A timeband framework for modelling real-time systems

Complex real-time systems must integrate physical processes with digital control, human operation and organisational structures. New scientific foundations are required for specifying, designing and implementing these systems. One key challenge is to cope with the wide range of time scales and dynamics inherent in such systems. To exploit the unique properties of time, with the aim of producing more dependable computer-based systems, it is desirable to explicitly identify distinct time bands in which the system is situated. Such a framework enables the temporal properties and associated dynamic behaviour of existing systems to be described and the requirements for new or modified systems to be specified. A system model based on a finite set of distinct time bands is motivated and developed in this paper

Treatment of chronic plantar fasciopathy with extracorporeal shock waves (review)

There is an increasing interest by doctors and patients in extracorporeal shock wave therapy (ESWT) for chronic plantar fasciopathy (PF), particularly in second generation radial extracorporeal shock wave therapy (RSWT). The present review aims at serving this interest by providing a comprehensive overview on physical and medical definitions of shock waves and a detailed assessment of the quality and significance of the randomized clinical trials published on ESWT and RSWT as it is used to treat chronic PF. Both ESWT and RSWT are safe, effective, and technically easy treatments for chronic PF. The main advantages of RSWT over ESWT are the lack of need for any anesthesia during the treatment and the demonstrated long-term treatment success (demonstrated at both 6 and 12 months after the first treatment using RSWT, compared to follow-up intervals of no more than 12 weeks after the first treatment using ESWT). In recent years, a greater understanding of the clinical outcomes in ESWT and RSWT for chronic PF has arisen in relationship not only in the design of studies, but also in procedure, energy level, and shock wave propagation. Either procedure should be considered for patients 18 years of age or older with chronic PF prior to surgical intervention

Radial Shock Wave Devices Generate Cavitation

Background Conflicting reports in the literature have raised the question whether radial extracorporeal shock wave therapy (rESWT) devices and vibrating massage devices have similar energy signatures and, hence, cause similar bioeffects in treated tissues. Methods and Findings We used laser fiber optic probe hydrophone (FOPH) measurements, high-speed imaging and x-ray film analysis to compare fundamental elements of the energy signatures of two rESWT devices (Swiss DolorClast;Electro Medical Systems, Nyon, Switzerland;D-Actor 200;Storz Medical, Tagerwillen, Switzerland) and a vibrating massage device (Vibracare;G5/General Physiotherapy, Inc.,Earth City, MO, USA). To assert potential bioeffects of these treatment modalities we investigated the influence of rESWT and vibrating massage devices on locomotion ability of Caenorhabditis elegans (C. elegans) worms. Results FOPH measurements demonstrated that both rESWT devices generated acoustic waves with comparable pressure and energy flux density. Furthermore, both rESWT devices generated cavitation as evidenced by high-speed imaging and caused mechanical damage on the surface of x-ray film. The vibrating massage device did not show any of these characteristics. Moreover, locomotion ability of C. elegans was statistically significantly impaired after exposure to radial extracorporeal shock waves but was unaffected after exposure of worms to the vibrating massage device. Conclusions The results of the present study indicate that both energy signature and bioeffects of rESWT devices are fundamentally different from those of vibrating massage devices

Epilepsy With Auditory Features: From Etiology to Treatment

Epilepsy with auditory features (EAF) is a focal epilepsy belonging to the focal epileptic syndromes with onset at variable age according to the new ILAE Classification. It is characterized by seizures with auditory aura or receptive aphasia suggesting a lateral temporal lobe involvement of the epileptic discharge. Etiological factors underlying EAF are largely unknown. In the familial cases with an autosomal dominant pattern of inheritance several genes have been involved, among which the first discovered, LGI1, was thought to be predominant. However, increasing evidence now points to a multifactorial etiology, as familial and sporadic EAF share a virtually identical electro-clinical characterization and only a few have a documented genetic etiology. Patients with EAF usually have an unremarkable neurological examination and a good response to antiseizure medications. However, it must be underscored that total remission might be lower than expected and that treatment withdrawal might lead to relapses. Thus, a proper understanding of this condition is in order for better patient treatment and counseling. Further studies are still required to further characterize the many facets of EAF

Radial extracorporeal shock wave therapy is efficient and safe in the treatment of fracture nonunions of superficial bones: a retrospective case series

