Semiparametric Regression and Mortality Rate Prediction

This dissertation is divided into two parts. In the first part we consider the general multivariate multiple sample semiparametric density ratio model. In this model one distribution serves as a reference or baseline, and all other distributions are weighted tilts of the reference. The weights are considered known up to a parameter. All the parameters in the model, as well as the reference distribution, are estimated from the combined data from all samples. A kernel-based density estimator can be constructed based on the semiparametric model. In this dissertation we discuss the asymptotic theory and convergence properties for the semiparametric kernel density estimator. The estimator is shown to be not only consistent, but also more efficient than the general kernel density estimator. Several ways for selecting the bandwidth are also discussed. This opens the door to regression analysis with random covariates from a semiparametric perspective where information is combined from multiple multivariate sources. Accordingly, each multivariate distribution and a corresponding conditional expectation (or regression) of interest is then estimated from the combined data from all sources. Graphical and quantitative diagnostic tools are suggested to assess model validity. The method is applied to real and simulated data. Comparisons are made with multiple regression, generalized additive models (GAM) and nonparametric kernel regression. In the second part we study mortality rate prediction. The National Center for Health Statistics (NCHS) uses observed mortality data to publish race-gender specific life tables for individual states decennially. At ages over 85 years, the reliability of death rates based on these data is compromised to some extent by age misreporting. The eight-parameter Heligman-Pollard parametric model is then used to smooth the data and obtain estimates/extrapolation of mortality rates for advanced ages. In States with small sub-populations the observed mortality rates are often zero, particularly among young ages. The presence of zero death rates makes the fitting of the Heligman-Pollard model difficult and at times outright impossible. In addition, since death rates are reported on a log scale, zero mortality rates are problematic. To overcome observed zero death rates, appropriate probability models are used. Using these models, observed zero mortality rates are replaced by the corresponding expected values. This enables using logarithmic transformations, and the fitting of the Heligman-Pollard model to produce mortality estimates for ages 0 - 130 years

THE INFLUENCE OF EMOTIONAL INTELLIGENCE IN PHYSICAL EDUCATION TEACHERS’ SELF-EFFICACY FOR THE INCLUSION OF STUDENTS WITH DISABILITIES

The inclusion of students with disabilities in the modern educational process is a necessity for removing barriers to participation, obviating social inequalities and reducing social exclusion. In the direction of equal opportunities, empowerment and social inclusion, the emotional intelligence and emotional literacy of teachers plays a decisive factor. The study investigated the relationship between physical education teachers' emotional intelligence and their self-efficacy, regarding the inclusion of students with physical, sensory and intellectual disabilities. One hundred and fifty physical education (PE) teachers participated in the study. The Wong and Law Emotional Intelligence Scale (WLEIS) was used to measure emotional intelligence and the Self-Efficacy Instrument for Physical Education Teachers Majors Toward Inclusion (SE-PETE) for the evaluation of self-effectiveness. The results showed that demographic factors such as gender, age, level of education, level of schooling employed and years of teaching experience greatly influence the emotional intelligence levels of physical education teachers. Regarding self-efficacy beliefs, no statistically significant differences were observed in terms of gender, age, level of education, level of schooling employed, in contrast to education in adapted physical education which seems to influence self-efficacy. Spearman’s Coefficient Correlation showed that emotionally intelligent teachers show increased self-efficacy, since they create appropriate learning conditions, and act supportive and encouraging, while adapting teaching to the needs of their students. The multiple regression analysis showed that the self-emotional appraisal, the emotional appraisal of students, and the ability to use and regulate teachers’ emotions have a significant predictive value for high self-efficacy in inclusive practices.  Article visualizations

Στρατηγικές αντιμετώπισης πόνου, ψυχολογικών ελλειμμάτων και ελλειμμάτων ποιότητας ζωής σε άτομα με Κάκωση Νωτιαίου Μυελού

