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Premorbid Social Functioning and Adult Schizophrenia Spectrum Disorders in the Copenhagen Perinatal Cohort
No full textSchizophrenia is a debilitating mental illness, best known for prominent positive symptoms. In addition to positive symptoms, symptoms related to social dysfunction are also often extremely impairing. For people living with schizophrenia, higher levels of social difficulties are associated with poorer functional outcomes. Research suggests individuals with schizophrenia experience difficulties with social functioning during development prior to reaching full criteria for illness. Retrospective and prospective methods have been the primary way to measure premorbid social functioning. Despite strengths of each approach, several confounds of both designs may limit interpretations of results. The high-risk longitudinal prospective method was developed to address some of the aforementioned methodological limitations. The current study investigates premorbid social functioning in a Danish schizophrenia high-risk longitudinal cohort. Participants were assessed at ages 10-13 years, prior to their development of a psychiatric disorder, through the use of multiple informants including the children themselves, parents, and teachers. Participants were then followed up with a clinical interview as adults. Adult diagnostic outcome was divided into three groups: schizophrenia-spectrum disorder, non-schizophrenia spectrum psychiatric disorder, and no mental illness. Results indicate that all informants reported significant differences in premorbid social functioning between participants who developed a schizophrenia-spectrum disorder and no mental illness. Teachers were found to be able to differentiate premorbid social functioning between participants who later developed a schizophrenia-spectrum disorder and a non-spectrum psychiatric disorder in addition to no mental illness, suggesting the potential importance of teacher ratings of premorbid social functioning as it pertains to adult schizophrenia-spectrum outcome
Dynamic Analysis of a Novel Geared Infinitely Variable Transmission
No full textA novel geared infinitely variable transmission (IVT) that can generate a continuous output-to-input speed ratio from zero to a certain value is developed and analyzed. The principle of changing the output-to-input speed ratio is to use a crank-slider mechanism; the output-to-input speed ratio is controlled by adjusting the crank length. Since the crank-slider mechanism can lead to relatively large variation of the output-to-input speed ratio in one rotation of the crank, the instantaneous input and output speeds and accelerations have variations and the corresponding forces exerted on each part of the IVT can have obvious changes in one rotation of the crank. Since forces on some parts of the IVT are critical and can cause failure of the IVT for vehicle and wind turbine applications, a dynamic analysis of the IVT is necessary to simulate the input and output speeds and accelerations. A method that combines Lagrangian dynamics and Newtonian dynamics is developed here to analyze the motion of the IVT. The dynamic analysis results can be used to evaluate the current design of the IVT
Identification and Characterization of 40S Ribosomal Protein 7 as a Novel Pim-1 Substrate
No full textProtein kinases constitute one of the largest and most pleiotropic families of proteins. Mutations leading to activation of protein kinases and loss of function of phosphatases can have deleterious consequences that lead to disease. Pim-1, a serine/threonine kinase, is one of many kinases that may play a role in the etiology of malignant diseases including lymphoma and prostate cancer. Recent studies indicate Pim-1 is overexpressed in prostate cancer and is a highly plausible therapeutic target. Paradoxically, a decrease in Pim-1 expression in later stages of prostate cancer correlates with poor prognosis. Pim-1 has been known to be a proto-oncogene for more than two decades, however, our understanding of how it functions is incomplete. A key underlying factor in this lack of knowledge is that, to date, fewer than fifteen Pim-1 substrates have been identified. The identification and validation of novel Pim-1 substrates could elucidate biomarkers of Pim-1 activity and provide insight into the molecular basis of Pim-1 function. Using an innovative kinase-substrate profiling method termed the Reverse In-gel Kinase Assay (RIKA), an active Pim-1 kinase was partially immobilized in a denaturing polyacrylamide gel to determine which substrates from cell lysates can be phosphorylated by the kinase within the gel. The potential substrates were excised from the gel and identified using mass spectrometry. Using a Pim-1 RIKA approach, 40S Ribosomal Protein 7 (RPS7) was identified as a potential novel Pim-1 substrate. In vitro studies demonstrated that Pim-1 robustly phosphorylates RPS7. Further studies were performed to identify sites of phosphorylation on RPS7, and alanine-substitution mutants were generated that completely abolished phosphorylation of RPS7 by Pim-1. Using immunofluorescence approaches in cultured cells, phosphorylation was shown to affect the cellular localization of RPS7. The data demonstrated that the lack of Pim-1 phosphorylation affects RPS7 nuclear export and, possibly incorporation into the 40S Ribosomal Subunit. Our observations indicate a role of Pim-1 phosphorylation in ribosome biogenesis and translational control in prostate cancer
Data Mining and Domain Knowledge: An Exploration of Methods to Advance Medical Research