Background: A substantial body of evidence supports the use of focused extracorporeal shock wave therapy (fESWT) in the non-invasive treatment of fracture nonunions. On the other hand, virtually no studies exist on the use of radial extracorporeal shock wave therapy (rESWT) for this indication. Methods: We retrospectively analyzed 22 patients treated with rESWT for fracture nonunions of superficial bones that failed to heal despite initial surgical fixation in most cases. Radial extracorporeal shock wave therapy was applied without anesthesia in three rESWT sessions on average, with one rESWT session per week and 3000 radial extracorporeal shock waves at an energy flux density of 0.18 mJ/mm(2) per session. Treatment success was monitored with radiographs and clinical examinations. Results: Six months after rESWT radiographic union was confirmed in 16 out of 22 patients (73%), which is similar to the success rate achieved in comparable studies using fESWT. There were no side effects. The tibia was the most common treatment site (10/22) and 70% of tibia nonunions healed within 6 months after rESWT. Overall, successfully treated patients showed a mean time interval of 8.8 +/- 0.8 (mean +/- standard error of the mean) months between initial fracture and commencement of rESWT whereas in unsuccessfully treated patients the mean interval was 26.0 +/- 10.1 months (p < 0.05). In unsuccessful tibia cases, the mean interval was 43.3 +/- 13.9 months. Conclusions: Radial extracorporeal shock wave therapy appears to be an effective and safe alternative in the management of fracture nonunions of superficial bones if diagnosed early and no fESWT device is available. The promising preliminary results of the present case series should encourage the implementation of randomized controlled trials for the early use of rESWT in fracture nonunions

Endoscopic Double-Pigtail Catheter (EDPC) Internal Drainage as First-Line Treatment of Gastric Leak: A Case Series during Laparoscopic Sleeve Gastrectomy Learning Curve for Morbid Obesity

Objectives. The prevalence of morbid obesity has dramatically increased over the last several decades worldwide, currently reaching epidemic proportions. Gastric leak (GL) remains the potentially fatal main complication after sleeve gastrectomy (SG) for morbid obesity. To our knowledge, there are no standardized guidelines for GL treatment after laparoscopic sleeve gastrectomy (LSG) yet. The aim of this study was to represent our institutional preliminary experience using the endoscopic double-pigtail catheter (EDPC) as the method of internal drainage and propose it as first-line treatment in case of GL after LSG. Methods. One hundred and seventeen patients were admitted to our surgical department and underwent laparoscopic sleeve gastrectomy (LSG) for morbid obesity from March 2014 to June 2019. In 5 patients (4.3%) of our series, GL occurred as a complication of LSG. EPDC was the stand-alone procedure of internal drainage and GL first-line treatment. The internal pig tail was endoscopically removed from 30th to 40th POD in all cases. Results. Present data (clinical, biochemical, and instrumental tests) showed a complete resolution of GL, with promotion of a pseudodiverticula and complete re-epithelialization of leak. Follow-up was more strict than usual (clinical visit and biochemical test on 7th, 14th, and 21st day after discharge; a CT scan with gastrografin on 30th day from discharge if clinical visit and exams were normal). Conclusion. This was a preliminary retrospective observational study, conducted on 5 patients affected by GL as a complication of LSG for morbid obesity. EDPC maintains the safety, efficacy, and nonexpensive characteristic and may be proposed as better first-line treatment in case of GL after bariatric surgery

The economic impact of moderate stage Alzheimer's disease in Italy: Evidence from the UP-TECH randomized trial

Background: There is consensus that dementia is the most burdensome disease for modern societies. Few cost-of-illness studies examined the complexity of Alzheimer's disease (AD) burden, considering at the same time health and social care, cash allowances, informal care, and out-of-pocket expenditure by families. Methods: This is a comprehensive cost-of-illness study based on the baseline data from a randomized controlled trial (UP-TECH) enrolling 438 patients with moderate AD and their primary caregiver living in the community. Results: The societal burden of AD, composed of public, patient, and informal care costs, was about �20,000/yr. Out of this, the cost borne by the public sector was �4,534/yr. The main driver of public cost was the national cash-for-care allowance (�2,324/yr), followed by drug prescriptions (�1,402/yr). Out-of-pocket expenditure predominantly concerned the cost of private care workers. The value of informal care peaked at �13,590/yr. Socioeconomic factors do not influence AD public cost, but do affect the level of out-of-pocket expenditure. Conclusion: The burden of AD reflects the structure of Italian welfare. The families predominantly manage AD patients. The public expenditure is mostly for drugs and cash-for-care benefits. From a State perspective in the short term, the advantage of these care arrangements is clear, compared to the cost of residential care. However, if caregivers are not adequately supported, savings may be soon offset by higher risk of caregiver morbidity and mortality produced by high burden and stress. The study has been registered on the website www.clinicaltrials.org (Trial Registration number: NCT01700556). Copyright � International Psychogeriatric Association 2015

