A comprehensive guide for business people, government administrators and specialists in management methodology, Methodological School of Management details the original and applied thinking, methods ...and approaches established by the school in the Soviet era and still operating successfully in modern Russia today. The Methodological School of Management is not an educational institution, but a range of management tools, which evolved as a part of the 'systems movement' during the second half of the twentieth century. The school was created by the pupils of Georgy Petrovich Shchedrovitsky (1929?1994) under whose leadership a body of knowledge ? the 'starting capital' of the Methodological School of Management ? took shape. The management tools developed by the school are used by its leaders in their current managerial practice. This practice extends to a number of fields: government administration, management of economic sectors, corporate governance and the management of individual corporations. Although the school is less well known to Western specialists in systems engineering methodology and management, this book aims to secure the school a place in the global systems engineering landscape. Its ideas have entered the tool kits of most major control systems and corporations in the world's leading economies, from NASA and Toyota to retail chains ? a clear testimony to the value of Georgy Shchedrovitsky's research, ideas and the body of knowledge he left behind. Shortlisted for the CMI Management Book of the Year award, Methodological School of Management offers solutions for resolving tricky managerial situations and achieving organisational targets ? essential reading for anyone learning how to manage people and issues alike.
Tourette syndrome is a heritable neurodevelopmental disorder whose pathophysiology remains unknown. Recent genome-wide association studies suggest that it is a polygenic disorder influenced by many ...genes of small effect. We tested whether these genes cluster in cellular function by applying gene-set analysis using expert curated sets of brain-expressed genes in the current largest available Tourette syndrome genome-wide association data set, involving 1285 cases and 4964 controls. The gene sets included specific synaptic, astrocytic, oligodendrocyte and microglial functions. We report association of Tourette syndrome with a set of genes involved in astrocyte function, specifically in astrocyte carbohydrate metabolism. This association is driven primarily by a subset of 33 genes involved in glycolysis and glutamate metabolism through which astrocytes support synaptic function. Our results indicate for the first time that the process of astrocyte-neuron metabolic coupling may be an important contributor to Tourette syndrome pathogenesis.
Inhaled antimicrobials enable high local concentrations where needed and, compared to orally administration, greatly reduce the potential for systemic side effects. In SARS-CoV-2 infections, ...hydroxychloroquine sulphate (HCQ) administered as dry powder via inhalation could be safer than oral HCQ allowing higher and therefore more effective pulmonary concentrations without dose limiting toxic effects. To assess the local tolerability, safety and pharmacokinetic parameters of HCQ inhalations in single ascending doses of 5, 10 and 20 mg using the Cyclops dry powder inhaler. Twelve healthy volunteers were included in the study. Local tolerability and safety were assessed by pulmonary function tests, electrocardiogram and recording adverse events. To estimate systemic exposure, serum samples were collected before and 0.5, 2 and 3.5 h after inhalation. Dry powder HCQ inhalations were well tolerated by the participants, except for transient bitter taste in all participants and minor coughing irritation. There was no significant change in QTc-interval or drop in FEV.sub.1 post inhalation. The serum HCQ concentration remained below 10 mug/L in all samples. Single doses of inhaled dry powder HCQ up to 20 mg are safe and well tolerated. Our data support that further studies with inhaled HCQ dry powder to evaluate pulmonary pharmacokinetics and efficacy are warranted.
The dynamics of spontaneous fluctuations in neural activity are shaped by underlying patterns of anatomical connectivity. While numerous studies have demonstrated edge-wise correspondence between ...structural and functional connections, much less is known about how large-scale coherent functional network patterns emerge from the topology of structural networks. In the present study, we deploy a multivariate statistical technique, partial least squares, to investigate the association between spatially extended structural networks and functional networks. We find multiple statistically robust patterns, reflecting reliable combinations of structural and functional subnetworks that are optimally associated with one another. Importantly, these patterns generally do not show a one-to-one correspondence between structural and functional edges, but are instead distributed and heterogeneous, with many functional relationships arising from nonoverlapping sets of anatomical connections. We also find that structural connections between high-degree hubs are disproportionately represented, suggesting that these connections are particularly important in establishing coherent functional networks. Altogether, these results demonstrate that the network organization of the cerebral cortex supports the emergence of diverse functional network configurations that often diverge from the underlying anatomical substrate.
We analysed differences in healthy life expectancy at age 50 (HLE
) between migrants and non-migrants in Belgium, the Netherlands, and England and Wales, and their trends over time between 2001 and ...2011 in the latter two countries. Population, mortality and health data were derived from registers, census or surveys. HLE
was calculated for non-migrants, western and non-western migrants by sex. We applied decomposition techniques to determine whether differences in HLE
between origin groups and changes in HLE
over time were attributable to either differences in mortality or health. The results show that in all three countries and among both sexes, older migrants, in particular those from non-western origin, could expect to live fewer years in good health than older non-migrants, mainly because of differences in self-rated health. Differences in HLE
between migrants and non-migrants diminished over time in the Netherlands, but they increased in England and Wales. Improvements in HLE
over time were mainly attributable to mortality decline. Interventions aimed at reducing the health and mortality inequalities between older migrants and non-migrants should focus on prevention, and target especially non-western migrants.
