scholarly journals Hidden Aspects of the Research-ADOS are Bound to Affect Autism Science

2019 ◽  
Author(s):  
Elizabeth B Torres ◽  
Richa Rai ◽  
Sejal Mistry ◽  
Brenda Gupta

AbstractThe research-grade ADOS is a broadly used instrument that informs and steers much of the science of Autism. Despite its broad use, little is known about the empirical variability inherently present in the scores of the ADOS scale, or their appropriateness to define change, to repeatedly use this test to characterize neurodevelopmental trajectories. Here we examine the empirical distributions of research-grade ADOS scores from 1,324 records in a cross-section of the population comprising participants with autism between 5-65 years of age. We find that these empirical distributions violate the theoretical requirements of normality and homogeneous variance, essential for independence between bias and sensitivity. Further, we assess a subset of 52 typical controls vs. those with autism and find lack of proper elements to characterize neurodevelopmental trajectories in a coping nervous system changing at non-uniform, non-linear rates. Lastly, longitudinally repeating the assessments over 4 visits in a subset of the participants with autism for whom verbal criteria kept the same appropriate ADOS modules over the timespan of the 4 visits, reveals that switching the clinician, changes the cutoff scores, and consequently, influences the diagnosis, despite maintaining fidelity in the same test’s modules, room conditions and tasks’ fluidity per visit. Given the changes in probability distribution shape and dispersion of these ADOS scores, the lack of appropriate metric spaces, and the impact that these elements have on sensitivity-bias co-dependencies, and on longitudinal tracking of autism, we invite a discussion on the use of this test for scientific purposes.

2020 ◽  
Vol 32 (3) ◽  
pp. 515-561 ◽  
Author(s):  
Elizabeth B. Torres ◽  
Richa Rai ◽  
Sejal Mistry ◽  
Brenda Gupta

The research-grade Autism Diagnostic Observational Schedule (ADOS) is a broadly used instrument that informs and steers much of the science of autism. Despite its broad use, little is known about the empirical variability inherently present in the scores of the ADOS scale or their appropriateness to define change and its rate, to repeatedly use this test to characterize neurodevelopmental trajectories. Here we examine the empirical distributions of research-grade ADOS scores from 1324 records in a cross-section of the population comprising participants with autism between five and 65 years of age. We find that these empirical distributions violate the theoretical requirements of normality and homogeneous variance, essential for independence between bias and sensitivity. Further, we assess a subset of 52 typical controls versus those with autism and find a lack of proper elements to characterize neurodevelopmental trajectories in a coping nervous system changing at nonuniform, nonlinear rates. Repeating the assessments over four visits in a subset of the participants with autism for whom verbal criteria retained the same appropriate ADOS modules over the time span of the four visits reveals that switching the clinician changes the cutoff scores and consequently influences the diagnosis, despite maintaining fidelity in the same test's modules, room conditions, and tasks' fluidity per visit. Given the changes in probability distribution shape and dispersion of these ADOS scores, the lack of appropriate metric spaces to define similarity measures to characterize change and the impact that these elements have on sensitivity-bias codependencies and on longitudinal tracking of autism, we invite a discussion on readjusting the use of this test for scientific purposes.


2020 ◽  
Vol 21 (15) ◽  
pp. 5475 ◽  
Author(s):  
Manuela Pennisi ◽  
Giuseppe Lanza ◽  
Luca Falzone ◽  
Francesco Fisicaro ◽  
Raffaele Ferri ◽  
...  

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii438-iii438
Author(s):  
Kathleen Dorris ◽  
Jessica Channell ◽  
Ashley Mettetal ◽  
Molly Hemenway ◽  
Natalie Briones ◽  
...  