Quantitative EEG biomarkers for STXBP1-related disorders

Objective: EEG patterns and quantitative EEG (qEEG) features have been poorly explored in monogenic epilepsies. Herein, we investigate regional differences in EEG frequency composition in patients with STXBP1 developmental and epileptic encephalopathy (STXBP1-DEE). Methods: We conducted a retrospective study collecting electroclinical data of patients with STXBP1-DEE and two control groups of patients with DEEs of different etiologies and typically developing individuals matched for age and sex. We performed a (1) visual EEG assessment, (b) qEEG analysis, and (c) electrical source imaging (ESI). We quantified the relative power (RP) of four frequency bands (α β, θ, δ), in two electrode groups (anterior/posterior), and compared their averages and dynamics (standard deviation [SD] over time). The ESI was performed by applying the standard Distributed Source Modeling algorithm. Results: We analyzed 42 EEG studies in 19 patients with STXBP1-DEE (10 female), with a median age at recordings of 9.6 years (range 9 months to 29 years). The δRP was higher in recordings of STXBP1-DEE (p &lt;.001) compared to both control groups, suggesting the pathogenicity and STXBP1-specificity of these findings. In STXBP1-DEE, the δRP was significantly higher in the anterior electrode group compared to the posterior one (p =.003). There was no correlation between the anterior δRP and the epilepsy focus, age at recordings, and concomitant medications The ESI modeling of this activity showed a widespread involvement of the dorsomesial frontal cortex, suggesting a large corticosubcortical pathologic network. Finally, we identified two groups of recordings: cluster.1 with higher anterior δRP and low dynamics and cluster.2 with lower δRP and higher dynamics. Patients in cluster.1 had a more severe epilepsy and neurological phenotype compared to patients in cluster 2. Significance: The qEEG analysis showed a predominant frontal slow activity as a specific STXBP1 feature that correlates with the severity of the phenotype and may represent a biomarker for prospective longitudinal studies of STXBP1-DEE

IRF2BPL as a novel causative gene for progressive myoclonus epilepsy

IRF2BPL has recently been described as a novel cause of neurodevelopmental disorders with multisystemic regression, epilepsy, cerebellar symptoms, dysphagia, dystonia, and pyramidal signs. We describe a novel IRF2BPL phenotype consistent with progressive myoclonus epilepsy (PME) in three novel subjects and review the features of the 31 subjects with IRF2BPL-related disorders previously reported. Our three probands, aged 28–40 years, harbored de novo nonsense variants in IRF2BPL (c.370C &gt; T, p.[Gln124*] and c.364C &gt; T; p.[Gln122*], respectively). From late childhood/adolescence, they presented with severe myoclonus epilepsy, stimulus-sensitive myoclonus, and progressive cognitive, speech, and cerebellar impairment, consistent with a typical PME syndrome. The skin biopsy revealed massive intracellular glycogen inclusions in one proband, suggesting a similar pathogenic pathway to other storage disorders. Whereas the two older probands were severely affected, the younger proband had a milder PME phenotype, partially overlapping with some of the previously reported IRF2BPL cases, suggesting that some of them might be unrecognized PME. Interestingly, all three patients harbored protein-truncating variants clustered in a proximal, highly conserved gene region around the “coiled-coil” domain. Our data show that PME can be an additional phenotype within the spectrum of IRF2BPL-related disorders and suggest IRF2BPL as a novel causative gene for PME.</p

Introduction to target trial emulation in rehabilitation: a systematic approach to emulate a randomized controlled trial using observational data

Rehabilitation providers and policymakers need valid evidence to make informed decisions about the healthcare needs of the population. Whenever possible, these decisions should be informed by randomized controlled trials (RCTs). However, there are circumstances when evidence needs to be generated rapidly, or when RCTs are not ethical or feasible. These situations apply to studying the effects of complex interventions, including rehabilitation as defined by Cochrane Rehabilitation. Therefore, we explore using the target trial emulation framework by Hernán and colleagues to obtain valid estimates of the causal effects of rehabilitation when RCTs cannot be conducted. Target trial emulation is a framework guiding the design and analysis of non-randomized comparative effectiveness studies using observational data, by emulating a hypothetical RCT. In the context of rehabilitation, we outline steps for applying the target trial emulation framework using real world data, highlighting methodological considerations, limitations, potential mitigating strategies, and causal inference and counterfactual theory as foundational principles to estimating causal effects. Overall, we aim to strengthen methodological approaches used to estimate causal effects of rehabilitation when RCTs cannot be conducted