ASSOCIATION BETWEEN IMU BASED ACCELEROMETRY ON THE TIBIA AND VERTICAL GROUND REACTION FORCE DURING DROP LANDING

Peak vertical ground reaction force is a fundamental biomechanical variable often used to assess lower extremity injury risk. Currently, the tools to measure vGRF are not cost effective. Therefore, the purpose of this study is to determine the association between the variables related to IMU-based accelerometry and vGRF as measured from a research grade force-plate during a drop-landing task. Correlations were run on the averages of the 8 trials for peak vGRF to MVA and MMVAD in the right, left, dominant, and non-dominant limb. The non-dominant limb showed the greatest correlation of peak vGRF to MVA (r=0.803, p<0.01) and MMVAD (r=0.779, p<0.01). The dominant limb showed the lowest correlation of peak vGRF to MVA (r=0.573, p<0.01) and MMVAD (r=0.563, p<0.01). The strength of the association between accelerometry and vGRF during a drop landing may be limb dependent. The strongest associations between vGRF, MVA and MMVAD were in the non-dominant limb.Master of Art

Potential clinical applications of quantum dots

The use of luminescent colloidal quantum dots in biological investigations has increased dramatically over the past several years due to their unique size-dependent optical properties and recent advances in biofunctionalization. In this review, we describe the methods for generating high-quality nanocrystals and report on current and potential uses of these versatile materials. Numerous examples are provided in several key areas including cell labeling, biosensing, in vivo imaging, bimodal magnetic-luminescent imaging, and diagnostics. We also explore toxicity issues surrounding these materials and speculate about the future uses of quantum dots in a clinical setting

Sensing polymer/DNA polyplex dissociation using quantum dot fluorophores

We characterized the dissociation of polymer/DNA polyplexes designed for gene delivery using water-soluble quantum dots (QDs). A pH-responsive pentablock copolymer was designed to form stable complexes with plasmid DNA via tertiary amine segments. Dissociation of the polyplex was induced using chloroquine where the efficiency of this process was sensed through changes in QD fluorescence. We found that increasing concentrations of pentablock copolymer and DNA led to quenching of QD fluorescence, while chloroquine alone had no measurable effect. The mechanism of quenching was elucidated by modeling the process as the combination of static and dynamic quenching from the pentablock copolymer and DNA, as well as self-quenching due the bridging of QDs. Tertiary amine homopolymers were also used to study the effect of chain length on quenching. Overall, these QDs were found to be highly effective at monitoring the dissociation of pentablock copolymer/DNA polyplexes in vitro and may have potential for studying the release of DNA within cells

Detection of circulating tumour DNA is associated with inferior outcomes in Ewing sarcoma and osteosarcoma: a report from the Children's Oncology Group.

BackgroundNew prognostic markers are needed to identify patients with Ewing sarcoma (EWS) and osteosarcoma unlikely to benefit from standard therapy. We describe the incidence and association with outcome of circulating tumour DNA (ctDNA) using next-generation sequencing (NGS) assays.MethodsA NGS hybrid capture assay and an ultra-low-pass whole-genome sequencing assay were used to detect ctDNA in banked plasma from patients with EWS and osteosarcoma, respectively. Patients were coded as positive or negative for ctDNA and tested for association with clinical features and outcome.ResultsThe analytic cohort included 94 patients with EWS (82% from initial diagnosis) and 72 patients with primary localised osteosarcoma (100% from initial diagnosis). ctDNA was detectable in 53% and 57% of newly diagnosed patients with EWS and osteosarcoma, respectively. Among patients with newly diagnosed localised EWS, detectable ctDNA was associated with inferior 3-year event-free survival (48.6% vs. 82.1%; p = 0.006) and overall survival (79.8% vs. 92.6%; p = 0.01). In both EWS and osteosarcoma, risk of event and death increased with ctDNA levels.ConclusionsNGS assays agnostic of primary tumour sequencing results detect ctDNA in half of the plasma samples from patients with newly diagnosed EWS and osteosarcoma. Detectable ctDNA is associated with inferior outcomes

