Abstract WP98: Characterizing Cerebral Morphometry Changes and Effects of 3K3A-APC in Ischemic Stroke

Introduction: Acute stroke treatment trials have long used radiological endpoints of infarct size and hemorrhage burden to quantify treatment effect. Automated imaging pipelines analyzing cerebral morphometry have become more ubiquitous and can provide more comprehensive insight by measuring specific brain compartments. We piloted a feasibility study to integrate these imaging analyses into an established multicenter stroke trial, the NeuroNEXT trial NN104 (RHAPSODY), which investigated the effect of 3K3A-APC, a recombinant variant of activated protein C active at PAR-1. Methods: Using a well-validated Advanced Normalization Tools (ANTs) pipeline and the MindBoggle OASIS-30 Atropos template, gross compartments of hemispheric white matter, cortical grey matter, and subcortical grey matter were calculated from MRIs from participants >7 days post stroke. Fourteen participants treated with placebo were included, and eleven treated with 3K3A-APC. Results: Participants treated with placebo had mean volumes of 220.0mL, 276.5mL, and 21.7mL in ipsilateral cortical grey matter, white matter, and subcortical grey matter, respectively. Participants in the treatment arm had mean volumes of 227.4mL, 243.7mL, and 21.4mL. Discussion: We present a novel application of dynamic cerebral morphometry software that can be implemented in future large scale multi center stroke trials. This study is limited by its small sample size, and while no treatment effect was observed in this feasibility study, we plan to further refine our algorithm to include more heterogenous, clinically acquired imaging protocols, define more specific compartments, and to ultimately correlate with clinical outcomes.

Download Full-text

CONTRIBUTION OF DNA COPY-NUMBER VARIATION (CNV) TO CANCER SUSCEPTIBILITY AND LARGE-SCALE GENOME ALTERATIONS IN OSTEOSARCOMA (OS)

Clinical & Investigative Medicine ◽

10.25011/cim.v31i4.4821 ◽

2008 ◽

Vol 31 (4) ◽

pp. 19

Author(s):

I Pasic ◽

A Shlien ◽

A Novokmet ◽

C Zhang ◽

U Tabori ◽

...

Keyword(s):

Genomic Instability ◽

Large Scale ◽

Structural Variation ◽

Age Of Onset ◽

Cancer Susceptibility ◽

Small Sample Size ◽

Snp Array ◽

Tumour Suppressor Gene ◽

Small Sample ◽

International Hapmap Project

Introduction: OS, a common Li-Fraumeni syndrome (LFS)-associated neoplasm, is a common bone malignancy of children and adolescents. Sporadic OS is also characterized by young age of onset and high genomic instability, suggesting a genetic contribution to disease. This study examined the contribution of novel DNA structural variation elements, CNVs, to OS susceptibility. Given our finding of excessive constitutional DNA CNV in LFS patients, which often coincide with cancer-related genes, we hypothesized that constitutional CNV may also provide clues about the aetiology of LFS-related sporadic neoplasms like OS. Methods: CNV in blood DNA of 26 patients with sporadic OS was compared to that of 263 normal control samples from the International HapMap project, as well as 62 local controls. Analysis was performed on DNA hybridized to Affymetrix genome-wide human SNP array 6.0 by Partek Genomic Suite. Results: There was no detectable difference in average number of CNVs, CNV length, and total structural variation (product of average CNV number and length) between individuals with OS and controls. While this data is preliminary (small sample size), it argues against the presence of constitutional genomic instability in individuals with sporadic OS. Conclusion: We found that the majority of tumours from patients with sporadic OS show CN loss at chr3q13.31, raising the possibility that chr3q13.31 may represent a “driver” region in OS aetiology. In at least one OS tumour, which displays CN loss at chr3q13.31, we demonstrate decreased expression of a known tumour suppressor gene located at chr3q13.31. We are investigating the role ofchr3q13.31 in development of OS.

Download Full-text

Exploring the laminar connectome

10.1101/2021.03.17.21253439 ◽

2021 ◽

Author(s):

Ittai Shamir ◽

Omri Tomer ◽

Ronnie Krupnik ◽

Yaniv Assaf

Keyword(s):

