Modelling correlated data : multilevel models and generalized estimating equations and their use with data from research in developmental disabilities

Background: The use of Multilevel Models (MLM) and Generalized Estimating Equations (GEE) for analysing clustered data in the field of intellectual and developmental disability (IDD) research is still limited. Method: We present some important features of MLMs and GEEs: main function, assumptions, model specification and estimators, sample size and power. We provide an overview of the ways MLMs and GEEs have been used in IDD research. Results: While MLMs and GEEs are both appropriate for longitudinal and/or clustered data, they differ in the assumptions they impose on the data, and the inferences made. Estimators in MLMs require appropriate model specification, while GEEs are more resilient to misspecification at the expense of model complexity. Studies on sample size seem to suggest that Level 1 coefficients are robust to small samples/clusters, with any higher-level coefficients less so. MLMs have been used more frequently than GEEs in IDD research, especially for fitting developmental trajectories. Conclusions: Clustered data from research in the IDD field can be analysed flexibly using MLMs and GEEs. These models would be more widely used if journals required the inclusion of technical specification detail, simulation studies examined power for IDD study characteristics, and researchers developed core skills during basic studies

Reduction of large-scale RLCk models via low-rank balanced truncation

Model order reduction (MOR) is an important step in the design process of integrated circuits. Specifically, the electromagnetic models extracted from modern complex designs result in a large number of passive elements that introduce limitations in the simulation process. MOR techniques based on balanced truncation (BT) can overcome these limitations by producing compact reduced-order models (ROMs) that approximate the behavior of the original models at the input/output ports. In this paper, we present a low-rank BT method that exploits the extended Krylov subspace and efficient implementation techniques for the reduction of large-scale models. Experimental evaluation on a diverse set of analog and mixed-signal circuits with millions of elements indicates that up to x5.5 smaller ROMs can be produced with similar accuracy to ANSYS RaptorX ROMs

Τριπλά Υδρόφιλα Στατιστικά Συμπολυμερή με Πολυμερισμό RAFT: Σύνθεση και Ιδιότητες σε Υδατικά Διαλύματα

Στην παρούσα εργασία συντέθηκαν καινοτόμα συμπολυμερή μεθακρυλικών εστέρων με πιθανές βιολογικές εφαρμογές. Η αυτο-οργάνωση των στατιστικών/τυχαίων συμπολυμερών σε υδατικά μέσα με την μορφή αυτο-οργανωμένων νανοσωματιδίων τα καθιστά ιδιαίτερα ελκυστικά για εφαρμογή σε έρευνες μεταφοράς φαρμακευτικών ουσιών σε ιστούς. Η μελέτη της εργασίας αφορά την σύνθεση τριπλά υδρόφιλων στατιστικών συμπολυμερών πολυ(μεθακρυλικού εστέρα της διαιθυλενογλυκόλης-co-μεθακρυλικού εστέρα της διμεθυλοαμινο αιθανόλης-co-μεθακρυλικού εστέρα της ολιγοαιθυλενογλυκόλης) ([poly(di(ethylene glycol) methyl ether methacrylate-co-2-(dimethylamino)ethyl methacrylate-co-oligoethylene glycol methyl ether methacrylate]), P(DEGMA-co-DMAEMA-co-OEGMA) μέσω της μεθόδου RAFT, σε τρεις διαφορετικές συστάσεις μονομερών. Στη συνέχεια ακολούθησε ο μοριακός χαρακτηρισμός των συντιθέμενων τριπολυμερών μέσω χρωματογραφίας αποκλεισμού μεγεθών (SEC) και φασματοσκοπικών μεθόδων (1H-NMR, ATR-FTIR). Η ενδελεχής μελέτη της αυτο-οργάνωσης των τριπολυμερών σε υδατικά διαλύματα και η αποκρισιμότητά τους σε εξωτερικά ερεθίσματα διεξάχθηκε μέσω πειραμάτων δυναμικής και ηλεκτροφορετικής σκέδασης φωτός (DLS, ELS) σε εύρος θερμοκρασιών, διαφορετικές τιμές pH και παρουσία άλατος διαφορετικών συγκεντρώσεων. Ο έλεγχος της ισορροπίας υδρόφιλου και υδρόφοβου χαρακτήρα κατά την επιβολή εξωτερικών ερεθισμάτων στα τριπολυμερή ελέγχθηκε μέσω φασματοσκοπίας φθορισμού (FS). Τέλος, μελετήθηκε η σύμπλεξη και η συνοργάνωση του μοναδικού έντονα θερμοαποκρινόμενου τριπολυμερούς με ταννικό οξύ και Tween 80 αντίστοιχα, καθώς και η επίδραση των δύο ενώσεων στην αυτο-οργάνωση του τριπολυμερούς σε υδατικό μέσο.In this work we report the synthesis of novel triple hydrophilic random copolymers consisted of three different methacrylates, that have the potential to be applied in the field of nanomedicine. Their ability to self-assemble into random morphologies of nanoparticles, when diluted in distilled water, makes them strong candidates to participate in research which target drug and gene delivery. The aim of this study is the synthesis of random terpolymers poly(di(ethylene glycol) methyl ether methacrylate- co -2- (dimethylamino)ethyl methacrylate- co- oligoethylene glycol methyl ether methacrylate), P(DEGMA-co-DMAEMA-co-OEGMA) of three different compositions, using the RAFT method. Their molecular characterization was carried out using size exclusion chromatography (SEC) and spectroscopic techniques 1H-NMR and ATR/FT-IR. As far as their self-assembly properties, studies of dynamic light scattering (DLS) were held, emphasizing their potential responsiveness regarding change of temperature, pH and at the presence of salt of different concentrations. In addition, we studied the change in hydrophilic/hydrophobic balance of the terpolymer during heating and cooling, using fluorescence spectroscopy (FS). Finally, experiments were processed with the complexation of the only thermoresponsive copolymer with tannic acid and Tween 80 and in particular we investigated their influence on the self-assembly of the terpolymer in aqueous solution

