Growth Rules for the Repair of Asynchronous Irregular Neuronal Networks after Peripheral Lesions

© 2021 Sinha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License. https://creativecommons.org/licenses/by/4.0/Several homeostatic mechanisms enable the brain to maintain desired levels of neuronal activity. One of these, homeostatic structural plasticity, has been reported to restore activity in networks disrupted by peripheral lesions by altering their neuronal connectivity. While multiple lesion experiments have studied the changes in neurite morphology that underlie modifications of synapses in these networks, the underlying mechanisms that drive these changes are yet to be explained. Evidence suggests that neuronal activity modulates neurite morphology and may stimulate neurites to selective sprout or retract to restore network activity levels. We developed a new spiking network model of peripheral lesioning and accurately reproduced the characteristics of network repair after deafferentation that are reported in experiments to study the activity dependent growth regimes of neurites. To ensure that our simulations closely resemble the behaviour of networks in the brain, we model deafferentation in a biologically realistic balanced network model that exhibits low frequency Asynchronous Irregular (AI) activity as observed in cerebral cortex. Our simulation results indicate that the re-establishment of activity in neurons both within and outside the deprived region, the Lesion Projection Zone (LPZ), requires opposite activity dependent growth rules for excitatory and inhibitory post-synaptic elements. Analysis of these growth regimes indicates that they also contribute to the maintenance of activity levels in individual neurons. Furthermore, in our model, the directional formation of synapses that is observed in experiments requires that pre-synaptic excitatory and inhibitory elements also follow opposite growth rules. Lastly, we observe that our proposed structural plasticity growth rules and the inhibitory synaptic plasticity mechanism that also balances our AI network both contribute to the restoration of the network to pre-deafferentation stable activity levels.Peer reviewe

A systematic review of the reporting of Data Monitoring Committees' roles, interim analysis and early termination in pediatric clinical trials

<p>Abstract</p> <p>Background</p> <p>Decisions about interim analysis and early stopping of clinical trials, as based on recommendations of Data Monitoring Committees (DMCs), have far reaching consequences for the scientific validity and clinical impact of a trial. Our aim was to evaluate the frequency and quality of the reporting on DMC composition and roles, interim analysis and early termination in pediatric trials.</p> <p>Methods</p> <p>We conducted a systematic review of randomized controlled clinical trials published from 2005 to 2007 in a sample of four general and four pediatric journals. We used full-text databases to identify trials which reported on DMCs, interim analysis or early termination, and included children or adolescents. Information was extracted on general trial characteristics, risk of bias, and a set of parameters regarding DMC composition and roles, interim analysis and early termination.</p> <p>Results</p> <p>110 of the 648 pediatric trials in this sample (17%) reported on DMC or interim analysis or early stopping, and were included; 68 from general and 42 from pediatric journals. The presence of DMCs was reported in 89 of the 110 included trials (81%); 62 papers, including 46 of the 89 that reported on DMCs (52%), also presented information about interim analysis. No paper adequately reported all DMC parameters, and nine (15%) reported all interim analysis details. Of 32 trials which terminated early, 22 (69%) did not report predefined stopping guidelines and 15 (47%) did not provide information on statistical monitoring methods.</p> <p>Conclusions</p> <p>Reporting on DMC composition and roles, on interim analysis results and on early termination of pediatric trials is incomplete and heterogeneous. We propose a minimal set of reporting parameters that will allow the reader to assess the validity of trial results.</p

Cost of hospital management of Clostridium difficile infection in United States - a meta-analysis and modelling study

Background: Clostridium difficile infection (CDI) is the leading cause of infectious nosocomial diarrhoea but the economic costs of CDI on healthcare systems in the US remain uncertain. Methods: We conducted a systematic search for published studies investigating the direct medical cost associated with CDI hospital management in the past 10 years (2005-2015) and included 42 studies to the final data analysis to estimate the financial impact of CDI in the US. We also conducted a meta-analysis of all costs using Monte Carlo simulation. Results: The average cost for CDI case management and average CDI-attributable costs per case were $42,316 (90$ 39,886, $44,765) and$ 21,448 (90 % CI: $21,152,$ 21,744) in 2015 US dollars. Hospital-onset CDIattributable cost per case was $34,157 (90$ 33,134, $35,180), which was 1.5 times the cost of communityonset CDI ($ 20,095 [ 90 % CI: $4991,$ 35,204]). The average and incremental length of stay (LOS) for CDI inpatient treatment were 11.1 (90 % CI: 8.7-13.6) and 9.7 (90 % CI: 9.6-9.8) days respectively. Total annual CDI-attributable cost in the US is estimated US$6.3 (Range:$ 1.9-$ 7.0) billion. Total annual CDI hospital management required nearly 2.4 million days of inpatient stay. Conclusions: This review indicates that CDI places a significant financial burden on the US healthcare system. This review adds strong evidence to aid policy-making on adequate resource allocation to CDI prevention and treatment in the US. Future studies should focus on recurrent CDI, CDI in long-term care facilities and persons with comorbidities and indirect cost from a societal perspective. Health-economic studies for CDI preventive intervention are needed.Sanofi PasteurSCI(E)[email protected]

