Narrative Inquiry into Postsecondary Transition Outcomes for Young Adults with Intellectual & Developmental Disabilities

Young adults with intellectual and developmental disabilities (IDD) continue to struggle with community engagement despite decades of research and policy initiatives addressing postsecondary transition. Evidence shows that persons with IDD are engaging in employment, postsecondary education, independent living, socialization, and other roles at significantly diminished rates, yet little data exists describing this participation in the voices of those affected. The purpose of this narrative inquiry was to describe community integration of persons with IDD in the decade following postsecondary transition in their own words. Critical disability theory was used as a lens to explore the successes and failures of public policy guiding this process. Research questions focused on types and frequency of community participation, personal perceptions of the transition journey, and how public policy supported or inhibited successful transition. Seven collaborators shared their transition narratives by creating comic books which revealed that: (a) transition began much earlier than addressed by policy, (b) bullying and paternalism were major obstacles that were insufficiently addressed, (c) sexuality was often ignored as an adult role, and (d) continued siloed service delivery led to fractured visions of adult roles and goals. Future research should explore benefits of updating public policy to address the transition beginning in early adolescence, prevalence of bullying for students with IDD, impact of siblings on social skills development, and if role participation should be emphasized over community integration to respect self-determination. Findings attest to the complexity and abilities of collaborators to enable positive social change by empowering overlooked voices to participate in the conversations guiding their futures

Average case analysis of empirical and explanation-based learning algorithms

We present an approach to modeling the average case behavior of learning algorithms. Our motivation is to mathematically model the performance of learning algorithms in order to better understand the nature of their empirical behavior. We are interested in how differences in learning algorithms influence the expected accuracy of the concepts learned.We present the Average Case Learning Model and apply the model to three learning algorithms: a purely empirical algorithm (Bruner's Wholist), an algorithm which prefers analytical (explanation-based) learning over empirical learning (EBL-FIRST-TM) and an algorithm integrating both analytical and empirical learning (lOSC-TM). The Average Case Learning Model is unique in that it is able to accurately predict the expected behavior of learning algorithms. We compare average case analysis to Valiant's Probably Approximately Correct (PAC) learning model

Dynamic EEG analysis during language comprehension reveals interactive cascades between perceptual processing and sentential expectations

Available online 18 October 2020.Understanding spoken language requires analysis of the rapidly unfolding speech signal at multiple levels: acoustic, phonological, and semantic. However, there is not yet a comprehensive picture of how these levels relate. We recorded electroencephalography (EEG) while listeners (N = 31) heard sentences in which we manipulated acoustic ambiguity (e.g., a bees/peas continuum) and sentential expectations (e.g., Honey is made by bees). EEG was analyzed with a mixed effects model over time to quantify how language processing cascades proceed on a millisecond-by-millisecond basis. Our results indicate: (1) perceptual processing and memory for fine-grained acoustics is preserved in brain activity for up to 900 msec; (2) contextual analysis begins early and is graded with respect to the acoustic signal; and (3) top-down predictions influence perceptual processing in some cases, however, these predictions are available simultaneously with the veridical signal. These mechanistic insights provide a basis for a better understanding of the cortical language network.This work was supported by NIH grant DC008089 awarded to BM. This work was partially supported by the Basque Government through the BERC 2018–2021 program and by the Spanish State Research Agency through BCBL Severo Ochoa excellence accreditation SEV-2015- 0490, as well as by a postdoctoral grant from the Spanish Ministry of Economy and Competitiveness (MINECO; reference FJCI-2016-28019), awarded to EK

The Development of Novel Radioimmunoconjugates for the PET Imaging and Radioimmunotherapy of Cancer

