Plenary Session II – Mobility Track: When the Wheels Fall Off

This session captures the consumer experience throughout the transition process, their struggle to maintain control and solutions to help them preserve independence and identity

Adaptive Motor Imagery: A Multimodal Study of Immobilization-Induced Brain Plasticity.

The consequences of losing the ability to move a limb are traumatic. One approach that examines the impact of pathological limb nonuse on the brain involves temporary immobilization of a healthy limb. Here, we investigated immobilization-induced plasticity in the motor imagery (MI) circuitry during hand immobilization. We assessed these changes with a multimodal paradigm, using functional magnetic resonance imaging (fMRI) to measure neural activation, magnetoencephalography (MEG) to track neuronal oscillatory dynamics, and transcranial magnetic stimulation (TMS) to assess corticospinal excitability. fMRI results show a significant decrease in neural activation for MI of the constrained hand, localized to sensorimotor areas contralateral to the immobilized hand. MEG results show a significant decrease in beta desynchronization and faster resynchronization in sensorimotor areas contralateral to the immobilized hand. TMS results show a significant increase in resting motor threshold in motor cortex contralateral to the constrained hand, suggesting a decrease in corticospinal excitability in the projections to the constrained hand. These results demonstrate a direct and rapid effect of immobilization on MI processes of the constrained hand, suggesting that limb nonuse may not only affect motor execution, as evidenced by previous studies, but also MI. These findings have important implications for the effectiveness of therapeutic approaches that use MI as a rehabilitation tool to ameliorate the negative effects of limb nonuse

Development of novel methods for non-canonical myeloma protein analysis with an innovative adaptation of immunofixation electrophoresis, native top-down mass spectrometry, and middle-down de novo sequencing

OBJECTIVES: Multiple myeloma (MM) is a malignant plasma cell neoplasm, requiring the integration of clinical examination, laboratory and radiological investigations for diagnosis. Detection and isotypic identification of the monoclonal protein(s) and measurement of other relevant biomarkers in serum and urine are pivotal analyses. However, occasionally this approach fails to characterize complex protein signatures. Here we describe the development and application of next generation mass spectrometry (MS) techniques, and a novel adaptation of immunofixation, to interrogate non-canonical monoclonal immunoproteins. METHODS: Immunoprecipitation immunofixation (IP-IFE) was performed on a Sebia Hydrasys Scan2. Middle-down de novo sequencing and native MS were performed with multiple instruments (21T FT-ICR, Q Exactive HF, Orbitrap Fusion Lumos, and Orbitrap Eclipse). Post-acquisition data analysis was performed using Xcalibur Qual Browser, ProSight Lite, and TDValidator. RESULTS: We adapted a novel variation of immunofixation electrophoresis (IFE) with an antibody-specific immunosubtraction step, providing insight into the clonal signature of gamma-zone monoclonal immunoglobulin (M-protein) species. We developed and applied advanced mass spectrometric techniques such as middle-down de novo sequencing to attain in-depth characterization of the primary sequence of an M-protein. Quaternary structures of M-proteins were elucidated by native MS, revealing a previously unprecedented non-covalently associated hetero-tetrameric immunoglobulin. CONCLUSIONS: Next generation proteomic solutions offer great potential for characterizing complex protein structures and may eventually replace current electrophoretic approaches for the identification and quantification of M-proteins. They can also contribute to greater understanding of MM pathogenesis, enabling classification of patients into new subtypes, improved risk stratification and the potential to inform decisions on future personalized treatment modalities

BFpack: Flexible Bayes Factor Testing of Scientific Theories in R

There have been considerable methodological developments of Bayes factors for hypothesis testing in the social and behavioral sciences, and related fields. This development is due to the flexibility of the Bayes factor for testing multiple hypotheses simultaneously, the ability to test complex hypotheses involving equality as well as order constraints on the parameters of interest, and the interpretability of the outcome as the weight of evidence provided by the data in support of competing scientific theories. The available software tools for Bayesian hypothesis testing are still limited however. In this paper we present a new R package called BFpack that contains functions for Bayes factor hypothesis testing for the many common testing problems. The software includes novel tools for (i) Bayesian exploratory testing (e.g., zero vs positive vs negative effects), (ii) Bayesian confirmatory testing (competing hypotheses with equality and/or order constraints), (iii) common statistical analyses, such as linear regression, generalized linear models, (multivariate) analysis of (co)variance, correlation analysis, and random intercept models, (iv) using default priors, and (v) while allowing data to contain missing observations that are missing at random

Identification and Quantification of Proteoforms by Mass Spectrometry

A proteoform is a defined form of a protein derived from a given gene with a specific amino acid sequence and localized post-translational modifications. In top-down proteomic analyses, proteoforms are identified and quantified through mass spectrometric analysis of intact proteins. Recent technological developments have enabled comprehensive proteoform analyses in complex samples, and an increasing number of laboratories are adopting top-down proteomic workflows. In this review, we outline some recent advances and discuss current challenges and future directions for the field