White Matter ◽

Grey Matter ◽

Structural Description ◽

Mri Imaging ◽

Healthy Human ◽

Cortical Grey Matter ◽

Cortical Laminar ◽

White Matter Connectivity ◽

Human Brains

The human connectome is the complete structural description of the network of connections and elements that form the wiring diagram of the brain. Because of the current scarcity of information regarding laminar end points of white matter tracts inside cortical grey matter, tractography remains focused on cortical partitioning into regions, while ignoring radial partitioning into laminar components. To overcome this biased representation of the cortex as a single homogenous unit, we use a recent data-derived model of cortical laminar connectivity, which has been further explored and corroborated in the macaque brain by comparison to published studies. The model integrates multimodal MRI imaging datasets regarding both white matter connectivity and grey matter laminar composition into a laminar-level connectome. In this study we model the laminar connectome of healthy human brains (N=20) and explore them via a set of neurobiologically meaningful complex network measures. Our analysis demonstrates a subdivision of network hubs that appear in the standard connectome into each individual component of the laminar connectome, giving a fresh look into the role of laminar components in cortical connectivity and offering new prospects in the fields of both structural and functional connectivity.

Download Full-text

Review of the Studies in the Use of Biofeedback Therapy in Rehabilitation and Physiatrics of Neurological Patients

Doctor Ru ◽

10.31550/1727-2378-2021-20-9-43-47 ◽

2021 ◽

Vol 20 (9) ◽

pp. 43-47

Author(s):

E.Yu. Mozheyko ◽

◽

O.V. Petryaeva ◽

◽

...

Keyword(s):

Large Scale ◽

Small Sample Size ◽

Small Sample ◽

Healthy Population ◽

Biofeedback Therapy ◽

Level Of Evidence ◽

Double Blind ◽

Key Points ◽

Neurological Patients ◽

Drug Free

Objective of the Review: To collect information, analyse and evaluate previous studies in the use of biofeedback in neurological patients. Key Points. Despite the wide practical application and a lot of available publications, the level of evidence of this method is low because of a small sample size and the challenges with biofeedback mechanism description. A review of various types of biocontrol, its mechanisms and developments shows that drug-free therapy using only patient’s resources (organic, psychological, emotional and volitional) can activate the mechanisms of neuroplasticity, which are poorly studied. Still, it does not prevent from using biocontrol for the therapy of patients and/or prevention of various diseases in healthy population. Conclusion. Biofeedback therapy has proven to be a safe, relatively efficient and easy-to-use method. However, organisation of a large-scale double blind randomized trial is one of the predominant directions in the future. Keywords: biofeedback, biocontrol, neurofeedback, biofeedback therapy.

Download Full-text

Combining Bayesian Approaches and Evolutionary Techniques for the Inference of Breast Cancer Networks

10.1101/115261 ◽

2017 ◽

Author(s):

Stefano Beretta ◽

Mauro Castelli ◽

Ivo Gonçalves ◽

Ivan Merelli ◽

Daniele Ramazzotti

Keyword(s):

Breast Cancer ◽

Graphical Models ◽

Protein Interactions ◽

Large Scale ◽

Small Sample Size ◽

Small Sample ◽

Cancer Data ◽

Correlation Networks ◽

Model Complex ◽

Cancer Networks

AbstractGene and protein networks are very important to model complex large-scale systems in molecular biology. Inferring or reverseengineering such networks can be defined as the process of identifying gene/protein interactions from experimental data through computational analysis. However, this task is typically complicated by the enormously large scale of the unknowns in a rather small sample size. Furthermore, when the goal is to study causal relationships within the network, tools capable of overcoming the limitations of correlation networks are required. In this work, we make use of Bayesian Graphical Models to attach this problem and, specifically, we perform a comparative study of different state-of-the-art heuristics, analyzing their performance in inferring the structure of the Bayesian Network from breast cancer data.

Download Full-text

Abstract W P20: A Model to Calculate the Expected Treatment Effect in Acute Endovascular Stroke Trials

Stroke ◽

10.1161/str.45.suppl_1.wp20 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Maarten G Lansberg ◽

Robin Lemmens ◽

Soren Christensen ◽

Nishant K Mishra ◽

Gregory W Albers

Keyword(s):