Ερευνητικός Σχεδιασμός: Συστηματική ανασκόπηση. Ιστορικό: Ο χρόνιος πόνος είναι ένα συνηθισμένο φαινόμενο σε άτομα που ζουν με κάκωση του νωτιαίου μυελού (Κ.Ν.Μ.). Οι πληθυσμοί με κάκωση Νωτιαίου Μυελού (Κ.Ν.Μ.) έχουν αυξημένο κίνδυνο κατάθλιψης, άγχους, πόνου και κακής ποιότητας ζωής. Σκοπός: Αυτή η συστηματική ανασκόπηση αποσκοπούσε στον εντοπισμό μελετών σχετικά με τη φροντίδα που παρέχεται σε άτομα με K.N.M. κατά τη διάρκεια της αποκατάστασης και συνθέτει τα στοιχεία των επιδράσεων και των χαρακτηριστικών αυτών των μελετών σχετικά με τις επιπτώσεις τους στην κατάθλιψη, το άγχος, τον πόνο και την κακή ποιότητα ζωής. Μέθοδοι: Αναζήτηση πραγματοποιήθηκε στις βάσεις δεδομένων από την πρώτη Οκτωβρίου 2020 έως τον Ιανουάριο 2020 (ενημερώθηκε τον Ιανουάριο 2020). Τα κριτήρια επιλεξιμότητας περιελάμβαναν την εκτίμηση τουλάχιστον μιας από τις κοινές δευτερογενείς συνέπειες της Κ.Ν.Μ. (δηλαδή κίνδυνος κατάθλιψης, άγχους, πόνου και ποιότητα ζωής). Αναζήτηση έγινε στις εξής βάσεις δεδομένων: Cochrane, MEDLINE, Embase, PsycINFO, καθώς και σε οκτώ άλλες βάσεις δεδομένων και μητρώα κλινικών δοκιμών. Οι λίστες αναφορών των επιλεγμένων άρθρων εξετάστηκαν για να βρεθούν πρόσθετα σχετικά άρθρα. Τα εργαλεία αξιολόγησης Cochrane Collaboration Risk of Bias και The Effective Public Health Practice Project Quality Assessment Tool χρησιμοποιήθηκαν για τις εκτιμήσεις της ποιότητας των ερευνών. Συλλογή και ανάλυση δεδομένων: Ένας συγγραφέας εξήγαγε τα δεδομένα και αξιολόγησε τον κίνδυνο μεροληψίας στις περιλαμβανόμενες μελέτες. Τα αποτελέσματα ήταν οποιοδήποτε μέτρο έντασης πόνου ή ανακούφισης από τον πόνο, άγχος, κατάθλιψη και ποιότητας ζωής. Αποτελέσματα: Δώδεκα μελέτες πληρούσαν τα κριτήρια ένταξης και είχαν ένα εύρος αποτελεσμάτων παρεμβάσεων που παραδόθηκαν μεμονωμένα, σε ομαδική μορφή, αυτοπροσώπως, αλλά και διαδικτυακά. Μόνο επτά μελέτες ανέφεραν σημαντικές μειώσεις στα αποτελέσματα που σχετίζονται με τον πόνο (με μέτρια μεγέθη επίδρασης), ενώ οι υπόλοιπες μελέτες (n = 5) δεν έδειξαν καμία αλλαγή. Τέσσερεις μελέτες βρήκαν μείωση των συμπτωμάτων κατάθλιψης και πέντε μείωση του άγχους. Η ποιότητα ζωής αξιολογήθηκε σε έξι μελέτες αν και σε τέσσερις μόνο μελέτες σημειώθηκαν σημαντικά οφέλη. Η ποιότητα των μελετών κυμαινόταν από υψηλή έως χαμηλή / αδύναμη. Συμπεράσματα: Αυτή η ανασκόπηση βρήκε πολλά υποσχόμενα δεδομένα για ορισμένες προσεγγίσεις σε άτομα με Κ.Ν.Μ. που μπορούν να βελτιώσουν την ανακούφιση από τον πόνο και την ψυχοκοινωνική προσαρμογή τους (πρόγραμμα διαχείρισης πόνου, γνωστική συμπεριφορική θεραπεία, τεχνικές ενσυνειδητότητας, άσκηση, ψυχολογική εκπαίδευση, διακρανιακή διέγερση συνεχούς ρεύματος). Αν και σημαντικοί μεθοδολογικοί περιορισμοί εξασθένησαν τα ευρήματα της ανασκόπησης. Επιπροσθέτως, επειδή οι μελέτες διεξήχθησαν σε λίγες ανεπτυγμένες χώρες με υποομάδες ασθενών που είχαν συγκεκριμένα χαρακτηριστικά ή σοβαρότητα των κλινικών συμπτωμάτων, η γενικευσιμότητα τους στον ευρύτερο πληθυσμό με Κ.Ν.Μ. είναι αβέβαιη. Επομένως, η μελλοντική έρευνα θα πρέπει να υιοθετήσει πιο αξιόπιστους ερευνητικούς σχεδιασμούς για να εξετάσει τις παρεμβάσεις που στοχεύουν στην ανακούφιση από τον πόνο και την ψυχολογική ευεξία των ασθενών με Κ.Ν.Μ. με διαφορετικά κοινωνικο-πολιτισμικά υπόβαθρα και διαφορετικές συνθήκες ψυχολογικής προσαρμογής στα αρχικά στάδια της αποκατάστασης.Study Design: Systematic review. Background: Chronic pain is a usual phenomenon in persons living with spinal cord injury (SCI). Populations with spinal cord injury (SCI) have an increased risk of depression, anxiety, pain, and poorer quality of life (QoL). Aim: This systematic review aimed to identify interventional research regarding the care provided for people with SCI during rehabilitation and synthesize the evidence of the effects and characteristics of these studies regarding their effects on depression, anxiety, pain, and poorer quality of life (QoL). Methods: Databases were reviewed from the 1st October 2020 to January 2020 (updated January 2020). Eligibility criteria included the assessment of at least one of the common secondary consequences of SCI (i.e. risk of depression, anxiety, pain, and QoL). We searched Cochrane, MEDLINE, Embase, PsycINFO, eight other databases and clinical trials registers. Reference lists of the identified articles were reviewed to find additional relevant articles. The Cochrane Collaboration Risk of Bias and The Effective Public Health Practice Project Quality Assessment Tools were utilized for quality appraisals. Data collection and analysis: One review author independently extracted data and assessed risk of bias in the included studies. The outcomes were any measure of pain intensity or pain relief, anxiety, depression and quality of life. Results: Twelve papers met the inclusion criteria, and demonstrated a range of results of interventions delivered individually, in a group format, in person, and online. Only seven studies reported significant reductions in pain-related outcomes (with moderate effect sizes), with the remaining studies (n = 5) demonstrating no change. Four studies described reductions in depressive symptoms and five reported reductions in anxiety. Quality of life was assessed in six studies although in only four studies significant gains where found. Study quality ranged from high to low/weak. Conclusions: This review found promising evidence that some approaches for people with SCI can improve their pain relief and psychosocial adaptation (pain management program, cognitive Behavioral therapy, mindfulness, exercise, psychological education, transcranial direct current stimulation). Although significant methodological limitations weakened study findings. Additionally, because studies were conducted in only a few developed countries with subgroups of patients having specific illness characteristics or severity, their generalizability to the wider SCI population is uncertain. Therefore, future research should adopt more robust study designs to test interventions targeting pain relief and the psychological well being of patients with SCI with different socio-cultural backgrounds and psychological adjustment conditions in the early stages of rehabilitation. Key Words: Spinal cord injury; Rehabilitation; Pain; Quality of life; Psychological adjustment; Mental healt