Australian and New Zealand Pulmonary Rehabilitation Guidelines

Background and objective: The aim of the Pulmonary Rehabilitation Guidelines (Guidelines) is to provide evidence-based recommendations for the practice of pulmonary rehabilitation (PR) specific to Australian and New Zealand healthcare contexts. Methods: The Guideline methodology adhered to the Appraisal of Guidelines for Research and Evaluation (AGREE) II criteria. Nine key questions were constructed in accordance with the PICO (Population, Intervention, Comparator, Outcome) format and reviewed by a COPD consumer group for appropriateness. Systematic reviews were undertaken for each question and recommendations made with the strength of each recommendation based on the GRADE (Gradings of Recommendations, Assessment, Development and Evaluation) criteria. The Guidelines were externally reviewed by a panel of experts. Results: The Guideline panel recommended that patients with mild-to-severe COPD should undergo PR to improve quality of life and exercise capacity and to reduce hospital admissions; that PR could be offered in hospital gyms, community centres or at home and could be provided irrespective of the availability of a structured education programme; that PR should be offered to patients with bronchiectasis, interstitial lung disease and pulmonary hypertension, with the latter in specialized centres. The Guideline panel was unable to make recommendations relating to PR programme length beyond 8 weeks, the optimal model for maintenance after PR, or the use of supplemental oxygen during exercise training. The strength of each recommendation and the quality of the evidence are presented in the summary. Conclusion: The Australian and New Zealand Pulmonary Rehabilitation Guidelines present an evaluation of the evidence for nine PICO questions, with recommendations to provide guidance for clinicians and policymakers

A chicken bioreactor for efficient production of functional cytokines

The global market for protein drugs has the highest compound annual growth rate of any pharmaceutical class but their availability, especially outside of the US market, is compromised by the high cost of manufacture and validation compared to traditional chemical drugs. Improvements in transgenic technologies allow valuable proteins to be produced by genetically-modified animals; several therapeutic proteins from such animal bioreactors are already on the market after successful clinical trials and regulatory approval. Chickens have lagged behind mammals in bioreactor development, despite a number of potential advantages, due to the historic difficulty in producing transgenic birds, but the production of therapeutic proteins in egg white of transgenic chickens would substantially lower costs across the entire production cycle compared to traditional cell culture-based production systems. This could lead to more affordable treatments and wider markets, including in developing countries and for animal health applications. Here we report the efficient generation of new transgenic chicken lines to optimize protein production in eggs. As proof-of-concept, we describe the expression, purification and functional characterization of three pharmaceutical proteins, the human cytokine interferon α2a and two species-specific Fc fusions of the cytokine CSF1. Our work optimizes and validates a transgenic chicken system for the cost-effective production of pure, high quality, biologically active protein for therapeutics and other applications

Playing Games with Tito:Designing Hybrid Museum Experiences for Critical Play

This article brings together two distinct, but related perspectives on playful museum experiences: Critical play and hybrid design. The article explores the challenges involved in combining these two perspectives, through the design of two hybrid museum experiences that aimed to facilitate critical play with/in the collections of the Museum of Yugoslavia and the highly contested heritage they represent. Based on reflections from the design process as well as feedback from test users, we describe a series of challenges: Challenging the norms of visitor behaviour, challenging the role of the artefact, and challenging the curatorial authority. In conclusion, we outline some possible design strategies to address these challenges

ICG-Fluorescence Imaging for Margin Assessment During Minimally Invasive Colorectal Liver Metastasis Resection

IMPORTANCE: Unintended tumor-positive resection margins occur frequently during minimally invasive surgery for colorectal liver metastases and potentially negatively influence oncologic outcomes. OBJECTIVE: To assess whether indocyanine green (ICG)-fluorescence-guided surgery is associated with achieving a higher radical resection rate in minimally invasive colorectal liver metastasis surgery and to assess the accuracy of ICG fluorescence for predicting the resection margin status. DESIGN, SETTING, AND PARTICIPANTS: The MIMIC (Minimally Invasive, Indocyanine-Guided Metastasectomy in Patients With Colorectal Liver Metastases) trial was designed as a prospective single-arm multicenter cohort study in 8 Dutch liver surgery centers. Patients were scheduled to undergo minimally invasive (laparoscopic or robot-assisted) resections of colorectal liver metastases between September 1, 2018, and June 30, 2021. EXPOSURES: All patients received a single intravenous bolus of 10 mg of ICG 24 hours prior to surgery. During surgery, ICG-fluorescence imaging was used as an adjunct to ultrasonography and regular laparoscopy to guide and assess the resection margin in real time. The ICG-fluorescence imaging was performed during and after liver parenchymal transection to enable real-time assessment of the tumor margin. Absence of ICG fluorescence was favorable both during transection and in the tumor bed directly after resection. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the radical (R0) resection rate, defined by the percentage of colorectal liver metastases resected with at least a 1 mm distance between the tumor and resection plane. Secondary outcomes were the accuracy of ICG fluorescence in detecting margin-positive (R1; <1 mm margin) resections and the change in surgical management. RESULTS: In total, 225 patients were enrolled, of whom 201 (116 [57.7%] male; median age, 65 [IQR, 57-72] years) with 316 histologically proven colorectal liver metastases were included in the final analysis. The overall R0 resection rate was 92.4%. Re-resection of ICG-fluorescent tissue in the resection cavity was associated with a 5.0% increase in the R0 percentage (from 87.4% to 92.4%; P < .001). The sensitivity and specificity for real-time resection margin assessment were 60% and 90%, respectively (area under the receiver operating characteristic curve, 0.751; 95% CI, 0.668-0.833), with a positive predictive value of 54% and a negative predictive value of 92%. After training and proctoring of the first procedures, participating centers that were new to the technique had a comparable false-positive rate for predicting R1 resections during the first 10 procedures (odds ratio, 1.36; 95% CI, 0.44-4.24). The ICG-fluorescence imaging was associated with changes in intraoperative surgical management in 56 (27.9%) of the patients. CONCLUSIONS AND RELEVANCE: In this multicenter prospective cohort study, ICG-fluorescence imaging was associated with an increased rate of tumor margin-negative resection and changes in surgical management in more than one-quarter of the patients. The absence of ICG fluorescence during liver parenchymal transection predicted an R0 resection with 92% accuracy. These results suggest that use of ICG fluorescence may provide real-time feedback of the tumor margin and a higher rate of complete oncologic resection