Literature Review ◽

Sample Size ◽

Endovascular Therapy ◽

Treatment Effect ◽

Small Sample Size ◽

Small Sample ◽

Absolute Difference ◽

Sample Size Calculations ◽

And Control ◽

Larger Sample

Background: Recent trials have shown no benefit of endovascular therapy. This may, in part, be explained by inaccurate estimates of the treatment effect used in the sample size calculations of these trials. A predictive model which includes variables that modify the expected treatment effect might yield more accurate estimates, and could be valuable in the design of future acute stroke trials. Methods: We conducted a literature review to obtain estimates of parameters that are associated with good functional outcome (GFO) following recanalization. We developed a model to estimate the treatment effect in endovascular stroke trials and applied this model to two recently published endovascular stroke trials. Results: We estimated a 40% absolute difference in the proportion of GFO (mRS 0-2 at 90 days) associated with reperfusion in patients with ICA or M1 occlusions who have a substantial ischemic penumbra at baseline. To estimate the effect size in trials, this value was multiplied by: 1) the proportion of patients undergoing endovascular therapy in the active treatment arm; 2) the proportion of patients with occlusions of the ICA or MCA-M1; 3) the proportion of patients with a substantial penumbra and a DWI lesion <50mL; and 4) the absolute difference in the proportion of patients with reperfusion, defined as TICI 2B-3, between the endovascular treatment and control arms. Based on literature review we assumed a reperfusion rate of 20% in the control arms of IMS III and MR Rescue, a 50% prevalence of patients with substantial penumbra and DWI lesions<50 mL in IMS III, and a 75% prevalence in the penumbral arms of MR Rescue. Based on these model inputs, a 2.2% increase in GFO with endovascular therapy was expected in IMS III, which closely matches the observed 2.1% increase. For MR Rescue, the model predicted a 1.5% increase in GFO with endovascular therapy. Considering the small sample size, this equates to 0.5 additional patients with GFO which closely matches the observed result of 3 fewer patients with GFO. Conclusion: A simple model shows promise for estimating the treatment effect of endovascular stroke trials. It may be useful for the design of future trials and could lead to different inclusion criteria or larger sample sizes compared to the recently conducted studies.

Download Full-text

Copy number variation analysis of twin pairs discordant for cleft lip with or without cleft palate

International Journal of Immunopathology and Pharmacology ◽

10.1177/2058738419855873 ◽

2019 ◽

Vol 33 ◽

pp. 205873841985587

Author(s):

Luca Scapoli ◽

Francesco Carinci ◽

Annalisa Palmieri ◽

Francesca Cura ◽

Alessandro Baj ◽

...

Keyword(s):

Cleft Palate ◽

Copy Number ◽

Large Scale ◽

Cleft Lip ◽

Small Sample Size ◽

Copy Number Variants ◽

Monozygotic Twins ◽

Monozygotic Twin ◽

Small Sample ◽

High Level

Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a frequent orofacial malformation. The comparison of concordance rate observed in monozygotic and dizygotic twins supports high level of heritability and a strong genetic component. However, phenotype concordance for orofacial cleft in monozygotic twins is about 50%. The aim of the present investigation was to detect postzygotic events that may account for discordance in monozygotic twins. High-density SNP microarrays hybridization was used to genotype two pairs of monozygotic twins discordant for nsCL/P. Discordant SNP genotypes and copy number variants were analyzed to identify genetic differences responsible of phenotype discrepancy. A number of differences were observed, none involving known nsCL/P candidate genes or genomic regions. Considering the limitation of the study, related to the small sample size and to the large-scale investigation method, the results suggest that the detection of discordant events in other monozygotic twin pairs would be remarkable and warrant further investigations.

Download Full-text

Regional brain volumes, microstructure and neurodevelopment in moderate–late preterm children

Archives of Disease in Childhood - Fetal and Neonatal Edition ◽

10.1136/archdischild-2019-317941 ◽

2020 ◽

Vol 105 (6) ◽

pp. 593-599 ◽

Cited By ~ 1

Author(s):

Claire E Kelly ◽

Deanne K Thompson ◽

Alicia J Spittle ◽

Jian Chen ◽

Marc L Seal ◽

...

Keyword(s):

White Matter ◽

Grey Matter ◽

Diffusion Tensor ◽

Brain Mri ◽

Developmental Outcomes ◽

Late Preterm ◽

Brain Volumes ◽

Regional Brain ◽

White Matter Microstructure ◽

Cortical Grey Matter

ObjectiveTo explore whether regional brain volume and white matter microstructure at term-equivalent age (TEA) are associated with development at 2 years of age in children born moderate–late preterm (MLPT).Study designA cohort of MLPT infants had brain MRI at approximately TEA (38–44 weeks’ postmenstrual age) and had a developmental assessment (Bayley Scales of Infant and Toddler Development and Infant Toddler Social Emotional Assessment) at 2 years’ corrected age. Relationships between cortical grey matter and white matter volumes and 2-year developmental outcomes were explored using voxel-based morphometry. Relationships between diffusion tensor measures of white matter microstructure (fractional anisotropy (FA) and axial (AD), radial (RD) and mean (MD) diffusivities) and 2-year developmental outcomes were explored using tract-based spatial statistics.Results189 MLPT children had data from at least one MRI modality (volumetric or diffusion) and data for at least one developmental domain. Larger cortical grey and white matter volumes in many brain regions, and higher FA and lower AD, RD and MD in several major white matter regions, were associated with better cognitive and language scores. There was little evidence that cortical grey matter and white matter volumes and white matter microstructure were associated with motor and behavioural outcomes.ConclusionsRegional cortical grey matter and white matter volumes and white matter microstructure are associated with cognitive and language development at 2 years of age in MLPT children. Thus, early alterations to brain volumes and microstructure may contribute to some of the developmental deficits described in MLPT children.