Abstract BACKGROUND Cannabinoids, including cannabidiol (CBD) and tetrahydrocannabinol (THC), are a class of compounds found in marijuana. Numerous studies in adults have examined cannabinoid use in management of cancer-related symptoms such as nausea, anorexia, and pain. Less is known about the use in the pediatric oncology population. METHODS A prospective observational study has been ongoing since 2016 at Children’s Hospital Colorado to evaluate cannabinoids’ impact using PedsQL™ modules on quality of life of pediatric patients with central nervous system (CNS) tumors who are 2–18 years old. Laboratory assessments of T-cell activity and pharmacokinetics of CBD, THC and associated metabolites are in process. Diaries with exploratory information on cannabinoid use patterns are being collected. RESULTS Thirty-three patients (14:19; male:female) have been enrolled with a median age of 6.4 years (range, 2.9–17.7 years). The most common tumor type in enrolled patients is embryonal tumors (13/33; 39%). Nine (27%) patients have low-grade glial/glioneuronal tumors, and eight (24%) had high-grade/diffuse midline gliomas. The remaining patients had ependymoma or craniopharyngioma. The median time on cannabinoids is 9 months. Most (n=20) patients have used oral products with CBD and THC. One patient continues on cannabinoid therapy in follow up. Preliminary immune function analyses identified impaired neutrophil superoxide anion production and chemotaxis in patients taking cannabinoids at early time points on therapy. CONCLUSIONS Families of children with various CNS tumors are pursuing cannabinoid therapy for both antitumor and supportive care purposes. Analysis of the impact of cannabinoids on patients’ quality of life is ongoing.


2020 ◽  
Vol 2020 (11) ◽  
Author(s):  
Claude Duhr ◽  
Falko Dulat ◽  
Bernhard Mistlberger

Abstract We present the production cross section for a lepton-neutrino pair at the Large Hadron Collider computed at next-to-next-to-next-to-leading order (N3LO) in QCD perturbation theory. We compute the partonic coefficient functions of a virtual W± boson at this order. We then use these analytic functions to study the progression of the perturbative series in different observables. In particular, we investigate the impact of the newly obtained corrections on the inclusive production cross section of W± bosons, as well as on the ratios of the production cross sections for W+, W− and/or a virtual photon. Finally, we present N3LO predictions for the charge asymmetry at the LHC.


Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 465
Author(s):  
Silvia Cerantola ◽  
Valentina Caputi ◽  
Gabriella Contarini ◽  
Maddalena Mereu ◽  
Antonella Bertazzo ◽  
...  

Antidopaminergic gastrointestinal prokinetics are indeed commonly used to treat gastrointestinal motility disorders, although the precise role of dopaminergic transmission in the gut is still unclear. Since dopamine transporter (DAT) is involved in several brain disorders by modulating extracellular dopamine in the central nervous system, this study evaluated the impact of DAT genetic reduction on the morpho-functional integrity of mouse small intestine enteric nervous system (ENS). In DAT heterozygous (DAT+/−) and wild-type (DAT+/+) mice (14 ± 2 weeks) alterations in small intestinal contractility were evaluated by isometrical assessment of neuromuscular responses to receptor and non-receptor-mediated stimuli. Changes in ENS integrity were studied by real-time PCR and confocal immunofluorescence microscopy in longitudinal muscle-myenteric plexus whole-mount preparations (). DAT genetic reduction resulted in a significant increase in dopamine-mediated effects, primarily via D1 receptor activation, as well as in reduced cholinergic response, sustained by tachykininergic and glutamatergic neurotransmission via NMDA receptors. These functional anomalies were associated to architectural changes in the neurochemical coding and S100β immunoreactivity in small intestine myenteric plexus. Our study provides evidence that genetic-driven DAT defective activity determines anomalies in ENS architecture and neurochemical coding together with ileal dysmotility, highlighting the involvement of dopaminergic system in gut disorders, often associated to neurological conditions.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii322-iii322
Author(s):  
Raoull Hoogendijk ◽  
Jasper van der Lugt ◽  
Dannis van Vuurden ◽  
Eelco Hoving ◽  
Leontien Kremer ◽  
...  