Overview of Stabilizing Ligands for Biocompatible Quantum Dot Nanocrystals

Luminescent colloidal quantum dots (QDs) possess numerous advantages as fluorophores in biological applications. However, a principal challenge is how to retain the desirable optical properties of quantum dots in aqueous media while maintaining biocompatibility. Because QD photophysical properties are directly related to surface states, it is critical to control the surface chemistry that renders QDs biocompatible while maintaining electronic passivation. For more than a decade, investigators have used diverse strategies for altering the QD surface. This review summarizes the most successful approaches for preparing biocompatible QDs using various chemical ligands

Mixed-surface, lipid-tethered quantum dots for targeting cells and tissues

Quantum dots (QDs), with their variable luminescent properties, are rapidly transcending traditional labeling techniques in biological imaging and hold vast potential for biosensing applications. An obstacle in any biosensor development is targeted specificity. Here we report a facile procedure for creating QDs targeted to the cell membrane with the goal of cell-surface protease biosensing. This procedure generates water-soluble QDs with variable coverage of lipid functional groups. The resulting hydrophobicity is quantitatively controlled by the molar ratio of lipids per QD. Appropriate tuning of the hydrophobicity ensures solubility in common aqueous cell culture media and while providing affinity to the lipid bilayer of cell membranes. The reaction and exchange process was directly evaluated by measuring UV-vis absorption spectra associated with dithiocarbamate formation. Cell membrane binding was assessed using flow cytometry and total internal reflection fluorescence imaging with live cells, and tissue affinity was measured using histochemical staining and fluorescence imaging of frozen tissue sections. Increases in cell and tissue binding were found to be regulated by both QD hydrophobicity and surface charge, underlying the importance of QD surface properties in the optimization of both luminescence and targeting capability.NOTICE: This is the author’s version of a work that was accepted for publication in Colloids and Surfaces B: Biointerfaces. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Colloids and Surfaces B: Bioinerfaces, 94, 1, (2012): doi: 10.1016/j.colsurfb.2012.01.015.</p

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

Sensing polymer/DNA polyplex dissociation using quantum dot fluorophores

We characterized the dissociation of polymer/DNA polyplexes designed for gene delivery using water-soluble quantum dots (QDs). A pH-responsive pentablock copolymer was designed to form stable complexes with plasmid DNA via tertiary amine segments. Dissociation of the polyplex was induced using chloroquine where the efficiency of this process was sensed through changes in QD fluorescence. We found that increasing concentrations of pentablock copolymer and DNA led to quenching of QD fluorescence, while chloroquine alone had no measurable effect. The mechanism of quenching was elucidated by modeling the process as the combination of static and dynamic quenching from the pentablock copolymer and DNA, as well as self-quenching due the bridging of QDs. Tertiary amine homopolymers were also used to study the effect of chain length on quenching. Overall, these QDs were found to be highly effective at monitoring the dissociation of pentablock copolymer/DNA polyplexes in vitro and may have potential for studying the release of DNA within cells.Reprinted (adapted) with permission from ACS Nano 5 (1), pp.129-138, doi: 10.1021/nn1018939. Copyright 2011 American Chemical Society.</p

Mixed-surface, Lipid-tethered Quantum Dots for Targeting Cells and Tissues

Quantum dots (QDs), with their variable luminescent properties, are rapidly transcending traditional labeling techniques in biological imaging and hold vast potential for biosensing applications. An obstacle in any biosensor development is targeted specificity. Here we report a facile procedure for creating QDs targeted to the cell membrane with the goal of cell-surface protease biosensing. This procedure generates water-soluble QDs with variable coverage of lipid functional groups. The resulting hydrophobicity is quantitatively controlled by the molar ratio of lipids per QD. Appropriate tuning of the hydrophobicity ensures solubility in common aqueous cell culture media and while providing affinity to the lipid bilayer of cell membranes. The reaction and exchange process was directly evaluated by measuring UV-vis absorption spectra associated with dithiocarbamate formation. Cell membrane binding was assessed using flow cytometry and total internal reflection fluorescence imaging with live cells, and tissue affinity was measured using histochemical staining and fluorescence imaging of frozen tissue sections. Increases in cell and tissue binding were found to be regulated by both QD hydrophobicity and surface charge, underlying the importance of QD surface properties in the optimization of both luminescence and targeting capability.NOTICE: This is the author’s version of a work that was accepted for publication in Colloids and Surfaces B: Biointerfaces. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Colloids and Surfaces B: Bioinerfaces, 94, 1, (2012): doi: 10.1016/j.colsurfb.2012.01.015.</p