize this challenging objective in a decentralized way is based on ADMM

Healthcare-associated bloodstream infections in a neonatal intensive care unit over a 20-year period (1992-2011) : trends in incidence, pathogens, and mortality

Objective. To analyze trends in the incidence and pathogen distribution of healthcare-associated bloodstream infections (HABSIs) over a 20-year period (1992-2011). Design. Historical cohort study. Setting. Thirty-two-bed neonatal intensive care unit (NICU) in a tertiary referral hospital. Patients. Neonates with HABSIs defined according to the criteria of the National Institute of Child Health and Development (NICHD). Methods. A hospital-based ongoing surveillance program was used to identify HABSI cases in neonates. A distinction between definite or possible HABSI was made according to the NICHD criteria. Incidence, incidence densities (HABSIs per 1,000 hospital-days and HABSIs per 1,000 total parenteral nutrition-days), and case fatality rate were calculated. Logistic regression analysis was used to find time trends. Four periods of 5 years were considered when executing variance analysis. Results. In total, 682 episodes of HABSIs occurred on 9,934 admissions (6.9%). The median total incidence density rate was 3.1 (interquartile range, 2.2-3.9). A significant increasing time trend in incidence density was observed for the period 1995-2011 (P < .003). A significant decrease in the case fatality rate was found in the last 5-year period (P < .001). No neonate died following possible HABSIs, whereas the case fatality rate among neonates with definite HABSIs was 9.7%. Most HABSIs were caused by coagulase-negative staphylococci (n = 414 [60.7%]). A significant increase in Staphylococcus aureus HABSI was observed in the last 10-year period (P < .001). Conclusions. An increase in incidence density rate occurred, while the case fatality rate dropped. Better perinatal care could be responsible for the latter. A decrease in days before infection and a high incidence of coagulase-negative Staphylococcus HABSIs indicate the need for vigorous application of evidence-based prevention initiatives, in particular for catheter care

Imagineering violence

info:eu-repo/semantics/publishe