Download Full-text

Distributed grey and white matter deficits in hyperkinetic disorder: MRI evidence for anatomical abnormality in an attentional network

Psychological Medicine ◽

10.1017/s0033291701004706 ◽

2001 ◽

Vol 31 (8) ◽

pp. 1425-1435 ◽

Cited By ~ 122

Author(s):

S. OVERMEYER ◽

E. T. BULLMORE ◽

J. SUCKLING ◽

A. SIMMONS ◽

S. C. R. WILLIAMS ◽

...

Keyword(s):

White Matter ◽

Basal Ganglia ◽

Large Scale ◽

Grey Matter ◽

Right Hemisphere ◽

Hyperkinetic Disorder ◽

Normal Children ◽

Pyramidal Tracts ◽

Icd 10 ◽

The Right

Background. Previous neuroimaging studies of children with attention deficit hyperactivity disorder (ADHD) have demonstrated anatomic and functional abnormalities predominantly in frontal and striatal grey matter. Here we report the use of novel image analysis methods, which do not require prior selection of regions of interest, to characterize distributed morphological deficits of both grey and white matter associated with ADHD.Methods. Eighteen children with a refined phenotype of ADHD, who also met ICD-10 criteria for hyperkinetic disorder (mean age 10·4 years), and 16 normal children (mean age 10·3 years) were compared using magnetic resonance imaging. The groups were matched for handedness, sex, height, weight and head circumference. Morphological differences between groups were estimated by fitting a linear model at each voxel in standard space, applying a threshold to the resulting voxel statistic maps to generate clusters of spatially contiguous suprathreshold voxels, and testing cluster ‘mass’, or the sum of suprathreshold voxel statistics in each 2D cluster, by repeated random resampling of the data.Results. The hyperkinetic children had significant grey matter deficits in right superior frontal gyrus (Brodmann area (BA) 8/9), right posterior cingulate gyrus (BA 30) and the basal ganglia bilaterally (especially right globus pallidus and putamen). They also demonstrated significant central white matter deficits in the left hemisphere anterior to the pyramidal tracts and superior to the basal ganglia.Conclusions. This pattern of spatially distributed grey matter deficit in the right hemisphere is compatible with the hypothesis that ADHD is associated with disruption of a large scale neurocognitive network for attention. The left hemispheric white matter deficits may be due to dysmyelination.

Download Full-text

Facebook as a platform for co-creating music festival experiences

International Journal of Event and Festival Management ◽

10.1108/ijefm-02-2016-0012 ◽

2016 ◽

Vol 7 (2) ◽

pp. 84-99 ◽

Cited By ~ 14

Author(s):

Emma Hoksbergen ◽

Andrea Insch

Keyword(s):

Young Adults ◽

Large Scale ◽

Small Sample Size ◽

Small Sample ◽

Survey Method ◽

Future Research ◽

Content Type ◽

Music Festival ◽

Alternative Means ◽

On Line

Purpose The purpose of this paper is to address the need to understand how younger music festival-goers use and engage with a music festival’s Facebook page, and how they perceive this social networking service (SNS) as a potential on-line platform for value co-creation. Design/methodology/approach Face-to-face in-depth interviews were conducted with 16 young adults who attended an annual New Year’s Eve music festival, Rhythm and Vines, in Gisborne, New Zealand. Findings Analysis of the interview data revealed that the majority of participants did not actively engage with this platform and could be categorised as passive viewers or information-seekers. In addition, participants perceived five types of value from using this SNS: functional, social, emotional, interactive and aesthetic value. Even though participants were not segmented due to the small sample size, patterns in their levels of engagement with Facebook, attendance status, reasons for attending the festival and the combinations of forms of value that they perceived were identified. Research limitations/implications Future research should use a large-scale survey method to obtain a representative sample that is generalisable to a specific population of music festival-goers. Practical implications Dominance of features on Facebook providing festival-goers with functional value suggests they prefer a passive or co-optation approach to value co-creation in this context. Due to the limited extent of participants actively co-creating value on this platform, alternative means of encouraging interaction to co-create value with festival-goers should be investigated. Originality/value This study demonstrates that this SNS provides this group of young adults with a means to connect their real-time festival experience, with their on-line Facebook social network during the year.

Download Full-text