No full textResearchers in the medical domain consider the double-blind placebo controlled clinical trial the gold standard. The data for these clinical trials are collected for a specifically defined hypothesis and there is very little in the realm of secondary data analyses conducted. The underlying purpose of this work is to demonstrate the value and relevance of data mining and artificial intelligence methods for both pre-processing needs and secondary data analyses in medical research. The selected medical domain for this demonstration is autism and in particular the data from IAN (Interactive Autism Network) obtained from Kennedy Krieger. During the process of predictive model building, numerous research issues were addressed at different phases. Solutions were provided for: (1) Statistical issues with metric-based data mining methods and (2) Provide guidelines for how to incorporate domain knowledge in data mining. Various statistical methods used in data mining, such as Na�ve Bayes, require metric data to ensure reliable and robust results. Many public data health sources, including the IAN dataset, primarily consist of non-metric data in the form of Likert scales and categorical data. MDS (Multi-Dimensional Scaling) will be presented as method which can effectively transform non-metric data to metric. For incorporating domain knowledge in data mining, the initial work of integrating autism domain knowledge in multi-level association rule mining is presented. Through the use of an external treatment ontology, more interesting association rules were extracted for autism treatments. In order to further explore the role of knowledge guidance, the hypothesis indicated that knowledge-guided mutation applied to classification rules will affect the search trajectory incrementally. This hypothesis builds on the underlying premise of gradualness. A pilot and full-fledged experiments were conducted where knowledge from the autism domain in the form of a drug taxonomy and autism comorbidity semantic net guided the mutation of classification rules. The experiments for the drug taxonomy confirmed the hypothesis that domain knowledge can be utilized to constrain the search space. This research is both novel and significant as it provides a practical resource for health informatics researchers who want to incorporate domain knowledge into data mining and artificial intelligence models
Retrieval of optical and microphysical properties of aerosols from a hybrid lidar dataset
No full textOver the past decade the development of inversion techniques for the retrievals of aerosol microphysical properties (e.g. effective radius, volume and surface-area concentrations) and aerosol optical properties (e.g. complex index of refraction and single scattering albedo) from multiwavelength lidar systems brought a new perspective in the study of the vertical distribution of aerosols. In this study retrievals of such parameters were obtained from a hybrid multiwavelength lidar dataset for the first time. In July of 2011, in the Baltimore-Washington DC region, synergistic profiling of optical and microphysical properties of aerosols with both airborne in-situ and ground-based remote sensing systems was performed during the first deployment of DISCOVER-AQ. The hybrid multiwavelength lidar dataset combines elastic ground-based measurements at 355 nm with airborne High Spectral Resolution Lidar (HSRL) measurements at 532 nm and elastic measurements at 1064 nm that were obtained less than 5 km apart of each other. This was the first study to our knowledge in which optical and microphysical retrievals from lidar were obtained during the day and directly compared to AERONET and in-situ measurements for eleven cases. Good agreement was observed between lidar and AERONET retrievals. Larger discrepancies were observed between lidar retrievals and in-situ measurements obtained by the aircraft and aerosol hygroscopic effects are believed to be the main factor of such discrepancies
Impact of process parameters on product titer and quality attributes during cell culture scale down
No full textQuality by Design and Process Analytical Technology regulatory initiatives aim to achieve consistent production of biopharmaceuticals of predefined quality. Extensive process development studies are imperative to establish such a production process. Currently, these studies are primarily being carried out in bench-scale systems. However, bench-scale bioreactor studies are costly, tedious and time consuming to set up. An in-house developed, novel high-throughput minibioreactor system shows a significant potential to improve and streamline process development studies. However, in order to fully qualify this system as a scale down model, comparability between the two scales needs to be established. Comparability of product titers and product quality aspects such as glycosylation profile, which is considered to be one of the major product quality attributes, would be of greatest relevance. Here, we investigate cell culture scale down on monoclonal antibody (mAb) titers and their N-glycan profiles produced by serum free mammalian cell culture in these two systems. Methods for purification of mAb and N-glycan analysis using high pH anion exchange chromatography (HPAEC) with pulsed amperometric detection (PAD) were developed. Structural determination of glycans was done using MALDI-TOF mass spectrometry. A comparability experiment indicated that DO and pH profiles, cell growth, glucose and lactate profiles were similar in bench-scale bioreactors and minibioreactors. Although the relative areas of major N-glycans were found