Exploring the assumptions underlying genetic variation in host nematode resistance (Open Access publication)

The wide range of genetic parameter estimates for production traits and nematode resistance in sheep obtained from field studies gives rise to much speculation. Using a mathematical model describing host – parasite interactions in a genetically heterogeneous lamb population, we investigated the consequence of: (i) genetic relationships between underlying growth and immunological traits on estimated genetic parameters for performance and nematode resistance, and (ii) alterations in resource allocation on these parameter estimates. Altering genetic correlations between underlying growth and immunological traits had large impacts on estimated genetic parameters for production and resistance traits. Extreme parameter values observed from field studies could only be reproduced by assuming genetic relationships between the underlying input traits. Altering preferences in the resource allocation had less pronounced effects on the genetic parameters for the same traits. Effects were stronger when allocation shifted towards growth, in which case worm burden and faecal egg counts increased and genetic correlations between these resistance traits and body weight became stronger. Our study has implications for the biological interpretation of field data, and for the prediction of selection response from breeding for nematode resistance. It demonstrates the profound impact that moderate levels of pleiotropy and linkage may have on observed genetic parameters, and hence on outcomes of selection for nematode resistance

Predictability studies of coastal marine ecosystem behavior

The study presented in this thesis is principally meant to analyze the genericity of a deterministic, comprehensive marine ecosystem model in combination with various refined representations of hydrodynamical processes, and to evaluate the potential predictability skills of this combined modelling system with specific applications in two rather different coastal basins. This objective has been realized by first developing a modular coupling interface between the Princeton Ocean Model (POM) and the European Regional Seas Ecosystem Model (ERSEM), called High-Resolution OpenSESAME POM ERSEM (HiROPE). Secondly, this model framework, embedding a composite of 'complex' conceptual principles of the functioning of the main biogeochemical processes, has been applied to substantially different marine systems, the Baltic proper and the northern Adriatic Sea. The generic biological first principles of the ERSEM ecosystem model have been throughly controlled for consistency, and a suitable mathematical syntax has been defined in order to accomodate the various biogeochemical cycles of the resolved elements. The model has been specifically applied in the chosen basins with different temporal and spatial resolutions: a one-dimensional (vertical, 1D-V), climatological implementation in the northern Adriatic Sea; a 1D-V implementation in the Baltic proper with realistic forcing functions in the period 1979-1991 and a fully three-dimensional, high-frequency realistic implementation in the northern Adriatic Sea (October 1995). General conclusions are that the representation of hydrodynamical variability, the definition and resolution of boundary processes, the introduction of new source terms or the implementation of new biological state variables, affect the predictability of the system behavior more than the utilization of incomplete initial conditions of biological variables in a complex comprehensive ecosystem model