A Characterization Method for Al Recovery from Dross Based on Compression at Elevated Temperatures

When aluminum or its alloys are melted, considerable amounts of dross are produced. The alloy type and the method used in the production of aluminum products play an important role in the amount of dross that will result as a byproduct. The current needs of the Al industry as well as economic and environmental factors demand the recovery of the pure material that is lost during dross removal by simple and efficient methods that can be applied within the foundry. Most cases of Al recovery employ methods of dross compression at high temperatures. This investigation attempts to develop a mathematical model to characterize the efficiency of the recovery process that can be implemented for any dross collection method or even compression device, facilitating the direct comparison of recovery methods

Analysis of leukocyte membrane protein interactions using protein microarrays

BACKGROUND: Protein microarrays represent an emerging class of proteomic tools to investigate multiple protein-protein interactions in parallel. A sufficient proportion of immobilized proteins must maintain an active conformation and an orientation that allows for the sensitive and specific detection of antibody and ligand binding. In order to establish protein array technology for the characterization of the weak interactions between leukocyte membrane proteins, we selected the human leukocyte membrane protein CD200 (OX2) and its cell surface receptor (hCD200R) as a model system. As antibody-antigen reactions are generally of higher affinity than receptor-ligand binding, we first analyzed the reactivity of monoclonal antibodies (mAb) to normal and mutant forms of immobilized CD200R. RESULTS: Fluorescently labelled mAb DX147, DX136 and OX108 were specifically reactive with immobilized recombinant hCD200R extracellular region, over a range of 0.1–40 μg ml(-1 )corresponding to a limit of sensitivity of 0.01–0.05 femtomol per spot. Orientating hCD200R using capture antibodies, showed that DX147 reacts with an epitope spatially distinct from the more closely related DX136 and OX108 epitopes. A panel of soluble recombinant proteins with mutations in hCD200R domain 1 produced by transiently transfected cells, was arrayed directly without purification and screened for binding to the three mAb. Several showed decreased binding to the blocking mAb DX136 and OX108, suggesting close proximity of these epitopes to the CD200 binding site. Binding of hCD200 to directly immobilized rat, mouse, and hCD200R was achieved with multimeric ligands, in the form of biotinylated-hCD200 coupled to FITC-labelled avidin coated beads. CONCLUSION: We have achieved sensitive, specific and reproducible detection of immobilized CD200R with different antibodies and mapped antigenic epitopes for two mAb in the vicinity of the ligand binding site using protein microarrays. We also detected CD200 binding to its receptor, a low affinity interaction, using beads presenting multivalent ligands. Our results demonstrate the quantitative aspects of protein arrays and their potential use in detecting simultaneously multiple protein-protein interactions and in particular the weak interactions found between leukocyte membrane proteins