Abstract BACKGROUND Variation in survival of pediatric central nervous system (CNS) tumors is large between countries. Within Europe, the Netherlands had one of the worst reported survival rates of malignant CNS (mCNS) tumors during 2000–2007. METHODS Using the Netherlands Cancer Registry, we evaluated trends in incidence and survival of pediatric mCNS tumors (behavior /3, 5th digit in the morphology code) diagnosed between 1990–2017. RESULTS 839 newly-diagnosed mCNS tumor patients <18 years were registered between 1990–2017. Incidence of mCNS tumors remained stable (average incidence rate, 21.6 per million person-years). However, an increased incidence of malignant gliomas, NOS was found (Estimated Annual Percentage Change (EAPC) 11.6% p<0.001). This appears to be related to a registration shift between 1990–1999 and 2000–2009 as brainstem tumors increased (+25%, n=79) for astrocytomas and other gliomas but decreased (-31%, n=32) for unspecified intracranial and intraspinal neoplasms. Overall, 5-year observed survival (5Y-OS) of mCNS tumors increased from 51% in 1990–1999 to 61% in 2010–2017 (P-for-trend<0.001). This increase was not constant over time, as 5Y-OS for the period 2000–2009 was 47%. The only significant decrease in survival was found for malignant astrocytomas and other gliomas with a 5Y-OS of 56% in 1990–1999 decreasing to 48% in 2010–2017 (P-for-trend<0.001). CONCLUSION Between 1990–2017 incidence of mCNS tumors in the Netherlands remained stable and survival increased. However, a decrease in survival was seen for malignant astrocytomas and other gliomas, which is partially explained by the registration shift of brainstem tumors. The impact of this shift on survival for all mCNS tumors is subject to further research.


2021 ◽  
Vol 13 (10) ◽  
pp. 5494
Author(s):  
Lucie Kucíková ◽  
Michal Šejnoha ◽  
Tomáš Janda ◽  
Jan Sýkora ◽  
Pavel Padevět ◽  
...  

Heating wood to high temperature changes either temporarily or permanently its physical properties. This issue is addressed in the present contribution by examining the effect of high temperature on residual mechanical properties of spruce wood, grounding on the results of full-scale fire tests performed on GLT beams. Given these tests, a computational model was developed to provide through-thickness temperature profiles allowing for the estimation of a charring depth on the one hand and on the other hand assigning a particular temperature to each specimen used subsequently in small-scale tensile tests. The measured Young’s moduli and tensile strengths were accompanied by the results from three-point bending test carried out on two groups of beams exposed to fire of a variable duration and differing in the width of the cross-section, b=100 mm (Group 1) and b=160 mm (Group 2). As expected, increasing the fire duration and reducing the initial beam cross-section reduces the residual bending strength. A negative impact of high temperature on residual strength has also been observed from simple tensile tests, although limited to a very narrow layer adjacent to the charring front not even exceeding a typically adopted value of the zero-strength layer d0=7 mm. On the contrary, the impact on stiffness is relatively mild supporting the thermal recovery property of wood.


1988 ◽  
Vol 40-41 ◽  
pp. 786-787
Author(s):  
Baozhu Luo ◽  
Jiaqi Yu ◽  
Guozhu Zhong
Keyword(s):  

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Andrius Slavickas ◽  
Raimondas Pabarčius ◽  
Aurimas Tonkūnas ◽  
Gediminas Stankūnas

The decomposition analysis of void reactivity coefficient for innovative BWR assemblies is presented in this paper. The innovative assemblies were loaded with high enrichment UO2and MOX fuels. Additionally the impact of the moderation enhancement on the void reactivity coefficient through a full fuel burnup discharge interval was investigated for the innovative assembly with MOX fuel. For the numerical analysis the TRITON functional module of SCALE code with ENDF/B-VI cross section library was applied. The obtained results indicate the influence of the most important isotopes to the void reactivity behaviour over a fuel burnup interval of 70 GWd/t for both UO2and MOX fuels. From the neutronic safety concern positive void reactivity coefficient values are observed for MOX fuel at the beginning of the fuel irradiation cycle. For extra-moderated assembly designs, implementing 8 and 12 water holes, the neutron spectrum softening is achieved and consequently the lower void reactivity values. Variations in void reactivity coefficient values are explained by fulfilled decomposition analysis based on neutrons absorption reactions for separate isotopes.


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