Salivary DNA methylation panel to diagnose HPV-positive and HPV-negative head and neck cancers

Background Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumours with a typical 5 year survival rate of INK4a, TIMP3, PCQAP/MED15) will allow us to diagnose HNSCC patients from a normal healthy control group as well as to discriminate between Human Papillomavirus (HPV)-positive and HPV-negative patients. Methods Methylation-specific PCR (MSP) was used to determine the methylation levels of RASSF1α, p16INK4a, TIMP3 and PCQAP/MED15 in DNA isolated from saliva. Statistical analysis was carried out using non-parametric Mann-Whitney’s U-test for individually methylated genes. A logistic regression analysis was carried out to determine the assay sensitivity when combing the five genes. Further, a five-fold cross-validation with a bootstrap procedure was carried out to determine how well the panel will perform in a real clinical scenario. Results Salivary DNA methylation levels were not affected by age. Salivary DNA methylation levels for RASSF1α, p16INK4a, TIMP3 and PCQAP/MED15 were higher in HPV-negative HNSCC patients (n = 88) compared with a normal healthy control group (n = 122) (sensitivity of 71 % and specificity of 80 %). Conversely, DNA methylation levels for these genes were lower in HPV-positive HNSCC patients (n = 45) compared with a normal healthy control group (sensitivity of 80 % and specificity of 74 %), consistent with the proposed aetiology of HPV-positive HNSCCs. Conclusions Salivary DNA tumour-suppressor methylation gene panel has the potential to detect early-stage tumours in HPV-negative HNSCC patients. HPV infection was found to deregulate the methylation levels in HPV-positive HNSCC patients. Large-scale double-blinded clinical trials are crucial before this panel can potentially be integrated into a clinical setting

Morphometric Stability of the Corneal Subbasal Nerve Plexus in Healthy Individuals: A 3-Year Longitudinal Study Using Corneal Confocal Microscopy

PURPOSE. We examined the age-dependent alterations and longitudinal course of subbasal nerve plexus (SNP) morphology in healthy individuals. METHODS. Laser-scanning corneal confocal microscopy, ocular screening, and health and metabolic assessment were performed on 64 healthy participants at baseline and at 12-month intervals for 3 years. At each annual visit, eight central corneal images of the SNP were selected and analyzed using a fully-automated analysis system to quantify corneal nerve fiber length (CNFL). Two linear mixed model approaches were fitted to examine the relationship between age and CNFL, and the longitudinal changes of CNFL over three years. RESULTS. At baseline, mean age was 51.9 6 14.7 years. The cohort was sex balanced (v 2 ¼ 0.56, P ¼ 0.45). Age (t ¼ 1.6, P ¼ 0.12) and CNFL (t ¼ À0.50, P ¼ 0.62) did not differ between sexes. A total of 52 participants completed the 36-month visit and 49 participants completed all visits. Age had a significant effect on CNFL (F CONCLUSIONS. The CNFL showed a stable course over a 36-month period in healthy individuals, although there was a slight linear reduction in CNFL with age. The findings of this study have implications for understanding the time-course of the effect of pathology and surgical or therapeutic interventions on the morphology of the SNP, and serves to confirm the suitability of CNFL as a screening/monitoring marker for peripheral neuropathies

第860回千葉医学会例会・第16回千葉大学放射線医学教室例会

Methylation pattern in tumours and normal tissues. The methylation signature of RASSF1Îą, TIMP3 and PCQAP in HNSCC and normal tissues from The Cancer Genome Atlas (TCGA) database. (DOCX 91 kb