Deconstruction of the beaten Path-Sidestep interaction network provides insights into neuromuscular system development

[EN] An 'interactome' screen of all Drosophila cell-surface and secreted proteins containing immunoglobulin superfamily (IgSF) domains discovered a network formed by paralogs of Beaten Path (Beat) and Sidestep (Side), a ligand-receptor pair that is central to motor axon guidance. Here we describe a new method for interactome screening, the Bio-Plex Interactome Assay (BPIA), which allows identification of many interactions in a single sample. Using the BPIA, we 'deorphanized' four more members of the Beat-Side network. We confirmed interactions using surface plasmon resonance. The expression patterns of beat and side genes suggest that Beats are neuronal receptors for Sides expressed on peripheral tissues. side-VI is expressed in muscle fibers targeted by the ISNb nerve, as well as at growth cone choice points and synaptic targets for the ISN and TN nerves. beat-V genes, encoding Side-VI receptors, are expressed in ISNb and ISN motor neurons.This work was supported by NIH grants to KZ (R37 NS28182), and to EO¨ (RO1 NS097161), by the Klingenstein-Simons Fellowship in the Neurosciences to EO¨ , and by SFI grants 07/IN.1/B913 and 08/ RFP/NSC1617 to J-P L. We thank Aref Arzan Zarin for preliminary genetic analysis. We thank Elena Armand and Suzanne Fisher for technical assistance, Maria Prats for preparation of AP supernatants for the experiments of Figs. S2 and S3, and Violana Nesterova for figure preparation. We thank Kaushiki Menon and Namrata Bali for help with larval staining. We acknowledge Dr. Elena Solomaha and the University of Chicago BioPhysics Core Facilities for training with and access to a Biacore 3000. We thank Laura Quintana Rio, Lalanti Venkatasubramanian, and Richard Mann (Columbia) for the Side-VI-T2A-GAL4 line.Li, H.; Watson, A.; Olechwier, A.; Anaya, M.; Sorooshyari, SK.; Harnett, DP.; Lee, H(.... (2017). Deconstruction of the beaten Path-Sidestep interaction network provides insights into neuromuscular system development. eLife. 6:1-24. doi:10.7554/eLife.28111S124

Uncertainty management in regulatory and health technology assessment decision-making on drugs: guidance of the HTAi-DIA Working Group

ObjectivesUncertainty is a fundamental component of decision making regarding access to and pricing and reimbursement of drugs. The context-specific interpretation and mitigation of uncertainty remain major challenges for decision makers. Following the 2021 HTAi Global Policy Forum, a cross-sectoral, interdisciplinary HTAi-DIA Working Group (WG) was initiated to develop guidance to support stakeholder deliberation on the systematic identification and mitigation of uncertainties in the regulatory-HTA interface. MethodsSix online discussions among WG members (Dec 2021-Sep 2022) who examined the output of a scoping review, two literature-based case studies and a survey; application of the initial guidance to a real-world case study; and two international conference panel discussions. ResultsThe WG identified key concepts, clustered into twelve building blocks that were collectively perceived to define uncertainty: "unavailable," "inaccurate," "conflicting," "not understandable," "random variation," "information," "prediction," "impact," "risk," "relevance," "context," and "judgment." These were converted into a checklist to explain and define whether any issue constitutes a decision-relevant uncertainty. A taxonomy of domains in which uncertainty may exist within the regulatory-HTA interface was developed to facilitate categorization. The real-world case study was used to demonstrate how the guidance may facilitate deliberation between stakeholders and where additional guidance development may be needed. ConclusionsThe systematic approach taken for the identification of uncertainties in this guidance has the potential to facilitate understanding of uncertainty and its management across different stakeholders involved in drug development and evaluation. This can improve consistency and transparency throughout decision processes. To further support uncertainty management, linkage to suitable mitigation strategies is necessary