7.5 Researching Equity and Effectiveness in Education: Examples from the UK and Germany

Many examples of educational research, including international comparative school achievement studies have clearly documented that school attainments and school careers of children are linked in many countries to their origins (ethnic and cultural) and the socioeconomic situation of the family they grow up in. However, the extent of the equity gap for specific student groups and explanations for it vary. As consequence, a number of longitudinal educational studies have been set up to investigate these phenomena and shed light on the question how to overcome such inequity. The current chapter first explores different definitions of equity and presents then two large, longitudinal studies conducted in England and Germany that investigate children’s development from preschool age through primary education. Both studies were set up to investigate the influences of individual child, family, home learning, preschool and primary school influences on children’s development. A core question of both studies is how (pre-)school can contribute to reducing the negative influence of early childhood disadvantage and thus potentially help reduce inequity in later educational outcomes (see Sammons, Anders and Hall, 2013 for further discussion). The Effective Provision of Pre-, Primary and Secondary Project in England (EPPSE) has tracked 3000+ children since 1996, whereas the German BiKS-study is investigating the development of around 550 children. The two studies share many similarities in their designs and methodological approaches, although there are also some important differences. Recent results of both studies are presented and discussed in terms of both the quantitative modeling strategies adopted and the interpretation of statistical findings

Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)

A panel of experts was convened by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) to update the 2010 clinical practice guideline on Clostridium difficile infection (CDI) in adults. The update, which has incorporated recommendations for children (following the adult recommendations for epidemiology, diagnosis, and treatment), includes significant changes in the management of this infection and reflects the evolving controversy over best methods for diagnosis. Clostridium difficile remains the most important cause of healthcare-associated diarrhea and has become the most commonly identified cause of healthcare-associated infection in adults in the United States. Moreover, C. difficile has established itself as an important community pathogen. Although the prevalence of the epidemic and virulent ribotype 027 strain has declined markedly along with overall CDI rates in parts of Europe, it remains one of the most commonly identified strains in the United States where it causes a sizable minority of CDIs, especially healthcare-associated CDIs. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, infection prevention, and environmental management

The fifth phase of Educational Effectiveness Research: The philosophy and measurement of equity

Educational Effectiveness Research (EER) investigates, and seeks to explain, the causal relationships in formal school settings between on the one hand outcomes (both academic-cognitive and educational-affective) and on the other, inputs (student intake characteristics such as social background and prior attainment). Of course, ratios of output-to-input are simply measures of efficiency, not effectiveness, but EER goes beyond this to look at the educative processes between inputs and outputs and the policy context in which these processes are set, and this is what justifies ‘effectiveness’ in the nomenclature. Recently there has been a certain nervousness within the field about the formality of the institutional setting within the EER paradigm - usually schools but more recently pre-schools and colleges of further education – and this has manifested itself in a desire to be more inclusive in how the field is defined, as if the mere fact of blurring the boundaries of the discipline will meet some higher social aspiration. The practical reality remains that usually only formal systems collect the kind of empirical data that underpins EER methodologies and enables modelling to take place at the level of the pupil, the teacher, the school and the system, although some EER studies have also added measures of out-of-school learning (e.g. engagement in private tutoring, time spent on homework and other home learning environment measures) to provide additional controls of intake differences between schools or cohorts and to provide insights into the potential importance of such out-of-school learning opportunities. The educative processes (broadly defined) within EER constitute the sub-field of School Improvement Research (SIR), which investigates factors such as classroom teaching, curriculum, school and classroom behaviour, learning climate, organisation and leadership, and their effect on student outcomes / outputs. These processes are closely linked to policy and system-level factors, just as inputs are intrinsically linked to the social and cultural milieu of the school, but in its forty-year-old morphology, EER has tended to overlook the impact of context on outcomes: the field measures what society deems valuable. This is not ‘context’ in the usual sense, but it is a context nevertheless - a philosophical one – and it is something that should not be ignored, especially as EER moves into a new phase where it is applied to the issue of equity.<br/