Antibodies have long played a vital role in nuclear medicine for both the diagnosis and therapy of various malignancies. The role and development of antibodies in nuclear medicine can be broadly separated into three different categories: 1) bioconjugation strategies, 2) immunoPET imaging, and 3) radioimmunotherapy. This dissertation will attempt to comprehensively cover each of these categories through a series of studies, protocols, and reviews. For the bioconjugation strategies, we will describe the development of a novel site-selective bioconjugation strategy using an innovative lysine-targeting reagent, PFP-bisN3, to prepare [89Zr]Zr-SSKDFO-pertuzumab for visualizing HER2+ breast cancer. Further, we introduce a new mAb with a catalytic domain that allows for the site-selective bioconjugation of chelators to yield [177Lu]Lu-CHX-A”-DTPA-PODS-HER2DVD for targeting HER2+ breast cancer. For immunoPET, several chapters of this dissertation are dedicated to discussing the development of a CD133- targeting monoclonal antibody — [89Zr]Zr-DFO-aCD133 — majorly focusing on immunoPET imaging of small cell lung cancer in traditional and advanced tumor murine models. We have recently begun to explore the therapeutic efficacy of this immunoconjugate as well using the 177Lu labeled derivative, [177Lu]Lu-DTPA-A”-CHX-aCD133. As for radioimmunotherapy, we describe creating a HER2-targeting nanobody with a residualizing prosthetic group for radiohalogenation to eventually be used for therapy of HER2+ malignancies. And lastly, we report a protocol for harnessing the inverse electron demand Diels-Alder (IEDDA) click reaction for diagnostic and therapeutic pretargeting; an overall introduction to antibodies in nuclear medicine; and a review based on the role of click chemistry and its advances in recent years

Prediction and diagnosis of clinical outcomes affecting restoration margins

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90130/1/j.1365-2842.2011.02267.x.pd

Inverse electron demand Diels-Alder click chemistry for pretargeted PET imaging and radioimmunotherapy

This approach leverages the rapid, bio-orthogonal inverse electron demand Diels-Alder reaction between a radiolabeled tetrazine and a trans-cyclooctene-bearing antibody to enable pretargeted positron emission tomography imaging and endoradiotherapy in a murine model of cancer. Radiolabeled antibodies have shown promise as tools for both the nuclear imaging and endoradiotherapy of cancer, but the protracted circulation time of radioimmunoconjugates can lead to high radiation doses to healthy tissues. To circumvent this issue, we have developed an approach to positron emission tomography (PET) imaging and radioimmunotherapy (RIT) predicated on radiolabeling the antibody after it has reached its target within the body. This in vivo pretargeting strategy is based on the rapid and bio-orthogonal inverse electron demand Diels-Alder reaction between tetrazine (Tz) and trans-cyclooctene (TCO). Pretargeted PET imaging and RIT using TCO-modified antibodies in conjunction with Tz-bearing radioligands produce high activity concentrations in target tissues as well as reduced radiation doses to healthy organs compared to directly labeled radioimmunoconjugates. Herein, we describe how to prepare a TCO-modified antibody (humanized A33-TCO) as well as how to synthesize two Tz-bearing radioligands: one labeled with the positron-emitting radiometal copper-64 ([Cu-64]Cu-SarAr-Tz) and one labeled with the beta-emitting radiolanthanide lutetium-177 ([Lu-177]Lu-DOTA-PEG(7)-Tz). We also provide a detailed description of pretargeted PET and pretargeted RIT experiments in a murine model of human colorectal carcinoma. Proper training in both radiation safety and the handling of laboratory mice is required for the successful execution of this protocol.Peer reviewe

Review of nanomaterials in dentistry: interactions with the oral microenvironment, clinical applications, hazards, and benefits.

Interest in the use of engineered nanomaterials (ENMs) as either nanomedicines or dental materials/devices in clinical dentistry is growing. This review aims to detail the ultrafine structure, chemical composition, and reactivity of dental tissues in the context of interactions with ENMs, including the saliva, pellicle layer, and oral biofilm; then describes the applications of ENMs in dentistry in context with beneficial clinical outcomes versus potential risks. The flow rate and quality of saliva are likely to influence the behavior of ENMs in the oral cavity, but how the protein corona formed on the ENMs will alter bioavailability, or interact with the structure and proteins of the pellicle layer, as well as microbes in the biofilm, remains unclear. The tooth enamel is a dense crystalline structure that is likely to act as a barrier to ENM penetration, but underlying dentinal tubules are not. Consequently, ENMs may be used to strengthen dentine or regenerate pulp tissue. ENMs have dental applications as antibacterials for infection control, as nanofillers to improve the mechanical and bioactive properties of restoration materials, and as novel coatings on dental implants. Dentifrices and some related personal care products are already available for oral health applications. Overall, the clinical benefits generally outweigh the hazards of using ENMs in the oral cavity, and the latter should not prevent the responsible innovation of nanotechnology in dentistry. However, the clinical safety regulations for dental materials have not been specifically updated for ENMs, and some guidance on occupational health for practitioners is also needed. Knowledge gaps for future research include the formation of protein corona in the oral cavity, ENM diffusion through clinically relevant biofilms, and mechanistic investigations on how ENMs strengthen the tooth structure

The impact of dental restorations' quality on caries risk

publishersversionPeer reviewe