to be comparable in two systems, mAb titers in bench-scale bioreactor were about 50% higher than in minibioreactor. While investigating this, a noticeable difference in the glutamine consumption in two systems was observed. Evidence in the literature related glutamine consumption to pCO2 levels. In order to investigate the role of pCO2, a novel pCO2 sensor patch was modified for use in mammalian cell culture. This sensor revealed a difference between the pCO2 profiles between two systems. CO2 stripping studies were conducted in order to match pCO2 stripping rate. A comparability study conducted at comparable pCO2 stripping rate showed similar pCO2 profiles and a significant improvement in product titers in minibioreactors was achieved. Finally, the effect of DO on cell culture in minibioreactors and bench-scale bioreactors was investigated and it was found to be comparable
Becoming Real: Undergraduates' Civic Agency Journeys
No full textResponding to calls for higher education to play a central role in renewing democracy, a growing number of U.S. colleges, universities, and national higher education networks are experimenting with strategies for developing students' civic agency: the capacity of ordinary people collectively to create and exert power in action. This study explores the developmental processes of University of Maryland, Baltimore County (UMBC) undergraduates who achieved and demonstrated exceptional civic agency, using a research methodology that combines phenomenology, the search for deep meanings in lived experience, with hermeneutics, an iterative meaning-making process grounded in the researcher's relationship with the topic being studied. By conveying the products of this exploration with poetic resonance, and surfacing aspects of everyday experience not ordinarily recognized by the conscious mind, this study aims to empower and inspire readers to take action to promote civic agency effectively in their own environments. For the UMBC undergraduates who participated in this study, coming to civic agency involved experiencing their own reality against the backdrop of everyday environments and relationships that often felt synthetic and scripted. In a variety of settings, the participants found opportunities to be the cause of meaningful changes in people and situations, from which they drew the inference that they were actually present in a world that could be altered through their actions. In relationships with older adults and peers that deviated from the usual scripts, the participants experienced themselves anew as subjects rather than objects, human beings rather than actors on a stage. Faculty and staff members contributed most to the participants' agency when they approached the teaching and learning process with a kind of directness and humility: a willingness to share power and status, forego pretensions, avoid assertions of absolute mastery, and allow collaborative work to unfold without knowing exactly where it would lead
Hybrid Artifacts: Collecting, Drawing, Queering, Mixing
No full textIn Hybrid Artifacts, I present two intermedia art works in which I combine drawing, animation, appropriation, installation, and video. The first, You Are What You Eat, is an animation of rotoscoped kitchen disaster scenes, the sources of which are Hollywood films, projected in a continuous frieze on three walls. The second, Butch, is a triptych of three looping videos, each featuring a still portrait of a male professional athlete who is crying animated tears. His image is superimposed on a live-action video of amateurs playing his sport. Through the work, I am seeking queer subjectivity in hybrid forms, bringing together queer reading strategies, the grammar of appropriation, cultural cataloging, and drawing's mix of informality and immediacy in hopes of revealing the latent psychological and cultural messages in the found media's in-between spaces
Validation of Surrogate Endpoints by Bayesian Equivalence Testing
No full textSurrogate endpoints are often used in clinical trials to serve as a substitute for a hard to achieve clinically meaningful endpoint. The surrogate endpoint is expected to predict the effect of the treatment on the true endpoint. Prentice (1989, Stat Med) proposed a set of criteria for surrogate endpoint validation. The main criterion is to show the conditional independence of the treatment and the true endpoint in the presence of a surrogate endpoint, and thereby showing that the surrogate endpoint captures the full effect of the treatment. To prove this criterion, one has to show the failure to reject the null hypothesis (acceptance of null) of conditional independence between treatment and the true endpoint, given a surrogate. In such settings, one could use an equivalence testing approach. In this research, an equivalence testing approach is studied for validation of surrogate endpoints using a Bayesian framework. Both normal endpoints and binary endpoints are evaluated by means of Bayes factors. The main idea of this research is to obtain an appropriate Bayes factor cutoff value or a rejection threshold, which can then be used to test for equivalence of true and surrogate endpoint. A calibrated Bayes approach is adopted to evaluate the Bayesian equivalence testing procedure. The validity of surrogate endpoints is assessed using different set of priors. The methodology is applied to a simple dataset. An equivalence testing criteria is also proposed for Relative Effect, an alternate measure of surrogacy (Buyse etal, 1998). In addition, exploratory investigation into non-parametric validation of surrogate endpoint is performed