Automated detection of spikes and seizures has been a subject of research for several decades now. There have been important advances, yet automated detection in EMU (Epilepsy Monitoring Unit) ...settings has not been accepted as standard practice. We intend to implement this software at our EMU and so carried out a qualitative study to identify factors that hinder (‘barriers’) and facilitate (‘enablers’) implementation.
Twenty-two semi-structured interviews were conducted with 14 technicians and neurologists involved in recording and reporting EEGs and eight neurologists who receive EEG reports in the outpatient department. The study was reported according to the Consolidated Criteria for Reporting Qualitative Studies (COREQ).
We identified 14 barriers and 14 enablers for future implementation. Most barriers were reported by technicians. The most prominent barrier was lack of trust in the software, especially regarding seizure detection and false positive results. Additionally, technicians feared losing their EEG review skills or their jobs. Most commonly reported enablers included potential efficiency in the EEG workflow, the opportunity for quantification of EEG findings and the willingness to try the software.
This study provides insight into the perspectives of users and offers recommendations for implementing automated spike and seizure detection in EMUs.
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Abstract Dental plaque accumulation may result in peri-implantitis, an inflammatory process causing loss of supporting bone that may lead to dental implant failure. The antimicrobial activities of ...six metal and metal oxide nanoparticles and two of their composites against bacterial pathogens associated with peri-implantitis were examined under anaerobic conditions. The activities of nanoparticles of silver (Ag), cuprous oxide (Cu2 O), cupric oxide (CuO), zinc oxide (ZnO), titanium dioxide (TiO2 ), tungsten oxide (WO3 ), Ag + CuO composite and Ag + ZnO composite were assessed by minimum inhibitory (bacteriostatic) concentration (MIC) and minimum bactericidal concentration (MBC) determination against Prevotella intermedia , Porphyromonas gingivalis , Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans . Time–kill assays were carried out to examine the dynamics of the antimicrobial activity with ZnO nanoparticles. MIC and MBC values were in the range of <100 μg/mL to 2500 μg/mL and <100 μg/mL to >2500 μg/mL, respectively. The activity of the nanoparticles tested in descending order was Ag > Ag + CuO > Cu2 O > CuO > Ag + ZnO > ZnO > TiO2 > WO3 . Time–kill assays with ZnO demonstrated a significant decrease in growth of all species tested within 4 h, reaching 100% within 2 h for P. gingivalis and within 3 h for F. nucleatum and P. intermedia . Coating titanium surfaces of dental and orthopaedic implants with antimicrobial nanoparticles should lead to an increased rate of implant success.
•Persyst has the highest sensitivity (95%), together with reasonable specificity.•Interrater agreement for Persyst and Encevis are similar to human review.•This report can help prospective users ...choose a software package.
We assessed three commercial automated spike detection software packages (Persyst, Encevis and BESA) to see which had the best performance.
Thirty prolonged EEG records from people aged at least 16 years were collected and 30-minute representative epochs were selected. Interictal epileptiform discharges (IEDs) were marked by three human experts and by all three software packages. For each 30-minutes selection and for each 10-second epoch we measured whether or not IEDs had occurred. We defined the gold standard as the combined detections of the experts. Kappa scores, sensitivity and specificity were estimated for each software package.
Sensitivity for Persyst in the default setting was 95% for 30-minute selections and 82% for 10-second epochs. Sensitivity for Encevis was 86% (30-minute selections) and 61% (10-second epochs). The specificity for both packages was 88% for 30-minute selections and 96%-99% for the 10-second epochs. Interrater agreement between Persyst and Encevis and the experts was similar than between experts (0.67–0.83 versus 0.63–0.67). Sensitivity for BESA was 40% and specificity 100%. Interrater agreement (0.25) was low.
IED detection by the Persyst automated software is better than the Encevis and BESA packages, and similar to human review, when reviewing 30-minute selections and 10-second epochs. This findings may help prospective users choose a software package.
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•Automated seizure detection software does not perform as well as technicians do.•This software can be used in an EMU setting, when the user know its weaknesses.•The persyst software has the best ...performance.
We assessed whether automated detection software, combined with live observation, enabled reliable seizure detection using three commercial software packages: Persyst, Encevis and BESA.
Two hundred and eighty-six prolonged EEG records of individuals aged 16–86 years, collected between August 2019 and January 2020, were retrospectively processed using all three packages. The reference standard included all seizures mentioned in the clinical report supplemented with true detections made by the software and not previously detected by clinical physiologists. Sensitivity was measured for offline review by clinical physiologists and software seizure detection, both in combination with live monitoring in an EMU setting, for all three software packages at record and seizure level.
The database contained 249 seizures in 64 records. The sensitivity of seizure detection was 98% for Encevis and Persyst, and 95% for BESA, when a positive results was defined as detection at least one of the seizures occurring within an individual record. When positivity was defined as recognition of all seizures, sensitivity was 93% for Persyst, 88% for Encevis and 84% for BESA. Clinical physiologists’ review had a sensitivity of 100% at record level and 98% at seizure level. The median false positive rate per record was 1.7 for Persyst, 2.4 for BESA and 5.5 for Encevis per 24 h.
Automated seizure detection software does not perform as well as technicians do. However, it can be used in an EMU setting when the user is aware of its weaknesses. This assessment gives future users helpful insight into these strengths and weaknesses. The Persyst software performs best.
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